WorldWideScience

Sample records for baclofen

  1. Baclofen Intoxication

    Directory of Open Access Journals (Sweden)

    Canan Bor

    2015-12-01

    Full Text Available Baclofen is a β-(ρ-chlorophenyl derivative of the neurotransmitter gamma-aminobutyric acid (GABA and is usually prescribed for spasticity of spinal cord origin, intractable hiccup, trigeminal neuralgia, hemifacial spasm, and tardive dyskinesia. The usual recommended daily dose ranges from 40-80 mg, and the total dose should not exceed 80 mg per day. A 41 year old woman using baclofen for migraine therapy intended suicide after a bitter headache attack by taking 37 tablets, 10 mg in each. On arrival to emergency room, she was conscious and co-operable, but somnolent, her pupils were normoisocoric and light reflex was intact bilaterally. On her follow up, respiratory insufficiency and unconsciousness was observed so she was entubated orotracheally and transferred to intensive care unit (ICU for advanced tests and therapy. No pathology was determined on cranial CT. On ICU follow up, she was unconscious and mechanically ventilated, her Glasgow Coma Scale was 3/15 (E1M1VE and pupils were mid-dilated with no light reflex. Since she was again conscious, oriented and co-operable on 19th hour of arrival to ICU and 20th hour of arrival to emergency room, spontaneous breathing trials was started. Extubation was carried out on her 31th hour of arrival to ICU and 32th hour of arrival to emergency room. In conclusion; since baclofen overdose may cause deep coma, it should also be included in differential diagnosis. According to our opinion, performing diagnostic toxicological tests is not always possible that’s why history and physical examination is fundamental in case of baclofen intoxication and we can get good results by giving frequent neurological examination, supportive and extracorporeal therapy in such a case.

  2. Speaking fluently with baclofen?

    NARCIS (Netherlands)

    Beraha, Esther; Bodewits, Pieter; van den Brink, Wim; Wiers, Reinout

    2017-01-01

    Baclofen is a new and promising pharmacological compound for the treatment of alcohol dependence (AD). Although several randomised trials found a reduction of craving and higher abstinence rates with low and high doses of baclofen, others failed to show positive effects. In this case study, the

  3. A Nationwide Register-Based Survey of Baclofen Toxicity

    DEFF Research Database (Denmark)

    Kiel, Louise Bendix; Hoegberg, Lotte Christine Groth; Jansen, Tejs

    2015-01-01

    was conducted with ICD-10 codes for poisoning, self-harm and suicide, and coupled with the baclofen ATC code. All enquiries about baclofen to the Danish Poison Information Centre (DPIC) in the same period were evaluated. Demographic and clinical data were extracted, and the poisonings were classified according......To study the use and misuse (poisonings) of baclofen in the time period of 2007-2012 and to evaluate the severity and clinical symptoms of poisonings including ingested baclofen. The National Patient Register (NPR) was searched for admissions due to baclofen poisonings from 2007 to 2012. The search...... to the Poison Severity Score. The number of baclofen poisonings did not increase from 2007 to 2012. Thirty-eight admissions with baclofen poisoning were registered at the NPR; however, only one-third of the reviewed DPIC cases were registered at the NPR with the correct coding. In the group of severely poisoned...

  4. Intrathecal Baclofen Therapy: Benefits and Complications

    Science.gov (United States)

    Zdolsek, Helena Aniansson; Olesch, Christine; Antolovich, Giuliana; Reddihough, Dinah

    2011-01-01

    Background: Spasticity and dystonia in children with cerebral palsy has been treated with intrathecal baclofen therapy (ITB) at the Royal Children's Hospital, Melbourne, Australia (RCH) since 1999. Methods: The records of children having received or still receiving ITB during the period September 1999 until August 2005 were studied to evaluate…

  5. Baclofen in the management of cannabis dependence syndrome

    OpenAIRE

    Imbert, Bruce; Labrune, Nathalie; Lancon, Christophe; Simon, Nicolas

    2014-01-01

    Cannabis is the most commonly used illicit drug in the world. However, only few studies have shown the efficacy of pharmacologic agents in targeting cannabis withdrawal symptoms or reducing the reinforcing effects of cannabis. Baclofen has been shown to reduce cannabis withdrawal symptoms and the subjective effects of cannabis. We think that the clinical utility of baclofen for cannabis dependence is a reasonable approach. A case report using baclofen is presented and provides preliminary sup...

  6. Intrathecal baclofen pump for spasticity: an evidence-based analysis.

    Science.gov (United States)

    2005-01-01

    To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen for spasticity. Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury (SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces mobility and independence, and interferes with activities of daily living, continence and sleep patterns. Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer. Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement, reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy, oral medications, injections of phenol or botulinum toxin, or surgical intervention. Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI and MS patients fail to respond to oral baclofen.(3;4) Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4% to 27%.(2) When baclofen is administered orally, only a small portion of the

  7. Changes in body composition after spasticity treatment with intrathecal baclofen.

    Science.gov (United States)

    Skogberg, Olle; Samuelsson, Kersti; Ertzgaard, Per; Levi, Richard

    2017-01-19

    To assess changes in body composition, body weight and resting metabolic rate in patients who received intrathecal baclofen therapy for spasticity. Prospective, longitudinal, quasi-experimental, with a pre/post design. Twelve patients with spasticity, fulfilling study criteria, and due for pump implantation for intrathecal baclofen therapy, completed the study. Data were obtained before, 6 months and 12 months after commencement of intrathecal baclofen therapy as regards body composition (by skinfold calliper), body weight, and resting metabolic rate (by resting oxygen consumption). Spasticity was assessed according to the Modified Ashworth Scale (MAS) and Penn Spasm Frequency Scale (PSFS). A reduction in spasticity according to MAS occurred. Mean fat body mass increased and mean lean body mass decreased. Mean body weight showed a non-significant increase and resting metabolic rate a non-significant decrease. This explorative study indicates that unfavourable changes in body composition might occur after intrathecal baclofen therapy. Since obesity and increased fat body mass contribute to an increased cardiovascular risk, these findings may indicate a need for initiation of countermeasures, e.g. increased physical activity and/or dietary measures, in conjunction with intrathecal baclofen therapy. Further studies, including larger study samples and control groups, are needed to corroborate these findings.

  8. Clinical experience of baclofen in alcohol dependence: A chart review.

    Science.gov (United States)

    Rozatkar, Abhijit R; Kapoor, Abhishek; Sidana, Ajeet; Chavan, Bir Singh

    2016-01-01

    Craving is recognized as a formidable barrier in the management of patients with alcohol dependence. Among pharmacological agents that have been used in experimental studies for reduction in craving, baclofen appears to have a significant advantage over other agents. The study is retrospective chart review of patients ( n = 113) who have been treated with baclofen for alcohol dependence in a tertiary hospital of North India. Baseline assessments included sociodemography, motivation, quantity-frequency of alcohol use, and other alcohol-related clinical parameters. Weekly assessments, for a period of 4 weeks, were extracted from records which included dose of baclofen, craving intensity, and alcohol consumption. The study sample was predominantly male, mean age of 41.49 (±9.75) years, most having a family history of substance use (70.97%), and many reporting binge use pattern in last year (49.46%). Baseline assessment revealed 48.7% of the sample was in precontemplation phase for alcohol use and 70% reported severe and persistent craving. This persistent craving was reported by only 15% of the sample by the end of 4 weeks treatment with baclofen (20-40 mg/day). Thirty-four percent of patients reported continued problematic use of alcohol by the end of 4 weeks. Our clinical experience suggests that baclofen reduces craving and alcohol consumption including in those with poor motivation. The drug causes few side effects and does not add to the intoxication effect of alcohol. Considering that baclofen is safe in those with liver cirrhosis and reduces withdrawal symptoms due to alcohol, a controlled trial comparing it with standard treatment is required.

  9. Clinical experience of baclofen in alcohol dependence: A chart review

    Directory of Open Access Journals (Sweden)

    Abhijit R Rozatkar

    2016-01-01

    Full Text Available Introduction: Craving is recognized as a formidable barrier in the management of patients with alcohol dependence. Among pharmacological agents that have been used in experimental studies for reduction in craving, baclofen appears to have a significant advantage over other agents. Methodology: The study is retrospective chart review of patients (n = 113 who have been treated with baclofen for alcohol dependence in a tertiary hospital of North India. Baseline assessments included sociodemography, motivation, quantity-frequency of alcohol use, and other alcohol-related clinical parameters. Weekly assessments, for a period of 4 weeks, were extracted from records which included dose of baclofen, craving intensity, and alcohol consumption. Results: The study sample was predominantly male, mean age of 41.49 (±9.75 years, most having a family history of substance use (70.97%, and many reporting binge use pattern in last year (49.46%. Baseline assessment revealed 48.7% of the sample was in precontemplation phase for alcohol use and 70% reported severe and persistent craving. This persistent craving was reported by only 15% of the sample by the end of 4 weeks treatment with baclofen (20–40 mg/day. Thirty-four percent of patients reported continued problematic use of alcohol by the end of 4 weeks. Conclusion: Our clinical experience suggests that baclofen reduces craving and alcohol consumption including in those with poor motivation. The drug causes few side effects and does not add to the intoxication effect of alcohol. Considering that baclofen is safe in those with liver cirrhosis and reduces withdrawal symptoms due to alcohol, a controlled trial comparing it with standard treatment is required.

  10. Intrathecal Baclofen Dosing Regimens: A Retrospective Chart Review.

    Science.gov (United States)

    Clearfield, Jacob S; Nelson, Mary Elizabeth S; McGuire, John; Rein, Lisa E; Tarima, Sergey

    2016-08-01

    To examine dosing patterns in patients receiving baclofen via intrathecal baclofen pumps to assess for common patterns by diagnosis, ambulation ability, and affected limbs distribution. This trial study included 25 patients with baclofen pumps selected from the 356 patients enrolled in our center's baclofen pump program. Selection was done by splitting all patients into diagnostic categories of stroke, multiple sclerosis, traumatic/anoxic brain injury, cerebral palsy, and spinal cord injury, and then, five patients were randomly selected from each diagnosis.A systematic chart review was then conducted for each patient from Jan 1, 2008, through September 16, 2013, to look at factors including mean daily dose at end of study, and among those implanted during the study mean initial stable dose and time to initial stable dose. Analysis of mean daily dose across diagnoses found significant differences, with brain injury, cerebral palsy, and spinal cord injury patients having higher doses while multiple sclerosis and stroke patients required lower doses. Nonambulatory patients strongly trended to have higher daily doses than ambulatory patients. Similar trends of mean initial stable dose being higher in a similar pattern as that of end mean daily dose were seen according to diagnoses and ambulatory status, although statistical significance could not be achieved with the small sample size. Significant differences in dosing were found between diagnoses and trended to differ by ambulatory status at the end of the study, and similar trends could be observed in achieving initial stable dose. © 2015 International Neuromodulation Society.

  11. Treatment of writer's cramp with sodium valproate and baclofen ...

    African Journals Online (AJOL)

    Treatment of a 27-year-old Black man with writer's cramp with a combin'ation of sodium valproate (Epilim) and baclofen (Lioresal) resulted in dramatic improvement of symptoms and signs. The possible mechanism of action of these drugs is discussed. This combination should be tried in the initial management of this ...

  12. Synthesis and pharmacological characterization of certain baclofen analogues

    DEFF Research Database (Denmark)

    Attia, M.I.; Herdeis, C.; Bräuner-Osborne, Hans

    2013-01-01

    (RS)-4-Amino-3-(4-chlorophenyl)butanoic acid (baclofen, 2) is the prototypic selective GABAR agonist and is used clinically for the treatment of spasticity associated with brain and spinal cord injuries. Synthesis and GABA receptor agonist activity of certain amino acids structurally related...

  13. Treatment of writer's sodium valproate and cramp with baclofen

    African Journals Online (AJOL)

    Treatment of a 27-year-old Black man with writer's cramp with a combin'ation of sodium valproate (Epi- lim) and baclofen (Lioresal) resulted in dramatic improvement of symptoms and signs. The possible mechanism of action of these drugs is discussed. This combination should be tried in the initial man- agement of this ...

  14. Intrathecal Baclofen Injection to Avoid Withdrawal in a Multiple Sclerosis Patient Undergoing Lumbar Spine Surgery: A Case Report.

    Science.gov (United States)

    Dupanovic, Mirsad; Devine, Robert P; Jackson, Sean R; Lynch, Sharon G

    2017-11-09

    Spasticity of spinal or cerebral origin is frequently treated with baclofen. Treatment interruption initially results in rebound spasticity; life-threatening withdrawal symptoms may follow. Severe rebound spasticity of leg muscles occurred in a multiple sclerosis patient after a 10-hour long perioperative pause of oral baclofen intake. In a subsequent spine surgery, recurrence was prevented by substituting a cumulative 12-hour oral baclofen dose with an intraoperative intrathecal injection. Administration of intrathecal baclofen during prolonged surgery in patients dependent on oral baclofen may improve patient comfort and prevent early withdrawal symptoms. The most optimal conversion ratio from oral to intrathecal baclofen is still undetermined.

  15. Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

    OpenAIRE

    Tae Hwan Kim; Gi-Young Park; Soyoung Shin; Dong Rak Kwon; Won Sik Seo; Jeong Cheol Shin; Jin Ho Choi; Sang Hoon Joo; Kwon-Yeon Weon; Byung Sun Min; Kyung Min Baek; Mahesh Upadhyay; Bing Tian Zhao; Mi Hee Woo; So Hee Kwon

    2014-01-01

    The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were ...

  16. Permanent mechanical deformation of an intrathecal baclofen pump secondary to scuba diving: a case report.

    Science.gov (United States)

    Draulans, N; Roels, E; Kiekens, C; Nuttin, B; Peers, K

    2013-11-01

    Case report. To describe the case of a spinal cord injury patient that went scuba diving resulting in a mechanical deformation of his intrathecal baclofen pump. University Hospitals Leuven, Belgium. Case report. Diving below 10 meters of depth can result in irreversible mechanical damage of the drug reservoir of an intrathecal baclofen pump. Patients with an intrathecal baclofen pump should be warned for the risks associated with scuba diving and should not dive more than 10 meters below sea level.

  17. Central inhibition of initiation of swallowing by systemic administration of diazepam and baclofen in anaesthetized rats.

    Science.gov (United States)

    Tsujimura, Takanori; Sakai, Shogo; Suzuki, Taku; Ujihara, Izumi; Tsuji, Kojun; Magara, Jin; Canning, Brendan J; Inoue, Makoto

    2017-05-01

    Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam, and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation. The effects of intraperitoneal or topical administration of each drug on swallowing function were studied. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topically applied diazepam or baclofen had no effect on swallowing. These data indicate that diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. NEW & NOTEWORTHY Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topical applied diazepam or baclofen was without effect on swallowing. Diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. Copyright © 2017 the American Physiological Society.

  18. Metabolic and Pharmacokinetic Differentiation of STX209 and Racemic Baclofen in Humans

    Directory of Open Access Journals (Sweden)

    Raymundo Sanchez-Ponce

    2012-09-01

    Full Text Available STX209 is an exploratory drug comprising the single, active R-enantiomer of baclofen which is in later stage clinical trials for the treatment of fragile x syndrome (FXS and autism spectrum disorders (ASD. New clinical data in this article on the metabolism and pharmacokinetics of the R- and S-enantiomers of baclofen presents scientific evidence for stereoselective metabolism of only S-baclofen to an abundant oxidative deamination metabolite that is sterically resolved as the S-enantiomeric configuration. This metabolite undergoes some further metabolism by glucuronide conjugation. Consequences of this metabolic difference are a lower Cmax and lower early plasma exposure of S-baclofen compared to R-baclofen and marginally lower urinary excretion of S-baclofen after racemic baclofen administration. These differences introduce compound-related exposure variances in humans in which subjects dosed with racemic baclofen are exposed to a prominent metabolite of baclofen whilst subjects dosed with STX209 are not. For potential clinical use, our findings suggest that STX209 has the advantage of being a biologically defined and active enantiomer.

  19. A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity

    NARCIS (Netherlands)

    Heetla, H. W.; Proost, J. H.; Molmans, B. H.; Staal, M. J.; van Laar, T.

    AimsIntrathecal baclofen (ITB) has proven to be an effective and safe treatment for severe spasticity. However, although ITB is used extensively, clinical decisions are based on very scarce pharmacokinetic-pharmacodynamic (PKPD) data. The aim of this study was to measure baclofen CSF concentrations

  20. Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

    Directory of Open Access Journals (Sweden)

    Tae Hwan Kim

    2014-01-01

    Full Text Available The potential pharmacokinetic (PK interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY and Achyranthes bidentata radix (AB extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW, OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42–4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (Cmax and longer time to reach Cmax (Tmax were observed in OY pretreated rats without changes in the area under the curve (AUC and the fraction excreted into urine (Furine. The absorption rate (Ka of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.

  1. Pharmacokinetic alteration of baclofen by multiple oral administration of herbal medicines in rats.

    Science.gov (United States)

    Kim, Tae Hwan; Park, Gi-Young; Shin, Soyoung; Kwon, Dong Rak; Seo, Won Sik; Shin, Jeong Cheol; Choi, Jin Ho; Joo, Sang Hoon; Weon, Kwon-Yeon; Min, Byung Sun; Baek, Kyung Min; Upadhyay, Mahesh; Zhao, Bing Tian; Woo, Mi Hee; Kwon, So Hee; Shin, Beom Soo

    2014-01-01

    The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42-4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a ) of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.

  2. [Anesthetic Management of an Adrenoleukodystrophy Patient for Intrathecal Baclofen Therapy].

    Science.gov (United States)

    Hashimoto, Yuichi; Takahashi, Kei; Yamamoto, Yuko; Ogata, Tokiko; Arai, Takero; Okuda, Yasuhisa

    2016-04-01

    A 34-year-old man with adrenoleukodystrophy (ALD) was scheduled for pump system insertion of intrathecal baclofen therapy under general anesthesia. ALD, a rare genetic disorder, is associated with a total body increase in long chain fatty acids caused by defective degradation, and includes various nervous system abnormalities, muscular weakness, in addition to adrenal insufficiency. He had contracture of the both legs, and muscular weakness of the left hand, and Mallampati class III, but no respiratory disability. In the operating room, we administered hydrocortisone 100 mg for steroid coverage, and low-dose midazolam, and fentanyl. As spontaneous breathing remained, we could easily see epiglottis and arytenoid cartilage by McGRATH. Therefore we selected rapid-induction of anesthesia with thiamylal, and rocuronium 40 mg, under cricoid pressure. We avoided propofol. Anesthsia was maintained with sevoflurane and remifentanil, monitoring BIS and train of four. No more rocuronium was administered, and anesthesia was uneventful. Intrathecal baclofen therapy is given to patients who have severe contracture. When we selected general anesthesia, we should be aware of the possibility of muscular weakness, and cannot intubate cannot ventilate scenario.

  3. Intrathecal baclofen for progressive neurological disease in childhood: A systematic review of literature

    NARCIS (Netherlands)

    Bonouvrié, L.A.; van Schie, P.E.M.; Becher, J.G.; van Ouwerkerk, W.J.R.; Vermeulen, R.J.

    2012-01-01

    Background: Intrathecal baclofen (ITB) treatment is frequently used for individuals with severe, but non-progressive, spasticity refractory to oral treatment. However, experiences with ITB in patients with progressive neurological disorders of childhood causing spasticity are limited. Aim: To

  4. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    Science.gov (United States)

    Reddy, Vikram K.; Girish, K.; Lakshmi, Pandit; Vijendra, R.; Kumar, Ajay; Harsha, R.

    2014-01-01

    Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. Results: The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Conclusion: Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide. PMID:25097273

  5. Intrathecal baclofen treatment in dystonic cerebral palsy: a randomized clinical trial: the IDYS trial.

    Science.gov (United States)

    Bonouvrié, Laura A; Becher, Jules G; Vles, Johannes S H; Boeschoten, Karin; Soudant, Dan; de Groot, Vincent; van Ouwerkerk, Willem J R; Strijers, Rob L M; Foncke, Elisabeth; Geytenbeek, Joke; van de Ven, Peter M; Teernstra, Onno; Vermeulen, R Jeroen

    2013-10-28

    Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex. The daily care of these patients can be difficult due to dystonic movements. Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice. Despite this widespread adoption, high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospective data are needed to judge the usefulness and indications for dystonic cerebral palsy. The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients. Furthermore, we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient. A double blind placebo-controlled multi-center randomized clinical trial will be performed in 30 children with dystonic cerebral palsy. Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy, Gross Motor Functioning Classification System level IV or V, with lesions in the cerebral white matter, basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included. Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment, both via an implanted pump. After this three month period, all patients will receive intrathecal baclofen treatment, with a follow-up after nine months. The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling. Secondary outcome measurements on the level of body functions include dystonia, spasticity, pain, comfort and sleep-related breathing disorders. Side effects will be monitored and we will study whether patient characteristics influence outcome. The results of

  6. Bi-directional effect of increasing doses of baclofen on reinforcement learning

    Directory of Open Access Journals (Sweden)

    Jean eTerrier

    2011-07-01

    Full Text Available In rodents as well as in humans, efficient reinforcement learning depends on dopamine (DA released from ventral tegmental area (VTA neurons. It has been shown that in brain slices of mice, GABAB-receptor agonists at low concentrations increase the firing frequency of VTA-DA neurons, while high concentrations reduce the firing frequency. It remains however elusive whether baclofen can modulate reinforcement learning. Here, in a double blind study in 34 healthy human volunteers, we tested the effects of a low and a high concentration of oral baclofen in a gambling task associated with monetary reward. A low (20 mg dose of baclofen increased the efficiency of reward-associated learning but had no effect on the avoidance of monetary loss. A high (50 mg dose of baclofen on the other hand did not affect the learning curve. At the end of the task, subjects who received 20 mg baclofen p.o. were more accurate in choosing the symbol linked to the highest probability of earning money compared to the control group (89.55±1.39% vs 81.07±1.55%, p=0.002. Our results support a model where baclofen, at low concentrations, causes a disinhibition of DA neurons, increases DA levels and thus facilitates reinforcement learning.

  7. Bruxism Associated with Anoxic Encephalopathy: Successful Treatment with Baclofen

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2013-01-01

    Full Text Available Introduction. Bruxism is a movement disorder characterized by grinding and clenching of the teeth. Etiology of bruxism can be divided into three groups: psychosocial factors, peripheral factors, and pathophysiological factors. Methods. The clinical investigation was conducted at King Khaled Hospital in Hail, Saudi Arabia, in 2012. Results. A 16-year-old Saudi female was brought to the hospital in a comatose state and with generalized convulsive seizures secondary to acute anoxic encephalopathy. In the third week of hospitalization, while still in a state of akinetic mutism, she developed incessant bruxism which responded favorably to a GABA receptor agonist (baclofen. Conclusion. Our data support the hypothesis that bruxism emanates from imbalance or dysregulation of the neurotransmitter system. Larger scale studies will be needed to confirm this hypothesis.

  8. Effects of baclofen on motor units paralysed by chronic cervical spinal cord injury

    Science.gov (United States)

    Häger-Ross, Charlotte K.; Klein, Cliff S.

    2010-01-01

    Baclofen, a gamma-aminobutyric acid receptorB agonist, is used to reduce symptoms of spasticity (hyperreflexia, increases in muscle tone, involuntary muscle activity), but the long-term effects of sustained baclofen use on skeletal muscle properties are unclear. The aim of our study was to evaluate whether baclofen use and paralysis due to cervical spinal cord injury change the contractile properties of human thenar motor units more than paralysis alone. Evoked electromyographic activity and force were recorded in response to intraneural stimulation of single motor axons to thenar motor units. Data from three groups of motor units were compared: 23 paralysed units from spinal cord injured subjects who take baclofen and have done so for a median of 7 years, 25 paralysed units from spinal cord injured subjects who do not take baclofen (median: 10 years) and 45 units from uninjured control subjects. Paralysed motor unit properties were independent of injury duration and level. With paralysis and baclofen, the median motor unit tetanic forces were significantly weaker, twitch half-relaxation times longer and half maximal forces reached at lower frequencies than for units from uninjured subjects. The median values for these same parameters after paralysis alone were comparable to control data. Axon conduction velocities differed across groups and were slowest for paralysed units from subjects who were not taking baclofen and fastest for units from the uninjured. Greater motor unit weakness with long-term baclofen use and paralysis will make the whole muscle weaker and more fatigable. Significantly more paralysed motor units need to be excited during patterned electrical stimulation to produce any given force over time. The short-term benefits of baclofen on spasticity (e.g. management of muscle spasms that may otherwise hinder movement or social interactions) therefore have to be considered in relation to its possible long-term effects on muscle rehabilitation

  9. Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

    Science.gov (United States)

    Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

    2013-12-01

    To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

  10. Consciousness recovery induced by intrathecal baclofen administration after subarachnoid hemorrhage -two case reports-.

    Science.gov (United States)

    Oyama, Hirofumi; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Tanahashi, Kuniaki

    2010-01-01

    Two patients with subarachnoid hemorrhage recovered consciousness after intrathecal baclofen administration using an implanted intrathecal baclofen pump delivering 50 microg per day using a simple infusion mode. Intrathecal baclofen resulted in significant reduction of spasticity 3 months after the implantation. Case 1 was reduced to a completely bedridden state with spasticity and could slightly move her fingers following commands. However, the patient could eat food and wash her face with minimal assistance at 3 months after the implantation, and could stand up in the parallel bars with assistance and speak several words at 8 months. Case 2 was in a completely bedridden state at 10 months after onset and could neither drink water nor follow instructions. However, the patient became oriented and could eat by herself within 3 to 4 weeks of implantation. She could walk with a cane and use the stairs with minimal assistance at 2 and 3 months after implantation. The patient could speak fluently within 6 months of implantation. Flatulence and dysuria happened during the screening test, but these symptoms were not repeated after implantation of a pump-catheter-system and continuous intrathecal baclofen infusion. Continuous intrathecal baclofen infusion caused both improvement in muscle tone and spasms and consciousness recovery from the vegetative state. This therapy is a strong candidate treatment for patients with spasticity and consciousness disturbance.

  11. Effect of Gabapentin and Baclofen on Histology Study in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Fifteen A. Fajrin

    2015-12-01

    Full Text Available Neuropathic pain resulted from injury to nerves is often resistant to current treatments and can seriously cause chronic pain if no appropriate treatment is given. This study was designed to prove the effectiveness of gabapentin and baclofen in increasing latency time toward thermal stimulus and recovering the morphology of dorsal horn of spinal cord in neuropathic-induced chronic pain. Forty mice were divided into 8 groups i.e sham, negative control, gabapentin at three different doses (10, 30, 100 nmol and baclofen at three different doses (1, 10, 30 nmol. Neuropathic condition was induced by ligation of sciatic nerve with Partial Sciatic Nerve Ligation (PSNL method. Gabapentin and baclofen were administrated intrathecally once a day for seven days, a week after neuropathic induction. Latency time toward thermal stimulus was measured on days 0, 1, 3, 5, 7, 8, 10, 12 and 14 after induction. Histology of the dorsal horn of spinal cord tissue was examined by haematoxylline-eosin staining. The results showed that intrathecal injection of gabapentin and baclofen significantly increased latency time of mice toward thermal stimulus compared with negative control. Gabapentin and baclofen are effective as treatment for neuropathic pain. They can also help the recovery process of the histology in dorsal horn in neuropathic pain.

  12. Intrathecal Baclofen Therapy for the Treatment of Spasticity in Sjögren-Larsson Syndrome.

    Science.gov (United States)

    Hidalgo, Eveline Teresa; Orillac, Cordelia; Hersh, Andrew; Harter, David H; Rizzo, William B; Weiner, Howard L

    2017-01-01

    Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjögren-Larsson syndrome who had pump implantation for intrathecal baclofen. We observed a positive response, with a decrease of spasticity, reflecting in the Modified Ashworth Scale, and parents and caregivers observed a functional improvement in both patients. One patient experienced skin irritation 15 months after surgery, necessitating pump repositioning. No infection occurred. Our report shows that intrathecal baclofen therapy can have a positive therapeutic effect on spasticity in patients with Sjögren-Larsson syndrome, and therefore may be a promising addition to current treatments.

  13. The effect of baclofen and diazepam on motor skill acquisition in healthy subjects

    DEFF Research Database (Denmark)

    Willerslev-Olsen, Maria; Lundbye-Jensen, Jesper; Petersen, Tue Hvass

    2011-01-01

    Antispastic medication is often used in the clinic together with physiotherapy. However, some of the antispastic drugs, e.g., baclofen and diazepam, may influence the plastic mechanisms that are necessary for motor learning and hence efficient physiotherapy. In the present study, we consequently...... investigated the influence of baclofen and diazepam on acquisition of a visuomotor skill. The study was designed as a semi-randomized, double-blinded, placebo-controlled, crossover study in 16 healthy human subjects. The motor skill task required the subjects to match a given force trajectory by increasing...... (coherence) domain during isometric dorsiflexion. Subjects receiving placebo showed statistically significant improvement in motor performance (q = 34.1, P = 0.014) accompanied by a statistically significant reduction in intramuscular coherence. Subjects receiving baclofen and diazepam conversely showed...

  14. The absorption, distribution, metabolism and elimination of β-(p-chlorophenyl)-GABA (Baclofen), 4

    International Nuclear Information System (INIS)

    Yamamoto, Hiroyuki; Kuki, Motoo; Ozaki, Masanobu

    1977-01-01

    Distribution of 14 C-baclofen was studied according to the autoradiography of a whole body in SD-JCL male rats after oral administration of 14 C-baclofen (100 μCi/kg). Distribution of radioactivity in kidney and liver was already apparent 15 min after administration. Radioactivity in kidney and liver was increased distribution of radioactivity in skeletal muscle was apparent 1 hr after administration. Radio and activity in various tissues decreased 3 hrs after administration. Distribution of radioactivity in brain and spinal cord remained low at any time after administration. Distribution of radioactivity of 14 C-baclofen in autoradiography was consistent with that in tracer study (Yamamoto et al 1977). (auth.)

  15. Effects of "in vivo" administration of baclofen on rat renal tubular function.

    Science.gov (United States)

    Donato, Verónica; Pisani, Gerardo Bruno; Trumper, Laura; Monasterolo, Liliana Alicia

    2013-09-05

    The effects of the in vivo administration of baclofen on renal tubular transport and aquaporin-2 (AQP2) expression were evaluated. In conscious animals kept in metabolic cages, baclofen (0.01-1mg/kg, s.c.) induced a dose-dependent increment in the urine flow rate (UFR) and in sodium and potassium excretion, associated with an increased osmolal clearance (Closm), a diminished urine to plasma osmolality ratio (Uosm/Posm) and a decrease in AQP2 expression. The above mentioned baclofen effects on functional parameters were corroborated by using conventional renal clearance techniques. Additionally, this model allowed the detection of a diminution in glucose reabsorption. Some experiments were performed with water-deprived or desmopressin-treated rats kept in metabolic cages. Either water deprivation or desmopressin treatment decreased the UFR and increased the Uosm/Posm. Baclofen did not change the Uosm/Posm or AQP2 expression in desmopressin-treated rats; but it increased the UFR and diminished the Uosm/Posm and AQP2 expression in water-deprived animals. These results indicate that in vivo administration of baclofen promotes alterations in proximal tubular transport, since glucose reabsorption was decreased. The distal tubular function was also affected. The increased Closm indicates an alteration in solute reabsorption at the ascending limb of the Henle's loop. The decreased Uosm/Posm and AQP2 expression in controls and in water-deprived, but not in desmopressin-treated rats, lead us to speculate that some effect of baclofen on endogenous vasopressin availability could be responsible for the impaired urine concentrating ability, more than any disturbance in the responsiveness of the renal cells to the hormone. © 2013 Elsevier B.V. All rights reserved.

  16. Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

    Directory of Open Access Journals (Sweden)

    Ahmadi-Abhari Seyed Ali

    2003-11-01

    Full Text Available Abstract Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence.

  17. Favorable response to intrathecal, but not oral, baclofen of priapism in a patient with spinal cord injury.

    Science.gov (United States)

    D'Aleo, Giangaetano; Rifici, Carmela; Kofler, Markus; Saltuari, Leopold; Bramanti, Placido

    2009-02-01

    Case report. To retrieve data about the utility of intrathecal baclofen for the treatment of otherwise refractory priapism that may occur in patients with spinal spasticity. Baclofen exerts well-known inhibitory effects on sexual function both in animals and humans. This observation led to the introduction of oral baclofen in the treatment of refractory and recurrent idiopathic priapism. We report a 41-year-old male patient who sustained a severe traumatic spinal cord injury in a motor vehicle accident. On clinical examination he presented with tetraplegia (motor level C3). Initial cervical magnetic resonance imaging showed a C3 to C4 lesion with a herniated disc and compression of the dural sac. One month later the patient developed priapism episodes. He received oral baclofen with only minimal beneficial effect on priapism. Eight months postinjury the patient underwent a test-trial with intrathecal baclofen bolus, which caused absence of priapism for 10 hours. One month later, an intrathecal pump system was implanted, leading to absence of priapism episodes. In the present case report, reduction of supraspinal control on the spinal cord may have induced an up-regulation of GABAB receptors, which are involved in penile tumescence. The trauma induced also liberation of penile reflexes with episodes of priapism. Normal full blood count and color duplex ultrasonography of the penis excluded a vascular genesis of priapism. This is the first report about the utility of intrathecal baclofen for the successful control of otherwise untreatable priapism in a patient with severe spinal spasticity. Hence, evaluation of intrathecal baclofen should be considered in patients suffering from severe and/or frequent priapism when oral baclofen and/or hormonal therapy are ineffective. The beneficial effect of intrathecal, but not oral baclofen, in our patient suggests a dose-dependent effect.

  18. Efficacy of intrathecal baclofen delivery in the management of severe spasticity in upper motor neuron syndrome.

    NARCIS (Netherlands)

    Rietman, J.S.; Geertzen, J.H.

    2007-01-01

    In the treatment of patients with severe spasticity, intrathecal administration of baclofen (ITB) was introduced in order to exert its effect directly at the receptor sites in the spinal cord, and have better therapeutic efficacy with smaller drug doses compared to oral antispasmodic medications.

  19. Cost analysis of the treatment of severe spinal spasticity with a continuous intrathecal baclofen infusion system

    NARCIS (Netherlands)

    Postma, TJBM; Oenema, D; Terpstra, S; Bouma, J; Kuipers-Upmeijer, H; Staal, MJ; Middel, BJ

    Objective: The purpose of our study was to analyse and evaluate the costs of continuous intrathecal baclofen administration as a modality in the treatment of severe spasticity in the Netherlands. Design: A cost analysis was conducted as part of a prospective, multicentre, multidisciplinary,

  20. Consensus on the appropriate use of intrathecal baclofen (ITB) therapy in paediatric spasticity

    NARCIS (Netherlands)

    Dan, B.; Motta, F.; Vles, J.S.; Vloeberghs, M.; Becher, J.G.S.J.S.; Eunson, P.; Gautheron, V.; Lutjen, S.; Mall, V.; Pascual-Pascual, S.I.; Pauwels, P.; Roste, G.K.

    2010-01-01

    Among features of motor disorders in children, spasticity is associated with considerable morbidity and problems in care, particularly in severely affected patients. Intrathecal baclofen (ITB) has been increasingly used as a relatively specific treatment modality for spasticity. To date, most of the

  1. Intrathecal baclofen therapy for adults with spinal spasticity: therapeutic efficacy and effect on hospital admissions.

    Science.gov (United States)

    Nance, P; Schryvers, O; Schmidt, B; Dubo, H; Loveridge, B; Fewer, D

    1995-02-01

    A prospective trial to demonstrate the efficacy of intrathecal baclofen therapy by implanted pump for adults with spasticity due to spinal cord injury or multiple sclerosis was initiated in our hospital. Of the 140 patients assessed, 7 met the following criteria for inclusion in the study: a modified Ashworth score > 3, a spasm frequency score > 2, and an inadequate response to oral anti-spasticity drugs, (i.e., baclofen, clonidine and cyproheptadine). All patients responded to intrathecal bolus injection of baclofen in the double blind, placebo-controlled screening phase (mean bolus dose = 42.8 micrograms). Programmable Medtronic pumps were implanted in 4 patients while 3 patients received non-programmable Infusaid pumps. Post-implantation, a marked decrease in spasticity occurred with a significant reduction of the Ashworth score (mean = 1.8, p pendulum test. These effects were maintained during a follow-up of 24-41 months (average infusion dose = 218.7 micrograms/day). The gross cost-savings due to reduced hospitalizations related to spasticity was calculated by comparing the cost for the two year period before pump implantation to the same period after treatment for 6 of the 7 patients. The cost of in-hospital implantation as well as the cost of the pumps were deducted from the gross savings. There was a net cost-saving of $153,120. Our findings agree with the reported efficacy and safety of intrathecal baclofen treatment, and illustrate the cost-effectiveness of this treatment.

  2. Baclofen as prophylaxis and treatment for alcohol withdrawal: a retrospective chart review.

    Science.gov (United States)

    Stallings, William; Schrader, Stuart

    2007-09-01

    Current standard of care for alcohol withdrawal is accomplished using benzodiazepines. There are no recommendations for prophylaxis of alcohol withdrawal in high risk populations. Baclofen has been studied for the treatment of alcohol withdrawal, but current research is limited. To determine if baclofen is an effective measure for prophylaxis and treatment of alcohol withdrawal in high risk populations upon admission to hospital wards. Design, Setting, Patients - Retrospective chart review of 42 inpatients at St. Anthony Hospital from November 2004 to April 2005. Patients were included if they were determined to be at risk for alcohol withdrawal. Patients were then divided into categories of prophylactic success versus failure and treatement success versus failure based on DSM-IV criteria for alcohol withdrawal. 17 patients were included in the study. 12 were categorized as prophylactic success and 2 were categorized as prophylactic failure. There was one treatment success and two treatment failures. The result was an 86% prophylactic success rate. Baclofen has potential in the prophylaxis of alcohol withdrawal. It is difficult to determine the clinical significance for the numbers found in this study. There are no prior studies for alcohol prophylaxis to compare what would be an acceptable success rate. Further studies that are double-blinded placebo controlled are needed to support or refute the usefulness of baclofen for alcohol withdrawal.

  3. Efficacy of intrathecal baclofen delivery in the management of severe spasticity in upper motor neuron syndrome

    NARCIS (Netherlands)

    Rietman, Johan Swanik; Geertzen, J.H.B.

    In the treatment of patients with severe spasticity, intrathecal administration of baclofen (ITB) was introduced in order to exert its effect directly at the receptor sites in the spinal cord, and have better therapeutic efficacy with smaller drug doses compared to oral antispasmodic medications.

  4. Effects of intrathecal baclofen on daily care in children with secondary generalized dystonia: A pilot study

    NARCIS (Netherlands)

    Bonouvrié, L.A.; van Schie, P.E.M.; Becher, J.G.; van Ouwerkerk, W.J.R.; Reeuwijk, A.; Vermeulen, R.J.

    2011-01-01

    Aim: Treatment options for dystonic cerebral palsy (CP) are limited. Our aims were to determine whether intrathecal baclofen (ITB) improves daily care, decreases dystonia and decreases pain in patients with dystonic CP. Methods: Patients received randomized blinded treatment with ITB or placebo.

  5. Baclofen dose-dependently disrupts learning in a place avoidance task requiring cognitive coordination

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Valeš, Karel

    2009-01-01

    Roč. 97, 3-4 (2009), s. 507-511 ISSN 0031-9384 R&D Projects: GA ČR(CZ) GA309/07/0341; GA ČR(CZ) GA309/09/0286 Institutional research plan: CEZ:AV0Z50110509 Keywords : Baclofen * avoidance learning Subject RIV: FH - Neurology Impact factor: 3.295, year: 2009

  6. Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

    NARCIS (Netherlands)

    Heetla, H. W.; Staal, M. J.; van Laar, T.

    Study design: Pilot study. Objective: To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, the

  7. Effects of GABA-B receptor agonist baclofen on cortical epileptic afterdischarges in rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Lindovský, Jiří; Šlamberová, Romana; Kubová, Hana

    2007-01-01

    Roč. 10, Suppl.1 (2007), s. 45-52 ISSN 1294-9361 R&D Projects: GA ČR(CZ) GA305/05/2581 Institutional research plan: CEZ:AV0Z50110509 Keywords : epileptic afterdischarges * evoked potentials * baclofen Subject RIV: ED - Physiology Impact factor: 0.919, year: 2007

  8. Intrathecal baclofen pump, useful and safe therapeutic intervention in spasticity? Report of four cases

    Directory of Open Access Journals (Sweden)

    Cáceres-Jerez, Luz Elena

    2016-10-01

    Full Text Available Spasticity may cause immobility, prostration, chronic pain, bedsores, infections, thrombosis and pneumonia; the purposes of its treatment are to control pain, improve mobility and quality of life, and reincorporate the patient to its daily activities by means of oral anti-spastic drugs; however, patients suffering from severe spasticity may require high oral doses of these medications, which may lead to adverse effects. In such cases, intrathecal baclofen has been proposed as a solution. This procedure has not been widely used in Colombia, so that protocols to perform it have not been established. We report the results obtained with the intrathecal administration of baclofen in four severely spastic patients, who had not previously responded to oral anti-spastic drugs, including high doses of baclofen. Pain, spasticity and quality of life significantly improved in three of them. The remaining one presented tolerance to the medication. Intrathecal baclofen pump is a useful and safe procedure for patients with severe spasticity and poor response to oral treatment.

  9. Intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a cost-effectiveness analysis

    NARCIS (Netherlands)

    Hoving, M.A.; Evers, S.M.A.A.; Ament, A.J.H.A.; van Raak, E.P.M.; Becher, J.G.; Rotteveel, J.; Vles, J.S.H.

    2008-01-01

    In a Dutch national study, we recently established the effectiveness and safety of continuous intrathecal baclofen infusion (CITB) in children with intractable spastic cerebral palsy (CP). Because prospective studies on the cost-effectiveness of CITB in children with spastic CP are lacking, we

  10. Intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a cost-effectiveness analysis.

    NARCIS (Netherlands)

    Hoving, M.A.; Evers, S.M.; Ament, A.J.; Raak, E.P. van; Vles, J.S.; Becher, J.G.; Vermeulen, R.; Brouwer, O.F.; Maathuis, C.G.B.; Catsman-Berrevoets, C.E.; Gerritsen, J.; Geerts, M.J.; Jongerius, P.H.; Nieuwenhuizen, O.F.; Rotteveel, J.J.; Speth, L.A.; Stroink, H.; Ziel, E.G. van der

    2008-01-01

    In a Dutch national study, we recently established the effectiveness and safety of continuous intrathecal baclofen infusion (CITB) in children with intractable spastic cerebral palsy (CP). Because prospective studies on the cost-effectiveness of CITB in children with spastic CP are lacking, we

  11. Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

    Science.gov (United States)

    Dube, T S; Ranpise, N S; Ranade, A N

    2014-01-01

    The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

  12. Intrathecal Versus Oral Baclofen: A Matched Cohort Study of Spasticity, Pain, Sleep, Fatigue, and Quality of Life.

    Science.gov (United States)

    McCormick, Zachary L; Chu, Samuel K; Binler, Danielle; Neudorf, Daniel; Mathur, Sunjay N; Lee, Jungwha; Marciniak, Christina

    2016-06-01

    Baclofen commonly is used to manage spasticity caused by central nervous system lesions or dysfunction. Although both intrathecal and oral delivery routes are possible, no study has directly compared clinical outcomes associated with these 2 routes of treatment. To compare spasticity levels, pain, sleep, fatigue, and quality of life between individuals receiving treatment with intrathecal versus oral baclofen. Cross-sectional matched cohort survey study. Urban academic rehabilitation outpatient clinics. Adult patients with spasticity, treated with intrathecal or oral baclofen for at least 1 year, matched 1:1 for age, gender, and diagnosis. Standardized surveys were administered during clinic appointments or by telephone. Surveys included the Penn Spasm Frequency Scale, Brief Pain Inventory, Epworth Sleepiness Scale, Fatigue Severity Scale, Life Satisfaction Questionnaire, and Diener Satisfaction with Life Scale. A total of 62 matched subjects were enrolled. The mean (standard deviation [SD]) age was 46 (11) years with a mean duration of intrathecal baclofen or oral baclofen treatment of 11 (6) and 13 (11) years, respectively. There were 40 (64%) male and 22 (36%) female subjects. Primary diagnoses included spinal cord injury (n = 38), cerebral palsy (n = 10), stroke (n = 10), and multiple sclerosis (n = 4). The mean (SD) dose of intrathecal and oral baclofen at the time of survey were 577 (1429) μg/day and 86 (50) mg/day, respectively. Patients receiving intrathecal compared with oral baclofen experienced significantly fewer (1.44 [0.92] versus 2.37 [1.12]) and less severe (1.44 [0.92] versus 2.16 [0.83]) spasms, respectively as measured by the Penn Spasm Frequency Scale (P life between groups. Subanalysis of patients with SCI mirrored results of the entire study sample, with significant decreases in spasm frequency and severity associated with intrathecal compared to oral baclofen (P < .01; P < .01), but no other between group differences. The mean (SD) percent

  13. Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy

    DEFF Research Database (Denmark)

    Overgård, Tinett Martesen; Kjærsgaard-Hansen, Lars; Søe, Morten

    2015-01-01

    infusion was 105.1-2,000 micrograms/day (mean 494.9 micrograms/day). Oral baclofen was reduced from 27.3 to 17.7 mg/day after ITB (p improvement in well-being, function and ease of care of their child had a mean score of 3.7, 2.2 and 3.4, respectively. 87.1% of parents...... by telephone interviews, and data were rated on a Likert scale ranging from one to five, where one was no effect and five was marked improvement. RESULTS: After ITB, spasticity was reduced from a median of four to two in the upper extremities and from a median of four to one in the lower extremities. Baclofen...

  14. Catheter Migration After Implantationan Intrathecal Baclofen Infusion Pump for Severe Spasticity: A Case Report

    Directory of Open Access Journals (Sweden)

    Tung-Chou Li

    2008-09-01

    Full Text Available We report a case of intrathecal baclofen infusion pump implantation complicated by migration of the catheter tip. A 55-year-old man required an intrathecal baclofen infusion for severe spasticity 4 years after a cervical spinal cord injury with incomplete tetraparesis. Twelve months after initial implantation of the device, the patient began to experience a recurrence of trunk tightness and spasticity. Subsequent X-ray and computed tomography evaluations of the catheter system revealed pooling of contrast medium outside of the intrathecal distribution in the lumbar subcutaneous region of the back and therefore migration of the pump catheter tip. At surgical revision, emphasis was placed on minimizing the length of catheter outside of the spine and securing the catheter in the supraspinous fascia with a right-angled anchor. The distance between the anchors and the entry point of the catheter into the supraspinous fascia was also reduced to prevent slipping when the patient bends forward. After surgery, the patient's spasticity improved and, 1 year later, he has experienced no further complications during follow-up, requiring an average baclofen dose of 150 mg/day. Here, we describe several surgical methods intended to secure the intrathecal catheter and prevent catheter migration. Other complications related to catheter failure are also highlighted.

  15. Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia-Induced Apoptosis through the Akt and PERK Pathways

    Directory of Open Access Journals (Sweden)

    Pingping Fu

    2016-11-01

    Full Text Available Retinal ganglion cells (RGCs consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist, of retinal ganglion cells against hypoxia-induced apoptosis. CoCl2 was applied to mimic hypoxia. Primary rat retinal ganglion cells (RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs. The viability and apoptosis of RGCs were assessed using cell viability and TUNEL assays, Hoechst staining, and flow cytometry. The expression of cleaved caspase-3, bcl-2, bax, Akt, phospho-Akt, PERK, phospho-PERK, eIF2α, phospho-eIF2α, ATF-4, and CHOP were measured using western blotting. GABAB2 mRNA expression was determined using quantitative real-time polymerase chain reaction (qRT-PCR analysis. Our study revealed that CoCl2 significantly induced RGC apoptosis and that baclofen reversed these effects. CoCl2-induced reduction of Akt activity was also reversed by baclofen. Baclofen prevented the activation of the PERK pathway and the increase in CHOP expression induced by CoCl2. Knockdown of GABAB2 and the inactivation of the Akt pathway by inhibitors reduced the protective effect of baclofen on CoCl2-treated RGCs. Taken together, these results demonstrate that baclofen protects RGCs from CoCl2-induced apoptosis by increasing Akt activity and by suppressing the PERK pathway and CHOP activation.

  16. Ability of baclofen in reducing alcohol craving and intake: II--Preliminary clinical evidence.

    Science.gov (United States)

    Addolorato, G; Caputo, F; Capristo, E; Colombo, G; Gessa, G L; Gasbarrini, G

    2000-01-01

    Accumulating evidence shows the efficacy of the gamma-aminobutyric acid (GABA(B)) receptor agonist baclofen in reducing alcohol intake in rats, but no studies have been performed in alcoholics. In the present preliminary study we investigated the effect of short-term baclofen administration on craving for alcohol, ethanol intake, and abstinence from alcohol in alcoholic individuals. Ten male current alcoholic individuals were admitted to the study. Baclofen was orally administered for 4 weeks, at a dose of 15 mg/day refracted in three times per day for the first 3 days, with the dose increased to 30 mg/day for the remaining 27 days. Each subject was checked as an outpatient every week for the 4 weeks; at each visit (T0-T4) craving level was evaluated by the Alcohol Craving Scale (ACS), and abstinence from alcohol was assessed based on the individual's self-evaluation, family member interview, and the main biological markers of alcohol abuse. A self-reported alcohol intake was recorded as the mean number of standard drinks consumed per day. Nine subjects completed the study; of these, two subjects continued to drink alcohol although they substantially reduced their daily drinks in the first week of treatment, whereas seven maintained abstinence throughout the experimental period. Craving was significantly reduced from the first week of the drug administration (p alcohol disappeared. Values of gamma-glutamyltranspeptidase, alanine aminotransferase, and mean cellular volume significantly decreased by the end of the study. Tolerability was fair in all participants; headache, vertigo, nausea, constipation, diarrhea, abdominal pain, hypotension, increased sleepiness, and tiredness were present as side effects in the first stage of the treatment. No participants showed craving for the drug. With the limitations of the low number of individuals evaluated and the open design, this preliminary clinical study supports the preclinical evidence on the effect of baclofen in

  17. Effects of severe spasticity treatment with intrathecal Baclofen in multiple sclerosis patients: Long term follow-up.

    Science.gov (United States)

    Stampacchia, Giulia; Gerini, Adriana; Mazzoleni, Stefano

    2016-04-06

    Intrathecal Baclofen is available to treat severe generalized spasticity in Multiple Sclerosis (MS) unresponsive to oral drug delivery. The aims of this study were to investigate the effects and the drug dosage of intrathecal Baclofen in a selected population of MS patients, affected by severe spasticity at long term follow-up. A prospective cohort study of 14 MS patients is presented. Spasticity and pain were periodically assessed and the Baclofen dosage was adjusted. The initial Baclofen dosage was 136.2 ± 109.3 μg, then it was increased at 12 months to 228.6 ± 179.2 μg (p Spasticity on the lower limbs decreased significantly from pre-implantation assessment (median: 3.5, IQR: 3.0-4.0) to 12 months evaluation (median: 0.5, IQR: 0.0-2.0) (p spasticity and pain was observed after the intrathecal Baclofen infusion for at least 76 months. To obtain these results a dosage adjustment was needed only in the first year after the implantation.

  18. Randomized placebo-controlled study of baclofen in the treatment of muscle cramps in patients with liver cirrhosis.

    Science.gov (United States)

    Elfert, Asem A; Abo Ali, Lobna; Soliman, Samah; Zakaria, Sherin; Shehab El-Din, Ibrahim; Elkhalawany, Walaa; Abd-Elsalam, Sherief

    2016-11-01

    Muscle cramps adversely influence the quality of life of patients with liver cirrhosis. Indeed, to date, a well-established therapy for this complication is still lacking. This is the first randomized placebo-controlled trial of baclofen in the treatment of muscle cramps in patients with liver cirrhosis. A total of 100 patients with liver cirrhosis and muscle cramps signed an informed consent to participate in this study. They were recruited from the Department of Tropical Medicine-Tanta University Hospital. They were randomized to receive either baclofen or placebo for 3 months. Patients were followed monthly and 1 month after withdrawal. At each visit, the clinicoepidemiological data were recorded, the muscle cramp questionnaire was filled, and any drug-related side effects were reported. In the baclofen group, the frequency of muscle cramps decreased significantly after 1 and 3 months of treatment (Pcramps (Pcramps disappeared completely in 72%, reduced in 20%, and led to no change in 8% of patients. No significant changes in the frequency, severity, and duration of muscle cramps were noted in the placebo group. There were few but nonsignificant side effects in the baclofen group compared with the placebo group. Baclofen was well tolerated, safe, and effective in the treatment of muscle cramps in patients with liver cirrhosis.

  19. Baclofen in the Therapeutic of Sequele of Traumatic Brain Injury: Spasticity

    Science.gov (United States)

    Pérez-Arredondo, Adán; Cázares-Ramírez, Eduardo; Carrillo-Mora, Paul; Martínez-Vargas, Marina; Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Alemón-Medina, Radamés; Sampieri, Aristides; Navarro, Luz; Carmona-Aparicio, Liliana

    2016-01-01

    Abstract Traumatic brain injury (TBI) is an alteration in brain function, caused by an external force, which may be a hit on the skull, rapid acceleration or deceleration, penetration of an object, or shock waves from an explosion. Traumatic brain injury is a major cause of morbidity and mortality worldwide, with a high prevalence rate in pediatric patients, in which treatment options are still limited, not available at present neuroprotective drugs. Although the therapeutic management of these patients is varied and dependent on the severity of the injury, general techniques of drug types are handled, as well as physical and surgical. Baclofen is a muscle relaxant used to treat spasticity and improve mobility in patients with spinal cord injuries, relieving pain and muscle stiffness. Pharmacological support with baclofen is contradictory, because disruption of its oral administration may cause increased muscle tone syndrome and muscle spasm, prolonged seizures, hyperthermia, dysesthesia, hallucinations, or even multisystem organ failure. Combined treatments must consider the pathophysiology of broader alterations than only excitation/inhibition context, allowing the patient's reintegration with the greatest functionality. PMID:27563745

  20. Detection of compatibility between baclofen and excipients with aid of infrared spectroscopy and chemometry.

    Science.gov (United States)

    Rojek, Barbara; Wesolowski, Marek; Suchacz, Bogdan

    2013-12-01

    In the paper infrared (IR) spectroscopy and multivariate exploration techniques: principal component analysis (PCA) and cluster analysis (CA) were applied as supportive methods for the detection of physicochemical incompatibilities between baclofen and excipients. In the course of research, the most useful rotational strategy in PCA proved to be varimax normalized, while in CA Ward's hierarchical agglomeration with Euclidean distance measure enabled to yield the most interpretable results. Chemometrical calculations confirmed the suitability of PCA and CA as the auxiliary methods for interpretation of infrared spectra in order to recognize whether compatibilities or incompatibilities between active substance and excipients occur. On the basis of IR spectra and the results of PCA and CA it was possible to demonstrate that the presence of lactose, β-cyclodextrin and meglumine in binary mixtures produce interactions with baclofen. The results were verified using differential scanning calorimetry, differential thermal analysis, thermogravimetry/differential thermogravimetry and X-ray powder diffraction analyses. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy

    DEFF Research Database (Denmark)

    Overgård, Tinett Martesen; Kjærsgaard-Hansen, Lars; Søe, Morten

    2015-01-01

    was introduced in 2003. METHODS: A total of 46 children who had a baclofen pump from April 2003 to January 2013 were included. The children's medical records were reviewed and clinical characteristics, efficacy and adverse events were registered. The efficacy of treatment experienced by parents was ascertained...... infusion was 105.1-2,000 micrograms/day (mean 494.9 micrograms/day). Oral baclofen was reduced from 27.3 to 17.7 mg/day after ITB (p parents' assessment of improvement in well-being, function and ease of care of their child had a mean score of 3.7, 2.2 and 3.4, respectively. 87.1% of parents...... stated that ITB had been worthwhile, and 90.3% would recommend it to other parents. Most infectious and mechanical adverse events were experienced during the first 200 days after pump implantation. The total complication rate was 0.40 per pump year. CONCLUSION: ITB resulted in reduced spasticity...

  2. Long-term outcomes of continuous intrathecal baclofen infusion for treatment of spasticity: a prospective multicenter follow-up study

    NARCIS (Netherlands)

    Delhaas, Elmar M.; Beersen, Nicoline; Redekop, W. Ken; Klazinga, Niek S.

    2008-01-01

    Long-term outcomes of 115 patients treated with continuous intrathecal baclofen infusion are reported. A prospective follow-up study was conducted in eight centers. Patients were followed up over a 12-month period. The follow-up scores on the three spasticity scales (Ashworth, spasm, and clonus

  3. Separate and combined effects of the GABAB agonist baclofen and Δ9-THC in humans discriminating Δ9-THC

    Science.gov (United States)

    Lile, Joshua A.; Kelly, Thomas H.; Hays, Lon R.

    2012-01-01

    Background Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ9-THC. The aim of the present study was to determine the potential involvement of the GABAB receptor subtype by assessing the separate and combined effects of the GABAB-selective agonist baclofen and Δ9-THC using pharmacologically specific drug-discrimination procedures. Methods Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received baclofen (25 and 50 mg), Δ9-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results Δ9-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50 mg) substituted for the Δ9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ9-THC-like subjective responses when administered alone. Conclusions These results suggest that the GABAB receptor subtype is involved in the abuse-related effects of Δ9-THC, and that GABAB receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABAA) to determine the contribution of the different GABA receptors in the effects of Δ9-THC, and by extension cannabis, in humans. PMID:22699093

  4. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    Science.gov (United States)

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

  5. Long-term intrathecal baclofen: outcomes after more than 10 years of treatment.

    Science.gov (United States)

    Mathur, Sunjay N; Chu, Samuel K; McCormick, Zack; Chang Chien, George C; Marciniak, Christina M

    2014-06-01

    To report outcomes of intrathecal baclofen (ITB) therapy for spasticity management in a cohort of patients who had received this treatment for at least 10 years. A cross-sectional survey and retrospective chart review. An academic rehabilitation outpatient clinic. Adult patients with spasticity treated with ITB for at least 10 years. Surveys included the Brief Pain Inventory, Penn Spasm Frequency Scale, Epworth Sleepiness Scale, Fatigue Severity Scale, Diener Satisfaction with Life, Life Satisfaction Questionnaire, and Intrathecal Baclofen Survey. Twenty-four subjects completed the surveys. The subjects had been treated with ITB from 10.0-28.4 years, with a mean (standard deviation) of 14.7 ± 4.2 years. The mean (standard deviation) dose of ITB was 627.9 ± 306.7 μg/d, with only 6 subjects averaging daily dose changes of more than 10% compared with 3 years earlier. The mean (standard deviation) scores on outcomes surveys were the following: 2.6 ± 2.3 for pain severity on the Brief Pain Inventory, 1.4 ± 0.7 for spasm severity on the Penn Spasm Frequency Scale, 7.9 ± 5.4 on the Epworth Sleepiness Scale, 4.1 ± 1.6 on the Fatigue Severity Scale, 19.4 ± 8.1 on the Diener Satisfaction with Life, 3.9 ± 0.9 on the Life Satisfaction Questionnaire, and 8.8 ± 1.9 for overall satisfaction with ITB on the Intrathecal Baclofen Survey. On the Brief Pain Inventory, the mean scores for pain severity and interference of pain with life showed moderate inverse correlations with ITB dose (r = -0.386, P = .115; and r = -0.447, P = .062, respectively). On the Life Satisfaction Questionnaire, the mean scores for life satisfaction showed statistically significant positive correlation with ITB dose (r = 0.549, P = .021). The subjects reported low levels of pain, moderate levels of life satisfaction, normal levels of sleepiness, low-to-moderate levels of fatigue, infrequent spasms at mild-to-moderate severity, and high levels of satisfaction. The efficacy and favorable adverse

  6. A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.

    Science.gov (United States)

    Girish, K; Vikram Reddy, K; Pandit, Lakshmi V; Pundarikaksha, H P; Vijendra, R; Vasundara, K; Manjunatha, R; Nagraj, Moulya; Shruthi, R

    2016-02-01

    Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  7. The comparative study of clinical efficacy and safety of baclofen vs tolperisone in spasticity caused by spinal cord injury

    Directory of Open Access Journals (Sweden)

    Dejun Luo

    2017-05-01

    Full Text Available In the present study we compared the clinical efficacy and safety of baclofen vs tolperisone in spasticity caused by spinal cord injury. A total of 150 patients were enrolled in the present study and were divided into two groups with 75 patients in each group, receiving baclofen or tolperisone, respectively. We used Modified Ashworth Scale, Medical research council scale, Barthel Index, and Coefficient of efficacy to measure clinical efficacy. After 6-week treatment, both groups demonstrated significant improvement in muscle tone, muscle strength and functional outcome (Group I, 1.55 ± 0.053, 2.79 ± 0.032, 59.31 ± 1.32; Group II, 1.57 ± 0.053, 3.04 ± 0.032, 73 ± 1.32 respectively. There was no significant difference regarding improvement in muscle tone and muscle strength between the two groups (Group I, 1.055 ± 0.053 vs Group II, 1.57 ± 0.053; Group I, 2.79 ± 0.032 vs Group II, 3.04 ± 0.032, p > 0.05. However, the improvement in functional outcomes was greater in group II as compared to that in group I (Group I, 59.31 ± 1.32 vs Group II, 73 ± 1.32, p < 0.05. In addition, overall efficacy coefficient was greater for group II as compared to group I (Group I, 3.6 vs Group II, 2.3, p < 0.05. Group I had more side effects compared to Group II. Compared to baclofen, tolperisone offers greater improvement in activities of daily living compared to baclofen.

  8. Modulation of adenylyl cyclase activity by baclofen in the developing rat brain: difference between cortex, thalamus and hippocampus

    Czech Academy of Sciences Publication Activity Database

    Hejnová, Lucie; Ihnatovych, Ivanna; Novotný, Jiří; Kubová, Hana; Mareš, Pavel; Svoboda, Petr

    2002-01-01

    Roč. 330, č. 1 (2002), s. 9-12 ISSN 0304-3940 R&D Projects: GA ČR GA309/99/0207; GA ČR GA309/01/0255 Institutional research plan: CEZ:AV0Z5011922 Keywords : GABA(B) receptors * baclofen * adenylyl cyclase Subject RIV: FH - Neurology Impact factor: 2.100, year: 2002

  9. Pharmacology of intracisternal or intrathecal glycine, muscimol, and baclofen in strychnine-induced thermal hyperalgesia of mice.

    Science.gov (United States)

    Lee, Il Ok; Son, Jin Kook; Lim, Eui-Sung; Kim, Yeon-Soo

    2011-10-01

    Glycine and γ-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are well known, little is known about the effect of GABA in strychnine-induced hyperalgesia. To investigate the effect of GABA and the role of the glycine receptor in thermal hyperalgesia, we designed an experiment involving the injection of muscimol (a GABA(A) receptor agonist), baclofen (a GABA(B) receptor agonist) or glycine with strychnine (strychnine sensitive glycine receptor antagonist). Glycine, muscimol, or baclofen with strychnine was injected into the cisterna magna or lumbar subarachnoidal spaces of mice. The effects of treatment on strychnine-induced heat hyperalgesia were observed using the pain threshold index via the hot plate test. The dosages of experimental drugs and strychnine we chose had no effects on motor behavior in conscious mice. Intracisternal or intrathecal administration of strychnine produced thermal hyperalgesia in mice. Glycine antagonize the effects of strychnine, whereas, muscimol or baclofen does not. Our results indicate that glycine has anti-thermal hyperalgesic properties in vivo; and GABA receptor agonists may lack the binding abilities of glycine receptor antagonists with their sites in the central nervous system.

  10. ACAMPROSATE AND BACLOFEN WERE NOT EFFECTIVE IN THE TREATMENT OF PATHOLOGICAL GAMBLING: PRELIMINARY BLIND RATER COMPARISON STUDY

    Directory of Open Access Journals (Sweden)

    Pinhas N Dannon

    2011-06-01

    Full Text Available Objectives: Pathological gambling (PG is a highly prevalent and disabling impulse control disorder. A range of psychopharmacological options are available for the treatment of PG, including selective serotonin reuptake inhibitors (SSRI, opioid receptor antagonists, anti-addiction drugs and mood stabilizers. In our preliminary study, we examined the efficacy of two anti-addiction drugs, Baclofen and Acamprosate, in the treatment of PG. Materials & Methods: 17 male gamblers were randomly divided into two groups. Each group received one of the two drugs without being blind to treatment. All patients underwent a comprehensive psychiatric diagnostic evaluation and completed a series of semi-structured interviews. During the six months of study, monthly evaluations were carried out to assess improvement and relapses. Relapse was defined as recurrent gambling behavior. Results: None of the 17 patients reached the six months abstinence. One patient receiving Baclofen sustained abstinence for 4 months. 14 patients succeeded in sustaining abstinence for 1-3 months. 2 patients stopped attending monthly evaluations. Conclusion: Baclofen and Acamprosate did not prove efficient in treating pathological gamblers.

  11. Acamprosate and Baclofen were Not Effective in the Treatment of Pathological Gambling: Preliminary Blind Rater Comparison Study.

    Science.gov (United States)

    Dannon, Pinhas N; Rosenberg, Oded; Schoenfeld, Netta; Kotler, Moshe

    2011-01-01

    Pathological gambling (PG) is a highly prevalent and disabling impulse control disorder. A range of psychopharmacological options are available for the treatment of PG, including selective serotonin reuptake inhibitors, opioid receptor antagonists, anti-addiction drugs, and mood stabilizers. In our preliminary study, we examined the efficacy of two anti-addiction drugs, baclofen and acamprosate, in the treatment of PG. Seventeen male gamblers were randomly divided into two groups. Each group received one of the two drugs without being blind to treatment. All patients underwent a comprehensive psychiatric diagnostic evaluation and completed a series of semi-structured interviews. During the 6-months of study, monthly evaluations were carried out to assess improvement and relapses. Relapse was defined as recurrent gambling behavior. None of the 17 patients reached the 6-months abstinence. One patient receiving baclofen sustained abstinence for 4 months. Fourteen patients succeeded in sustaining abstinence for 1-3 months. Two patients stopped attending monthly evaluations. Baclofen and acamprosate did not prove efficient in treating pathological gamblers.

  12. How should an infected perinephric haematoma be drained in a tetraplegic patient with baclofen pump implanted in the abdominal wall? – A case report

    Directory of Open Access Journals (Sweden)

    Watt John WH

    2002-09-01

    Full Text Available Abstract Background We present a case to illustrate controversies in percutaneous drainage of infected, perinephric haematoma in a tetraplegic patient, who had implantation of baclofen pump in anterior abdominal wall on the same side as perinephric haematoma. Case presentation A 56-year-old male with C-4 tetraplegia had undergone implantation of programmable pump in the anterior abdominal wall for intrathecal infusion of baclofen to control spasticity. He developed perinephric haematoma while he was taking warfarin as prophylactic for deep vein thrombosis. Perinephric haematoma became infected with a resistant strain of Pseudomonas aeruginosa, and required percutaneous drainage. Positioning this patient on his abdomen without anaesthesia, for insertion of a catheter from behind, was not a realistic option. Administration of general anaesthesia in this patient in the radiology department would have been hazardous. Results and Conclusion Percutaneous drainage was carried out by anterior approach under propofol sedation. The site of entry of percutaneous catheter was close to cephalic end of baclofen pump. By carrying out drainage from anterior approach, and by keeping this catheter for ten weeks, we took a risk of causing infection of the baclofen pump site, and baclofen pump with a resistant strain of Pseudomonas aeruginosa. The alternative method would have been to anaesthetise the patient and position him prone for percutaneous drainage of perinephric collection from behind. This would have ensured that the drainage track was far away from the baclofen pump with minimal risk of infection of baclofen pump, but at the cost of incurring respiratory complications in a tetraplegic subject.

  13. Modulation of TLR3/TLR4 inflammatory signaling by the GABAB receptor agonist baclofen in glia and immune cells: relevance to therapeutic effects in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Tadhg eCrowley

    2015-07-01

    Full Text Available The GABAB receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in a number of disorders including Multiple Sclerosis (MS, but its precise mechanism of action is unknown. Neuroinflammation drives the central pathology in MS and is mediated by both immunoreactive glial cells and invading lymphocytes. Furthermore, a body of data indicates that the Toll-like receptor (TLR family of innate immune receptors is implicated in MS progression. In the present study we investigated whether modulation of GABAB receptors using baclofen can exert anti-inflammatory effects by targeting TLR3 and(or TLR4-induced inflammatory signaling in murine glial cells and human peripheral blood mononuclear cells (PBMCs isolated from healthy control individuals and patients with the relapse-remitting (RR form of MS. TLR3 and TLR4 stimulation promoted the nuclear sequestration of NF-κB and pro-inflammatory cytokine expression in murine glia, while TLR4, but not TLR3, promoted pro-inflammatory cytokine expression in PBMCs isolated from both healthy donors and RR-MS patients. Importantly, this effect was exacerbated in RR-MS patient immune cells. We present further evidence that baclofen dose-dependently attenuated TLR3- and TLR4-induced inflammatory signaling in primary glial cells. Pre-exposure of PBMCs isolated from healthy donors to baclofen attenuated TLR4-induced TNF-α expression, but did not affect TLR4-induced TNF-α expression in RR-MS patient PBMCs. Interestingly, mRNA expression of the GABAB receptor was reduced in PBMCs from RR-MS donors when compared to healthy controls, an effect that might contribute to the differential sensitivity to baclofen seen in healthy and RR-MS patient cells. Overall these findings indicate that baclofen differentially regulates TLR3 and TLR4 signaling in glia and immune cells, and offers insight on the role of baclofen in the treatment of neuroinflammatory disease states including MS.

  14. Effect of baclofen on liquid and solid gastric emptying in rats Efeito do baclofen no esvaziamento gástrico de líquido e de sólidos em rato

    Directory of Open Access Journals (Sweden)

    Edgard Ferro Collares

    2010-09-01

    Full Text Available CONTEXT: Gamma-aminobutyric acid (GABA is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. OBJECTIVE: To assess the intracerebroventricularly (ICV and intravenously (IV effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. METHODS: Adult male Wistar rats weighing 250-300 g (n = 6-8 animals were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention (%GR 10 and 15 min after orogastric administration of saline and 10% glucose meals, respectively. Baclofen was injected ICV (1 and 2 µg/animal through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 µg/animal or IV (1 and 2 mg/kg immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution ICV or IV. RESULTS: The group of animals receiving baclofen ICV (2 mg/animal presented a significantly lower (PCONTEXTO: O ácido gama-aminobutírico (GABA é um potente neurotransmissor inibitório. Há evidências que receptores GABA>B localizados no complexo dorsal do vago e em fibras aferentes do nervo vago participam no controle da motricidade gastrointestinal. OBJETIVO: Avaliar o efeito intracerebroventricular (ICV e intravenoso (IV do baclofen, um agonista para receptores GABA B, sobre o esvaziamento gástrico de líquidos e de sólidos em ratos. M

  15. Respiratory Function Under Intrathecal Baclofen Therapy in Patients With Spastic Tetraplegia.

    Science.gov (United States)

    Kishima, Haruhiko; Yanagisawa, Takufumi; Goto, Yuko; Oshino, Satoru; Maruo, Tomoyuki; Tani, Naoki; Khoo, Hui Ming; Hosomi, Koichi; Hirata, Masayuki; Yoshimine, Toshiki

    2016-08-01

    Intrathecal baclofen (ITB) therapy is an effective treatment for patients with severe spasticity. However, the effect of ITB therapy on respiratory function has not been reported in detail. In this study we quantitatively analyzed the effects of ITB on the respiratory function of patients with spastic tetraplegia. We retrospectively reviewed 23 patients who were administrated ITB therapy from January 2009 to December 2012. Six of these 23 patients, who had spastic tetraplegia and were able to undergo spirometric testing, were included this study. The spasticity derived from cervical spinal cord injury in four patients and cerebral palsy (CP) in two patients. Patients' Ashworth Scale scores and spirometer measurements obtained before and 1-6 months after the start of ITB therapy were evaluated and compared. Before ITB therapy, %FVC of all six patients was below 80%, and a restrictive respiratory disorder was diagnosed in five patients and a combined respiratory disorder in one patient. Ashworth Scale scores for both the lower and upper extremities improved significantly with ITB therapy. Forced vital capacity (FVC), %FVC, and forced expiratory volume at one sec also improved significantly with ITB therapy. Respiratory disorders were indeed present in our SCI and CP patients with spastic tetraplegia, and the respiratory function of these patients improved with ITB therapy. Our results suggest that ITB therapy is safe and efficacious in patients with spastic tetraplegia and respiratory dysfunction. © 2016 International Neuromodulation Society.

  16. A Novel Skin and Fascia Opening for Subfascial Inserting of Intrathecal Baclofen Pump.

    Science.gov (United States)

    Fiaschi, Pietro; Cama, Armando; Piatelli, Gianluca; Moretti, Paolo; Pavanello, Marco

    2018-02-01

    The aim of this article is to introduce a new skin and fascia opening for intrathecal baclofen pump implantation in the abdomen, with the purpose of reducing complications related to wound breakdown. We introduce a novel way of cutaneous and fascial opening that leads two opposed "L shaped" incisions. This method entails numerous advantages. The first advantage is avoiding the direct alignment of overlapped sutures, which creates a locus minoris resistentiae that can weaken and break under the push of the pump. Another advantage consists of an increased obstruction against deep extension of infective processes from cutaneous origin. The wide opening of the subfascial pocket permits the implantation of any type of pump available, and it reduces complexities in reopening the pouch for pump replacement. It also permits the fastening of all anchoring systems usually present in pumps. Another advantage is the improved possibility of careful muscle cauterization thanks to the wide fascia opening, with reduced risk of postsurgical hematoma. Our results showed a reduction of wound complications with this method. This method could contribute to reducing the rate of wound complications and patient discomfort. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Treatment of severe spacticity in multiple sclerosis by continuous intrathecal baclofen

    Directory of Open Access Journals (Sweden)

    Perić Predrag

    2006-01-01

    Full Text Available Background. Successful treatment of severe spasticity represents an imperative of symptomatic therapy of multiple sclerosis (MS due to a significant improvement of physical, psychic and social rehabilitation of MS patients, as well as a longterm cost savings for the additional treatments of conditions arising from uncontrolled severe spasticity. Continuous intrathecal administration of baclofen (ITB, using a subcutaneously implanted programmable infusion pump, is a minimally invasive, reversible method for the treatment of severe diffuse spasticity of the spinal origin. Case report. The first two cases in our country, treated by ITB due to severe spasticity caused by MS, were reported. Despite the local complications of surgical wound healing above the implanted components of the ITB-system in one patient, the optimal reduction of spasticity the with complete elimination of spastic pain was obtained in both patients. Conclusion. Our initial experiences confirmed ITB as a safe and effective therapeutical option for the treatment of intractable spasticity in patients with MS. Major prerequisites for this were adequate patient selection and good control of the basic disease. The use of the minimal invasive implantation technique and the experience in choosing of the adequate ITB-system components, could successfully prevent the occurrence of local complications related to the impaired healing of the ITB-system implantation site.

  18. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

    Science.gov (United States)

    Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

    2016-01-26

    In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice.

    Science.gov (United States)

    Li, Xia; Risbrough, Victoria B; Cates-Gatto, Chelsea; Kaczanowska, Katarzyna; Finn, M G; Roberts, Amanda J; Markou, Athina

    2013-07-01

    γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory. In addition, the effects of BHF177 were compared with the agonist baclofen. Unlike the anxiolytic chlordiazepoxide, baclofen (0.5, 1.5, and 2.5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or Vogel conflict test. Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen. At the highest dose tested (2.5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i.e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects. BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific. At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze. These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Chronic baclofen therapy improves the blunted growth hormone response to intravenous arginine in subjects with spinal cord injury.

    Science.gov (United States)

    Bauman, W A; Spungen, A M; Zhong, Y G; Tsitouras, P D

    1994-05-01

    Human GH (hGH) secretion is stimulated by vigorous physical activity, whereas immobilization reduces its release. In paralyzed subjects with spinal cord injury (SCI), it has recently been shown that the release of hGH to provocative stimulation and plasma insulin-like growth factor-I (IGF-I) levels are reduced. The acute administration of baclofen, a gamma-aminobutyric acid derivative, has been shown to stimulate hGH release. The present study investigated the effect of chronic administration of baclofen on the provocative testing of hGH secretion and plasma IGF-I levels. Sixteen subjects with SCI were studied; eight subjects were treated (40-80 mg/day; > 6 months) with baclofen (Bac+), and eight were not (Bac-). Additionally, 8 non-SCI subjects were studied as controls. The groups were matched for gender and age. The subjects were not receiving any medications known to influence hGH secretion. After an overnight fast, arginine hydrochloride (30 g/subject) was infused iv over 30 min, with blood drawn for hormone determinations at baseline and 30, 60, 90, and 120 min. In the Bac- group compared with the Bac+ group, the arginine-stimulated mean plasma hGH levels at 30 and 60 min (P hGH levels (P hGH response between the Bac+ group and the control group. Plasma IGF-I levels may reflect the integrated tissue response to hGH. A significant inverse relationship was present between age and plasma IGF-I levels for the control and Bac+ groups, but not for the Bac- group. The mean plasma IGF-I level was significantly reduced in the Bac- compared with the Bac+ group. No significant differences in mean plasma IGF-I levels were noted between the Bac+ and control groups. SCI is associated with body composition changes and metabolic alterations that may be exacerbated by reduced activity of the hGH-IGF-I axis. Oral chronic baclofen therapy appears to reverse the deleterious effects of paralysis and immobilization on hGH physiology.

  1. Does Intrathecal Baclofen Therapy Increase Prevalence and/or Progression of Neuromuscular Scoliosis?

    Science.gov (United States)

    Walker, Kevin R; Novotny, Susan A; Krach, Linda E

    2017-11-01

    Retrospective, case-matched review. Compare a group of individuals with cerebral palsy (CP) who had intrathecal baclofen (ITB) pumps to a group of individuals with CP who did not have ITB pumps in order to determine if there was a difference in the prevalence of new-onset neuromuscular scoliosis, an increased rate of progression of preexisting neuromuscular scoliosis, or an increased rate of posterior spine fusion surgery in skeletally immature individuals with CP who had ITB pumps. Various authors report conflicting findings, with some reporting an increased incidence or prevalence of scoliosis in individuals with CP who have ITB pumps whereas others report no difference in the rate of scoliosis between groups. Retrospective chart and radiographic case-matched study in which individuals were matched by gender and Gross Motor Function Classification Scale (GMFCS) level. We found no difference in the rates of new-onset neuromuscular scoliosis for those with CP and ITB pumps and those without ITB pumps. However, we did see a higher rate of progression as well as an increased rate of posterior spine fusion surgery in individuals with CP who had ITB pumps than for those with CP who did not have an ITB pump. We continue to recommend ITB pump therapy for individuals with severe spasticity associated with CP (GMFCS IV and V). There is a significant risk of complications for individuals in general. The risk of neuromuscular scoliosis is relatively high in this population. Our findings suggest that individuals with CP who have ITB pumps and who do or do not have preexisting scoliosis should be monitored closely for either developing new neuromuscular scoliosis or progression of preexisting scoliosis. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  2. Infection as a Complication of Intrathecal Baclofen Treatment in Children With Cerebral Palsy.

    Science.gov (United States)

    Bayhan, Ilhan A; Sees, Julieanne P; Nishnianidze, Tristan; Rogers, Kenneth J; Miller, Freeman

    2016-01-01

    Children with cerebral palsy (CP) and spasticity are often managed with intrathecal baclofen treatment (ITB). Complications of ITB include infection at the pump or catheter site and late complications as well as revisions of the pump and catheter because of events such as battery expiration or implant malfunction. The goal of this study is to report the short-term and long-term incidence, risk factors, and treatment outcomes of ITB infections in children. This was a retrospective review of 294 children with CP. The number of ITB surgeries per patient, risk of infection for primary and secondary ITB-related procedures, microorganisms responsible, and associated factors, such as concurrent orthopaedic interventions, medical comorbidities, and subsequent management of ITB-related infections, were evaluated. Infection occurred in 28/294 patients (9.5%) with a 4.9% rate per procedure. There were 14 acute (within 90 d of surgery) and 14 late infections. The infection risk per ITB procedure was 2.4%. Risk of late infection over 5-year mean follow-up was 0.95% per year. Pump removal with acute contralateral implantation was the most successful treatment of infections. Gross Motor Function Classification System level V and G-tube were the main risk factors for infection. A total of 133 concurrent orthopaedic procedures were performed during 277 ITB procedures with no increased risk of infection. ITB in children with CP has a relatively low and manageable risk of infection. It is important to always consider infection as a complication with ITB because with prompt treatment the positive impact of ITB is still possible. It is safe to perform concurrent orthopaedic procedures with ITB procedures. Level III-therapeutic study.

  3. Neurosurgical Management of Childhood Spasticity: Functional Posterior Rhizotomy and Intrathecal Baclofen Infusion Therapy

    Science.gov (United States)

    MOROTA, Nobuhito; IHARA, Satoshi; OGIWARA, Hideki

    2015-01-01

    A paradigm shift is currently ongoing in the treatment of spasticity in childhood in Japan. Functional posterior rhizotomy (FPR), which was first introduced to Japan in 1996, is best indicated for children with spastic cerebral palsy, regardless of the clinical severity of spasticity. Surgery is generally carried out in the cauda equina, where the posterior root is separated from the anterior one, and neurophysiological procedures are used to judge which nerve root/rootlet should be cut. The outcome of FPR is favorable for reducing spasticity in the long-term follow-up. Intrathecal baclofen (ITB) treatment for childhood spasticity was approved in 2007 in Japan and the number of children undergoing ITB pump implantation has been gradually increasing. ITB treatment is best indicated for children with severe spasticity, especially those with dystonia, regardless of the pathological background. Since it is a surgery performed to implant foreign bodies, special attention should be paid to avoid perioperative complications such as CSF leakage, meningitis, and mechanical failure. Severely disabled children with spasticity would benefit most from ITB treatment. We would especially like to emphasize the importance of a strategic approach to the treatment of childhood spasticity. The first step is to reduce spasticity by FPR, ITB, and botulinum toxin injection. The second step is to aim for functional improvement after controlling spasticity. Traditional orthopedic surgery and neuro-rehabilitation form the second step of treatment. The combination of these treatments that allows them to complement each other is the key to a successful treatment of childhood spasticity. PMID:26227057

  4. Differential effects of sodium oxybate and baclofen on EEG, sleep, neurobehavioral performance, and memory.

    Science.gov (United States)

    Vienne, Julie; Lecciso, Gianpaolo; Constantinescu, Irina; Schwartz, Sophie; Franken, Paul; Heinzer, Raphaël; Tafti, Mehdi

    2012-08-01

    Sodium oxybate (SO) is a GABAβ agonist used to treat the sleep disorder narcolepsy. SO was shown to increase slow wave sleep (SWS) and EEG delta power (0.75-4.5 Hz), both indexes of NREM sleep (NREMS) intensity and depth, suggesting that SO enhances recuperative function of NREM. We investigated whether SO induces physiological deep sleep. SO was administered before an afternoon nap or before the subsequent experimental night in 13 healthy volunteers. The effects of SO were compared to baclofen (BAC), another GABAβ receptor agonist, to assess the role of GABAβ receptors in the SO response. As expected, a nap significantly decreased sleep need and intensity the subsequent night. Both drugs reversed this nap effect on the subsequent night by decreasing sleep latency and increasing total sleep time, SWS during the first NREMS episode, and EEG delta and theta (0.75-7.25 Hz) power during NREMS. The SO-induced increase in EEG delta and theta power was, however, not specific to NREMS and was also observed during REM sleep (REMS) and wakefulness. Moreover, the high levels of delta power during a nap following SO administration did not affect delta power the following night. SO and BAC taken before the nap did not improve subsequent psychomotor performance and subjective alertness, or memory consolidation. Finally, SO and BAC strongly promoted the appearance of sleep onset REM periods. The SO-induced EEG slow waves seem not to be functionally similar to physiological slow waves. Our findings also suggest a role for GABAβ receptors in REMS generation.

  5. Improved Gait Performance in a Patient With Hereditary Spastic Paraplegia After a Continuous Intrathecal Baclofen Test Infusion and Subsequent Pump Implantation : A Case Report

    NARCIS (Netherlands)

    Heetla, Herre W.; Halbertsma, Jan P.; Dekker, Rienk; Staal, Michiel J.; van Laar, Teus

    Objective: To show the benefits of a continuous intrathecal baclofen (ITB) test infusion in a patient with hereditary spastic paraplegia (HSP), with an improved gait performance after ITB pump implantation. Design: Case report. Setting: University hospital. Participant: A 49-year old man with HSP

  6. Long-term follow-up on continuous intrathecal Baclofen therapy in non-ambulant children with intractable spastic Cerebral Palsy

    NARCIS (Netherlands)

    Vles, G.F.; Soudant, D.L.; Hoving, M.A.; Vermeulen, R.J.; Bonouvrié, L.A.; van Oostenbrugge, R.J.; Vles, J.S.

    2013-01-01

    Background: Little is known about the long-term effects of Continuous intrathecal Baclofen (CITB) therapy in non-ambulant children with intractable spastic Cerebral Palsy (CP). Aim: To determine whether short-term beneficial effects of CITB therapy are present at the long-term, and whether

  7. The gamma-aminobutyric acid type B (GABAB receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Fu Zhenyu

    2012-07-01

    Full Text Available Abstract Background Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. Methods We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. Results The present study demonstrated that morphine challenge (3 mg/kg, s.c. obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Conclusions Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.

  8. Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin

    NARCIS (Netherlands)

    Zahavi, A; Geertzen, JHB; Middel, B; Staal, M; Rietman, JS

    2004-01-01

    Objectives: To evaluate long term change in impairment, disability, and health related functional status in patients with severe spasticity who received intrathecal baclofen. Methods: A long term ( more than five years) observational longitudinal follow up study assessing 21 patients who received

  9. Effect of intrathecal baclofen delivered by an implanted programmable pump on health related quality of life in patients with severe spasticity

    NARCIS (Netherlands)

    Middel, B.; Kuipers-Upmeijer, H.; Bouma, J.; Staal, M.J.; Oenema, D.G.; Postma, T.J.B.M.; Terpstra, S.; Stewart, R.

    Objectives-To compare clinical effectiveness and health related quality of life in patients with severe spasticity who received intrathecal baclofen or a placebo. Methods-In a double blind, randomised, multicentre trial 22 patients were followed up during 13 weeks and subsequently included in a 52

  10. Comparison of long-term outcomes of patients with severe traumatic or hypoxic brain injuries treated with intrathecal baclofen therapy for dysautonomia.

    Science.gov (United States)

    Hoarau, Xavier; Richer, Edwidge; Dehail, Patrick; Cuny, Emmanuel

    2012-01-01

    To compare the long-term outcome of patients with severe traumatic brain injury and patients with hypoxic brain injury with dysautonomia and hypertonia treated with intrathecal baclofen therapy. Fifty-three patients with severe traumatic (n = 43/53) or hypoxic (n = 10/53) brain injuries treated by intrathecal baclofen therapy were included to be evaluated with the Coma Recovery Scale-Revised, the Barthel Index, the Glasgow Outcome Scale, the Ashworth scale, the scores of hypertonic attacks, of sweating episode and of voluntary motor responses. A retrospective analysis highlighted patients' characteristics at admission and before surgery and their complications. After a mean follow-up time of 9.6 years, 13/53 (24.5%) patients had died. Alive patients with traumatic brain injury had a higher level of consciousness recovery (p dysautonomia and limb hypertonia also significantly improved, contrary to patients with hypoxic brain injury who needed higher doses of baclofen (p dysautonomia associated with uncontrolled hypertonia, despite the use of intrathecal baclofen.

  11. Intrathecal baclofen pumps do not accelerate progression of scoliosis in quadriplegic spastic cerebral palsy.

    Science.gov (United States)

    Rushton, Paul R P; Nasto, Luigi A; Aujla, Ranjit K; Ammar, Amr; Grevitt, Michael P; Vloeberghs, Michael H

    2017-06-01

    To compare scoliosis progression in quadriplegic spastic cerebral palsy with and without intrathecal baclofen (ITB) pumps. A retrospective matched cohort study was conducted. Patients with quadriplegic spastic cerebral palsy, GMFCS level 5, treated with ITB pumps with follow-up >1 year were matched to comparable cases by age and baseline Cobb angle without ITB pumps. Annual and peak coronal curve progression, pelvic obliquity progression and need for spinal fusion were compared. ITB group: 25 patients (9 female), mean age at pump insertion 9.4 and Risser 0.9. Initial Cobb angle 25.6° and pelvic tilt 3.2°. Follow-up 4.3 (1.0-7.8) years. Cobb angle at follow-up 76.1° and pelvic tilt 18.9°. Non-ITB group: 25 patients (14 female), mean age at baseline 9.2 and Risser 1.0. Initial Cobb angle 29.7° and pelvic tilt 7.1°. Follow-up 3.5 (1.0-7.5) years. Cobb angle at follow-up 69.1° and pelvic tilt 21.0°. The two groups were statistically similar for baseline age, Cobb angle and Risser grade. Mean curve progression was 13.6°/year for the ITB group vs 12.6°/year for the non-ITB group (p = 0.39). Peak curve progression was similar between the groups. Pelvic tilt progression was comparable; ITB group 4.5°/year vs non-ITB 4.6°/year (p = 0.97). During follow-up 5 patients in the ITB group and 9 in the non-ITB group required spinal fusion surgery for curve progression (p = 0.35). Patients with quadriplegic spastic cerebral palsy with and without ITB pumps showed significant curve progression over time. ITB pumps do not appear to alter the natural history of curve progression in this population.

  12. Early outcomes after intrathecal baclofen therapy in ambulatory patients with multiple sclerosis.

    Science.gov (United States)

    Lee, Bryan S; Jones, Jaes; Lang, Min; Achey, Rebecca; Dai, Lu; Lobel, Darlene A; Nagel, Sean J; Machado, Andre G; Bethoux, Francois

    2017-12-01

    OBJECTIVE Multiple sclerosis (MS) is a chronic autoimmune disease that causes demyelination and axonal loss. Walking difficulties are a common and debilitating symptom of MS; they are usually caused by spastic paresis of the lower extremities. Although intrathecal baclofen (ITB) therapy has been reported to be an effective treatment for spasticity in MS, there is limited published evidence regarding its effects on ambulation. The goal of this study was to characterize ITB therapy outcomes in ambulatory patients with MS. METHODS Data from 47 ambulatory patients with MS who received ITB therapy were analyzed retrospectively. Outcome measures included Modified Ashworth Scale, Spasm Frequency Scale, Numeric Pain Rating Scale, and the Timed 25-Foot Walk. Repeated-measures ANOVA was used to test for changes in outcome measures between baseline and posttreatment (6 months and 1 year). Significance was set at p Ashworth Scale scores (from 14.8 ± 1.0 before ITB therapy to 5.8 ± 0.8 at 6 months posttreatment and 6.4 ± 0.9 at 1 year [p Scale scores (4.4 ± 0.5 before ITB, 2.8 ± 0.5 at 6 months, and 2.4 ± 0.4 at 1 year [p < 0.05]); 3) spasm frequency (45.7% of the patients reported a spasm frequency of ≥ 1 event per hour before ITB therapy, whereas 15.6% and 4.3% of the patients reported the same at 6 months and 1 year posttreatment, respectively [p < 0.05]); and 4) the number of oral medications taken for spasticity (p < 0.05). Of the 47 patients, 34 remained ambulatory at 6 months, and 32 at 1 year posttreatment. There was no statistically significant change in performance on the Timed 25-Foot Walk test over time for those patients who remained ambulatory. CONCLUSIONS In this retrospective study, the authors found that ITB therapy is effective in reducing spasticity and related symptoms in ambulatory patients with MS. Because the use of ITB therapy is increasing in ambulatory patients with MS, randomized, prospective studies are important to help provide a more useful

  13. Outcomes of intrathecal baclofen therapy in patients with cerebral palsy and acquired brain injury.

    Science.gov (United States)

    Yoon, Young Kwon; Lee, Kil Chan; Cho, Han Eol; Chae, Minji; Chang, Jin Woo; Chang, Won Seok; Cho, Sung-Rae

    2017-08-01

    Intrathecal baclofen (ITB) has been known to reduce spasticity which did not respond to oral medications and botulinum toxin treatment. However, few results have been reported comparing the effects of ITB therapy in patients with cerebral palsy (CP) and acquired brain injury. This study aimed to investigate beneficial and adverse effects of ITB bolus injection and pump therapy in patients with CP and to compare outcomes to patients with acquired brain injury such as traumatic brain injury and hypoxic brain injury. ITB test trials were performed in 37 patients (19 CP and 18 acquired brain injury). Based on ambulatory function, CP patients were divided into 2 groups: 11 patients with nonambulatory CP and 8 patients with ambulatory CP. Change of spasticity was evaluated using the Modified Ashworth Scale. Additional positive or negative effects were also evaluated after ITB bolus injection. In patients who received ITB pump implantation, outcomes of spasticity, subjective satisfaction and adverse events were evaluated until 12 months post-treatment. After ITB bolus injection, 32 patients (86.5%) (CP 84.2% versus acquired brain injury 88.9%) showed a positive response of reducing spasticity. However, 8 patients with CP had negative adverse effects. Particularly, 3 ambulatory CP patients showed standing impairment and 1 ambulatory CP patient showed impaired gait pattern such as foot drop because of excessive reduction of lower extremity muscle tone. Ambulatory CP patients received ITB pump implantation less than patients with acquired brain injury after ITB test trials (P = .003 by a chi-squared test). After the pump implantation, spasticity was significantly reduced within 1 month and the effect maintained for 12 months. Seventeen patients or their caregivers (73.9%) were very satisfied, whereas 5 patients (21.7%) suffered from adverse events showed no subjective satisfaction. In conclusion, ITB therapy was effective in reducing spasticity in patients with CP and

  14. Intrathecal baclofen: effects on spasticity, pain, and consciousness in disorders of consciousness and locked-in syndrome.

    Science.gov (United States)

    Pistoia, Francesca; Sacco, Simona; Sarà, Marco; Franceschini, Marco; Carolei, Antonio

    2015-01-01

    Disorders of consciousness (DOCs) include coma, vegetative state (VS), and minimally conscious state (MCS). Coma is characterized by impaired wakefulness and consciousness, while VS and MCS are defined by lacking or discontinuous consciousness despite recovered wakefulness. Conversely, locked-in syndrome (LIS) is characterized by quadriplegia and lower cranial nerve paralysis with preserved consciousness. Intrathecal baclofen (ITB) is a useful treatment to improve spasticity both in patients with DOCs and LIS. Moreover, it supports the recovery of consciousness in some patients with VS or MCS. The precise mechanism underlying this recovery has not yet been elucidated. It has been hypothesized that ITB may act by reducing the overload of dysfunctional sensory stimuli reaching the injured brain or by stabilizing the imbalanced circadian rhythms. Although the current indication of ITB is the management of severe spasticity, its potential use in speeding the recovery of consciousness merits further investigation.

  15. Regional anesthesia for a total knee arthroplasty on an adult patient with spastic diplegia and an intrathecal baclofen pump.

    Science.gov (United States)

    Bojaxhi, Elird; Salek, David R; Sherman, Courtney E; Greengrass, Roy A

    2017-04-01

    We describe the clinical presentation of a patient with spastic diplegia, and its unique perioperative challenges. Opioids and antispasmodic medications are the primary therapy for managing pain and spasticity in the perioperative setting. However, such combination results in several side-effects and their sedative properties are synergistic. A 64-year-old woman with a history of spastic diplegia and an intrathecal baclofen pump for the treatment of her lower extremity spasticity was scheduled for a third elective left knee arthroplasty. She requested a regional anesthetic for the anticipated surgery and an opioid sparing postoperative analgesic regiment. We describe the successful use of a lumbar plexus and a sciatic nerve block as the primary anesthetic for the surgery and the use of a continuous lumbar plexus catheter for the postoperative course. Based on our patient's past anesthetic history, a regional anesthetic/analgesic technique is the ideal strategy in controlling perioperative pain and spasticity.

  16. Long-Term Dosing of Intrathecal Baclofen in the Treatment of Spasticity After Acquired Brain Injury.

    Science.gov (United States)

    Maneyapanda, Mithra B; McCormick, Zachary L; Marciniak, Christina; Reger, Christopher

    2017-06-01

    Intrathecal baclofen (ITB) often is used to treat severe spasticity of cerebral origin. Although literature exists regarding the efficacy of ITB, there has been minimal investigation related to dosing in the adult-acquired brain injury population, particularly at long-term duration. To investigate long-term dosing of ITB in adult patients with spasticity of cerebral origin due traumatic brain injury (TBI), stroke, and hypoxic-ischemic encephalopathy (HIE). Retrospective cohort study. An academic outpatient rehabilitation clinic. Forty-two adult patients with spasticity secondary to TBI, stroke, or HIE treated with ITB for greater than 3 years. Medical records and device manufacturer records of included patients were reviewed to obtain demographic data, dosing information, dates of pump and catheter placements, and revisions. Average daily ITB doses and mean change in ITB dose over 1, 2, and 3 years. Goal of ITB treatment (active function versus comfort/care/positioning) also was compared. Of 42 total patients, spasticity was attributed to either TBI (n = 19), stroke (n = 11), or HIE (n = 12). The mean (standard deviation) age was 35.21 (10.17), 56.7 (13.1), and 35.1 (12.4) years for the TBI, stroke, and HIE groups, respectively (P < .001). There was a significant difference in the goal of therapy with "improving functional independence," accounting for 27.8%, 72.8%, and 0% in the TBI, stroke, and HIE groups, respectively (P = .002). The mean duration of ITB therapy was 8.5 (5.0), 7.8 (3.4), and 9.1 (4.6) years in the TBI, stroke, and HIE groups, respectively (P = .79). The mean daily ITB dose was 596.9 (322.8) μg/d, 513.2 (405.7) μg/d, and 705.2 (271.7) μg/d for the TBI, stroke, and HIE groups, respectively (P = .39). In the subset of the cohort with ITB therapy for more than 5 years, the mean percent change in daily ITB dose between time of chart review and 1, 2, and 3 years previously was 7.3% (13.6), 12.7% (16), and 24.7% (50.3), respectively. A complex

  17. R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice.

    Science.gov (United States)

    Stoppel, Laura J; Kazdoba, Tatiana M; Schaffler, Melanie D; Preza, Anthony R; Heynen, Arnold; Crawley, Jacqueline N; Bear, Mark F

    2018-02-01

    Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ~27 genes, 16p11.2 microdeletion syndrome is characterized by ID, impaired language, communication and socialization skills, and ASD. Studies in animal models where a single copy of the syntenic 16p11.2 region has been deleted have revealed morphological, behavioral, and electrophysiological abnormalities. Previous studies suggested the possibility of some overlap in the mechanisms of pathophysiology in 16p11.2 microdeletion syndrome and fragile X syndrome. Improvements in fragile X phenotypes have been observed following chronic treatment with R-baclofen, a selective agonist of GABA B receptors. We were therefore motivated to investigate the effects of chronic oral R-baclofen administration in two independently generated mouse models of 16p11.2 microdeletion syndrome. In studies performed across two independent laboratories, we found that chronic activation of GABA B receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models. Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome.

  18. A 10-year follow-up study of patients with severe traumatic brain injury and dysautonomia treated with intrathecal baclofen therapy.

    Science.gov (United States)

    Hoarau, Xavier; Richer, Edwige; Dehail, Patrick; Cuny, Emmanuel

    2012-01-01

    To describe the long-term disorders of consciousness in patients with dysautonomia and hypertonia treated with intrathecal baclofen therapy (IBT). Forty-three patients with severe traumatic brain injuries who were previously implanted with an intrathecal baclofen pump were included to be evaluated in the long-term with the Coma Recovery Scale-Revised. The Barthel Index, the Glasgow Outcome Scale, the Ashworth scale, the scores of hypertonic attacks, of sweating episodes and of voluntary motor responses were used to describe functional abilities and residual impairments. A retrospective analysis highlighted patients' characteristics at admission, before surgery and their complications. After a mean follow-up of 10 years, nine of 43 (20.9%) patients had died, 13/43 (30.2%) patients were severely disabled or in an unresponsive wakefulness syndrome and 21/43 (48.8%) patients had good recovery of consciousness. The latter patients tended to receive IBT later, suggesting a later development of uncontrolled symptoms of dysautonomia and hypertonia. They needed lower doses of baclofen, suggesting that they had less severe symptoms. Their dysautonomia, limb hypertonia and voluntary motor responses improved significantly compared to patients with poor outcome. Recovery of good long-term consciousness is possible. A low level of consciousness recovery and the early development of severe and persistent symptoms of dysautonomia associated with hypertonia could be linked to poor long-term outcome.

  19. Is it time for baclofen to be included in the official recommendations concerning the treatment of alcoholism?

    Directory of Open Access Journals (Sweden)

    Masternak Sebastian

    2016-06-01

    Full Text Available Alcohol dependence and its treatment is not an exactly resolved problem. Based on the EZOP [Epidemiology of Mental Disorders and Accessibility of Mental Health Care] survey, which included a regular analysis of the incidence of mental disorders in the population of adult Polish citizens, we were able to estimate that the problem of alcohol abuse in any period of life affects even 10.9% of the population aged 18-64 years, and those addicted represent 2.2% of the country’s population. The typical symptoms of alcohol dependence according to ICD-10, include alcohol craving, impaired ability to control alcohol consumption, withdrawal symptoms which appear when a heavy drinker stops drinking, alternating alcohol tolerance, growing neglect of other areas of life, and persistent alcohol intake despite clear evidence of its destructive effect on life. At the moment, the primary method of alcoholism treatment is psychotherapy. It aims to change the patient’s habits, behaviours, relationships, or the way of thinking. It seems that psychotherapy is irreplaceable in the treatment of alcoholism, but for many years now attempts have been made to increase the effectiveness of alcoholism treatment with pharmacological agents. In this article we will try to provide a description of medications which help patients sustain abstinence in alcoholism therapy with particular emphasis on baclofen.

  20. Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France.

    Science.gov (United States)

    Auffret, Marine; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Cottencin, Olivier; Bordet, Régis; Gautier, Sophie; Rolland, Benjamin

    2017-03-01

    Off-label prescribing (OLP) may raise serious safety concerns that traditional spontaneous reporting of adverse drug reactions (ADRs) may not identify in a timely manner. In France, the 'Multidisciplinary Consultation Service for Off-Label Prescribing in Addiction Medicine' (CAMTEA) is a proactive regional system established to identify ADRs associated with the OLP of baclofen for alcohol dependence. The aim was to demonstrate, using the French pharmacovigilance database (FPVD), that CAMTEA allowed for the reporting of a substantial amount of ADRs, comparable in nature to those provided via spontaneous reporting. The 2012-2013 FPVD notifications associated with baclofen OLP were extracted. The ten most frequent types of ADRs among 'serious' and 'non-serious' reports were listed. The frequency of each type of ADR was compared between CAMTEA and spontaneous reporting, and the magnitudes of the differences were assessed using standardized differences. A total of 428 baclofen reports (1043 ADRs) were identified, among which 221 (51.64%) originated from CAMTEA. The ten most frequent ADRs in 'serious' reports were (1) confusion (17.3%), (2) seizures (11.5%), (3) drowsiness/sedation (11.5%), (4) agitation (10.9%), (5) coma (9.6%), (6) hallucinations (7.7%), (7) falls (7.1%), (8) behavioral disorders (5.8%), (9) withdrawal syndrome (5.1%), and (10) space-time disorientation (5.1%). A standardized difference of pharmacovigilance system could collect a substantial amount of safety data on a specific OLP practice. The profile of the ADRs collected was similar to that seen in the nationwide spontaneous reporting system.

  1. An algorithmic approach to the management of unrecognized hydrocephalus in pediatric candidates for intrathecal baclofen pump implantation.

    Science.gov (United States)

    Hanak, Brian W; Tomycz, Luke; Oxford, Robert G; Hooper, Erin; Apkon, Susan D; Browd, Samuel R

    2016-01-01

    Complications of intrathecal baclofen (ITB) pump implantation for treatment of pediatric patients with spasticity and dystonia associated with cerebral palsy remain unacceptably high. To address the concern that some patients may have underlying arrested hydrocephalus, which is difficult to detect clinically because of a low baseline level of neurological function, and may contribute to the high rates of postoperative cerebrospinal fluid leak, wound breakdown, and infection associated with ITB pump implantation, the authors implemented a standardized protocol including mandatory cranial imaging and assessment of intracranial pressure (ICP) by lumbar puncture prior to ITB pump implantation. A retrospective case series of patients considered for ITB pump implantation between September 2012 and October 2014 at Seattle Children's Hospital is presented. All patients underwent lumbar puncture under general anesthesia prior to ITB pump implantation and, if the opening pressure was greater than 21 cmH 2 O, ITB pump implantation was aborted and alternative management options were presented to the patient's family. Eighteen patients were treated during the study time period. Eight patients (44.4%) who had ICPs in excess of 21 cmH 2 O on initial LP were identified. Eleven patients (61.1%) ultimately underwent ITB pump implantation (9/10 in the "normal ICP" group and 2/8 in the "elevated ICP" group following ventriculoperitoneal shunt placement), without any postoperative complications. Given the potentially high rate of elevated ICP and arrested hydrocephalus, the authors advocate pre-implantation assessment of ICP under controlled conditions and a thoughtful consideration of the neurosurgical management options for patients with elevated ICP.

  2. Treatment of severe, disabling spasticity with continuous intrathecal baclofen therapy following acquired brain injury: the experience of a tertiary institution in Singapore.

    Science.gov (United States)

    Wang, Zhe Min; Law, Jia Hao; King, Nicolas Kon Kam; Rajeswaran, Deshan Kumar; Soh, Samantha; Rao, Jai Prashanth; Ng, Wai Hoe; Chua, Karen Sui Geok

    2016-01-01

    Intrathecal baclofen (ITB) therapy is a proven, effective treatment for disabling cortical spasticity. We describe the first local series of five patients with acquired brain injury (ABI) who received ITB and were followed up for 63.8 months. A retrospective review of medical and rehabilitation records of patients who received ITB therapy was carried out. Data studied included baseline demographic and injury variables, implantation data, spasticity and function, ITB dosage over time and complications. From 2006 to 2010, a total of five patients received ITB therapy via implanted pumps about 39.4 months after ABI. Four out of five patients experienced significant reductions in their lower limb spasticity scores and improvements in global function and dependency. One patient had minor adverse events associated with baclofen-related sedation. The mean ITB dose at one year was 182.7 ± 65.6 mcg/day. Our preliminary study showed encouraging long-term outcomes and safety for ITB therapy after ABI-related intractable spasticity. Individual ITB responses over time were variable, with gender differences. The outcomes experienced by our centre were comparable to those in the general ABI population, supporting the efficacy of ITB therapy for chronic disabling spasticity. Copyright © Singapore Medical Association.

  3. Co-application of the GABAB receptor agonist, baclofen, and the mGlu receptor agonist, L-CCG-I, facilitates [(3)H]GABA release from rat cortical nerve endings.

    Science.gov (United States)

    Samengo, Irene A; Scotti, Valerio; Martire, Maria

    2013-12-01

    Interaction between different transmitter receptor systems is an emerging feature of neurotransmission at central synapses. G protein-coupled receptors' ability to form dimers or larger hetero-oligomers probably serves to facilitate the integration of diverse signals within the cell. We found that, in nerve terminals isolated from the cerebral cortices of rats, co-application of the GABAB agonist, baclofen, and of the non-selective mGlu agonist, L-CCG-I, potentiates the basal and depolarization-evoked release of [(3)H]GABA via a mechanism that involves mobilization of intracellular Ca(2+) ions. The effect of L-CCG-I + baclofen was abolished by the phospholipase C inhibitor U73122, reduced by Xestospongin C (an IP3 receptor blocker), and blocked by 2-APB, an IP3 receptor antagonist. Pretreatment of the synaptosomes with the lipid-soluble Ca(2+) chelator BAPTA-AM also inhibited the effects of L-CCG-I + baclofen. Subtype-selective non-competitive group I mGlu receptor antagonists, MPEP and CPCCOEt, had no effect on the release enhancement produced by baclofen + L-CCG-I. The enhancement was reversed by the GABAB receptor antagonist, CGP54626, and by the group I/group II mGlu receptor antagonist (R,S)-MCPG. The GABA release-enhancing effects of L-CCG-I + baclofen in our model might reflect the presence on cortical nerve endings of GABAB/group I mGlu receptor heteromers with pharmacological properties distinct from those of the component receptors. Activation of these heteromeric receptors might modify the function of the GABAB receptor in such a way that it facilitates GABAergic transmission, an effect that might be useful under conditions of excessive glutamatergic activity.

  4. Intrathecal Baclofen: a discussion on impact that medical advances can have on the individual and the implications this has for a society that is built on an ethic of social medicine.

    Science.gov (United States)

    Baddeley, Anika A

    2008-01-01

    The intention of this article is to examine the impact of medical advances and new medical technologies on the lives of individuals with disabilities and chronic illness. It looks at the problem of balancing social expectation, cost and individuals quality of life. A personal case study that looks at the use of Intrathecal Baclofen to relieve the spasticity related to cerebral palsy; improving personal function and enhancing quality of life. Advances in medical technology such as Intrathecal Baclofen can undoubtedly greatly enhance quality of life. We live in a society that has heath provision at its heart and an expectation that all needs will be met. With ever more costly treatments, will it ultimately prove to be need or cost that will define health treatment in the future?

  5. The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain Efeito do baclofeno sobre a expressão comportamental espontânea e evocada da dor crônica neuropática experimental

    Directory of Open Access Journals (Sweden)

    TEREZINHA DE JESUS T. SANTOS

    1999-09-01

    Full Text Available Baclofen (beta-p-chlorophenyl-GABA has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988, taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p O baclofeno (beta-p-clorofenil-GABA é usado em seres humanos para tratar espasticidade, assim como neuralgia do trigêmeo. Como o GABA (ácido amino-gama-butírico tem sido implicado em efeitos inibitórios e analgésicos no sistema nervoso, tornou-se de interesse estudar o efeito do baclofeno em dor neuropática experimental. Com esse objetivo, foram realizados experimentos em 17 ratos neuropáticos com lesão constritiva do nervo ciático, como descrito por Bennet e Xie (1988, tomando como parâmetros de dor o comportamento de coçar-se (scratching e a latência ao estímulo térmico nociceptivo. Os resultados mostraram que o baclofeno induziu, de forma dose-dependente, diminuição significativa (p < 0,05 do comportamento de coçar-se e aumento significativo (p < 0,05 da latência ao estímulo térmico nociceptivo. A ausência de antagonismo pela naloxona sugere a não participação de mecanismo opióide-mediado nesse efeito analgésico do baclofeno em dor neuropática experimental.

  6. Anticonvulsant action of GABA-B receptor agonist SKF97541 Differs from that of Baclofen

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel

    2008-01-01

    Roč. 57, č. 5 (2008), s. 789-792 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/05/2581 Institutional research plan: CEZ:AV0Z50110509 Keywords : PTZ seizures * GABA -B * ontogeny Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

  7. Preparation of (+)- and (-)- β-phenyl- and β-(4-chlorophenyl)-γ- butyro lactones: Key intermediates in the synthesis of β-phenyl-Gaba and baclofene

    International Nuclear Information System (INIS)

    Gomez G, J.; Melendez R, M.; Suarez C, O. R.; Castelan D, L. E.; Fragoso V, M. J.; Lopez V, E.; Sanchez Z, M.

    2014-01-01

    the preparation of β-phenyl- and β-(4-chlorophenyl)-γ-butyro lactones (±)-4 and their resolution to the corresponding (+)-(S)-3, (-)-(R)-3 and (+)-(S)-4, (-)-(R)-4 through formation, flash column chromatography separation and subsequent hydrolysis of dia stereoisomeric 4-hydroxybutyramide s (2'R,3S)-5, (2'R,3R)-5, (2'R,3S)-6 and (2'R,3R)-6 is described. The absolute configuration assignment of enantiopure 3 and 4 was supported by X-ray crystallographic structures of (2'R,3R)-5, (2'R,3S)-6 and (2'R,3R)-6. (Author)

  8. Preparation of (+)- and (-)- β-phenyl- and β-(4-chlorophenyl)-γ- butyro lactones: Key intermediates in the synthesis of β-phenyl-Gaba and baclofene

    Energy Technology Data Exchange (ETDEWEB)

    Gomez G, J.; Melendez R, M.; Suarez C, O. R.; Castelan D, L. E.; Fragoso V, M. J.; Lopez V, E.; Sanchez Z, M., E-mail: melendez@uaeh.edu.mx [Universidad Autonoma del Estado de Hidalgo, Area Academica de Quimica, Carretera Pachuca-Tulancingo Km. 4.5, Mineral de la Reforma 42184, Hidalgo (Mexico)

    2014-07-01

    the preparation of β-phenyl- and β-(4-chlorophenyl)-γ-butyro lactones (±)-4 and their resolution to the corresponding (+)-(S)-3, (-)-(R)-3 and (+)-(S)-4, (-)-(R)-4 through formation, flash column chromatography separation and subsequent hydrolysis of dia stereoisomeric 4-hydroxybutyramide s (2'R,3S)-5, (2'R,3R)-5, (2'R,3S)-6 and (2'R,3R)-6 is described. The absolute configuration assignment of enantiopure 3 and 4 was supported by X-ray crystallographic structures of (2'R,3R)-5, (2'R,3S)-6 and (2'R,3R)-6. (Author)

  9. Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice

    OpenAIRE

    Li, Xia; Risbrough, Victoria B.; Cates-Gatto, Chelsea; Kaczanowska, Katarzyna; Finn, M. G.; Roberts, Amanda J; Markou, Athina

    2013-01-01

    γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicy...

  10. Wilson Disease

    Science.gov (United States)

    ... tremor may include anticholinergics, tizanidine, baclofen, levodopa, or clonazepam. × Treatment WD requires lifelong treatment, generally using drugs ... tremor may include anticholinergics, tizanidine, baclofen, levodopa, or clonazepam. View Full Treatment Information Definition Wilson disease (WD) ...

  11. GABA-B receptor activation and conflict behavior

    International Nuclear Information System (INIS)

    Ketelaars, C.E.J.; Bollen, E.L.; Rigter, H.; Bruinvels, J.

    1988-01-01

    Baclofen and oxazepam enhance extinction of conflict behavior in the Geller-Seifter test while baclofen and diazepam release punished behavior in Vogel's conflict test. In order to investigate the possibility that the effect of the selective GABA-B receptor agonist baclofen is mediated indirectly via the GABA-A/benzodiazepine receptor complex, the effect of pretreatment of rats with baclofen on [ 3 H]-diazepam binding to washed and unwashed cortical and cerebellar membranes of rats has been studied. Baclofen pretreatment increase Bmax in washed cerebellar membranes when bicuculline was present in the incubation mixture. No effect was seen in cortical membranes. The present results render it unlikely that the effect of baclofen on extinction of conflict behavior and punished drinking is mediated via the GABA-A/benzodiazepine receptor complex. 50 references, 1 figure, 4 tables

  12. Celiac Family Health Education Video Series

    Medline Plus

    Full Text Available ... Heart Syndrome Go to all conditions» Treatments Baclofen Pump Liver Transplant Bladder Augmentation Go to all treatments» ... Heart Syndrome Go to all conditions» Treatments Baclofen Pump Liver Transplant Bladder Augmentation Go to all treatments» ...

  13. Intratekal baclofenbehandling ved svaer spastisk tetraplegi og dystoni hos børn og unge

    DEFF Research Database (Denmark)

    Illum, Niels Ove; Hansen, Flemming Juul; Fischer, Claudia

    2003-01-01

    with baclofen, tizanidine, dantrolene and/or diazepam. Intrathecal baclofen has therefore been applied in a group of young patients. MATERIAL AND METHODS: Eight children and young adults from East Denmark with spasticity and 12 with dystonia aged 3-18 years (median 10.9 years) were tested, operated and treated...

  14. Celiac Family Health Education Video Series

    Medline Plus

    Full Text Available ... Conditions Inguinal Hernia ACL Tear Hypoplastic Left Heart Syndrome Go to all conditions» Treatments Baclofen Pump Liver ... Conditions Inguinal Hernia ACL Tear Hypoplastic Left Heart Syndrome Go to all conditions» Treatments Baclofen Pump Liver ...

  15. Hypertonia

    Science.gov (United States)

    ... in a variety of directions. View Full Definition Treatment Muscle relaxing drugs such as baclofen, diazepam, and dantrolene may be prescribed to reduce spasticity. All of these drugs can be taken by ...

  16. Primary Lateral Sclerosis

    Science.gov (United States)

    ... as baclofen, tizanidine, and the benzodiazepines may reduce spasticity. Other drugs may relieve pain and antidepressants can help treat depression. Physical therapy, occupational therapy, and rehabilitation may prevent joint immobility ...

  17. Author Details

    African Journals Online (AJOL)

    1983) - Articles Treatment of writer's cramp with sodium valproate and baclofen. Abstract PDF · Vol 68, No 17 (1983) - Articles Parkinsonism secondary to neurosyphilis. Abstract PDF · Vol 68, No 15 (1983) - Articles The Tolosa-Hunt syndrome

  18. Maintien de l'abstinence chez les patients alcoolo-dependants ...

    African Journals Online (AJOL)

    Maintien de l'abstinence chez les patients alcoolo-dependants: étude comparee de la disponibilite et du cout du traitement par le baclofene, l'acamprosate, et la naltrexone a Cotonou (Benin) et a Lome (Togo)

  19. Celiac Family Health Education Video Series

    Medline Plus

    Full Text Available ... by U. S. News & World Report Centers Brain Center Heart Center Orthopedic Center Pediatric Transplant Center Services Endocrinology ... today . Conditions Inguinal Hernia ACL Tear Hypoplastic Left Heart Syndrome Go to all conditions» Treatments Baclofen Pump ...

  20. Celiac Family Health Education Video Series

    Medline Plus

    Full Text Available ... Talk to your healthcare provider about getting your child immunized today . Conditions Inguinal Hernia ACL Tear Hypoplastic Left Heart Syndrome Go to all conditions» Treatments Baclofen Pump Liver ...

  1. Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Qvortrup, Camilla; Eckhoff, Lise

    2015-01-01

    , the best available data supports a moderate recommendation for treatment with duloxetine and evidence is inconclusive regarding the use of tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine. CONCLUSION: Research...

  2. Celiac Family Health Education Video Series

    Medline Plus

    Full Text Available ... by U. S. News & World Report Centers Brain Center Heart Center Orthopedic Center Services Endocrinology Gastroenterology, Hepatology and ... today . Conditions Inguinal Hernia ACL Tear Hypoplastic Left Heart Syndrome Go to all conditions» Treatments Baclofen Pump ...

  3. Piracetam and aniracetam antagonism of centrally active drug-induced antinociception.

    Science.gov (United States)

    Galeotti, N; Ghelardini, C; Bartolini, A

    1996-04-01

    The effects of the nootropic drugs piracetam and aniracetam on antinociception induced by baclofen, bicuculline, and picrotoxin and on baclofen-induced muscle relaxation were studied in mice. Antinociception was investigated using both the hot plate (thermal stimulus) and abdominal constriction (chemical stimulus) tests. Both behaviour inhibition and muscle relaxation were observed by using the rota-rod test. Piracetam (30 mg/kg, IP) and aniracetam (10 mg/kg, PO) reduced baclofen, bicuculline, and picrotoxin antinociception without modifying analgesia induced by non-GABAergic drugs such as morphine, physostigmine, clomipramine, and diphenhydramine. In this concentration range, piracetam, and aniracetam were also able to reduce the inhibition of rota-rod performance. At higher doses piracetam (100 mg/kg, IP) and aniracetam (100 mg/kg, PO) were able to completely prevent baclofen antinociception. However, when prevention of GABAergic antinociception was complete, piracetam and aniracetam were able to block non-GABAergic antinociception also. comparing the effects of piracetam and aniracetam with those exerted by the GABAB antagonist CGP 35348, a reduction of non-GABAergic analgesia was also observed using higher doses of CGP 35348 (2.5 micrograms per mouse ICV). The present results indicate that piracetam and aniracetam, by preventing both of the investigated effects of baclofen, have some selectivity against GABAB-mediated inhibition. The well-known activity of piracetam and aniracetam on learning and memory might, therefore, depend, at least in part, on the removal of inhibitory GABAB mechanisms that impair attention and cognitive functions.

  4. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P

    1994-01-01

    chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S......)-baclofen and the antagonist (-)-(R)-phaclofen suggests that these ligands interact with the GABAB receptor sites in a similar manner. Thus, it may be concluded that the different pharmacological effects of these compounds essentially result from the different spatial and proteolytic properties of their acid groups....

  5. Nigerian Journal of Paediatrics - Vol 39, No 3 (2012)

    African Journals Online (AJOL)

    Prolonged trismus post tetanus in a Nigerian boy: The role of oral baclofen- A case report and literature review · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. DD Umoru, O Oyetundun, S Anikoh, K Osisami, H Mohammed, F Abdulrahaman, 133-135.

  6. Author Details

    African Journals Online (AJOL)

    Abdulrahaman, F. Vol 39, No 3 (2012) - Articles Prolonged trismus post tetanus in a Nigerian boy: The role of oral baclofen- A case report and literature review. Abstract PDF. ISSN: 0302-4660. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

  7. SCI with Brain Injury: Bedside-to-Bench Modeling for Developing Treatment and Rehabilitation Strategies

    Science.gov (United States)

    2012-10-01

    used for pain management), baclofen (used for spasticity control), and topiramate (used for controlling seizures), all identified as common treatment ...Modeling for Developing Treatment and Rehabilitation Strategies PRINCIPAL INVESTIGATOR: Michael S. Beattie, Ph.D...September 2012 4. TITLE AND SUBTITLE SCI with Brain Injury: Bedside To Bench Modeling For Developing Treatment And Rehabilitation Strategies 5a

  8. Spasticity : Revisiting the role and the individual value of several pharmacological treatments

    NARCIS (Netherlands)

    Lapeyre, Eric; Kuks, Jan B. M.; Meijler, Andwillem J.

    2010-01-01

    Though in the last few decades only a few new drugs have come available for the treatment of spasticity, new insights may revise the role and individual value of several pharmacological treatments. Diazepam, baclofen and tizanidine are the most prescribed drugs for the treatment of spasticity.

  9. Discordance in Informed Consent Response on the Basis of Demographic Factors: Brief Report

    Science.gov (United States)

    Nunez-Wallace, Karen R.; Gill, Chandler E.; Harrison, Courtney H.; Taylor, Henry M.; Charles, P. David

    2010-01-01

    During an outcomes study of spasticity treatment at a developmental center for 62 residents with profound intellectual disabilities, either botulinum toxin A (BTX-A), intrathecal baclofen (ITB), or both were recommended with physical and occupational therapy. Conservators consented to BTX-A more than ITB (p = 0.021). Court-appointed conservators…

  10. A Comparison of Robotic, Body Weight-Supported Locomotor Training and Aquatic Therapy in Chronic Motor Incomplete Spinal Cord Injury Subject

    Science.gov (United States)

    2012-10-01

    5012 DISTRIBUTION STATEMENT: Approved for public release; distribution unlimited The views, opinions and/or...Sept 2012 Peer Reviewed Article Atypical Autonomic Dysreflexia during Robotic Assisted Body Weight Supported Treadmill Training in an Individual with...managed with oral baclofen at ten mg three times per day. He manages his bladder with external condom catheter drainage and his bowel routine includes

  11. The use of hydrotherapy for the management of spasticity.

    Science.gov (United States)

    Kesiktas, N; Paker, N; Erdogan, N; Gülsen, G; Biçki, D; Yilmaz, H

    2004-12-01

    Spasticity is a major problem for the rehabilitation team. Physiotherapy is a vital component of therapy. Oral medication and other modalities such as heat, cold, ultrasound, electrical stimulation, and surgery (neuro-surgical or orthopedic) can also be used. The aim of this study was to compare the effects of hydrotherapy on spasticity and Functional Independence Measure (FIM) scores of patients with spinal cord injury (SCI). This is a control case matched study. Twenty SCI patients were divided into 2 groups and matched for age, gender, injury time, Ashworth scores, oral baclofen intake, American Spinal Injury Association, and FIM scores. The control group received passive range of motion exercise twice a day and oral baclofen for 10 weeks. The study group also received passive range of motion and oral baclofen, as well as 20 min of water exercises (at 71 degrees F, full immersion) 3 times per week. The authors evaluated spasm severity, FIM scores, oral baclofen intake, and Ashworth scales, between groups at the beginning and at the end of the treatment period. Both groups demonstrated a significant increase in FIM scores. However, the hydrotherapy group demonstrated a larger increase (P hydrotherapy group (P hydrotherapy produced a significant decrease in spasm severity (P hydrotherapy to the rehabilitation program can be helpful in decreasing the amount of medication required. Future studies must evaluate benefits of hydrotherapy for rehabilitation.

  12. Combinational Spinal GAD65 Gene Delivery and Systemic GABA-Mimetic Treatment for Modulation of Spasticity

    Czech Academy of Sciences Publication Activity Database

    Kakinohana, O.; Hefferan, M. P.; Miyanohara, A.; Nejime, T.; Marsala, S.; Juhás, Štefan; Juhásová, Jana; Motlík, Jan; Kucharova, K.; Strnádel, Ján; Platoshyn, O.; Lazar, P.; Galik, J.; Vinay, L.; Marsala, M.

    2012-01-01

    Roč. 7, č. 1 (2012), s. 1-13 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50450515 Keywords : INTRATHECAL BACLOFEN * CORD - INJURY * UPTAKE INHIBITOR Subject RIV: FH - Neurology Impact factor: 3.730, year: 2012

  13. Activation of the GABAB receptor prevents nicotine-induced locomotor stimulation in mice

    Directory of Open Access Journals (Sweden)

    Carla eLobina

    2011-12-01

    Full Text Available Recent studies demonstrated that activation of the GABAB receptor, either by means of orthosteric agonists or positive allosteric modulators (PAMs, inhibited different nicotine-related behaviors, including intravenous self-administration and conditioned place preference, in rodents. The present study investigated whether the anti-nicotine effects of the GABAB receptor agonist, baclofen, and GABAB PAMs, CGP7930 and GS39783, extend to nicotine stimulant effects. To this end, CD1 mice were initially treated with baclofen (0, 1.25, and 2.5 mg/kg, i.p., CGP7930 (0, 25, and 50 mg/kg, i.g., or GS39783 (0, 25, and 50 mg/kg, i.g., then treated with nicotine (0 and 0.05 mg/kg, s.c., and finally exposed to an automated apparatus for recording of locomotor activity. Pretreatment with doses of baclofen, CGP7930, or GS39783 that did not alter locomotor activity when given with nicotine vehicle fully prevented hyperlocomotion induced by 0.05 mg/kg nicotine. These data extend to nicotine stimulant effects the capacity of baclofen and GABAB PAMs to block the reinforcing, motivational, and rewarding properties of nicotine. These data strengthen the hypothesis that activation of the GABAB receptor may represent a potentially useful, anti-smoking therapeutic strategy.

  14. Venovenøs hæmodiafiltrering til baclofenforgiftet patient

    DEFF Research Database (Denmark)

    Nielsen, Simon Uhl; Jansen, Tejs; Johansen, Sys Stybe

    2011-01-01

    Twice a young man was admitted to hospital upon having taken baclofen overdoses by intention. The ingested dose was 1,850 mg at the first episode and up to 2,500 mg at the second. In both cases the patient had severe overdose symptoms and scored 4-5 on the Glascow Coma Scale and was admitted...

  15. Neuromodulation Therapies for Alcohol Addiction: A Literature Review.

    Science.gov (United States)

    Azevedo, Celeste A; Mammis, Antonios

    2018-02-01

    The goal of this review is to explore alternative neurological therapies in the treatment of alcohol use disorder; including transcranial direct current stimulation (tDCS), transcranial magnetic stimulation, deep brain stimulation (DBS), electroconvulsive therapy (ECT), and the off-label use of the GABA B receptor agonist baclofen. A comprehensive literature search was conducted through EBSCOhost regarding the neurological therapies in the treatment of alcoholism discussed in this paper. To date, few studies have been conducted on the subject, sample sizes are consistently small, and long-term abstinence appears a common problem. tDCS has shown to temporarily reduce alcohol cravings but with a high number of long-term relapses, 50-70%. DBS and TMS, similarly, fail to overcome high relapse rates. In one DBS study, for example, only two of five patients achieved prolonged abstinence. ECT seems to avoid such problems, but only a single case study exists to date. As such, no solid conclusions can be made regarding its success in alcohol addiction treatment. Baclofen, however, implicated in studies with comparatively larger patient samples and higher efficacy rates, presents with great promise, particularly in patients with more severe forms of AUD. In one of the largest observational studies to date (100 subjects) 92% of patients reported craving suppression and long-term relapse rates were low. The side-effects of oral baclofen (i.e., somnolence, insomnia, dizziness, paresthesia, etc.) though, pose a principle limitation to its administration in alcohol addiction. Based on current information in the literature, the authors advocate that, following more extensive research on oral baclofen and its indications in the treatment of alcohol addiction, intrathecal administration be the next logical therapeutic option to be explored. In particular, those patients with severe AUD, requiring high doses of the medication, may benefit, as it eliminates the systemic side effects

  16. Rhizotomibehandling af børn med svaer spastisk cerebral parese

    DEFF Research Database (Denmark)

    Illum, Niels Ove; Torp-Pedersen, Lisbeth; Midholm, Steen

    2006-01-01

    or posterior rhizotomy (SDR) approach, afferent sensory nerve fibers are cut while efferent motor fibers are preserved. In this way spasticity is reduced and motor functions can improve. SDR is an established treatment method, and the first Danish study is reported. MATERIAL AND METHODS: Twenty Danish children......INTRODUCTION: Severe spasticity is a limiting factor for motor development in children with spastic cerebral palsy. Botulinum toxin, intrathecal baclofen and peroral baclofen all reduce spasticity but might also limit improvements in functional development over time. In the selective dorsal...... with severe spastic cerebral palsy were evaluated, operated on and trained over a 10-year period from 1992 to 2002. Those on whom operation was performed ranged from 4 to 16 years of age (median 8 years), and training and follow-up took place during the ensuing 60 months. At time of operation, 20-40% of 100...

  17. Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

    Science.gov (United States)

    Tyurenkov, I N; Borodkina, L E; Bagmetova, V V; Berestovitskaya, V M; Vasil'eva, O S

    2016-02-01

    GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

  18. SCI Survey to Determine Pressure Ulcer Vulnerability in the Outpatient Population

    Science.gov (United States)

    2016-03-01

    their pressure ulcers as outpatients, while residing in the community. The Veterans Health Administration (VHA) provides medical care for a large number...in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg 2012;255:1069...Kirshblum SC, Morrison NG, Cirnigliaro CM, Zhang RL, Spungen AM. Effect of low-dose baclofen administration on plasma insulin-like growth factor-1 in

  19. Pharmacotherapy of Spasticity in Children With Cerebral Palsy

    OpenAIRE

    Chia-Ying Chung; Chia-Ling Chen; Alice May-Kuen Wong

    2011-01-01

    Spasticity is a common disability in children with cerebral palsy. Pharmacological and non-pharmacological treatments, including physical therapy, occupational therapy, orthotics, rhizotomy, and orthopedic surgery, all play important roles in the management of spasticity. The purpose of this article is to provide an overview of available medications for treatment of spasticity in children with cerebral palsy. Common medications include benzodiazepines, dantrolene sodium, baclofen, tizanidine,...

  20. STUDY OF ANTIDEPRESSANT LIKE EFFECT OF CORIANDRUM SATIVUM AND INVOLVEMENT OF MONOAMINONERGIC AND GABANERGIC SYSTEM

    OpenAIRE

    Naikwade Nilofer; Gumate Deepak; Kokane Sushant; Patil Vipul; Kharade Sudha

    2011-01-01

    The aim of this study was to examine possible mechanism of action of aqueous extract of Coriandrum sativum seed central nervous system of mice. We investigated the antidepressant-like mechanism of Coriandrum sativum by the combination of the Sulpiride (a selective dopamine D2 receptor antagonist), Prazosin (a α1 adrenoceptor antagonist), and Baclofen (GABA agonist). The results show that Coriandrum sativum (200 mg/kg, 400mg/kg, p.o.), significantly reduced the immobility time during Tail Susp...

  1. Discriminative Stimulus Effects of the GABAB Receptor-Positive Modulator rac-BHFF: Comparison with GABAB Receptor Agonists and Drugs of Abuse

    Science.gov (United States)

    Cheng, Kejun; Rice, Kenner C.

    2013-01-01

    GABAB receptor-positive modulators are thought to have advantages as potential medications for anxiety, depression, and drug addiction. They may have fewer side effects than GABAB receptor agonists, because selective enhancement of activated receptors could have effects different from nonselective activation of all receptors. To examine this, pigeons were trained to discriminate the GABAB receptor-positive modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) from its vehicle. The discriminative stimulus effects of rac-BHFF were not mimicked by the GABAB receptor agonists baclofen and γ-hydroxybutyrate (GHB), not by diazepam, and not by alcohol, cocaine, and nicotine, whose self-administration has been reported to be attenuated by GABAB receptor-positive modulators. The discriminative stimulus effects of rac-BHFF were not antagonized by the GABAB receptor antagonist 3-aminopropyl (diethoxymethyl)phosphinic acid (CGP35348) but were attenuated by the less efficacious GABAB receptor-positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol (CGP7930), suggesting the possibility that rac-BHFF produces its discriminative stimulus effects by directly activating GABAB2 subunits of GABAB receptors. At a dose 10-fold lower than the training dose, rac-BHFF enhanced the discriminative stimulus effects of baclofen, but not of GHB. This study provides evidence that the effects of GABAB receptor-positive modulators are not identical to those of GABAB receptor agonists. In addition, the results suggest that positive modulation of GABAB receptors does not produce discriminative stimulus effects similar to those of benzodiazepines, alcohol, cocaine, and nicotine. Finally, the finding that rac-BHFF enhanced effects of baclofen but not of GHB is consistent with converging evidence that the populations of GABAB receptors mediating the effects of baclofen and GHB are not identical. PMID:23275067

  2. Ontogenetic Development of GABA(B)-Receptor Signaling Cascade in Plasma Membranes Isolated From Rat Brain Cortex; the Number of GABA(B)-Receptors Is High Already Shortly After the Birth

    Czech Academy of Sciences Publication Activity Database

    Kagan, Dmytro; Dlouhá, Kateřina; Roubalová, Lenka; Svoboda, Petr

    2012-01-01

    Roč. 61, č. 6 (2012), s. 629-635 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP207/12/0919 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : postnatal development * GABAB-receptors * G-protein coupling/activation * baclofen * SKF97541 Subject RIV: CE - Biochemistry Impact factor: 1.531, year: 2012

  3. Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract.

    Science.gov (United States)

    Mei, Lin; Zhang, Jing; Mifflin, Steve

    2003-12-01

    Previous studies have demonstrated that microinjection of baclofen, a GABA(B) receptor agonist, into the nucleus of the solitary tract (NTS) results in an enhanced pressor response in hypertensive (HT) rats compared with normotensive (NT) rats, suggesting a possible alteration in the responses of neurons in this area to activation of GABA(B) receptors. The following studies were designed to determine whether HT alters the sensitivity of neurons in the NTS to GABA receptor agonists. Sham-operated NT and unilateral nephrectomized, renal-wrap HT Sprague-Dawley rats were anesthetized, and the responses of NTS neurons receiving aortic nerve (AN) afferent inputs to iontophoretic application of GABA, the GABA(A) receptor agonist muscimol, and the GABA(B) agonist baclofen were examined. The AN input was classified as monosynaptic (MSN) if the cell responded to each of two stimuli separated by 5 ms with an action potential. If the cell did not respond, the input was considered polysynaptic (PSN). In MSNs, inhibition of AN-evoked discharge by GABA was not altered in 1 wk of HT but was reduced in 4 wk of HT, whereas in PSNs, sensitivity to GABA was reduced at 1 and 4 wk of HT. In HT rats, inhibition of AN-evoked discharge by baclofen was enhanced in MSNs, but not in PSNs, after 1 and 4 wk of HT, whereas inhibition by muscimol was reduced in MSNs and PSNs at 1 and 4 wk of HT. Changes in sensitivity to muscimol and baclofen within MSNs were the same whether the MSN received a slowly or a rapidly conducted AN afferent input. The results demonstrate that early in HT the sensitivity of NTS neurons to inhibitory amino acids is altered and that these changes are maintained for > or =4 wk. The alterations are dependent on the subtype of GABA receptor being activated and whether the neuron receives a mono- or polysynaptic baroreceptor afferent input.

  4. Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation

    Science.gov (United States)

    2015-10-01

    even if they are uncommon. Thus daily or more frequent pain assessment, combined with slower periodic adjustment of stimulation parameters that...rates had been determined, we explored other parameters, such as the best monopolar or bipolar combination of active contacts among the four on each...many medications, including gabapentin, various antidepressants and opioids. He continued to use an intrathecal baclofen pump for pain and spasm

  5. Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

    Directory of Open Access Journals (Sweden)

    Riccardo Porta

    2016-12-01

    Full Text Available The metal-free reduction of nitro compounds to amines mediated by trichlorosilane was successfully performed for the first time under continuous-flow conditions. Aromatic as well as aliphatic nitro derivatives were converted to the corresponding primary amines in high yields and very short reaction times with no need for purification. The methodology was also extended to the synthesis of two synthetically relevant intermediates (precursors of baclofen and boscalid.

  6. Development of sustained release tablets containing solid ...

    African Journals Online (AJOL)

    The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2) and for up to 10 h in intestinal fluid (pH 6.8). A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly ...

  7. Combined selective dorsal rhizotomy and scoliosis correction procedure in patients with cerebral palsy.

    Science.gov (United States)

    Muquit, Samiul; Ammar, Amr; Nasto, Luigi; Moussa, Ahmad A; Mehdian, Hossein; Vloeberghs, Michael H

    2016-02-01

    Intrathecal baclofen (ITB) therapy for spasticity has been suggested to accelerate the development of scoliosis. We present the case of a 17-year-old female patient with cerebral palsy who had ITB therapy from the age of 11 years. During this period, she developed a severe scoliosis measuring 86° from T11 to L4, with pain due to costo-pelvic impingement. Her baclofen pump had reached its end of life and required replacement if ITB therapy was to continue. This coincided with plans for scoliosis corrective surgery. We performed scoliosis correction along with removal of baclofen pump and selective dorsal rhizotomy (SDR), as a single combined procedure. SDR was performed instead of ITB pump replacement for management of spasticity. Following surgery, scoliosis improved to 24°. At 6 month follow-up, there was significant improvement in spasticity and quality of life. This report illustrates the feasibility of a combined procedure to correct scoliosis and manage spasticity with SDR. We present the case details, our management and review of the published literature regarding the factors influencing treatment of scoliosis and spasticity.

  8. Walking with Neuropathic Pain: Paradoxical Shift from Burden to Support?

    Directory of Open Access Journals (Sweden)

    David J. Kopsky

    2015-01-01

    Full Text Available Baclofen 5% cream can be used for the treatment of neuropathic pain. We describe an unusual case of a neuropathic pain patient with spinal cord injury. A 71-year-old woman with a partial spinal cord injury lesion at L4 complained of tingling, pins and needles, and burning in her legs. She scored her pain as 6 before adding baclofen 5% cream to her pain medication (pregabalin 450 mg, acetaminophen 3000 mg, and diclofenac 150 mg daily. One month later she experienced complete pain relief, though experienced increased difficulties in walking, leading to frequent falls. Her steadier walking without stumbling and falling was more important to her than pain reduction. Thus she decided to stop using baclofen. This unusual case report discusses two important issues that relate to pain medicine and rehabilitation in patients with painful spinal cord lesions: (1 the presence of wide areas of sensory loss “covered” by the presence of painful sensations and (2 pathological sensations that can be used and integrated in the body schema to create an improved spatiovisual orientation and thus mobility. Both these aspects have to be taken into account when treating pain and design rehabilitation programs.

  9. Treatment of severe lipophilic intoxications with intravenous lipid emulsion: a case series (2011–2014

    Directory of Open Access Journals (Sweden)

    Becker MD

    2017-10-01

    Full Text Available Michael D Becker, Brian C YoungEmergency and Critical Care, Animal Specialty Group, Los Angeles, CA, USAAbstract: The objective of this retrospective study was to describe the responses to treatment with intravenous lipid emulsion (ILE and the outcomes for a variety of severe intoxications. This case series includes 10 client-owned animals, 9 dogs and 1 cat, that underwent treatment with ILE for a variety of severe intoxications over a 4-year period. History, physical examination findings, clinical signs, clinicopathological test results, treatment, response to treatment, and outcome were recorded. Eight of the 10 patients survived to discharge. The toxicities included in this case series were baclofen, ivermectin and spinosad plus milbemycin oxime, baclofen and tadalafil, carbamate, methamphetamine, dextroamphetamine sulfate, amlodipine, bromethalin, and organophosphate. The two patients who died were intoxicated with bromethalin and an organophosphate. Six of the 10 patients developed lipemia secondary to ILE administration, and there were no other known adverse effects. Overall, ILE was a safe therapeutic option. This case series provides clinical evidence of successful treatment with ILE as an antidote for previously unpublished toxicities (amlodipine, carbamate, methamphetamine, and dextroamphetamine sulfate, additional evidence of success in treating baclofen and ivermectin toxicosis, as well as unsuccessful treatment of bromethalin and organophosphate toxicities.Keywords: intravenous lipid emulsion, toxicity, amlodipine 

  10. Pharmacotherapy of Spasticity in Children With Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Chia-Ying Chung

    2011-04-01

    Full Text Available Spasticity is a common disability in children with cerebral palsy. Pharmacological and non-pharmacological treatments, including physical therapy, occupational therapy, orthotics, rhizotomy, and orthopedic surgery, all play important roles in the management of spasticity. The purpose of this article is to provide an overview of available medications for treatment of spasticity in children with cerebral palsy. Common medications include benzodiazepines, dantrolene sodium, baclofen, tizanidine, botulinum toxins, phenol, alcohol and intrathecal baclofen. In general, oral medications and intrathecal baclofen are used for treating generalized spasticity, whilst chemodenervation agents (botulinum toxins, phenol, and alcohol are used to treat localized spasticity. There is more sufficient evidence for the recommendation of botulinum toxin A as an effective anti-spasticity treatment in children with cerebral palsy. However, more data concerning safety and long-term effects of botulinum toxin A is needed. Further study is needed to determine which kinds of medications can cause substantial improvement in daily activity, participation level, self-competence, or quality of life in children with cerebral palsy.

  11. Altered consciousness following head injury in advanced renal failure: Find the culprit

    Directory of Open Access Journals (Sweden)

    Kun-Lin Wu

    2016-01-01

    Full Text Available Conscious change following head injury needs a scrutiny of the "nontraumatic" cause to avoid inappropriate management and catastrophic complication. We described an 81-year-old diabetic woman with advanced chronic kidney disease (CKD (estimated glomerular filtration rate: 6 ml/min/1.73 m 2 re-presented to Emergency Department with altered mentality and generalized muscular hypotonia 2 days after falling with a head injury. Her initial mentality was alert, and computed tomography of the brain was negative for organic lesions; she has been given oral baclofen 10 mg daily to control her associated spastic back pain. The repeated laboratory and imaging studies were still unrevealing. Her serum baclofen concentration was markedly elevated (1437 ng/ml. With emergent hemodialysis for two sessions, complete elimination of serum baclofen concentration was accompanied by full recovery of her consciousness. Nontraumatic causes, especially drug-induced neurotoxicity, must be kept in mind in traumatic patients with CKD and unexplained neurological feature.

  12. GABAB receptor subtypes differentially modulate synaptic inhibition in the dentate gyrus to enhance granule cell output.

    Science.gov (United States)

    Foster, Joshua D; Kitchen, Ian; Bettler, Bernhard; Chen, Ying

    2013-04-01

    Activation of GABAB receptors in the dentate gyrus (DG) enhances granule cell (GC) activity by reducing synaptic inhibition imposed by hilar interneurons. This disinhibitory action facilitates signal transfer from the perforant path to the hippocampus. However, as the two main molecular subtypes, GABA(B(1a,2)) and GABA(B(1b,2)) receptors, prefer axonal terminal and dendritic compartments, respectively, they may modulate the hilar pathways at different synaptic localizations. We examined their relative expression and functions in the DG. The localization of GABAB subtypes was revealed immunohistochemically using subunit-selective antibodies in GABA(B1a)(-/-) and GABA(B1b)(-/-) mice. Effects of subtype activation by the GABAB receptor agonist, baclofen, were examined on the perforant path-stimulated GC population activities in brain slices. GABA(B(1a,2)) receptors were concentrated in the inner molecular layer, the neuropil of the hilus and hilar neurons at the border zone; while GABA(B(1b,2)) receptors dominated the outer molecular layer and hilar neurons in the deep layer, showing their differential localization on GC dendrite and in the hilus. Baclofen enhanced the GC population spike to a larger extent in the GABA(B1b)(-/-) mice, demonstrating exclusively disinhibitory roles of the GABA(B(1a,2)) receptors. Conversely, in the GABA(B1a)(-/-) mice baclofen not only enhanced but also inhibited the population spike during GABAA blockade, revealing both disinhibitory and inhibitory effects of GABA(B(1b,2)) receptors. The GABA(B(1a,2)) and GABA(B(1b,2)) receptor subtypes differentially modulate GC outputs via selective axonal terminal and dendritic locations in the hilar pathways. The GABA(B(1a,2)) receptors exclusively mediate disinhibition, thereby playing a greater role in gating signal transfer for hippocampal spatial and pattern learning. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  13. Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis.

    Science.gov (United States)

    Cevikbas, Ferda; Braz, Joao M; Wang, Xidao; Solorzano, Carlos; Sulk, Mathias; Buhl, Timo; Steinhoff, Martin; Basbaum, Allan I

    2017-08-01

    Despite recent insights into the pathophysiology of acute and chronic itch, chronic itch remains an often intractable condition. Among major contributors to chronic itch is dysfunction of spinal cord gamma aminobutyric acidergic (GABAergic) inhibitory controls. We sought to test the hypothesis that selective GABA agonists as well as cell transplant-derived GABA are antipruritic against acute itch and in a transgenic mouse model of atopic dermatitis produced by overexpression of the T H 2 cell-associated cytokine, IL-31 (IL-31Tg mice). We injected wild-type and IL-31Tg mice with combinations of GABA-A (muscimol) or GABA-B (baclofen) receptor agonists 15 to 20 minutes prior to injection of various pruritogens (histamine, chloroquine, or endothelin-1) and recorded spontaneous scratching before and after drug administration. We also tested the antipruritic properties of intraspinal transplantation of precursors of GABAergic interneurons in the IL-31Tg mice. Systemic muscimol or baclofen are antipruritic against both histamine-dependent and -independent pruritogens, but the therapeutic window using either ligand alone was very small. In contrast, combined subthreshold doses of baclofen and muscimol produced a significant synergistic antipruritic effect, with no sedation. Finally, transplant-mediated long-term enhancement of GABAergic signaling not only reduced spontaneous scratching in the IL-31Tg mice but also dramatically resolved the associated skin lesions. Although additional research is clearly needed, existing approved GABA agonists should be considered in the management of chronic itch, notably atopic dermatitis. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment.

    Directory of Open Access Journals (Sweden)

    Elena Elizabeth Bagley

    2014-06-01

    Full Text Available Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1 currents in periaqueductal gray (PAG neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than Ek. Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1

  15. Antiglycine receptor-related stiff limb syndrome in a patient with chronic lymphocytic leukaemia.

    Science.gov (United States)

    Derksen, Angelika; Stettner, Mark; Stöcker, Winfried; Seitz, Rüdiger J

    2013-05-20

    We report a 61-year-old man presenting with rapidly progressive stiffness and painful muscle spasms in the lower extremity muscles. The patient was diagnosed with chronic lymphocytic leukaemia (CLL) approximately a year before symptom onset. Electromyography displayed continuous motor unit activity and immunocytochemistry showed a positive staining for antiglycine receptor (anti-GlyR) antibodies. The clinical course was complicated by autonomic instability and cardiac arrest, but stabilised under continuous therapy with plasma exchange and symptomatic treatment with baclofen and clonazepam. Anti-GlyR antibodies induce rare, but severe, variants of stiff person syndrome that can be of paraneoplastic origin and life threatening due to autonomic dysfunction.

  16. Development and Application of a High-Performance Liquid Chromatography Stability-Indicating Assay for Beyond-Use Date Determination of Compounded Topical Gels Containing Multiple Active Drugs.

    Science.gov (United States)

    Gorman, Gregory; Sokom, Simara; Coward, Lori; Arnold, John J

    2017-01-01

    Topical gels compounded by pharmacists are important clinical tools for the management of pain. Nevertheless, there is often a dearth of information about the chemical stability of drugs included in these topical formulations, complicating the assignment of beyond-use dating. The purpose of this study was to develop a high-performance liquid chromatography photodiode array-based stability-indicating assay that could simultaneously resolve six drugs (amitriptyline, baclofen, clonidine, gabapentin, ketoprofen, lidocaine) commonly included in topical gels for pain management and their potential degradation products. Furthermore, this method was applied to the determination of beyond-use dating of combinations of these drugs prepared in commonly utilized bases (Lipobase, Lipoderm, Pluronic organogel). Gabapentin was determined to be the least stable component in all formulations tested. Measured stability ranged between 7 to 49 days depending on the base and other active drugs present in the formulation. In the absence of gabapentin, baclofen was the next least stable component, lasting for 120 days, regardless of the type of formulating base used. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  17. GABAergic Neural Activity Involved in Salicylate-Induced Auditory Cortex Gain Enhancement

    Science.gov (United States)

    Lu, Jianzhong; Lobarinas, Edward; Deng, Anchun; Goodey, Ronald; Stolzberg, Daniel; Salvi, Richard J.; Sun, Wei

    2011-01-01

    Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate-induced hyperexcitability and “increased central gain”, we examined the effects of γ-aminobutyric acid (GABA) receptor agonists and antagonists on salicylate-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of salicylate significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of salicylate also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the salicylate-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the salicylate-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the salicylate-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by salicylate may arise from a salicylate-induced suppression GABAergic inhibition in the AC. PMID:21664433

  18. Clinical safety of magnetic resonance imaging in patients with implanted SynchroMed EL infusion pumps

    Energy Technology Data Exchange (ETDEWEB)

    Diehn, Felix E.; Wood, Christopher P.; Watson, Robert E.; Hunt, Christopher H. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Mauck, William D. [Mayo Clinic, Department of Anesthesiology, Rochester, MN (United States); Burke, Michelle M. [Mayo Clinic, Department of Psychiatry and Psychology, Rochester, MN (United States)

    2011-02-15

    Patients with implanted SynchroMed spinal infusion pumps (Medtronic, Inc., Minneapolis, MN) routinely undergo magnetic resonance imaging at our institution. In August 2008, Medtronic issued an urgent medical device correction report regarding several pumps. Because of the rare potential ''for a delay in the return of proper drug infusion'' and ''for a delay in the logging of motor stall events,'' ''a patient's pump must be interrogated after MRI exposure in order to confirm proper pump functionality.'' This is particularly important in patients receiving intrathecal baclofen, for whom a delay in return of proper pump infusion could lead to life-threatening baclofen withdrawal syndrome. The objective of this report is to present our experience and protocol of performing magnetic resonance imaging in patients with implanted SynchroMed EL pumps. We retrospectively reviewed records of 86 patients with implanted SynchroMed EL spinal infusion pumps who underwent 112 examinations on 1.5-T magnetic resonance imaging scanners from September 1, 1998 to July 7, 2004. No SynchroMed EL pumps were damaged by magnetic resonance imaging, and the programmable settings remained unchanged in all patients. Our data suggest that SynchroMed EL pump malfunction is indeed rare after routine clinical 1.5-T magnetic resonance imaging examinations. However, based on the Medtronic correction report, we perform pump interrogation before and after imaging. (orig.)

  19. Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9.

    Science.gov (United States)

    Ng, G Y; McDonald, T; Bonnert, T; Rigby, M; Heavens, R; Whiting, P; Chateauneuf, A; Coulombe, N; Kargman, S; Caskey, T; Evans, J; O'neill, G P; Liu, Q

    1999-03-15

    Query of the expressed sequence tag database with the rat metabotropic GABABR1A receptor amino acid sequence using the TFASTA algorithm revealed two partial cDNA fragments whose sequence information was then used to isolate by PCR a novel full-length human cDNA encoding a putative G-protein-coupled receptor (GPCR), termed GPR 51. Sequence analysis revealed that it encoded a protein of 941 amino acids, similar in size and homology to GABAB receptors followed by metabotropic glutamate receptors but not other GPCRs. GPR 51 expressed in COS-1 cells showed no specific binding for [3H](+)baclofen and when expressed in Xenopus oocyte and Xenopus melanophore functional assays showed no activity to GABA, (-)baclofen, and glutamic acid. Northern blot analysis and in situ hybridization revealed that GPR 51 transcripts were predominantly expressed in the central nervous system with highest abundance in the cortex, thalamus, hippocampus, amygdala, cerebellum, and spinal cord. In contrast, GPR 51 receptor transcripts were almost not detected in the peripheral tissues. Gene GPR 51 was localized by radiation hybrid mapping to chromosome 9, 4.81 cR from the WI-8684 marker, and proximal to the hereditary sensory neuropathy type 1 locus. Copyright 1999 Academic Press.

  20. Incompatibilidad química y estabilidad térmica del baclofeno por análisis térmico

    Directory of Open Access Journals (Sweden)

    Luis Martínez Álvarez

    1998-04-01

    Full Text Available Se realizó un estudio de las posibles interacciones químicas entre el baclofeno, principio activo, y los distintos excipientes preseleccionados en la preformulación del baclofeno tableta, y al mismo tiempo un estudio de estabilidad térmica con el empleo de la calorimetría diferencial de barrido como técnica fundamental, la cual fue complementada con la cromatografía de capa fina y la espectroscopia infrarroja. Se obtuvo como resultado la no interacción química entre el principio activo y los excipientes; además se estableció un orden de estabilidad térmica con el propósito de realizar posibles sustituciones de algunos excipientes en la preformulación, con vistas a garantizar una mayor estabilidad del producto final.A study of the possible chemical interactions between baclofen, active principle, and the different excipients preselected in the preformulation of baclofen tablet was conducted. A study of thermic stability by using the differential scanning calorimetry, which was complemented with thin layer chromatography and infrared spectroscopy, was carried out at the same time. As a result, the non-chemical interaction between the active principle and the excipients was obtained, and an order of thermic stability was established aimed at making possible substitutions of some excipients in the preformulation in order to guarantees a greater stability of the final product.

  1. Clinical safety of magnetic resonance imaging in patients with implanted SynchroMed EL infusion pumps

    International Nuclear Information System (INIS)

    Diehn, Felix E.; Wood, Christopher P.; Watson, Robert E.; Hunt, Christopher H.; Mauck, William D.; Burke, Michelle M.

    2011-01-01

    Patients with implanted SynchroMed spinal infusion pumps (Medtronic, Inc., Minneapolis, MN) routinely undergo magnetic resonance imaging at our institution. In August 2008, Medtronic issued an urgent medical device correction report regarding several pumps. Because of the rare potential ''for a delay in the return of proper drug infusion'' and ''for a delay in the logging of motor stall events,'' ''a patient's pump must be interrogated after MRI exposure in order to confirm proper pump functionality.'' This is particularly important in patients receiving intrathecal baclofen, for whom a delay in return of proper pump infusion could lead to life-threatening baclofen withdrawal syndrome. The objective of this report is to present our experience and protocol of performing magnetic resonance imaging in patients with implanted SynchroMed EL pumps. We retrospectively reviewed records of 86 patients with implanted SynchroMed EL spinal infusion pumps who underwent 112 examinations on 1.5-T magnetic resonance imaging scanners from September 1, 1998 to July 7, 2004. No SynchroMed EL pumps were damaged by magnetic resonance imaging, and the programmable settings remained unchanged in all patients. Our data suggest that SynchroMed EL pump malfunction is indeed rare after routine clinical 1.5-T magnetic resonance imaging examinations. However, based on the Medtronic correction report, we perform pump interrogation before and after imaging. (orig.)

  2. Pharmacotherapy of alcoholism - an update on approved and off-label medications.

    Science.gov (United States)

    Soyka, Michael; Müller, Christian A

    2017-08-01

    Only a few medications are available for the treatment of alcohol use disorders (AUDs). Areas covered: This paper discusses approved AUD medications, including the opioid antagonists naltrexone and nalmefene (the latter is licensed for reduction of alcohol consumption only), the putative glutamate receptor antagonist acamprosate and the aldehyde dehydrogenase inhibitor disulfiram. It also covers off-label medications of interest, including topiramate, gabapentin, ondansetron, varenicline, baclofen, sodium oxybate and antidepressants. Clinical implications, benefits and risks of treatment are discussed. Expert opinion: Acamprosate, naltrexone, nalmefene and disulfiram are the only approved 'alcohol-specific' drugs. Acamprosate and naltrexone have been evaluated in numerous clinical trials and represent evidence-based treatments in AUDs. Nalmefene use, however, is controversial. Supervised disulfiram is a second-line treatment approach. Compounds developed and licensed for different neuropsychiatric disorders are potential alternatives. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence. The GABA (γ-aminobutyric acid)-B receptor agonist baclofen has shown mixed results; it is currently licensed for the treatment of AUDs in France only. Gabapentin may be close to approval in the USA. Further studies of these novel treatment approaches in AUDs are needed.

  3. Influence of Previous Failed Antispasticity Therapy on the Efficacy and Tolerability of THC:CBD Oromucosal Spray for Multiple Sclerosis Spasticity.

    Science.gov (United States)

    Haupts, Michael; Vila, Carlos; Jonas, Anna; Witte, Kerstin; Álvarez-Ossorio, Lourdes

    2016-01-01

    Sativex® (THC:CBD oromucosal spray) is indicated as add-on treatment for patients with moderate to severe multiple sclerosis (MS) spasticity. We aimed to determine whether antispasticity treatment history influenced the efficacy and safety of add-on THC:CBD oromucosal spray in MS spasticity patients. Post hoc analysis of an enriched-design clinical trial of THC:CBD oromucosal spray versus placebo, using records of patients under previous and current ineffective antispasticity therapies. Subgroups were patients with at least 1 failed therapy attempt with either baclofen or tizanidine (Group 1) or at least 2 failed therapy attempts with both baclofen and tizanidine (Group 2). Of 241 patients in the intent-to-treat population, 162 and 57 patients met the criteria for Groups 1 and 2, respectively. In all groups, response on the spasticity 0-10 Numerical Rating Scale was significantly greater with THC:CBD oromucosal spray versus placebo, for minimal clinically important difference (MCID ≥18% improvement vs. baseline) and clinically important difference (CID, ≥30% improvement vs. baseline). THC:CBD oromucosal spray improved spasticity-related symptoms such as sleep quality and timed 10-meter walk independent of the number of prior failed therapy attempts. Tolerability was not influenced by pre-treatment history. THC:CBD oromucosal spray provided consistent relief with good tolerability in MS spasticity patients irrespective of their antispasticity pre-treatment history. © 2016 S. Karger AG, Basel.

  4. Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice.

    Science.gov (United States)

    Abdel Salam, Omar M E

    2006-01-01

    The effect of vinpocetine or piracetam on thermal and visceral pain was studied in mice. In the hot plate test, vinpocetine (0.9 and 1.8 mg/kg), but not piracetam, produced a reduction in nociceptive response. Vinpocetine (0.45-1.8 mg/kg, ip) or piracetam (75-300 mg/kg, ip) caused dose-dependent inhibition of the abdominal constrictions evoked by ip injection of acetic acid. The effect of vinpocetine or piracetam was markedly potentiated by co-administration of propranolol, guanethidine, atropine, naloxone, yohimbine or prazosin. The marked potentiation of antinociception occurred upon a co-administration of vinpocetine and baclofen (5 or 10 mg/kg). In contrast, piracetam antagonized antinociception caused by the low (5 mg/kg), but not the high (10 mg/kg) dose of baclofen. The antinociception caused by vinpocetine was reduced by sulpiride; while that of piracetam was enhanced by haloperidol or sulpiride. Either vinpocetine or piracetam enhanced antinociception caused by imipramine. The antinociceptive effects of vinpocetine or piracetam were blocked by prior administration of theophylline. Low doses of either vinpocetine or piracetam reduced immobility time in the Porsolt's forced-swimming test. This study indicates that vinpocetine and piracetam possess visceral antinociceptive properties. This effect depends on activation of adenosine receptors. Piracetam in addition inhibits GABA-mediated antinociception.

  5. Presynaptic control of nociceptor signalling: Differential influence of Mu Opioid and GABAergic Systems

    Directory of Open Access Journals (Sweden)

    Ruth C Riley

    2000-01-01

    Full Text Available The relative contribution of pre- and postsynaptic controls to the flow of nociceptive information at the level of the spinal cord has been one of Ron Melzack's longstanding interests and a key issue in the formulation of the gate control theory. The authors review their own studies, in which they monitored internalization of the neurokinin-1 receptor to examine specifically the action of two classically inhibitory systems - mu opioid and gamma-amino butyric acid (GABA - on noxious stimulus-evoked tachykinin signalling in the rat spinal cord. Evidence that opioids and GABAergic controls operate differently on the central consequences of any noxious stimulus-induced substance P release is provided. Whereas at least 80% of the tachykinin signalling remained intact after even the highest concentration of spinal morphine or D-Ala2, NMe-phe4, Glyol5-enkephalin administration, spinal administration of the GABAB receptor agonist baclofen had a dramatic inhibitory effect. These findings are discussed in light of the disappointing clinical utility of baclofen and neurokinin-1 receptor antagonists to combat pain.

  6. Prevention of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    V A Parfenov

    2011-01-01

    Full Text Available The paper gives the data available in the literature on the treatment of spasticity in poststroke patients. Therapeutic exercises that should be started just on the first days of stroke are noted to play a leading role in the treatment of poststroke spasticity. The local administration of botulinum toxin preparations (botox, dysport, xeomin may be effective for managing local spasticity that deteriorates motor functions. Baclofen (baklosan, tizanidine (sirdalud, and tolperisone hydrochloride (mydocalm may be used as oral medications. The paper also presents the results of a placebo-controlled trial that has indicated that mydocalm given in a dose of 300 to 900 mg/day may be effective in treating poststroke spasticity.

  7. [Selection of treatment modalities in patients with spasticity].

    Science.gov (United States)

    Ota, Tetsuo

    2014-09-01

    Spasticity is the most common abnormality of muscle tone. Typically, oral antispastic drugs, phenol blocks, motor-point blocks, selective dorsal rhizotomies, and selective peripheral neurotomies are used to reduce muscle tone and/or improve ranges of motion. Recently, botulinum toxin injections and intrathecal baclofen have been used as treatment modalities. The selection of the most appropriate treatment modality by doctors treating patients with spasticity is critical. Furthermore, rehabilitation techniques, such as physiotherapy, occupational therapy, therapeutic electrical nerve stimulation, and orthosis, are useful as combination therapy for the treatment of spasticity. The purpose of this study was to outline the various modalities that are currently used for the treatment of spasticity. Regardless of the modality selected, it is imperative that treatment goals are carefully identified. The reduction of spasticity is not an appropriate treatment goal. Appropriate goals include improving gait, activities of daily living, and the quality of life.

  8. Advances in treatment of muscle cramp in liver cirrhosis

    Directory of Open Access Journals (Sweden)

    ZHAO Wenshan

    2017-10-01

    Full Text Available Muscle cramp is one of the common symptoms of patients with liver cirrhosis and significantly affects patients′ quality of life. In general, the research on liver cirrhosis mainly focuses on the management and prevention of causes or common complications, and there are relatively few studies on the treatment of muscle cramp. Therefore, it is very important to find safe and effective therapeutic regimens. This article describes the pathogenesis and manifestations of muscle cramp in patients with liver cirrhosis, summarizes the therapeutic regimens with clinical value, including new drugs such as baclofen, L-carnitine, and taurine, and further elaborates on the protective effect of taurine against liver fibrosis via its activation of extracellular matrix and hepatic stellate cells, in order to provide new evidence for the treatment of muscle cramp in liver cirrhosis.

  9. Pharmacological management of spasticity in multiple sclerosis

    DEFF Research Database (Denmark)

    Otero-Romero, Susana; Sastre-Garriga, Jaume; Comi, Giancarlo

    2016-01-01

    Background and objectives: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. Methods...... improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity...... and suboptimal response to oral drugs. Conclusion: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence...

  10. Synthesis of high specific activity tritium labelled compounds

    International Nuclear Information System (INIS)

    Parent, P.

    1986-01-01

    Tritiated methyl iodide of high specific activity is synthetized by Fischer-Tropsch reaction of tritium with carbon monoxide, tritiated methanol obtained is reacted with hydriodic acid. It is used for the synthesis of S-adenosyl L-methionine 3 H-methyl and of diazepam 3 H-methyl derivatives. Synthesis of 3-PPP 3 H: (hydroxy-3 phenyl)-3N-n propyl [ 3 H-2.3] piperidine [ 3 H-2.3] with a specific activity of 4.25 T Bq/mM (115 Ci/mM) and of baclofene 3 H with a specific activity of 0.925 TBq (25 Ci/mM) are also described [fr

  11. Excellent functional outcome following selective dorsal rhizotomy in a child with spasticity secondary to transverse myelitis.

    Science.gov (United States)

    Mazarakis, N K; Ughratdar, I; Vloeberghs, M H

    2015-11-01

    Selective dorsal rhizotomy (SDR) is a neurosurgical procedure used to treat spasticity in children with cerebral palsy (CP). The vast majority of studies to date suggest SDR is particularly effective in reducing lower limb spasticity in spastic diplegia with long-lasting effect. We report, to the best of our knowledge for the first time, the case of a teenager who underwent SDR for the management of spasticity secondary to transverse myelitis. This is an unusual indication for SDR which resulted in completely loose lower limbs and an excellent functional outcome. At a follow-up 18 months following the procedure, the child had no re-occurrence of his symptoms. This report raises the possibility that the use of SDR could be expanded to include other pathologies. We discuss the case and the relevant literature. Our spasticity service at NUH has to date inserted 300 baclofen pumps and performed 60 SDRs mainly in children with cerebral palsy.

  12. Neurosurgical treatment of spasticity and other pediatric movement disorders.

    Science.gov (United States)

    Albright, A Leland

    2003-09-01

    For children whose spasticity and movement disorders are inadequately treated by oral medications and botulinum toxins, neurosurgical procedures are now available to effectively treat spasticity, tremor, and many cases of dystonia. Spastic diplegia can be treated with selective lumbar rhizotomies, which significantly decrease spasticity, increase range of motion, and improve Gross Motor Function Measure scores. Children with spastic quadriparesis and those with secondary dystonia can be treated with intrathecal baclofen, which diminishes both spasticity and dystonia and is associated with improved function and quality of life. Children with primary dystonia and those with tremor can be treated with deep brain stimulation of the internal globus pallidus and thalamus, respectively. Some children with chorea respond to deep brain stimulation. There are no effective neurosurgical treatments for athetosis or ataxia. The effectiveness of neurosurgical treatments of pediatric movement disorders has increased significantly in the past 15 years.

  13. [Movement disorders in childhood: therapeutic update].

    Science.gov (United States)

    Roubertie, A; Leydet, J; Rivier, F; Humbertclaude, V; Cheminal, R; Echenne, B

    2004-08-01

    Abnormal movements are not uncommon in childhood. Due to the severity of the abnormal movements or to the functional disability, a medical treatment is often required; the wide range of available pharmacological molecules and the absence of therapeutic consensus highlight the limited efficacy of the medical treatment on dystonic or athetoid movements, or severe tic disorders. The recent identification of the enzymatic defect implicated in metabolic diseases led to the development of specific treatment for newly recognized disorders, with more or less interesting results (creatine ou biotine supplementation). Recent progress in functional neurosurgery opened new fields in the treatment of movement disorders. Intrathecal baclofen was proved effective in the treatment of secondary dystonia, especially in patients with cerebral palsy. Deep brain stimulation is now an established therapy for patients with a generalized dystonic syndrome. Given the successful results of pallidal stimulation in dystonia, the indication of this procedure has been discussed in other types of abnormal movements.

  14. Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn.

    Science.gov (United States)

    Patil, Rupali A; Jagdale, Swati C; Kasture, Sanjay B

    2006-12-01

    Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract.

  15. Neuroimaging the Effectiveness of Substance Use Disorder Treatments.

    Science.gov (United States)

    Cabrera, Elizabeth A; Wiers, Corinde E; Lindgren, Elsa; Miller, Gregg; Volkow, Nora D; Wang, Gene-Jack

    2016-09-01

    Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy ((1)H MRS), and functional magnetic resonance imaging (fMRI), are powerful tools for assessing neurobiological mechanisms underlying the response to treatments in substance use disorders. Here, we review the neuroimaging literature on pharmacological and behavioral treatment in substance use disorder. We focus on neural effects of medications that reduce craving (e.g., naltrexone, bupropion hydrochloride, baclofen, methadone, varenicline) and that improve cognitive control (e.g., modafinil, N-acetylcysteine), of behavioral treatments for substance use disorders (e.g., cognitive bias modification training, virtual reality, motivational interventions) and neuromodulatory interventions such as neurofeedback and transcranial magnetic stimulation. A consistent finding for the effectiveness of therapeutic interventions identifies the improvement of executive control networks and the dampening of limbic activation, highlighting their values as targets for therapeutic interventions in substance use disorders.

  16. Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest].

    Science.gov (United States)

    Santos, Cynthia; Olmedo, Ruben E; Kim, Jeremy

    2017-03-22

    Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms. [Points & Pearls is a digest of Emergency Medicine Practice].

  17. [A decreased frequency of peeking out from the dark compartment--the only constant index of the effect of anxiogens on the behavior of mice in a "light-darkness" chamber].

    Science.gov (United States)

    Lapin, I P

    1999-01-01

    Special measurements of the effects of anxiolytics and anxiogens on the commonly used parameters of behavior of mice in a dark-light chamber (the rate of transitions and time spent in a dark and light compartments) demonstrated their low reproducibility in consecutive experiments. Therefore, these indices are not reliable (Lapin, 1992). One more parameter was tested in the present study. A decrease in the rate of leanings out of the dark compartment appeared to be a constant effect of standard anxiety-inducing drugs: caffeine, pentylenetetrazole, yohimbine, and a putative endogenous anxiogen phenylethylamine. Increase in the rate of leanings out, like increase in the rate of transitions and shortening of the time spent in a dark compartment produced by anxiolytics diazepam, chlordiazepoxide, hydroxyzine, phenibut and baclofen were not significant in the majority of experiments. That is why these effects of anxiolytics are not reliable for measuring the activity of anxiolytics in a dark-light chamber.

  18. Management of chronic neuropathic pain with single and compounded topical analgesics.

    Science.gov (United States)

    Knezevic, Nebojsa Nick; Tverdohleb, Tatiana; Nikibin, Farid; Knezevic, Ivana; Candido, Kenneth D

    2017-11-01

    The goal of our review was to emphasize important aspects that physicians should take into consideration when prescribing topical analgesics as part of chronic neuropathic pain treatment. We discuss the dermatopharmacokinetics and microstructural components of the skin, differences between topical and transdermal drug delivery, and topical medication effects on peripheral neuropathy and central sensitization. Even though the US FDA approved topical analgesics are 8%-capsaicin and 5%-lidocaine patches for treating postherpetic neuralgia, there are many other studies conducted on the efficacy of topical ketamine cream, clonidine gel, topical gabapentin, topical baclofen and topical phenytoin for peripheral neuropathic pain, either alone or in combination with other formulations. Furthermore, we discuss new compounded topical analgesics that are becoming more popular and that are showing promising results in the management of chronic peripheral neuropathies. However, more studies are needed for elucidation of the role of topical analgesics and their effects, especially when combined with other treatments.

  19. Resolution of chronic migraine headaches with intrathecal ziconotide: a case report

    Directory of Open Access Journals (Sweden)

    Narain S

    2015-09-01

    Full Text Available Sachin Narain,1 Lama Al-Khoury,2 Eric Chang3–6 1Department of Anesthesiology and Perioperative Care, 2Department of Neurology, 3Department of Physical Medicine and Rehabilitation, 4Department of Neurosurgery, 5Department of Orthopedics, 6Reeve-Irvine Research Center for Spinal Cord Injury, University of California Irvine, Irvine, CA, USA Background: Migraine headaches are a common and functionally debilitating disorder affecting approximately 17% of women and 5.6% of men. Compared to episodic migraine patients, chronic migraineurs are more likely to be occupationally disabled, miss family activities, have comorbid anxiety and/or chronic pain disorders, and utilize significantly more health care dollars. Ziconotide is a calcium channel blocker used for the treatment of chronic severe pain without issues of tolerance or dependency found with opioid therapy. Case: A 59-year-old female had an intrathecal baclofen pump placed for spasticity secondary to multiple sclerosis. Her symptoms also included lower extremity neuropathic pain and severe migraine headaches with 22 migraine headache days per month. Prior treatments included nonsteroidal anti-inflammatory drugs, triptans, anticonvulsants, antihypertensives, and Botox injections which reduced her symptoms to four migraine days per month at best. While her spasticity had markedly improved with intrathecal baclofen, ziconotide was added to help her neuropathic pain complaints. Following initiation of low-dose ziconotide (1 µg/day, the patient noted both lower extremity pain improvement and complete resolution of migraine headaches resulting in zero migraine days per month. She has now been migraine free for 8 months. Conclusion: Upon review of the available literature, there are no published cases of migraine improvement with intrathecal ziconotide. This represents the first case describing resolution of migraine symptoms with low-dose ziconotide. Keywords: ziconotide, migraine, symptoms, chronic

  20. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de, E-mail: erosaa@cardiol.br [Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2015-02-15

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABA{sub B} receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABA{sub B} receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABA{sub B} receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  1. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

  2. Unusually severe case of dermatosis neglecta.

    Science.gov (United States)

    Turrentine, Jake E; Blalock, Travis W; Davis, Loretta S

    2012-01-01

    An 18-year-old black woman with cerebral palsy was admitted for evaluation of an intrathecal baclofen pump site infection. The dermatology service was consulted for treatment suggestions of a presumed diagnosis of chronic tinea capitis. Three courses of oral griseofulvin during the past 2 years failed to resolve the patient's chronic scalp dermatosis. Scalp lesions first began about 2 years earlier after hospitalization for placement of an intrathecal baclofen pump. The patient was unable to care for her scalp due to her cerebral palsy, and her mother interpreted the scalp condition as infectious. No routine shampoo care, scalp care, or topical treatment was performed for more than 1 1/2 years. The mother felt that touching the patient's scalp might cause pain and noted that the majority of her time was spent concentrating on more critical medical issues. Physical examination revealed coalescing hyperkeratotic plaques extending dorsally from the anterior hairline to the occipital scalp with small flecks of keratinous debris throughout the remaining hair (Figure 1). The plate-like plaques were devoid of hair, except at a few fissures where a few tufts of hair emerged. No cervical lymph nodes were appreciated on palpation. Treatment was initiated with compresses consisting of large warm water-soaked towels 4 times daily. Three times a day, a nursing staff applied 5% salicylic acid in olive oil to the scalp under a shower cap for approximately 1 hour. Over the following 2 days, a significant reduction in keratinous debris was appreciated. Within 2 weeks, the bulk of the plaques had been removed (Figure 2). At 6-week follow-up, the underlying scalp showed areas of fibrosis and possible scarring with a few emerging tufts of hair. On the basis of history and response to treatment with salicylic acid and routine scalp care, the patient was diagnosed with an unusually severe case of dermatosis neglecta.

  3. GABA(B) receptor modulation of serotonin neurons in the dorsal raphé nucleus and escalation of aggression in mice.

    Science.gov (United States)

    Takahashi, Aki; Shimamoto, Akiko; Boyson, Christopher O; DeBold, Joseph F; Miczek, Klaus A

    2010-09-01

    The serotonin (5-HT) system in the brain has been studied more than any other neurotransmitter for its role in the neurobiological basis of aggression. However, which mechanisms modulate the 5-HT system to promote escalated aggression is not clear. We here explore the role of GABAergic modulation in the raphé nuclei, from which most 5-HT in the forebrain originates, on escalated aggression in male mice. Pharmacological activation of GABA(B), but not GABA(A), receptors in the dorsal raphé nucleus (DRN) escalated aggressive behaviors. In contrast, GABA agonists did not escalate aggressive behaviors after microinjection into the median raphé nucleus. The aggression-heightening effect of the GABA(B) agonist baclofen depended on the activation of 5-HT neurons in the DRN because it was blocked by coadministration of the 5-HT(1A) agonist 8-OH-DPAT [((+/-)-8-hydroxy-2-(di-n-propylamino)tetralin) hydrobromide] (DPAT), which acts on autoreceptors and inhibits 5-HT neural activity. In vivo microdialysis showed that GABA(B) activation in the DRN increased extracellular 5-HT level in the medial prefrontal cortex. This may be attributable to an indirect action via presynaptic GABA(B) receptors. The presynaptic GABA(B) receptors suppress Ca(2+) channel activity and inhibit neurotransmission, and the coadministration of N-type Ca(2+) channel blocker facilitated the effect of baclofen. These findings suggest that the indirect disinhibition of 5-HT neuron activity by presynaptic GABA(B) receptors on non-5-HT neurons in the DRN is one of the neurobiological mechanisms of escalated aggression.

  4. Neonatal treatment with monoamine uptake inhibitors alters later response in behavioural 'despair' test to beta and GABA-B receptor agonists.

    Science.gov (United States)

    Hilakivi, L A; Taira, T; Hilakivi, I; Loikas, P

    1988-07-01

    The administration of monoamine uptake-inhibiting antidepressant drugs to rats during the early postnatal period was previously shown to lengthen the duration of subsequent immobility in Porsolt's swim test, hence suggesting increased behavioural 'despair' in these animals. Because the mechanism of the antidepressant action may be related to changes in the cerebral monoamine or gamma-aminobutyric acid (GABA) function, the present study was carried out to examine the response in the swim test to a beta-receptor agonist salbutamol, or to the GABA-B receptor agonists progabide and baclofen in rats treated with antidepressant drugs during the second and third postnatal week: either desipramine 5 mg/kg, nomifensine 10 mg/kg or zimeldine 25 mg/kg. When tested a month later i.e. at the age of two months these rats were immobile in water for a longer period than the controls. Salbutamol 10 mg/kg and progabide 100 mg/kg increased the immobility time in the control rats but neither drug affected the rats treated with desipramine, nomifensine or zimeldine. When the animals were 5 months of age, salbutamol 10 mg/kg and baclofen 10 mg/kg shortened the immobility time in the desipramine-treated rats. The control rats and those treated with zimeldine were not affected by the drugs. The results indicate that in the rats which were neonatally treated with antidepressants, the immobility time in water is lengthened in adulthood. Moreover, the response to beta-receptor and GABA-B receptor agonists is increased from the response observed in the control rats.

  5. [Comprehensive management of a child with a post-traumatic brain stem and spinal cord injury. A case study and presentation of current therapeutic modalities].

    Science.gov (United States)

    Kobylarz, Krzysztof; Kwiatkowski, Stanisław; Inglot, Barbara; Mróz, Adam

    2008-01-01

    Less than twenty years ago, a high spinal cord injury accompanied by paralysis of the diaphragm and the resulting apnea and tetraplegia led to certain death within a short time after the trauma, mostly due to respiratory complications associated with ventilatory therapy in hospitals. The objective of this paper is to present the case of a paediatric brain stem trauma with spinal cord injury, consisting of spinal cord rupture in the upper cervical segment. Thanks to appropriate management at all treatment stages (prompt, fully professional assistance in the ambulance, followed by appropriate management at ICU), the child survived. Owing to currently available technical solutions, the boy has achieved considerable self-dependence and an opportunity of having post-traumatic complications treated using a diaphragm pacing stimulator and a baclofen pump. The report presents therapeutic problems encountered in children with post-traumatic spinal cord injury, emphasizing technical opportunities of managing diaphragm paralysis, as exemplified by the five-year treatment and rehabilitation process of a boy with spinal cord injury at C1 level managed at the University Children's Hospital of Cracow, Poland, in whom phrenic nerve stimulation was employed. The implanted stimulator and a specially constructed controller have allowed the boy to achieve mobility using a wheelchair, being able to use a PC and being taught by an individual teacher at home despite his tetraparesis. Recurrent respiratory tract infections and occasional decubitus required periodic hospitalizations. As the patient grew, in consequence of uncontrolled sudden increases of muscle tone of the trunk spine. Increased muscle tone was increasingly resistant to pharmacotherapy and negatively affected the effectiveness of home rehabilitation. In consequence, a decision was made to implant an intraspinal baclofen pump.

  6. Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

    Science.gov (United States)

    Uschakov, Aaron; Grivel, Jeremy; Cvetkovic-Lopes, Vesna; Bayer, Laurence; Bernheim, Laurent; Jones, Barbara E; Mühlethaler, Michel; Serafin, Mauro

    2011-02-08

    We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α(2)-adrenergic receptor (α(2)-AR) agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC), it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations of clonidine up to a thousand times (100 µM) higher than those effective in SDC (100 nM), were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B) agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2)-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2)-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2)-ARs associated with GIRK channels is normally down-regulated (or desensitized) in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

  7. The effect of GABA receptor ligands in experimental spina bifida occulta.

    Science.gov (United States)

    Briner, W

    2001-01-01

    The pathophysiology behind spina bifida and other neural tube defects (NTDs) is unclear. Folic acid is one variable, but other factors remain. Studies suggest that substances active at the GABA receptor may produce NTDs. To test this hypothesis pregnant rats were exposed to either the GABA a agonist muscimol (1, 2 or 4 mg/kg), the GABA a antagonist bicuculline (.5, 1, or 2 mg/kg), the GABA b agonist baclofen (15, 30, 60 mg/kg), or the GABA b antagonist hydroxysaclofen (1, 3, or 5 mg/kg) during neural tube formation. Normal saline was used as a control and valproic acid (600 mg/kg) as a positive control. The embryos were analyzed for the presence of a spina bifida like NTD. After drug administration the pregnancies were allowed to proceed to the 21st day of gestation. Then embryos were removed and skeletons staining and cleared. Vertebral arch closure was measured. Results indicate that the GABAa receptor agonist muscimol, the GABAa receptor antagonist bicuculline, and the GABAb agonist baclofen produced NTDs characterized by widening of the vertebral arch. Oppositely the GABAb antagonist hydroxysaclofen produced narrowing of the vertebral arches. The findings indicate that GABA a or b ligands are capable of altering neural formation. GABA may play a greater than appreciated role in neural tube formation and may be important in NTDs. The narrowing of the vertebral arch produced by the GABA b antagonist hydroxysalcofen suggests that GABA b receptor may play an undefined role in neural tube closure that differs from the GABA a receptor.

  8. Nootropic potential of Bauhinia variegata: A systematic study on murine model

    Directory of Open Access Journals (Sweden)

    Nishikant Jatav

    2014-01-01

    Full Text Available Objectives: Bauhinia variegata Linn (leguminosae is one of the important medicinal herbs used traditionally to treat fever, as tonic, astringent, diarrhea, dysentery, hemorrhoids, piles, edema. Recent findings on Bauhinia variegata Linn have demonstrated its antioxidant, anti-hyperlipidemic, and hepatoprotective potential. The present work is focused to evaluate nootropic potential of Bauhinia variegata Linn in rats. Materials and Methods: The leaves of Bauhinia variegata were collected in the month of January from Jawaharlal Nehru Krishi Vishwavidyalaya Jabalpur (Madhya Pradesh. Leaves were subjected for isolation of crude flavonoids and characterized by total flavonoid content assay. Flavonoid-rich extract of Bauhinia variegata was studied for acute oral toxicity as per revised Organization for Economic Cooperation & Development guidelines No. 423. Nootropic activity was determined by elevated plus maze, rotating rod apparatus, baclofen-induced catatonia, diazepam-induced amnesia. Results: Flavonoid-rich fraction of Bauhinia variegata caused no alteration in locomotion in animals. In the current study, animals treated with flavonoid-rich fraction of Bauhinia variegata (400 mg/kg showed a significant decrease in transfer latency as compared to the control group, which indicates cognitive enhancement effect flavonoid-rich fraction of Bauhinia variegata. In rota rod studies, flavonoid-rich fraction of Bauhinia variegata increased fall of time as compared to diazepam. In baclofen-induced catatonia, administration of flavonoid-rich fraction of Bauhinia variegata demonstrated protective effect on rats. Over all, flavonoid-rich fraction of Bauhinia variegata was found to enhance the performance of murine models. Conclusion: Thus, it could be concluded that flavonoids from Bauhinia variegata possess nootropic potential. However, more systematic studies are required to determine its exact mechanism of action.

  9. Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

    Directory of Open Access Journals (Sweden)

    Aaron Uschakov

    Full Text Available We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA of hypocretin/orexin (hcrt/orx neurons was changed to an inhibition following sleep deprivation (SD. Here we describe that in control condition (CC, i.e. following 2 hours of natural sleep in the morning, the α(2-adrenergic receptor (α(2-AR agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC, it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK channels. Since concentrations of clonidine up to a thousand times (100 µM higher than those effective in SDC (100 nM, were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2-ARs associated with GIRK channels is normally down-regulated (or desensitized in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

  10. Interventions for eye movement disorders due to acquired brain injury.

    Science.gov (United States)

    Rowe, Fiona J; Hanna, Kerry; Evans, Jennifer R; Noonan, Carmel P; Garcia-Finana, Marta; Dodridge, Caroline S; Howard, Claire; Jarvis, Kathryn A; MacDiarmid, Sonia L; Maan, Tallat; North, Lorraine; Rodgers, Helen

    2018-03-05

    in Germany and the USA. These studies investigated two classes of pharmacological interventions: GABAergic drugs (gabapentin, baclofen) and aminopyridines (4-aminopyridines (AP), 3,4-diaminopyridine (DAP)). We judged the evidence from all three studies as very low-certainty because of small numbers of participants (which led to imprecision) and risk of bias (they were cross-over studies which did not report data in a way that permitted estimation of effect size).One study compared gabapentin (up to 900 mg/day) with baclofen (up to 30 mg/day) in 21 people with pendular and jerk nystagmus. The follow-up period was two weeks. This study provides very low-certainty evidence that gabapentin may work better than baclofen in improving ocular motility and reducing participant-reported symptoms (oscillopsia). These effects may be different in pendular and jerk nystagmus, but without formal subgroup analysis it is unclear if the difference between the two types of nystagmus was chance finding. Quality of life was not reported. Ten participants with pendular nystagmus chose to continue treatment with gabapentin, and one with baclofen. Two participants with jerk nystagmus chose to continue treatment with gabapentin, and one with baclofen. Drug intolerance was reported in one person receiving gabapentin and in four participants receiving baclofen. Increased ataxia was reported in three participants receiving gabapentin and two participants receiving baclofen.One study compared a single dose of 3,4-DAP (20 mg) with placebo in 17 people with downbeat nystagmus. Assessments were made 30 minutes after taking the drug. This study provides very low-certainty evidence that 3,4-DAP may reduce the mean peak slow-phase velocity, with less oscillopsia, in people with downbeat nystagmus. Three participants reported transient side effects of minor perioral/distal paraesthesia.One study compared a single dose of 4-AP with a single dose of 3,4-DAP (both 10 mg doses) in eight people with

  11. Incidence estimate and guideline-oriented treatment for post-stroke spasticity: an analysis based on German statutory health insurance data

    Directory of Open Access Journals (Sweden)

    Egen-Lappe V

    2013-03-01

    Full Text Available Veronika Egen-Lappe, Ingrid Köster, Ingrid SchubertPMV Research Group, Department of Child and Adolescence Psychiatry and Psychotherapy, University of Cologne, Cologne, GermanyBackground: Spasticity after stroke has been internationally recognized as an important health problem causing impairment of mobility, deformity, and pain. The aim of this study was to assess the frequency of first-ever and recurrent stroke and of subsequent spastic and flaccid paresis. Factors influencing the development of spasticity were analyzed. A further major aim was to provide a "real-life" assessment of the treatment of spasticity in Germany and to discuss this in view of the treatment recommended by German and international clinical guidelines.Methods: The database used in this study comprised a cohort of 242,090 insurants from a large statutory health insurance fund in the federal state of Hesse, Germany. A first hospital discharge diagnosis in 2009 with any of the International Classification of Diseases, Tenth Revision (ICD-10 codes I60–I64 was used to identify patients with acute stroke (hemorrhage and ischemic. These patients were followed up six months after stroke to monitor whether they developed spastic or flaccid paresis (hospital or ambulatory care diagnoses ICD-10 code G81–G83 [excluding G82.6/G83.4/G83.8]. For patients with spastic paresis after stroke the spasticity treatment was analyzed for a six-month period (physiotherapy, oral muscle relaxants, intrathecal baclofen, and botulinum toxin.Results: Standardized to the population of Germany, 3.7 per 1000 persons suffered a stroke in 2009 (raw 5.2/1000. Of all surviving patients, 10.2% developed spasticity within 6 months. Cox regression revealed no significant influence of patient age, gender, morbidity (diabetes, hypertensive diseases, ischemic heart diseases or type of stroke on development of spasticity. 97% of surviving patients with spasticity received physiotherapy (inpatient care 89

  12. Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.

    Science.gov (United States)

    Corleto, Jose A; Bravo-Hernández, Mariana; Kamizato, Kota; Kakinohana, Osamu; Santucci, Camila; Navarro, Michael R; Platoshyn, Oleksandr; Cizkova, Dasa; Lukacova, Nadezda; Taylor, Julian; Marsala, Martin

    2015-01-01

    The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the

  13. The effect of BLA GABAB receptors in anxiolytic-like effect and aversive memory deficit induced by ACPA

    Directory of Open Access Journals (Sweden)

    Katayoon Kangarlu Haghighi

    2016-07-01

    Full Text Available Background: As a psychoactive plant, Cannabis sativa (Marijuana is widely used throughout the world. Several investigations have indicated that administration of Marijuana affects various cognitive and non-cognitive behaviors. These include anxiety-like behaviors and learning and memory deficit. It has been shown that three main cannabinoid receptors [i.e. CB1, CB2 and CB3 are involved in cannabinoids’ functions. CB1 receptors are abundantly expressed in the central nervous system regions such as hippocampus, amygdala, cerebellum and the cortex. Therefore, the neuropsychological functions of endocannabinoids are thought to be more linked to CB1 receptors. Among other brain regions, CB1 is highly expressed in the amygdala which is an integral component of the limbic circuitry. The amygdala plays a major role in the control of emotional behavior, including conditioned fear and anxiety. In present study we examined the possible roles of basolateral amygdala (BLA GABAB receptors in arachydonilcyclopropylamide (ACPA-induced anxiolytic-like effect and aversive memory deficit in adult male mice. Methods: This experimental study was conducted from September 2013 to December 2014 in Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran and Male albino NMRI mice (Pasture Institute, Iran, weighting 27-30 g, were used. Bilateral guide-cannulae were implanted to allow intra BLA microinjection of the drugs. We used Elevated Plus Maze (EPM to examine memory and anxiety behavior (test-retest protocol. ACPA administrate intra-peritoneal and GABAB agonist and antagonist administrated intra-amygdala. Results: Data showed that pre-test treatment with ACPA induced anxiolytic-like and aversive memory deficit The results revealed that pre-test intra-BLA infusion of baclofen (GABAB receptor agonist impaired the aversive memory while phaclofen (GABAB receptor antagonist improved it. Interestingly, pretreatment with a sub

  14. Tratamento da doença de Meige com droga agonista de receptores GABA

    Directory of Open Access Journals (Sweden)

    Luiz Augusto Franco de Andrade

    1985-09-01

    Full Text Available A doença de Meige é distúrbio de movimento que consiste no aparecimento espontâneo de blefarospasmo associado a movimentos distônicos de musculatura orofacial. Associadamene podem ser encontrados torcicolo espasmódico, disfonia espástica e distonia de extremidades. Várias hipóteses foram formuladas para explicar esse distúrbio, tendo em vista a resposta a drogas com ação conhecida nos sistemas de neurotransmissores do cérebro. Algumas evidências apontam para um estado de preponderância dopaminérgica e, nesse sentido, justifica-se a estimulação da atividade GABA, sabendo-se que esse neurotrans-missor age sobre uma das alças de controle da produção de dopamina na substância negra. Por essa razão investigamos a ação de um agonista GABA, o baclofen, sobre a doença de Meige. Foram incluídos no protocolo 5 pacientes, 4 mulheres e um homem, com idade variando entre 50 e 63 anos e duração da doença variando entre 4 meses e 18 anos. Todos apresentavam blefaros-pasmo-distonia orofacial e, além disso três apresentavam disfonia espástica e um distonia de extremidades. A droga era iniciada em dose de 20mg/dia, aumentada em lOmg a cada três dias até ser obtida resposta ou surgirem efeitos colaterais. Um dos pacientes apresentou melhora marcada do blefaros-pasmo-distonia orofacial e outro melhora moderada dos mesmos sintomas, em avaliação 30 dias após estabilização da dose. Não houve melhora da disfonia espástica e ocorreu melhora moderada da distonia de extremidades. Não podemos afirmar que a melhora observada ao fim de um mês se mantenha, ou mesmo que melhora mais significativa fosse observada em avaliação feita mais tardiamente. Concluimos que o baclofen pode ser útil, pelo menos por algum tempo, na doença de Meige.

  15. Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.

    Directory of Open Access Journals (Sweden)

    Jose A Corleto

    Full Text Available The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI. The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9 complete transection model of muscle spasticity in Sprague-Dawley (SD rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i ankle-rotation-evoked peripheral muscle resistance (PMR and corresponding electromyography (EMG activity, ii Hoffmann reflex, and iii EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist, tizanidine (α2-adrenergic agonist and NGX424 (AMPA receptor antagonist was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the

  16. Clinical potential, safety, and tolerability of arbaclofen in the treatment of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Frye RE

    2014-05-01

    Full Text Available Richard E FryeArkansas Children's Hospital Research Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USAAbstract: Autism spectrum disorder (ASD is a behaviorally defined disorder which has increased in prevalence over the last two decades. Despite decades of research, no effective treatment is currently available. Animal models, as well as other lines of evidence, point to abnormalities in the balance of cortical excitation to inhibition in individuals with ASD, with this imbalance resulting in an overall increase in cortical excitation. To reduce cortical excitatory glutamate pathways, arbaclofen, a selective agonist of the gamma aminobutyric acid receptor type B, has been developed. This article reviews the evidence for this treatment for ASD using a systematic review methodology. Overall, a systematic search of the literature revealed 148 relevant references with the majority of these being review papers or news items that mentioned the potential promise of arbaclofen. Five original studies were identified, four of which used STX209, a form of arbaclofen developed by Seaside Therapeutics, Inc., and one which used R-baclofen. In an animal model, treatment of Fragile X, a genetic disease with ASD features, demonstrated a reversal of behavioral, neurological, and neuropathological features associated with the disease. One double-blind, placebo-controlled study treated children and adults with Fragile X. Results from this study were promising, with signs of improvement in social function, especially in the most severely socially impaired. Two studies, one open-label and one double-blind, placebo-controlled, were conducted in children, adolescents, and young adults with ASD. These studies suggested some improvements in socialization, although the effects were limited and may have been driven by individuals with ASD that were higher-functioning. These studies and others that have used arbaclofen for

  17. Alcoholic liver disease and hepatitis C virus infection.

    Science.gov (United States)

    Novo-Veleiro, Ignacio; Alvela-Suárez, Lucía; Chamorro, Antonio-Javier; González-Sarmiento, Rogelio; Laso, Francisco-Javier; Marcos, Miguel

    2016-01-28

    Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection.

  18. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease

    Directory of Open Access Journals (Sweden)

    Stefano Gitto

    2016-01-01

    Full Text Available Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption.

  19. Central Neuropathic Pain in Spinal Cord Injury

    Science.gov (United States)

    Lee, Sujin; Zhao, Xing; Hatch, Maya; Chun, Sophia; Chang, Eric

    2015-01-01

    Spinal cord injury (SCI) is a devastating medical condition affecting 1.2 million people in the United States. Central neuropathic pain is one of the most common medical complications of SCI. Current treatment options include opioids, antiepileptic agents such as gabapentin, antispastic agents such as baclofen or tizanidine, and tricyclic acid. Other options include complementary, nonpharmacological treatment such as exercise or acupuncture, interventional treatments, and psychological approaches. Although these treatment options exist, central neuropathic pain in patients with SCI is still extremely difficult to treat because of its complexity. To develop and provide more effective treatment options to these patients, proper assessment of and classification tools for central neuropathic pain, as well as a better understanding of the pathophysiology, are needed. A combination of approaches, from standard general pain assessments to medically specific questions unique to SCI pathophysiology, is essential for this population. A multidisciplinary approach to patient care, in addition with a better understanding of pathophysiology and diagnosis, will lead to improved management and treatment of patients with SCI displaying central neuropathic pain. Here we summarize the most recent classification tools, pathophysiology, and current treatment options for patients with SCI with central neuropathic pain. PMID:25750485

  20. Methamphetamine-evoked depression of GABAB receptor signaling in GABA neurons of the VTA

    Science.gov (United States)

    Padgett, CL; Lalive, AL; Tan, KR; Terunuma, M; Munoz, MB; Pangalos, MN; Martínez-Hernández, J; Watanabe, M; Moss, SJ; Luján, R; Lüscher, C; Slesinger, PA

    2012-01-01

    Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABAB receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels, however, are poorly understood. Here, we show that one day after methamphetamine (METH) or cocaine exposure, both synaptically-evoked and baclofen-activated GABABR-GIRK currents were significantly depressed in VTA GABA neurons, and remained depressed for 7 days. Presynaptic inhibition mediated by GABABRs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABAB1R and GIRK2, which occurred coincident with dephosphorylation of Ser783 in GABAB2R, a site implicated in regulating GABABR surface expression. Inhibition of protein phosphatases recovered GABABR-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABABR signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system. PMID:22405207

  1. GABA(B) receptor GTP-binding is decreased in the prefrontal cortex but not the hippocampus of aged rats.

    Science.gov (United States)

    McQuail, Joseph A; Bañuelos, Cristina; LaSarge, Candi L; Nicolle, Michelle M; Bizon, Jennifer L

    2012-06-01

    Gamma aminobutyric acid (GABA)(B) receptors (GABA(B)Rs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABA(B)R expression and signaling. Thus, we investigated GABA(B)R expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABA(B)R1 and GABA(B)R2 proteins were reduced in the prefrontal cortex of aged rats but these reductions were not associated with spatial learning abilities. In contrast, hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal GABA(B)R1 expression was observed in aged rats with spatial learning impairment. These data demonstrate marked regional differences in GABA(B)R complexes in the adult and aged brain and could have implications for both understanding the role of GABAergic processes in normal brain function and the development of putative interventions that target this system. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. GABAB receptor GTP-binding is decreased in the prefrontal cortex but not the hippocampus of aged rats

    Science.gov (United States)

    McQuail, Joseph A.; Bañuelos, Cristina; LaSarge, Candi L.; Nicolle, Michelle M.; Bizon, Jennifer L.

    2011-01-01

    GABAB receptors (GABABRs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABABR expression and signaling. Thus, we investigated GABABR expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABABR1 and GABABR2 proteins were reduced in the PFC of aged rats but these reductions were not associated with spatial learning abilities. In contrast, hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal GABABR1 expression was observed in aged rats with spatial learning impairment. These data demonstrate marked regional differences in GABABR complexes in the adult and aged brain and could have implications for both understanding the role of GABAergic processes in normal brain function and the development of putative interventions that target this system. PMID:22169202

  3. Regulation of (/sup 3/H)GABA release from strips of guinea pig urinary bladder

    Energy Technology Data Exchange (ETDEWEB)

    Shirakawa, J.; Taniyama, K.; Iwai, S.; Tanaka, C.

    1988-12-01

    The presence of receptors that regulate the release of gamma-aminobutyric acid (GABA) was studied in strips of the guinea pig urinary bladder. GABA (10(-8)-10(-5) M) and muscimol (10(-8)-10(-5) M), but not baclofen (10(-5) M), reduced the Ca2+-dependent, tetrodotoxin-resistant release of (/sup 3/H)GABA evoked by high K+ from the urinary bladder strips preloaded with (/sup 3/H)GABA. The inhibitory effect of muscimol was antagonized by bicuculline and potentiated by diazepam, clonazepam, and pentobarbital sodium. The potentiating effect of clonazepam was antagonized by Ro 15-1788. Acetylcholine (ACh) inhibited the high K+-evoked release of (/sup 3/H)GABA. The inhibitory effect of ACh was antagonized by atropine sulfate and pirenzepine but not by hexamethonium. Norepinephrine (NE) inhibited the evoked release of (/sup 3/H)GABA. The inhibitory effect of NE was mimicked by clonidine, but not by phenylephrine, and was antagonized by yohimbine but not by prazosin. These results provide evidence that the release of GABA from strips of guinea pig urinary bladder is regulated via the bicuculline-sensitive GABAA receptor, M1-muscarinic, and alpha 2-adrenergic receptors.

  4. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  5. CXCL12 chemokine and GABA neurotransmitter systems crosstalk and their putative roles

    Directory of Open Access Journals (Sweden)

    Guyon eAlice

    2014-04-01

    Full Text Available Since CXCL12 and its receptors, CXCR4 and CXCR7, have been found in the brain, the role of this chemokine has been expanded from chemoattractant in the immune system to neuromodulatory in the brain. Several pieces of evidence suggest that this chemokine system could crosstalk with the GABAergic system, known to be the main inhibitory neurotransmitter system in the brain. Indeed, GABA and CXCL12 as well as their receptors are colocalized in many cell types including neurons and there are several examples in which these two systems interact. Several mechanisms can be proposed to explain how these systems interact, including receptor-receptor interactions, crosstalk at the level of second messenger cascades, or direct pharmacological interactions, as GABA and GABAB receptor agonists/antagonists have been shown to be allosteric modulators of CXCR4.The interplay between CXCL12/CXCR4-CXCR7 and GABA/GABAA-GABAB receptors systems could have many physiological implications in neurotransmission, cancer and inflammation. In addition, the GABAB agonist baclofen is currently used in medicine to treat spasticity in patients with spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis and other disorders. More recently it has also been used in the treatment of alcohol dependence and withdrawal. The allosteric effects of this agent on CXCR4 could contribute to these beneficial effects or at the opposite, to its side effects.

  6. In vivo temporal property of GABAergic neural transmission in collateral feed-forward inhibition system of hippocampal-prefrontal pathway.

    Science.gov (United States)

    Takita, Masatoshi; Kuramochi, Masahito; Izaki, Yoshinori; Ohtomi, Michiko

    2007-05-30

    Anatomical evidence suggests that rat CA1 hippocampal afferents collaterally innervate excitatory projecting pyramidal neurons and inhibitory interneurons, creating a disynaptic, feed-forward inhibition microcircuit in the medial prefrontal cortex (mPFC). We investigated the temporal relationship between the frequency of paired synaptic transmission and gamma-aminobutyric acid (GABA)ergic receptor-mediated modulation of the microcircuit in vivo under urethane anesthesia. Local perfusions of a GABAa antagonist (-)-bicuculline into the mPFC via microdialysis resulted in a statistically significant disinhibitory effect on intrinsic GABA action, increasing the first and second mPFC responses following hippocampal paired stimulation at interstimulus intervals of 100-200 ms, but not those at 25-50 ms. This (-)-bicuculline-induced disinhibition was compensated by the GABAa agonist muscimol, which itself did not attenuate the intrinsic oscillation of the local field potentials. The perfusion of a sub-minimal concentration of GABAb agonist (R)-baclofen slightly enhanced the synaptic transmission, regardless of the interstimulus interval. In addition to the tonic control by spontaneous fast-spiking GABAergic neurons, it is clear the sequential transmission of the hippocampal-mPFC pathway can phasically drive the collateral feed-forward inhibition system through activation of a GABAa receptor, bringing an active signal filter to the various types of impulse trains that enter the mPFC from the hippocampus in vivo.

  7. [Limb torsion and developmental regression for one month after hand, foot and mouth disease in an infant].

    Science.gov (United States)

    Feng, Li-Fang; Chen, Xiao-Hong; Li, Dong-Xiao; Ding, Yuan; Jin, Ying; Song, Jin-Qing; Yang, Yan-Ling

    2016-05-01

    A one-year-old girl visited the hospital due to limb torsion and developmental regression for one month after hand, foot and mouth disease. At the age of 11 months, she visited a local hospital due to fever for 5 days and skin rash with frequent convulsions for 2 days and was diagnosed with severe hand, foot and mouth disease, viral encephalitis, and status epilepticus. Brain MRI revealed symmetric abnormal signals in the bilateral basal ganglia, bilateral thalamus, cerebral peduncle, bilateral cortex, and hippocampus. She was given immunoglobulin, antiviral drugs, and anticonvulsant drugs for 2 weeks, and the effect was poor. Blood and urine screening for inherited metabolic diseases were performed to clarify the etiology. The analysis of urine organic acids showed significant increases in glutaric acid and 3-hydroxyglutaric acid, which suggested glutaric aciduria type 1, but her blood glutarylcarnitine was normal, and free carnitine significantly decreased. After the treatment with low-lysine diets, L-carnitine, and baclofen for 1 month, the patient showed a significant improvement in symptoms. Hand, foot and mouth disease is a common viral infectious disease in children, and children with underlying diseases such as inherited metabolic diseases and immunodeficiency may experience serious complications. For children with hand, foot and mouth disease and unexplained encephalopathy, inherited metabolic diseases should be considered.

  8. An update on the pharmacotherapy for lower urinary tract dysfunction.

    Science.gov (United States)

    Abraham, Nitya; Goldman, Howard B

    2015-01-01

    The lower urinary tract (LUT) stores and evacuates urine. It is controlled by autonomic, somatic and sensory innervation. Pharmacotherapy has been developed to optimize neural control of the LUT in pathologic states. The bladder can be overactive or underactive. For overactive bladder, medications targeting various receptors include i) antimuscarinics, ii) mixed-action drugs, iii) β-adrenergic receptor agonists and iv) other medications. There is no effective pharmacotherapy for underactive bladder, although medications have been used with limited success, including i) muscarinic receptor agonists, ii) anticholinesterase inhibitors and iii) α-adrenergic receptor antagonists. At the level of the outlet, there can be decreased resistance resulting in stress urinary incontinence (SUI) or increased resistance resulting in bladder outflow obstruction (BOO). The classes of medications for SUI include i) α-adrenergic receptor agonists, ii) β-adrenergic receptor agonists and iii) antidepressants. Medications used to treat BOO include i) α-adrenergic receptor antagonists, ii) 5-α reductase inhibitors, iii) benzodiazepines, iv) baclofen and v) PDE inhibitors. Pharmacotherapy for the LUT must be individualized based on degree of bother, medication side-effect profile, concomitant comorbidities, current medication regimen, and insurance coverage. This review describes current medical therapies for the LUT.

  9. Clonus: definition, mechanism, treatment

    Directory of Open Access Journals (Sweden)

    Ismail Boyraz

    2015-02-01

    Full Text Available Clonus is involuntary and rhythmic muscle contractions caused by a permanent lesion in descending motor neurons. Clonus may be found at the ankle, patella, triceps surae, wrist, jaw, biceps brachii. In general, clonus may occur in any muscle with a frequency of 5-8 Hz and the average period of oscillations of the ankle clonus is approximately 160–200 ms. Plantar flexion (PF comprises 45% of the period, dorsifleksion (DF comprises 55% of the period. The first beat is always longer, with the time shortening in continuing beats and becoming stable in the 4th or 5th period. The exact mechanism of clonus remains unclear. Two different hypotheses have been asserted regarding the development of clonus. The most widely accepted explanation is that hyperactive stretch reflexes in clonus are caused by self-excitation. Another alternative explanation for clonus is central generator activity that arises as a consequence of appropriate peripheral events and produces rhythmic stimulation of the lower motor neurons. The durations of clonus burst were found longer than the durations of Soleus medium-latency reflex (MLR. There is a similarity in their nature, although the speed and cause of the stretch of triceps surae differ in the MLR and the clonus, and there is a sufficient period of time for group II afferents and for other spinal mechanisms to be involved in the clonus, together with Ia afferents. Clonus can be treated by using baclofen, applying cold, botox or phenol injections.

  10. Adolescent cocaine self-administration induces habit behavior in adulthood: sex differences and structural consequences

    Science.gov (United States)

    DePoy, L M; Allen, A G; Gourley, S L

    2016-01-01

    Adolescent cocaine use increases the likelihood of drug abuse and addiction in adulthood, and etiological factors may include a cocaine-induced bias towards so-called ‘reward-seeking' habits. To determine whether adolescent cocaine exposure indeed impacts decision-making strategies in adulthood, we trained adolescent mice to orally self-administer cocaine. In adulthood, males with a history of escalating self-administration developed a bias towards habit-based behaviors. In contrast, escalating females did not develop habit biases; rather, low response rates were associated with later behavioral inflexibility, independent of cocaine dose. We focused the rest of our report on understanding how individual differences in young-adolescent females predicted long-term behavioral outcomes. Low, ‘stable' cocaine-reinforced response rates during adolescence were associated with cocaine-conditioned object preference and enlarged dendritic spine head size in the medial (prelimbic) prefrontal cortex in adulthood. Meanwhile, cocaine resilience was associated with enlarged spine heads in deep-layer orbitofrontal cortex. Re-exposure to the cocaine-associated context in adulthood energized responding in ‘stable responders', which could then be reduced by the GABAB agonist baclofen and the putative tyrosine receptor kinase B (trkB) agonist, 7,8-dihydroxyflavone. Together, our findings highlight resilience to cocaine-induced habits in females relative to males when intake escalates. However, failures in instrumental conditioning in adolescent females may precipitate reward-seeking behaviors in adulthood, particularly in the context of cocaine exposure. PMID:27576164

  11. Targeting the Glutamatergic System to Treat Pathological Gambling: Current Evidence and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Mauro Pettorruso

    2014-01-01

    Full Text Available Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.

  12. Deficient Sleep in Mouse Models of Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    R. Michelle Saré

    2017-09-01

    Full Text Available In patients with fragile X syndrome (FXS, sleep problems are commonly observed but are not well characterized. In animal models of FXS (dfmr1 and Fmr1 knockout (KO/Fxr2 heterozygote circadian rhythmicity is affected, but sleep per se has not been examined. We used a home-cage monitoring system to assess total sleep time in both light and dark phases in Fmr1 KO mice at different developmental stages. Fmr1 KOs at P21 do not differ from controls, but genotype × phase interactions in both adult (P70 and P180 groups are statistically significant indicating that sleep in Fmr1 KOs is reduced selectively in the light phase compared to controls. Our results show the emergence of abnormal sleep in Fmr1 KOs during the later stages of brain maturation. Treatment of adult Fmr1 KO mice with a GABAB agonist, R-baclofen, did not restore sleep duration in the light phase. In adult (P70 Fmr1 KO/Fxr2 heterozygote animals, total sleep time was further reduced, once again in the light phase. Our data highlight the importance of the fragile X genes (Fmr1 and Fxr2 in sleep physiology and confirm the utility of these mouse models in enhancing our understanding of sleep disorders in FXS.

  13. Pharmacology of M & B 18,706, a drug which selectively reduces decrebrate rigidity

    Science.gov (United States)

    Maxwell, D.R.; Read, M.A.; Sumpter, Eileen A.

    1974-01-01

    1 (±)-10-(3-Dimethylamino-2-methylpropyl)-2-valeroylphenothiazine hydrochloride (M & B 18,706) has been compared with dimethothiazine, chloropromazine, diazepam and baclofen for potency in reducing decerebrate rigidity in the cat and rat and for activity in causing ataxia or sedation. 2 When given intravenously M & B 18,706 had seven times the potency of dimethothiazine and one-half the potency of chlorpromazine in reducing the rigidity of the intercollicular decerebrate cat. When administered orally M & B 18,706 and chlorpromazine were equi-potent in reducing rigidity but M & B 18,706 was less effective than chlorpromazine in producing ataxia in this species. 3 In the rat, M & B 18,706 had one-quarter the potency of chlorpromazine for reducing decerebrate rigidity but had from 1/20th to 1/200th its potency in tests for sedative or tranquillizing activity. 4 M & B 18,706, like dimethothiazine and chlorpromazine, had little effect on the rigidity of ischaemic decerebrate cats and failed to inhibit polysynaptic spinal reflexes. 5 M & B 18,706 had intravenous potency comparable to chlorpromazine in reducing the pressor action of noradrenaline in the spinal cat. PMID:4150889

  14. The adjuvant use of lansoprazole, clonazepam and dimenhydrinate for treating intractable hiccups in a patient with gastritis and reflux esophagitis complicated with myocardial infarction: a case report

    Science.gov (United States)

    2013-01-01

    Background Hiccup (Singultus) is a sudden and involuntary contraction of the diaphragm followed by a sharp closure of the epiglottis which results in the production of a specific “hic” sound. Normally, hiccups are treated without intervention. Intractable hiccups occur rarely but are a disturbing symptom underlying other health related disorders. Case presentation We report the clinical case of a 67-year-old male patient with myocardial infarction accompanied by intractable hiccups during the course of 8 months, and who was non-responsive to chlorpromazine or metoclopramide, and baclofen; drugs routinely used to treat this condition. This sustained hiccup had severely restricted the patient's ability to intake food and sleep. To explore alternative treatments, we investigated the adjuvant administration of lansoprazole, dimenhydrinate and clonazepam in this patient. We discovered that this drug combination was capable of successfully terminating his intractable hiccups, with no further evidence of recurrence. No similar treatment is previously reported for intractable hiccups. We further suggest a hypothesis concerning a potential mechanism on the anti-hiccup effect of dimenhydrinate. Conclusion We identified that the adjuvant use of lansoprazole, clonazepam and dimenhydrinate was capable of attenuating the symptoms of our patient with intractable hiccups. PMID:23954069

  15. Selectivity Enhancement in Molecularly Imprinted Polymers for Binding of Bisphenol A

    Directory of Open Access Journals (Sweden)

    Noof A. Alenazi

    2016-10-01

    Full Text Available Bisphenol A (BPA is an estrogen-mimicking chemical that can be selectively detected in water using a chemical sensor based on molecularly imprinted polymers (MIPs. However, the utility of BPA-MIPs in sensor applications is limited by the presence of non-specific binding sites. This study explored a dual approach to eliminating these sites: optimizing the molar ratio of the template (bisphenol A to functional monomer (methacrylic acid to cross-linker (ethylene glycol dimethacrylate, and esterifying the carboxylic acid residues outside of specific binding sites by treatment with diazomethane. The binding selectivity of treated MIPs and non-treated MIPs for BPA and several potential interferents was compared by capillary electrophoresis with ultraviolet detection. Baclofen, diclofenac and metformin were demonstrated to be good model interferents to test all MIPs for selective binding of BPA. Treated MIPs demonstrated a significant decrease in binding of the interferents while offering high selectivity toward BPA. These results demonstrate that conventional optimization of the molar ratio, together with advanced esterification of non-specific binding sites, effectively minimizes the residual binding of interferents with MIPs to facilitate BPA sensing.

  16. Actions of insecticides on the insect GABA receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J. (School of Biological and Molecular Sciences, Oxford Polytechnic, Headington, Oxford (England))

    1991-01-01

    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using (35S)t-butylbicyclophosphorothionate (( 35S)TBPS) binding and voltage-clamp techniques. Specific binding of (35S)TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 {plus minus} 2.9 nM and a Bmax value of 1770 {plus minus} 40 fmol/mg protein. (35S)TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of (35S)TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on (35S)TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current.

  17. Selective dorsal rhizotomy for spastic diplegia secondary to stroke in an adult patient.

    Science.gov (United States)

    Eppinger, Melissa Ann; Berman, Casey Melissa; Mazzola, Catherine Anne

    2015-01-01

    Selective dorsal rhizotomy (SDR) is often recommended for children with spastic paraparesis and cerebral palsy. SDR reduces spasticity in the lower extremities for these children with spastic paraplegia. However, SDR is infrequently recommended for adults with spasticity. Spastic diplegia in adult patients can be due to stroke, brain or spinal cord injury from trauma, infection, toxic-metabolic disorders, and other causes. Although rarely considered, SDR is an option for adult patients with spastic diplegia as well. The authors describe a patient who underwent a SDR with a successful postoperative outcome. This man suffered a hypertensive and hemorrhagic stroke secondary to intravenous drug abuse at age 46. A SDR was performed after two failed intrathecal baclofen pump placements due to recurrent infections, likely resulting from his immunocompromised status. The patient underwent lumbar laminectomies and dorsal rhizotomies at levels L1-S1 bilaterally. Postoperatively, the patient's spasticity was significantly reduced. His Ashworth spasticity score decreased from 4/5 to 1/5, and the reduction in tone has been durable over 3 years. SDR in older patients with spastic paraparesis may be considered as a treatment option.

  18. Prevention of severe contractures might replace multilevel surgery in cerebral palsy: results of a population-based health care programme and new techniques to reduce spasticity.

    Science.gov (United States)

    Hägglund, Gunnar; Andersson, Sofia; Düppe, Henrik; Lauge-Pedersen, Henrik; Pedertsen, Henrik Lauge; Nordmark, Eva; Westbom, Lena

    2005-07-01

    During the 1990s three new techniques to reduce spasticity and dystonia in children with cerebral palsy (CP) were introduced in southern Sweden: selective dorsal rhizotomy, continuous intrathecal baclofen infusion and botulinum toxin treatment. In 1994 a CP register and a health care programme, aimed to prevent hip dislocation and severe contractures, were initiated in the area. The total population of children with CP born 1990-1991, 1992-1993 and 1994-1995 was evaluated and compared at 8 years of age. In non-ambulant children the passive range of motion in hip, knee and ankle improved significantly from the first to the later age groups. Ambulant children had similar range of motion in the three age groups, with almost no severe contractures. The proportion of children treated with orthopaedic surgery for contracture or skeletal torsion deformity decreased from 40 to 15% (P = 0.0019). One-fifth of the children with spastic diplegia had been treated with selective dorsal rhizotomy. One-third of the children born 1994-1995 had been treated with botulinum toxin before 8 years of age. With early treatment of spasticity, early non-operative treatment of contracture and prevention of hip dislocation, the need for orthopaedic surgery for contracture or torsion deformity is reduced, and the need for multilevel procedures seems to be eliminated.

  19. Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome.

    Science.gov (United States)

    Quezada, Julio; Coffman, Keith A

    2018-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

  20. Rescue of inhibitory synapse strength following developmental hearing loss.

    Directory of Open Access Journals (Sweden)

    Vibhakar C Kotak

    Full Text Available Inhibitory synapse dysfunction may contribute to many developmental brain disorders, including the secondary consequences of sensory deprivation. In fact, developmental hearing loss leads to a profound reduction in the strength of inhibitory postsynaptic currents (IPSCs in the auditory cortex, and this deficit persists into adulthood. This finding is consistent with the general theory that the emergence of mature synaptic properties requires activity during development. Therefore, we tested the prediction that inhibitory strength can be restored following developmental hearing loss by boosting GABAergic transmission in vivo. Conductive or sensorineural hearing loss was induced surgically in gerbils prior to hearing onset and GABA agonists were then administered for one week. IPSCs were subsequently recorded from pyramidal neurons in a thalamocortical brain slice preparation. Administration of either a GABA(A receptor a1 subunit specific agonist (zolpidem, or a selective GABA reuptake inhibitor (SGRI, rescued IPSC amplitude in hearing loss animals. Furthermore, this restoration persisted in adults, long after drug treatment ended. In contrast, a GABA(B receptor agonist baclofen did not restore inhibitory strength. IPSCs could also be restored when SGRI administration began 3 weeks after sensory deprivation. Together, these results demonstrate long-lasting restoration of cortical inhibitory strength in the absence of normal experience. This suggests that in vivo GABA(A receptor activation is sufficient to promote maturation, and this principle may extend to other developmental disorders associated with diminished inhibitory function.

  1. Hypoventilation in glycine-receptor antibody related progressive encephalomyelitis, rigidity and myoclonus.

    Science.gov (United States)

    Bourke, David; Roxburgh, Richard; Vincent, Angela; Cleland, James; Jeffery, Oliver; Dugan, Niels; Abernethy, David; King, Allison; Anderson, Neil

    2014-05-01

    Glycine receptor (GlyR) antibodies have been identified in patients with rigidity and hyperekplexia, but the clinical phenotype associated with these antibodies has not been fully elucidated. The clinical features in two additional patients with GlyR antibodies are described. A 55-year-old man presented with stimulus-induced hyperekplexia and rigidity in the lower limbs and trunk. He initially responded to benzodiazepines, but presented after 18 months with severe, painful, prolonged spasms associated with supraventricular and ventricular arrhythmias, hypoventilation and oxygen desaturation requiring intubation. He improved following treatment with clonazepam, baclofen and immunomodulatory therapies. A 58-year-old woman presented with stiffness in the legs and hyperekplexia associated with hypoventilation, at times leading to loss of consciousness. She responded to benzodiazepines and has remained in remission. The clinical picture associated with GlyR antibodies includes autonomic dysfunction, cardiac arrhythmias and hypoventilation. It is important to recognise these serious complications early to limit mortality from this treatable condition. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  2. Clinical presentation and management of dyskinetic cerebral palsy.

    Science.gov (United States)

    Monbaliu, Elegast; Himmelmann, Kate; Lin, Jean-Pierre; Ortibus, Els; Bonouvrié, Laura; Feys, Hilde; Vermeulen, R Jeroen; Dan, Bernard

    2017-09-01

    Cerebral palsy is the most frequent cause of severe physical disability in childhood. Dyskinetic cerebral palsy (DCP) is the second most common type of cerebral palsy after spastic forms. DCP is typically caused by non-progressive lesions to the basal ganglia or thalamus, or both, and is characterised by abnormal postures or movements associated with impaired tone regulation or movement coordination. In DCP, two major movement disorders, dystonia and choreoathetosis, are present together most of the time. Dystonia is often more pronounced and severe than choreoathetosis, with a major effect on daily activity, quality of life, and societal participation. The pathophysiology of both movement disorders is largely unknown. Some emerging hypotheses are an imbalance between indirect and direct basal ganglia pathways, disturbed sensory processing, and impaired plasticity in the basal ganglia. Rehabilitation strategies are typically multidisciplinary. Use of oral drugs to provide symptomatic relief of the movement disorders is limited by adverse effects and the scarcity of evidence that the drugs are effective. Neuromodulation interventions, such as intrathecal baclofen and deep brain stimulation, are promising options. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators.

    Science.gov (United States)

    Filip, Małgorzata; Frankowska, Małgorzata; Sadakierska-Chudy, Anna; Suder, Agata; Szumiec, Lukasz; Mierzejewski, Paweł; Bienkowski, Przemyslaw; Przegaliński, Edmund; Cryan, John F

    2015-01-01

    γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which may have therapeutic effects similar to those of agonists but with superior side-effect profiles. This review summarizes current preclinical evidence supporting a role of GABAB receptor PAMs in drug addiction in several paradigms with relevance to reward processes and drug abuse liability. Extensive behavioral research in recent years has indicated that PAMs of GABAB receptors may have a therapeutic efficacy in cocaine, nicotine, amphetamine and alcohol dependence. The magnitude of the effects observed are similar to that of the clinically approved drug baclofen, an agonist at GABAB receptors. Moreover, given that anxiolytic effects are also reported with such ligands they may also benefit in mitigating the withdrawal from drugs of abuse. In summary, a wealth of data now supports the benefits of GABAB receptor PAMs and clinical validation is now warranted. Copyright © 2014. Published by Elsevier Ltd.

  4. Tonic dystonia: an uncommon complication of reflex sympathetic dystrophy syndrome. A review of five cases.

    Science.gov (United States)

    Morelet, Aude; Gagneux-Lemoussu, Laurence; Brochot, Pascal; Ackah-Miezan, Stanley; Colmet-Daage, Jean-François; Gaillard, François; Boyer, François; Eschard, Jean-Paul; Etienne, Jean-Claude

    2005-05-01

    Tonic dystonia is an underrecognized complication of reflex sympathetic dystrophy syndrome (RSDS) characterized by an increase in muscle tone at the site of injury. Case-reports.- We describe five cases of tonic dystonia complicating RSDS of the lower extremity. There were four women and one man, with a mean age of 52 years. In addition to the typical features of RSDS, the patients had fixed equinovarus of the foot with hyperextension or hyperflexion of the great toe. In two patients, examination after spinal anesthesia showed that the deformity was reducible. Spontaneous resolution of the dystonia occurred in one patient. Another patient failed to experience meaningful improvement after a motor block followed by botulinic toxin injections. In two patients, the same treatment was followed by a slight improvement. Treatment options are still being evaluated in the last patient. Discussion.- Tonic dystonia is an underrecognized complication of RSDS that often develops after a minor injury yet causes prolonged pain and disability. Spread of the dystonia to other sites is not infrequent. The underlying mechanisms remain unclear but may involve dysfunction of the central or peripheral nervous system or psychogenic factors. Suggested treatments include motor block, intrathecal baclofen, sympathetic block, and sympathectomy. However, none of these treatments has been proved effective. Conclusion.- The five cases described here provide useful information on RSDS-associated tonic dystonia, a condition that runs a protracted course and remains difficult to manage.

  5. Actions of insecticides on the insect GABA receptor complex

    International Nuclear Information System (INIS)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J.

    1991-01-01

    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using [35S]t-butylbicyclophosphorothionate [( 35S]TBPS) binding and voltage-clamp techniques. Specific binding of [35S]TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 ± 2.9 nM and a Bmax value of 1770 ± 40 fmol/mg protein. [35S]TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of [35S]TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on [35S]TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current

  6. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

    Directory of Open Access Journals (Sweden)

    Mathew Jobin

    2012-02-01

    Full Text Available Abstact Background Gamma amino butyric acid (GABA, the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P Aά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P Aά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

  7. [A case of prolonged paroxysmal sympathetic hyperactivity].

    Science.gov (United States)

    Yamamoto, Akiko; Ide, Shuhei; Iwasaki, Yuji; Kaga, Makiko; Arima, Masataka

    2016-03-01

    We report the case of a 4-year-old girl who presented with paroxysmal sympathetic hyperactivity (PSH), after developing severe hypoxic-ischemic-encephalopathy because of cardiopulmonary arrest. She showed dramatic paroxysmal sympathetic activity with dystonia. She was treated with wide variety of medications against PSH, which were found to be effective in previous studies. Among them, morphine, bromocriptine, propranolol, and clonidine were effective in reducing the frequency of her attacks while gabapentin, baclofen, dantrolene, and benzodiazepine were ineffective. Though the paroxysms decreased markedly after the treatment, they could not be completely controlled beyond 500 days. Following the treatment, levels of plasma catecholamines and their urinary metabolites decreased to normal during inter- paroxysms. However, once a paroxysm had recurred, these levels were again very high. This case study is considered significant for two rea- sons. One is that PSH among children have been rarely reported, and the other is that this case of prolonged PSH delineated the transition of plasma catecholamines during the treatment. The excitatory: inhibitory ratio (EIR) model proposed by Baguley was considered while dis- cussing drug sensitivity in this case. Accumulation of similar case studies will help establish more effective treatment strategies and elucidate the pathophysiology of PSH.

  8. A septal-hypothalamic pathway drives orexin neurons which is necessary for conditioned cocaine preference

    Science.gov (United States)

    Sartor, Gregory C.; Aston-Jones, Gary

    2012-01-01

    Orexins (also called hypocretins) have been shown to be importantly involved in reward and addiction, but little is known about the circuitry that regulates orexin neuronal activity during drug-seeking behaviors. Here, we examined inputs to the lateral hypothalamic (LH) orexin cell field from the lateral septum (LS) using tract-tracing and Fos immunohistochemistry after cocaine (10mg/kg) conditioned place preference (CPP) in Sprague Dawley rats. We found that neurons in rostral LS (LSr) that project to LH are Fos-activated in proportion to cocaine CPP, and that inhibition of LSr neurons with local baclofen and muscimol microinjection (0.3/0.03 nmol) blocks expression of Fos in LH orexin cells and cocaine preference. In addition, using local inactivation in LS and orexin antisense Morpholinos in LH, we found that LSr influences on LH orexin neurons are critical for the expression of cocaine preference. These results indicate that LSr activates LH orexin neurons during cocaine place preference, and that this circuit is essential for expression of cocaine place preference. PMID:22457508

  9. [Spasmodic torticollis and vertebral hemangioma].

    Science.gov (United States)

    Durán, E; Chacón, J R

    Spasmodic torticollis in young patients should give rise to a clinical suspicion that this is secondary to another primary disorder. Therefore a series of diagnostic tests should be carried out before it is labelled as idiopathic. The patient was a thirty year old man who had had difficulty in writing with his right hand since childhood. At the age of 20 years he was diagnosed as having writer's cramp and idiopathic spasmodic torticollis. On general physical examination no abnormalities were found. On neurological examination he had: absence of reflexes of both arms, limited but painless rotation of the neck towards the left and hypertrophy of the left trapezius muscle. Laboratory, neurophysiological and neuroimaging investigations seeking a secondary cause for the torticollis were all normal. There were no Keyser-Fleischer rings. Chest X-ray showed, dorsal scoliosis with convexity to the left. CAT and MR of the spine showed a hemangioma in the body of T1. On arteriography of the supra-aortic and vertebral trunks a hemangioma was found at T1 which received contrast material via a branch of the right thyro-bi-cervico-scapular trunk. Various treatments were tried (diazepam, Botox, Dysport, tetrabenazine, baclofen, etc.) with no improvement. A definite diagnosis of secondary torticollis could not be made since the hemangioma was supplied by a very narrow vascular pedicle, so embolization was contraindicated. Cervical spinal cord alterations may cause focal dystonia due to increased excitability of the spinal motor neurone, due to dysfunction of the disinhibitory descending reciprocal paths.

  10. Medical management of trigeminal neuropathic pains.

    Science.gov (United States)

    Zakrzewska, Joanna M

    2010-06-01

    Although trigeminal neuralgia has traditionally been considered the prime neuralgic condition in the face region, other forms of neuropathic pain are now being more frequently recognized and require recognition and a different management approach. This review principally covers medical management of trigeminal neuralgia; but also included is glossopharyngeal neuralgia, trigeminal neuropathic pain (atypical odontalgia) and burning mouth syndrome. Systematic reviews and guidelines will be discussed. An update will be provided of drug therapy for these relatively rare facial pains. Trigeminal neuralgia continues to be best managed using anticonvulsant drugs, the primary ones being carbamazepine and oxcarbazepine; baclofen may be helpful and, of the newly emerging drugs, pregabalin has potential. Glossopharyngeal neuralgia remains managed in the same way as trigeminal neuralgia. Trigeminal neuropathic pain is probably best managed according to guidelines used for the management of neuropathic pain, which include the use of tricyclic antidepressants, gabapentin, pregabalin, duloxetine, venalafaxine and topical lidocaine. Burning mouth syndrome is a neuropathic pain managed initially with topical clonazepam and then with other neuropathic drugs. Patients need to be involved in their management.

  11. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease

    Science.gov (United States)

    Gitto, Stefano; Golfieri, Lucia; Caputo, Fabio; Grandi, Silvana; Andreone, Pietro

    2016-01-01

    Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption. PMID:26784248

  12. Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity.

    Science.gov (United States)

    Koehler, Jürgen; Feneberg, Wolfgang; Meier, Martin; Pöllmann, Walter

    2014-09-01

    This detailed medical charts' data collection study conducted at a multiple sclerosis (MS) clinic in Germany evaluated the effectiveness of tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray in patients with resistant MS spasticity. Over a 15-month timeframe, THC:CBD spray was initiated in 166 patients. Mean follow-up was 9 months. In all, 120 patients remained on treatment for a response rate of 72%. THC:CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. Among responders, the mean spasticity 0-10 numerical rating scale (NRS) score decreased by 57%, from 7.0 before treatment to 3.0 within 10 days of starting THC:CBD spray. The mean dosage was 4 sprays/day. Most patients who withdrew from treatment (40/46) had been receiving THC:CBD spray for less than 60 days. Main reasons for treatment discontinuation were: adverse drug reactions, mainly dizziness, fatigue and oral discomfort (23 patients; 13.9%); lack of efficacy (14 patients; 8.4%); or need for a baclofen pump (9 patients; 5.4%). No new safety signals were noted with THC:CBD spray during the evaluation period. In this routine clinical practice setting at an MS clinic in Germany, THC:CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.

  13. A functional assay to measure postsynaptic gamma-aminobutyric acidB responses in cultured spinal cord neurons: Heterologous regulation of the same K+ channel

    Energy Technology Data Exchange (ETDEWEB)

    Kamatchi, G.L.; Ticku, M.K. (Univ. of Texas Health Science Center, San Antonio (USA))

    1991-02-01

    The stimulation of postsynaptic gamma-aminobutyric acid (GABA)B receptors leads to slow inhibitory postsynaptic potentials due to the influx of K(+)-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABAB receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen. Apart from the GABAB receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT1 alpha agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABAB, adenosine1 and 5-HT1 alpha receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K(+)-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K(+)-channel through the Gi/Go proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABAB synaptic pharmacology in vitro, using spinal cord neurons.

  14. GABA modulates baroreflex in the ventral tegmental area in rat.

    Science.gov (United States)

    Hatam, Masoumeh; Rasoulpanah, Minoo; Nasimi, Ali

    2015-12-01

    There are some reports demonstrating the cardiovascular functions of the ventral tegmental area (VTA). About 20-30% of the VTA neurons are GABAergic, which might play a role in baroreflex modulation. This study was performed to find the effects of GABA(A), GABA(B) receptors and reversible synaptic blockade of the VTA on baroreflex. Drugs were microinjected into the VTA of urethane anesthetized rats, and the maximum change of blood pressure and the gain of the reflex bradycardia in response to intravenous phenylephrine (Phe) injection were compared with the preinjection and the control values. Microinjection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA(A) antagonist, into the VTA strongly decreased the Phe-induced hypertension, indicating that GABA itself attenuated the baroreflex. Muscimol, a GABA(A) agonist (30 mM, 100 nl), produced no significant changes. Baclofen, a GABA(B) receptor agonist (1000 pmole/100 nl), moderately attenuated the baroreflex, however phaclofen, a GABA(B) receptor antagonist (1000 pmole/100 nl), had no significant effect. In conclusion, for the first time, we demonstrated that GABA(A) receptors of the VTA strongly attenuate and GABA(B) receptors of the VTA moderately attenuate baroreflex in rat. © 2015 Wiley Periodicals, Inc.

  15. Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.

    Science.gov (United States)

    Tazir, Meriem; Hamadouche, Tarik; Nouioua, Sonia; Mathis, Stephane; Vallat, Jean-Michel

    2014-12-15

    Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed. In this regard, peripheral nerve lesions in GDAP1 mutations (AR CMT1A), such as mitochondrial abnormalities, have been newly demonstrated. Otherwise, while demyelinating autosomal recessive CMT used to be classified as CMT4 (A, B, C …), we propose a simplified classification such as AR CMT1 (A, B, C …), and AR CMT2 for axonal forms. Also, we stress that next generation sequencing techniques, now considered to be the most efficient methods of genetic testing in CMT, will be helpful in molecular diagnosis and research of new genes involved. Finally, while no effective therapy is known to date, ongoing new therapeutic trials such as PXT3003 (a low dose combination of the three already approved drugs baclofen, naltrexone, and D-sorbitol) give hopes for potential curative treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Interventions for managing skeletal muscle spasticity following traumatic brain injury.

    Science.gov (United States)

    Synnot, Anneliese; Chau, Marisa; Pitt, Veronica; O'Connor, Denise; Gruen, Russell L; Wasiak, Jason; Clavisi, Ornella; Pattuwage, Loyal; Phillips, Kate

    2017-11-22

    pharmacological (baclofen, botulinum toxin A) and non-pharmacological (casting, physiotherapy, splints, tilt table standing and electrical stimulation) interventions, often in combination. The studies which tested the effect of baclofen and tizanidine did not report their results adequately. Where outcome data were available, spasticity and adverse events were reported, in addition to some secondary outcome measures.Of the five studies with results, three were funded by governments, charities or health services and two were funded by a pharmaceutical or medical technology company. The four studies without useable results were funded by pharmaceutical or medical technology companies.It was difficult to draw conclusions about the effectiveness of these interventions due to poor reporting, small study size and the fact that participants with TBI were usually only a proportion of the overall total. Meta-analysis was not feasible due to the paucity of data and heterogeneity of interventions and comparator groups. Some studies concluded that the intervention they tested had beneficial effects on spasticity, and others found no difference between certain treatments. The most common adverse event was minor skin damage in people who received casting. We believe it would be misleading to provide any further description of study results given the quality of the evidence was very low for all outcomes. The very low quality and limited amount of evidence about the management of spasticity in people with TBI means that we are uncertain about the effectiveness or harms of these interventions. Well-designed and adequately powered studies using functional outcome measures to test the interventions used in clinical practice are needed.

  17. Selective dorsal rhizotomy for the treatment of severe spastic cerebral palsy: efficacy and therapeutic durability in GMFCS grade IV and V children.

    Science.gov (United States)

    D'Aquino, Daniel; Moussa, Ahmad A; Ammar, Amr; Ingale, Harshal; Vloeberghs, Michael

    2018-04-01

    Selective dorsal rhizotomy (SDR) has been established as an effective surgical treatment for spastic diplegia. The applicability of SDR to the full spectrum of spastic cerebral palsy and the durability of its therapeutic effects remain under investigation. There are currently limited data in the literature regarding efficacy and outcomes following SDR in Gross Motor Function Classification System (GMFCS) IV and V patients. Intrathecal baclofen has traditionally been the surgical treatment of choice for these patients. When utilised primarily as a treatment for the relief of spasticity, it is proposed that SDR represents a rational and effective treatment option for this patient group. We report our outcomes of SDR performed on children with severe cerebral palsy (GMFCS grade IV and V). The commensurate improvement in upper as well as lower limb spasticity is highlighted. Apparent benefit to urological function following SDR in this patient group is also discussed. A retrospective review of prospectively collected data for 54 paediatric patients with severe cerebral palsy (GMFCS IV-V) who received SDR plus specialised physiotherapy. Mean age was 10.2 years (range, 3.0-19.5). SDR guided by electrophysiological monitoring was performed by a single experienced neurosurgeon. All subjects received equivalent physiotherapy. The primary outcome measure was change to the degree of spasticity following SDR. Spasticity of upper and lower limb muscle groups were quantified and standardised using the Ashworth score. Measures were collected at baseline and at 2-, 8- and 14-month postoperative intervals. In addition, baseline and 6-month postoperative urological function was also evaluated as a secondary outcome measure. The mean lower limb Ashworth score at baseline was 3.2 (range, 0-4). Following SDR, significant reduction in lower limb spasticity scores was observed at 2 months and maintained at 8 and 14 months postoperatively (Wilcoxon rank, p SDR was also observed (mean

  18. Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo

    Directory of Open Access Journals (Sweden)

    Bettler Bernhard

    2009-11-01

    Full Text Available Abstract Background γ-aminobutyric acid (GABA is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABAA and metabotropic (GABAB receptors. GABAB receptors are widely expressed in the central and the peripheral nervous system. Although there is evidence for a key function of GABAB receptors in the modulation of pain, the relative contribution of peripherally- versus centrally-expressed GABAB receptors is unclear. Results In order to elucidate the functional relevance of GABAB receptors expressed in peripheral nociceptive neurons in pain modulation we generated and analyzed conditional mouse mutants lacking functional GABAB(1 subunit specifically in nociceptors, preserving expression in the spinal cord and brain (SNS-GABAB(1-/- mice. Lack of the GABAB(1 subunit precludes the assembly of functional GABAB receptor. We analyzed SNS-GABAB(1-/- mice and their control littermates in several models of acute and neuropathic pain. Electrophysiological studies on peripheral afferents revealed higher firing frequencies in SNS-GABAB(1-/- mice compared to corresponding control littermates. However no differences were seen in basal nociceptive sensitivity between these groups. The development of neuropathic and chronic inflammatory pain was similar across the two genotypes. The duration of nocifensive responses evoked by intraplantar formalin injection was prolonged in the SNS-GABAB(1-/- animals as compared to their control littermates. Pharmacological experiments revealed that systemic baclofen-induced inhibition of formalin-induced nociceptive behaviors was not dependent upon GABAB(1 expression in nociceptors. Conclusion This study addressed contribution of GABAB receptors expressed on primary afferent nociceptive fibers to the modulation of pain. We observed that neither the development of acute and chronic pain nor the analgesic effects of a systematically-delivered GABAB agonist was significantly

  19. Hippocampal Gαq/11 but not Gαo-coupled receptors are altered in aging

    Science.gov (United States)

    McQuail, Joseph A.; Davis, Kathleen N.; Miller, Frances; Hampson, Robert E.; Deadwyler, Samuel A.; Howlett, Allyn C.; Nicolle, Michelle M.

    2013-01-01

    Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/11 is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/11 and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344×BNF1 hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/11 was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/11 with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/11 function was measured in hippocampal subregion CA1 by determining changes in [Ca2+]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca2+]i was lower in aged CA1 relative to young while mGluR-mediated integrated [Ca2+]i responses tended to be larger in aged. GPCR modulation of [Ca2+]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/11 within the hippocampus leading to deficient modulation of [Ca2+]i following stimulation of mAChRs but these changes are not related to spatial learning. PMID:23347951

  20. Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats.

    Science.gov (United States)

    Beas, B S; McQuail, J A; Ban Uelos, C; Setlow, B; Bizon, J L

    2017-03-14

    The prefrontal cortex (PFC) is critical for the ability to flexibly adapt established patterns of behavior in response to a change in environmental contingencies. Impaired behavioral flexibility results in maladaptive strategies such as perseveration on response options that no longer produce a desired outcome. Pharmacological manipulations of prefrontal cortical GABAergic signaling modulate behavioral flexibility in animal models, and prefrontal cortical interneuron dysfunction is implicated in impaired behavioral flexibility that accompanies neuropsychiatric disease. As deficits in behavioral flexibility also emerge during the normal aging process, the goal of this study was to determine the role of GABAergic signaling, specifically via prefrontal cortical GABA(B) receptors, in such age-related deficits. Young and aged rats were trained in a set shifting task performed in operant chambers. First, rats learned to discriminate between two response levers to obtain a food reward on the basis of a cue light illuminated above the correct lever. Upon acquisition of this initial discrimination, the contingencies were shifted such that rats had to ignore the cue light and respond on the levers according to their left/right positions. Both young and aged rats acquired the initial discrimination similarly; however, aged rats were impaired relative to young following the set shift. Among aged rats, GABA(B) receptor expression in the medial prefrontal cortex (mPFC) was strongly correlated with set shifting, such that lower expression was associated with worse performance. Subsequent experiments showed that intra-mPFC administration of the GABA(B) receptor agonist baclofen enhanced set shifting performance in aged rats. These data directly link GABAergic signaling via GABA(B) receptors to impaired behavioral flexibility associated with normal aging. Copyright © 2016. Published by Elsevier Ltd.

  1. Role of orbitofrontal cortex neuronal ensembles in the expression of incubation of heroin craving

    Science.gov (United States)

    Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R.M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.

    2012-01-01

    In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin-seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6-h/d for 10 d) and assessed cue-induced heroin-seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin-seeking increased from 1 day to 14 days and was accompanied by increased Fos expression in ~12% of OFC neurons. Non-selective inactivation of OFC neurons with the GABA agonists baclofen+muscimol decreased cue-induced heroin-seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin-seeking after 14 withdrawal days. We trained cfos-lacZ transgenic rats to self-administer heroin and 11 days later re-exposed them to heroin-associated cues or novel cues for 15 min (induction day) followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 days later. Daun02 selectively decreased cue-induced heroin-seeking in rats previously re-exposed to the heroin-associated cues on induction day, but not in rats previously exposed to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving. PMID:22915104

  2. Progressive Encephalomyelitis with Rigidity and Myoclonus Associated With Anti-GlyR Antibodies and Hodgkin’s Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Linda Borellini

    2017-08-01

    Full Text Available IntroductionA 60-year-old man presented with a 6-month history of low back pain and progressive rigidity of the trunk and lower limbs, followed by pruritus, dysphonia, hyperhydrosis, and urinary retention. Brain and spinal imaging were normal. EMG showed involuntary motor unit hyperactivity. Onconeural, antiglutamic acid decarboxylase (anti-GAD, voltage-gated potassium channel, and dipeptidyl peptidase-like protein 6 (DPPX autoantibodies were negative. CSF was negative. Symptoms were partially responsive to baclofen, gabapentin, and clonazepam, but he eventually developed severe dysphagia. Antiglycine receptor (anti-GlyR antibodies turned out positive on both serum and CSF. A plasmapheresis cycle was completed with good clinical response. A PET scan highlighted an isolated metabolically active axillary lymphnode that turned out to be a classic type Hodgkin lymphoma (HL, in the absence of bone marrow infiltration nor B symptoms. Polychemotherapy with ABVD protocol was completed with good clinical response and at 1-year follow-up the neurological examination is normal.BackgroundProgressive encephalomyelitis with rigidity and myoclonus (PERM is a rare and severe neurological syndrome characterized by muscular rigidity and spasms as well as brain stem and autonomic dysfunction. It can be associated with anti-GAD, GlyR, and DPPX antibodies. All of these autoantibodies may be variably associated with malignant tumors and their response to immunotherapy, as well as to tumor removal, is not easily predictable.ConclusionProgressive encephalomyelitis with rigidity and myoclonus has already been described in association with HL, but this is the first case report of a HL manifesting as anti-GlyR antibodies related PERM. Our report highlights the importance of malignancy screening in autoimmune syndromes of suspected paraneoplastic origin.

  3. Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

    Directory of Open Access Journals (Sweden)

    van Rhijn Lodewijk W

    2010-06-01

    Full Text Available Abstract Background Cerebral palsy (CP may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. Methods We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS, Gross Motor Function Measure (GMFM and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS for spasticity, pain and ease of care. Results A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. Conclusion RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial.

  4. Evaluation of usefulness of scintigraphic imaging in diagnosis of intrathecal drug delivery system malfunction – a preliminary report

    International Nuclear Information System (INIS)

    Teodorczyk, Jacek; Szmuda, Tomasz; Siemiński, Mariusz; Lass, Piotr; Słoniewski, Paweł

    2013-01-01

    Implantable intrathecal drug delivery systems (IDDS) are basic tool enabling chronic intrathecal pharmacotherapy. Lack of expected clinical results of IDDS therapy necessitates search for the cause with the help of diagnostic imaging methods among other things. Beside radiological techniques, it is also possible to visually assess IDDS systems by nuclear medicine methods. In this study we assess utility of radioisotopic methods in differential diagnosis of failure of therapy with IDDS systems. Scintigraphic studies were performed in selected patients with neurological diseases associated with spasticity, who had IDDS system implanted and were unable to maintain satisfying clinical effect of inrathecally infused baclofen. After emptying the IDDS system of the drug, radiotracer (99mTc-DTPA) solution was injected into the pump reservoir. Subsequently, a series of scintigraphic images was registered, demonstrating passage and distribution of the infused radiotracer. In all investigated cases, scintigraphic study resulted in acquiring relevant additional diagnostic information. Normal or disrupted distribution of radiotracer in spinal canal allowed for a diagnosis drug resistance or demonstrated presence of arachnoid adhesions respectively. Early appearance of radiotracer in blood was considered a proof of leak. Our examinations had decisive influence on further patient treatment, allowing for diagnosis of drug resistance in one patient or complication related to IDDS system in three other cases including breakage of a catheter, pump malfunction and arachnoid adhesions. Scintigraphic methods carry significant amount of information facilitating final diagnosis of the cause of IDDS therapy failure. They should become an important element complementing the diagnostic strategy in patients with suspected failure of intrathecal drug administration systems. Interpretation of radioisotopic studies, since they are purely functional, must be performed in strict relation to

  5. The Treatment of Chronic Coccydynia and Postcoccygectomy Pain With Pelvic Floor Physical Therapy.

    Science.gov (United States)

    Scott, Kelly M; Fisher, Lauren W; Bernstein, Ira H; Bradley, Michelle H

    2017-04-01

    Coccydynia is a challenging disorder that often is refractory to treatments such as medications and injections. Physical therapy for coccydynia rarely has been studied. To evaluate the efficacy of pelvic floor physical therapy for reducing pain levels in patients with coccydynia. Retrospective chart review. The pelvic floor rehabilitation clinic of a major university hospital. A total of 124 consecutive patients over age 18 with a chief complaint of coccydynia between 2009 and 2012. A subgroup of 17 of the 124 patients had previously undergone coccygectomy with continued pain postoperatively. The primary treatment intervention was pelvic floor physical therapy aimed at pelvic floor muscle relaxation. Secondary treatment interventions included the prescription of baclofen for muscle relaxation (19% of patients), ganglion impar blocks (8%), or coccygeus trigger point injections (17%). Primary outcome measures included final minimum, average, and maximum pain numeric rating scales. A secondary outcome measure was the patient's subjective percent global improvement assessment. Baseline demographics were used to determine which pretreatment characteristics were correlated with treatment outcomes. Of the 124 patients, 93 participated in pelvic floor physical therapy and were included in statistical analysis. For the 79 patients who completed treatment (with a mean of 9 physical therapy sessions), the mean average pain ratings decreased from 5.08 to 1.91 (P physical therapy. Pain duration and history of trauma did not affect treatment outcomes. Pelvic floor physical therapy is a safe and effective method of treating coccydynia. III. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  6. An integrative pharmacological approach to radio telemetry and blood sampling in pharmaceutical drug discovery and safety assessment

    Directory of Open Access Journals (Sweden)

    Kamendi Harriet W

    2011-01-01

    Full Text Available Abstract Background A successful integration of the automated blood sampling (ABS and telemetry (ABST system is described. The new ABST system facilitates concomitant collection of physiological variables with blood and urine samples for determination of drug concentrations and other biochemical measures in the same rat without handling artifact. Method Integration was achieved by designing a 13 inch circular receiving antenna that operates as a plug-in replacement for the existing pair of DSI's orthogonal antennas which is compatible with the rotating cage and open floor design of the BASi Culex® ABS system. The circular receiving antenna's electrical configuration consists of a pair of electrically orthogonal half-toroids that reinforce reception of a dipole transmitter operating within the coil's interior while reducing both external noise pickup and interference from other adjacent dipole transmitters. Results For validation, measured baclofen concentration (ABST vs. satellite (μM: 69.6 ± 23.8 vs. 76.6 ± 19.5, p = NS and mean arterial pressure (ABST vs. traditional DSI telemetry (mm Hg: 150 ± 5 vs.147 ± 4, p = NS variables were quantitatively and qualitatively similar between rats housed in the ABST system and traditional home cage approaches. Conclusion The ABST system offers unique advantages over traditional between-group study paradigms that include improved data quality and significantly reduced animal use. The superior within-group model facilitates assessment of multiple physiological and biochemical responses to test compounds in the same animal. The ABST also provides opportunities to evaluate temporal relations between parameters and to investigate anomalous outlier events because drug concentrations, physiological and biochemical measures for each animal are available for comparisons.

  7. New effects of GABAB receptor allosteric modulator rac-BHFF on ambient GABA, uptake/release, Em and synaptic vesicle acidification in nerve terminals.

    Science.gov (United States)

    Pozdnyakova, N; Dudarenko, M; Borisova, T

    2015-09-24

    Positive allosteric modulators of GABAB receptors have great therapeutic potential for medications of anxiety, depression, etc. The effects of recently discovered modulator rac-BHFF on the key characteristics of GABAergic neurotransmission were investigated in cortical and hippocampal presynaptic nerve terminals of rats (synaptosomes). The ambient level of [(3)H]GABA that is a balance between release and uptake of the neurotransmitter increased significantly in the presence of rac-BHFF (at concentrations 10-30μM). The initial velocity of synaptosomal [(3)H]GABA uptake was suppressed by the modulator. In the presence of GABA transporter blocker NO-711, it was shown that rac-BHFF increased tonic release of [(3)H]GABA from synaptosomes (at concentrations 3-30μM). Rac-BHFF within the concentration range of 0.3-30μM did not enhance inhibiting effect of (±)-baclofen on depolarization-induced exocytotic release of [(3)H]GABA. Rac-BHFF (0.3-30μM) caused dose-dependent depolarization of the plasma membrane and dissipation of the proton gradient of synaptic vesicles in synaptosomes that was shown in the absence/presence of GABAB receptor antagonist saclofen using fluorescent dyes rhodamine 6G and acridine orange, respectively, and so, the above effects of rac-BHFF were not associated with the modulation of presynaptic GABAB receptors. Therefore, drug development strategy of positive allosteric modulation of GABAB receptors is to eliminate the above side effects of rac-BHFF in presynapse, and vice versa, these new properties of rac-BHFF may be exploited appropriately. Copyright © 2015. Published by Elsevier Ltd.

  8. Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats.

    Science.gov (United States)

    Arguello, Amy A; Wang, Rong; Lyons, Carey M; Higginbotham, Jessica A; Hodges, Matthew A; Fuchs, Rita A

    2017-08-01

    Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation. Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol (BM)) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e., non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in experiment 2 received vehicle or BM into the AI after a 15-min reexposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later. BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine memory reconsolidation. These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.

  9. KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats.

    Science.gov (United States)

    Li, Xia; Sturchler, Emmanuel; Kaczanowska, Katarzyna; Cameron, Michael; Finn, M G; Griffin, Patrick; McDonald, Patricia; Markou, Athina

    2017-05-01

    GABA B receptors (GABA B R) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABA B R positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABA B receptor agonists such as baclofen. The present study was aimed at developing novel, selective, and potent GABA B R PAMs with efficacy on abuse-related effects of nicotine. We synthetized ~100 analogs of BHF177, a GABA B R PAM that has been shown to inhibit nicotine taking and seeking, and tested their activity in multiple cell-based functional assays. Among these compounds, KK-92A displayed superior PAM properties at the GABA B R. Interestingly, our results revealed the existence of pathway-selective differential modulation of GABA B R signaling by the structurally related GABA B R allosteric modulators BHF177 and KK-92A. In vivo, similarly to BHF177, KK-92A inhibited intravenous nicotine self-administration under both fixed- and progressive-ratio schedules of reinforcement in rats. In contrast to BHF177, KK-92A had no effect on food self-administration. Furthermore, KK-92A decreased cue-induced nicotine-seeking behavior without affecting food seeking. These results indicate that KK-92A is a selective GABA B R PAM with efficacy in inhibition of the primary reinforcing and incentive motivational effects of nicotine, and attenuation of nicotine seeking, further confirming that GABA B R PAMs may be useful antismoking medications.

  10. Granular insular cortex inactivation as a novel therapeutic strategy for nicotine addiction.

    Science.gov (United States)

    Forget, Benoit; Pushparaj, Abhiram; Le Foll, Bernard

    2010-08-01

    Nicotine is the principal component of tobacco smoke, resulting in addiction, and recent evidence suggests that damage to the insular cortex (insula) disrupts tobacco addiction in human smokers. However, the effect of an inactivation of this structure in an animal model of nicotine addiction has yet to be evaluated. To study this question, we investigated the effects of reversible inactivation of the granular insula by local injection of a gamma-aminobutyric acid agonists mixture (baclofen/muscimol) on nicotine self-administration (SA) under fixed and progressive ratio and on reinstatement of nicotine seeking induced by nicotine priming or nicotine-associated cues in rats. We also evaluated the effects of granular insula inactivation on food SA and relapse as a control. The inactivation of the granular insula decreased nicotine SA under both fixed and progressive ratios without affecting the SA of food under the same schedules of reinforcement. This inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues or nicotine priming without modifying the reinstatement of food seeking. Our study indicates that the integrity of the granular insula is necessary for exhibiting motivation to take nicotine and to relapse to nicotine seeking but not for consuming food pellets or to relapse for food seeking. Indeed, it might be interesting to study the effect of methods that are able to modulate the activity of the insula--such as repetitive transcranial magnetic stimulation or deep brain stimulation--on tobacco addiction and relapse in humans. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Developmental changes in central O2 chemoreflex in Rana catesbeiana: the role of noradrenergic modulation.

    Science.gov (United States)

    Fournier, Stéphanie; Allard, Mathieu; Roussin, Stéphanie; Kinkead, Richard

    2007-09-01

    The in vitro brainstem preparation from Rana catesbeiana shows a functional central O(2) chemoreflex. Acute brainstem exposure to hypoxic superfusate elicits lung burst frequency responses that change over the course of development. Based on studies suggesting that brainstem noradrenergic neurons are involved in this reflex, we tested the following two hypotheses in vitro: (1) activation of adrenoceptors is necessary for the expression of the fictive lung ventilation response to hypoxia, and (2) changes in fast, Cl(-)-dependent neurotransmission (GABA/glycine) contribute to developmental changes in noradrenergic modulation. Experiments were performed on preparations from pre-metamorphics tadpoles (TK stages V-XIII) and adult bullfrogs. Acute exposure to hypoxic superfusate (98% N(2), 2% CO(2)) increased fictive lung ventilation frequency in the pre-metamorphic group, whereas a decrease was observed in adults. Buccal burst frequency was unchanged by hypoxia. Noradrenaline (NA; 5 micromol l(-1)) bath application mimicked both fictive breathing responses and application of the alpha(1)-antagonist prazosine (0.5 micromol l(-1)) blocked the lung burst response to hypoxia in both groups. Blocking GABA(A)/glycine receptors with a bicuculine/strychnine mixture (1.25 micromol l(-1)/1.5 micromol l(-1), respectively) or activation of GABA(B) pre-synaptic autoreceptors with baclofen (0.5 micromol l(-1)) prevented the lung burst response to hypoxia and to the alpha(1)-agonist phenylephrine (25 micromol l(-1)) in both stage groups. We conclude that NA modulation contributes to the central O(2) chemoreflex in bullfrog, which acts via GABA/glycine pathways. These data suggest that maturation of GABA/glycine neurotransmission contributes to the developmental changes in this chemoreflex.

  12. Spasticity management in the child with spastic quadriplegia.

    Science.gov (United States)

    Gormley, M E; Krach, L E; Piccini, L

    2001-11-01

    In children with spastic quadriplegia, also described as 'whole body involvement', spasticity can interfere with motor function, contributes to the development of deformities and adversely impacts on care, positioning, and comfort. In this population, spasticity interventions address goals such as improving comfort, reducing pain, easing the burden of carers, slowing the progression of musculoskeletal deformities and perhaps improving function. Children with severe diplegia are distinguished from those with quadriplegia by their ability to ambulate, as well as by a greater emphasis being placed on functional motor goals even though similar treatment modalities are often employed to manage spasticity. The many treatment options currently available include, but are not limited to, botulinum toxin type A, phenol neurolysis, oral medications, intrathecal baclofen, selective dorsal rhizotomy, and orthopaedic surgery. The integration of these treatment modalities can help to optimize the overall care and function for a child with spastic quadriplegia or severe diplegia. However, the development of a management programme is complex and needs to take into account many factors, including age, weight and nutritional status, rate of progression of musculoskeletal deformities, developmental potential, comorbid conditions, current functional status and prognosis, and family and patient treatment goals. Children with marked spasticity are likely to benefit from a combination of interventions, rather than a single treatment modality. Because of these complexities, management should be planned and coordinated by a multidisciplinary team of medical and allied health professionals which recognizes the central role of the family in all decisions. Once the special characteristics of the child with spastic quadriplegia and the various treatment options are understood, outcomes can be maximized.

  13. Characterization of GABA/sub A/ receptor-mediated 36chloride uptake in rat brain synaptoneurosomes

    International Nuclear Information System (INIS)

    Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

    1987-01-01

    γ-Aminobutyric acid (GABA) receptor-mediated 36 chloride ( 36 Cl - ) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated 36 Cl - uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated 36 Cl - uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated 36 Cl - uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br - >Cl - ≥NO 3 - >I - ≥SCN - >>C 3 H 5 OO - ≥ClO 4 - >F - , consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl - channel. 43 references, 4 figures, 3 tables

  14. Deficits in the activity of presynaptic γ-aminobutyric acid type B receptors contribute to altered neuronal excitability in fragile X syndrome.

    Science.gov (United States)

    Kang, Ji-Yong; Chadchankar, Jayashree; Vien, Thuy N; Mighdoll, Michelle I; Hyde, Thomas M; Mather, Robert J; Deeb, Tarek Z; Pangalos, Menelas N; Brandon, Nicholas J; Dunlop, John; Moss, Stephen J

    2017-04-21

    The behavioral and anatomical deficits seen in fragile X syndrome (FXS) are widely believed to result from imbalances in the relative strengths of excitatory and inhibitory neurotransmission. Although modified neuronal excitability is thought to be of significance, the contribution that alterations in GABAergic inhibition play in the pathophysiology of FXS are ill defined. Slow sustained neuronal inhibition is mediated by γ-aminobutyric acid type B (GABA B ) receptors, which are heterodimeric G-protein-coupled receptors constructed from R1a and R2 or R1b and R2 subunits. Via the activation of G i/o , they limit cAMP accumulation, diminish neurotransmitter release, and induce neuronal hyperpolarization. Here we reveal that selective deficits in R1a subunit expression are seen in Fmr1 knock-out mice (KO) mice, a widely used animal model of FXS, but the levels of the respective mRNAs were unaffected. Similar trends of R1a expression were seen in a subset of FXS patients. GABA B receptors (GABA B Rs) exert powerful pre- and postsynaptic inhibitory effects on neurotransmission. R1a-containing GABA B Rs are believed to mediate presynaptic inhibition in principal neurons. In accordance with this result, deficits in the ability of GABA B Rs to suppress glutamate release were seen in Fmr1-KO mice. In contrast, the ability of GABA B Rs to suppress GABA release and induce postsynaptic hyperpolarization was unaffected. Significantly, this deficit contributes to the pathophysiology of FXS as the GABA B R agonist ( R )-baclofen rescued the imbalances between excitatory and inhibitory neurotransmission evident in Fmr1-KO mice. Collectively, our results provided evidence that selective deficits in the activity of presynaptic GABA B Rs contribute to the pathophysiology of FXS. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design

    Directory of Open Access Journals (Sweden)

    Keppel Hesselink JM

    2017-03-01

    , cream, gel, dose-finding, formulation, ketamine, amitriptyline, baclofen, enrichment

  16. Pharmacotherapy of binge-eating disorder: a review.

    Science.gov (United States)

    Goracci, Arianna; di Volo, Silvia; Casamassima, Francesco; Bolognesi, Simone; Benbow, Jim; Fagiolini, Andrea

    2015-01-01

    The purpose of this article is to provide a comprehensive review of pharmacotherapy for binge eating disorder, including new therapeutic approaches such as centrally acting sympathomimetics, nootropics, lisdexamfetamine, and substance abuse treatment agents such as acamprosate, sodium oxybate, baclofen, and naltrexone. The study was conducted by searching the MEDLINE database using the keywords "binge eating disorder," "obesity," and "pharmacological therapy."All available studies on each drug dating from 1988 to the present were considered, focusing mainly on randomized controlled trials (RCTs). Other types of studies were considered when no RCTs were found. We drafted separate tables for open-label studies (), RCT (), and retrospective studies (). Each study is detailed by the number of subjects, additional design considerations, doses, results, additional main comparators, and study limitations. The data emerging from this study seem to show that, at least in the short term, some specific medications within the classes of antidepressants, anticonvulsants, and antiobesity agents may prove promising in achieving the main objectives in the treatment of binge eating disorder: reducing the frequency of binge eating, reducing weight, and improving the associated psychopathology. The major limitation in interpreting these results is the short duration of the studies and the lack of adequately sized trials, or trials including patients with medical comorbidities.Good results are being obtained with new combinations of drugs and with substance abuse treatment agents. Although the precise nature of the relationship between substance use disorders and binge eating disorder remains to be clarified, the evidence suggests that treatments recognized as effective for substance use disorders may be useful as novel treatments for binge eating disorder. This field of research remains open to future studies with more precise methodological approaches and more detailed parameter

  17. Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating

    Directory of Open Access Journals (Sweden)

    Matthew M. Hurley

    2016-08-01

    Full Text Available While pituitary adenylate cyclase activating polypeptide (PACAP signaling in the hypothalamic ventromedial nuclei (VMN has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger and hedonic-related (palatability drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding; surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding. In contrast, inhibition of the nucleus accumbens (NAc, through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive.

  18. Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task.

    Science.gov (United States)

    Martig, Adria K; Mizumori, Sheri J Y

    2011-02-01

    Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

  19. Ventral, but not dorsal, hippocampus inactivation impairs reward memory expression and retrieval in contexts defined by proximal cues.

    Science.gov (United States)

    Riaz, Sadia; Schumacher, Anett; Sivagurunathan, Seyon; Van Der Meer, Matthijs; Ito, Rutsuko

    2017-07-01

    The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well-established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal-based contextual memory processing in appetitively motivated tasks. Thus, the present study sought to investigate the individual roles of the dHPC and the vHPC in contextual biconditional discrimination (CBD) performance and memory retrieval. To this end, we examined the effects of transient post-acquisition pharmacological inactivation (using a combination of GABA A and GABA B receptor agonists muscimol and baclofen) of functionally distinct subregions of the HPC (CA1/CA3 subfields of the dHPC and vHPC) on CBD memory retrieval. Additional behavioral assays including novelty preference, light-dark box and locomotor activity test were also performed to confirm that the respective sites of inactivation were functionally silent. We observed robust deficits in CBD performance and memory retrieval following inactivation of the vHPC, but not the dHPC. Our data provides novel insight into the differential roles of the ventral and dorsal HPC in reward contextual processing, under conditions in which the context is defined by proximal cues. © 2017 Wiley Periodicals, Inc.

  20. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  1. Movement disorder emergencies in childhood.

    Science.gov (United States)

    Kirkham, F J; Haywood, P; Kashyape, P; Borbone, J; Lording, A; Pryde, K; Cox, M; Keslake, J; Smith, M; Cuthbertson, L; Murugan, V; Mackie, S; Thomas, N H; Whitney, A; Forrest, K M; Parker, A; Forsyth, R; Kipps, C M

    2011-09-01

    The literature on paediatric acute-onset movement disorders is scattered. In a prospective cohort of 52 children (21 male; age range 2mo-15y), the commonest were chorea, dystonia, tremor, myoclonus, and Parkinsonism in descending order of frequency. In this series of mainly previously well children with cryptogenic acute movement disorders, three groups were recognised: (1) Psychogenic disorders (n = 12), typically >10 years of age, more likely to be female and to have tremor and myoclonus (2) Inflammatory or autoimmune disorders (n = 22), including N-methyl-d-aspartate receptor encephalitis, opsoclonus-myoclonus, Sydenham chorea, systemic lupus erythematosus, acute necrotizing encephalopathy (which may be autosomal dominant), and other encephalitides and (3) Non-inflammatory disorders (n = 18), including drug-induced movement disorder, post-pump chorea, metabolic, e.g. glutaric aciduria, and vascular disease, e.g. moyamoya. Other important non-inflammatory movement disorders, typically seen in symptomatic children with underlying aetiologies such as trauma, severe cerebral palsy, epileptic encephalopathy, Down syndrome and Rett syndrome, include dystonic posturing secondary to gastro-oesophageal reflux (Sandifer syndrome) and Paroxysmal Autonomic Instability with Dystonia (PAID) or autonomic 'storming'. Status dystonicus may present in children with known extrapyramidal disorders, such as cerebral palsy or during changes in management e.g. introduction or withdrawal of neuroleptic drugs or failure of intrathecal baclofen infusion; the main risk in terms of mortality is renal failure from rhabdomyolysis. Although the evidence base is weak, as many of the inflammatory/autoimmune conditions are treatable with steroids, immunoglobulin, plasmapheresis, or cyclophosphamide, it is important to make an early diagnosis where possible. Outcome in survivors is variable. Using illustrative case histories, this review draws attention to the practical difficulties in

  2. Functional activation of Gαq via serotonin2A (5-HT2A) and muscarinic acetylcholine M1 receptors assessed by guanosine-5׳-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding/immunoprecipitation in rat brain membranes.

    Science.gov (United States)

    Odagaki, Yuji; Kinoshita, Masakazu; Toyoshima, Ryoichi

    2014-03-05

    Functional coupling between serotonin2A (5-HT2A) receptors and Gαq proteins in native brain membranes has been sparsely reported thus far. In the present study, the guanosine-5׳-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding assay combined with immunoprecipitation using magnetic beads (Dynabeads Protein A) coated with anti-Gαq antibody was developed. Under experimental conditions optimised for assay constituents (GDP, MgCl2, and NaCl), for contents of membrane protein, anti-Gαq antibody, and Dynabeads Protein A, and for the incubation period, 5-HT stimulated specific [35S]GTPγS binding to Gαq in rat cerebral cortical membranes in a concentration-dependent and saturable manner, with a signal/noise ratio that was sufficiently high for further detailed pharmacological characterisation. This characterisation revealed an involvement of 5-HT2A receptors. Activation of Gαq proteins was also detectable by the addition of carbachol via muscarinic acetylcholine M1 receptors, (-)-epinephrine, and dopamine, but not by L-glutamate or (±)-baclofen. When 5-HT2A receptors and M1 receptors were stimulated simultaneously, there were non-additive effects, indicating that the two receptors were coupled to the same components of Gαq proteins in the rat cerebral cortex. This method will serve as an efficacious strategy for neurobiological investigations aimed at elucidating the physiological and pathological implications of signal transduction systems mediated via Gαq proteins coupled with 5-HT2A receptors and muscarinic acetylcholine M1 receptors.

  3. Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine.

    Science.gov (United States)

    Stringfield, Sierra J; Palmatier, Matthew I; Boettiger, Charlotte A; Robinson, Donita L

    2017-04-01

    Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Assessing and treating pain in movement disorders, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness, dementia, oncology and neuroinfectivology. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

    Science.gov (United States)

    Bartolo, Michelangelo; Chiò, Adriano; Ferrari, Sergio; Tassorelli, Cristina; Tamburin, Stefano; Avenali, Micol; Azicnuda, Eva; Calvo, Andrea; Caraceni, Augusto T; Defazio, Giovanni; DE Icco, Roberto; Formisano, Rita; Franzoni, Simone; Greco, Elena; Jedrychowska, Iwona; Magrinelli, Francesca; Manera, Umberto; Marchioni, Enrico; Mariotto, Sara; Monaco, Salvatore; Pace, Andrea; Saviola, Donatella; Springhetti, Isabella; Tinazzi, Michele; DE Tanti, Antonio

    2016-12-01

    Pain is an important non-motor symptom in several neurological diseases, such as Parkinson's disease, cervical dystonia, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness and dementia, as well as in oncology and neuroinfectivology. To overcome the lack of evidence-based data on pain management in these diseases, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) has defined criteria for good clinical practice among Italian neurorehabilitation professionals. Here a review of the literature (PubMed, EMBASE and gray literature) on pain characteristics, treatment and impact of pain in a neurorehabilitation setting is provided. Despite the heterogeneity of data, a consensus was reached on pain management for patients with these diseases: it is an approach originating from an analysis of the available data on pain characteristics in each disease, the evolution of pain in relation to the natural course of the disease and the impact of pain on the overall process of rehabilitation. There was unanimous consensus regarding the utility of a multidisciplinary approach to pain therapy, combining the benefits of pharmacological therapy with the techniques of physiotherapy and neurorehabilitation for all the conditions considered. While some treatments could be different depending on pathology, a progressive approach to the pharmacological treatment of pain is advisable, starting with non-opioid analgesics (paracetamol) and nonsteroidal anti-inflammatory drugs as a first-line treatment, and opioid analgesics as a second-line treatment. In cases of pain secondary to spasticity, botulinum neurotoxin, and, in some cases, intrathecal baclofen infusion should be considered. Randomized controlled trials and prospective multicenter studies aimed at documenting the efficacy of pain treatment and their risk-benefit profile are recommended for these conditions.

  5. Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus.

    Science.gov (United States)

    Kunisawa, Kazuo; Kido, Kiwamu; Nakashima, Natsuki; Matsukura, Takuya; Nabeshima, Toshitaka; Hiramatsu, Masayuki

    2017-02-05

    GABA mediated neuronal system regulates hippocampus-dependent memory and stress responses by controlling plasticity and neuronal excitability. Here, we demonstrate that betaine ameliorates water-immersion restraint stress (WIRS)-induced memory impairments. This improvement was inhibited by a betaine/GABA transporter-1 (GABA transporter-2: GAT2) inhibitor, NNC 05-2090. In this study, we investigated whether memory amelioration by betaine was mediated by the GABAergic neuronal system. Adult male mice were co-administered betaine and GABA receptor antagonists after WIRS. We also examined whether memory impairment after WIRS was attenuated by GABA receptor agonists. The memory functions were evaluated using a novel object recognition test 3-6 days after WIRS and/or the step-down type passive avoidance test at 7-8 days. The co-administration of the GABA A receptor antagonist bicuculline (1mg/kg) or the GABA B receptor antagonist phaclofen (10mg/kg) 1h after WIRS suppressed the memory-improving effects induced by betaine. Additionally, the administration of the GABA A receptor agonist muscimol (1mg/kg) or the GABA B receptor agonist baclofen (10mg/kg) 1h after WIRS attenuated memory impairments. These results were similar to the data observed with betaine. The treatment with betaine after WIRS significantly decreased the expression of GABA transaminase, and this effect was partially blocked by NNC 05-2090 in the hippocampus. WIRS caused a transient increase in hippocampal GABA levels and the changes after WIRS were not affected by betaine treatment in an in vivo microdialysis study. These results suggest that the beneficial effects of betaine may be mediated in part by changing the GABAergic neuronal system. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Improving quality of life of children with cerebral palsy: a systematic review of clinical trials.

    Science.gov (United States)

    Tsoi, W S E; Zhang, L A; Wang, W Y; Tsang, K L; Lo, S K

    2012-01-01

    To systematically review the impact of different interventions on quality of life (QoL) for children with cerebral palsy. English articles were sought from five major English databases from inceptions until March 2010. Keywords used consisted of four components (and their variants): (i) clinical condition: cerebral palsy; (ii) outcome measures: quality of life, well-being; (iii) study design: clinical trials; and (iv) target population: people aged 0-18. Eight studies satisfied the inclusion criteria, all of which are of good to excellent quality (a Jadad score of 4 or above). The Pediatric Evaluation of Disability Inventory, the Pediatric Quality of Life Inventory, the TNO-AZL Children's Health-Related Quality of Life and the Caregiver Priorities and Child Health Index of Life with Disabilities were used to measure QoL. Significant positive results were reported by two studies using medicinal interventions (diazepam and intrathecal baclofen therapy, effect sizes 5.9, 9.1 respectively) and two studies employing motor control approach training (strength training and exercise training, former effect size being 3.8). Current review suggests that positive effect was shown in medicinal and motor control interventions on QoL. However, no single interventional approach can demonstrate a consistent positive impact on QoL across different studies. Future studies are recommended to (i) provide a clear definition of QoL, and investigate the relationship between symptoms' severity and QoL; (ii) measure outcome at different time points to capture real effects of interventions; and (iii) make more use of valid outcome instruments, either self-report or parent/caregiver proxy reports. © 2011 Blackwell Publishing Ltd.

  7. THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

    Science.gov (United States)

    Trojano, Maria

    2016-01-01

    The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013. Web-based real-time data collection techniques are combined with traditional patients' diaries to capture a wide spectrum of outcomes associated with this innovative cannabis-based medication. After surpassing the recruitment threshold of 300 patients, an interim analysis was performed to determine whether the data collected to date align with those from MOVE 2-Germany and the largest phase III randomized controlled trial (RCT) of THC:CBD oromucosal spray. In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months' observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT. While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity. © 2016 S. Karger AG, Basel.

  8. Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology.

    Science.gov (United States)

    Bhidayasiri, Roongroj; Fahn, Stanley; Weiner, William J; Gronseth, Gary S; Sullivan, Kelly L; Zesiewicz, Theresa A

    2013-07-30

    To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966-2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).

  9. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders.

    Science.gov (United States)

    Aigner, Martin; Treasure, Janet; Kaye, Walter; Kasper, Siegfried

    2011-09-01

    The treatment of eating disorders is a complex process that relies not only on the use of psychotropic drugs but should include also nutritional counselling, psychotherapy and the treatment of the medical complications, where they are present. In this review recommendations for the pharmacological treatment of eating disorders (anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED)) are presented, based on the available literature. The guidelines for the pharmacological treatment of eating disorders are based on studies published between 1977 and 2010. A search of the literature included: anorexia nervosa bulimia nervosa, eating disorder and binge eating disorder. Many compounds have been studied in the therapy of eating disorders (AN: antidepressants (TCA, SSRIs), antipsychotics, antihistaminics, prokinetic agents, zinc, Lithium, naltrexone, human growth hormone, cannabis, clonidine and tube feeding; BN: antidepressants (TCA, SSRIs, RIMA, NRI, other AD), antiepileptics, odansetron, d-fenfluramine Lithium, naltrexone, methylphenidate and light therapy; BED: antidepressants (TCA, SSRIs, SNRIs, NRI), antiepileptics, baclofen, orlistat, d-fenfluramine, naltrexone). In AN 20 randomized controlled trials (RCT) could be identified. For zinc supplementation there is a grade B evidence for AN. For olanzapine there is a category grade B evidence for weight gain. For the other atypical antipsychotics there is grade C evidence. In BN 36 RCT could be identified. For tricyclic antidepressants a grade A evidence exists with a moderate-risk-benefit ratio. For fluoxetine a category grade A evidence exists with a good risk-benefit ratio. For topiramate a grade 2 recommendation can be made. In BED 26 RCT could be identified. For the SSRI sertraline and the antiepileptic topiramate a grade A evidence exists, with different recommendation grades. Additional research is needed for the improvement of the treatment of eating disorders. Especially for anorexia nervosa

  10. Effects of lisdexamfetamine in a rat model of binge-eating.

    Science.gov (United States)

    Vickers, Steven P; Hackett, David; Murray, Fraser; Hutson, Peter H; Heal, David J

    2015-12-01

    Binge-eating disorder is a common psychiatric disorder affecting ~2% of adults. Binge-eating was initiated in freely-fed, lean, adult, female rats by giving unpredictable, intermittent access to ground, milk chocolate over four weeks. The rats avidly consumed chocolate during 2 hr binge sessions, with compensatory reductions of normal chow intake in these sessions and the days thereafter. Bodyweights of binge-eating rats were normal. The model's predictive validity was explored using nalmefene (0.1-1.0mg/kg), R-baclofen (1.0-10mg/kg) and SB-334867 (3.0-30 mg/kg) (orexin-1 antagonist), which all selectively decreased chocolate bingeing without reducing chow intake. Sibutramine (0.3-5.0mg/kg) non-selectively reduced chocolate and chow consumption. Olanzapine (0.3-3.0mg/kg) was without effect and rolipram (1.0-10mg/kg) abolished all ingestive behaviour. The pro-drug, lisdexamfetamine (LDX; 0.1-1.5mg/kg), dose-dependently reduced chocolate bingeing by ⩽ 71% without significantly decreasing normal chow intake. Its metabolite, D-amphetamine (0.1-1.0mg/kg), dose-dependently and preferentially decreased chocolate bingeing ⩽ 56%. Using selective antagonists to characterize LDX's actions revealed the reduction of chocolate bingeing was partially blocked by prazosin (α1-adrenoceptor; 0.3 and 1.0mg/kg) and possibly by SCH-23390 (D1; 0.1mg/kg). RX821002 (α2-adrenoceptor; 0.1 and 0.3mg/kg) and raclopride (D2; 0.3 and 0.5mg/kg) were without effect. The results indicate that LDX, via its metabolite, d-amphetamine, reduces chocolate bingeing, partly by indirect activation of α1-adrenoceptors and perhaps D1 receptors. © The Author(s) 2015.

  11. Effects of centrally acting antihypertensive drugs on the microcirculation of spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Estato V.

    2004-01-01

    Full Text Available We investigated the acute effects of centrally acting antihypertensive drugs on the microcirculation of pentobarbital-anesthetized spontaneously hypertensive rats (SHR. The effects of the sympatho-inhibitory agents clonidine and rilmenidine, known to activate both alpha2-adrenoceptors and nonadrenergic I1-imidazoline binding sites (I1BS in the central nervous system, were compared to those of dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H -pyrrol-2-yl-amine hydrochloride (LNP 509, which selectively binds to the I1BS. Terminal mesenteric arterioles were observed by intravital microscopy. Activation of the central sympathetic system with L-glutamate (125 µg, ic induced marked vasoconstriction of the mesenteric microcirculation (27 ± 3%; N = 6, P < 0.05. In contrast, the marked hypotensive and bradycardic effects elicited by intracisternal injection of clonidine (1 µg, rilmenidine (7 µg and LNP 509 (60 µg were accompanied by significant increases in arteriolar diameter (12 ± 1, 25 ± 10 and 21 ± 4%, respectively; N = 6, P < 0.05. The vasodilating effects of rilmenidine and LNP 509 were two-fold higher than those of clonidine, although they induced an identical hypotensive effect. Central sympathetic inhibition elicited by baclofen (1 µg, ic, a GABA B receptor agonist, also resulted in vasodilation of the SHR microvessels. The acute administration of clonidine, rilmenidine and LNP 509 also induced a significant decrease of cardiac output, whereas a decrease in systemic vascular resistance was observed only after rilmenidine and LNP 509. We conclude that the normalization of blood pressure in SHR induced by centrally acting antihypertensive agents is paralleled by important vasodilation of the mesenteric microcirculation. This effect is more pronounced with substances acting preferentially (rilmenidine or exclusively (LNP 509 upon I1BS than with those presenting important alpha2-adrenergic activity (clonidine.

  12. Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS).

    Science.gov (United States)

    Poklis, Justin L; Mohs, Amanda J; Wolf, Carl E; Poklis, Alphonse; Peace, Michelle R

    2016-10-01

    In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOF TM time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Hippocampal Gαq/₁₁ but not Gαo-coupled receptors are altered in aging.

    Science.gov (United States)

    McQuail, Joseph A; Davis, Kathleen N; Miller, Frances; Hampson, Robert E; Deadwyler, Samuel A; Howlett, Allyn C; Nicolle, Michelle M

    2013-07-01

    Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/₁₁ is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/₁₁ and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344 × BNF₁ hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/₁₁ was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/₁₁ with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/₁₁ function was measured in hippocampal subregion CA₁ by determining changes in [Ca(2+)]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca(2+)]i was lower in aged CA₁ relative to young while mGluR-mediated integrated [Ca(2+)]i responses tended to be larger in aged. GPCR modulation of [Ca(2+)]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/₁₁ within the hippocampus leading to deficient modulation of [Ca(2+)]i following stimulation of mAChRs but these changes are not related to spatial learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Uptake of 3-[{sup 125}I]iodo-{alpha}-methyl-L-tyrosine into colon cancer DLD-1 cells: characterization and inhibitory effect of natural amino acids and amino acid-like drugs

    Energy Technology Data Exchange (ETDEWEB)

    Shikano, Naoto [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan)], E-mail: sikano@ipu.ac.jp; Ogura, Masato [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Okudaira, Hiroyuki [School of Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa 920-0942 (Japan); Nakajima, Syuichi; Kotani, Takashi [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kobayashi, Masato [School of Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa 920-0942 (Japan); Nakazawa, Shinya [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Baba, Takeshi; Yamaguchi, Naoto [Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kubota, Nobuo [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Iwamura, Yukio [Center for Humanities and Sciences, Ibaraki Prefectural University of Health Sciences, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kawai, Keiichi [School of Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa 920-0942 (Japan)

    2010-02-15

    Introduction: We examined 3-[{sup 123}I]iodo-{alpha}-methyl-L-tyrosine ([{sup 123}I]IMT) uptake and inhibition by amino acids and amino acid-like drugs in the human DLD-1 colon cancer cell line, to discuss correlation between the inhibition effect and structure. Methods: Expression of relevant neutral amino acid transporters was examined by real-time PCR with DLD-1 cells. The time course of [{sup 125}I]IMT uptake, contributions of transport systems, concentration dependence and inhibition effects by amino acids and amino acid-like drugs (1 mM) on [{sup 125}I]IMT uptake were examined. Results: Expression of system L (4F2hc, LAT1 and LAT2), system A (ATA1, ATA2) and system ASC (ASCT1) was strongly detected; system L (LAT3, LAT4) and MCT8 were weakly detected; and B{sup 0}AT was not detected. [{sup 125}I]IMT uptake in DLD-1 cells involved Na{sup +}-independent system L primarily and Na{sup +}-dependent system(s). Uptake of [{sup 125}I]IMT in Na{sup +}-free buffer followed Michaelis-Menten kinetics, with a K{sub m} of 78 {mu}M and V{sub max} of 333 pmol/10{sup 6} cells per minute. Neutral D- and L-amino acids with branched or aromatic large side chains inhibited [{sup 125}I]IMT uptake. Tyrosine analogues, tryptophan analogues, L-phenylalanine and p-halogeno-L-phenylalanines, and gamma amino acids [including 3,4-dihydroxy-L-phenylalanine (L-DOPA), DL-threo-{beta}-(3,4-dihydroxyphenyl)serine (DOPS), 4-[bis(2-chloroethyl)amino]-L-phenylalanine and 1-(aminomethyl)-cyclohexaneacetic acid] strongly inhibited [{sup 125}I]IMT uptake, but L-tyrosine methyl ester and R(+)/S(-)-baclofen weakly inhibited uptake. The substrates of system ASC and A did not inhibit [{sup 125}I]IMT uptake except L-serine and D/L-cysteine. Conclusions: [{sup 125}I]IMT uptake in DLD-1 cells involves mostly LAT1 and its substrates' (including amino acid-like drugs derived from tyrosine, tryptophan and phenylalanine) affinity to transport via LAT1. Whether transport of gamma amino acid analogues is

  15. Development of spasticity with age in a total population of children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Wagner Philippe

    2008-11-01

    Full Text Available Abstract Background The development of spasticity with age in children with cerebral palsy (CP has, to our knowledge, not been studied before. In 1994, a register and a health care program for children with CP in southern Sweden were initiated. In the programme the child's muscle tone according to the modified Ashworth scale is measured twice a year until six years of age, then once a year. We have used this data to analyse the development of spasticity with age in a total population of children with cerebral palsy. Methods All measurements of muscle tone in the gastrocnemius-soleus muscle in all children with CP from 0 to 15 years during the period 1995–2006 were analysed. The CP subtypes were classified according to the Surveillance of Cerebral Palsy in Europe network system. Using these criteria, the study was based on 6218 examinations in 547 children. For the statistical analysis the Ashworth scale was dichotomized. The levels 0–1 were gathered in one category and levels 2–4 in the other. The pattern of development with age was evaluated using piecewise logistic regression in combination with Akaike's An Information Criterion. Results In the total sample the degree of muscle tone increased up to 4 years of age. After 4 years of age the muscle tone decreased each year up to 12 years of age. A similar development was seen when excluding the children operated with selective dorsal rhizotomy, intrathecal baclofen pump or tendo Achilles lengthening. At 4 years of age about 47% of the children had spasticity in their gastro-soleus muscle graded as Ashworth 2–4. After 12 years of age 23% of the children had that level of spasticity. The CP subtypes spastic bilateral and spastic unilateral CP showed the same pattern as the total sample. Children with dyskinetic type of CP showed an increasing muscle tone up to age 6, followed by a decreasing pattern up to age 15. Conclusion In children with CP, the muscle tone as measured with the Ashworth

  16. The pharmacological management of post-stroke muscle spasticity.

    Science.gov (United States)

    Bakheit, Abdel Magid O

    2012-12-01

    important prerequisites to treatment. The best treatment outcomes are usually achieved when pharmacological and non-pharmacological treatment modalities are used in tandem. Different drugs are available for the management of spasticity, including oral muscle relaxants, anticonvulsant drugs, intrathecal baclofen, cannabis extract, phenol and alcohol (for peripheral nerve blocks) and botulinum toxin injections. Similarly, there is a range of non-pharmacological methods of treatment, e.g. regular muscle stretching, the use of splints and orthoses, electrical stimulation, etc. Although these are not discussed here, this should not detract from the importance of combining them with antispasticity drugs in order to maximize the clinical benefit of treatment.

  17. Combinational Spinal GAD65 Gene Delivery and Systemic GABA-Mimetic Treatment for Modulation of Spasticity

    Science.gov (United States)

    Kakinohana, Osamu; Hefferan, Michael P.; Miyanohara, Atsushi; Nejime, Tetsuya; Marsala, Silvia; Juhas, Stefan; Juhasova, Jana; Motlik, Jan; Kucharova, Karolina; Strnadel, Jan; Platoshyn, Oleksandr; Lazar, Peter; Galik, Jan; Vinay, Laurent; Marsala, Martin

    2012-01-01

    Background Loss of GABA-mediated pre-synaptic inhibition after spinal injury plays a key role in the progressive increase in spinal reflexes and the appearance of spasticity. Clinical studies show that the use of baclofen (GABAB receptor agonist), while effective in modulating spasticity is associated with major side effects such as general sedation and progressive tolerance development. The goal of the present study was to assess if a combined therapy composed of spinal segment-specific upregulation of GAD65 (glutamate decarboxylase) gene once combined with systemic treatment with tiagabine (GABA uptake inhibitor) will lead to an antispasticity effect and whether such an effect will only be present in GAD65 gene over-expressing spinal segments. Methods/Principal Findings Adult Sprague-Dawley (SD) rats were exposed to transient spinal ischemia (10 min) to induce muscle spasticity. Animals then received lumbar injection of HIV1-CMV-GAD65 lentivirus (LVs) targeting ventral α-motoneuronal pools. At 2–3 weeks after lentivirus delivery animals were treated systemically with tiagabine (4, 10, 20 or 40 mg/kg or vehicle) and the degree of spasticity response measured. In a separate experiment the expression of GAD65 gene after spinal parenchymal delivery of GAD65-lentivirus in naive minipigs was studied. Spastic SD rats receiving spinal injections of the GAD65 gene and treated with systemic tiagabine showed potent and tiagabine-dose-dependent alleviation of spasticity. Neither treatment alone (i.e., GAD65-LVs injection only or tiagabine treatment only) had any significant antispasticity effect nor had any detectable side effect. Measured antispasticity effect correlated with increase in spinal parenchymal GABA synthesis and was restricted to spinal segments overexpressing GAD65 gene. Conclusions/Significance These data show that treatment with orally bioavailable GABA-mimetic drugs if combined with spinal-segment-specific GAD65 gene overexpression can represent a novel

  18. Contributions of basolateral amygdala and nucleus accumbens subregions to mediating motivational conflict during punished reward-seeking.

    Science.gov (United States)

    Piantadosi, Patrick T; Yeates, Dylan C M; Wilkins, Mathew; Floresco, Stan B

    2017-04-01

    The involvement of different nodes within meso-cortico-limbic-striatal circuitry in mediating reward-seeking has been well described, yet comparatively less is known about how such circuitry may regulate appetitively-motivated behaviors that may be punished. The basolateral amygdala (BLA) is one nucleus that has been implicated in suppressing punished reward-seeking, and this structure can modulate goal-directed behavior via projections to subregions of the nucleus accumbens (NAc). Here, we examined the effects of reversible inactivations of the BLA, NAc Shell (NAcS), and core (NAcC) on performance of a "Conflict" task where rats pressed a lever for sucrose reinforcement during three distinct 5min phases. During the first and last phases of a session, rats lever-pressed for food reward delivered on a VI-15/FR5 schedule. In between these phases was a signaled "Conflict" period, where each lever-press yielded food, but 50% of presses were also punished with foot-shock. Under control conditions, well-trained rats responded vigorously during the two "safe" VI-15/FR5 periods, but reduced responding during the punished Conflict period. Inactivation of either the BLA or the NAcS via infusions of baclofen/muscimol disinhibited punished seeking, increasing lever-pressing during the conflict period, while attenuating pressing during VI-15/FR5 phases. In contrast, NAcC inactivation markedly decreased responding across all three phases. Similar inactivation of the BLA or NAcS did not alter responding in a separate control experiment where rats pressed for food on schedules identical to the Conflict task in the absence of any punishment, while NAcC inactivation again suppressed responding. These results imply that BLA and NAcS are part of a circuit that suppresses reward-seeking in the face of danger, which in turn may have implications for disorders characterized by punishment resistance, including substance abuse and obsessive-compulsive disorder. Copyright © 2017 Elsevier

  19. Botulinum toxin type A for the treatment of the upper limb spasticity after stroke: a meta-analysis Toxina botulínica tipo A para o tratamento da espasticidade de membros superiores pós-AVC: metanálise

    Directory of Open Access Journals (Sweden)

    Eduardo Cardoso

    2005-03-01

    Full Text Available Muscle over-activity is one of the cardinal features of spasticity and it is a common disability of stroke patients. In this group, spasticity is responsible for several limitations that interfere in their daily activities and quality of life. To treat spasticity, neurologists usually prescribe drugs as baclofen, tizanidine or benzodiazepines or even use definitive treatment as phenol or surgery. Authors suggest the use of botulinum toxin type A (BTX-A for spasticity in the upper limbs after stroke, but there are few papers with adequate methodology supporting this idea. In this article we summarize the data of previous double-blind, randomised clinical trials to asses, with a meta-analysis, if BTX-A is an adequate treatment for spasticity due to stroke. The results show a statistical superiority of BTX-A ov%r placebo on reducing muscle tone by the Modified Ashworth Scale (WMD= 0.95 [0.74 to 1.17] in patients with post-stroke upper limb spasticity.Hiperatividade muscular é um dos principais sinais encontrados na espasticidade e seqüela comum após acidente vascular encefálico (AVC. Nesse grupo de pacientes, a espasticidade é responsável por limitações que interferem nas atividades diárias e qualidade de vida. Para tratar a espasticidade, neurologistas geralmente prescrevem drogas como baclofeno, tizanidina, benzodiazepínicos ou mesmo intervenções definitivas como fenol e cirurgia. Há quase duas décadas que a toxina botulínica tipo A (BTX-A vem sendo utilizada para tratamento da espasticidade nos membros superiores pós-AVC; no entanto, há poucos artigos com metodologia adequada apoiando esta assertiva. Neste artigo avaliamos todos os dados de ensaios clínicos duplo-cegos e randomizados para definir, através de metanálise, se BTX-A é um tratamento adequado para espasticidade pós-AVC. Os nossos resultados mostram superioridade estatística da BTX-A sobre o placebo na redução do tônus muscular pela escala de Ashworth

  20. Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

    Science.gov (United States)

    Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

    2016-02-01

    Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of

  1. Treatment for cramps in amyotrophic lateral sclerosis/motor neuron disease.

    Science.gov (United States)

    Baldinger, Reto; Katzberg, Hans Dieter; Weber, Markus

    2012-04-18

    Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. We included all randomised and quasi-randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L-threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta-analysis of two small

  2. Alcohol abuse and related disorders treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Yu. P. Sivolap

    2014-01-01

    medications, including baclofen, gabapentin, pregabalin, ondansetron, modafinil, and aripiprazole, are able to decrease alcoholic needs and to alleviate the manifestations of alcohol dependence. The Russian narcological practice in using antipsychotics to suppress a craving for alcohol (as well as other psychoactive substances contradicts the principles of evidence-based medicine and has no scientific base.

  3. Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Campbell, Erin J; Whitaker, Leslie R; Harvey, Brandon K; Kaganovsky, Konstantin; Adhikary, Sweta; Hope, Bruce T; Heins, Robert C; Prisinzano, Thomas E; Vardy, Eyal; Bonci, Antonello; Bossert, Jennifer M; Shaham, Yavin

    2016-03-16

    In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock. Here, we studied the role of projections to nucleus accumbens (NAc) shell from ventral subiculum (vSub), basolateral amygdala, paraventricular thalamus, and ventral medial prefrontal cortex in context-induced relapse after punishment-imposed abstinence. First, we measured double-labeling of the neuronal activity marker Fos with the retrograde tracer cholera toxin subunit B (injected in NAc shell) and demonstrated that context-induced relapse is associated with selective activation of the vSub→NAc shell projection. Next, we reversibly inactivated the vSub with GABA receptor agonists (muscimol+baclofen) before the context-induced relapse tests and provided evidence for a causal role of vSub in this relapse. Finally, we used a dual-virus approach to restrict expression of the inhibitory κ opioid-receptor based DREADD (KORD) in vSub→NAc shell projection neurons. We found that systemic injections of the KORD agonist salvinorin B, which selectively inhibits KORD-expressing neurons, decreased context-induced relapse to alcohol seeking. Our results demonstrate a critical role of vSub in context-induced relapse after punishment-imposed abstinence and further suggest a role of the vSub→NAc projection in this relapse. In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol use. Until recently, an

  4. Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

    Science.gov (United States)

    Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C

    2017-08-30

    Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central

  5. Hypoxanthine-guanine phosophoribosyltransferase (HPRT deficiency: Lesch-Nyhan syndrome

    Directory of Open Access Journals (Sweden)

    Puig Juan G

    2007-12-01

    lack of precise understanding of the neurological dysfunction has precluded development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation, including management of dysarthria and dysphagia, special devices to enable hand control, appropriate walking aids, and a programme of posture management to prevent deformities are recommended. Self-injurious behaviour must be managed by a combination of physical restraints, behavioural and pharmaceutical treatments.

  6. New developments in the management of narcolepsy

    Directory of Open Access Journals (Sweden)

    Abad VC

    2017-03-01

    investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen, melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed. Keywords: narcolepsy, cataplexy, emerging treatment, sodium oxybate, pitolisant, JZP-110, hypocretin peptide, immunotherapy 

  7. Ongoing behavioral state information signaled in the lateral habenula guides choice flexibility in freely moving rats

    Directory of Open Access Journals (Sweden)

    Phillip Michael Baker

    2015-11-01

    Full Text Available The lateral habenula (LHb plays a role in a wide variety of behaviors ranging from maternal care, to sleep, to various forms of cognition. One prominent theory with ample supporting evidence is that the LHb serves to relay basal ganglia and limbic signals about negative outcomes to midbrain monoaminergic systems. This makes it likely that the LHb is critically involved in behavioral flexibility as all of these systems have been shown to contribute when flexible behavior is required. Behavioral flexibility is commonly examined across species and is impaired in various neuropsychiatric conditions including autism, depression, addiction, and schizophrenia; conditions in which the LHb is thought to play a role. Therefore, a thorough examination of the role of the LHb in behavioral flexibility serves multiple functions including understanding possible connections with neuropsychiatric illnesses and additional insight into its role in cognition in general. Here we assess the LHb’s role in behavioral flexibility through comparisons of the roles its afferent and efferent pathways are known to play. Additionally, we provide new evidence supporting the LHb contributions to behavioral flexibility through organization of specific goal directed actions under cognitively demanding conditions. Specifically, in the first experiment, a majority of neurons recorded from the LHb were found to correlate with velocity on a spatial navigation task and did not change significantly when reward outcomes were manipulated. Additionally, measurements of local field potential in the theta band revealed significant changes in power relative to velocity and reward location. In a second set of experiments, inactivation of the LHb with the GABA agonists baclofen and muscimol led to an impairment in a spatial/response based repeated probabilistic reversal learning task. Control experiments revealed that this impairment was likely due to the demands of repeated switching

  8. Characterizing Treatment Utilization Patterns for Trigeminal Neuralgia in the United States.

    Science.gov (United States)

    Zakrzewska, Joanna M; Wu, Ning; Lee, John Y K; Werneburg, Brian; Hoffman, Deborah; Liu, Ying

    2018-02-19

    Trigeminal neuralgia (TN) is a rare orofacial disorder characterized by severe unilateral paroxysmal pain in the region of the fifth cranial nerve. Clinical guidelines recommend carbamazepine (only US Food and Drug Administration-approved drug for TN) and oxcarbazepine as first-line therapies. We utilized the US Truven Health MarketScan database to examine treatment patterns among patients with TN. Included patients were aged ≥18 years, newly diagnosed with TN (≥2 TN diagnoses ≥14 days apart; no diagnosis in the prior year), continuously enrolled 1 year pre-index, with ≥3 years' follow-up post-index. We assessed utilization of selected pharmacotherapies (carbamazepine, oxcarbazepine, pregabalin, gabapentin, baclofen, duloxetine, topiramate), surgery (posterior fossa, radiosurgery), and injections (peripheral anesthetic injections, Gasserian ganglion procedures) for TN. 3685 patients were included (2425 commercial, 1260 Medicare; 71.8% female; mean[SD] age, 59 [15] years). Overall, 72.5% of patients received at least 1 studied medication, most commonly carbamazepine (51.7%) or gabapentin (48.6%). Sixty-five percent of pharmacologically treated patients had ≥2 treatment episodes; 41.6% had ≥3 (defined by a change in pharmacotherapy [monotherapy/combination] regimen). Overall, 12.3% had surgery and 7.3% injections; 42.9% received opioids for TN. In the 3 years after diagnosis, patients with TN in the United States receive a variety of pharmacological treatments, including opioids, despite carbamazepine being the only approved medication. A notable proportion utilize surgeries/injections. A high proportion of pharmacologically treated patients receive multiple treatment episodes, suggesting frequent therapy switching, perhaps due to suboptimal efficacy/tolerability. Our data suggest a high burden of illness associated with TN.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License

  9. Functional outcomes of childhood dorsal rhizotomy in adults and adolescents with cerebral palsy.

    Science.gov (United States)

    Hurvitz, Edward A; Marciniak, Christina M; Daunter, Alecia K; Haapala, Heidi J; Stibb, Stacy M; McCormick, Sarah F; Muraszko, Karin M; Gaebler-Spira, Deborah

    2013-04-01

    after the SDR. Seventy-four percent of participants underwent orthopedic surgery. Thirty-eight percent were currently taking oral medications for tone, and 53% had received botulinum toxin injections for spasticity treatment. Thirteen patients (15%) had an intrathecal baclofen pump placed. The majority of adults who had undergone SDR as children would recommend the procedure to others. Very few reported negative impressions of the procedure. Levels of satisfaction with life were generally high. Pain prevalence was similar to what has been reported in the literature for adults with cerebral palsy. Despite the SDR, further interventions, both surgical and nonsurgical, were used in the majority of patients.

  10. Off-label prescriptions: how to identify them, frame them, announce them and monitor them in practice?

    Science.gov (United States)

    Le Jeunne, Claire; Billon, Nathalie; Dandon, Anne; Berdaï, Driss; Adgibi, Yolande; Bergmann, Jean-François; Bordet, Régis; Carpentier, Anne; Cohn, Emmanuelle; Courcier, Soizic; Girault, Danièle; Goni, Sylvia; Jolliet, Pascale; Liard, François; Prot-Labarthe, Sonia; Simon, Tabassome; Vernotte, Christine; Westerloppe, Jérémie

    2013-01-01

    Following the Mediator crisis and the passage of the Health and Safety Law of December 2011, off-label prescriptions are a real concern shared by all those involved in healthcare system. Off-label, in the strictest sense of the term, is defined as all prescriptions that do not correspond to the summary of product characteristics (SPC), particularly those that fail to comply with the indications and dosage regimens defined by the marketing authorization (MA) for clear safety reasons. There are various rasons for off-label prescriptions, both conscious and unconscious. They are intended to respond to unmet medical needs, the needs of poorly studied populations or not studied at all in trials, but in relation to whom it is reasonable to extrapolate that MA would be given (common-sense prescriptions) and, additionally, to urgent public health needs (such as baclofen, pregnant women, and HIV drugs). All these prescriptions would deserve to be studied for a potential MA. However, there are off-label prescriptions that need to be restricted or even penalized in the case of compassionate prescriptions or unjustified prescriptions or prescriptions not based on any scientific grounds. Off-label prescriptions are not easy to track down because if the prescriber has to write "off-label" on his prescription, then clearly, in practice, he will only do so in exceptional cases. Neither the pharmacists who dispense the drug nor the Social Security that reimburses it, have access to the diagnosis (or targeted indication). Thus, in order to identify the off-label prescription, we must be able to cross reference the available databases (such as pharmacovigilance database, medicalized information system program [programme de médicalisation des systèmes d'information, PMSI], hospital drug formularies, general sample of beneficiaries [échantillon généraliste de bénéficiaires, EGB] or national inter-regional Health Insurance Information System [système national d

  11. Weakness and numbness of extremities with bowel and bladder dysfunction for four years

    Directory of Open Access Journals (Sweden)

    Han-hui FU

    2017-03-01

    :640 (<1:40, antineutrophilic cytoplasmic antibody (ANCA, antiphospholipid antibody were negative. DNA-immunofluorescence (IF 1:10 (<1:5, DNS-enzyme-linked immunosorbent assay (ELISA 296IU/ml (<100IU/ml; Tumor biomarkers screening showed no positive finding. Serum iron 8.243umol/L (8.59-30.43 umol/L, transferrin 18.06umol/L (22.72-40.90 umol/L, total iron binding capacity 41.35umol/L (44.75-80.55 umol/L, transferrin saturation 16.70% (25-50%. The cerebrospinal fluid (CSF was clear. The routine, biochemistry and lactic acid of CSF were within normal range. Cytological examination was negative. AQP-4 antibody (also named NMO-IgG in CSF was 1:100. No abnormal finding showed in the chest CT and cranial MRI. Thoracic spinal cord MRI showed a longitudinally extensive high intensity lesion on spinal cord of C7-T7 segments in sagittal T2WI and compression fractures of T7-10, especially T7-8. Labial salivary gland biopsy showed lymphocytes infiltration. Diagnosis and treatment: After admission, she was treated with vitamin B (vitamin B1 10mg 3 times/d and mecobalamine 0.5mg 3 times/d, ginkgo capsule 400mg 3 times/d and baclofen 5mg 3 times/d orally. She was diagnosed as neuromyelitis optica spectrum disorder (NMOSD, connective tissue disease (CTD, systemic lupus erythematosus (SLE , secondary Sjögren’s Syndrome (SS. Thyroxine replacement therapy (levothyroxine sodium 50μg/d and calcium supplements (calcium carbonate 500mg/d, calcitriol 0.3μg 2 times/d, alendronate sodium 70mg/week and orthosis were taken according to the endocrinologists and orthopedists. She was treated with azathioprine (50mg/d and methyprednisolone pulse therapy (500mg/d, intravenous drip followed by oral methylprednisolone (50mg/d. The dose of methylprednisolone decreases by 5mg/d every two weeks. Two months later, the patients showed improvement in walking while no obvious change was noticed of other symptoms and signs.   DOI: 10.3969/j.issn.1672-6731.2017.03.014