AV-block and conduction slowing prevail over TdP arrhythmias in the methoxamine-sensitized pro-arrhythmic rabbit model.

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Varkevisser, Rosanne; Vos, Marc A; Beekman, Jet D; Tieland, Ralph G; Van Der Heyden, Marcel A

2015-01-01

The methoxamine-sensitized rabbit model is widely used to screen drugs for proarrhythmic properties, especially repolarization-dependent TdP arrhythmias. With the change of anesthesia and/or sensitizing agent, conduction disturbances have been reported as well. Therefore, we compared currently available in-house anesthetics in order to preserve arrhythmia sensitivity and preclude conduction disturbances. Rabbits were randomly assigned to 3 groups: (1) 35 mg/kg ketamine + 5 mg/kg xylazine; (2) 0.5 mL/kg hypnorm + 3 mg/kg midazolam; (3) 35 mg/kg ketamine + 20 mg/kg propofol. Anesthesia was maintained by 1.5% isoflurane. Concomitant infusion of methoxamine (17 μg/kg/min for 40 minutes) and dofetilide (10 μg/kg/min for 30 minutes) was used to induce arrhythmias. Sole methoxamine infusion exclusively decreased HR in groups 1 and 3. Dofetilide lengthened repolarization, followed in time by PQ/QRS prolongation, second-degree AV block, and subsequently TdP arrhythmias. TdP was seen in 80%, 0%, and 33% of the rabbits in groups 1, 2, and 3, respectively. Decreasing the dose of dofetilide to 5 μg/kg/min in ketamine/xylazine anesthetized rabbits resulted in a drop in TdP incidence (25%) while conduction disturbances persisted. Flunarizine (n = 6) suppressed all TdP arrhythmias while conduction disturbances remained present. TdP incidence in the methoxamine-sensitized rabbit could be dramatically influenced by anesthesia, drug dose, and flunarizine, while conduction slowing remained present. Thus, conduction slowing seems to be the integral outcome in this model. © 2014 Wiley Periodicals, Inc.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

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Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-11-15

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

[Headache Treatment].

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Diener, Hans Christoph; Holle-Lee, Dagny; Nägel, Steffen; Gaul, Charly

2017-03-01

A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used. In cluster headache verapamil (in combination with steroids) is the most frequently used prophylactic agent. This article focusses on the current acute and prophylactic treatment of common headache syndromes. © Georg Thieme Verlag KG Stuttgart · New York.

Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.

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Heinz, Christoph; Lutz, J Patrick; Simmons, Eric M; Miller, Michael M; Ewing, William R; Doyle, Abigail G

2018-02-14

This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via α-amino radical formation. Accordingly, application of catalytic conditions to an intramolecular reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.

Otimizando o componente farmacológico da terapia integrada da vertigem Optimizing the pharmacological component of integrated balance therapy

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Maurício Malavasi Ganança

2007-02-01

Full Text Available A farmacoterapia é opção importante no tratamento das vestibulopatias periféricas. OBJETIVO: Identificar a medicação que otimiza a terapia integrada da vertigem (TIV na doença de Ménière e em outras vestibulopatias periféricas. MATERIAL E MÉTODO: Estudo de casos em que pacientes com doença de Ménière ou outras vestibulopatias periféricas receberam TIV com betaistina, cinarizina, clonazepam, flunarizina, Ginkgo biloba ou sem medicação durante 120 dias. RESULTADOS: Na doença de Ménière, TIV com qualquer um dos medicamentos foi mais eficaz do que TIV sem medicação, após 60 dias; a betaistina foi mais efetiva que todas as outras drogas, após 60 e 120 dias. Nas outras vestibulopatias periféricas, diferenças significantes foram observadas entre TIV com betaistina, cinarizina, clonazepam ou flunarizina e TIV sem medicação após 60 dias e todas as drogas foram mais efetivas que TIV sem medicação após 120 dias; betaistina, cinarizina ou clonazepam foram igualmente efetivos e betaistina foi mais efetiva que flunarizina e Ginkgo biloba. Os tratamentos foram bem tolerados. CONCLUSÕES: TIV incluindo medicação é mais efetiva que sem medicação na doença de Ménière ou em outras vestibulopatias periféricas. Betaistina foi o medicamento mais efetivo na doença de Ménière e tão eficaz quanto cinarizina ou clonazepam em outras vestibulopatias periféricas.Drug treatment is an important option for the treatment of peripheral vestibular diseases. AIM: To identify the drug component associated with optimal integrated balance therapy (IBT for Ménière’s disease or other peripheral vestibular disorders. MATERIALS AND METHODS: Analysis of a series of patients with Ménière’s disease patients or patients with other peripheral vestibular disorders that received IBT involving either no medication or betahistine, cinnarizine, clonazepam, flunarizine or Ginkgo biloba during 120 days. RESULTS: In Ménière’s disease

Veratridine increases the survival of retinal ganglion cells in vitro

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S.P.F. Pereira

1997-12-01

Full Text Available Neuronal cell death is an important phenomenon involving many biochemical pathways. This degenerative event has been studied to understand how the cells activate the mechanisms that lead to self-destruction. Target cells and afferent cells play a relevant role in the regulation of natural cell death. We studied the effect of veratridine (1.5, 3.0, 4.5 and 6.0 µM on the survival of neonatal rat retinal ganglion cells in vitro. Veratridine (3.0 µM, a well-known depolarizing agent that opens the Na+ channel, promoted a two-fold increase in the survival of retinal ganglion cells kept in culture for 48 h. This effect was dose-dependent and was blocked by 1.0 µM tetrodotoxin (a classical voltage-dependent Na+ channel blocker and 30.0 µM flunarizine (a Na+ and Ca2+ channel blocker. These results indicate that electrical activity is also important for the maintenance of retinal ganglion cell survival in vitro

Migraine - Prophylactic Treatment

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Chowdhury Debashish

2002-01-01

Full Text Available Preventive therapy in migraine constitutes an important aspect of migraine management especially in patients who are not controlled or have significant disability despite taking drugs for acute management. In spite of te recent advances in understanding of the pathophysiology of migraine, the mechanisms of action of many preventive drugs are largely unknown. Further, these provide only about 50% reduction in frequency in about 2/3rds of migraine sufferers. Hence, risk-benefit ratio must be considered while prescribing these agents. Recent efforts to undertake large-scale meta-analysis to assess the efficacy of these agents have been rewarding and consensus guidelines have evolved. Propanolol, metoprolol, amitriptyline, sodium valproate, flunarizine and lisuride have emerged as first line drugs. The role of newer anti-convulsants and botox injections in refractory cases are being investigated. Availability, co-morbidities, medical contraindications, concomitant acute therapy and costs are important determinants for choosing a particular agent. This article reviews the guidelines to be followed in choosing the prophylactic treatment options for migraine.

Characterization of [125I]endothelin-1 binding sites in rat cardiac membrane fragments

International Nuclear Information System (INIS)

Gu, X.H.; Casley, D.J.; Nayler, W.G.

1989-01-01

Standard binding and displacement techniques were used to identify high-affinity binding sites for [ 125 I]-labeled endothelin-1 (ET-1) in membranes harvested from the hearts of adult female Sprague-Dawley rats. A single population of binding sites was identified, with a KD of 0.20 +/- 0.03 nM at 37 degrees C, and a Bmax of 93.5 +/- 6.4 fmol/mg protein. Bound [ 125 I]ET-1 was displaced by ET-1 (10(-13)-10(-8) M), with a Ki of 0.08 nM. Neither (-)Bay K 8644 (10(-11)-10(-5) M), prenylamine (10(-11)-10(-5) M), (+)-cis-diltiazem (10(-10)-10(-5) M), (-)D888 (10(-10)-10(-5) M), nicardipine (10(-10)-10(-5) M), lidoflazine (10(-11)-10(-5) M), flunarizine (10(-11)-10(-5) M), omega-conotoxin (10(-13)-10(-7) M), nor prazosin (10(-10)-10(-5) M) displaced the bound ligand. Binding occurred in the absence of Ca2+ and was absent in heat-denatured membranes. These results are interpreted to mean that [ 125 I]ET-1 binds to a single class of high-affinity binding sites that differ from those occupied by known regulators of voltage activated L- and N-type Ca2+ channels

Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

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Liu, Shuyuan; Yue, Longtao; Gu, Wenrui; Li, Xiuyun; Zhang, Liuping; Sun, Shujuan

2016-01-01

Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers), amlodipine (AML), nifedipine (NIF), benidipine (BEN) and flunarizine (FNZ) with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1) expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI) <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2). The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin) and YVC1 (encoding calcium channel protein in vacuole membrane).

Characterization of transport of calcium by microsomal membranes from roots maize

International Nuclear Information System (INIS)

Vaughan, M.A.

1985-01-01

This study investigates calcium transport by membranes of roots of maize isolated by differential centrifugation. The preparation was determined to be enriched in plasma membrane using market enzyme and electron microscopy. Using the 45 Ca filtration technique and liquid scintillation counting, vesicular calcium uptake was shown to be stimulated by added calmodulin and specific for and dependent on ATP. Conditions for maximal calcium accumulation were found to be 30 min incubation in the presence of 5 mM ATP, 5 mM MgCl 2 , 50 μM CaCl 2 , at 23 0 C, and at pH 6.5. Calcium uptake was inhibited by the ionophores A23187, X-537A, and ionomycin. Sodium fluoride, ruthenium red, and p-chloromercuribenzoate completely inhibited transport: diamide and vanadate produced slight inhibition; caffeine, caffeic acid, oligomycin, and ouabain produced little or no inhibition. Chlorpromazine, W7, trifluoperazine, and R 24 571 inhibit calcium uptake irrespective of added calmodulin, while W5 showed little effect on uptake. Verapamil, nifedipine, cinnarizine, flunarizine, lidoflazine, and diltiazem decreased calcium uptake by 17%-50%. Electron microscopic localization of calcium by pyroantimonate showed vesicles incubated with calmodulin and ATP showed the greatest amount of precipitate. These results suggest that these vesicles accumulate calcium in an ATP-dependent, calmodulin-stimulated manner

Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

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Shuyuan Liu

Full Text Available Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers, amlodipine (AML, nifedipine (NIF, benidipine (BEN and flunarizine (FNZ with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1 expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2. The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin and YVC1 (encoding calcium channel protein in vacuole membrane.

Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.

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Goñi-Allo, Beatriz; Puerta, Elena; Hervias, Isabel; Di Palma, Richard; Ramos, Maria; Lasheras, Berta; Aguirre, Norberto

2007-05-21

Amiloride and several of its congeners known to block the Na(+)/Ca(2+) and/or Na(+)/H(+) antiporters potentiate methamphetamine-induced neurotoxicity without altering methamphetamine-induced hyperthermia. We now examine whether amiloride also exacerbates 3,4-methylenedioxymethamphetamine (MDMA)-induced long-term serotonin (5-HT) loss in rats. Amiloride (2.5 mg/kg, every 2 h x 3, i.p.) given at ambient temperature 30 min before MDMA (5 mg/kg, every 2 h x 3, i.p.), markedly exacerbated long-term 5-HT loss. However, in contrast to methamphetamine, amiloride also potentiated MDMA-induced hyperthermia. Fluoxetine (10 mg/kg i.p.) completely protected against 5-HT depletion caused by the MDMA/amiloride combination without significantly altering the hyperthermic response. By contrast, the calcium channel antagonists flunarizine or diltiazem did not afford any protection. Findings with MDMA and amiloride were extended to the highly selective Na(+)/H(+) exchange inhibitor dimethylamiloride, suggesting that the potentiating effects of amiloride are probably mediated by the blockade of Na(+)/H(+) exchange. When the MDMA/amiloride combination was administered at 15 degrees C hyperthermia did not develop and brain 5-HT concentrations remained unchanged 7 days later. Intrastriatal perfusion of MDMA (100 microM for 8 h) in combination with systemic amiloride caused a small depletion of striatal 5-HT content in animals made hyperthermic but not in the striatum of normothermic rats. These data suggest that enhancement of MDMA-induced 5-HT loss caused by amiloride or dimethylamiloride depends on their ability to enhance MDMA-induced hyperthermia. We hypothesise that blockade of Na(+)/H(+) exchange could synergize with hyperthermia to render 5-HT terminals more vulnerable to the toxic effects of MDMA.

Canadian Headache Society guideline for migraine prophylaxis.

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Pringsheim, Tamara; Davenport, W Jeptha; Mackie, Gordon; Worthington, Irene; Aubé, Michel; Christie, Suzanne N; Gladstone, Jonathan; Becker, Werner J

2012-03-01

The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. This guideline is focused on patients with episodic migraine (headache on ≤ 14 days a month). Through a comprehensive search strategy, randomized, double blind, controlled trials of drug treatments for migraine prophylaxis and relevant Cochrane reviews were identified. Studies were graded according to criteria developed by the US Preventive Services Task Force. Recommendations were graded according to the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. In addition, a general literature review and expert consensus were used for aspects of prophylactic therapy for which randomized controlled trials are not available. Prophylactic drug choice should be based on evidence for efficacy, side-effect profile, migraine clinical features, and co-existing disorders. Based on our review, 11 prophylactic drugs received a strong recommendation for use (topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan, butterbur, riboflavin, coenzyme Q10, and magnesium citrate) and 6 received a weak recommendation (divalproex sodium, flunarizine, pizotifen, venlafaxine, verapamil, and lisinopril). Quality of evidence for different medications varied from high to low. Prophylactic treatment strategies were developed to assist the practitioner in selecting a prophylactic drug for specific clinical situations. These strategies included: first time strategies for patients who have not had prophylaxis before (a beta-blocker and a tricyclic strategy), low side effect strategies (including both drug and herbal/vitamin/mineral strategies), a strategy for patients with high body mass index, strategies for patients with co-existent hypertension or with co-existent depression and /or

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area.

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Wang, Yu; Tian, Miao-Miao; Wang, Xian-Hong; Zhu, Xiao-Qun; Liu, Ying; Lu, Ya-Nan; Pan, Qing-Qing

2014-06-26

A headache circumscribed in a line-shaped area but not confined to the territory of one particular nerve had ever been described in Epicrania Fugax (EF) of which the head pain is moving and ultrashort. In a 25-month period from Feb 2012 to Mar 2014, we encountered 12 patients with a paroxysmal motionless head pain restricted in a linear trajectory. The head pain trajectory was similar to that of EF, but its all other features obviously different from those of EF. We named this distinctive but undescribed type of headache linear headache (LH). A detailed clinical feature of the headache was obtained in all cases to differentiate with EF, trigeminal autonomic cephalalgias (TACs) and cranial neuralgia. Similarities and differences in clinical features were compared between LH and migraine. The twelve LH patients (mean age 43.9 ± 12.2) complained of a recurrent, moderate to severe, distending (n = 9), pressure-like (n = 3) or pulsating (n = 3) pain within a strictly unilateral line-shaped area. The painful line is distributed from occipital or occipitocervical region to the ipsilateral eye (n = 5), forehead (n = 6) or parietal region (n = 1). The pain line has a trajecory similar to that of EF but no characteristics of moving. The headache duration would be ranged from five minutes to three days, but usually from half day to one day in most cases (n = 8). Six patients had the accompaniment of nausea with or without vomiting, and two patients had the accompaniment of ipsilateral dizziness. The attacks could be either spontaneous (n = 10) or triggered by noise, depression and resting after physical activity (n = 1), or by stress and staying up late (n = 1). The frequency of attacks was variable. The patients had well response to flunarizine, sodium valproate and amitriptyline but not to carbamazepine or oxcarbazepine. LH is different from EF, trigeminal autonomic cephalalgias (TACs) and cranial neuralgia, but it had couple of features similar to that of migraine. The

Prophylactic treatment of vestibular migraine

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Márcio Cavalcante Salmito

Full Text Available Abstract Introduction: Vestibular migraine (VM is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including β-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce. Objective: To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic. Methods: Review of medical records from patients with VM according to the criteria of the Bárány Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used. Associations with clinical subgroups of patients were also assessed. Results: Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p < 0.001. Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p < 0.001 and headache (p < 0.015. The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug

Depressogenic medications and other risk factors for depression among Polish patients with epilepsy

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Bosak M

2015-09-01

Full Text Available Magdalena Bosak,1 Wojciech Turaj,1 Dominika Dudek,2 Marcin Siwek,2 Andrzej Szczudlik1 1Department of Neurology, 2Department of Psychiatry, Jagiellonian University Medical College, Krakow, Poland Purpose: The aim of this study was to assess the prevalence of depression among patients with epilepsy and to establish the risk factors of depression in that group, with special focus on the use of potentially depressogenic medications. Patients and methods: We studied 289 consecutive patients who visited epilepsy outpatient clinic (University Hospital of Krakow and met inclusion criteria. All patients were screened with Beck Depression Inventory (BDI, and those with BDI score ≥12 were further evaluated by a psychiatrist. Results: Mean age of patients was 35.7 years, and mean duration of epilepsy was 14.7 years. Idiopathic generalized epilepsy was diagnosed in 63 patients (21.8%, focal epilepsy was found in 189 subjects (65.4%, and unclassified epilepsy was diagnosed in 37 patients (12.8%. Frequent seizures (>1 per month were reported in 107 patients (37.0%. Thirty-five patients (12.1% reported an ongoing treatment with one or more of the predefined potentially depressogenic medication (ß-blockers, combined estrogen and progestogen, corticosteroid, or flunarizine. In a group of 115 patients (39.8% who scored ≥12 points in BDI, depression was finally diagnosed in 84 subjects (29.1% after psychiatric evaluation. Only 20 of those patients (23.8% were treated with antidepressant. Independent variables associated with the diagnosis of depression in the logistic regression model included frequent seizures (odds ratio [OR] =2.43 [95% confidence interval, 95% CI =1.38–4.29], P=0.002, use of potentially depression-inducing medications (OR =3.33 [95% CI =1.50–7.39], P=0.003, age (OR =1.03 [95% CI =1.01–1.05] per year], P=0.005, and use of oxcarbazepine (OR =2.26 [95% CI =1.04–4.9], P=0.038. Conclusion: The prevalence of depression among consecutive

Epigone migraine vertigo (EMV): a late migraine equivalent.

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Pagnini, P; Vannucchi, P; Giannoni, B; Pecci, R

2014-02-01

Migrainous headache is determined by pathogenetic mechanisms that are also able to affect the peripheral and/or central vestibular system, so that vestibular symptoms may substitute and/or present with headache. We are convinced that there can be many different manifestations of vestibular disorders in migrainous patients, representing true different clinical entities due to their different characteristics and temporal relashionship with headache. Based on such considerations, we proposed a classification of vertigo and other vestibular disorders related to migraine, and believe that a particular variant of migraine-related vertigo should be introduced, namely "epigone migraine vertigo" (EMV): this could be a kind of late migraine equivalent, i.e. a kind of vertigo, migrainous in origin, starting late in the lifetime that substitutes, as an equivalent, pre-existing migraine headache. To clarify this particular clinical picture, we report three illustrative clinical cases among 28 patients collected during an observation period of 13 years (November 1991 - November 2004). For all patients, we collected complete personal clinical history. All patients underwent standard neurotological examination, looking for spontaneous-positional, gaze-evoked and caloric induced nystagmus, using an infrared video camera. We also performed a head shaking test (HST) and an head thrust test (HTT). Ocular motility was tested looking at saccades and smooth pursuit. To exclude other significant neurological pathologies, a brain magnetic resonance imaging (MRI) with gadolinium was performed. During the three months after the first visit, patients were invited to keep a diary noting frequency, intensity and duration of vertigo attacks. After that period, we suggested that they use prophylactic treatment with flunarizine (5 mg per day) and/or acetylsalicylic acid (100 mg per day), or propranolol (40 mg twice a day). All patients were again recommended to note in their diary the frequency

Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?

International Nuclear Information System (INIS)

Baudelet, Christine; Ansiaux, Reginald; Jordan, Benedicte F; Havaux, Xavier; Macq, Benoit; Gallez, Bernard

2004-01-01

T2*-weighted gradient-echo magnetic resonance imaging (T2*-weighted GRE MRI) was used to investigate spontaneous fluctuations in tumour vasculature non-invasively. FSa fibrosarcomas, implanted intramuscularly (i.m.) in the legs of mice, were imaged at 4.7 T, over a 30 min or 1 h sampling period. On a voxel-by-voxel basis, time courses of signal intensity were analysed using a power spectrum density (PSD) analysis to isolate voxels for which signal changes did not originate from Gaussian white noise or linear drift. Under baseline conditions, the tumours exhibited spontaneous signal fluctuations showing spatial and temporal heterogeneity over the tumour. Statistically significant fluctuations occurred at frequencies ranging from 1 cycle/3 min to 1 cycle/h. The fluctuations were independent of the scanner instabilities. Two categories of signal fluctuations were reported: (i) true fluctuations (TFV), i.e., sequential signal increase and decrease, and (ii) profound drop in signal intensity with no apparent signal recovery (SDV). No temporal correlation between tumour and contralateral muscle fluctuations was observed. Furthermore, treatments aimed at decreasing perfusion-limited hypoxia, such as carbogen combined with nicotinamide and flunarizine, decreased the incidence of tumour T2*-weighted GRE fluctuations. We also tracked dynamic changes in T2* using multiple GRE imaging. Fluctuations of T2* were observed; however, fluctuation maps using PSD analysis could not be generated reliably. An echo-time dependency of the signal fluctuations was observed, which is typical to physiological noise. Finally, at the end of T2*-weighted GRE MRI acquisition, a dynamic contrast-enhanced MRI was performed to characterize the microenvironment in which tumour signal fluctuations occurred in terms of vessel functionality, vascularity and microvascular permeability. Our data showed that TFV were predominantly located in regions with functional vessels, whereas SDV occurred in regions

Anticonvulsants for tinnitus.

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Hoekstra, Carlijn El; Rynja, Sybren P; van Zanten, Gijsbert A; Rovers, Maroeska M

2011-07-06

Tinnitus is the perception of sound or noise in the absence of an external or internal acoustic stimulation. It is a common and potentially distressing symptom for which no adequate therapy exists. To assess the effectiveness of anticonvulsants in patients with chronic tinnitus. We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, CENTRAL (2010, Issue 2), MEDLINE, EMBASE, bibliographies and additional sources for published and unpublished trials. The date of the most recent search was 26 May 2010. We selected randomised controlled trials in patients with chronic tinnitus comparing orally administered anticonvulsants with placebo. The primary outcome was improvement in tinnitus measured with validated questionnaires. Secondary outcomes were improvement in tinnitus measured with self-assessment scores, improvement in global well-being or accompanying symptoms, and adverse drug effects. Three authors assessed risk of bias and extracted data independently. Seven trials (453 patients) were included in this review. These studies investigated four different anticonvulsants: gabapentin, carbamazepine, lamotrigine and flunarizine. The risk of bias of most studies was 'high' or 'unclear'. Three studies included a validated questionnaire (primary outcome). None of them showed a significant positive effect of anticonvulsants. One study showed a significant negative effect of gabapentin compared to placebo with an increase in Tinnitus Questionnaire (TQ) score of 18.4 points (standardised mean difference (SMD) 0.82, 95% confidence interval (CI) 0.07 to 1.58). A second study showed a positive, non-significant effect of gabapentin with a difference compared to placebo of 2.4 points on the Tinnitus Handicap Inventory (THI) (SMD -0.11, 95% CI -0.48 to 0.25). When the data from these two studies are pooled no effect of gabapentin is found (SMD 0.07, 95% CI -0.26 to 0.40). A third study reported no differences on the THI after treatment with gabapentin

[Prophylactic treatments of migraine].

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Massiou, H

2000-01-01

Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. It is usually proposed to patients who suffer from two or more attacks per month. It should also be considered in patients who suffer from less frequent, but prolonged, disabling attacks with a poor response to abortive treatment, and who consider that their quality of life is reduced between attacks. Excessive intake of acute medication, more than twice a week, is a strong indication for prophylactic treatment. In order to obtain a good compliance to treatment, the patient must be informed of the expected efficacy of the drugs, and of their most frequent side effects. Thus, the choice of a prophylactic drug is made together with the patient. Based on the results of published controlled trials, the main prophylactic drugs are some betablockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, and sodium valproate. Some less evaluated drugs such as aspirin, DHE, indoramine, verapamil, may be useful. Other substances such as riboflavin and new antiepileptic dugs are being evaluated. The choice of the drug to start with depends on several considerations. The first step is to make sure that there are no contra indications, and no possible interaction with the abortive medications. Then, possible side effects will be taken into account, for example, weight gain is a problem for most young women and patients who practice sports may not tolerate betablockers. Associated pathologies have to be checked. For example, a hypertensive migraine sufferers may benefit from betablockers; in a patient who suffers both from migraine and tension type headaches or from depression, amitriptyline is the first choice drug. The type of migraine should also be considered; for instance, in frequent attacks with aura, aspirin is recommended and betablockers avoided. In most cases, prophylaxis should be given as monotherapy, and it is often necessary to try successively several drugs

Etiology of parkinsonism in a Brazilian movement disorders clinic Etiologia de parkinsonismo em uma clínica brasileira de distúrbios do movimento

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FRANCISCO CARDOSO

1998-06-01

Full Text Available OBJECTIVE: The aim of the present study is to investigate whether there are geographic differences in the etiology of parkinsonism (PA. BACKGROUND: 72% of patients with PA evaluated at movement disorders clinics in the Northern Hemisphere are diagnosed with Parkinson's disease (PD. Data regarding other regions are not available. METHODS: We reviewed the charts of all patients with PA seen at the Federal University of Minas Gerais Movement Disorders Clinic from July 1993 through October 1995. PA was diagnosed by the presence of at least two of the following: rest tremor, bradykinesia, rigidity, and postural instability. The different etiologies were diagnosed based on standard clinical criteria RESULTS: During the period of the study, PA was recognized in 338 subjects. The following clinical diagnoses were made: PD (68.9%, drug-induced PA (DIP (13.3%, vascular PA (4.7%, Progressive supranuclear palsy (PSP (2%, multiple system atrophy (MSA (1.8%, others (9.7%. Cinnarizine, haloperidol and flunarizine were the commonest drugs related to DIP. CONCLUSIONS: Similarly to other studies, PD accounts for about 70% of PA patients. However, there are differences between our results and previous series. DIP is much more common in the present series. This may be accounted for a more liberal use of antidopaminergic drugs in our environment, especially Calcium channel blockers. The lower frequency of MSA and PSP in our study may reflect a short follow-up, since many patients initially diagnosed with PD later are found to have Parkinson-plus syndromes.OBJETIVO: O objetivo deste estudo é investigar se há diferenças geográficas na etiologia de parkinsonismo (PA. PANORAMA: 72% dos pacientes com PA avaliados em Clínicas de Distúrbios do Movimento no hemisfério norte são diagnosticados com doença de Parkinson (DP. Dados a respeito de outras regiões não se encontram disponíveis. MÉTODOS: Nós revisamos os prontuários de todos pacientes com PA vistos na