Treatment of essential tremor: current status.

Essential tremor is the most common cause of tremor involving upper limbs, head and voice. The first line of treatment for limb tremor is pharmacotherapy with propranolol or primidone. However, these two drugs reduce the tremor severity by only half. In medication refractory and functionally disabling tremor, alternative forms of therapy need to be considered. Botulinum toxin injections are likely efficacious for limb, voice and head tremor but are associated with side effects. Surgical interventions include deep brain stimulation; magnetic resonance-guided focused ultrasound and thalamotomy for unilateral and deep brain stimulation for bilateral procedures. Recent consensus classification for essential tremor has included a new subgroup, 'Essential tremor plus', who have associated subtle neurological 'soft signs', such as dystonic posturing of limbs and may require a different treatment approach. In this review, we have addressed the current management of essential tremor with regard to different anatomical locations of tremor as well as different modalities of treatment.

Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins.

OBJECTIVES: Patients with epilepsy have excess morbidity and mortality due to ischemic cardiovascular disease. Many of these patients have elevated concentrations of plasma total homocysteine (Hcy), which is an acknowledged risk factor for cardiovascular disease, venous thromboembolic disease, foetal malformations and dementia. Hyperhomocysteinemia may have negative effects through mechanisms involving oxidative damage. In the present study, we have investigated the aminothiol redox-status in patients on antiepileptic drugs. Thereafter, in a subset of patients with elevated total Hcy, we evaluated the effect of B-vitamin therapy. METHODS: In the first part of the study, 101 patients on antiepileptic drugs were compared with 101 matched healthy controls. The redox-species of Hcy, cysteine and cysteinylglycine, the major aminothiols in plasma, were analyzed by high-performance liquid chromatography (HPLC). Hyperhomocysteinemia was defined as fasting total Hcy above 12 micromol/L and/or post-methionine load concentrations above 38 micromol/L. In the second part of the study, 33 patients identified with hyperhomocysteinemia were supplemented with three B-vitamins for 30 days; folic acid (B9), pyridoxine (B6) and riboflavin (B2). RESULTS: All redox-species of Hcy were significantly elevated in the patients, except the fasting concentrations of reduced Hcy (p=0.09). The reduced/total ratio of cysteine in fasting plasma was lower in the patients than in the controls: 5.20% vs. 6.19%, respectively (p=0.006). After 30 days of B-vitamin supplementation, the plasma concentrations of reduced, oxidized and protein-bound Hcy species were significantly lowered by 17%, 22% and 28%, respectively. The reduced/total ratio of cysteine rose from 4.9% to 7.9% (p=0.007). CONCLUSIONS: Patients on antiepileptic drugs have abnormal aminothiol redox-status associated with hyperhomocysteinemia. This is similar to findings in patients with cardiovascular disease. B-vitamin supplementation partially corrects the abnormal aminothiol redox-status. Possibly, B-vitamin supplementation may be useful in drug-induced hyperhomocysteinemia.

[Therapeutical strategies for essential tremor]. / Estrategias terapéuticas en el temblor esencial.

Essential tremor is the most common adult movement disorder. Traditionally considered as a benign disease, it can cause an important physical and psychosocial disability. Drug treatment remains poor and often unsatisfactory. Current therapeutical strategies are reviewed according to the level of discomfort caused by tremor: mild tremor, non-pharmacological strategies, alcohol, acute pharmacological therapy; moderate tremor, pharmacological therapies (propranolol, gabapentin, primidone, topiramate, alprazolam and other drugs), and severe tremor, the role of functional surgery is emphasized (thalamic deep brain stimulation, thalamotomy). It is also described the more specific treatment of head tremor with the use botulinum toxin. Finally, several points are exposed to guide the immediate research of this disease in near future.

Essential tremor: differential diagnosis and current therapy.

Essential tremor is a common movement disorder that affects between 5 and 10 million persons in the United States. It is characterized primarily by an action and postural tremor most often affecting the arms, but it can also affect other body parts. Essential tremor is a progressive neurologic disorder and can cause substantial disability in some patients. Although there is no cure for essential tremor, pharmacologic and surgical treatments can provide some benefit. Primidone and propranolol are first-line treatments. Other medications with potential efficacy include benzodiazepines, gabapentin, topiramate, and botulinum toxin. Patients with medication-resistant tremor may benefit from thalamotomy or deep brain stimulation of the thalamus. The use of medical and surgical therapies can provide benefit in up to 80% of patients with essential tremor.

Tremor.

PURPOSE OF REVIEW: Tremors can be encountered in a variety of disease states but the most common causes are Parkinson disease and essential tremor. This review was undertaken to highlight advances in the field during the last 12 months. RECENT FINDINGS: Kinetic tremor may be more prominent in essential tremor than postural tremor. Clinically Parkinson disease and essential tremor may be confused with each other but it may be possible to distinguish between these two nitrites using sophisticated electrophysiology. Monosymptomatic rest tremor has recently been shown to be associated with decreased fluorodopa uptake on the positron emission tomography scan suggesting its relationship to Parkinson disease. SUMMARY: Significant advances have been made in the understanding of the pathophysiology, genetics and therapy of tremor disorders during the last 12 months. This review will consider Parkinson disease, essential tremor and other tremors and highlight advances in the field.

Benefits and risks of pharmacological treatments for essential tremor.

Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide.

Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for four weeks, each separated by a two-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol.

Epilepsia do lobo temporal em psiquiatria / Temporal lobe epilepsy in psychiatry

A epilepsia do lobo temporal é uma das principais condiçöes médicas que o psiquiatra deve afastar durante a avaliaçäo de pacientes com transtornos mentais. Os autores realizam breve revisäo da literatura sobre a história, fisiopatologia, diagnóstico e tratamento das crises epilépticas do lobo temporal, enfatizando os aspectos psicopatógicos e o diagnóstico diferencial com transtornos psiquiátricos como o pânico e a esquizofrenia. Dentre os avanços na área, a ressonância nuclear magnética tem demonstrado eficiência diagnóstica superior à da tomografia computadorizada na detecçäo da esclerose temporal mesial - a causa mais freqüente de epilepsia do lobo temporal. A detecçäo da esclerose temporal mesial é importante devido à freqüente indicaçäo de cirurgia nesses casos

Anticonvulsant drugs in alcohol withdrawal: use of phenytoin, primidone, carbamazepine, valproic acid, and the sedative anticonvulsants.

The evidence for the efficacy of anticonvulsant drugs in the control of seizures during alcohol withdrawal is examined. The literature on the use of anticonvulsants to control anxiety, irritability, tension, and other symptoms of abstinence syndrome is reviewed. The data on benzodiazepines, phenobarbital, hydroxyzine, and neuroleptics are discussed briefly. There is no evidence to support the routine use of phenytoin for seizure prophylaxis in detoxication. However, phenytoin may be valuable in patients at a high risk for seizures, such as skid-row alcoholics. Only one retrospective study has been done on primidone; it claimed primidone was an efficacious adjuvant. Carbamazepine and valproic acid may be useful in the treatment of anxiety, dysphoric mood, somatization, and other symptoms of abstinence syndrome, as well as for seizure prophylaxis. The benzodiazepines, diazepam and chlordiazepoxide, are recognized as primary therapeutic agents in the detoxication of alcoholic patients. The major difficulty with the use of phenobarbital is that it cannot be used over as wide a range as the benzodiazepines. Hydroxyzine has been shown to be inferior to chlorazepate dipotassium. Most neuroleptics appear to be inappropriate for detoxication because they lower the seizure threshold; however, haloperidol has been found efficacious in acutely abstinent alcoholics. Carbamazepine, valproic acid, primidone, and phenobarbital should be tested against standard drugs such as chlordiazepoxide and diazepam in the detoxication of alcoholic patients.

Flow-dependent salivary primidone levels in epileptic children.

In 36 epileptic children treated with primidone alone or in combination with additional anticonvulsants, salivary drug levels were compared in resting (I) and in flow-stimulated (II) saliva and were related to the corresponding serum levels. Primidone levels in saliva I and saliva II were highly correlated (r = 0.97) but were significantly (p less than 0.001) lower in saliva II; the mean difference was -38%. Serum primidone levels were highly correlated to salivary primidone levels both in saliva I (r = 0.92) and in salvia II (r = 0.91). A significant negative correlation could be established between the salivary flow rate and the saliva/serum ratio of primidone, especially in saliva I (r = 0.61; p less than 0.001). The mean saliva I/serum ratio was 1.115, reflecting drug accumulation in resting saliva. The reason primidone accumulates remains unclear. When salivary flow was stimulated, the mean saliva/serum ratio decreased to 0.7, indicating the development of a drug concentration slope from blood to saliva. This is explained by the limited permeation of the drug through cellular membranes due to its rather low lipid solubility. From the data it can be concluded that saliva is suitable for monitoring primidone levels provided the conditions of sample collection are standardized.

[Laboratory controls in long-term treatment with anticonvulsive drugs (author's transl)]. / Laborkontrolle bei Langzeittherapie mit Antiepileptika

In the treatment of epilepsy often several substances with anticonvulsive effect are combined. Possible drug interactions in these cases can change the desired effect of treatment. Simultaneous administration of clonazepam or dipropylacetate (the latter in a short term combination) with diphenylhydantoin can cause a significant increase of diphenylhydantoin serum concentrations and intoxications. The combination of carbamazepin with diphenylhydantoin can cause a decrease of diphenylhydantoin serum concentrations. The simultaneous administration of diphenylhydantoin and phenobarbital can produce a significant increase of phenobarbital levels in the statistical average and in the case of a combination of primidon and diphenylhydantoin an intoxication by the primidon metabolite phenobarbital. These possible interactions which are not obvious at the beginning of therapy are supplemented by other factors as intercurrent diseases or erratic drug intake. With routine measurements of serum concentrations of anticonvulsive drugs some of these interfering factors can be eliminated by realizing them in time. Treatment becomes more effective and side effects are reduced. The development of a new check list for the treatment of epileptic patients should also improve the control and give better informations about the course of the disease.