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Essential tremor is a common movement disorder in adults that interferes with the performance of functional and social activities. Differentiation of essential tremor from other tremor syndromes is important in order to provide appropriate patient education and therapy. The mainstays of pharmacotherapy are propranolol and primidone; however, in selected patients, agents such as alcohol, benzodiazepines, botulinum toxin, and gabapentin may provide symptomatic benefits. Advances in surgical interventions, such as stereotactic thalamotomy and thalamic deep brain stimulation, offer patients an alternative treatment modality when pharmacotherapy is inadequate. A treatment algorithm is provided to guide clinicians in the management of patients with essential tremor.

To test the feasibility of comparing epilepsy treatment policies and outcome, a secondary and a tertiary epilepsy care facility have been audited in a previous study (1). Marked differences were observed in the treatment policies and outcome and in the distribution of seizure types and duration of epilepsy. For this reason the patients of that study were matched according to seizure type and duration of epilepsy, resulting in two groups each of 32 patients per centre. The outcome of treatment was assessed by using clinimetrical indexes for seizure frequency and severity and toxicity of medication, resulting in the Composite Index of Impairments (CII), reflecting all treatment-related impairments. For the statistical analysis the X2-test and the Kruskal-Wallis test were used. Differences were found to be statistically significant when p < 0.05. No distinct differences were found in the treatment policies of both centres. However, differences were observed in the outcome of treatment. The toxicity ratings in this study were significantly higher for the Epilepsy Centre. Also the Composite Index of Impairments (CII) was significantly higher at the Epilepsy Centre. The number of patients with a CII score of > 100 did not differ significantly for both centres. The finding that pharmacotherapy is similar in both centres, suggests that pharmacotherapy is pushed to its limits in both, and that referral to a tertiary facility is mainly for the non-pharmacotherapeutic care modalities available. For the corroboration of this assumption the use of a quality of life index would be more appropriate than the CII.

1. The pharmacokinetics and metabolism of primidone at steady-state were studied in 10 elderly patients aged 70-81 years and eight control subjects aged 18-26 years. 2. Primidone half-lives and clearance values (mean +/- s.d.) were similar in the elderly and in the young (12.1 +/- 4.6 vs 14.7 +/- 3.5 h and 34.8 +/- 9.0 vs 33.2 +/- 7.2 ml h-1 kg-1 respectively. 3. The serum concentrations of the metabolites phenylethylmalonamide (PEMA) and phenobarbitone relative to those of parent drug were higher in the elderly than in the young, the difference being significant (P less than 0.01) in the case of PEMA. 4. The renal clearances of primidone, phenobarbitone and PEMA were moderately decreased in the elderly but this reduction was statistically significant only for PEMA. Elderly patients excreted a reduced proportion of unchanged primidone and an increased proportion of PEMA in urine. 5. Ageing is associated with a greater accumulation of PEMA, which is unlikely to have a major clinical significance.

A comparison was made between the levels of derived Phenobarbitone in three groups of patients who were taking Primidone as a single drug, Primidone with Phenytoin and Primidone in combination with Phenytoin and Carbamazepine. The levels of ingested Phenobarbitone when this drug was taken as a single drug were compared with the levels when Phenobarbitone was taken in combination with Phenytoin in two other groups of patients. A significant increase in derived Phenobarbitone levels occurred when Primidone was used in combination with Phenytoin alone or with Phenytoin and Carbamazepine. The highest level occurred in a group of patients taking the three drug combination. There was no significant difference between the levels of ingested Phenobarbitone when this drug was used as single therapy or in combination with Phenytoin. We suggest that the increase in derived Phenobarbitone levels relates to the effect of Phenytoin on liver enzyme systems, and that the greater increase with triple therapy was related to the combined effect of Carbamazepine and Phenytoin on microsomal enzymes. As there was no increase in ingested Phenobarbitone levels when this drug was taken in combination with Phenytoin, we were unable to confirm previous suggestions that Phenytoin either inhibits the hydroxylation of Phenobarbitone or impairs its renal excretion.

Primidone was compared to the unselective beta adrenoceptor antagonist propranolol in the suppression of essential tremor. In a 4-week single-blind placebo-controlled study primidone was given in increasing doses from 62.5 mg X 1 up to 250 mg X 3 daily and propranolol 20 mg X 3 daily. The drugs produced a similar reduction in the degree of tremor after 2 and 1 weeks' medication respectively. This indicates that primidone can be an alternative to propranolol when beta-blockers are contraindicated. However, primidone was significantly even more effective in the beginning after only 2 doses, when at the same time 10 of 13 patients showed a maximum of acute toxic side-effects producing nausea, vomiting, giddiness and/or sedation. Correlation analysis between the individual tremor amplitude reductions and plasma primidone concentrations showed on the second day a tendency towards a greater reduction in tremor in those patients with the highest primidone plasma concentration. By the fourteenth day tremor had increased compared with the second day and correlation analysis between individual increase in tremor amplitude and plasma phenobarbital concentrations showed the highest degree of tremor increase in those patients who had the highest levels of phenobarbital. These and other data suggest that after the first doses, tremor suppression and acute toxicity is related to the initial exposure to primidone and the plasma level of the drug itself rather than its metabolites phenobarbital and phenylethylmalanomide. The individual tremor frequency spectrums did not change significantly during the placebo and propranolol periods, whereas the frequency tended to decrease during the primidone period.

Fifteen epileptic patients had their dose of anticonvulsant drugs changed twice, each time by 30-50 per cent of the initial medication. Before the dose change, the patients were given six especially adapted mental performance tests, which were designed to measure vigilance, reaction time and certain aspects of memory. Serum drug levels were also monitored. The main results include assessment of effects of drugs on mental performance and evaluation of the psychological tests used. (1) Vigilance and reaction time test were the most useful in evaluation of effects of various doses of the medication; the memory tasks showed similar, but less definite, trends; and rote calculation and block design were of no particular value in this study. (2) On the tests for vigilance and reaction time, the greatest number of patients performed best on the lowest dose of their medication, the respective percentages being 45.8 and 56. By comparison, fewest patients performed best on their highest dose, the percentages being 16.7 for vigilance and 12.5 for reaction time; while the percentages on medium dose were 37.5 and 31.2 on the respective tests. (3) Use of well-standardized, yet simplified, mental performance tests in combination with changes in the dosage of medication can help in reaching a compromise between acceptable seizure control and avoidance of excessive slowing of mental activity.

The recurrence rate of febrile convulsions is assessed in 108 children who had had either prolonged or repeated initial fits or had both a positive family history and persisting neurological disorder. Only 7 of 40 (17%) who received continuous prophylactic phenobarbitone or primidone for at minimum of 18 months had another fit compared with 40 of 68 (59%) children who were untreated (p less than 0.0005). Indications for continuous therapy are discussed.