The contribution of mortality statistics to the study of multiple sclerosis in Australia.

Mortality statistics provided a valuable source of support for data obtained from prevalence surveys of multiple sclerosis in Australia. Firstly, multiple sclerosis mortality data for the decade 1971-80 in the States of Australia confirmed the relationship between increasing disease frequency and increasing south latitude shown by State and regional point prevalence surveys based on the national census day 30 June 1981. Secondly, a comparison with mortality data from the decade 1950-59 showed that in most States there had been a substantial fall in multiple sclerosis mortality in the more recent decade and this was clearly an important contributing factor to the rise in prevalence noted between the morbidity surveys of 1961 and 1981. Thirdly, multiple sclerosis mortality in the UK-born migrant population dying in Australia was found to be similar to that of the Australian-born population and very much lower than that found in the UK. This observation corroborated evidence from the 1981 morbidity surveys and suggested that migration from the UK to Australia may lower the risk of developing multiple sclerosis either through a reduction in disease incidence or the operation of environmental factors curbing disease expression.

Limbic encephalitis associated with malignant thymoma.

A case of limbic encephalitis associated with recurrent malignant thymoma in a 41-year-old male is described. The patient presented with confusion, loss of memory, hallucinations, abnormal behaviour, tachycardia and profuse sweating. Investigations were unrewarding and the patient's clinical state deteriorated until his death 1 month after presentation. The diagnosis was made at autopsy when bilateral extensive neuronal loss with reactive gliosis, confined to the medial temporal cortex and Ammon's horn, was revealed.

Survey of disability that is associated with Parkinson's disease.

Parkinson's disease is a relatively-common and disabling neurological condition. The aim of this study was to gather clinical and sociodemographic data on a sample of patients with Parkinson's disease in Tasmania, and to determine the impact of the disease on the patients. Sixty patients were studied. The median age of the sample was 71 years, and the median duration of Parkinson's disease was six years. About two-thirds of the patients experienced difficulty with simple everyday activities, such as dressing and getting out of a chair. Disability was related significantly to the duration of the disease. The number of antiparkinsonian drugs that were prescribed increased in proportion with the duration of the disease and the disability of the patient. Parkinson's disease was responsible apparently for 40% of the patients retiring from employment early; 32% of patients who had been drivers had lost their driver's licence because of the disease. Although the condition affects motor function progressively, few patients received physiotherapy as part of their management.

The clinical profile of MS in Australia: a comparison between medium- and high-frequency prevalence zones.

Recent epidemiologic studies of multiple sclerosis (MS) in Australia defined the State of Queensland as a medium-frequency zone and the more southerly placed cities of Perth, Newcastle, and Hobart as high-frequency zones. Clinical profiles in the patient populations of both frequency zones were remarkably similar in most respects to each other and to MS populations in the northern hemisphere. However, male patients in Queensland differed from their counterparts in the three cities by showing a greater tendency to develop a progressive disease course and, hence, more disability. The explanation for these observations is uncertain; we speculate that the hotter climate in Queensland may be relevant.

The epidemiology of multiple sclerosis in three Australian cities: Perth, Newcastle and Hobart.

An epidemiological survey of multiple sclerosis (MS) in three Australian cities, Perth, Newcastle and Hobart, was undertaken with its prevalence day being the national census day on June 30, 1981, exactly twenty years after a previous survey of the same cities. The relationship between increasing prevalence and increasing south latitude found in the 1961 survey was confirmed in this present study. Prevalence rates had increased significantly over the twenty years between the studies. Over the same time period incidence rates had also increased in Newcastle and Hobart but had remained essentially stable in Perth although these changes were not significant. The rise in prevalence was due to a combination of factors of differing importance in each city. These factors included better case ascertainment, increased recognition of the less severely disabled patient, increased survival time and differential immigration of a population at a higher risk of developing MS than the indigenous population. Finally, analysis of MS prevalence rates amongst migrant populations in Perth and Hobart suggested that either the risk of acquisition of MS may extend over a wider age range than is generally accepted or that environmental factors prevalent in the former city have modified disease expression there.

Visual evoked responses in diabetes.

In view of the conflicting evidence concerning prolongation of the VERs in diabetes, pattern reversal VERs were performed on 60 diabetic inpatients. Only in one patient was the VER unequivocally delayed without some other explanation and in 2 other patients it was prolonged in association with proliferative retinopathy. In the latter instance the latency may have been increased by involvement of the maculo-papillary fibres of the optic nerve which may occur during their passage through the retina. Otherwise the study does not strongly support the concept of optic neuropathy or central encephalopathy of the visual system in diabetes, at least as far as can be demonstrated by visual evoked cortical responses to pattern reversal stimuli.

The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders.

The pharmacokinetics of tetrabenazine and a metabolite, hydroxytetrabenazine, have been investigated in seven patients being treated for involuntary movement disorders. Tetrabenazine had a very low oral systemic availability (mean 0.049 +/- 0.032 SD). First-pass metabolism to hydroxytetrabenazine was extensive, and the systemic availability for this metabolite was high (mean 0.81 +/- 0.30 SD). Since hydroxytetrabenazine has been reported to be as active as tetrabenazine in depleting brain amines, and is present at much higher plasma concentrations than the parent drug, it is likely that this metabolite is the more important therapeutic moiety.

Food does not affect the bioavailability of baclofen.

It is recommended that baclofen, a centrally acting muscle relaxant, be administered with food or milk to minimize its gastrointestinal side-effects. However, there are no published data on the influence of food on the bioavailability of the drug. The extent and rate of absorption of baclofen were investigated after the oral administration of single 20-mg doses to five healthy volunteers. The drug was administered either under fasting conditions or with a standard meal, according to a crossover design. Food did not significantly influence either the rate or the relative extent of absorption of baclofen. Therefore, it is unlikely that the administration of baclofen with food to reduce the likelihood of gastrointestinal toxicity will adversely affect the clinical response to the drug.

Audit of a monitoring service for free phenytoin.

This study assessed the value of introducing the measurement of free phenytoin levels in a public hospital. After publicising the availability and purpose of the assay, free phenytoin levels were determined either (a) on the doctor's request or (b) when the total level was requested and the patient's record showed evidence of factors predisposing to an elevated unbound fraction. Total phenytoin was measured by EMIT, and the unbound fraction by ultrafiltration at 37 degrees C using [14C]-phenytoin as a tracer. During a 9 month period, 70 free level determinations were performed on 46 patients. These comprised 20% of all phenytoin assays. The median free phenytoin fraction was 13.6% (range 9.3-28.6%). While total phenytoin levels were below the normal optimum range in 61% cases, free levels were probably therapeutic or above in 70% cases. Dosage adjustments were recommended on the basis of the free level, and were followed more often when the doctor had requested the free level assay (P less than 0.05). The results suggest that a free phenytoin level assay can improve the usefulness of therapeutic drug monitoring, particularly when the doctor understands the purpose of the assay.

A randomised trial of strategies to improve patient compliance with anticonvulsant therapy.

Fifty-three hospital outpatients with epilepsy were randomly allocated to either a control or an intervention group. Patients in the intervention group were subjected to a combination of compliance-improving strategies: patient counselling, a special medication container, self-recording of medication intake and seizures, and mailed reminders to collect prescription refills and attend clinic appointments. Compliance with anticonvulsant therapy (as measured by plasma anticonvulsant levels and prescription refill frequencies), and seizure frequency, were evaluated in each patient prior to intervention and 6 months afterwards. Patient compliance and clinical control improved significantly in the intervention group patients. Seizure frequency was, on average, halved following intervention. Compliance and seizure frequency were unaltered in the control group. Intervention failed to improve clinic appointment keeping. Poor compliance with drug therapy commonly confounds the treatment of epilepsy. This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients.

Determinants of patient compliance with anticonvulsant therapy.

Determinants of compliance were examined in 101 hospital outpatients with epilepsy. Self-reported patient compliance was associated with plasma anticonvulsant levels, prescription refill frequencies, and appointment keeping. Factors independently related to compliance were worry about one's health, having generalized tonic-clonic seizures, and the absence of barriers to good compliance. Seizure frequency indirectly contributed to patient compliance through worry about one's health. Removing potential barriers to compliance and counselling patients who have been relatively seizure-free may improve compliance with anticonvulsant therapy.

Plasma protein binding of phenytoin in 100 epileptic patients.

The plasma protein binding of phenytoin was investigated in 100 epileptic patients, using equilibrium dialysis at 37 degrees C. The unbound fractions of phenytoin in plasma formed a skewed distribution, with a range of 9.7 to 24.7% and a median value of 12.3%. Most (80%) patients appeared to form one group with free phenytoin fractions from 9.7 to 14.5%, while the remainder formed a group with elevated free fractions (greater than 14.5%). Total and unbound plasma concentrations of phenytoin were strongly correlated (r=0.95, P less than 0.0001). There was a weak correlation between increasing age and the unbound phenytoin fraction (r=0.28, P less than 0.01). The results indicate that measurement of the total phenytoin concentration in plasma should usually provide a reliable index of anticonvulsant effect. However, determination of the unbound phenytoin fraction would be beneficial in the management of those patients in whom this fraction may be elevated, due to interacting drugs or biochemical abnormalities.

Determination of therapeutic plasma concentrations of tetrabenazine and an active metabolite by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method for the determination of tetrabenazine and a hydroxy metabolite in plasma is described. Tetrabenazine and the hydroxy metabolite are quantified as their dehydro derivatives using fluorescence detection. This method has been applied to the analysis of plasma samples from patients with Huntington's chorea and has been found to be sensitive, reliable and specific for tetrabenazine and the hydroxy metabolite. The plasma concentrations of tetrabenazine found in patients were lower than could be detected using previously published methods.

Neuropathies and myopathies.

The manner of dealing with this subject is to be strictly clinical and practical. Classifications will not be all-embracing but will include only those conditions likely to be encountered at some time in the career of the ordinary family practitioner. Only occasionally, in the interests of clarity, will an uncommon disorder receive brief mention. The amphasis will be on bedside diagnosis; electrodiagnostic tests will not be described.

Idiopathic communicating hydrocephalus: the prognostic significane of ventricular size after shunting.

A description is given of the dramatic, sustained recovery of 3 demented and neurologically disable patients with idiopathic communicating hydrocephalus after they underwent ventriculo-atrial shunting. In those patients there was no significant change in ventricular size after the ventriculo-atrial shunting. 1 of the patients also had cortical atrophy. Hypertensive vasculopathy and multiple infarcts may be the explanation in 2 of the patients. Reveiw of the literature results in the following conclusions: 1) the CAT scan alone, perhaps combined with intrathecal "Amipaque' cisternography, provides the maximum information with the last trauma and may assist in the selection of patients for shunting. 2) Test removal of 20 to 30ml of CSF may be as satisfactory as pressure monitoring and infusion techniques in the prediction of successful shunting. The following do not have a reliable predictive value: a) The presence of cortical atrophy (shunting may sometimes be effective in mild to moderate cortical atrophy) b) The period of onset of symptoms c) The ventricular size before shunting and its alteration after shunting.

Epilepsy and driving.

205 actual and potential drivers suffering from epilepsy were examined over a period of nine years in Tasmania under a State scheme whereby all such persons are referred to one neurologist. In Tasmania 0.3% of all road traffic accidents were due to epilepsy. 16% of the total who had had an accident had failed to disclose their disability and another 10% who were non-accident cases had similarly concealed their epilepsy. Only about 28% of the expected number (per year) of new cases of epilepsy in drivers disclose their complaint. Alcohol was a significant association with epilepsy in just over 8%. Medication should continue for at least three consecutive fit-free years and preferable five years. Only two out of 170 drivers approved to drive had a subsequent accident due to epilepsy.