Objectives-To report on a 10 year follow up of patients with idiopathic Parkinson's disease, particularly with respect to mortality and the eVect of early treatment with bromocriptine. Methods-The patients are from the 149 new patients recruited for a double blind, randomised study of low dose levodopacarbidopa versus low dose bromocriptine. Patients were examined neurologically at least yearly. Neuropsychological examinations were performed at 0, 3, 5, and 10 years. Mortality and cause of death in these patients were compared with the Australian population using standardised mortality ratios (SMRs). Mortality and disease progression were compared by sex and treatment group. Predictors of death within 10 years, nursing home admission, and progression in Columbia score of >20 points were examined by logistic regression analysis. Results-Thirteen patients were excluded as having atypical Parkinsonism and six were lost to follow up. All available patients have been followed up for 10 years. Fifty patients (38%) were dead by 10 years and 63 by the last follow up. The SMR was 1.58 for all patients (p<0.001). There was no significant diVerence in SMRs between the sexes. The mean duration of disease until death was 9.1 years. Parkinson's disease was thought to have contributed substantially to the death of 30 patients. The most common cause of death was pneumonia. Women progressed at a similar rate to men until 8 years, when the severity of their disease as measured by Hoehn and Yahr stage became greater (p<0.05). Older age of onset correlated with increased risk of death but the SMR was increased even in those aged <70 years (SMR 1.80, p=0.03). Early use of bromocriptine did not reduce mortality or slow progression of disease. One quarter of all patients had been admitted to nursing homes by 10 years. Only four patients were still employed. Conclusions-Mortality in Parkinson's disease remains increased despite low dose levodopa-carbidopa therapy and no additional benefit was gained from early use of bromocriptine. Duration of disease was similar to that in the era before levodopa. (J Neurol Neurosurg Psychiatry 1999;67:300-307)

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149 previously untreated patients with Parkinson's disease were recruited over a three year period and randomly allocated to either low dose levodopa-carbidopa

Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder caused by mutations in SGCE.We investigated the frequency and type of SGCE mutations with emphasis on gene dosage alterations and explored the associated phenotypes. We tested 35 M-D index patients by multiplex ligation-dependent probe amplification (MLPA) and genomic sequencing. Mutations were found in 26% (9/35) of the cases, all but three with definite M-D. Two heterozygous deletions of the entire SGCE gene and flanking DNA and a heterozygous deletion of exon 2 only were detected, accounting for 33% (3/9) of the mutations found. Both large deletions contained COL1A2 and were additionally associated with joint problems. Further, we discovered one novel small deletion (c.771_772delAT, p.C258X) and four recurrent point mutations (c.289C>T, p.R97X; c.304C>T, p.R102X; c.709C>T, p.R237X; c.1114C>T, p.R372X). A Medline search identified 22 articles on SGCE mutational screening. Sixty-four unrelated M-D patients were described with 41 different mutations. No genotype-phenotype association was found, except in patients with deletions encompassing additional genes. In conclusion, a rigorous clinical preselection of patients and careful accounting for non-motor signs should precede mutational tests. Gene dosage studies should be included in routine SGCE genetic testing.

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This is the second neuropathological report detailing bilateral electrodes targeting the subthalamic nucleus (STN) in idiopathic Parkinson's disease (PD). The patient presented with unilateral tremor-dominant parkinsonism. Bilateral STN stimulation was carried out 7 years later due to significant disease progression and severe motor fluctuations. The patient exhibited bilateral improvements in rigidity and bradykinesia both intraoperatively and postoperatively. The patient died 2 months later from aspiration pneumonia. Neuropathological examination confirmed both the diagnosis of PD and the electrode placements. The tip of the left electrode was located medially and posteriorly in the left STN and the tip of the right electrode entered the base of the thalamus/zona incerta immediately above the right STN. Tissue changes associated with the subthalamic electrode tracts included mild cell loss, astrogliosis, and some tissue vacuolation. Our postmortem analysis indicates little tissue damage associated with STN stimulation for PD.

In a previous study of the human anterior tibial nerve (Swallow, 1966), it was concluded that 'the wide range of variation found in young as well as old subjects would seem to limit the usefulness of anterior tibial nerve biopsy as a diagnostic procedure in patients with generalized neurological disease.The present work was undertaken to establish the range of variation in the fibre size and content of the sural and radial nerves, and to assess their suitability for diagnostic biopsy. MATERIALS AND METHODSSpecimens of radial and sural nerves were taken at necropsy from subjects without evidence of peripheral nerve disease. The age, sex, and cause of death in each case are shown in Table I.The radial nerve was exposed on the lateral side of the wrist where it overlies the head of the radius. At this level some branching had already occurred, the nerve consisting of-one main branch with one or more smaller branches accompanying it. Only the main branch was taken for study. Specimens were obtained from 21 cases, nerves being taken from both wrists in six subjects; in all, 27 radial nerves were examined.The sural nerve was exposed behind the lateral mnalleolus. In three cases a single nerve trunk was present at this level, but in the remainder some branching had occurred; the largest branch was then taken for study. Specimens were obtained from 23 cases, nerves being taken from both ankles in four patients; in all, 27 sural nerves were examined.About 1 cm of each nerve was removed; the specimen was gently stretched over a small piece of card, to which the ends were made to adhere by light pressure. Mounting under slight tension ensured. that the nerve remained straight during the subsequent preparation. After mounting, the specimens were placed immediately into Flemming's solution at room temperature for 18 to 24 hr. They were then dehydrated in alcohol and embedded in paraffin. Sections 5 s thick were cut and stained with Kultschitzky's haematoxylin, as described by Gutmann and Sanders (1943). They were then dehydrated, cleared, and mounted.'Overseas Scholar, Royal Australasian College of Physicians.

Factors at presentation which influenced the course of the disease and response to treatment were assessed in 125 de novo patients with Parkinson's disease. Ninety‐eight patients were available for re‐assessment at 5 years. Older patients presented earlier after the onset of symptoms, deteriorated more rapidly, and were significantly more likely to develop dementia and impairment of balance. Increasing age and symmetrical disease predicted the new appearance of imbalance. Age of onset did not predict dyskinesia or end of dose failure. A low tremor score at baseline and female gender were predictive of the early appearance of dyskinesia. Patients who experienced end of dose failure were taking a significantly higher dose of levodopa. Once dose and duration of treatment were corrected for, no baseline features were predictive of end of dose failure. The dose of levodopa at 5 years was positively correlated to baseline disease severity as measured by the Columbia score. We conclude that the age of onset of symptoms of Parkinson's disease is a major determinant of the course of the disease and response to treatment.