We have studied the effects of unilateral ventral medial pallidotomy in 26 patients with medically intractable Parkinson's disease with marked drug-induced dyskinesias. Preoperatively, all patients were assessed during one 5-day admission according to the Core Assessment Programme for Intracerebral Transplantation (CAPIT) protocol, including rating in the 'practically defined off' and 'best on' states before and during a single-dose levodopa challenge. Motor performance was assessed with subset categories of the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating scale. Pallidotomy was performed under stereotaxic CT guidance with intra-operative extracellular microelectrode recording made from the basal ganglia. All patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so far also been re-assessed after 1 year. Pre- and postoperative performance scores were compared in order to determine which categories of performance improved postoperatively. Significance was accepted at P < 0.005 in order to take into account the multiple number of comparisons performed. Patient medication was compared pre- and postoperatively and the morbidity associated with surgery was also recorded. The most significant improvement postoperatively was the diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however, ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score improved by 27% (P = 0.001) and a significant improvement was also observed in contralateral rigidity by 25% (P = 0.001). There were trends towards improvement in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013) scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral motor scores did not alter significantly. The 'off' gait/postural instability score and 'off' walking time showed marginally significant improvements by 7% (P = 0.007) and 29% (P = 0.014), respectively. On medication, no significant postoperative improvements in parkinsonism were detected. Anti-parkinsonian medication increased by 11% postoperatively. In the subgroup who were available for assessment 1 year postoperatively, responses were generally maintained. Two (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and one haemorrhagic infarct) directly related to surgery. Among the remaining 24 patients, four (15.4% of the total 26) had major complications (two persisting and two transient). Ten patients (38.5%) had minor complications. The majority of the complications (major and minor) occurred in the earlier operated patients and the complication rate subsequently declined with increasing operative experience. The remaining 10 patients (38.5%) had no significant side-effects. One of these 10 patients died from an incidental malignant glioma 6 months postoperatively. These findings confirm that levodopa-induced dyskinesias are dramatically reduced following ve...

Spinocerebellar ataxia 2 (SCA2) belongs to the family of autosomal dominant cerebellar ataxias (ADCA), a genetically heterogeneous group of neurodegenerative diseases. The SCA2 gene maps to chromosome 12q24 and the causative mutation involves the expansion of a CAG repeat within the coding region of the gene. Pathologically, SCA2 presents as olivo-ponto-cerebellar atrophy (OPCA). We present the cases of a 41-year-old man and a 54-year-old woman who died after a long illness characterized by severe cerebellar ataxia. Diagnosis of SCA2 was confirmed by genetic analysis. The brains were moderately to severely atrophic and atrophy was particularly obvious in the cerebellum and brainstem. Histological examination revealed extreme loss of pontine and olivary nuclei and Purkinje cells, with preservation of the dentate nuclei, and of the pigmented cells in the substantia nigra. The whole spinal cord was also severely affected, with shrinkage of the dorsal columns and reduction in the number of neurones in the motor pool and Clarke's nuclei. Immunohistochemistry with 1C2 antibody showed granular neuronal cytoplasmic deposits in all the areas examined and widespread intranuclear inclusions, which were particularly numerous in the residual pontine nuclei. Intranuclear inclusions were not considered a feature in SCA2. Our results support the view that intranuclear inclusions are an integral part of the pathology of this mutation.

The pathogenesis of neuropsychological abnormalities in patients with human immunodeficiency virus type 1 (HIV-1) encephalitis is obscure because neurons are not the target of infection and severe neuronal loss occurs only late during the disease. Moreover, there is evidence indicating that HIV dementia is not a homogeneous entity and could partially reverse after treatment with zidovudine. The finding that impaired axonal flow, evidenced by beta-amyloid precursor protein immunoreactivity, could contribute to the neuropsychological deficits prompted the present study. Brains of patients with full-blown acquired immunodeficiency syndrome (AIDS) were studied and findings compared with those of normal and abnormal control subjects. The presence of HIV-1 DNA was investigated by nested polymerase chain reaction; axonal abnormalities were detected by beta-amyloid precursor protein, ubiquitin immunohistochemistry, and silver staining. Accumulation of beta-amyloid precursor protein was observed in all the HIV encephalitis brains studied; the appearance of the immunostaining varied from globular structures to bundles of parallel formations. In 2 AIDS brains without pathological abnormalities, only the latter pattern was detected. The brains with trauma were strongly reactive with beta-amyloid precursor protein antibody and the different reactivity within them correlated with posttrauma survival, only globular structures being detected in the older cases. No correlation was found between the different pattern of beta-amyloid precursor protein reactivity and dementia in AIDS patients. These results show that widespread axonal injury is a constant feature in AIDS brains and suggest that it could play a role in the pathogenesis of the neuropsychological abnormalities of these patients.

Parkinson's disease (PD) is a chronic, progressive, disabling movement disorder with a clear impact on Health-Related Quality of Life (HRQoL). We investigated the correlations between HRQoL and sleep disorders measured with the Parkinson's disease Sleep Scale (PDSS) and the motor and non-motor aspects of the disease. A correlation was found between HRQoL and the scores from PDSS, motor and depression scales. We conclude that more attention should be paid to the non-motor aspects of PD to attempt to improve HRQoL.

Neuropathological studies have revealed that the brains of HIV-1-infected AIDS patients show the typical encephalitis and, in addition, neuronal loss. More recently, this neuronal cell loss has been thought to take place via programmed cell death (apoptosis) which has been demonstrated by an in situ end labelling (ISEL) technique. In this study 54 brains of HIV-1-positive patients were investigated by the ISEL technique to investigate whether apoptosis is also present in the brains of patients at the asymptomatic stage. Of these, 10 patients suffered from HIV encephalitis (HIVE), 8 had AIDS without neuropathological disorders and 36 were HIV-1-positive pre-AIDS patients. Apoptotic cells were detected in 6 of the 10 HIVE, 1 of the 8 AIDS without central nervous system (CNS) disease and 4 of the 36 asymptomatic individuals. A difference seen between the AIDS and pre-AIDS cases was that, in the latter, apoptotic cells were found in the white matter in all 4 cases, while only 2 of these 4 showed apoptotic neurons. The presence of apoptotic cells in a number, albeit small, of brains of HIV-1-positive pre-AIDS individuals, combined with abnormalities described previously in the same group of patients gives further support to the opinion that brain damage already occurs during the early stages of HIV infection.