Association between apolipoprotein E genotypes and Parkinson's disease.

Previous studies on the association between apolipoprotein E (APOE) alleles and Parkinson's disease (PD) have shown contradictory results. A recent study showed that APOE is involved in a molecular pathway of α-synuclein-induced neurodegeneration. We therefore conducted the first Thai study on APOE genotypes in patients with PD. We analysed the frequencies of APOE genotypes in our case-control study of 155 patients with sporadic PD and 158 control participants. We identified a higher frequency of the APOE-ε2 allele among patients with PD than among controls (odds ratio=2.309, 95% confidence interval=1.111-4.799). Genetic association is a powerful tool for detecting disease susceptibility alleles, but there are many pitfalls to consider before claiming any association. The discrepancy among the results of the genetic association studies of APOE genotypes as a risk of susceptibility to PD emphasises that this association merits clarification by the study of a single large homogeneous population.

Levodopa induced motor complications in Thai Parkinson's disease patients.

BACKGROUND: Long-term levodopa usage in Parkinson's disease (PD) patients is known to cause several motor complications. It may be related to several factors such as levodopa dosage, duration of treatment and severity of disease. OBJECTIVE: To study the prevalence of levodopa motor complications and associated factors in Thai Parkinson's disease patients. MATERIAL AND METHOD: The authors prospectively collected baseline characteristics of PD patients, details of treatment and complications from 3 hospitals in various parts of Thailand. These patients were diagnosed by UK PD Brain Bank criteria. RESULTS: A total of 154 patients aged 68.1 +/- 9.5 years were recruited. Age of onset was 61.2 +/- 9.8 years. Most patients were in Hoehn-Yahr stage 1-3. The common clinical features were bradykinesia, rigidity and resting tremor Treatments were levodopa (98.1 per cent), anticholinergic (29.9 per cent), dopamine agonists (26 per cent) and COMT inhibitor (9.1 per cent). Eighty-five per cent of the patients had excellent response to levodopa. However, 25 per cent of patients developed motor complications, which were wearing off (79 per cent), on-off fluctuation (45 per cent), freezing (42 per cent), morning dyskinesia (10.5 per cent) and permanent dyskinesia (23.7 per cent). Twelve patients developed severe levodopa induced chorea. Factors associated with levodopa side effects were earlier age of onset, long duration of disease, advanced stage, higher levodopa dosage and long duration of levodopa treatment. In the present study, age of onset was inversely correlated with H-Y stage, while dosage of levodopa was positively correlated with H-Y stage but inversely correlated with lower ADL score, which may be due to advanced disease state. CONCLUSION: Levodopa motor complications are common in Thai PD patients. Wearing off on-off fluctuation and freezing are common forms of motor complications.

Tumor-like manifestation, uncommon form of multiple sclerosis: report of a patient.

Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system, characterised by focal neurological dysfunction with relapsing and remitting course. Acute widespread or tumor-like manifestation is one of the rare clinical variants and has poor prognosis. Here, the authors report a 36-year-old man who presented with left hemifacial and left hemibody anesthesia for one month. His symptoms gradually progressed MRI brain showed multiple large hypersignal intensity lesions in both right and left frontoparietal lobes, surrounding with brain edema. Brain biopsy showed perivenous infiltration of mature lymphocyte with demyelination. He was dramatically improved with high dose steroid. However, he later developed transverse myelitis syndrome. The second MRI showed new foci in both sides of splenium of corpus callosum and T9-10 spinal cord. The findings were compatible with an unusual form of multiple sclerosis that is rarely seen.

Neuromyotonia: autoimmune pathogenesis and response to immune modulating therapy.

BACKGROUND: Neuromyotonia (NMT) has been postulated to be an autoimmune channelopathy, probably by affecting voltage gated potassium channels (VGKC) leading to excitation and abnormal discharges [Sinha et al., Lancet 338 (1991) 75]. OBJECTIVE: To report three patients with NMT who had other associated immune-mediated conditions, i.e., myasthenia gravis, thymoma and various types of peripheral neuropathies. One patient had peripheral neuropathy and involvement of pre- and post-synaptic neuromuscular junction. RESULTS: All three patients had evidence of polyneuropathy and neuromyotonic discharges on electrodiagnostic studies. Elevated acetylcholine receptor antibodies were noted in all patients and malignant thymoma was found in two patients with metastasis. All three patients showed moderate to marked response to plasma exchange. CONCLUSIONS: These findings strongly suggest a humoral autoimmune pathogenesis of NMT, probably by K(+) channel involvement, affecting acetylcholine quantal release and postsynaptic membrane. Clinicians should be aware of this association of immune-mediated conditions in NMT patients and marked improvement with plasma exchange.

Retinol-binding protein in idiopathic intracranial hypertension (IIH).

OBJECTIVE: We postulated that an alteration in endogenous vitamin A (retinol) metabolism plays a causal role in the pathogenesis of idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: Serum retinol was determined by a fluorometric method from 40 control subjects and 58 patients with idiopathic intracranial hypertension (IIH). Retinol binding protein (RBP) was also assayed by quantitative radial immunodiffusion in 17 control subjects and 30 patients with IIH. RESULTS: Mean retinol values were higher in the IIH group compared with the control group, but did not reach a significant level. However, seven of 30 patients with IIH had high RBP levels, but none of the control subjects did. CONCLUSION: This data suggests that IIH is associated with an abnormality in vitamin A metabolism that is linked to its transport system.

Seizures in neurofibromatosis 1.

Neurofibromatosis 1 is a common, genetically transmitted neurodevelopmental disorder with a high potential to cause subcortical focal brain lesions. Although seizures occasionally complicate neurofibromatosis 1, they have not been characterized adequately in the disease. Other phacomatoses with attendant subcortical focal brain lesions have been associated with an evolution from generalized to focal-onset epilepsy. This evolution may be related to the cortical dysplasias that also appear in such disorders. Cortical dysplasias, although occasionally found in neurofibromatosis 1 epileptic patients, are not as frequent as in other phacomatoses. The authors retrospectively screened 499 neurofibromatosis 1 patients for the prevalence and etiology of seizures, their response to therapy, and the evolution of seizure type over time. The prevalence of epileptic seizures (4.2%) was about twice the prevalence in the general population. There were no significant cortical dysplasias identified radiographically nor was there a relationship among the presence of subcortical focal brain lesions and seizure type, response to treatment, or evolution of epilepsy in the neurofibromatosis 1 population. The authors' data do not suggest an ontogeny of epilepsy in neurofibromatosis 1 that is different from the general epileptic population.

MRI in Lhermitte-Duclos disease.

Lhermitte-Duclos disease (LDD) is a disorder sometimes referred to as a dysplastic gangliocytoma of the cerebellum. This is a focally indolent growth of the cerebellar cortex in which the folia enlarge due to a profusion of dysplastic cortical neurons and a thickening of the molecular layer. Loss of Purkinje cells and thinning of medullary white matter results. The enlarged folia lose their secondary foldings and asymmetrically expand the cerebellar hemisphere. These morphologic features produce a characteristic pattern on some CTs and all MRIs, affording an opportunity for a preoperative diagnosis. MRI of a pathologic specimen suggested that the abnormal T1 and T2 signals corresponded to the atrophic folial white matter, thickened granule cell layer, and outer molecular layer. Because of inherent Hounsfield artifact in posterior fossa with CT, MRI is the imaging modality of choice, with better visualized striated pattern. The uniqueness of these imaging features obviates the need for an obligatory biopsy for asymptomatic patients and either permits more definitive planning for surgical decompression or, in restricted lesions, guides more assuredly complete excision of the cerebellar mass.