Differential effects of various treatment combinations on cardiovascular dysfunction in patients with Parkinson's disease.

OBJECTIVES: Patients with Parkinson's disease (PD) frequently suffer from cardiovascular dysfunction, which may be enhanced to various extents by different antiparkinsonian drugs. MATERIALS AND METHODS: We analysed electrocardiogram (ECG) abnormalities, cardiovascular reflexes (CVR) and orthostatic hypotension (OH) in 148 patients with idiopathic PD assigned to five different combination therapies of levodopa (LD) plus either bromocriptine (BRO), ropinirole (ROP), selegiline (SEL), anticholinergic (ACH) or amantadine (AMA) or to LD monotherapy before and after a 1-week washout of the add-on drug. Patients were matched for age and disease severity (Hoehn and Yahr stage 2-3). Rater-blinded cardiovascular testing was performed at baseline, and following a 1-week washout period of the add-on drugs. RESULTS: We found that the incidence of cardiovascular dysfunction was generally higher in patients receiving a combination therapy compared with patients on LD monotherapy. ECG abnormalities were found in 40-52% of patients in combination therapy, but in only 20% of the patients receiving LD monotherapy. After discontinuation of BRO and SEL, there were significant improvements in ECG, OH and CVR. After washout of ACH and AMA, a significant improvement was found only in the CVR score. AMA and ROP were the add-on drugs with the least adverse cardiovascular effects. CONCLUSION: We conclude that pre-existing cardiovascular autonomic dysfunction should be investigated and taken into account when deciding which combination therapy to choose in the treatment of parkinsonian patients.

A point mutation in PTPRC is associated with the development of multiple sclerosis.

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is widely accepted that a dysregulated immune response against brain resident antigens is central to its yet unknown pathogenesis. Although there is evidence that the development of MS has a genetic component, specific genetic factors are largely unknown. Here we investigated the role of a point mutation in the gene (PTPRC) encoding protein-tyrosine phosphatase, receptor-type C (also known as CD45) in the heterozygous state in the development of MS. The nucleotide transition in exon 4 of the gene locus interferes with mRNA splicing and results in altered expression of CD45 isoforms on immune cells. In three of four independent case-control studies, we demonstrated an association of the mutation with MS. We found the PTPRC mutation to be linked to and associated with the disease in three MS nuclear families. In one additional family, we found the same variant CD45 phenotype, with an as-yet-unknown origin, among the members affected with MS. Our findings suggest an association of the mutation in PTPRC with the development of MS in some families.

Autonomic dysfunction in Parkinson's disease assessed by sympathetic skin response: a prospective clinical and neurophysiological trial on 50 patients.

To verify possible dysfunction of sympathetic skin activity in Parkinson's disease (PD), we studied the electrically evoked sympathetic skin responses (SSR) bilaterally at hands and feet in a group of 50 PD patients and in normal subjects. SSR was present in all patients. Nevertheless, significant differences in the latency and amplitude values were noted. In the group of patients prolongation of latency as well as the reduction of SSR amplitude correlates with age. The longer the disease the more SSR abnormalities could be found. Gender, type of clinical manifestation of PD or medication had no statistically significant effects. However, motor symptom asymmetries evaluated separately for each body side correlated well with interside asymmetries of SSR.

IgA producing primary intracerebral lymphoma.

The first case of a primary and solitary IgA (lambda) producing tumour (possibly a non-Hodgkin's lymphoma) in the CNS is reported. Clinical and neuroimaging findings are described. Early diagnosis without brain biopsy and successful therapy were possible by CSF and serum immunoglobulin analysis which proved local paraprotein production restricted to the CNS.

Progressive inflammatory lesions of the brain parenchyma in localized scleroderma of the head.

A patient with localized scleroderma of the head, uveitis, and Raynaud's phenomenon presented with generalized seizures, spastic hemiparesis, and local IgG production in the cerebrospinal fluid. Magnetic resonance imaging revealed progressive cortical and subcortical brain parenchymal lesions mainly adjacent to the cutaneous and bony lesions and probably of inflammatory origin.

[Retinal periphlebitis and multiple sclerosis. Incidence, cerebrospinal fluid and results of visual evoked potentials]. / Zur Periphlebitis retinae und multipler Sklerose. Häufigkeit, Liquor- und VEP-Befunde.

In a retrospective study 323 patients with multiple sclerosis were screened for the incidence of retinal periphlebitis. The results of lumbar puncture and the visual evoked potentials were related to the eye disease. Retinal periphlebitis was seen in 19 patients (5.9%). Of the patients with retinal periphlebitis, 79% developed the eye pathology within the first 10 years of multiple sclerosis. The cerebrospinal fluid and visual evoked potentials were no different than the results in a control group of multiple sclerosis patients without periphlebitis. Multiple sclerosis should always be considered as one of the potential underlying diseases in retinal periphlebitis since it is found in 30% before or at the same time as the first neurological symptoms of multiple sclerosis.

Motor neuropathy with activity of monoclonal IgM antibody to GD1a ganglioside.

A patient with motor neuropathy associated with monoclonal IgM protein is reported. Using enzyme-linked immunosorbent assays, the antibody activity of the monoclonal IgM was shown to be directed against GD1a ganglioside, a new and so far unreported specificity.

Meningeal carcinomatosis: origin of local IgG production in the CSF.

We found that eight of 22 patients with meningeal carcinomatosis from different primary tumors produced local IgG in the CSF, as indicated by elevated IgG index and/or oligoclonal IgG subfractions. Local IgG production, when present, appears in an early stage of the leptomeningeal manifestation and remains detectable over extended observation periods. In autopsied cases with local IgG production, we observed numerous perivascular round-cell infiltrates containing plasma cells and large lymphocytes within the leptomeningeal tumor tissue. After incubation with immunoperoxidase, only these cells showed IgG-specific staining, indicating the site of local IgG production.

Microheterogeneity of paraproteins. I. Diagnostic value of isoelectric focusing followed by immunoblotting.

Isoelectric focusing (IEF) in thin-layer polyacrylamide gels followed by immunoblotting on nitrocellulose membranes is presently the most sensitive method in the routine detection of IgG paraproteins. With this technique, immunoglobulin class and light chain composition can be as reliably identified as in immunoelectrophoresis. The problem of firm adherence between IEF polyacrylamide gels and nitrocellulose membranes can be overcome by brief incubation in sodium dodecyl sulfate. After isoelectric focusing, IgG paraproteins display a characteristic pattern of limited electrophoretic heterogeneity. This pattern is easily recognized even in the few cases with a constant tendency to aggregate under IEF conditions and in the surprisingly high percentage of paraproteins with very alkaline isoelectric points in which it is altered due to a cathodal collection effect. It is independent of the total amount of IgG in serum and remains stable intraindividually over extended observation periods. On the other hand, there is a very high degree of interindividual variability while common paraprotein characteristics still remain recognizable.

Difficulties in the diagnosis of brain abscesses.

The diagnosis of brain abscesses has been improved during the last 10 years because to introduction of computerized tomography (CCT) and improved methods for the analysis of cerebrospinal fluid (CSF). Typical ring-like enhancement in the CT and an elevated CSF cell count combined with disturbances of the blood-brain barrier and elevated CSF lactate are common and confirm preliminary diagnoses. However, in spite of these procedures, brain abscess is still sometimes misdiagnosed because of the lack of pathological CT findings or a misleading case history sometimes causing cerebral affections. We present the case histories of two young patients in whom diagnosis of brain abscess was delayed. We recommend the immediate performance of contrast-enhanced CT and CSF analysis. If these procedures do not exclude a brain abscess, antibiotic treatment should be begun immediately.

Cerebrospinal fluid paraproteins in neurological disorders.

Paraproteins display a characteristic pattern of limited heterogeneity on isoelectric focusing. In a group of 50 patients with various neurological disorders and paraproteinaemia this pattern could be demonstrated in serum and cerebrospinal fluid simultaneously, regardless of the form of nervous system involvement or of the function of the blood-cerebrospinal fluid barrier. Although there were no qualitative differences in the pattern between paraproteins from benign and malignant cases, a distinct quantitative difference was found: Paraproteins from myeloma patients had significantly more subfractions extending over a wider pH range than paraproteins from patients with benign monoclonal gammopathy. Due to the high sensitivity of isoelectric focusing, more paraproteins could be detected in cases where other electrophoretic methods including immunoelectrophoresis were negative. A surprisingly high percentage of patients was found with benign monoclonal gammopathy and vascular lesions of the central nervous system.

Computed tomography in late-onset metachromatic leucodystrophy.

In late-onset metachromatic leucodystrophy (MLD), early clinical diagnosis is difficult since initial symptoms frequently consist of misleading nonspecific psychopathological alterations. On cranial computed tomography (CT), however, symmetrical attenuation decrease of the white matter and mild cerebral atrophy can already be found in an early stage of the disease, and may even precede clinical symptoms. On the basis of observations in four patients with late-onset MLD who were followed between 1 and 5 years, characteristic CT appearances in different stages of the disease are outlined and compared with the literature.

[Rubella embryopathy with meningoencephalitis and demonstration of oligoclonal IgG in the cerebrospinal fluid]. / Rötelnembryopathie mit Meningoencephalitis und Nachweis von oligoclonalem IgG im Liquor cerebrospinalis.

A first case of congenital rubella with evidence of oligoclonal IgG in serum and cerebrospinal fluid during early manifestation is reported. The mother contracted the rubella infection during the first month of gestation. In addition to the more frequent symptoms of rubella embryopathy there were signs of active meningoencephalitis in the newborn. As a rare eye defect, bilateral congenital glaucoma was observed. Cranial computed tomography gave evidence predominantly for white matter involvement. Elevated IgG levels and oligoclonal IgG were found in both cerebrospinal fluid and serum. By means of quantitative estimation, a local synthesis of IgG in the central nervous system could be demonstrated.

Relationship between neurological features and intrathecal synthesis of IgG antibodies to Treponema pallidum in untreated and treated human neurosyphilis.

In syphilitic patients with or without CNS involvement the correlation of Treponema-specific IgG titre per milligram total IgG in CSF and serum (ITPA index) is a dependable source of information on the synthesis of treponemal IgG antibodies in the CNS. This index also provides a more reliable definition of asymptomatic neurosyphilis. Further, a discrimination between Treponema-specific and Treponema-non-specific IgG synthesis in the CNS is possible. Of 261 patients with clinical symptoms of neurosyphilis, 82% had a local production of treponemal IgG antibodies as shown by an elevated ITPA index. In patients with neurosyphilis and intrathecal synthesis of Treponema-specific IgG antibodies, 94% had oligoclonal IgG in the CSF. Comparison of different CSF protein alteration groups in untreated and treated neurosyphilitic patients showed that early diagnosis (and early treatment) led to improvement of the impairment of the blood-CSF barrier and reduction of the immune reaction in the CNS. However, synthesis of treponemal IgG antibodies in the CNS could persist as a 'scar syndrome' even after adequately cured infection.

Myelin protein composition in the rat spinal cord in culture and in vivo: a developmental comparison.

Biochemical characterization of the development of myelin in vitro was extended to an analysis of myelin protein composition in cultures of explanted foetal rat spinal cord. Myelin fractions were isolated from pooled explants after 12-30 days in vitro and, for comparison, from the spinal cords of rats of equivalent developmental ages. Electron microscopic examination of the culture myelin fractions revealed the presence of multilamellar myelin fragments and some single membranes. All fractions were analyzed using a micro-polyacrylamide gel electrophoresis technique. Qualitatively similar protein profiles were observed for myelin isolated from either cultures or from spinal cords. Fractions from cultures contained a greater proportion of high molecular weight proteins than those from spinal cords, although with respect to the 'major' myelin proteins, a quantitatively similar developmental pattern was observed both in vivo and in vitro.