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.

Idiopathic Parkinson's disease (PD) can be subdivided by its patterns of motor symptoms into tremor-dominant (TDT), akinetic-rigid (ART), and mixed type (MT). Our objective was to determine whether age at onset and family history are different in these three types. In total, 366 patients with PD were assigned in a standardized approach to one of the three subtypes. Age at onset and family history were obtained in all patients and all presumably affected family members were examined. Mean ages at disease onset were similar in all three groups, but distribution of age at onset was markedly different: monophasic in TDT with a peak around 60 years, biphasic in ART with two peaks, one in the middle of the sixth decade (earlier onset, ART-EO), another during the first half of the seventh decade (later onset, ART-LO), and increasing with age only in MT patients A positive family history was significantly associated only with TDT (odds ratio = 5.7) and ART-EO (odds ratio = 7.8), but not with MT or ART-LO patients. Segregation analysis suggested an autosomal recessive mode of transmission in ART-EO and an autosomal dominant mode of transmission in TDT.

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.

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.

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.