[Epidemiology and causes of Parkinson's disease]. / Epidemiologie und Ursachen der Parkinson-Erkrankung.

Parkinson's disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (<5%) are monogenic, i. e. caused by mutations in single genes. At present, six genes have been established for the clinically classical form of parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1). In addition, there are a plethora of genes causing atypical forms of parkinsonism. In contrast, idiopathic PD is of a multifactorial nature. Genome-wide association studies have established a total of 26 genetic loci for this form of the disease; however, for most of these loci the underlying functional genetic variants have not yet been identified and the respective disease mechanisms remain unresolved. Furthermore, there are a number of environmental and life style factors that are associated with idiopathic PD. Exposure to pesticides and possibly a history of head trauma represent genuine risk factors. Other PD-associated factors, such as smoking and intake of coffee and alcohol may not represent risk factors per se and the cause-effect relationship has not yet been elucidated for most of these factors. A patient with a positive family history and/or an early age of disease onset should undergo counseling with respect to a possible monogenic form of the disease. Disease prediction based on genetic, environmental and life style factors is not yet possible for idiopathic PD and potential gene-specific therapies are currently in the development or early testing phase.

Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS.

BACKGROUND: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. METHODS: MOG(35-55) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. RESULTS: EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. CONCLUSIONS: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.

[The genetic profile of multiple sclerosis: risk genes and the "dark matter"]. / Genetisches Profil der Multiplen Sklerose: Risikogene und die "dunkle Materie"

Multiple sclerosis (MS) is a genetically complex disease caused by the interplay of genetic and environmental factors. While it shows substantial familial accumulation, there is no evidence for typical Mendelian transmission within families. Instead, MS risk is likely governed by dozens to hundreds of genetic variants, which can also be present in the general population. The strongest genetic risk factor for MS was identified 40 years ago and lies within the HLA locus. It increases the risk of developing MS by two- to threefold. Within the last few years, genome-wide association studies (GWAS) have led to the identification of nearly 60 additional genetic risk loci. Each of these loci yields a modest to moderate risk increase (odds ratios of 1.1-1.3). Even in combination, however, the currently known risk variants merely account for a small fraction of the disease's heritability. It is likely that a major fraction of genetic MS risk that cannot be explained by GWAS, sometimes termed the "dark matter" of GWAS, is caused by other factors, such as structural variations of the genome, rare sequence variants, or inherited epigenetic modifications.

Bilateral stroke following pituitary apoplexy.

Pituitary apoplexy followed by cerebral infarction is rare. We report a 59-year-old male with a known pituitary macroadenoma who was admitted to our emergency department for treatment of an acute myocardial infarction. He underwent coronary angioplasty and was subsequently treated with aspirin, clopidogrel and full-dose enoxaparin. He developed pituitary apoplexy with bilateral compression of both internal carotid arteries, and infarction of both anterior and middle hemispheres; consequently, he died. This patient illustrates the difficulties of administering aggressive anticoagulative and antiplatelet therapy to patients who have a known pituitary adenoma.