No abstract

This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF -2578AA genotype with increased susceptibility to ALS in males reappraises the link between reduced VEGF concentrations and ALS, as originally revealed by the fortuitous mouse genetic studies.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(−13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-009-5124-4) contains supplementary material, which is available to authorized users.

Accumulating evidence indicates that alterations in glial activation and disturbances in glial glutamate metabolism may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). Metabotropic glutamate receptors (mGluRs) are involved in glutamate homeostasis as well as in glial proliferation. Using in situ hybridization and immunohistochemistry we found a strong upregulation of group I and group II mGluR mRNA and protein in ALS spinal cord as compared to controls (mGluR5 > mGluR1 > mGluR2/3). In vitro, the mGluR group I agonist 3,5-dihydroxyphenylglycine induced proliferation in chick spinal cord astroglial cultures. Moreover, addition of cerebrospinal fluid (CSF) from ALS patients resulted in significantly higher proliferation rates than control CSF. In both cases, the effect could be blocked by addition of the mGluR group I antagonist 1-aminoindan-1,5-dicarboxylic acid. Taken together, our data suggest that stimulation of glial mGluRs through mediators present in the CSF may contribute to glial proliferation and astrogliosis in ALS.

The construct 'meaning in life' (MiL) has become increasingly important in palliative care. Several meaning-focused interventions have been developed recently. The aim of this study was to investigate MiL in patients with amyotrophic lateral sclerosis (ALS) and compare the findings with a representative sample of the German population. In the newly developed 'Schedule for Meaning in Life Evaluation' (SMiLE), respondents first list individual areas that provide meaning to their life before rating their current level of importance and satisfaction with each area. Overall indices of weighting (IoW, range 20-100), satisfaction (IoS, range 0-100), and weighted satisfaction (IoWS, range 0-100) are calculated. Results of our study showed that 46 ALS patients completed the SMiLE: the IoS was 74.7 ± 20.2, the IoW 88.1 ± 10.1, and the IoWS 76.3 ± 20.5. Satisfaction with MiL was negatively associated with disease duration and degree of functional impairment. After adjustment for age, sex, and marital status, the representative sample (n = 977) scored significantly higher in the IoS (82.8 ± 14.7) and the IoWS (83.3 ± 14.8). Compared to the general population, ALS patients list more meaning-relevant areas, are more likely to list partner, and less likely to list health. Thus, response shift seems to be a central coping mechanism in ALS patients. Regarding their major MiL areas, they shift their focus away from decreasing health status and towards supportive relationships.