Repetitive transcranial magnetic stimulation (rTMS) appears to have effects on cortical excitability that extend beyond the train of rTMS itself. These effects may be inhibitory or facilitatory and appear to depend on the frequency, intensity, duration and intertrain interval of the rTMS. Many studies assume facilitatory effects of high-frequency rTMS and inhibitory effects of low-frequency rTMS. Nevertheless, the interindividual variability of this modulation of cortical excitability by rTMS has not been systematically investigated. In this study, we applied 240 pulses of rTMS at 90% of the subjects' motor threshold to their motor cortex at different frequencies (1, 10, 15 and 20 Hz) and examined the effects on motor evoked potentials (frequency tuning curve). Although the averaged group data showed a frequency-dependent increase in cortical excitability, each subject had a different pattern of frequency tuning curve, i.e. a different modulatory effect on cortical excitability at different rTMS frequencies. The interindividual variability of these modulatory effects was still high, though less so, when the number of rTMS pulses was increased to 1,600. These findings illustrate the degree of variability of the rTMS effects in the human brain.
Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a "pure cerebellar" or "cerebello-olivary" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia.
Aspirin non-responder status may contribute to failure of aspirin therapy in the secondary prevention of cerebrovascular incidents in as much as 30-40 % of patients. Quantitative assessment of platelet functions may provide a means to predict aspirin treatment failure in individual patients and to re-direct therapeutic strategies.
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