Post-Stroke Fatigue May Be Associated with the Promoter Region of a Monoamine Oxidase A Gene Polymorphism.

BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). RESULTS: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. CONCLUSIONS: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

Biochemical aspirin resistance and recurrent lesions in patients with acute ischemic stroke.

BACKGROUND: The effect of biochemical aspirin resistance (BAR) on ischemic stroke has not been well established. Early recurrent ischemic lesions (ERILs) on diffusion-weighted imaging (DWI) are proposed as potential surrogate markers of clinically recurrent stroke. METHODS: We included 117 consecutive patients who (1) were admitted within 24 h of symptom onset; (2) had an ischemic stroke confirmed by DWI; (3) underwent follow-up DWI within seven days after onset, and (4) received aspirin treatment. BAR was measured using the VerifyNow(R) Aspirin Assay. We analyzed the associations between BAR and any ERILs (overall ERILs), and between BAR and ERILs occurring outside the vascular territories of index stroke (distant ERILs). RESULTS: BAR was observed in 16 (13.7%) patients. Overall ERILs were detected in 34 (29.1%), and distant ERILs in 10 (8.5%) patients. Patients with BAR were more likely to develop ERILs, but the association was not significant (OR 2.13; 95% CI 0.72-6.29; p = 0.234). However, BAR was independently related to distant ERILs by logistic regression analysis (OR 6.01; 95% CI 1.29-28.09; p = 0.023). CONCLUSIONS: BAR was associated with distant ERILs but not with overall ERILs during the first week after ischemic stroke.

Poststroke emotional disturbances and a tryptophan hydroxylase 2 gene polymorphism.

Objectives: Emotional dysfunction is a common finding in stroke patients. Despite reports on serotonergic involvement in the etiology of poststroke emotional dysfunction (PSED), the role of serotonin synthesizing tryptophan hydroxylase 2 (TPH2) genes in the development of PSED remains unclear. Methods: Genotyping of TPH2 rs4641528 and rs10879355 was performed from genomic DNA of 383 stroke patients collected previously and stored at -70°C. Potential associations between TPH2 genes and poststroke depression (PSD), poststroke emotional incontinence (PSEI), and poststroke anger proneness (PSAP) were investigated 3 months poststroke. Results: Among the 383 patients, 69 (18%) had PSD, 41 (11%) had PSEI, and 93 (24%) had PSAP. The TPH2 rs4641528 genotype frequencies differed significantly between patients with and without either PSD or PSEI, although no significant differences were found between the patients with and without PSAP. In multiple logistic regression analysis, PSD was related to the National Institutes of Health Stroke Scale (NIHSS) score at admission (95% confidence interval [CI]: 1.047-1.230, p < .01), modified Rankin scale score at 3 months (95% CI: 0.135-0.848, p < .05), and TPH2 rs4641528 C allele (95% CI: 1.039-5.631, p < .05), whereas PSEI was associated only with the NIHSS score at admission (95% CI: 1.053-1.259, p < .01) and the TPH2 rs4641528 C allele (95% CI: 1.029-11.678, p < .05). Conclusions: Our findings suggest that the TPH2 rs4641528 C allele may play a role in the pathogenesis of PSD and PSEI but not PSAP in Korean stroke patients.