Polymorphisms in the lymphotoxin alpha gene and the risk of ischemic stroke in the Japanese population. The Fukuoka Stroke Registry and the Hisayama Study.

BACKGROUND AND PURPOSE: Lymphotoxin alpha (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population. METHODS: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study. RESULTS: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke. CONCLUSIONS: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.

Apathy and functional recovery following first-ever stroke.

Apathy is defined as lack of feeling, emotion, or concern. The objective of this study was to examine the frequency of apathy after a first-ever stroke and to prospectively study the impact of apathy on functional recovery. The patients enrolled in this study had the following characteristics: (i) they had experienced a first ischemic or hemorrhagic stroke; (ii) they ranged from 45 to 90 years of age; (iii) the interval from onset to admission ranged from 21 to 90 days; and (iv) they did not demonstrate either marked dementia or aphasia. The functional status was assessed by the Barthel index and the functional independence measures on admission and after a 3-month rehabilitation period. On the basis of the apathy scale, the patients were grouped into those experiencing apathy and those who did not. Next, the scores of the functional measures in the two groups were compared. A total of 67 patients--38 males and 29 females--were analyzed. Fourteen patients (21%) were diagnosed as being apathetic. The apathetic patients tended to be older and more cognitively impaired than the nonapathetic patients. The severity of neurological deficits, the frequency of depression, and the functional status on admission did not differ substantially in the patients with or without apathy. Although the difference was marginal, apathetic patients showed less improvement in the Barthel index or the subscore of functional independence measures than nonapathetic patients after rehabilitation. Thus, we concluded that apathy is not a rare condition after first-ever stroke and it may impair stroke recovery.

Role of substantia innominata in cerebral blood flow autoregulation.

Ascending projections from the substantia innominata (SI) may have an important role in the regulation of cerebral blood flow (CBF). However, several reports have suggested that unilateral lesion of the SI does not affect CBF autoregulation. On the other hand, it is also reported that several cortical and subcortical functions may be regulated not only by ipsilateral SI, but also by contralateral SI. Thus, the objective of this study is to test the hypothesis that bilateral lesions of the SI affect CBF autoregulation. Experiments were performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or physiological saline was microinjected into bilateral SI. Rats were classified into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected bilaterally), left or right SI lesion rats (ibotenic acid was injected into the unilateral SI and saline into the contralateral SI), and control rats (saline was injected bilaterally). Ten days after injection, CBF in the left frontal cortex was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic hypotension. In bilateral SI lesion rats, CBF was started to decrease significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in bilateral SI lesion rats were significantly different from the other groups (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some compensatory effects from the contralateral SI may maintain CBF autoregulation.