Yuichi Komaba

Crossed Cerebellar Diaschisis in Patients With Cortical Infarction Logistic Regression Analysis to Control for Confounding Effects

Background and Purpose— Crossed cerebellar diaschisis (CCD) refers to reduced metabolism and blood flow in the cerebellar hemisphere contralateral to a cerebral lesion. Many cortical areas have been reported to cause CCD without consideration of confounding factors. We performed single-photon emission computed tomography (SPECT) in patients with cortical infarction to identify regions independently related to CCD, controlling for possible confounding effects. Methods— Patients with unilateral cortical infarction (n=113; 75 male, 38 female; mean±SD age, 66±13 years) underwent SPECT of the brain with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). Regional cerebral blood flow was measured autoradiographically. Asymmetry indices (AIs) were calculated on the basis of ratios representing symmetrical regional cerebral blood flow in the cerebellum and 16 cerebral regions. CCD was defined as AI for cerebellum >0.1. AIs for 16 cortical regions were considered for both dichotomous and continuous variables for analysis of CCD occurrence by means of backward logistic regression. Results— For dichotomized variables, hypoperfusion of postcentral (odds ratio [OR]=7.607; 95% CI, 2.299 to 25.174) and supramarginal (OR=3.916; 95% CI, 1.394 to 11.003) regions independently influenced CCD. For continuous variables, hypoperfusion of postcentral (OR=1.044; 95% CI, 1.019 to 1.068) and supramarginal (OR=1.021; 95% CI, 1.001 to 1.041) regions (and, as a negative factor, medial occipital regions; OR=0.942; 95% CI, 0.895 to 0.991) independently influenced CCD. Conclusions— Many cortical areas apparently do not contribute to CCD. Correspondence of CCD between dichotomized and continuous analyses suggests that location of a lesion, not severity, is the main determinant of CCD.

Crossed cerebellocerebral diaschisis in patients with cerebellar stroke

Objectives– We performed single‐photon emission computed tomography (SPECT) to investigate crossed cerebellocerebral diaschisis (CCCD) in patients with cerebellar stroke. Material and methods– Fifteen patients with unilateral cerebellar stroke underwent SPECT of the brain with N‐isopropyl‐p‐[123I] iodoamphetamine (123I‐IMP). Regional cerebral blood flow (rCBF) was measured by the autoradiographic method. Regions of interest were defined in the cerebral cortex, striatum, thalamus and cerebellum to compare structures (contralateral to the cerebellar lesion) with counterparts ipsilateral to the stroke. Results– In the frontal and parietal cortices, especially the posterior superior frontal, anterior midfrontal, precentral, postcentral, and supramarginal areas, rCBF contralateral to the lesion was significantly lower than on the side of the lesion (showing CCCD). Conclusion– This CCCD phenomenon is important to be aware of in clinical reading of images.

Early Depressive Symptoms after Ischemic Stroke Are Associated with a Left Lenticulocapsular Area Lesion

BACKGROUND Poststroke depression is one of the most frequent and important complications of stroke. Although many studies of depression after stroke have been reported, clinical association between the risk of depression after stroke and the lesion location remains unclear. The presence of depression after stroke reportedly confers a poor prognosis; however, early recognition of depressive symptoms may improve outcomes. We examined the relation between lesion location and presence of depressive symptoms 1 month after ischemic stroke, with a view toward early management of depressive symptoms. METHODS In all, 134 consecutive patients with ischemic stroke were followed up to determine whether depression was present 1 month after stroke onset. Depressive symptoms were assessed by means of the Zung Self-rating Depression Scale. The lesion location was determined on magnetic resonance or computed tomography images. RESULTS The incidence of depressive symptoms 1 month after stroke onset was 34.3%. Backward stepwise logistic regression analysis showed hypertension, education, and the presence of a left lenticulocapsular infarct, in particular, to be independent predictors of depressive symptoms. CONCLUSIONS Patients with ischemic stroke, particularly in the left lenticulocapsular area, should be carefully evaluated for early detection and treatment of depressive symptoms, which may greatly influence outcome.

Aneurysmal subarachnoid hemorrhage in a patient with Wegener’s granulomatosis

A 34-year-old Japanese man admitted to hospital with pneumonia had previously undergone surgery for paranasal sinusitis and also for the clipping of an aneurysm at the origin of the anterior choroidal artery after subarachnoid hemorrhage. Laboratory tests performed at the present admission showed renal insufficiency and serological findings of raised proteinase 3 antineutrophil cytoplasmic antibody level. A renal biopsy was performed that showed diffuse necrotizing glomerulonephritis with fibrocellular crescents. The diagnosis of Wegener’s granulomatosis(WG) was confirmed on the basis of the clinical picture, laboratory findings, and biopsies of renal tissues. The disease responded to prednisolone and cyclophosphamide. The association of WG with a ruptured intracranial aneurysm is rare and has not previously been confirmed.

BILATERAL REPRESENTATION OF LANGUAGE FUNCTION

A 33‐year‐old right‐handed man with intermittent headache was found to have agenesis of the corpus callosum. He underwent magnetic resonance imaging, positron emission tomography (PET), and detailed neuropsychologic tests, including a Wada test There was bilateral representation of language, and a PET activation study with word repetition revealed bilateral areas of activation that were not completely symmetric. These findings and the literature concerning agenesis of the corpus cal losum are discussed as is the possible compensatory mechanism for absence of the corpus callosum, which is important for cross‐communication.

Correlation between insulin resistance and white matter lesions among non-diabetic patients with ischemic stroke

Abstract Objective: We investigated whether a correlation exists between insulin resistance and the severity of cerebral white matter lesions among non-diabetic patients with ischemic stroke. Methods: The subjects were 105 consecutive patients without diabetes who were hospitalized due to non-cardioembolic stroke. The insulin resistance was evaluated by a homeostasis model assessment of insulin resistance (HOMA-IR). The degrees of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) were evaluated by the brain MRI. The HOMA-IR values ≥2·5 were indicative of the insulin resistance. Results: The presence of PVH and DSWMH were 86·7 and 83·8%, respectively. The ratio of insulin resistance increased with higher grades of PVH and DSWMH. The HOMA-IR level in grade 3 PVH was significantly higher than those in grades 0 and 1. The HOMA-IR level in grade 3 DSWMH was significantly higher than those in grades 0–2. Multiple linear regression analysis showed that HOMA-IR was significantly associated with PVH or DSWMH. Conclusion: It was found that insulin resistance correlated with white matter lesions among non-diabetic patients with non-cardiogenic ischemic stroke.

Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

Benzodiazepine receptor imaging with iomazenil SPECT in aphasic patients with cerebral infarction

To investigate the relationship between prognosis of aphasia and neuronal damage in the cerebral cortex, we evaluated the distribution of central-type benzodiazepine receptor (BZR) binding in post-stroke aphasics with [123I]iomazenil and SPECT. We performed iomazenil SPECT in six aphasie patients (aged from 45 to 75 years; all right-handed) with unilateral left cerebral infarction. Three patients showed signs of Broca’s aphasia and the other three Wernicke’s aphasia. Cerebral blood flow (CBF) imaging was performed with [123I]iodoamphetamine (IMP). The regions of interest (ROIs) on both images were set in the cerebral cortex, cerebellar cortex and language-relevant area in both hemispheres. Three patients were classified in the mild prognosis group and the other three in the moderate prognosis group. The left language-relevant area was more closely concerned with the difference in aphasie symptoms than the right one in both BZR and CBF distribution, but the ipsilateral to the contralateral ratio (I/C ratio) in the language-relevant areas in the BZR distribution was significantly lower in the moderate prognosis group than in the mild prognosis group, although no difference was seen for these values between the two groups in the CBF distribution. These results suggest that BZR imaging, which makes possible an increase in neuronal cell viability in the cerebral cortex, is useful not only for clarifying the aphasie symptoms but also for evaluating the prognosis of aphasia in patients with cerebral infarction.

Thrombosis in Japanese patients with Fabry disease

Fabry disease is an X-linked lysosomal storage disease resulting from deficient activity of the enzyme alpha-galactosidase (alpha-Gal) A. It has been postulated that the accumulation of globotriaosylceramide in the endothelial cells of blood vessels may lead to thrombosis of the brain and other tissues. Recently, enzyme replacement therapy (ERT) for Fabry disease is available. A high incidence of thrombotic accidents in Fabry disease has been postulated. However, a systemic study on thrombosis in cases of Fabry disease has not been undertaken. To clarify the incidence of thrombosis in Fabry disease, we screened 65 patients with Fabry disease (49 hemizygotes and 16 heterozygotes) from 39 unrelated Japanese families. We found that ten patients with Fabry disease (7 hemizygous males and 3 heterozygous females) had experienced thrombotic accidents, under 45-years-old in 8 cases. These 10 patients showed the gene mutations of classical Fabry disease. Nine of these thrombotic patients developed brain infarctions, one man who had the complication of recurrent thrombophlebitis, and the remaining woman showed central retinal artery occlusion and thrombophlebitis. We demonstrated a high incidence of thrombosis in Fabry disease (15%). ERT should be performed in patients not only in hemizygous males but also in heterozygous females and started at their early ages.

Recurrent strokes in a young adult patient with Fabry's disease

Sirs, Fabry’s disease is an X-linked disorder resulting from a deficiency of lysosomal a–galactosidase A (a–Gal A) (Desnick et al., 2001). Systemic accumulation of glycosphingolipids, predominantly globotriaosylceramide, results in diverse clinical manifestations. Several investigators have reported that strokes were a frequent complication of Fabry’s disease in relatively young patients (Grewal, 1994; Mitsias and Levine, 1996; Utsumi et al., 1997). In this report we describe recurrent strokes during a 2-month period in a young man with Fabry’s disease. A 24-year-old man was admitted to the hospital because of weakness of his right hand and dysarthria. In childhood he had experienced occasional mild pain in the extremities when he had a fever. He was diagnosed with mitral valve prolapse at the age of 21 years. On admission, he was alert. His temperature was 37.5 C, and the pulse rate was 60/min. Blood pressure was 124/ 72 mmHg. Physical examination disclosed no abnormalities except for angiokeratoma over the extremities, chest, abdomen, and back. He had no signs of left ventricular hypertrophy and no proteinuria. Neurologic examination confirmed weakness of the right hand and dysarthria. T2-weighted magnetic resonance images (MRI) revealed an area of high signal intensity in the pons (Fig. 1a and b). He was diagnosed with brainstem infarction in the territory of the basilar artery, and was treated with intravenous heparin sodium (10 000 U/day), ozagrel sodium (160 mg/day), and glycerin (400 ml/day). Given the occurrence of stroke in a relatively young patient with angiokeratoma, activities of several lysosomal enzymes were examined to rule out lysosomal diseases. No activity of aGal A could be detected in plasma or leukocytes; he was diagnosed with Fabry’s disease. The patient’s brother had very low aGal A activity, whilst their mother had moderate reduction of aGal A activity. Accordingly, his brother also was diagnosed with Fabry’s disease, similarly manifest as angiokeratoma over extremities from childhood, and echocardiographically detected mitral valve prolapse. His mother was diagnosed as an asymptomatic carrier. Sequencing of cDNA disclosed a C-to-T transition at cDNA number 334 in exon 2 of the aGal A gene, resulting in L