Hisashi Yonezawa

Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging.

Alzheimer disease (AD) is pathologically characterized by cortical atrophy. Changes in the white matter and their relation to the pathogenesis of AD remain to be studied. To quantitatively investigate the integrity and organization of white matter fiber tracts in patients with AD, we used diffusion tensor (DT) imaging to study the diffusion anisotropy of white matter regions. DT imaging was performed using a 3.0 Tesla magnetic resonance scanner in ten probable AD patients with no or only mild changes in the white matter in T2 weighted magnetic resonance imagings and ten group-matched controls. The values of fractional anisotropy were significantly lower in the temporal subcortical white matter, posterior part of the corpus callosum, and anterior and posterior cingulate bundles in patients with AD compared with controls. Possible relationships of these selective impairments in the white matter with pathological changes in the posterior cerebral cortices and hippocampus were discussed.

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes

Abstract Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimers type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O, respectively. rCBF and CMRO2 were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion.

Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E ϵ4 allele

Abstract Hippocampal size on magnetic resonance imaging was compared between normal subjects with the apolipoprotein E (apo E) ϵ4 allele (ϵ4/4, ϵ4/3, and ϵ4/2) and those without the ϵ4 allele (ϵ3/3, ϵ3/2, and ϵ2/2) in the age range of 39–80 years. The Mini-Mental State Examination (MMSE) scores did not differ between the two groups. The right hippocampal area and its ratio to hemisphere area and intracranial cavity area were significantly smaller in ϵ4 carriers than non-carriers, whereas hemisphere area did not differ between the two groups. These results suggest that as early as their forties, apo E ϵ4 allele carriers have a markedly smaller right hippocampus with no apparent cognitive impairment, which may have some significance in the high prevalence of the ϵ4 allele in Alzheimers disease as well as other conditions that cause dementia.

Cerebral blood flow and oxygen metabolism before and after a stroke-like episode in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)

Cerebral blood flow and oxygen metabolism were examined in two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) using positron emission tomography (PET). Regional cerebral blood flow (rCBF), regional cerebral oxygen metabolic rate (rCMRO2) and regional oxygen extraction fraction (rOEF) were determined with the steady-state technique using oxygen-15-labeled tracers (15O2, C15O2 and C15O). Case 1, a 45-year-old woman, presented with abrupt onset of fluent aphasia. T2-weighted magnetic resonance imaging (MRI) showed a high signal intensity lesion in the left temporoparietal region. The first PET study on day 16 showed increased rCBF and decreased rCMRO2 in the temporal region. In the second PET study, on day 35, rCBF in the temporal region had decreased. Case 2 was a 19-year-old male; the second son of Case 1. He complained of transient blurring of vision, and then generalized tonic-clonic convulsion occurred. A PET study six days before this stroke-like episode demonstrated increased rCBF in both frontal lobes and putamen, where MRI showed lesions after the episode. Focal hyperemia of the lesion antedated and lasted for at least sixteen days after the stroke-like episode in these MELAS patients. These stroke-like episodes appear to be the result of metabolic dysfunction in neural tissue, although the role of an ischemic vascular event cannot be ruled out.

Prosopagnosia without topographagnosia and object agnosia associated with a lesion confined to the right occipitotemporal region.

A patient is presented who developed prosopagnosia with a recent occipitotemporal infarct in the distribution of the right posterior cerebral artery. H ve topographical agnosia or object agnosia. He regained the ability to recognize faces of familiar persons, whereas he remained unable to identify faces of persons whom he met after the of persons whom he met after the disease onset. This case demonstrate that prosopagnosia may occur as a deficit of matching a perceived face to a memory store of the face, and that the failure to recognize unfamiliar faces may be due to the inability to form memory stores of new faces. These deficits can occur in association with a lesion confined to the right occipitotemporal region.

The side and somatotopical location of single small infarcts in the corona radiata and pontine base in relation to contralateral limb paresis and dysarthria

The aim of this study was to investigate whether the side and location of single small infarcts (< or = 3 cm) in the corona radiata (28 patients) and pontine base (36 patients) influence the incidence of contralateral upper or lower limb paresis and dysarthria. While the severity of contralateral limb paresis was not significantly different between right and left corona radiata lesions, infarcts presenting with contralateral limb paresis and/or dysarthria presented significantly more often in the left than in the right hemisphere, and left infarcts were significantly smaller than right infarcts. Lesions related to dysarthria and upper and lower limb paresis were arranged anterior-posteriorly in the paraventricular corona radiata region. Pontine base infarcts presenting with dysarthria also presented significantly more often in the left than in the right pons. Dysarthria showed a significant correlation with lesions presenting in the dorsomedial portion of the pontine base, upper limb paresis with those in the dorsomedial and dorsolateral portions, and lower limb paresis with lesions in the ventromedial portion. These results suggest greater influence of the left descending motor fibers on contralateral limb movement and articulation than of the right and face-arm-leg somatotopy of motor fibers in the paraventricular corona radiata region (anteroposterior) and in the pontine base (dorsoventral).

Effects of FK506 on myasthenia gravis patients with high interleukin‐2 productivity in peripheral blood mononuclear cells

We compared the early effects of FK506 on clinical severity, interleukin‐2 (IL‐2) production by phytohemagglutinin‐stimulated peripheral blood mononuclear cells (PBMs), and serum levels of acetylcholine receptor antibodies between myasthenia gravis (MG) patients with elevated (>1250 pg/ml, n = 9) or normal (<1250 pg/mL, n = 10) levels of PBM IL‐2 production. Reduction in clinical severity and PBM IL‐2 production were significantly greater in the patients with elevated IL‐2 production than those with normal PBM IL‐2 production in the first month of treatment. Muscle Nerve 27: 245–248, 2003

The effect of trihexyphenidyl, an anticholinergic agent, on regional cerebral blood flow and oxygen metabolism in patients with Parkinson’s disease

Cerebral blood flow and oxygen metabolism were studied in six previously untreated patients with Parkinsons disease (PD) before and after anticholinergic treatment using positron emission tomography (PET) and compared with six controls. The PET study and an assessment of the disability and cognitive impairment were performed before and after administration of 6 mg trihexyphenidyl for 5 to 11 weeks. All PD patients showed improvements in motor symptoms after the trihexyphenidyl treatment. Cognitive function did not significantly differ between before and after trihexyphenidyl treatment. However, after trihexyphenidyl treatment, rCBF and rCMRO2 decreased by 15% in the striatum and by 10% in all cortical areas contralateral to predominantly symptomatic limbs, and by 10% in the ipsilateral striatum and all cortical areas, significantly below the values of controls in most cerebral cortices and striatum. These findings suggest that trihexyphenidyl inhibits the cortical cholinergic system and significantly decreases rCBF and rCMRO2 in the cerebral cortices without cognitive impairment in untreated patients with PD.

Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease.

Yokukansan (YKS), a traditional herbal medicine, has been used to treat behavioral and psychological symptoms of dementia (BPSD). The present study is the first double‐blind, randomized, placebo‐controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimers disease (AD).

Interleukin-2 Production by Peripheral Blood Mononuclear Cells from Patients with Myasthenia gravis

We examined interleukin-2 (IL-2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMs) from 75 untreated myasthenia gravis (MG) patients and 48 control patients. Patients with MG consisted of those with elevated PBM IL-2 production (>1,250 pg/ml; mean + 2SD of the controls) (n = 29, 39%) and those with normal PBM IL-2 production (<1,250 pg/ml) (n = 46, 61%). Significant characteristics of patients with elevated PBM IL-2 production included elevated serum levels of anti-acetylcholine receptor antibodies, severe generalized symptoms, thymic hyperplasia, and marked effects of thymectomy (p < 0.05). These findings suggest that elevated PBM IL-2 production can reflect functional abnormalities of T cells in some patients with MG, and that PBM IL-2 production should be considered as a candidate target of therapy.