Tomohiko Ohshita

Serial diffusion-weighted imaging in MELAS

Abstract Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS.

Association between central systolic blood pressure, white matter lesions in cerebral MRI and carotid atherosclerosis.

White matter hyperintensities (WMHs) observed on cerebral magnetic resonance images (MRIs) are associated with age and hypertension, suggesting a vascular mechanism of pathogenesis. Central systolic blood pressure (cSBP) correlates more closely with measures of cardiovascular disease risk than brachial pressure. We sought to determine whether cSBP correlates with WMHs and if cSBP is predictive of cerebrovascular disease. Radial applanation tonometric measurements for cSBP and augmentation index (AI) were carried out in unselected individuals undergoing carotid ultrasound. WMHs were assessed retrospectively using fluid-attenuated inversion recovery (FLAIR)-MRIs as periventricular (PVH) and deep white matter hyperintensities (DWMH), and they were rated using the Fazekas scale. A total of 179 patients, 94 (53%) men and 85 (47%) women, with a mean age of 66±13 years were included in the study. On MRI, 17, 74, 67 and 21 patients had PVH grades 0, 1, 2 and 3, respectively. Forty-eight, 69, 49 and 13 had DWMH grades 0, 1, 2 and 3, respectively. In our study population, PVH correlated with age, brachial SBP, cSBP and AI (r=0.49, 0.28, 0.23; P<0.002 and r=0.13; P<0.05, respectively). DWMH also correlated with age, brachial SBP and cSBP (r=0.41, 0.30, 0.22; P<0.003, respectively), but not with AI. cSBP values were associated with PVH/DWMH grades 2 and 3, but brachial SBP correlated only with grade 3. Mean carotid intima–media thickness (common carotid arteries (CCA)-IMT) was 0.68±0.13 mm. CCA-IMT and plaque score (PS) correlated with PVH/DWMH. Multivariate regression analysis showed cSBP, age and PS to be independently associated with PVH and DWMH. Correlation of cSBP with PVH and DWMH was independent of PS. Central SBP correlated with PVH and DWMH in FLAIR-MRIs and can better predict WMHs than brachial SBP in earlier stages.

Diffusion tensor imaging of peripheral nerve in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a feasibility study

IntroductionThe purpose of this study was to assess the clinical feasibility of diffusion tensor imaging (DTI) for the evaluation of peripheral nerves in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsUsing a 3-T magnetic resonance imaging scanner, we obtained DTI scans of the tibial nerves of 10 CIDP patients and 10 sex- and age-matched healthy volunteers. We prepared fractional anisotropy (FA) maps, measured the FA values of tibial nerves, and compared these values in the two study groups. In nine patients, we also performed tibial nerve conduction studies and analyzed the correlation between the FA values and parameters of the nerve conduction study.ResultsThe tibial nerve FA values in CIDP patients (median 0.401, range 0.312–0.510) were significantly lower than those in healthy volunteers (median 0.530, range 0.469–0.647) (Mann–Whitney test, p < 0.01). They were significantly correlated with the amplitude of action potential (Spearman correlation coefficient, p = 0.04, r = 0.86) but not with nerve conduction velocity (p = 0.79, r = 0.11).ConclusionOur preliminary data suggest that the noninvasive DTI assessment of peripheral nerves may provide useful information in patients with CIDP.

Abnormal signals on proton density-weighted MRI of the superior cerebellar peduncle in progressive supranuclear palsy

Objective– To assess MRI signal abnormalities of the superior cerebellar peduncle (SCP) in progressive supranuclear palsy (PSP) patients. Material and methods– Signal changes were examined on proton density‐weighted images (PDWI) and on T2‐weighted images (T2WI) of SCP in 9 PSP patients, and findings were compared to those in 20 Parkinsons disease patients and 20 age‐matched control subjects. Results– We observed effacement or lack of clarity of the low signal on PDWI in SCP in 4 of 9 PSP patients, but not in any of the Parkinsons disease patients or control subjects. These signal changes were not observed on T2WI. Conclusions– The signal changes on PDWI may be a specific finding reflecting demyelination and gliosis of SCP in PSP. Our findings suggest that evaluation of SCP on PDWI may be helpful in the diagnosis of PSP patients.

Association between cerebral microbleeds on T2*-weighted MR images and recurrent hemorrhagic stroke in patients treated with warfarin following ischemic stroke.

BACKGROUND AND PURPOSE: Although accumulating evidence suggests the presence of microbleeds as a risk factor for intracerebral hemorrhage (ICH), little is known about its significance in anticoagulated patients. The aim of this study was to determine whether the presence of microbleeds is associated with recurrent hemorrhagic stroke in patients who had received warfarin following atrial fibrillation–associated cardioembolic infarction. MATERIALS AND METHODS: A total of 87 consecutive patients with acute recurrent stroke, including 15 patients with ICH and 72 patients with cerebral infarction, were enrolled in this study. International normalized ratios (INRs), vascular risk factors, and imaging characteristics, including microbleeds on T2*-weighted MR images and white matter hyperintensity (WMH) on T2-weighted MR images, were compared in the 2 groups. RESULTS: Microbleeds were noted more frequently in patients with ICH than in patients with cerebral infarction (86.7% versus 38.9%, P = .0007). The number of microbleeds was larger in patients with ICH than in patients with cerebral infarction (mean, 8.4 versus 2.1; P = .0001). INR was higher in patients with ICH than in patients with cerebral infarction (mean, 2.2 versus 1.4; P < .0001). The frequency of hypertension was higher in patients with ICH than in patients with cerebral infarction (86.7% versus 45.8%, P = .0039). Multivariate analysis revealed that the presence of cerebral microbleeds (odds ratio, 7.383; 95% confidence interval, 1.052–51.830) was associated with ICH independent of increased INR and hypertension. CONCLUSION: The presence of cerebral microbleeds may be an independent risk factor for warfarin-related ICH, but more study is needed because of strong confounding associations with elevated INR and hypertension.

Voltage-gated potassium channel antibodies associated limbic encephalitis in a patient with invasive thymoma

Recently, limbic encephalitis (LE) associated with Voltage-gated potassium channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive thymoma. There was a close temporal relationship between the clinical course and the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab-associated LE cases, our cases showed the more extensive high intensity lesions on MRI and the absence of seizure and hyponatremia.

Incidence of dementia, Alzheimer disease, and vascular dementia in a Japanese population: Radiation Effects Research Foundation adult health study.

Objective: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population. Methods: 2,286 dementia-free subjects, aged ≧60 years, were followed for 5.9 years through biennial two-phase examinations. Results: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26). Conclusion: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype.

A prospective follow-up study of the association of radiation exposure with fatal and non-fatal stroke among atomic bomb survivors in Hiroshima and Nagasaki (1980–2003)

Objective Use of medical radiotherapy has increased markedly in recent decades. Whether the consequence includes an increased risk of cardiovascular disease remains to be determined. The purpose of this study was to examine the association between radiation exposure and the incidence of stroke among Japanese atomic bomb survivors. Design A prospective follow-up study. Setting and participants Radiation exposure from the atomic bombing was assessed in 9515 subjects (34.8% men) with 24-year follow-up from 1980. Subjects were free of prevalent stroke when follow-up began. Outcome measures Stroke events and the underlying cause of death were reviewed to confirm the first-ever stroke. Subtypes (ischaemic and haemorrhagic events) were categorised based on established criteria according to the definitions of typical/atypical stroke symptoms. Results Overall mean radiation dose (±SD) in units of gray (Gy) was 0.38±0.58 (range: 0–3.5). During the study period, 235 haemorrhagic and 607 ischaemic events were identified. For men, after adjusting for age and concomitant risk factors, the risk of haemorrhagic stroke rose consistently from 11.6 to 29.1 per 10 000 person-years as doses increased from <0.05 to ≥2 Gy (p=0.009). Incidence also rose within the dose range <1 Gy (p=0.004) with no dose threshold. In women, the risk of haemorrhagic stroke rose with increasing radiation exposure but not until doses reached a threshold of 1.3 Gy (95% CI 0.5 to 2.3). Among women, for doses <1.3 Gy, differences in stroke risk were modest (13.5 per 10 000 person-years), while it increased to 20.3 per 10 000 person-years for doses that ranged from 1.3 to <2.2 Gy and to 48.6 per 10 000 person-years for doses that were higher (p=0.002). In both sexes, dose was unrelated to ischaemic stroke. Conclusion While the risk of haemorrhagic stroke increases with rising radiation exposure for both sexes, effects in women are less apparent until doses exceed a threshold at 1.3 Gy.

Magnetization transfer measurements of cerebral white matter in patients with myotonic dystrophy

To determine whether patients with myotonic dystrophy (MyD) have structural changes in the cerebral white matter, we performed magnetization transfer (MT) imaging of the cerebral white matter in 14 MyD patients and 11 age-matched normal controls. We calculated MT ratios in both the white matter lesions (WMLs) and the normal-appearing white matter (NAWM) of MyD patients using region of interest (ROI) analysis. MT ratios in WMLs were markedly decreased, and all ROIs in NAWM also showed significantly lower MT ratios in MyD patients than in normal controls. The average MT ratio of all ROIs in WMLs and NAWM in each patient showed a significant negative correlation with duration of illness, but not with the patients age or age at onset. The results of the present study indicate not only the presence of pathological changes in WMLs but also the widespread involvement of NAWM in MyD patients. The results also suggest that structural changes in the white matter may be progressive during the clinical course of MyD.

Magnetization Transfer Measurements of Brain Structures in Patients with Multiple System Atrophy

To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.