Yoshiharu Nakae

Anti-TIF1-γ antibody and cancer-associated myositis A clinicohistopathologic study

Objective:We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti–transcriptional intermediary factor 1 &ggr; antibody (anti-TIF1-&ggr;-Ab), a marker of cancer association. Methods:We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-&ggr;-Ab[+] CAM) and without anti-TIF1-&ggr;-Ab (anti-TIF1-&ggr;-Ab[−] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. Results:Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-&ggr;-Ab. In anti-TIF1-&ggr;-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-&ggr;-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-&ggr;-Ab(−) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-&ggr;-Ab(−) and exhibited no dC5b-9 or VFs. Conclusions:CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-&ggr;-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-&ggr;-Ab(−) CAM.

Cilostazol versus aspirin therapy in patients with chronic dizziness after ischemic stroke

BACKGROUND Chronic dizziness is frequently reported by patients in the chronic stage after ischemic stroke. The aim of this study was to determine the efficacy of cilostazol versus that of aspirin for the chronic dizziness that follows ischemic stroke. METHODS We performed a prospective, randomized, open-label, blinded endpoint trial. One hundred six patients who suffered supratentorial ischemic stroke within the previous 1-6 months and subsequently complained of persistent dizziness without other obvious sequelae were enrolled. Patients were randomly given cilostazol (200mg/day) or aspirin (100mg/day) for 6 months. Rates of improvement in the dizziness were then evaluated. Changes in fixation suppression of the vestibulo-ocular reflex (an indicator of cerebral control over the brainstem reflex related to balance), regional cerebral blood flow (CBF) in the cerebrum, cerebellum, and brainstem; and the Zung Self-Rating Depression Scale (SDS) were also evaluated. RESULTS Dizziness was significantly improved in the cilostazol group versus the aspirin group (P<0.0001) after the 6-month therapy. The capacity for fixation suppression of the vestibulo-ocular reflex was improved (P<0.0001), and regional CBF in the cerebrum (relative to that in the brainstem [P=0.003] and to that in the cerebello-brainstem [P=0.012]) was increased only in the cilostazol group. There was no statistical difference in the change in SDS scores between the two groups. CONCLUSION Cilostazol improves the chronic dizziness that follows ischemic stroke and increases supratentorial CBF and cerebral function for adaptation of the brainstem reflex related to the sense of balance.

Hemichorea in a thymoma patient without anti-CRMP-5 antibody

We reported a 72-year-old man with thymoma who presented with hemichorea. Although his brain CT and MRI revealed no abnormality, regional cerebral blood flow changes, identified by single photon emission computed tomography, suggested that the mechanism underlying the chorea seemed to be a dysfunction of the subthalamic nucleus and pallidum. His hemichorea was completely resolved after thymectomy. Absence of serum anti-neural autoantibodies, including small-cell lung carcinoma-related chorea anti-CRMP-5 antibody, suggests that mechanisms different from cross-talk neural-targeted tumor immune response can be responsible for the thymoma-associated paraneoplastic chorea.

Spinal cord infarction with cervical angina

Cervical angina is defined as chest pain resembling true cardiac angina but originating from disorders of the cervical spine. Cervical angina is caused by cervical spondylosis in most cases. A 66-year-old man presented with bilateral arm palsy after chest pain resembling angina pectoris. Neurological examination revealed motor and sensory disturbances of the C7 to T1 level, and magnetic resonance imaging showed a hyperintense spinal cord lesion on T2-weighted imaging. Spinal cord infarction was diagnosed. Severe sinus bradycardia was identified on admission, and improved over the course of 5 weeks. Sympathetic afferent fibers from the heart and coronary arteries generally have their cell bodies in the dorsal root ganglia of the C8 to T9 spinal segments. Electrical stimulation of cardiopulmonary afferent fibers excites spinothalamic tract cells in the T1 to T6 segments of the spinal cord. Spinal cord injury can result in the loss of supraspinal control of the sympathetic system and can cause bradycardia, as commonly seen in patients with severe lesions of the cervical or high-thoracic (T6 or above) spinal cord. Bradycardia in the present case suggested impairment of the sympathetic system at the cervical and thoracic levels. These findings indicated that cervical angina in this case was mediated through the sympathetic nervous system. This represents only the second report of cervical angina caused by spinal cord infarction.

Wrong-way deviation: Contralateral conjugate eye deviation in acute supratentorial stroke

BACKGROUND AND PURPOSE Supratentorial stroke can cause conjugate eye deviation directed contralateral to the affected side (wrong-way deviation). It is rare and thought to be associated exclusively with hemorrhagic stroke. We prospectively investigated the clinical features and prognostic significance of this wrong-way deviation. METHODS Subjects were 12 patients who manifested wrong-way deviation subsequent to supratentorial stroke. These patients were from a group of 968 consecutive patients hospitalized for acute supratentorial stroke during the period April 2007 through March 2010. Clinical features of wrong-way deviation were evaluated. RESULTS The overall incidence of wrong-way deviation was 1.2%. The causative lesion was a huge intracranial hemorrhage (n=7) or an extensive hemispheric infarction (n=5). Left-sided lesions were most frequent (66.7% of patients). Wrong-way deviation usually appeared a few days after the initial insult and was frequently accompanied by transient downward eye deviation (58.3% of patients). Although the outcomes for patients treated conservatively were generally poor, patients who underwent surgical decompression regained consciousness. CONCLUSION Wrong-way deviation can result not only from hemorrhagic but also ischemic stroke if the stroke is extensive. Secondary damage to the adjacent rostral brainstem where oculomotor pathways cross over from the contralateral hemisphere can explain the phenomenon, its temporal evolution, and associated eye signs. Immediate surgical decompression may be necessary to improve the prognosis in such cases.

White matter hyperintensities on MRI in dementia with Lewy bodies, Parkinson's disease with dementia, and Alzheimer's disease

BACKGROUND In dementia with Lewy bodies (DLB) and Parkinsons disease with dementia (PDD), it is still debated whether white matter hyperintensities (WMH) on MRI reflect atherosclerotic cerebrovascular changes or Alzheimers disease (AD)-related pathology such as cerebral amyloid angiopathy. To examine AD-related pathology in DLB and PDD, we compared the severity of WMH and medial temporal lobe atrophy among patients with DLB, PDD, non-demented PD (PDND), and AD. METHODS We retrospectively studied sex- and age-matched outpatients with AD, DLB, PDD, and PDND, as well as subjects without central nervous system disorders as normal controls (n=50 each). All subjects underwent 1.5-T MRI examinations, and WMH detected by T2-weighted images or fluid-attenuated inversion recovery images were semiquantified according to the Fazekas method. Medial temporal lobe atrophy (MTA) was visually assessed by the MTA score. RESULTS WMH were more prominent in AD, DLB, and PDD patients than in PDND patients and normal controls (NCs). DLB as well as AD showed more severe WMH than PDD. Visual assessment of medial temporal lobe atrophy showed that AD patients had the most severe atrophy, followed by DLB, PDD, and PDND patients, and NC subjects in that order. MTA scores showed significant correlations with WMH severity. CONCLUSION Our results indicated that DLB was more similar to AD than to PDD in terms of MRI findings, suggesting that WMH in DLB may reflect mainly AD-related pathology rather than atherosclerotic cerebrovascular changes.

D-Dimer versus International Normalized Ratio of Prothrombin Time in Ischemic Stroke Patients Treated with Sufficient Warfarin

BACKGROUND In patients receiving chronic warfarin therapy, the international normalized ratio of prothrombin time (PT-INR) reportedly correlates with the incidence, size, severity, and outcome of ischemic stroke, and thus there are guidelines for the optimal PT-INR range that is to be maintained during secondary or primary prevention of ischemic stroke. However, the details of ischemic stroke in patients in whom an optimal PT-INR is maintained by warfarin therapy have not been thoroughly investigated. We conducted a retrospective study to determine the predictors of the size, severity, and outcome of ischemic stroke occurring in patients under chronic warfarin therapy and maintenance of an optimum PT-INR. METHODS The study group comprised 22 consecutive acute ischemic stroke patients who were receiving warfarin and whose PT-INR was within the optimal range on admission. The PT-INR and plasma D-dimer level of these patients on admission were analyzed in relation to infarction volume, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale score at discharge. RESULTS PT-INR did not correlate with infarction volume, severity, or outcome. The D-dimer level correlated positively and significantly with the volume (r = .49, P < .05), severity (r = .54, P < .05), and outcome of ischemic stroke (r = .61, P < .01) and did not correlate with the PT-INR (r = -.27, P = .23). CONCLUSIONS When the PT-INR is within optimal range in patients receiving chronic warfarin therapy but who suffer an ischemic stroke, the admission D-dimer level, but not PT-INR, correlates with the size, severity, and outcome of the stroke. Thus, monitoring the D-dimer level in patients receiving long-term warfarin therapy is important, regardless of whether the optimal PT-INR is maintained.

The Mechanism of Ipsilateral Ataxia in Lacunar Hemiparesis: SPECT Perfusion Imaging

Background and Purpose: Although ataxic hemiparesis is a common lacunar syndrome, the precise mechanism underlying hemiataxia is not clear. We attempted to identify ataxia-related, cerebral blood flow changes in patients presenting with ataxic hemiparesis after acute capsular infarct. Methods: We used 99mTc-ECD brain perfusion single-photon emission computed tomography to evaluate regional cerebral blood flow in 12 patients with ataxic hemiparesis caused by capsular infarct, and we compared the regional blood flow of these patients with that of 11 patients with pure motor hemiparesis caused by similar lesions. Results: The ipsilateral red nucleus blood flow was significantly decreased in the ataxic hemiparesis patients, whereas the ipsilateral red nucleus blood flow was increased in the pure motor hemiparesis patients. Crossed cerebellar diaschisis (decreased contralateral cerebellar blood flow) was seen in ataxic hemiparesis patients; similarly, it was seen in pure motor hemiparesis patients. Conclusions: Our findings suggest that ataxia in hemiparetic patients with capsular infarct can be caused by ipsilateral red nucleus dysfunction secondary to cortico-rubral pathway disruption at the internal capsule. i 2014 S. Karger AG, Basel

Acute Autonomic, Sensory and Motor Neuropathy with Oral Hypoesthesia Leading to Split Tongue

A 29-year-old man with acute autonomic, sensory and motor neuropathy (AASMN) developed a split tongue resulting from inadvertent tongue biting because he had lost all feeling in his tongue ( fig. 1 ). Severe cranial nerve involvement in patients with AASMN, as seen in our case, has not been described previously [1] . Received: September 29, 2011 Accepted after revision: February 27, 2012 Published online: May 22, 2012