Tomohide Ohnuki

Recommendations for the Management of Intracranial Haemorrhage – Part I: Spontaneous Intracerebral Haemorrhage

This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European s

Stroke Risk of Asymptomatic Intra- and Extracranial Large-Artery Disease in Apparently Healthy Adults

Background: The predictive value of asymptomatic intracranial artery stenosis for future stroke remains uncertain. The aim of this study is to assess the stroke risk of asymptomatic intracranial artery stenosis and to compare it with that of extracranial artery disease. Methods: The study subjects were 2,924 participants (mean age 55 years) without any history of stroke. We examined the relation between intra- or extracranial large-artery disease and subsequent cerebrovascular events (mean follow-up 63 months). Results: The incidence rate of total cerebrovascular events in persons with intracranial artery stenosis was 1.3% per year. In the group without plaque in the extracranial carotid arteries, the annual rate of total cerebrovascular events was only 0.6%, but in the group with plaque, the rate was 3.6%. Kaplan-Meier analysis of total events showed a significant difference between the 2 groups (p = 0.002). Conclusions: The stroke risk in subjects with asymptomatic extracranial artery disease is markedly increased if intracranial artery stenosis is also present.

The role of high-sensitivity C-reactive protein in asymptomatic intra- and extracranial large artery diseases.

Background: It remains unclear whether high-sensitivity CRP (hs-CRP) is predictive of atherosclerosis in the intracranial artery. The aim of this study is to assess the role of hs-CRP in asymptomatic intracranial artery occlusive diseases. Methods: Of the 3,366 apparently healthy subjects who received a brain checkup, 138 with ≧25% intracranial artery stenosis on magnetic resonance angiography, 267 with ≧25% extracranial carotid artery stenosis on B-mode ultrasonography and 435 without intracranial artery or extracranial carotid artery stenosis (age-matched controls) were selected for this study. Results: The mean CRP concentration in the subjects with intracranial artery stenosis was not significantly different from that in the control subjects, and the differences of mean CRP concentrations among the subgroups with 25–49, 50–74 and 75% or greater stenosis in the intracranial artery were not significant. The odds ratios of hs-CRP for extracranial carotid artery stenosis tended to increase with increasing CRP concentrations, but those of hs-CRP for intracranial artery stenosis showed no significant difference. Conclusion: The degree of atherogenic inflammation in asymptomatic intracranial artery stenosis may be less than that in extracranial carotid artery stenosis.

Neurological safety of fingolimod: An updated review

Fingolimod (FTY) is the first oral medication approved for treatment of relapsing–remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long‐term post‐marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side‐effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post‐marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy‐related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.

Fingolimod-induced leukoencephalopathy in a patient with neuromyelitis optica spectrum disorder

Fingolimod (FTY720) is used for reducing the annualized relapse rate and slowing progression of neurological disability in relapsing-remitting forms of multiple sclerosis (MS). However, its safety is not confirmed in patients with neuromyelitis optica spectrum disorder (NMOSD), who characteristically have positive aquaporin-4 (AQP-4) antibody. A 54-year-old female with a relapsing-remitting course of optic neuritis and myelitis for six years, diagnosed initially as MS, had been treated with interferon beta-1b and oral corticosteroid. Magnetic resonance imaging (MRI) consistently revealed lesions on the optic nerve and spinal cord, but never on the brainstem or cerebral white matter during acute exacerbation. After treatment was switched to fingolimod from interferon beta-1b, multiple new lesions appeared at the brainstem and cerebral white matter. Following discontinuation of fingolimod, these lesions completely cleared, concomitantly with clinical improvement. During fingolimod treatment, she was recognized to be positive for AQP-4 antibody. Fingolimod may be contraindicated in patients with NMOSD.

Postural deformities in Parkinson's disease -Mutual relationships among neck flexion, fore-bent, knee-bent and lateral-bent angles and correlations with clinical predictors.

BackgroundVarious postural deformities appear during progression of Parkinson’s disease (PD), but the underlying pathophysiology of these deformities is not well understood. The angle abnormalities seen in individual patients may not be due to distinct causes, but rather they may have occurred in an interrelated manner to maintain a balanced posture.MethodsWe measured the neck flexion (NF), fore-bent (FB), knee-bent (KB) and lateral-bent (LB) angles in 120 PD patients, and examined their mutual relationships, and correlations with clinical predictors such as sex, age, disease duration, Hoehn and Yahr (H&Y) stage, medication dose (levodopa equivalent dose, LED; total dose of dopamine agonists, DDA). The relationship between the side of the initial symptoms and the direction of LB angle was also investigated.ResultsOur main findings were: (1) Significant relationships between NF and KB, NF and LB, FB and KB, KB and LB were observed. (2) NF angle was larger in males than in females, but FB, KB and LB angles showed no significant difference between the sexes. (3) FB and KB angles became larger with advancing age. (4) NF and FB angles were associated with disease duration. (5) NF, FB, KB and LB angles all increased significantly with increase of H&Y stage. (6) FB angle was significantly associated with LED, but DDA did not show a significant relationship with any of the measured angles. (7) Direction of LB angle was not associated with the side of initial symptoms.ConclusionsPostural abnormalities are interrelated, possibly to maintain a balanced posture.

123I-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in patients showing scans without evidence of dopaminergic deficits (SWEDDs)

OBJECTIVE Scans without evidence of dopaminergic deficits (SWEDDs) in dopamine transporter single-photon emission computed tomography (DAT-SPECT) are found in 3.6-19.6% of patients with clinically suspected Parkinsons disease (PD). We investigated whether combined use of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy would be helpful to differentiate PD among SWEDDs patients. PATIENTS AND METHODS 145 patients with clinically suspected PD underwent both DAT-SPECT and MIBG myocardial scintigraphy. Striatal binding ratio (SBR) of DAT-SPECT and heart-to-mediastinal (H/M) ratio and washout rate (WR) of MIBG myocardial scintigraphy were calculated. RESULTS Among 18 SWEDDs patients (12.4%), 11 were finally diagnosed with PD based on follow-up for at least two years after the DAT-SPECT and MIGB myocardial scintigraphy scans. Among the latter group, 8 patients showed an H/M ratio of less than 2.2, and 9 showed WR above 30%. CONCLUSION Our results indicate that the combination of low H/M ratio and high WR of MIBG myocardial scintigraphy of SWEDDs patients may be helpful for detection of PD patients.

Possible coexisting autoimmunity in a variant case of familial amyotrophic lateral sclerosis associated with anti-GM2 immunoglobulin M antibody

A 43‐year‐old man presented with bilateral facial palsy, and muscle weakness and numbness in the upper limbs after an episode of antecedent infection. He rapidly developed muscle weakness in all limbs and bulbar palsy, and subsequently required artificial ventilation. Serum samples were weakly positive for anti‐GM2 immunoglobulin M antibody. Plasmapheresis and intravenous immunoglobulin therapy resulted in partial and temporary improvement of symptoms. The patient subsequently developed complete tetraplegia. The patients father and uncle had been previously diagnosed with amyotrophic lateral sclerosis. Mutational analysis of the patients blood showed a Cys6Gly mutation in the Cu/Zn superoxide dismutase 1 gene. Here, we report a variant case of familial amyotrophic lateral sclerosis suggesting a possible coexisting autoimmunity.

Early Motor Fluctuations in a Patient with Striatonigral Degeneration

We report a 44-year-old female with striatonigral degeneration (SND) who showed wearing-off oscillations after 4 months of levodopa treatment. The patient presented with asymmetric left-side dominant rigidity, and levodopa was effective at first. However, she began to show wearing-off oscillations of motor symptoms, which gradually worsened thereafter. Fluid-attenuated inversion recovery sequence magnetic resonance imaging (MRI) showed linear lateral putamen hyperintensities, and positron emission tomography (PET) studies using 18F-fluorodopa (FD) and 11C-N-methylspiperon (NMSP) showed a marked decrease of radioactivity in the right putamen, especially in the posterior putamen. The results of MRI and 2 PET studies with FD and NMSP were well consistent with the diagnosis of SND.

Simultaneous Cardiogenic Embolism in Bilateral Internal Carotid Arteries – Carotid Ultrasonography, MRI and Autopsy Findings

Introduction Simultaneous cardiogenic embolism in the bilateral internal carotid arteries (ICAs) has rarely been reported [1–4]. The advent of new technology during the past decade has made it possible to detect the emboli and subsequent cerebral infarction even in the extreme acute phase. Here, we present a patient with simultaneous bilateral ICA emboli, in whom real-time carotid ultrasonography and MRI detected the emboli and the infarcted area, respectively, in the extreme acute phase, and autopsy findings confirmed the presence of bilateral fresh emboli. Case Report A 70-year-old man with atrial fibrillation and a history of mitral valve commissurotomy, who had been receiving 4 mg/day of warfarin, was found to be comatose at 8:50 a.m. on the floor in his office and was transferred to our hospital at 9:40 a.m.; he had been on the phone with no speech disturbance at 10:00 p.m. on the day before admission. On admission, blood pressure was 180/110 mm Hg, pulse rate was 92 beats per minute, and Cheyne-Stokes breathing was observed. He was in a deep coma, and was quadriplegic with decorticate posture. The ocular position was midline, the oculo-cephalic reflex was present, and the size of both pupils was 2.5 mm with sluggish light reflex. Bilateral limb hypertonia, hyperactive reflexes and extensor toe signs were present. In the emergency room, blood examination gave the following results: white blood cells 10,800/Ìl, red blood cells 424 ! 104/Ìl, hemoglobin 12.5 g/dl, platelets 14.6 ! 104/Ìl, and international normalized ratio 2.27. ECG showed atrial fibrillation, and an echocardiogram showed mitral valve stenosis with calcification, tricuspid valve regurgitation, and enlargement of both atria, but no thrombus was found. In B-mode ultrasonography on the day of admission, the thickness of the intima-media complex in both carotid arteries was 1.0 mm. Sequential parallel longitudinal color Doppler images displayed a homogenous oscillating intraluminal mass echo (8 ! 6 mm)