From an appearance of recombinant tissue plasminogen activator (rt-PA) in the clinical therapy on 2005 in Japan, the therapeutic strategy of ischemic stroke therapy is now changing dramatically. Many experimental data from animal stroke and clinical trials of neuroprotective agents failed to clinical useful therapeutic strategy. A free radical scavenger, edaravone is the first clinical drug for neuroprotection in the world which has been used in almost all ischemic stroke patients in Japan from 2001. Now, it is especially useful in thrombolytic therapy with rt-PA, whereas we still need the newly more effective neuroprotective drugs which can be applied to many ischemic stroke patients. Therefore, we review and describe the future neuroprotective strategies in the post-thrombolysis era.

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Immune-mediated heparin-induced thrombocytopenia (HIT) is a rare but serious side effect of heparin therapy which presents various thromboembolic events associated with high mortality and morbidity. There have been few reports about the prevalence of HIT in acute ischemic stroke, which our retrospective study and a multi-center prospective cohort study respectively estimated as 0.5% and 1.7% of unfractionated heparin-treated acute ischemic stroke patients. Once the onset of HIT is suspected, its therapy should be started immediately because treatment delay of HIT will bring a poor outcome. Stroke physicians should be aware of HIT, as heparin use will become increased more than ever in clinical practice with the development of new intravascular treatment techniques.

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Background: Patients with Parkinson's disease (PD) suffer from various symptoms. In order to identify untreated symptoms within the limited time of a clinical interview, we developed a new self-completing questionnaire (MASAC-PD 31). The questionnaire consists of two parts (5 domains, 31 items); part I intended at rating the motor symptoms and activities of daily living (ADL) during both "on" and "off" periods, and Part II aimed at screening and assessing mainly the non-motor symptoms, such as sleep-related difficulties, autonomic symptoms, cognition, mood and others. The purpose of this study was to evaluate the validity, reliability, and clinical usefulness of the questionnaire.
Subjects and Methods: Based on the number of valid answers in a pilot trial, MASAC-PD 31 was refined by improving the expression and layout. Of the initially enrolled 107 patients attending three hospitals, 102 patients were included in the final analysis. Correlations of the scores on the MASAC-PD 31 with other clinical scales were evaluated. A second trial consisting of 57 participants was conducted a month later to assess the test-retest reproducibility of the questionnaire.
Results: The average time needed to complete MASAC-PD 31 was 17 min (range: 3-90 min). Each of the domains in Part I showed high internal consistency (Cronbach's α: 0.663 for "on" motor) and strong correlations with preexisting indices (Spearman's correlation coefficient: 0.547, 0.544, and 0.571 for "on" motor against "on" UPDRS, PDQ-39, and Schwab & England ADL scale, respectively). The questions in the Part II domains also showed strong correlations with preexisting scales. Most of the items showed high reproducibility (weighted κ coefficient) and consistency.
Conclusion: This new comprehensive questionnaire was shown to be valid and reliable for assessing the motor disability in patients with PD. Moreover, it may be useful in clinical management for identifying clinically unrecognized symptoms, especially non-motor problems.

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A 49-year old woman noticed her skin rash several days after taking supplements containing Spirulina, a planktonic blue-green alga. Her skin rash was spreading over large parts of her body, even after stop ingestion two months later. Five months later, she developed muscle weakness of neck flexor and left proximal upper extremity. On admission, creatine kinase (CK) was elevated to 1,268IU/ml in the serum. A muscle specimen revealed many necrotizing muscle fibers and the infiltration of mononuclear cells in the peri- and endomysium including a lot of eosinophils. Immunohistochemical staining showed the infiltration of CD4 positive cells in the peri- and endomysium and that of CD20 positive B cells in the perivascular regions. She was diagnosed as having inflammatory myopathy with widely skin rash. Therapy with administration of prednisolone and cyclophosphamide followed by methyl-prednisolone pulse improved her clinical symptoms.
There is a similar report describing a case of dermatomyositis after ingestion of Spirulina, which is known to have immune-stimulating property such as accelerating tumor necrosis factor (TNF)-α production. Also, TNF-α single nucleotide polymorphisms (TNF-308A) was demonstrated to have strong association with onset of myositis in Caucasians. The use of Spirulina could result in inflammatory myopathy under some specific conditions.

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We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) concomitant with acquired von Willebrand syndrome. A 33-year-old man developed motor and sensory polyneuropathy with electrophysiological conduction slowing. At this time, M-protein was absent. He was diagnosed with CIDP and received intravenous immunoglobulin and subsequent oral corticosteroids, which resulted in almost complete remission for over 10 years. At the age of 44, he presented with chronic anemia. Laboratory tests and colonoscopy revealed that he had acquired von Willebrand syndrome with monoclonal gammopathy of undetermined significance (IgG λ type) and colon cancer. Bleeding symptoms were resolved with intravenous immunoglobulin, but not with supplementation of factor VIII. Shortly after successful excision of the cancer, CIDP and acquired von Willebrand syndrome simultaneously recurred. Intravenous immunoglobulin produced rapid improvement of both neurological and hematological abnormalities. Concurring CIDP and acquired von Willebrand syndrome in the present case may indicate that the conditions have a partly common immunological background including monoclonal gammopathy and a potential common autoantibody-mediated mechanism. Alternatively, dysfunction of von Weillebrand factor may increase blood-nerve barrier permeability, inducing the recurrence of CIDP.

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The pathophysiology of convulsive movements in patients with convulsive syncope remains unclear. Here, we report a patient with convulsive syncope whose convulsive movements seemed to be associated with transient hemodynamic ischemia in the basal ganglia. A 74-year-old man had 1-year history of orthostatic hypotension and transient clonic jerks in the limbs and trunk, predominantly in the right upper limb. His convulsive movements were evoked approximately 1 minute after sitting up or standing up from the supine position and lasted for several tens of seconds. He felt mild faint while the convulsive movements lasted, but he was oriented and could follow simple commands. He was diagnosed as pure autonomic failure. Video-electroencephalogram (EEG) recorded generalized slows without any epileptiform discharges when the symptoms appeared. Single-photon emission computed tomography (SPECT) was performed using split-dose method to evaluate the change in blood flow when the convulsive movements appeared. During symptoms, a significant decrease in blood flow was revealed in the anterior part of the left basal ganglia, bilateral frontal areas, and right cerebellar hemisphere. An alteration in the functional balance between the basal ganglia and the cerebral cortices may play a role in the generation of convulsive movements in patients with convulsive syncope.

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We report here in a 61-year-old woman in whom sensory disturbance predominantly affecting the distal portion of the limbs progressed over the course of 1 year. Blood tests showed IgM monoclonal gammopathy as well as the presence of anti-myelin-associated glycoprotein (MAG) antibody. Nerve conduction studies revealed significant prolongation of distal latency, and sural nerve biopsy showed IgM deposition on the myelin sheath. She was diagnosed as suffering anti-MAG neuropathy. High-dose intravenous immunoglobulin therapy proved to be ineffective and her symptoms progressed. Therefore, rituximab was administered and the sensory disturbance improved. Although no detailed studies on rituximab therapy for anti-MAG neuropathy have been reported in Japan, the present findings suggest that rituximab may be more effective than immunoglobulin therapy and other conventional therapies that have been used for autoimmune neuropathies.

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A 65 year-old man showed bilateral, but more marked on the right, instinctive grasp reaction, utilization and imitation behavior after a right parietotemporal lobe infarction. Attention disturbance, left unilateral spatial neglect, and constructional disturbance were also observed. Fluid attenuated inversion recovery (FLAIR) MRI revealed high intensity lesions over the right parietotemporal cortex and white matter. Magnetic resonance angiography showed occlusion of the right internal carotid artery, and ultrasonography revealed left moderate internal carotid artery stenosis. Utilization and imitation behavior is usually attributed to a frontal lesion, rarely to a basal ganglionic or thalamic lesion, but not to a parietotemporal lesion. In this patient, the utilization and imitation behavior was thought to be attributed to right frontal lobe dysfunction without apparent MRI abnormalities, supposedly because of the right internal carotid artery occlusion in addition to the right parietal lobe infarction, both of which are thought to suppress the executive center in the left parietal lobe.

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A 66-year-old, right-handed male, was admitted to our hospital with difficulty in recognizing faces and colors. He had suffered a stroke in the right occipital region three years earlier that had induced left homonymous hemianopsia, but not prosopagnosia. A neurological examination revealed prosopagnosia, color agnosia, constructional apraxia, and topographical disorientation, but not either hemineglect or dressing apraxia. The patient was unable to distinguish faces of familiar persons such as his family and friends, as well as those of unfamiliar persons such as doctors and nurses. Brain MRI demonstrated an old infarction in the right medial occipital lobe and a new hemorrhagic infarction in the left medial occipital lobe, including the fusiform and lingual gyrus.
It is unclear whether a purely right medial occipital lesion can be responsible for prosopagnosia, or whether bilateral medial occipital lesions are necessary for this occurrence.
The current case indicated that bilateral medial occipital lesions play an important role in inducing porsopagnosia.

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