In 2006, Takahashi and Yamanaka reported a groundbreaking study showing mouse and human somatic cells that can be reprogrammed to the pluripotent state by expression of only a few transcription factors (Oct4, Sox2, Klf4, and c-Myc). This novel strategy can be used for transplantation therapies without immune rejection providing additional advantages regarding ethic issues of oocyte donation. For neurological diseases, disease-specific induced pluripotent stem (iPS) cells may serve as an invaluable model for clarifying pathogenesis and for screening new drug therapies. In particular, differentiated neurons derived from patient iPS cells could infinitely provide an alternative cellular-biochemical material for research instead of biopsy and autopsy. This review summarizes the current studies applying iPS cells in the field of neurology and discusses their potential and limitations for therapy against neurological diseases.

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In order to determine predictive factors of stroke recurrence during anticoagulant therapy and to estimate prognosis, we retrospectively examined clinical data of 197 consecutive patients with acute ischemic stroke. The subjects were divided into two groups, within the therapeutic range group and below therapeutic range group, based on Japanese guidelines for the management of stroke 2004.
Univariate analysis revealed that cardioembolic stroke patients were less frequent in the therapeutic range group (61% vs 77%; p=0.03), while more lacunar stroke patients were experienced (17% vs 6%; p=0.01). In patients with past history of cardioembolic stroke, significant favorable outcomes as of Barthel index (54 vs 33; p=0.03) and modified Rankin Scale (3 vs 4; p=0.04) were found within the therapeutic range group. There is a possibility that adequate anticoagulation prevents thrombogenesis or lead to early recanalization, especially in patients with past history of cardioembolic stroke.

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A 31-year-old woman with Crohn's disease that had been refractory to drug therapies for 7 years had been treated with infliximab for a year. She was admitted to our hospital because of truncal ataxia and bulbar palsy, which presented following aseptic meningitis. Neurological examination revealed abducens paresis on the left, gaze-evoked nystagmus on upward and rightward gaze, right facial muscle weakness, bulbar palsy, weakness in the right upper extremity, limb ataxia predominantly on the left side, diminished sense in the lower extremities predominantly on the right, diffuse hyperreflexia in all extremities. Antibodies to Epstein-Barr virus (EBV) in serum demonstrated a previous infection pattern, and EBV-DNA was detected in peripheral blood and cerebrospinal fluid (CSF) by PCR. CSF analysis indicated pleocytosis, an elevation of IgG index and a marked increase in the level of myelin basic protein. FLAIR MRI images revealed multiple hyperintense lesions in the brainstem, subcortical white matter, and cervical spinal cord. Accordingly, we diagnosed her as having acute disseminated encephalomyelitis (ADEM) , associated with reactivated EBV infection. Although gancyclovir, plasma exchange and intravenous high dose immunoglobulins were not effective, repetitive use of methylprednisolone pulse therapy alleviated her symptoms and the abnormal MRI lesions. It is suggested that the reactivated EBV infection caused by infliximab may have contributed to the development of ADEM in this case. Besides the demyelinating event directly induced by anti-TNF-α therapy, we should pay attention to the occurrence of reactivated EBV-triggered ADEM during anti-TNF-α therapy.

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We report a case of paraneoplastic neurological syndrome with anti-neuronal antibodies, namely anti-Hu and anti-GluRε2 antibodies in sera. A 72-year-old male had a transient history of eye movement disorder and sensory neuropathy, which improved spontaneously. Two years later, he was admitted to another hospital because of gait disturbance, numbness of the hands and an attack of unconsciousness with generalized convulsion. He was admitted to our hospital with prolonged consciousness disturbance and muscular weakness of all extremities. On admission his consciousness deteriorated slightly without neck stiffness. His cranial nervous system was normal except for incomplete abduction and elevation of both eyes. The patient had severe distal dominant weakness and atrophy in the muscles of all four limbs. Muscle tonus was decreased and hyporeflexia was noted in the four extremities. Plantar response was extensor. Neither sensory disturbance nor ataxia was observed. Cranial MRI showed T₂-weighted high intensity lesions in the bilateral mesial temporal lobes, including the hippocampi. A nerve conduction study revealed motor-dominant peripheral neuropathy with prolonged latency; the amplitudes of compound muscle action potentials were severely reduced in all four limbs and those of sensory nerve action potentials were moderately reduced in the right upper and lower extremities. We also found a left hilar lymphadenopathy showing accumulation of FDG on PET, suggesting a possibility of malignancy. Anti-Hu and anti-GluRε2 antibodies were detected in sera but not in CSF. We diagnosed him with limbic encephalitis and peripheral neuropathy due to paraneoplastic neurological syndrome and treated him with two courses of intravenous immunoglobulin (IVIg) (400mg/kg, 5 days) . The consciousness disturbance, and prolonged distal latency revealed by motor nerve conduction studies improved slightly. Although the roles of anti-neuronal antibodies in paraneoplastic conditions remain unknown, we consider that IVIg may be worth using to treat cases with anti-Hu and anti-GluRε2 antibodies.

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We present 3 patients with transient global amnesia (TGA). Patient 1 was a 67-year-old man who had developed TGA 5 years ago. He showed sudden onset amnesia immediately after he quarreled with his wife loudly during driving. Three-Tesla (3T) diffusion-weighted magnetic resonance imaging (DWI) taken 18 hours after onset revealed a small hyperintense signal area in the right CA1 subfield of the hippocampus. Patient 2 was a 66-year-old woman who showed sudden onset amnesia immediately after she walked for about 20 minutes holding a heavy luggage with her arms. 3T DWI taken 64 hours after onset revealed a small hyperintense signal area in the left CA1 subfield of the hippocampus. Patient 3 was a 68-year-old woman who showed sudden onset amnesia immediately after she hurriedly cleaned up her house with a cleaner. 3T DWI taken 48 hours after onset revealed small hyperintense signal areas in the left CA1 subfield and the right subiculum proper of the hippocampus. She developed TGA recurrence 6 months after the first episode of TGA. All these 3 patients had no cardiovascular diseases. Their amnesia resolved within 5-6 hours. Magnetic resonance venography (MRV) revealed hypoplasia of the left transverse sinus in Patient 1 and Patient 3, and aplasia of the left transverse sinus in Patient 2. Ultrasound studies revealed a retrograde flow component of internal jugular vein during Valsalva maneuver in Patient 2.
We speculate that an increased venous pressure might have precipitated cerebral venous ischemia in the hippocampus, which is most vulnerable to ischemic insults.

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A 52-year-old man was admitted to our hospital due to drop attack accompanied with progressive right hand's clumsiness and recent memory impairment. Neurological examination revealed postural involuntary movement of the right hand, and impaired finger fine movements. He showed mild mental deterioration with lower MMSE score. Toreponema Pallidum Latex immuno Assay (TPLA) titers in serum and cerebrospinal fluid (CSF) were remarkably elevated. MRI revealed cerebral atrophy in the left hemisphere. The ^99mTc-ECD SPECT analysis showed reduced cerebral blood flow in the left hemisphere. EEG showed slow background activity in the left hemisphere. Drop attacks and involuntary movement were diminished by the administration of the valproate. We diagnosed this case as Lissauer's general paresis and treated with intravenous benzylpenicillin potassium 24 million units per day for 2 weeks. After this treatment, the titer of TPLA in the serum and CSF decreased. The clinical symptoms and signs, the score of MMSE, findings of SPECT and EEG also improved. Although Lissauer's general paresis is a rare form of neurosyphilis, it is important to distinguish this disease in case of progressive dementia and focal neurological signs. Early diagnosis and treatment are the only way to prevent irreversible neurological damage in this disease.

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We report a case of mononeuropathy multiplex with idiopathic thrombocytopenic purpura (ITP). A 78-year-old man developed patches of purpura on his left forearm. His platelet count was 11,000/μl and platelet-associated IgG was elevated. He was diagnosed as having ITP. At the beginning of the following month, he noticed dysesthesia and weakness of his left finger and left lower limb, as well as dysesthesia of his bilateral lower thighs. Neurological examination revealed weakness in the area of the left ulnar nerve and of the left anterior tibial muscle. Dysesthesia presented in the area of the left ulnar nerve and bilateral superficial peroneal nerves. Nerve conduction studies revealed asymmetric axonal sensorimotor neuropathy (mononeuropathy multiplex). A cerebrospinal fluid specimen showed a normal cell count and normal protein level. Serum anti-ganglioside antibody was negative. The platelet count gradually increased after the introduction of corticosteroid therapy. His neurological deficits and electrophysiological findings also improved. Immune-mediated neuropathy was suggested as the cause of his mononeuropathy multiplex with ITP.

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We report a 75-year-old, right-handed man, presenting with supplementary motor area (SMA) seizure. The patient had suffered from frequent attacks of transient inability to speak and move without loss of awareness. On admission, he presented with vertical gaze paresis, axial rigidity, paratonia of extremities and gait disturbance. The attacks were preceded by discomfort on the head, followed by inability to move the whole body and arrest of vocalization with tonic posture and exaggerated breathing. Consciousness and cognitive function were preserved throughout the attacks. Electroencephalography recorded intermittently slow theta waves in the bifrontal regions. Brain MRI showed atrophy of the midbrain tegmentum with lacunar state suggesting progressive supranuclear palsy. SPECT with ¹²³I-iomazenil revealed decreased uptake in the medial frontal areas including SMA, bilaterally. The seizures resolved completely following treatment with carbamazepine. Based on clinical features and neuroimagings, we speculated that the negative motor area within SMA was responsible for his seizure. Physicians should keep in mind that SMA seizure comprising negative motor phenomenon can occur in the elderly.

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A 70-year-old woman visited our hospital because of a chronic headache four years ago. MRI demonstrated almost symmetrically thickened dura mater in the frontal and parietal regions. She was diagnosed with idiopathic hypertrophic pachymeningitis and received corticosteroid therapy. Corticosteroid therapy improved her clinical symptoms and thickening of the dura mater. She remained free of neurological symptoms after prednisolone was tapered to 5mg/day. However, three years ago, she developed ear pain, otorrhea and hearing loss on the left side. She was diagnosed as having otitis media with cholesteatoma last year, and underwent mastoidectomy and tympanoplasty on the left side three months ago. After surgery, she recovered from the ear symptoms, but noticed a headache on the left side. Three months after the surgery, MRI demonstrated the recurrence of hypertrophic pachymeningitis in the frontal and parietal regions, particularly on the left side. Corticosteroid therapy again improved the headache and thickening of the dura mater. The finding that the patient recovered after corticosteroid therapy alone suggests that non-infectious inflammation played a major role in the pathogenesis. Chronic inflammation associated with otitis media with cholesteatoma or surgical invasiveness might induce the recurrence of idiopathic hypertrophic pachymeningitis.

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