The author reviews the lesion localization of non-aphasic alexia and agraphia and proposes a new classification of alexia and agraphia on this basis. The newly proposed alexia and agraphia are pure alexia for kana (Japanese phonograms), or more generally pure alexia for letters, caused by a lesion in the posterior occipital area (posterior fusiform/inferior occipital gyri), and pure agraphia for kanji (Japanese morphograms) caused by a lesion in the posterior middle temporal gyrus and also a lesion restricted to the angular gyrus. In addition, the anatomical lesions presumably responsible for the parietal apraxic agraphia, frontal pure agraphia and thalamic agraphia are discussed.

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Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies against acetylcholine receptors (AChR) and muscle-specific receptor tyrosine kinase (MuSK). These seropositivity rates in AChR positive and MuSK positive MG in Japan are 80-85% and 5-10%, respectively. The incidence of late-onset MG has been increasing all over the world. A nationwide epidemiological survey in Japan also revealed that the rates of late-onset MG (onset after 50 years) had increased from 20% in 1987 to 42% in 2006. In 2010, a guideline for standard treatments in late-onset MG was published from Japanese Scoiety of Neurological Therapeutics. Based on individual experiences and the limited evidence, epidemiological characteristics of MG onset age, clinical features, and the standard treatment for late-onset patients are included in it. In this guideline summary, the ocular form was more frequent in late-onset compared to early-onset group, the indication of thymectomy in late-onset MG is less than that of early-onset MG and the combination of corticosteroids and immunosuppressive agents are recommended in order to reduce doses of corticosteroids in late-onset MG.

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An 84-year-old man presented with acute bilateral visual impairment 2 weeks after an upper respiratory tract infection. A few days later, he developed left hemiparesis, followed by paraplegia. The brain magnetic resonance imaging (MRI) showed high-intensity lesions in the right cerebellum, pons, left and right corona radiata, and right putamen. The diffusion weighted image also showed these high-intensity lesions. The spinal MRI showed an edematous, longitudinally extensive, cord lesion at the C5-Th6 level of the spine. Intravenous corticosteroid therapy was initiated, but the patient showed mild improvement. Although methylprednisolone pulse therapy was administered 5 times, he continued to present with clinical relapse and died on day 50. Anti-aquaporin-4 (AQP4) antibodies were detected in the patient's serum. Autopsy findings showed necrotic lesions at the spinal cord, brain, and optic chiasma and nerves. An immunohistopathological study showed the loss of AQP4- and glial fibrillary acidic protein (GFAP)-positive cells, with relatively preserved myelin basic protein (MBP)-positive myelin in the necrotic lesions. We diagnosed the patient as having neuromyelitis optica (NMO) because of the seropositivity for anti-AQP4 antibodies and on the basis of above-mentioned other immunohistochemical findings. It is difficult to distinguish NMO from ADEM clinically, when the patient has a preceding infection. NMO should be considered in patients with multifocal lesions in the central nervous system who have prominent myelitis and optic neuritis, irrespective of the postinfectious onset of the lesions and the sex and age of the patient.

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A 57 year-old man developed broad-based unsteady gait and memory loss over a period of one year. On admission, bradykinesia and impairment of postural reflex were evident. Mini-mental state examination scored 27/30. Urinary control was normal. MRI revealed symmetric dilatation of lateral and 3rd ventricles, but the 4th ventricle appeared normal. Partial obstruction of the aqueduct with a membranous structure was disclosed by fast imaging employing steady state acquisition (FIESTA), and the diagnosis of late-onset aqueductal membranous occlusion (LAMO) was made. The symptoms were ameliorated shortly after endoscopic aqueductoplasty (EAP) and endoscopic third ventriculostomy (ETV). Membranous occlusion of the aqueduct can be detected by FIESTA and it can be cured by neuro-endoscopic measures.

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Charles Bonnet syndrome refers to visual hallucinations in patients with visual acuity loss or visual field loss without dementia. We report a case of Charles Bonnet syndrome following syphilitic optic neuritis. A 62-year-old man was admitted to our hospital suffering acute bilateral visual loss in a few months. On admission, he was almost blind and his optic discs were found to be atrophic on fundoscopy. In addition to increased cell counts and protein concentration in cerebrospinal fluid (CSF), serum and CSF rapid plasma reagin tests were positive. A diagnosis of syphilitic optic neuritis was made and he was treated with intravenous penicillin G (24 million units per day for 14 days) without any recovery. After treatment finished, he began to experience complex, vivid, elaborate and colored visual hallucinations. He recognized these visions as unreal and felt distressed by them. No cognitive impairment was observed on several neuropsychological tests. We diagnosed the patient as suffering from Charles Bonnet syndrome. Brain MRI revealed diffuse mild atrophy of the cerebral cortex and multiple T₂ high signal intensity lesions in the deep cerebral white matter. Single photon emission computed tomography revealed decreased regional cerebral blood flow in bilateral medial occipital lobes. Administration of olanzapine resulted in a partial remission of visual hallucinations.
Charles Bonnet syndrome following syphilitic optic neuritis is rare. In the present case, visual loss and dysfunction of bilateral medial occipital lobes may have triggered the visual hallucinations, which were alleviated by olanzapine.

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A 31-year-old woman with a 5-year history of recurrent optic neuritis and encephalomyelitis underwent repeated steroid therapy. She developed general malaise and fever in October 2009. Laboratory tests revealed marked reduction in serum Na (106mEq/L). Because the plasma osmotic pressure was lower than the urinary osmotic pressure and the serum antidiuretic hormone (ADH) level was elevated, she was diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Magnetic resonance imaging (MRI) revealed high signal intensities on symmetrical T₂ weighted and fluid attenuated inversion recovery (FLAIR) images of both sides of the hypothalamus. The serum samples tested positive for the antibody to aquaporin-4 (AQP4). Previously conducted cervical MRI had revealed a longitudinally extending lesion in the cervical cord, and brain MRI had revealed brainstem lesions. We diagnosed the patient with neuromyelitis optica (NMO) according to the revised diagnostic criteria for NMO proposed by Wingerchuk in 2006. Furthermore, she complained of excessive daytime sleepiness. The concentration of orexin in the cerebrospinal fluid was mildly reduced and the orexin levels returned to normal when her sleepiness decreased. ADH and orexin neurons localized in the hypothalamus; hence, we considered the above-mentioned symptoms to be caused by bilateral hypothalamic lesions.

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We investigated fixed basal ganglia specimens, including globus pallidus and putamen, with 21.1-Tesla MRI allowing us to achieve a microscopic level resolution from a patient with pathologically confirmed dementia with Lewy bodies (DLB) and a neurologically normal control case. We acquired T₂ and T₂* weighted images that demonstrated diffuse and patchy lower intensities in the basal ganglia compared to control. There are several paramagnetic substances in brain tissue that could potentially reduce both T₂ and T₂* relaxation times, including ferritin, iron (Fe³⁺), manganese, copper and others. Because iron is most abundant, low intensities on T₂ and T₂* weighted images most likely reflect iron deposition. Iron, especially Fe³⁺, deposition was visible in the pathological specimens stained with Prussian blue after images were obtained. Although radiological-pathological comparisons are not straightforward with respect to either the MRI signal or relaxation quantification, there appears to be a correlation between the relative increase in iron as assessed by Prussian blue staining and the decrease in T₂* value between the DLB and control specimens. As such, this exceptionally high field MRI technique may provide details about the role that iron deposition plays either directly or indirectly as a biomarker in neurodegenerative processes.

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We report a patient with Villaret's syndrome (left hypoglossopharyngeal nerve, vagus nerve, accessory nerve, and hypoglossal nerve palsies and left Horner's sign) caused by internal carotid artery dissection. He had neck pain on the left side, Horner's sign on the left side and paralysis of the left hypoglossopharyngeal nerve, vagus nerve, accessory nerve, and hypoglossal nerve. Brain MRI revealed no signal from the left internal carotid artery and no brain infarction, although a tumor-like lesion was observed in the left internal carotid artery. Subsequent MRI studies revealed intramural hematoma in the left internal carotid artery, and on the basis of this finding, he was diagnosed with internal carotid artery dissection. He received anticoagulant and antiplatelet therapy. His symptoms improved gradually.
The symptoms of internal carotid artery dissection are neck pain, Horner's sign, brain infarction, and lower cranial nerve palsy. A characteristic feature in this case was that brain infarction was not observed. Only 3 similar cases have been reported in the past. In all these cases, the patients had a good clinical course and showed complete recovery from the symptoms. Compared with western countries, in Japan, carotid artery dissection is rare. Carotid artery dissection should be considered as a differential diagnosis of lower cranial nerve palsy.

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Success of a multicenter clinical trial relies on the good and stable support system including a number of experienced people and sufficient funds. In Japan, lack of the experienced and well-funded support system makes conducting of the multicenter clinical trials very difficult. In the US, substantial amount of governmental funds have been injected to develop the clinical trial infrastructure. The cooperative group system is a model of the US governmental-funded clinical trial support system, in which the researchers can plan and conduct the clinical trials effectively and reliably, cooperating with other clinical research professionals including biostatisticians. Although there are some active oncology cooperative groups in Japan, this system remains unfamiliar to the researchers in neurology. It should be more noticed and utilized widely.

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