Eighty-five percent of patients with multiple sclerosis (MS) initially present with a single demyelinating event, referred to as a clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Following the onset of CIS, 38 to 68% of patients develop clinically definite MS (CDMS). Clinically silent brain lesions are seen on MRI in 50 to 80% of patients with CIS at first clinical presentation and 56 to 88% of CIS patients with abnormal MRI are at high risk of conversion to CDMS. Axonal damage, that is considered to underlie the development of persistent disability in MS, occurs in the CIS stage. Treatment with disease-modifying therapies (DMTs), that might prevent axonal damage and result in slowing the progression of disability, should be initiated early during the disease course. Clinical trials demonstrated that early treatment of CIS patients with the standard dose of interferon beta (IFNβ) significantly reduced the risk of progression to CDMS by 44 to 50%. After 5 years of follow-up, the results of the IFNβ treatment extension studies confirmed that the risk of conversion to CDMS was significantly reduced by 35 to 37% in patients receiving early treatment compared to that in those receiving delayed treatment. However, not every patient with CIS will progress to CDMS; the IFNβ treatment is appropriately indicated for CIS patients who are diagnosed with MS by McDonald diagnostic criteria based on MRI findings of dissemination in space and time and are at high risk for conversion to CDMS. Development of more reliable prognostic markers will enable DMTs to be targeted for those who are most likely to benefit.

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A 30-year-old healthy woman experienced speech disturbance and swallowing difficulty at two months of pregnancy. She was diagnosed as myasthenia gravis (MG) with anti-MuSK antibodies. At eight months of pregnancy, bulbar palsy, eye movement disturbance, and muscle weakness worsened unexpectedly. Plasma exchange was performed three times daily starting from the 1st day of the 37th pregnancy week (2L/day, albumin substitution of 5%) and the patient underwent caesarean section and gave birth to the girl safely. The infant had anti-MuSK antibodies in the serum and umbilical cord blood. The infant's suckling power was weak. The infant was diagnosed as transient neonatal myasthenia gravis. There is no case where management of MG has been performed from the period of pregnancy for anti-MuSK positive patients. For the control of Anti-MuSK positive patients in addition to normal care for Anti-AChR antibodies positive patients, it is important to carefully observe symptoms caused by bulbar palsy, draw attentions on malnutrition and polyhydramnios, and perform simple plasmapheresis on regular basis without any delay.

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We treated a 25-year-old woman with encephalitis. Following delivery, the patient developed fever, consciousness disturbance, cognitive dysfunction, and progressive motor dysfunction. In addition, mycobacterium tuberculosis was found in the lung, though there was no evidence of such infection in the central nervous system. Cerebrospinal fluid analysis revealed a slight elevation of mononuclear cells with a normal protein level, indicating a possible viral infection. We could not find the origin of the infection, though the serum anti-glutamate ε2 receptor antibody was positive. Intravenous administration of methylprednisolone (1,000mg/day for 3 days) was temporarily effective for improvement of the clinical signs and symptoms. However, she finally demonstrated rapid deterioration resulting in death. Diffusion-weighted brain magnetic resonance imaging demonstrated abnormal high intensity lesions in the bilateral pulvinar and gray matter, with an abnormal appearance mimicking pulvinar sign.

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A 65 year old woman presented with progressive gait disturbance. She complained of appetite loss for 3 months. Her gait gradually became unsteady, and she was admitted to our hospital. On admission, slow mentation, bathyhypesthesia in left upper and both lower extremites, positive Romberg sign and wide-based gait were observed. Gd-enhanced MRI revealed mass lesions in the left temporal fossa and the cervical spinal canal with focal meningeal enhancement. Besides lesions in the central nervous system (CNS), systematic examination detected no additional malignancy. Repeated cytology of the cerebrospinal fluid was negative. After admission, her consciousness became reduced gradually. At 2 months after admission, she died of central respiratory failure. On autopsy, diffuse extension of the tumor cells was observed on the surface of CNS, and the mass lesions observed by MRI were extra-parenchymal. On microscopic examination, the mass was consisted of GFAP positive malignant cells, and included perivascular pseudorosette, pseudopalisading necrosis and many mitotic cells. The diagnosis of the case was made as primary diffuse leptomeningeal gliomatosis (PDLG). PDLG is a rare disorder that is difficult to diagnose by CSF cytology. The progress of PDLG is rapid, and appropriate treatment is rarely taken. However, the combination of temozolomide and the radiotherapy performed for a glioblastoma has been reported as a possible treatment for PDLG. We emphasize that, in possible cases of PDLG, a biopsy should be performed in the early stages, especially in cases showing features similar to those of metastatic meningeal carcinomatosis and have no malignant tumors by whole body examination.

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A 44-year-old woman was admitted to our hospital because of meningitis, with symptoms of an altered mental state and flaccid quadriparesis. Neurological examination revealed nuchal rigidity, flaccid quadriparesis without tendon reflexes, septic rash and urinary retention. Nerve conduction studies showed diminished F-wave ratios. However, the amplitudes and conduction velocities for bilateral motor and sensory nerves of the upper (medial and ulnar nerves) and lower (posterior tibial and sural nerves) limbs were all normal. Spinal MRI showed gadolinium enhancement of the bilateral sacral nerve roots, indicating radiculitis. In addition, T₂^*-weighed MRI of the brain revealed multiple microbleeds. Infectious endocarditis was detected on admission, and Staphylococcus aureus infection was confirmed by blood culturing. The patient was diagnosed with meningoradiculitis caused by S. aureus. Although antibiotic therapy did not improve quadriparesis, administration of dexamethasone led to a marked amelioration of the quadriparesis with a resultant complete recovery of the limb muscle powers in three months. Furthermore, as the quadriparesis improved, F-wave ratios gradually returned to normal and hearing loss remained as the only sequela. Therefore, adrenocorticosteroid therapy attenuated radiculitis-induced quadriparesis. Although radiculitis due to S. aureus is extremely rare, it should be considered because delayed treatment can lead to permanent injury and impairment.

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A 65-year-old man presented with complaints of general malaise and severe disturbance of consciousness since 2 months prior to admission. MRI of the head showed high intensity area in FLAIR image in the left basel ganglia, the medial side of the left temporal lobe and both sides of the frontal lobe and brainstem. The contrasting effect was insignificant. Laboratory investigations showed positive results of EBV antibody titer and elevated EBV-DNA in the spinal fluid. We suspected encephalitis due to Epstein-Barr virus and the patient was treated with acyclovir and high dosage of steroids. However, the patient's consciousness gradually deteriorated and he died on day 146 of admission. Autopsy revealed proliferation of large atypical cells with clear and irregular nuclei in the brain tissue. Immunohistochemistry expressed positive EBER-ISH. This case was finally diagnosed as the central nervous system involvement by age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorder.

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A 68-year-old woman was admitted to our hospital because of sudden onset of involuntary movements, similar to those associated with chorea, of the right side of the body and for further evaluation of thrombocythemia. She had no family history of chorea. Neurological findings did not show any abnormality except for chorea of the right side. Laboratory studies showed increased number of white blood cells (14,000/μl) and platelets (188.3×10⁴/μl). Lupus anticoagulant, anti-cardiolipin antibody, and ceruloplasmin levels were within the normal range. Her NAP score was 240, and result for bcr-abl gene expression was negative. Bone marrow puncture showed hypercellularity and increased number of megakaryocytes (550/μl), but there was no atypism. On the basis of these laboratory findings, she was diagnosed with essential thrombocythemia. T₁-weighted magnetic resonance imaging (MRI) showed a hyperintense lesion extending from the region around the left globus pallidum to putamen. The MRI findings of our study were similar to those related to diabetic hemichorea; however, the results of some tests did not indicate diabetes mellitus. An MRI scan showing high T₁ signal intensity in the basal ganglia might not be specific for diabetic hemichorea. In this case, MRI revealed the cause of hemichorea to be micocirculatory failure or small cerebral hemorrahages.

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Three months prior to presentation, a 76-year-old woman suffered from insomnia and was prescribed some antidepressants and hypnotics. At that time, brain MRI showed no cerebral infarcts. Having developed an action tremor of the left hand, bradykinesia, and unstable gait, she visited our hospital. Neurological examination revealed rigidity of the neck and left limbs, clumsiness of the left hand, action tremor, and decreasing swing of the left arm while walking. ¹²³I-metaiodobenzylguanidine scintigraphy showed no decrease of the heart/mediastinum ratio. The second MRI showed an old cerebral infarct located just in the right external segment of the globus pallidus. Since drug-induced parkinsonism was suspected, paroxetine and trazodone were discontinued, but her symptoms did not improve. We concluded that her hemiparkinsonism was due to the cerebral infarct in the right external segment of the globus pallidus, because her symptoms did not respond to dopamine agonist and L-dopa therapy, and the onset of symptoms corresponded with the time of appearance of the cerebral infarct. This is a rare case that is important for understanding the mechanism of parkinsonism.

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A 78-year-old man was admitted to our hospital with headache, nasal pain, left-sided ptosis, loss of visual field in his left eye, and left ophthalmoplegia. Serum levels of β-D-glucan were elevated. T₁-weighted magnetic resonance imaging with gadolinium enhancement showed hyperintense lesions in the left orbital apex and dura mater of the left middle cranial fossa. A few days later, culture of specimens collected by surgical debridement from the left sphenoidal sinus revealed numerous branching hyphae. The aspergillus antigen was found in the cerebrospinal fluid (CSF). Therefore, aspergillosis causing orbital apex syndrome was diagnosed. Administration of amphotericin B prevented further worsening of the patient's infection. Although noninvasive sinus aspergillosis showed that fungus did not destroy tissues in general, the condition resulted in intracranial impairments observed in this case, including orbital apex syndrome and hypertrophic pachymeningitis. Furthermore, detection of the aspergillus antigen in CSF was a clue for the diagnosis of aspergillosis, and administration of antifungal drugs in the early stages of infection was an effective treatment.

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