During the past 10 years, our understanding of the pathomechanism and pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has improved through clinical examination, imaging studies, pathological studies, cell experiments and the development of transgenic mice. Although epidemiological studies of CADASIL in Japan have been limited, more than 100 cases of this condition have been diagnosed in Japan. In our laboratory, we diagnosed 37 CADASIL cases genetically and identified three features common to Japanese cases. One is the wide distribution of onset age for clinical symptoms other than migraine, with the onset of symptoms being later than age 60 in 22% of cases. Second, the majority (65%) of Japanese CADASIL cases have stroke risk factors, such as hypertension, hyperlipidemia, or smoking. Third, in 22% cases there was no definite family history of stroke. However, the previous diagnostic criteria proposed by Dabous excluded several definite cases in our cohort. Therefore, to avoid missing undiagnosed cases of CADASIL, we have generated new diagnostic criteria for Japanese CADASIL based on the knowledge accumulated during the past 10 years, and compared sensitivity of two criteria. In our diagnosed Japanese CADASIL cases, the sensitivity of the new criteria was 19% and 78% for probable and possible cases, respectively, and only one case was (Fig. 3) missed when using the new criteria. In comparison, the sensitivity of Dabous's was 11% and 51% for probable and possible cases, respectively, and 24% cases were excluded due to hypertension, elderly onset or no family history, although these cases showed recurrent strokes, white matter lesions and NOTCH3 mutations. Using our new criteria, diagnosis of CADASIL can be made even in cases with elderly onset, stroke risk factors, and obscure family history.

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Twelve cases (one Gerstmann-Sträussler-Scheinker syndrome (P102L; definite), one genetic Creutzfeldt-Jakob disease (CJD) (V180I; definite) and ten sporadic CJD (7 MM1-type definite, 3 probable)), who reached the akinetic mutism state, were investigated with regard to their clinical course and treatment. They were hospitalized for a total of 3,968 days in the akinetic mutism state. In the nine definite cases, the median period from the akinetic mutism state to death was 22 months (average: 27.0±23.3 months, range: 3-80 months) and median total disease duration was 27 months (average: 34.2±30.1 months, range: 5-102 months). In the seven definite sporadic CJD cases, the median period from akinetic mutism to death was 21 months (average: 17.0±9.6 months, range 3-28 months), and median total disease duration was 24 months (average: 20.6±10.0 months, range: 5-31 months). Nasal-tube feeding was performed in all cases. Symptomatic treatments such as parenteral nutrition and antibiotic drugs were administered for complications such as respitory and urinary tract infections and digestive symptoms. Patients received rehabilitation and hot spring therapy regularly until death. Gastrostomy and/or tracheotomy was not performed in any case, the patients were not intubated nor was mechanical ventilation (including non-invasive positive pressure ventilation) applied. Vasoactive drugs were not administered. Clonazepam was administered for myoclonus in four patients but not in another three when myoclonus appeared. It is unclear whether the treatment influenced the duration of myoclonus.
Our observations indicate that the extended survival period among Japanese prion disease patients is likely due to the management procedures implemented for prion disease in Japan, which are usually continued after the patients reach the akinetic mutism state. We speculate that nasal-tube feeding is the crucial factor that results in the prolonged disease duration of prion disease patients in the akinetic mutism state.

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It is essential that we know the real situation of at-home patients with amyotrophic lateral sclerosis (ALS) in order to improve their medical support system. We indirectly investigated the daily living status of ALS patients and their families at home by conducting on individual questionnaires survey for nurses working at public health centers in Aichi prefecture, Japan. Detailed information about 136 cases was obtained, and we could clarify the need for variety of communication methods, plasticity of medical interrelations and care between neurologists and home doctors, incomplete utilization of social resources including various official support, overwork among single caregivers, and underdeveloped immature individual medical care support programs for them. Thus it might be important that we should promote the sure utilization of social resources and programming the individual medical care support in their earlier stages. And moreover, we should also consider constructing a general support system for at-home patients with ALS, in which each professional would owe the dividing responsibility, without role duplications. These strategies would lead to overall the better quality of life among ALS patients, and their families.

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A 65-year-old man had suffered contusion of the left frontal lobe of the brain with a skull base fracture, pneumocephalus, and cerebrospinal fluid (CSF) leakage. He was treated with ceftriaxone 4 g/day for 14 days, but after 1 month he developed multiple cranial nerve palsies (bilateral III-X). CSF contained increased levels of protein (96 mg/dl) and mononuclear cells (72 cells/mm³), and low glucose levels (40 mg/dl, blood sugar 120 mg/dl), but no malignant cells were detected. Magnetic resonance imaging (MRI) disclosed swelling in multiple cranial nerves with Gd enhancement. Anti-biotic and antifungal therapy remitted the facial, glossopharyngeal, and vagus nerve palsies and reduced the Gd-enhancement lesion, as detected by MRI. However, the eyes were bilaterally dilated and medially fixed, and hearing impairments persisted. After 3 months, follow-up MRIs revealed the presence of Gd-enhanced small masses at the ventral pontine base, medulla, and cervicomedullary junctions despite a lack of change in neurological symptoms. Those lesions subsided favorably upon treatment with intravenous and oral corticosteroids. After 1 year and 9 months, Gd-enhanced small cystic masses appeared on the medulla and cerebellum. An open biopsy of the cerebellar tonsillar lesions revealed diffuse large B cell lymphoma. Although the development of primary central nervous system lymphoma after open head injury and infection has not been reported to date, central nervous system lymphomas may mimic diverse neurological diseases. Brain biopsy remains the only definitive diagnosis, and thus should be pursued if blood and CSF markers appear normal.

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A 45-year-old man was admitted to our hospital with flaccid paraplegia. Neurological examination at a local hospital, 2 months before admission to our hospital, showed sensory impairment of the right posterior surface of the thigh and a decreased Achilles tendon reflex. Spinal magnetic resonance imaging (MRI) showed a T₂ weighted high-intensity area at the Th10-11 level that was more pronounced in the gray matter. The patient developed flaccid paraparesis and urinary retention. No improvement was observed after 2 rounds of methylprednisolone (mPSL) pulse therapy. Spinal cord biopsy showed demyelinated axons and myelinophagia without any tumorous lesion. Myelopathy exacerbated, and hence, plasma exchange was performed. However, this was ineffective. We suspected that myelopathy was caused by intravascular lymphoma (IVL) because of the presence of a low-grade fever, weight loss, and elevated serum soluble IL-2 receptor titers. Random biopsies, including skin, rectal, bone marrow, muscle, and renal biopsies, and splenectomy were performed to make a definite diagnosis of IVL myelopathy. Among these biopsies, the diagnosis of IVL myelopathy was confirmed from the renal specimen. The patient underwent chemotherapy at our hospital, and the IVL remitted. The results of this study confirm that sufficient systemic investigation by using tissue biopsy specimens should be performed in order to confirm the diagnosis of IVL myelopathy.

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A 79-year-old female had a spinal lesion that was definitely diagnosed as intravascular large B-cell lymphoma on the basis of skin biopsy findings, and she was treated by rituximab-containing chemotherapy. The spinal lesion showed high and low signal intensities on T₂ weighted magnetic resonance imaging (MRI) scans, those low signal intensity lesions were suspected to be hemorrhages. The hemorrhages were thought to have been caused by interaction between atypical lymphoma cells and the endothelial cells of spinal blood vessels, by hemorrhagic infarction or by rupture of the capillary endothelium due to interaction between rituximab and lymphoma cells. Intravascular large B-cell lymphoma cases rarely show low signal intensity on spinal T₂ weighted MRI scans.

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We present a case of slowly progressive gait ataxia with a 16-year history in an 87-year-old woman. In 1994 she became aware of a slight unsteadiness while walking and cortical cerebellar atrophy was diagnosed. She had no familial history of neurological disorders. In 2007, idiopathic thrombocytopenic purpura (ITP) was diagnosed. The symptoms gradually worsened, and she was admitted in 2010 because she could not walk without support. MRI voxel-based morphometry (VBM) imaging showed atrophy of the entire cerebellum, and SPECT using eZIS showed reduced perfusion in the same regions. Her blood was positive for both anti-TPO antibody (42IU/ml) and anti-gliadin antibody (20.2 EU). We therefore diagnosed autoimmune cerebellar atrophy. The patient showed a positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. Her posture and gait disturbance scores on the International Cooperative Ataxia Rating Scale had improved from 20 to 9. Even 16 years after onset, intravenous immunoglobulins were effective. In cases of prolonged disease, immunotherapy can be effective in autoimmune cerebellar atrophy and should not be excluded from the treatment choices.

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We report two patients who presented with altered mental status and involuntary movement under administration of cefepime (CFPM). Both cases had impaired renal function. Electroencephalogram (EEG) revealed generalized periodic discharges (GPD) or generalized rhythmic delta activity (GRDA): 3Hz in the case 1 and 1 to 2Hz in the case 2. In spite of the severe abnormality in the EEG, both patients could respond to simple commands, which suggested possible dissociation between clinical findings and EEG. The patients recovered several days after discontinuation of CFPM, and had no clear residuals. We sometimes have difficulty in determining the cause of non-specific altered mental status; drug-induced, toxic, or metabolic encephalopathies are possible differential diagnoses. Arguably, the EEG findings shown here can be a clue to correct diagnosis of CFPM induced encephalopathy.

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A 73-year old man was brought to our hospital because of acute onset of fever and consciousness disturbance. He had been hemodialyzed three times a week because of chronic renal failure since 13 years ago. Neurological examination revealed deteriorated consciousness and neck stiffness. A lumbar puncture yielded clouded fluid with a WBC 7,912/mm³ (polymorphonuclear cells 88%, mononuclear cells 12%), 786mg/dl of protein and 4mg/dl of glucose (blood glucose 118mg/dl). Brain CT and MRI were unremarkable. He was treated with ceftriaxone and ampicillin. Streptococcus salivarius was isolated from the blood sample, but not from cerebrospinal fluid. The patient responded promptly to antibiotics therapy (ampicillin 3g/day, ceftriaxone 1g/day), and within several days he became lucid and afebrile. Isolated S. salivarius was sensitive for ampicillin and ceftriaxone. We diagnosed this case as S. salivarius bacteremia/meningoencephalitis. A gastrointestinal diagnostic workup revealed an asymptomatic gastric adenocarcinoma. S. salivarius is a common inhabitant of the oral mucosa that has been associated with infection in different sites. Meningeal infection by S. salivarius generally related to neoplasia of colon or iatrogenia, has been described on few occasions. This is the first report of S. salivarius bacteremia/meningoencephalitis associated with gastric neoplasm. Neurologist should be aware of the association of S. salivarius bacteremia/meningoencephalitis and gastrointestinal disease.

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