[A case of leptomeningeal melanomatosis presenting with right abducens nerve palsy].

A 39 year-old man was admitted to this hospital because of severe headache and vomiting. He had been suffering from lumbago about one month previously, and diplopia ten days previously. The neurological examination revealed disturbance of right eye abduction, no nuchal rigidity. The cerebrospinal fluid (CSF) at the time of admission included erythrocytes (1,490/µl), white blood cell (62/µl) and increased level of protein (531 mg/dl), but no malignant cells were detected. He was treated as meningitis. Cranial magnetic resonance imaging (MRI) demonstrated heterogeneous intensity lesion in the left maxillary sinus and gadolinium enhancement of diffuse meninges and cranial nerves. Spine MRI showed gadolinium enhancement of lumbar spinal meninges and the cauda equina. Biopsy of the lesion in the left maxillary sinus was performed. The pathological findings demonstrated malignant melanoma. Because malignant cells were also observed in CSF, we diagnosed this case as leptomeningeal melanomatosis. Leptomeningeal carcinomatosis should be suspected when headache accompanied with pleomorphic clinical manifestations.

Chemical library screening identifies a small molecule that downregulates SOD1 transcription for drugs to treat amyotrophic lateral sclerosis.

Familial amyotrophic lateral sclerosis (fALS) accounts for 10% of ALS cases, and about 25% of fALS cases are due to mutations in superoxide dismutase 1 (SOD1). Mutant SOD1-mediated ALS is caused by a gain of toxic function of the mutant protein, and the SOD1 level in nonneuronal neighbors, including astrocytes, determines the progression of ALS (non-cell-autonomous toxicity). Therefore, the authors hypothesized that small molecules that reduce SOD1 protein levels in astrocytes might slow the progression of mutant SOD1-mediated ALS. They developed and optimized a cell-based, high-throughput assay to identify low molecular weight compounds that decrease SOD1 expression transcriptionally in human astrocyte-derived cells. Screening of a chemical library of 9600 compounds with the assay identified two hit compounds that selectively and partially downregulate SOD1 expression in a dose-dependent manner, without any detectable cellular toxicity. Western blot analysis showed that one hit compound significantly decreased the level of endogenous SOD1 protein in H4 cells, with no reduction in expression of ß-actin. The assay developed here provides a powerful strategy for discovering novel lead molecules for treating familial SOD1-mediated ALS.

[An overwhelming post-splenectomy infection with toxic shock syndrome by group B Streptococcus].

Patients receiving splenectomy are at risk of a fatal fulminant infection called overwhelming post-splenectomy infection (OPSI). Here we report a rare case of toxic shock syndrome (TSS) evoked by group B streptococcus (GBS) in an asplenic young woman, which we considered a case of OPSI. A 34-year old woman consulted our hospital complaining of vomiting, diarrhea and fever that developed early in the morning. As the physical examination and routine laboratory tests did not disclose any serious abnormalities, she returned home after symptomatic treatment under a provisional diagnosis of acute enterocolitis. However, the next morning, she was transferred to the hospital complicated by acute renal failure, severe liver damage, respiratory insufficiency, disseminated intravascular coagulation and hypotension. She was admitted to ICU and treated with intravenous antibiotics, frequent transfusions of platelet concentrates, hemodialysis, and non-invasive positive pressure ventilation. Blood cultures grew gram-positive cocci, which later proved to be Streptococcus agalactiae (GBS). We diagnosed the patient with TSS due to GBS. Organ damage and symptoms improved gradually with intensive treatment, she was discharged from the hospital 26 days after admission. Although cases of TSS due to GBS are very rare, we must be aware of the potential risk of OPSI in a splenectomized patient.

Heidenhain variant of Creutzfeldt-Jakob disease: diffusion-weighted MRI and PET characteristics.

Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressive dementia with a variety of neurological disorders and a fatal outcome. The authors present a case with visual disturbance as a leading symptom and rapid deterioration in global cognitive functions. The cerebrospinal fluid was positive for 14-3-3 protein, and diffusion-weighted magnetic resonance imaging (MRI) showed marked hyperintensity in the parieto-occipital cortices, where hypometabolism was clearly detected on positron emission tomography (PET). Pattern-reversal visual evoked potentials showed prolonged P100 latencies and increased N/5/P100 amplitudes. All these findings supported a diagnosis of the Heidenhain variant of CJD, whereas a long clinical course, a lack of myoclonus, and an absence of periodic synchronous discharges on electroencephalography were atypical. Diffusion-weighted MRI and PE1 in combination with visual evoked potential recording and 14-3-3 protein detection may be useful for the early diagnosis of CJD.