Makoto Kawahara

Humanin inhibits cell death of serum-deprived PC12h cells

Humanin (HN) and S14G HN (HNG) are recently discovered polypeptides that rescue cells from death induced by multiple different types of familial Alzheimers disease genes and by amyloid-&bgr;. However, the cytoprotective activity of these peptides against other cell death-inducing stimuli remains unclear. In this study, we demonstrated, using three different methods (MTS assay, caspase-3 assay, and detection of DNA fragmentation), that both HN and HNG protect PC12 cells from death elicited by serum deprivation. This implies the potential of the peptides to rescue cells from a broad spectrum, if not all, of cell death-inducing factors. Further investigations on HN may lead the possible application of this peptide as therapeutic agent for the treatment of other neurodegenerative diseases.

Characteristic Neuroimaging in Patients with Tumefactive Demyelinating Lesions Exceeding 30 mm

Features of tumefactive demyelinating lesion (TDL) on magnetic resonance imaging (MRI) can facilitate the differential diagnosis of TDL and neoplastic lesions, but vary considerably among patients. The larger TDL grows, the more difficult it becomes to differentiate TDL from neoplastic lesions. The purpose of this study was to elucidate typical MRI features in 12 patients with large TDL (>30 mm in diameter).

Treatable fluctuating Parkinsonism and dementia in a patient with a dural arteriovenous fistula.

weight loss, the relationship between BMI loss (adjusted for age) and the increase in total plasma organochlorine concentration explained more than 50% of the variance observed (adjusted for age R2 0.51; P 0.01). At steady-state weight, there was no relationship between BMI and the initial total plasma organochlorine concentration. At steady-state weight, age was the most important predictor of the total organochlorine concentration (greater concentration for older persons) and could predict by itself 45% of the variance observed (adjusted for BMI R2 0.45; P 0.01). The striking and important result with regard to Uc and colleagues’ work1 is the significant relationship observed between weight loss and the total organochlorine concentration. There is a growing body of information linking pesticide exposures with PD.6–13 Although the association between exposure to moderate levels of pesticide and the development of PD is still debated, our observations and that of Uc and colleagues1 suggest the importance of examining more closely the impact of weight loss when parkinsonian signs progress. It may well be that, for these patients, weight loss contributes to worsening of parkinsonism.

Renin-angiotensin system blockers affect cognitive decline and serum adipocytokines in Alzheimer's disease.

Accumulating evidence indicates an association of Alzheimers disease (AD) with the metabolic syndrome (MetS), characterized by visceral fat accumulation with insulin resistance and altered secretion of adipocytokines such as adiponectin and leptin. The renin‐angiotensin system (RAS) regulates blood pressure and insulin resistance. Recent studies suggest that the RAS plays crucial roles in cognitive functions and that adipocytokines exert neuroprotective activity in the brain. We investigated whether RAS blockers (RASB) affect adipocytokines and cognitive function in patients with AD.

Diffuse neurodeficits in intravascular lymphomatosis with ADAMTS13 inhibitor

Inhibitory antibody to von Willebrand factor (vWF)-cleaving protease (ADAMTS13) was detected in a patient with intravascular lymphomatosis. The increased serum level of the antibody paralleled an increase in the expression of uncleaved vWF, which might cause microvascular thrombosis and platelet consumption. Malignant cell proliferations with superimposed thrombosis within the lumina throughout the entire vasculature account for diffuse neurodeficits observed in the patient.

Infarction Limited to Both Middle Cerebellar Peduncles

The middle cerebellar peduncle (MCP) is supplied mainly by the anterior inferior cerebellar artery and partly by the superior cerebellar artery. The bilateral MCP infarctions in previous patients were attributed to alternations of two vessels, such as the unilateral vertebral artery and basilar artery or both vertebral arteries.

Novel splice variants increase molecular diversity of aprataxin, the gene responsible for early-onset ataxia with ocular motor apraxia and hypoalbuminemia.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is one of the most common forms of autosomal recessive cerebellar ataxia. We identified six new alternative transcripts produced by the aprataxin gene responsible for EAOH. Total eight transcripts encoded truncated proteins that were located within the nucleus or cytoplasm and showed different binding abilities to wild-type (WT) aprataxin. Thus, the alternative splicing increases the molecular diversity of aprataxin and the expression profiles of these transcripts in various tissues may be related to the tissue-specific phenotypes.

Fixed epiglottis associated with subthalamic nucleus stimulation in Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor disability of patients with Parkinson’s disease (PD). Mental changes and other adverse events are common, but typically transient. Severe complications such as intracerebral haemorrhage or infection are rare,1 but 6 of 73 patients who underwent STN-DBS died of pneumonia, cardiac failure or pulmonary embolism.1 We describe a patient with PD who had sudden respiratory difficulty due to a fixed epiglottis after STN-DBS. This symptom was confirmed to be related to STN stimulation on fibre-optic examination of the larynx. In December 1995, a 76-year-old man noticed slowness of movements. He had moderate parkinsonism, associated with masked face, stooped posture, bradykinesia, right-side-dominant rigidity and resting tremor. Bradykinesia and rigidity responded to treatment with levodopa. In August 2006, he became severely disabled due to “on–off” phenomena and hallucinations while receiving levodopa, cabergoline, pergolide, quetiapine and risperidone. In September, the patient underwent STN-DBS. Because the right stimulator was located slightly medially to the STN, he underwent a second operation to adjust its position in October (fig 1). Motor disability and hallucinations then decreased at the following STN-DBS settings: cathodic bipolar stimulation, 90 μsec pulse width, 1.7 V and …

Biphasic paraneoplastic brainstem encephalitis associated with anti-Ri antibody.

Brainstem encephalitis is not a classic paraneoplastic syndrome and usually involves monophasic neurological deterioration and has negative magnetic resonance imaging (MRI) findings. We describe a patient with brainstem encephalitis who had elevated anti-Ri antibody levels and double-step neurological deterioration associated with different abnormal lesions on MRI. Immunosuppression with steroids and intravenous immune globulin combined with aggressive treatment of the tumor successfully led to the resolution of brainstem symptoms and MRI lesions. In patients with unusual signs and symptoms of paraneoplastic encephalitis mimicking multiple sclerosis, onconeural antibody studies are recommended.

A successfully treated case of herpes simplex encephalitis complicated by subarachnoid bleeding: a case report

IntroductionHistopathologically, herpes simplex virus type 1 causes hemorrhagic necrosis. Overt hemorrhage is infrequent in herpes simplex virus encephalitis but can lead to poor outcomes. This report describes a successfully treated case of herpes simplex virus encephalitis associated with subarachnoid bleeding in which real-time polymerase chain reaction was useful for diagnosis.Case presentationA 30-year-old previously healthy Japanese woman who had fever and headache for five days presented with disorganised speech, unusual behavior and delusional thinking. Real-time polymerase chain reaction amplification of herpes simplex virus type 1 in cerebrospinal fluid was positive (38,000 copies/mL) and antivirus treatment was started. During the course of her illness, the level of her consciousness decreased in association with desaturation and tachycardia. Thrombosis of the right pulmonary artery trunk with pulmonary embolism was evident on enhanced chest computed tomography. In addition, cranial computed tomography revealed subarachnoid and intraventricular bleeding. Intravenous heparin (12,000 U/day) was started and the dose was adjusted according to the activated partial thromboplastin time for about a month (maximum dose of heparin, 20,400 U/day). After the treatments, her Glasgow coma score increased and the thrombosis of the pulmonary artery trunk had disappeared.ConclusionsThe present case raises the question of whether anticoagulant treatment is safe in patients with herpes simplex virus encephalitis complicated by subarachnoid bleeding.