Self-Contained Induction of Neurons from Human Embryonic Stem Cells

BACKGROUND: Neurons and glial cells can be efficiently induced from mouse embryonic stem (ES) cells in a conditioned medium collected from rat primary-cultured astrocytes (P-ACM). However, the use of rodent primary cells for clinical applications may be hampered by limited supply and risk of contamination with xeno-proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an alternative method for unimpeded production of human neurons under xeno-free conditions. Initially, neural stem cells in sphere-like clusters were induced from human ES (hES) cells after being cultured in P-ACM under free-floating conditions. The resultant neural stem cells could circumferentially proliferate under subsequent adhesive culture, and selectively differentiate into neurons or astrocytes by changing the medium to P-ACM or G5, respectively. These hES cell-derived neurons and astrocytes could procure functions similar to those of primary cells. Interestingly, a conditioned medium obtained from the hES cell-derived astrocytes (ES-ACM) could successfully be used to substitute P-ACM for induction of neurons. Neurons made by this method could survive in mice brain after xeno-transplantation. CONCLUSION/SIGNIFICANCE: By inducing astrocytes from hES cells in a chemically defined medium, we could produce human neurons without the use of P-ACM. This self-serving method provides an unlimited source of human neural cells and may facilitate clinical applications of hES cells for neurological diseases

Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Alexander disease (ALX) is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP). Three subtypes are distinguished according to age at onset: infantile (under age 2), juvenile (age 2 to 12) and adult (over age 12). Following the identification of heterozygous mutations in <it>GFAP </it>that cause this disease, cases of adult-onset ALX have been increasingly reported.</p> <p>Case Presentation</p> <p>We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the <it>GFAP </it>gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX.</p> <p>Conclusion</p> <p>The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the <it>GFAP </it>gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX.</p

Subregional 6-[18F]fluoro-ʟ-m-tyrosine Uptake in the Striatum in Parkinson's Disease

<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[¹⁸F]fluoro-ʟ-<it>m</it>-tyrosine (FMT).</p> <p>Methods</p> <p>We assessed 101 patients with PD and 19 healthy volunteers. PD was diagnosed based on the UK Brain Bank criteria by two experts on movement disorders. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale (UPDRS). FMT uptake in the subregions of the striatum was analyzed using semi-automated software for region-of-interest demarcation on co-registered magnetic resonance images.</p> <p>Results</p> <p>In all PD patients, FMT uptake was decreased in the posterior putamen regardless of predominant motor symptoms and disease duration. Smaller uptake values were found in the putamen contralateral to the side with more affected limbs. The severity of bradykinesia, rigidity, and axial symptoms was correlated with the decrease of FMT uptake in the putamen, particularly in the anterior part. No significant correlation was observed between tremors and FMT uptake.</p> <p>Conclusions</p> <p>Decrease of FMT uptake in the posterior putamen appears to be most sensitive in mild PD and uptake in the anterior putamen may reflect the severity of main motor symptoms, except for tremor.</p

Reversible limbic encephalitis with antibodies against the membranes of neurones of the hippocampus

The authors report a patient with limbic encephalitis associated with an ovarian teratoma. An antibody against the membranes of neurones of the hippocampus was identified in both serum and CSF. Immunosuppressive treatments such as plasmapheresis and high-dose intravenous immunoglobulin administration resulted in a rapid clinical recovery

Nationwide survey on the epidemiology of syringomyelia in Japan

Background: Syringomyelia is a rare disease characterized by abnormal fluid-filled cavities within the spinal cord, and is associated with Chiari malformations, arachnoiditis, or spinal cord tumors. The widespread availability of magnetic resonance imaging (MRI) in Japan has allowed for easy identification of syrinxes. The aim of this study was to survey the clinicoepidemiological characteristics of syringomyelia in Japan. Methods: A 2-stage postal survey was conducted in late 2009. The first survey aimed to estimate the number of patients with syringomyelia, and the second survey aimed to elucidate clinicoepidemiological characteristics. Diagnosis of syringomyelia was based on the findings of MRI or computed tomographic myelography. Results: In the first survey, we received 2133 responses from 2937 randomly selected departments and collected data of 1215 syringomyelia patients (543 men and 672 women). The total response rate for the first survey was 73%. The estimated prevalence of ambulatory syringomyelia patients in Japan was 1.94 per 100 000. In the second survey, the proportion of asymptomatic syringomyelia patients was 22.7%. Chiari type I malformations and idiopathic syringomyelia were the first and second most common etiologies. Conclusions: Our nationwide survey indicated that widespread MRI availability has contributed to the diagnosis of both asymptomatic and idiopathic cases

Is Lesion of Exner’s Area Linked to Progressive Agraphia in Amyotrophic Lateral Sclerosis with Dementia? An Autopsy Case Report

Agraphia, as a neuropsychological symptom of ALS, especially ALS with dementia (ALS-D), has recently attracted more attention. However, the brain lesion responsible has not been identified. Here we present an autopsy case of ALS-D of a patient with obvious agraphia, without aphasia, that also presented cerebrospinal degeneration with TDP-43-pathology compatible with ALS-D. Of the pre-motor frontal lobe cortices, degeneration and immuno-histochemical pathology were most obvious in the caudal area of the left middle frontal gyrus, or Exner’s area. Assuring this area plays a pivotal role in the kanji and kana formation used in writing the Japanese language, this case of ALS-D showed both agraphia and Exner's area stressed pathological lesions. It may thus be the first case to indicate an intimate relationship between the neuropsychological symptoms and an associated lesion for ALS-D