Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome.

The mechanisms driving the intrathecal synthesis of IgG in multiple sclerosis (MS) are unknown. We combined high-throughput sequencing of transcribed immunoglobulin heavy-chain variable (IGHV) genes and mass spectrometry to chart the diversity and compartmentalization of IgG-producing B cells in the cerebrospinal fluid (CSF) of MS patients and controls with other neuroinflammatory diseases. In both groups, a few clones dominated the intrathecal IGHV transcriptome. In most MS patients and some controls, dominant transcripts matched the CSF IgG. The IGHV transcripts in CSF of MS patients frequently carried IGHV4 genes and had more replacement mutations compared to controls. In both groups, dominant IGHV transcripts were identified within clusters of clonally related B cells that had identical or related IGHV transcripts in the blood. These findings suggest more pronounced affinity maturation, but an equal degree of diversity and compartmentalization of the intrathecal B-cell response in MS compared to other neuroinflammatory diseases.

Familial ALS with SOD1 mutation misdiagnosed with polyradiculopathy and myopathy.

We report a 54-year-old male with progressive and asymmetrical lower extremity weakness caused by familial amyotrophic lateral sclerosis (FALS) with a Cu/Zn superoxidase dismutase 1 (SOD1) gene mutation. He was initially misdiagnosed with a lumbosacral polyradiculopathy because of spinal stenosis and underwent a laminectomy surgery with no benefit. He was also misdiagnosed with a myopathy due to moderate CK elevation from acute denervation and pseudomyopathic changes on muscle biopsies from chronic denervation. He eventually developed respiratory muscle weakness and upper motor neuron signs, consistent with familial ALS.

Chronic polyradiculoneuropathy of infancy. A report of three cases with familial incidence.

Two siblings and a third child exhibited a syndrome of progressive muscular weakness and wasting, closely resembling Werdnig-Hoffmann's disease. Autopsy of one of the siblings and the third child showed nearly total absence of myelin sheaths in the cranial and spinal nerve roots, relative preservation of axons, and normal neurons in the motor cranial nerve nuclei and anterior spinal gray matter. The mother of the siblings had bilateral pes cavus, and the father of the third child had a sensory-motor polyneuropathy dating to childhood, associated with pes cavus and scoliosis. The disorder in these children and in a few similar cases in the literature shares some features of Charcot-Marie-Tooth disease and the hypertrophic neuropathy of Dejerine-Sottas, but it is difficult to classify as either of these familial neuropathies as presently defined. Elevation of cerebrospinal fluid protein is a useful finding in distinguishing such children from patients with Werdnig-Hoffmann's disease.

Conus medulla-cauda compression from nerve root hypertrophy in a child with Dejerine-Sottas syndrome: improvement with laminectomy and duraplasty. Case report.

This 7-year-old boy with Dejerine-Sottas syndrome caused by a mutation in the myelin protein zero gene began to suffer rapid deterioration with increasing leg weakness, loss of the ability to ambulate, and bowel and bladder incontinence. Magnetic resonance imaging of the spine revealed nerve root hypertrophy resulting in compression of the conus medullaris and cauda equina. Decompressive surgery was successful in reversing some of his deficits.

Chronic sensorimotor polyradiculopathy with antibodies to P2: an electrophysiological and immunoproteomic analysis.

In this study we report a patient with chronic progressive sensory ataxia, proximal weakness, immunoglobulin M (IgM) monoclonal gammopathy, and elevated protein levels in the cerebrospinal fluid, who showed a good response to prednisone. Electrophysiological study disclosed abnormalities predominantly of late responses (F waves and H reflexes), with no evidence of demyelination in the peripheral nerves, suggesting motor and preganglionic sensory nerve roots as the site of the lesion. An immune-mediated pathogenesis was considered and, to identify possible target antigens, we performed bidimensional electrophoresis and a Western blot study. Based on the suspected lesion site, we used human anterior and posterior root extracts. We identified IgM reactivity against peripheral nerve myelin protein P2. Enzyme-linked immunosorbent assay confirmed IgM reactivity toward one synthetic peptide from P2. To our knowledge, reactivity against P2 has not been reported previously in a paraproteinemic neuropathy. Furthermore, we demonstrated that bidimensional electrophoresis and Western blot of the tissue involved, as determined by clinical and electrophysiological studies, may be useful to establish clinical-immunological correlations in paraproteinemic neuropathies.

Increases in COX II mRNA in the rat spinal cord induced by cauda equina traction.

This article investigated the time response of COX II induction by traction of the cauda equina assessed by a quantified RT-PCR method. Under deep GOI anesthesia, male Wistar rats were fixed in the prone position and a laminectomy of the dorsal part of the first and second sacral vertebrae was performed. Following, COX II-mRNA levels in the cervical, thoracic, lumbar, sacral, and caudal segments were measured at 2, 4, 6, and 24 h after traction by a quantified RT-PCR method. After cauda equina traction, significant levels of COX II mRNA were detected in all segments of the spinal cord examined. Maximum levels in each segment were determined 4 h after traction of the cauda equina. Particularly in the sacrocaudal segments significantly higher levels of COX II mRNA were measured 24 h after traction. These results indicate that significant induction of spinal COX II mRNA was caused by cauda equina traction and that such induction plays a regulatory role in the nociceptive pain pathway.