Post-infectious sensory neuropathy with anti-GT1a and GQ1b antibodies associated with cold urticaria.

A 64 years-old woman presented subacute onset distal paraesthesia concurrently with cold-induced urticaria, a rare form of physical urticaria. Both the disturbances developed a fortnight after an upper respiratory tract infection. EMG confirmed an exclusively sensory polyneuropathy, with prolongation of distal latencies and reduction of amplitudes. Anti-GQ1b and anti-GT1a antigangliosides antibodies were found in serum. The clinical workout included CSF analysis, cryoglobulin and paraprotein search, neurotropic infective agents, neoplastic markers and extensive autoimmune disease antibodies analysis, all of which resulted negative. Intravenous immunoglobulins were administered, leading to progressive resolution of the sensory disturbance, while a combination of steroid and anti-histaminics treatment was used for the urticaria. The positivity for anti-ganglioside search with an EMG pattern characterized by a mixture of demyelinating and axonal features may suggest a nodo-paranodopathy at early stages. This is the first case of an association between an acute sensory neuropathy and cold urticaria, two immune mediated conditions apparently due to very different hypersensitivity pathways. A proposed mechanism for the co-occurence of these two conditions is presented, whereas this case expands the clinical spectrum of autoimmune diseases associated with anti-GQ1b and anti-GT1a antibodies.

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study.

Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored ≥4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient-reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy.

Cysteinyl leukotriene correlated with 8-isoprostane levels as predictive biomarkers for sensory dysfunction in autism.

BACKGROUND: Autism is a neurodevelopmental disorder that clinically presented as cognitive deficits, social impairments and sensory dysfunction. An increasing body of evidence has shown that oxidative stress and inflammation are involved in the pathophysiology of autism. Recording biomarkers as measure of the severity of autistic features might help in understanding the pathophysiology of autism. METHODS: This study investigates the plasma levels of 8-isoprostane and Cysteinyl leukotrienes (CysLTs) in 44 autistic children and 40 healthy controls. The recruited autistic patients were assessed for behavior, cognitive and sensory deficits by using different autism severity rating scales, including the Childhood Autism Rating Scales (CARS), Social responsiveness scale (SRS) and Short Sensory Profile (SSP). Receiver Operating Characteristics analysis (ROC) of the obtained data was performed to measure the predictive value of 8-isoprostane and Cysteinyl leukotrienes (CysLTs) as oxidative stress- related parameters. Pearson's correlations between the measured parameters was also performed. RESULTS: The concentrations of 8-isoprostane and CysLTs in autistic patients were significantly higher than those in controls. While cognitive and social impairments did not show any significant differences, the SSP results were strongly correlated with the levels of both of the biomarkers assessed. However, autistic children showed improvements in oxidative stress status (as determined by 8-isoprostane levels) at increasing ages. CONCLUSION: This study indicates that 8-isoprostane and CysLTs can be used as markers for the early recognition of autistic patients through sensory deficits phenotypes which might help early intervention.

Childhood exposure to manganese and postural instability in children living near a ferromanganese refinery in Southeastern Ohio.

Airborne manganese (Mn) exposure can result in neurotoxicity and postural instability in occupationally exposed workers, yet few studies have explored the association ambient exposure to Mn in children and postural stability. The goal of this study was to determine the association between Mn and lead (Pb) exposure, as measured by blood Pb, blood and hair Mn and time weighted distance (TWD) from a ferromanganese refinery, and postural stability in children. A subset of children ages 7-9 years enrolled in the Marietta Community Actively Researching Exposure Study (CARES) were invited to participate. Postural balance was conducted on 55 children residing in Marietta, Ohio and the surrounding area. Samples of blood were collected and analyzed for Mn and Pb, and samples of hair were analyzed for Mn. Neuromotor performance was assessed using postural balance testing with a computer force platform system. Pearson correlations were calculated to identify key covariates. Associations between postural balance testing conditions and Mn and Pb exposure were estimated with linear regression analyses adjusting for gender, age, parent IQ, and parent age. Mean blood Mn was 10 µg/L (SEM=0.36), mean blood Pb was 0.85 µg/dL (SEM=0.05), and mean hair Mn was 0.76 µg/g (SEM=0.16). Mean residential distance from the refinery was 11.5 km (SEM=0.46). All three measures of Mn exposure were significantly associated with poor postural balance. In addition, low-level blood Pb was also negatively associated with balance outcomes. We conclude that Mn exposure and low-level blood Pb are significantly associated with poor postural balance.

Paraneoplastic sensory neuronopathy and spontaneous regression of small cell lung cancer.

BACKGROUND: Spontaneous tumour regression in small cell lung cancer has previously been suggested in patients with paraneoplastic neurologic syndromes. Rare documentation of this event has occurred in the literature. CASE REPORT: The authors report a patient with anti-Hu associated paraneoplastic sensory neuronopathy who had a spontaneous regression of her small cell lung cancer. CONCLUSIONS: This case supports the hypothesis that anti-Hu neurologic syndromes are the consequence of a misdirected immune response to small cell tumours.

Primary hyperoxaluria in an adult with renal failure, livedo reticularis, retinopathy, and peripheral neuropathy.

We present the case of a young woman who developed renal failure of unknown cause, and after 2 months of maintenance hemodialysis developed livedo reticularis, retinopathy, and peripheral sensory neuropathy. The patient was subsequently shown to have primary oxalosis type I, a rare autosomal recessive error of metabolism characterized by accumulation of calcium oxalate crystals in the kidneys, eyes, skin, and other organs. Intravascular obstruction, caused by deposition of calcium oxalate crystals in cutaneous arterioles, is thought to be responsible for the ischemic livedo reticularis lesions observed in this patient. A method is described for measuring serum glycolate by isotope dilution gas chromatography-mass spectrometry (GC-MS). An approach to the diagnosis and management is also briefly mentioned.

Indications for an immune-mediated etiology of idiopathic sensory neuronopathy.

To investigate immune mechanisms in the etiology of idiopathic sensory neuronopathy (ISN), we studied neurite outgrowth inhibition and antibody binding to neuronal tissue of serum from 4 patients with ISN. Rat dorsal root ganglion (DRG) cells were cultured in the presence of serum from ISN patients and controls. After 48 h of incubation, neurite outgrowth was quantified with a neurofilament ELISA. Serum from ISN patients significantly inhibited DRG neurite outgrowth compared to controls. ISN serum also strongly immunostained fixed cultured and cryostat rat DRG neurons (at dilutions up to 1:10,240), whereas serum from controls did not. Western blots showed unique binding patterns to DRG proteins in 3 ISN patients compared with controls, but a single band corresponding in all ISN patients was not found. The inhibitory effect of ISN serum on neurite outgrowth and the presence of circulating anti-DRG antibodies in the acute phase of the disease supports an immune-mediated pathogenesis of ISN.

[Equilibrium disorders and neuropathy associated with serum anti-Mag activity]. / Troubles de l'équilibre et neuropathie associée à une activité sérique anti-Mag.

We report the case of a 65 year-old man with a dysglobulinemic neuropathy associated with anti-Mag antibodies. Central (cerebellar) or peripheric (proprioceptive) origin of the gate disorder are discussed.

Sera from some patients with antibody-associated paraneoplastic encephalomyelitis/sensory neuronopathy recognize the Ro-52K antigen.

Screening a small cell lung cancer cDNA library with serum from a patient with antibody-associated paraneoplastic sensory neuronopathy (Anti-Hu syndrome) resulted in the isolation of a cDNA clone encoding the Ro-52 kD antigen. The Ro-52 kD antigen is one of the major antigens recognized by the sera of patients with Sjögren's syndrome and systemic lupus erythematosus. Further investigation revealed that the sera of only a small percentage (4%) of patients with the Hu syndrome reacted with Ro-52 kD antigen. The cross-reactivity may result from a domain of high homology between Ro-52 kD and HuD antigen. These results emphasize the necessity of using recombinant antigens whenever possible when assaying for assaying for specific antibodies.