Faculty Bibliography

Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation. Differential gene expression may help distinguish between CIDP, VAS and NN in sural nerve biopsies and identify genes that may be involved in disease pathogenesis

BACKGROUND: Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy. OBJECTIVE: To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms. DESIGN: Case series. SETTING: Academic peripheral neuropathy clinic. PATIENTS: Eight patients with CD and neuropathy symptoms.Intervention Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. MAIN OUTCOME MEASURE: Clinical data and ENF density. RESULTS: All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. CONCLUSIONS: Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study

OBJECTIVE: To determine normative cutoffs and sensitivities for median distal latency (MDL), median-thenar to ulnar-thenar latency difference (TTLD), and median-thenar to ulnar-hypothenar latency difference (THLD) at various amplifier gains for carpal tunnel syndrome (CTS) electrodiagnosis. A prior study utilized only an amplifier gain of 0.2 mV/division. METHODS: Abnormal cutoffs for MDL, TTLD and THLD were determined based on 34 control hands at gains of 0.2, 0.5, 1, 2, and 5 mV. Diagnostic sensitivities were determined for 50 patients (80 hands) with clinically and electrodiagnostically defined CTS. RESULTS: At a gain of 0.2 and 0.5 mV/division, abnormal cutoffs for MDL, THLD, and TTLD were: 3.7, 1.2, and 0.8 ms. At gains of 1, 2, and 5 mV the abnormal cutoffs were 4, 1.2, and 1 ms. The sensitivities at gains of 0.2, 0.5, 1, 2, and 5 mV for MDL, THLD, and TTLD were: 65, 66, 53, 57, 61/86, 83, 88, 86, 86/91, 91, 76, 73, 59. CONCLUSIONS: MDL and THLD sensitivities are gain-independent. THLD is substantially more sensitive than MDL at all gains. TTLD sensitivity is maximized with 0.2 and 0.5 mV gains. SIGNIFICANCE: TTLD and THLD increase diagnostic sensitivity with minimal additional effort. TTLD sensitivity is maximized with 0.2 or 0.5 mV gains. The electromyographer's preferred gain may be used

Peripheral neuropathy (PN) in inflammatory bowel disease (IBD) patients has been reported as individual cases or small series; however, its clinical and electrodiagnostic features have not been well characterized. We conducted a retrospective review of patients with PN and either Crohn's disease (CD) or ulcerative colitis (UC). Eighteen patients with CD and 15 patients with UC were identified after other PN causes were excluded. Male predominance and mean age of PN presentation in the fifties was seen in both groups. Demyelinating neuropathy (CIDP or MMN) occurred in close to 30% of the patients, in a higher percentage of women, than in the non-demyelinating patients. One-third of CD and UC patients had small-fibre or large-fibre sensory axonal PN, while approximately 40% of the CD and UC patients had large-fibre axonal sensorimotor PN. PN symptoms began earlier in the course of CD than in UC (P < 0.05). Patients with large-fibre axonal PN were older than patients with small-fibre sensory axonal PN (P < 0.05). Close to 60% of each group received immunotherapy with different agents. Half of those treated with CD and 40% with UC had demyelinating PN. Most of the patients who completed immunotherapy in both groups improved; all the patients with demyelinating neuropathy had either moderate or major improvement. The PN syndromes in IBD patients are diverse. Demyelinating forms may occur at any time, but early in the IBD course, pure sensory neuropathy is more common. Response to immunotherapy may occur in both demyelinating and axonal neuropathies

The extra-intestinal manifestations of celiac disease (CD), including ataxia and peripheral neuropathy, are increasingly being recognized as the presenting symptoms of this autoimmune disease. Although there is a greater understanding of the pathogenesis of the intestinal lesions in CD the mechanisms behind the neurologic manifestations of CD have not been elucidated. In this article, the authors review the cellular and molecular mechanisms behind the histopathologic changes in the intestine, discuss the presentation and characteristics of neurologic manifestations of CD, review the data on the mechanisms behind these manifestations, and discuss the diagnosis and treatment of CD. Molecular mimicry and intermolecular help may play a role in the development of neurologic complications

Neurologic complications of celiac disease (CD) include ataxia and peripheral neuropathy, which can be the presenting symptoms and signs. Early diagnosis and intervention could prevent development of further neurologic and systemic complications. Questions remain regarding the prevalence of the neurologic complications, the pathophysiological mechanisms, and the effectiveness of therapy or response to a gluten-free diet

Neurological syndromes that follow vaccination or infection are often attributed to autoimmune mechanisms. We report six patients who developed neuropathy or cognitive impairment, within several days to 2 months, following vaccination with the OspA antigen of Borrelia burgdorferi. Two of the patients developed cognitive impairment, one chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy, one both cognitive impairment and CIDP, and one cognitive impairment and sensory axonal neuropathy. The patients with cognitive impairment had T2 hyperintense white matter lesions on magnetic resonance imaging. The similarity between the neurological sequelae observed in the OspA-vaccinated patients and those with chronic Lyme disease suggests a possible role for immune mechanisms in some of the manifestations of chronic Lyme disease that are resistant to antibiotic treatment

The objective of this study was to report that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) can present with a clinical picture of cryptogenic sensory neuropathy. Patients with distal sensory neuropathy and electrodiagnostic studies that are minimally abnormal or consistent with an axonal pathology are usually diagnosed as having cryptogenic sensory neuropathy if no cause for neuropathy can be found. Some of these patients, however, may have sensory CIDP. We reviewed the records of eight patients with CIDP, diagnosed by sural nerve biopsy, who presented with sensory neuropathy and electrodiagnostic studies that were minimally abnormal or revealed changes consistent with axonal neuropathy. All patients reported distal numbness and paresthesias and, on examination, had predominantly large fiber distal sensory loss and normal muscle strength. In most patients, deep tendon reflexes were reduced or absent. Sural nerve biopsies in all patients were consistent with chronic myelinopathy, with quantitative teased fiber analysis revealing segmental remyelination in 13-40% of the fibers. The four patients who received IVIg therapy had improved sensation and gait. Of the remaining four patients, one is being followed, one had spontaneous remission, one was lost to follow-up, and one, with contraindications to therapy, reported disease progression. Sensory CIDP may present as cryptogenic sensory polyneuropathy with normal or axonal electrophysiologic features. Sural nerve biopsy should be considered in patients with progressive, predominantly large fiber sensory neuropathy of otherwise unknown etiology, as they may have sensory CIDP that responds to therapy