Effect of intravenous immunoglobulin on cerebellar ataxia and neuropathic pain associated with celiac disease.

BACKGROUND: Cerebellar syndrome and small fiber neuropathy may complicate celiac disease (CD) and may be resistant to a strict gluten-free diet. METHODS: Case series. RESULTS: We report three patients with biopsy-proven CD who developed cerebellar ataxia and neuropathic pain despite strict adherence to a gluten-free diet. A small fiber neuropathy was suggested by skin biopsy findings in two patients. All patients' symptoms, including small fiber neuropathy symptoms, responded to treatment with intravenous immunoglobulin (IVIG). Discontinuation of IVIG in two patients resulted in worsened ataxia that reversed after resumption of IVIG. CONCLUSION: Intravenous immunoglobulin may be effective in treating cerebellar ataxia and small fiber neuropathy associated with CD, suggesting an immune pathogenesis. Further prospective, controlled studies are necessary to determine the long-term response to IVIG or other immunomodulation therapy.

Non-length dependent small fibre neuropathy/ganglionopathy.

OBJECTIVE: To describe the clinical and laboratory features of a painful non-length dependent, small fibre ganglionopathy (SFG). BACKGROUND: The syndrome of generalised SFG with early involvement of the face, trunk or proximal limbs is not well recognised and contrasts with the burning feet syndrome of small fibre neuropathy (SFN) and classical large fibre features of sensory ganglionopathy. METHODS: Retrospective case review including skin biopsies from four neuromuscular centres. Patients with pre-existing diseases associated with ganglionopathies were excluded. RESULTS: 12 men and 11 women, with an average age of 50 years, were studied. Neuropathic pain developed over days in eight and over months in the other patients. The face (n = 12), scalp (n = 10), tongue (n = 6), trunk (n = 15) and acral extremities (n = 21) were involved. Symptoms began in the hands or face before the legs in 10. The pain was characterised as burning (n = 22), prickling (n = 13), shooting (n = 13) or allodynic (n = 11). There was loss of pinprick sensation in affected regions in 19, with minimal or no loss of large fibre sensibility. Laboratory findings included abnormal glucose metabolism in six patients, Sjögren syndrome in three and monoclonal gammopathy, sprue and hepatitis C infection in one each, with the remainder idiopathic. Sensory nerve action potentials were normal in 12 and were reduced in the hands but normal in the legs in six. Skin biopsy in 14 of 17 showed reduced nerve fibre density in the thigh equal to or more prominent than in the calf. Two of seven patients improved with immune therapies, 13 symptomatically with analgesic medications and the remainder had little improvement. Ten considered the pain disabling at the last follow-up (mean 2 years). CONCLUSION: The pattern of symmetric, non-length dependent neuropathic pain with face and trunk involvement suggests a selective disorder of the dorsal ganglia cells subserving small nerve fibres. It can be distinguished from distal SFN. A potential metabolic or immune process was detected in half of the cases and the disorder was often refractory to treatment.

Anti-MAG/SGPG associated neuropathy does not commonly cause distal nerve temporal dispersion.

Patients with anti-myelin associated glycoprotein (anti-MAG) neuropathy have uniform slowing without temporal dispersion, but do usually have disproportionately distal slowing. We evaluated distal compound muscle action potential (CMAP) dispersion in 29 patients with anti-MAG/sulphated glucuronyl paragloboside (SGPG) neuropathy (titres > or = 12,800). Among 138 motor responses, 15% (tibial), 7.3% (peroneal), 10.7% (median) and 13.8% (ulnar) had distal CMAP duration > 9 ms. Disproportionate distal slowing with normal distal CMAP duration in the arms may be useful to differentiate chronic inflammatory demyelinating polyneuropathy from anti-MAG/SGPG associated neuropathy.

Characteristics of patients with sensory neuropathy diagnosed with abnormal small nerve fibres on skin biopsy.

Clinical, laboratory and electrodiagnostic (EDX) characteristics of 62 patients with sensory neuropathy with abnormal skin biopsies were reviewed. Reduced epidermal nerve fibre density (ENFD) was seen in 71% and morphological changes with normal ENFD were seen in 29% of the patients. Patients with small fibre sensory neuropathy may have associated large fibre loss undetected by routine EDX. Identified associations included abnormal glucose metabolism, Lyme vaccination, monoclonal gammopathy, vitamin B12 deficiency, coeliac disease, and diseases of the connective tissue, inflammatory bowel and thyroid. Sensory neuropathy remained undetermined in 50% of the patients.

Multifocal axonal polyneuropathy in celiac disease.

The authors report six patients with multifocal axonal polyneuropathy and the subsequent diagnosis of celiac disease (CD). Five patients did not improve or had only modest improvement following dietary intervention or immune therapies; one patient with marked weakness and mild electrodiagnostic findings had complete resolution of the neuropathy following immunomodulatory therapy. CD may be a cause of multifocal axonal polyneuropathy.

Correlation of clinical and demyelinating features in patients with neuropathy of otherwise unknown etiology.

PURPOSE: To correlate the electrodiagnostic and clinical features of patients with demyelinating abnormalities and neuropathy of otherwise unknown etiology. METHODS: We examined the records of patient with demyelinating abnormalities and no other cause for neuropathy that were evaluated in our electrophysiology laboratory over the course of a year, to correlate the clinical and electrodiagnostic features. RESULTS: Eight percent of all patients had one or more demyelinating abnormalities. Demyelinating features were significantly more numerous in generalized or asymmetric neuropathy than in distal polyneuropathy. The peroneal nerve was the most commonly affected in all phenotypes, and none of the patients with distal neuropathy had F-wave prolongation in the demyelinating range. CONCLUSIONS: The number and type of demyelinating abnormalities in patients with polyneuropathy vary with the clinical phenotype. The clinical presentation should be considered in developing or evaluating electrodiagnostic criteria for demyelinating neuropathies.

Mechanisms underlying celiac disease and its neurologic manifestations.

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.

Peripheral neuropathy in patients with inflammatory bowel disease.

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.

Celiac neuropathy.

BACKGROUND: Celiac disease (CD) is a chronic inflammatory enteropathy resulting from sensitivity to ingested gluten. Neurologic complications are estimated to occur in 10% of affected patients, with ataxia and peripheral neuropathy being the most common problems. The incidence and clinical presentation of patients with CD-associated peripheral neuropathy have not previously been investigated. OBJECTIVE: To determine the incidence of CD in patients with neuropathy and to characterize the clinical presentation. METHODS: The records of 20 patients with neuropathy and biopsy-confirmed CD were reviewed. RESULTS: Six of the 20 patients had neuropathic symptoms alone without gastrointestinal involvement, and neuropathic symptoms preceded other CD symptoms in another 3 patients. All patients had burning, tingling, and numbness in their hands and feet, with distal sensory loss, and nine had diffuse paresthesias involving the face, trunk, or lumbosacral region. Only two had weakness. Results of electrophysiologic studies were normal or mildly abnormal in 18 (90%) of the patients. Sural nerve biopsies, obtained from three patients, revealed mild to severe axonopathy. Using the agglutination assay, 13 (65%) of the patients were positive for ganglioside antibodies. Excluding patients who were referred with the diagnosis of celiac neuropathy, CD was seen in approximately 2.5% of all neuropathy patients and in 8% of patients with neuropathy and normal electrophysiologic studies seen at our center. CONCLUSION: CD is commonly associated with sensory neuropathy and should be considered even in the absence of gastrointestinal symptoms.

Clinical course of gamma-hydroxybutyrate overdose.

STUDY OBJECTIVE: To describe the clinical characteristics and course of gamma-hydroxybutyrate (GHB) overdose. METHODS: We assembled a retrospective series of all cases of GHB ingestion see in an urban public-hospital emergency department and entered in a computerized database January 1993 through December 1996. From these cases we extracted demographic information, concurrent drug use, vital signs, Glasgow Coma Scale (GCS) score, laboratory values, and clinical course. RESULTS: Sixty-one (69%) of the 88 patients were male. The mean age was 28 years. Thirty-four cases (39%) involved coingestion of ethanol, and 25 (28%) involved coingestion of another drug, most commonly amphetamines. Twenty-five cases (28%) had a GCS score of 3, and 28 (33%) had scores ranging from 4 through 8. The mean time to regained consciousness from initial presentation among nonintubated patients with an initial GCS of 13 or less was 146 minutes (range, 16-389). Twenty-two patients (31%) had an initial temperature of 35 degrees C or less. Thirty-two (36%) had asymptomatic bradycardia; in 29 of these cases, the initial GCS score was 8 or less. Ten patients (11%) presented with hypotension (systolic blood pressure < or = 90 mm Hg); 6 of these patients also demonstrated concurrent bradycardia. Arterial blood gases were measured in 30 patients; 21 had a PCO2 of 45 or greater, with pH ranging from 7.24 to 7.34, consistent with mild acute respiratory acidosis. Twenty-six patients (30%) had an episode of emesis; in 22 of these cases, the initial GCS was 8 or less. CONCLUSION: In our study population, patients who overdosed on GHB presented with a markedly decreased level of consciousness. Coingestion of ethanol or other drugs is common, as are bradycardia, hypothermia, respiratory acidosis, and emesis. Hypotension occurs occasionally. Patients typically regain consciousness spontaneously within 5 hours of the ingestion.

Development of ventricular fibrillation after intravenous calcium chloride administration in a patient with supraventricular tachycardia.

The i.v. administration of calcium before or shortly after treatment of supraventricular tachycardia with verapamil has been suggested to counteract a hypotensive response to verapamil. We discuss the case of a patient who presented to the emergency department with an accelerated wide-complex tachycardia and minimal symptoms. Immediately after i.v. administration, of 1 g calcium chloride as pretreatment for verapamil administration, ventricular fibrillation developed. Emergency physicians should be aware of potential dangers after the administration of i.v. calcium preparations when trying to prevent known hypotensive side effects of i.v. verapamil administration.

Gas gangrene from subcutaneous insulin administration.

A case of gas gangrene that caused intractable shoulder pain refractory to narcotics in an immunocompromised host is presented. Gas gangrene has been associated with severe trauma involving penetrating wounds, compound fractures, extensive soft-tissue injury, intramuscular injection of epinephrine, and interruption of arterial blood supply. This case describes an elderly insulin-dependent diabetic woman who developed gas gangrene in her arm and leg at the site of her subcutaneous insulin injections. The responsible organism was Clostridium septicum. Emergency medicine physicians must consider gas gangrene Clostridium infection in immunocompromised individuals without evidence of trauma who present with localized and intractable pain.