Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications.

AIMS: The Michigan Neuropathy Screening Instrument (MNSI) is used to assess distal symmetrical peripheral neuropathy in diabetes. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes. The purpose of this study was to evaluate the performance of the MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type 1 diabetes and to develop new scoring algorithms. METHODS: The MNSI was performed by trained personnel at each of the 28 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications clinical sites. Neurologic examinations and nerve conduction studies were performed during the same year. Confirmed clinical neuropathy was defined by symptoms and signs of distal symmetrical peripheral neuropathy based on the examination of a neurologist and abnormal nerve conduction findings in ≥ 2 anatomically distinct nerves among the sural, peroneal and median nerves. RESULTS: We studied 1184 subjects with Type 1 diabetes. Mean age was 47 years and duration of diabetes was 26 years. Thirty per cent of participants had confirmed clinical neuropathy, 18% had ≥ 4 and 5% had ≥ 7 abnormal responses on the MNSI questionnaire, and 33% had abnormal scores (≥ 2.5) on the MNSI examination. New scoring algorithms were developed and cut points defined to improve the performance of the MNSI questionnaire, examination and the combination of the two. CONCLUSIONS: Altering the cut point to define an abnormal test from ≥ 7 abnormal to ≥ 4 abnormal items improves the performance of the MNSI questionnaire. The MNSI is a simple, non-invasive and valid measure of distal symmetrical peripheral neuropathy in Type 1 diabetes.

Chlorpyrifos exposure and biological monitoring among manufacturing workers.

AIM: To use biological monitoring data to evaluate the soundness of job based exposure classifications. METHODS: The authors studied 52 chlorpyrifos manufacturing workers and 60 referent workers to compare chlorpyrifos exposure estimations from job titles and work areas to urinary excretion of 3,5,6 trichloro-2-pyridinol (TCP), a metabolite of chlorpyrifos. Work history records and industrial hygiene monitoring data were used to establish cumulative interim exposure. Chlorpyrifos exposure during the study year was assessed biologically by urinary excretion of TCP. RESULTS: Exposure as measured by three urinary TCP samples was significantly higher among the chlorpyrifos workers (188 microg/l) than it was for the referent subjects (7 microg/l). Urinary TCP also correlated well with specific exposure categories of negligible (0.73-1.98 mg/m3 days), low (1.99-4.91 mg/m3 days), and moderate (4.92-15.36 mg/m3 days). The weighted Kappa coefficient was 0.80 (95% CI 0.72 to 0.87) for the mean TCP over the study period. CONCLUSIONS: The estimates of chlorpyrifos exposure based on job classifications and industrial hygiene measurements were significantly related to urinary TCP excretion, indicating that the ambient estimates are useful for providing exposure estimates among chlorpyrifos manufacturing workers.

Juvenile progressive bulbar palsy. Clinical and electrodiagnostic findings.

Differentiation of juvenile progressive bulbar palsy from bulbar myasthenia gravis is difficult. Characteristics of both may include ocular involvement, fluctuant course, abnormal fatigability, and normal acetylcholine receptor (AChR) antibody titers. Electrodiagnostic evaluation may demonstrate moment-to-moment variability in motor unit action potential amplitude, fibrillation potentials, and decremental motor evoked responses. Increased jitter with blocking may be the most prominent electrodiagnostic abnormality in either disorder, even in asymptomatic extremity muscles. Complete paralysis of facial muscles with electrical silence on needle electromyography, low-amplitude facial evoked responses without a decrement to repetitive stimulation, increased jitter and fiber density in asymptomatic extremity muscles, and normal AChR antibody levels suggested juvenile progressive bulbar palsy in two patients initially thought to have bulbar myasthenia. Early differentiation of these disorders is important because of therapeutic, genetic, and prognostic implications.

Unusual cause of 'piriformis muscle syndrome'.

The piriformis muscle syndrome is a controversial "clinical" syndrome primarily characterized by signs and symptoms of sciatic nerve compression at the region of the piriformis muscle as it passes through the greater sciatic notch. The syndrome is often referred to; however, cases are rarely reported, and it is generally an uncommon diagnosis. Of those cases reported, the incidence is six times more frequent in females than in males, and is typically temporally related to minor pelvic or buttock trauma. We describe a case of a 40-year-old woman presenting with signs and symptoms suggestive of piriformis muscle syndrome following a gynecologic procedure performed in the dorsal lithotomy position. Electromyographic findings were consistent with this clinical entity. Operative exploration, however, revealed the source of neural compression to be a pseudoaneurysm of the inferior gluteal artery adjacent to the piriformis muscle. The diagnostic features of this clinical syndrome are discussed.

Myelomalacia and hypoglycorrhachia in malignant atrophic papulosis.

A 25-year-old man with the skin lesions of malignant atrophic papulosis had clinical and electrodiagnostic evidence of a multifocal asymmetric myelomalacia or polyradiculopathy in association with elevated CSF protein and hypoglycorrhachia. Autopsy findings included widespread infarctions and necrosis of brain, brainstem, and spinal cord. The combined clinical and laboratory findings were similar to those seen in systemic lupus erythematosus, sarcoidosis, or meningeal carcinomatosis. Thus, malignant atrophic papulosis should be added to the differential diagnosis of either polyradiculopathy or myelomalacia.

Presentation and initial clinical course in patients with chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients without and with monoclonal gammopathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may occur in association with a monoclonal gammopathy of undetermined significance (MGUS) or a variety of other systemic illnesses. It is not known if the clinical features of CIDP are altered by the presence of an MGUS. We compared demographic features, clinical presentation, improvement and outcome after initial treatment, and electrodiagnostic features of a group of 77 patients with idiopathic CIDP (CIDP-I, no associated systemic illness) with 26 patients with CIDP in whom an MGUS was found during evaluation of the neuropathy (CIDP-MGUS). Patients with CIDP-MGUS had, on average, a more indolent course and less severe weakness than patients with CIDP-I, despite similar motor conduction studies. CIDP-MGUS patients also demonstrated less functional impairment, more frequent sensory loss, and more abnormal sensory conduction studies than patients with CIDP-I. Because of the greater improvement of CIDP-I patients with treatment, both groups had similar outcomes from their initial episodes of weakness. Subgroup analysis of CIDP-MGUS patients did not demonstrate differences between groups with IgM and IgG or IgA gammopathies.

Familial recurrent Bell's palsy with ocular motor palsies.

We studied a family in which the father and 7 of 10 children had episodes of Bell's palsy. Five of the eight affected family members also had ocular motor palsies. Facial nerve and blink reflex studies in four affected siblings demonstrated asymmetrically reduced amplitude of evoked responses without delayed conduction. EMG revealed signs of chronic denervation and reinnervation in all four patients; two had synkinesis. Three siblings had diabetes mellitus, but with no clinically evident polyneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients with and without an associated monoclonal gammopathy.

We reviewed our data from patients with the clinical diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventy patients had no demonstrable underlying disease to account for their polyneuropathy and were classified as idiopathic CIDP (CIDP-I). We detected a monoclonal gammopathy of uncertain significance (MGUS) in 30 patients who were classified as CIDP-MGUS; 17 had an IgG gammopathy, 12 an IgM gammopathy, and one an IgA gammopathy. Compared with CIDP-I patients, CIDP-MGUS patients were older and slightly more likely to be males. When compared with patients with an MGUS but without polyneuropathy reported in the literature, CIDP-MGUS patients had similar distributions of age, sex, and immunoglobulin class. There were no significant differences in motor and sensory nerve conduction measures between CIDP-I and CIDP-MGUS patients, nor between CIDP-MGUS patients with IgM and those with IgG or IgA gammopathy. Strict electrodiagnostic criteria for primary demyelination were fulfilled by 54% of CIDP-I patients and 40% of CIDP-MGUS patients, but these were not significantly different. Our study suggests that (1) the demographic features and immunoglobulin class distribution of CIDP-MGUS patients largely reflect those of patients with an MGUS, but without polyneuropathy, (2) CIDP-MGUS patients as a group cannot be distinguished from CIDP-I patients on the basis of nerve conduction studies, and (3) IgM CIDP-MGUS patients cannot be distinguished from those with other immunoglobulin classes.

Neuromuscular transmission in rheumatoid arthritis, with and without penicillamine treatment.

Electroneuromyographic studies were performed on patients with rheumatoid arthritis, some of whom were received penicillamine, to determine whether a subclinical defect of neuromuscular transmission existed. There were no significant differences between patients and controls with respect to nerve conduction studies or repetitive ulnar nerve stimulation. Four patients (three receiving penicillamine) demonstrated mild neurogenic changes distally on needle electromyography. Mean jitter was slightly higher for patients receiving penicillamine than in other patients or controls, but the differences were not significant. No significant correlations existed between of the studies and daily, cumulative, or average penicillamine dosage. A significant positive correlation (p less than 0.001) existed between jitter and duration of disease in patients receiving penicillamine. Results were consistent with the hypothesis that penicillamine predisposes certain individuals to develop myasthenia gravis rather than interfering directly with neuromuscular transmission.

Sneddon's syndrome: an antiphospholipid antibody syndrome?

A 44-year-old woman with livedo reticularis, multiple ischemic strokes, and transient ischemic attacks (Sneddon's syndrome) had antiphospholipid antibodies--the lupus anticoagulant and anticardiolipin antibodies. This patient provides support for the hypothesis that these antibodies are involved in the pathogenesis of this rare but now potentially treatable disorder.

Penicillamine-associated myasthenia gravis.

Electroneuromyographic studies have been reported as abnormal in only 9 of 23 cases of penicillamine-associated myasthenia gravis (MG). We report a patient with rheumatoid arthritis who developed clinical and electrodiagnostic evidence of myasthenia 7 months after beginning penicillamine therapy. Six months after discontinuing penicillamine, it was possible to discontinue anticholinesterase medications. With clinical improvement, electrodiagnostic studies (including single-fiber electrmyography) improved, serum antibody titers to human muscle acetylcholine receptor fell, and lymphocytes became more responsive to the nonspecific mitogen phytohemagglutinin. Evidence suggests that penicillamine-associated myasthenia is a distinct syndrome rather than the chance occurrence of two diseases. This syndrome is clinically and electrophysiologically distinguishable from idiopathic myasthenia only by the high remission rate after penicillamine is discontinued.

Asymptomatic sensorimotor polyneuropathy in workers exposed to elemental mercury.

Neurologic and electrodiagnostic evaluations and urine mercury level determinations were performed on 138 chlor-alkali plant workers, some of whom were chronically exposed to inorganic mercury vapor. Eighteen subjects had a mild polyneuropathy on clinical examination. These subjects had significantly (p less than 0.05) elevated urine mercury indexes, reduced sensation on quantitative testing, prolonged distal latencies with reduced sensory evoked response amplitudes, and increased likelihood of abnormal needle electromyography compared with the remaining 120 subjects. Similar results were found for subgroups matched by sex and age. We conclude that elemental mercury exposure is associated with a sensorimotor polyneuropathy of the axonal type; the degree of neurologic impairment appears related to the magnitude of exposure.

Nerve conduction measures in mild diabetic neuropathy in the Early Diabetes Intervention Trial: the effects of age, sex, type of diabetes, disease duration, and anthropometric factors. Tolrestat Study Group for the Early Diabetes Intervention Trial.

We evaluated nerve conduction measures at baseline from 429 patients enrolled in a multicenter diabetic neuropathy study. We defined neuropathy by using recently proposed recommendations but included only patients who had measurable sural and peroneal responses and quantitative vibration thresholds. Patients with type II diabetes were older than type I patients (54.5 versus 39.1 years), were heavier (body mass index [BMI] of 30.9 versus 25.5 kg/m2, and in general had lower evoked amplitudes. The effects of diabetes type upon nerve conduction measures disappeared when age and BMI were included in regression models. The men had lower amplitudes and conduction velocities and longer latencies than the women. The effect of gender was greatly reduced when height was included in the regression models, but gender continued to be a significant predictor of median sensory amplitude, most conduction velocities, and most latencies in these models. The relationships between nerve conduction measures and age, sex, and anthropometric factors were similar for patients with type II, but not those with type I, diabetes to the relationships reported for normal subjects. This may be a result of greater homogeneity with respect to degree of neuropathy for type II patients than for type I patients. These findings are important in designing and interpreting clinical studies of diabetic neuropathy.

Acute sensory neuropathy-neuronopathy from pyridoxine overdose.

We report two patients who developed an acute, profound, and permanent sensory deficit after treatment with massive doses of parenteral pyridoxine. Aside from rapid onset, their clinical picture resembles that described in chronic pyridoxine neurotoxicity. It also is consonant with experimental models of acute pyridoxine intoxication and is probably secondary to a sensory ganglion neuronopathy. These patients also had transient autonomic dysfunction, mild weakness, nystagmus, lethargy, and respiratory depression. These previously undocumented features may be attributable to either the preservative used in the parenteral pyridoxine preparation or to the exceptionally high doses of pyridoxine these patients received.

Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease.

We studied a patient with an IgM M-protein and lower motor neuron disease to identify the antigens to which the M-protein bound. Gangliosides from peripheral nerve and spinal cord were separated by high-performance thin-layer chromatography and immunostained with the patient's serum. The serum IgM immunostained two gangliosides identified as GM1 and GD1b, and immunostaining was specific for the M-protein light chain type. IgM-binding to the two gangliosides was detectable by ELISA at serum dilutions of greater than 1:10,000, and the M-protein was selectively immunoabsorbed by liposomes containing GM1 or GD1b. The IgM M-protein also bound to asialo-GM1, indicating reactivity to the galactosyl(beta 1-3)N-acetylgalactosaminyl moiety shared by GM1, GD1b, and asialo-GM1.

Obturator mononeuropathy caused by pelvic cancer: six cases.

OBJECTIVE: To report the clinical and pelvic CT findings in six patients with obturator mononeuropathy caused by cancer. DESIGN: A clinical case series of six patients followed for 2 months to 10 years (one patient lost to follow-up). SETTING: Three referral centers. PATIENTS: Three men and three women, ages 52 to 81 years. Three patients had transitional cell carcinoma of the bladder, and one patient each had pelvic papillary carcinoma, carcinoma of unknown origin, and lymphoma. MAIN RESULTS: In each patient, symptoms of obturator mononeuropathy were the sole presenting sign of new or recurrent pelvic cancer. Three patients had ipsilateral leg edema in addition to the typical sensory and motor findings of obturator mononeuropathy. Tumor sites detected on pelvic CT that correlated with obturator nerve compression or infiltration, singly or in combination, included the posterolateral wall of the upper pelvis or midpelvis, the anterior wall of the lower pelvis, and the external obturator and pectineus muscles extrinsic to the bony pelvis. Antineoplastic treatment provided symptomatic relief in four patients. CONCLUSIONS: Pelvic CT or MRI should be performed to exclude pelvic tumor in patients with obturator mononeuropathy if there is no temporal association with pelvic trauma or intra-abdominal, pelvic, or hip surgery.

Summated auditory evoked potentials in the cerebellum and inferior colliculus in the young rat.

The summated auditory evoked responses recorded at the superior surface and depth of the cerebellum of the young rat had a similar latency and configuration as did summated auditory evoked potentials in the inferior colliculus. Electric stimulation of the inferior colliculus did not evoke a response (other than the shock-artifact response) at the cerebellum. Stimulation of the cerebellum did not modify the evoked responses to click in the inferior colliculus (unless current levels were large enough to cause current spread to the brain stem). There is insufficient evidence to conclude that the cerebellum has an auditory receiving area in the young rat.

Measurements of autonomic function before, during, and after transcutaneous stimulation in patients with chronic pain and in control subjects.

Transcutaneous stimulation (TCS) has been reported to modify peripheral blood flow, skin temperature, blood pressure, and heart rate, all of which are under the influence of the autonomic nervous system (ANS). In 20 patients with intractable pain and in 10 control subjects, TCS was not found to alter significantly any of the observed properties of ANS function of control subjects or patients, except to decrease skin impedance in the patient group after the stimulation. Patients reporting pain relief during TCS were found to have significantly higher systolic blood pressure under all test conditions than patients reporting no pain relief (p less than 0.05). No other significant differences were found between these two groups. Finally, in the patients, no significant localized autonomic changes were demonstrated in the painful area by comparison with the homologous body part.

Prognosis in long-term immunosuppressive treatment of refractory chronic inflammatory demyelinating polyradiculoneuropathy.

Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) frequently includes use of immunosuppressive agents. Controlled treatment trials demonstrating efficacy are available only for prednisone and therapeutic plasma exchange (TPE). When these fail to achieve lasting chemical improvement after reduction or cessation of therapy, subsequent regimens are empiric, often leading to prolonged immunosuppression. It is not possible to predict who will respond to which agent and when. Administered individually, immunosuppressive agents may pose an acceptable risk, but cumulative effects of multiple agents in refractory patients may suppress the immune system and contribute to increased morbidity and mortality. Treatment difficulties with refractory CIDP patients have not been emphasized, and long-term effects of immunosuppression have focused on the risk of malignancy. In reviewing our clinical experience treating over 100 CIDP patients we identified approximately 20 patients who could be considered refractory to multiple immunosuppressive therapies and dependent upon long-term intermittent TPE. Two of these patients exemplify the morbidity associated with CIDP and its associated treatment. Our review of the clinical course of these patients raised issues about the use of multiple immunosuppressive agents, long-term goals, and long-term prognosis in CIDP.

Single motor unit and fiber action potentials during fatigue.

Muscle fatigue is defined as a loss of tension development during constant stimulation. Although the relationship is not well documented, muscle fatigue has been inferred from electromyogram (EMG) signals. The purpose of this study was to determine the relationship between the amplitude and duration of single motor unit action potentials (MUAPs) and the loss of tension development (fatigue) in the medial gastrocnemius muscles of cats. Single motor units were fatigued by continuous stimulation at 10 or 80 Hz or with trains of 40-Hz stimuli. When motor units were stimulated at 10 Hz and with trains at 40 Hz (low frequency), tension declined and remained depressed during recovery. The changes in the MUAP correlated poorly with changes in tension. During and after stimulation at 80 Hz (high frequency), changes in the amplitude and duration of MUAPs correlated highly with changes in tension development. Since the EMG signal is dependent on a summation and cancellation of individual MUAPs, the EMG provides a reasonable estimate of high-frequency fatigue but an unreliable measure of low-frequency fatigue.