Louis H. Weimer

Quantitative sensory testing Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). Methods: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. Results: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. Conclusions: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.

Electrophysiologic studies in critical illness associated weakness: myopathy or neuropathy--a reappraisal.

OBJECTIVE Unexplained weakness in critically ill patients is recognized with increasing frequency. However, it is debated whether the condition is a peripheral neuropathy or a myopathy. Diagnostic difficulties can arise from multiple sources that are not generally a factor in other neuromuscular conditions. Conventional electrodiagnostic techniques may provide only non-specific data, clinical examination is often hampered, and muscle biopsy is not a practical screening tool. METHOD To improve diagnostic yield, we studied 22 consecutive patients with critical illness associated weakness with additional electrodiagnostic techniques, including direct muscle stimulation, quantitative electromyography, and motor unit number estimation. RESULTS The applied techniques supported an underlying myopathy in all the patients examined. The diagnosis was confirmed by muscle biopsy in 9 patients. Additional lesser features of neuropathy were concomitantly present in one patient who also underwent sural nerve biopsy. CONCLUSIONS The study suggests that myopathy is much more common than polyneuropathy in critical illness. Suspicion of this entity should be high in this setting even without exposure to corticosteroids or non-depolarizing blocking agents.

Medication-induced exacerbation of neuropathy in Charcot Marie Tooth Disease

Toxin or medication-induced worsening of preexisting peripheral neuropathy is a generally accepted but not well-studied phenomenon in humans. Drug-induced exacerbation of Charcot Marie Tooth disease (CMT) neuropathy is a common concern; a list of potential drugs to avoid is maintained by the CMT Association but with limited direct evidence or advice on relative risk. An extensive literature search for reported cases of drug effects in CMT patients found the vast majority concerned excessive vincristine toxicity in patients with undiagnosed demyelinating forms of CMT, many after 1 or 2 doses. The CMT North American database was also queried for all drug-related effects. All but one drug cited as worsening neuropathy was present on a compiled inclusive list. These results and other available evidence were used to develop a revised risk stratified list for CMT patients and clinicians to consult prior to discussing risk to benefit ratios and making treatment decisions.

Antisulfatide antibodies in neuropathy Clinical and electrophysiologic correlates

Objective: To investigate the clinical and electrophysiologic characteristics of the neuropathy associated with elevated serum antisulfatide antibodies. Methods: Clinical, electrophysiologic, morphologic, and laboratory data of 25 patients with significantly elevated (>25,600) antisulfatide antibodies were reviewed. Results: Four groups were distinguished based on clinical and electrophysiologic data: Group 1, eight patients with predominantly small fiber sensory neuropathy (32%); Group 2, five patients with mixed large and small fiber sensory neuropathy (20%); Group 3, seven patients with axonal sensorimotor neuropathy (28%); and Group 4, three patients with demyelinating sensorimotor neuropathy (12%). One additional patient had mononeuritis multiplex and one had ALS. An immunoglobulin M (IgM) monoclonal gammopathy was found in 30% of the patients tested, but not in any of the Group 1 patients with small fiber sensory neuropathy. Serum IgM level was elevated in 12 patients, of whom six had a concomitant monoclonal gammopathy. Morphologic studies in five patients showed predominantly axonal degeneration, with three of the patients also exhibiting additional features of demyelination. Conclusions: Antisulfatide antibodies are associated with several subtypes of peripheral neuropathy. Predominantly sensory or sensorimotor axonal neuropathies are most common in this series, with the sensory component either small fiber or mixed fiber type. A smaller demyelinating group indistinguishable from patients with chronic inflammatory demyelinating polyradiculopathy was also seen. One third of patients had a concomitant IgM monoclonal gammopathy, and approximately one half had elevated serum IgM.

The utility of segmental nerve conduction studies in ulnar mononeuropathy at the elbow

Patients with clinical evidence of ulnar mononeuropathy at the elbow may have normal routine motor and sensory nerve conduction studies, suggesting a low sensitivity for these methods. Other, more specialized techniques may have a higher sensitivity, increasing diagnostic yield, and provide more specific localization of the lesion. We compared the sensitivity and specificity of ulnar segmental nerve conduction studies (SgNCS or “inching”) at 2‐cm intervals with those of routine ulnar motor and sensory studies. We studied 21 arms with symptoms or signs of ulnar neuropathy and 25 asymptomatic control arms. SgNCS proved significantly more sensitive than more routine studies in diagnosing ulnar neuropathy at the elbow, with a sensitivity of 81%, whereas motor conduction velocity in a longer (10–14 cm) segment across the elbow was the next most sensitive at 24%. Recording from the first dorsal interosseous muscle did not improve sensitivity when compared with recording from the abductor digiti quinti. Short SgNCS significantly improves detection of ulnar mononeuropathy at the elbow and should be considered when routine studies are negative and clinical suspicion remains high. Muscle Nerve 27: 46–50, 2003

Randomized controlled phase II trial of glatiramer acetate in ALS

The authors conducted a randomized controlled trial to test the safety and immunology of glatiramer acetate in ALS. Twenty treated patients were randomly assigned to daily or biweekly injections. Ten control patients were selected from another trial and followed up concurrently. Injection reactions were the only common adverse event (p = 0.01). Treated patients showed enhanced lymphocyte proliferation (p = 0.02). The safety profile and immune effects support conducting larger trials of dose selection and efficacy.

Experience with the Awaji Island modifications to the ALS diagnostic criteria

Amyotrophic lateral sclerosis (ALS) remains a clinical diagnosis without validated biomarkers. To increase diagnostic sensitivity, an expert group modified the Airlie House diagnostic criteria and formulated new recommendations at a meeting on Awaji Island. Our retrospective analysis of patients referred over a 6‐month period to the electromyography (EMG) laboratory for suspected motor neuron disease (MND) showed a higher agreement of the Awaji modifications than the Airlie House criteria with the clinical diagnosis of ALS. Muscle Nerve, 2010

Serial studies of carpal tunnel syndrome during and after pregnancy

Carpal tunnel syndrome (CTS) is a frequent and underdiagnosed complication of pregnancy. Conservative therapies are common initial measures, but data on the course of improvement are limited. We report a case of pregnancy‐associated CTS with unusually detailed serial electrophysiologic studies before and after wrist splinting. Physiologic measures reached a nadir and then rapidly improved following conservative therapy, paralleling clinical improvement. Responses took between 6 and 20 months postpartum to approach baseline values.

Syncope and orthostatic intolerance

Syncope and orthostatic intolerance remain common and significant clinical problems with many undocumented, misdiagnosed, or cryptogenic cases. Careful clinical assessment and application of advancing laboratory support can further improve diagnosis and treatment. Despite the depth of existing research into these common problems, many underlying mechanisms remain unproven.

Autonomic Symptoms in Carriers of the m.3243A>G Mitochondrial DNA Mutation

BACKGROUND The m.3243A>G mutation can cause multisystem medical problems and can affect the autonomic nervous system. OBJECTIVE To study the frequency and spectrum of autonomic symptoms associated with the m.3243A>G mitochondrial DNA point mutation. Design, Setting, and Patients We studied a cohort of 88 matrilineal relatives from 40 families, including 35 fully symptomatic patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), 53 carrier relatives, and 16 controls using a questionnaire based on existing standard instruments for the evaluation of autonomic dysfunction. We compared the questionnaire with an expert evaluation. We compared data among the 3 groups using the Mantel-Haenszel chi(2) test to determine the statistical significance of differences between groups. RESULTS Mutation carriers frequently had symptoms of autonomic dysfunction, specifically gastrointestinal and orthostatic intolerance. CONCLUSIONS Carriers of the m.3243A>G mutation have frequent autonomic symptoms. The m.3243A>G mutation should be considered as an etiological factor in patients with autonomic dysfunction and a medical or family history suggestive of mitochondrial disease. Because some autonomic symptoms are treatable, early detection and proactive management may mitigate the burden of morbidity.