Inter-rater reliability determination for two tests of ulnar nerve conduction across the elbow.

INTRODUCTION: The inter-rater variability in determination of ulnar nerve conduction across the elbow compromises test accuracy. The extent of this variability is unknown. The objective of this study was to determine and compare inter-rater reliability of variables derived from 2 different ulnar nerve conduction studies (NCSs) across the elbow. METHODS: Two investigators performed a standard ulnar NCS and a 6-cm conduction time (Six-Centimeter Conduction Time test, SCCT) on 60 extremities of asymptomatic subjects. In the standard test, below-elbow (BE) and above-elbow (AE) stimulation points were ≥ 10 cm apart, measured along a curved path, to calculate across-elbow NCV. In SCCT, BE and AE were precisely 6 cm apart measured linearly to calculate CTE (conduction time elbow). Inter-rater reliability was assessed by means of intraclass correlation coefficients (ICC). RESULTS: ICC for across-elbow NCV and CTE were 0.726 and 0.801, respectively. CONCLUSIONS: Reliability of CTE and across-elbow NCV are similar. Shorter distances, if measured linearly, can be used to determine across-elbow ulnar nerve conduction. Muscle Nerve 55: 664-668, 2017.

Genetic polymorphisms associated with exertional rhabdomyolysis.

Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), α-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility.

Serum creatine kinase after exercise: drawing the line between physiological response and exertional rhabdomyolysis.

INTRODUCTION: In this investigation we assessed the spectrum of creatine kinase (CK) responses in military recruits undergoing basic training. METHODS: Musculoskeletal examination data, questionnaire findings, and CK levels were obtained from 499 recruits at days 0, 3, 7, and 14 of training. Correlations of CK with ethnicity, age, body mass index, exercise, muscle pain, and climate were obtained. RESULTS: None of the subjects developed clinical exertional rhabdomyolysis (ER). The mean/median serum CK values were 223/157, 734/478, 1226/567, and 667/486 IU/L at days 0, 3, 7, and 14, respectively, with a wide overall range (34-35,056 IU/L). African-American subjects had higher mean CK levels. CONCLUSIONS: CK elevations and muscle pain are common during basic training. Widely accepted laboratory diagnostic values for ER are routinely exceeded in this military recruits, suggesting that CK levels >50 times the upper limit of normal are more specific. The findings support using CK as a marker for ER. Normal laboratory reference ranges for CK should be published by ethnicity.

Investigation of the relationship between serum creatine kinase and genetic polymorphisms in military recruits.

Genetic polymorphisms may explain why certain individuals will develop exertional rhabdomyolysis (ER) or markedly elevated serum creatine kinase (CK) levels following exertion, while others in the same environment, performing the same exertion, do not. Prospectively, 499 recruits were evaluated during the initial fortnight of Army basic training. Serum CK levels were determined before and during that time. Eleven candidate genetic polymorphisms were studied and compared to CK levels. No subjects developed ER. Baseline CK was significantly greater in interleukin-6 G174C GG and myosin light chain kinase 2 (MLCK 2) AA subjects. Intertraining levels were significantly greater in angiotensin I-converting enzyme D/D and interleukin-6 GG subjects. Among African-Americans, those with MLCK2 AA had greater baseline CK (1,352 +/- 1,102.8 IU/L) than AC and CC genotypes (536.9 +/- 500.6). African-American men have the highest baseline levels and are more likely to have MLCK AA genotype. Whether this finding is associated with an increased incidence of ER requires further study.

Light therapy and supplementary Riboflavin in the SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis (FALS).

BACKGROUND AND OBJECTIVE: Familial amyotrophic lateral sclerosis (FALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and death. Mitochondrial dysfunction and oxidative stress play an important role in motor neuron loss in ALS. Light therapy (LT) has biomodulatory effects on mitochondria. Riboflavin improves energy efficiency in mitochondria and reduces oxidative injury. The purpose of this study was to examine the synergistic effect of LT and riboflavin on the survival of motor neurons in a mouse model of FALS. STUDY DESIGN/MATERIALS AND METHODS: G93A SOD1 transgenic mice were divided into four groups: Control, Riboflavin, Light, and Riboflavin+Light (combination). Mice were treated from 51 days of age until death. A single set of LT parameters was used: 810 nm diode laser, 140-mW output power, 1.4 cm(2) spot area, 120 seconds treatment duration, and 12 J/cm(2) energy density. Behavioral tests and weight monitoring were done weekly. At end stage of the disease, mice were euthanized, survival data was collected and immunohistochemistry and motor neuron counts were performed. RESULTS: There was no difference in survival between groups. Motor function was not significantly improved with the exception of the rotarod test which showed significant improvement in the Light group in the early stage of the disease. Immunohistochemical expression of the astrocyte marker, glial fibrilary acidic protein, was significantly reduced in the cervical and lumbar enlargements of the spinal cord as a result of LT. There was no difference in the number of motor neurons in the anterior horn of the lumbar enlargement between groups. CONCLUSIONS: The lack of significant improvement in survival and motor performance indicates study interventions were ineffective in altering disease progression in the G93A SOD1 mice. Our findings have potential implications for the conceptual use of light to treat other neurodegenerative diseases that have been linked to mitochondrial dysfunction.

Evaluation and management of peripheral nerve injury.

Common etiologies of acute traumatic peripheral nerve injury (TPNI) include penetrating injury, crush, stretch, and ischemia. Management of TPNI requires familiarity with the relevant anatomy, pathology, pathophysiology, and the surgical principles, approaches and concerns. Surgical repair of TPNI is done at varying time intervals after the injury, and there are a number of considerations in deciding whether and when to operate. In neurapraxia, the compound muscle and nerve action potentials on stimulating distal to the lesion are maintained indefinitely; stimulation above the lesion reveals partial or complete conduction block. The picture in axonotmesis and neurotmesis depends on the time since injury. The optimal timing for an electrodiagnostic study depends upon the clinical question being asked. Although conventional teaching usually holds that an electrodiagnostic study should not be done until about 3 weeks after the injury, in fact a great deal of important information can be obtained by studies done in the first week. Proximal nerve injuries are problematic because the long distance makes it difficult to reinnervate distal muscles before irreversible changes occur. Decision making regarding exploration must occur more quickly, and exploration using intraoperative nerve action potential recording to guide the choice of surgical procedure is often useful.

Statin myopathy.

Many different classes of medications can cause toxic myopathy. One of the most frequently implicated classes is the statins. Statin myotoxicity ranges from asymptomatic creatine kinase elevations or myalgias to muscle necrosis and fatal rhabdomyolysis. Statins may also cause an autoimmune myopathy requiring immunosuppressive treatment. The mechanisms of statin myotoxicity are unclear. If unrecognized in its early manifestations, complications from continued statin therapy may lead to rhabdomyolysis and death. Risk factors for myotoxicity include concomitant medication use and medical conditions, and the patient's underlying genetic constitution. We review these considerations along with the recommended evaluation and treatment for patients presenting with statin myotoxicity.

Botulinum toxin type-a in the prevention of migraine: a double-blind controlled trial.

INTRODUCTION: Migraine is a frequent medical complaint. In military populations, migraine can be detrimental to productivity and troop readiness, and can be disqualifying for service in some military duty specialties. This study assessed the effectiveness of botulinum neurotoxin type-A (BTX-A) in reducing the frequency of migraines in known migraineurs. METHODS: There were 32 subjects (control = 17, test n = 15) who completed the assessment battery at baseline and monthly for 3 mo. Adult subjects with migraine headaches occurring more than 5 times/month were recruited and randomized to receive placebo saline injection vs. BTX-A. The primary efficacy parameter was the average frequency of headache days for 3 mo. Secondary outcome measures were severity of attacks and quality of life. RESULTS: Quadratic trends were noted for headache severity (F (2,29) = 14.1, p = 0.001) and headache indexes (F (2,29) = 4.5, p = 0.042) for both groups, suggesting changes in severity of head pain and overall intensity of headaches experienced over time; however, results were not significant for headache frequency and severity between groups. Paired t-tests of the headache index scores for the control group revealed a significant increase from the first to the third follow-up periods (t = -2.58, p = 0.020). Such a trend was not observed for the BTX-A group. Both groups, however, reported similarly low to moderate quality of life as a result of their migraines. CONCLUSIONS: This controlled trial failed to demonstrate efficacy of BTX-A in reducing the frequency of migraine headaches. The pattern headache index in the botox group, however, suggested a protective effect for botox against the headache severity.

Potential outcome factors in subacute combined degeneration: review of observational studies.

BACKGROUND: Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging. PURPOSE: To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration. DATA SOURCE: We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION: Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS: We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS: Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in < or = 7 segments and age less than 50 also appear to have higher rates of complete resolution. CONCLUSIONS: B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis.

Ulnar neuropathy at the elbow: Five new things.

Ulnar neuropathy at the elbow (UNE) is the second most frequent compression neuropathy. While other diagnostic imaging tools are emerging to assist in the diagnosis of UNE, electrodiagnosis remains the gold standard. However, the electrodiagnostic approach to UNE presents unique challenges limiting its diagnostic accuracy. We review advances in 5 areas relevant to the diagnosis of UNE: technologic advancements with modern EMG machines have allowed for reconsideration of the question of experimental error and lesion detection; how temperature effects can lead to misdiagnosis; the effect of body mass index on the electrodiagnosis of UNE; the validation of short segment studies; and the emerging role of high-resolution sonography as a diagnostic tool.

The difference between fibrillations and positive sharp waves is due to tissue filtering.

Fibrillation potentials and positive sharp waves share many characteristics, and in general have the same clinical importance. Whether they are two species of the same potential or two different waveforms has been a long-standing controversy. The blocking hypothesis and inadvertent intracellular recording are two theories proposed to explain the difference between the two potentials, but neither is entirely satisfactory. In this study, waveforms with fibrillation potential configurations are modified by the standard filter settings on an electromyograph to attain positive sharp wave configurations. Single-fiber muscle action potentials were recorded at a low-frequency filter of 500 Hz and a high-frequency filter of 20 kHz, and had the appearance of a fibrillation potential. Changing the low-frequency filter and high-frequency filter to 0.2 Hz and 100 Hz respectively caused these same potentials to have a positive sharp wave configuration. Similarly, fibrillation potentials recorded from patients at a low-frequency filter and a high-frequency filter of 20 Hz and 10 kHz respectively had the appearance of positive sharp waves when the low-frequency filter and high-frequency filter were changed to 0.2 Hz and 500 Hz respectively. The authors propose that tissue filtering and the spatial relationship of the fibrillating fiber to the recording electrode determine whether the waveform will have a fibrillation potential configuration or a positive sharp wave configuration. The ability to model these waveforms artificially simply by changing the bandpass suggests that the passive electrical properties of the recording environment may suffice to explain much of the difference between fibrillation potentials and positive sharp waves.

Clinical features and electrodiagnosis of ulnar neuropathies.

In this review, we delineate clinical, electrodiagnostic, and radiographic features of ulnar mononeuropathies. Ulnar neuropathy at the elbow (UNE) is most commonly due to lesions at the level of the retroepicondylar groove (RTC), with approximately 25% at the humeroulnar arcade (HUA). The term 'cubital tunnel syndrome' should be reserved for the latter. The diagnostic accuracy of nerve conduction studies is limited by biological (e.g. low elbow temperature) and technical factors. Across-elbow distance measurements greater than 10 cm improve diagnostic specificity at the expense of decreased sensitivity. Short-segment incremental studies can differentiate lesions at the HUA from those at the RTC.

Multiple cranial neuropathies.

Patients presenting with multiple cranial neuropathies are not uncommon in neurologic clinical practice. The evaluation of these patients can often be overwhelming due to the vast and complicated etiologies as well as the potential for devastating neurologic outcomes. Dysfunction of the cranial nerves can occur anywhere in their course from intrinsic brainstem dysfunction to their peripheral courses. The focus of this review will be on the extramedullary causes of multiple cranial neuropathies as discussion of the brainstem syndromes is more relevant when considering intrinsic disorders of the brainstem. The goals are to provide the reader with an overview of those extramedullary conditions that have a predilection for causing multiple cranial nerve palsies. In turn, this will serve to provide a practical and systematic approach to allow for a more targeted diagnostic evaluation of this, often cumbersome, presentation.

Conduction time for a 6-cm segment of the ulnar nerve across the elbow: reference values for the 6-cm conduction time test.

Current electrodiagnostic studies for Ulnar nerve mononeuropathy at the elbow have substandard sensitivity and specificity. Reference values for a novel, screening electrodiagnostic test for ulnar nerve mononeuropathy at the elbow were obtained bilaterally from 72 subjects without any upper extremity signs or symptoms. The test used two, 3-cm straight line distances, one proximal, and one distal to the medial epicondyle to avoid a curvilinear measurement. The mean conduction times (CTE) were 1.16 +/- 0.16 milliseconds, 1.23 +/- 0.18 milliseconds, 1.33 +/- 0.24 milliseconds, for subjects 20 to 40, 40 to 60, and >60 years old, respectively. A CTE >1.50 milliseconds, >1.60 milliseconds, and >1.80 milliseconds for each age group would be considered abnormal conferring 98% specificity. The median side-to-side difference of CTE (CTE-diff) was 0.10 milliseconds with a range of 0.00 to 0.55 milliseconds. A CTE-diff >0.45 milliseconds has a specificity of 97%. Potential advantages to this method include straight-line measurement distances to reduce experimental error, and a distance less than 10 cm to improve lesion detection.

Controversial entrapment neuropathies.

There is no significant disagreement about the major common entrapment neuropathies, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow, and peroneal neuropathy at the knee. In contrast, there is a group of entrapment syndromes about which there is major disagreement, including whether or not they even exist. There are other entrapment syndromes about which clinical questions arise on a regular basis, and which are the subject of this discussion. These include thoracic outlet syndrome, radial tunnel syndrome, ulnar nerve entrapment at the arcade of Struthers, piriformis syndrome, and tarsal tunnel syndrome.

Sensory physiology assessed by evoked potentials in survivors of poliomyelitis.

Evidence suggests that sensory loss may occur in a proportion of patients affected by poliomyelitis. We hypothesize that sensory problems may be a lasting sequela in some polio survivors. Sensory pathways in polio survivors were evaluated clinically and electrophysiologically using sensory evoked potentials (SEPs). Patients with sensory deficits or abnormal SEPs were further evaluated by magnetic resonance imaging (MRI). Twenty-two patients were studied. The mean age was 64.7 years (age range: 56-81 years). Clinically, sensory impairments were found in 4 patients. Upper limb SEPs were normal. Lower limb SEPs were abnormal in 10 patients. In 1 patient, clinical and electrographic findings correlated with a patch of atrophy in the spinal cord, as shown by MRI. Sensory derangements may be found in a proportion of aging polio survivors. SEP studies may add sensitivity when evaluating sensory function in this cohort. It remains unclear whether these sensory abnormalities are related to remote poliomyelitis. Further studies are necessary.

Physiology of the motor cortex in polio survivors.

We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal. In 17 subjects whose legs were affected by polio and 13 healthy controls, single- and paired-pulse TMS was used to assess motor cortex excitability while recording from tibialis anterior (TA) muscles at rest and following maximal contraction until fatigue. In polio survivors the slope of the recruitment curve was normal, but maximal motor evoked potentials (MEPs) were larger than in controls. MEPs were depressed after fatiguing exercise. Three patients with central fatigue by twitch interpolation had a trend toward slower recovery. There was no association with symptoms of post-polio syndrome. These changes occurring after polio may allow the motor cortex to activate a greater proportion of the motor neurons innervating affected muscles.