Sensitivity and specificity of repetitive nerve stimulation with lower cutoffs for abnormal decrement in myasthenia gravis.

INTRODUCTION: The sensitivity of repetitive nerve stimulation (RNS) in myasthenia gravis (MG) is dependent on the cutoff for abnormal decrement. METHODS: RNS data of adults with and without MG from 2014 to 2017 were reviewed retrospectively. The maximum reliable RNS amplitude/area decrement before and after exercise from facial, spinal accessory (SA), ulnar, and fibular nerves was recorded. Sensitivity/specificity using 5%, 7%, and 10% cutoffs were calculated. RESULTS: Seventy-nine of 141 patients had MG (46 generalized, 21 ocular, 12 bulbar). A total of 608 unique RNS recordings were analyzed. Overall RNS sensitivity/specificity at ≥5%, ≥7%, and ≥10% amplitude cutoffs were as follows: SA, 65.6%/86.3%, 49.2%/94.1%, and 29.5%/96.1%; facial, 51.0%/82.5%, 43.1%/95.0%, and 37.3%/100%; ulnar, 43.6%/100%, 41.0%/100%, and 41.0%/100%; and fibular, 52.6%/89.5%, 42.1%/94.7%, and 42.1%/100%. DISCUSSION: Lowering amplitude cutoff from 10% to 7% increased or maintained sensitivity with little loss in specificity. Post-exercise and area analysis resulted in increased sensitivity in some circumstances.

Characteristics and significance of doublets on needle EMG.

INTRODUCTION: Voluntary doublets are electrophysiological phenomena thought to be associated with metabolic derangements or neuromuscular conditions. METHODS: We prospectively studied 232 consecutive patients examined by a single examiner during routine electromyography (EMG) to determine the frequency of doublets in individual patients, specific muscles, neuromuscular conditions, electrolyte levels, and doublet characteristics. RESULTS: Of 232 patients, 25 (10.7%) exhibited doublets. The mean age was 59 (52% men). Only 32 of 1,303 (2.5%) muscles exhibited doublets. Lower extremity and paraspinal groups represented 91% of muscles with doublets. Doublet frequency grouped by EMG diagnoses was: ALS (3 of 11; 27.1%), myopathy (3 of 10; 30.0%), axonal polyneuropathy (7 of 29; 24.1%), and no disease (7 of 109; 6.4%). There were no differences in serum electrolytes between doublet and matched subjects. CONCLUSIONS: Doublets occur in approximately 10% of patients, more commonly in lower extremity and paraspinal muscles, and are not correlated with a specific metabolic abnormality or neuromuscular condition. Muscle Nerve 55: 598-600, 2017.

The role of electrodiagnosis in focal neuropathies.

Electrodiagnostic (EDX) testing plays an important role in confirming a mononeuropathy, localizing the site of nerve injury, defining the pathophysiology, and assessing the severity and prognosis. The combination of nerve conduction studies (NCS) and needle electromyography findings provides the necessary information to fully assess a nerve. The pattern of NCS abnormalities reflects the underlying pathophysiology, with focal slowing or conduction block in neuropraxic injuries and reduced amplitudes in axonotmetic injuries. Needle electromyography findings, including spontaneous activity and voluntary motor unit potential changes, complement the NCS findings and further characterize chronicity and degree of axon loss and reinnervation. EDX is used as an objective marker to follow the progression of a mononeuropathy over time.

Motor unit potential recruitment reference values in common upper and lower extremity muscles.

OBJECTIVE: To define reference values for motor unit (MU) recruitment during needle EMG of six commonly examined muscles at low to moderate contraction. METHODS: Needle examination was performed for each muscle in a total of 111 subjects without neuromuscular disorders. Fastest firing rates and recruitment ratios (RRs) were calculated in at least 5 sites within each muscle. Upper limits of normal based on 97th percentile for fastest MU firing rates and RRs were calculated for each muscle. The means of fastest firing rates were compared among muscles using the Friedman and Wilcoxon signed rank tests. RESULTS: The upper limits of normal were 12-15 Hz for fastest firing rates and were slightly higher in the deltoid and triceps than the other muscles. CONCLUSION: Firing rates >15 Hz recorded at multiple sites within a single muscle exceed the 97th percentile of normal subjects and may suggest reduced MU recruitment. In some muscles, rates >12 Hz might support mildly reduced recruitment. Recruitment ratios varied depending on number of firing MUs, whereas the fastest firing MU rate did not. SIGNIFICANCE: The determination of reference values for fastest MU firing rates can help to identify mild reduction in recruitment with more accuracy.

Comparison of Proximal and Distal Techniques for the Medial Antebrachial Cutaneous Sensory Nerve Conduction Study.

PURPOSE: The medial antebrachial cutaneous (MAC) sensory nerve conduction study (NCS) is a technique performed to evaluate for medial cord/lower trunk plexopathies. Low-amplitude responses and muscle artifact pose technical challenges for MAC NCS. To compare the recorded sensory NCS responses using a proximal MAC (pMAC) NCS technique with a distal (dMAC) technique.To compare the recorded sensory NCS responses using a proximal MAC (pMAC) NCS technique with a distal (dMAC) technique. METHODS: Adults referred to our neurophysiology laboratory for whom MAC NCS were clinically indicated were included. Medial antebrachial cutaneous NCS were performed using dMAC (stimulating at the elbow) and pMAC (stimulating in upper arm) techniques. Amplitudes and peak latencies were compared. RESULTS: Forty-eight patients (82 arms: 39 right and 43 left) were studied. The mean amplitude difference (95% confidence interval) in right pMAC over right dMAC was 4.4 µV (range, 2.78-6.09 µV; P < 0.0001) and that of left pMAC over left dMAC was 5.23 µV (range, 3.35-7.12 µV; P < 0.0001). CONCLUSIONS: The pMAC technique recorded larger mean amplitudes than the dMAC technique, which may improve the technical reliability and diagnostic accuracy when identifying plexopathies.

Electrodiagnostic Characteristics Suggestive of Muscle-Specific Kinase Myasthenia Gravis.

Background and Objectives: Muscle-specific kinase (MuSK) antibody-positive myasthenia gravis (MuSK + MG) is a form of MG with bulbar-predominant symptoms often resistant to conventional treatments. Patients with MuSK + MG may have an electrodiagnostic (EDX) profile distinct from other MG. This study compares EDX features of MuSK + MG with acetylcholine receptor (AChR) antibody-positive MG (AChR + MG) to discern whether any unique EDX pattern exists that can aid in clinical diagnosis. Methods: From January 1, 2010, through December 31, 2020, all patients with MuSK + MG at our institution were identified and randomly matched to an AChR + MG cohort in a 1:2 ratio based on sex, age at onset, and subsequently Myasthenia Gravis Foundation of America (MGFA) clinical severity for a case-control study. Each patient's clinical profile, treatment, and EDX testing were summarized and analyzed. Results: Twenty-two patients with MuSK + MG (18 female) and 44 patients with AChR + MG were studied. The average symptom duration at presentation was shorter in the MuSK + MG group (4.7 years) compared with AChR + MG (10.9 years). Myotonic discharges were rare in both groups but more frequently observed in patients with MuSK + MG (10%) identified in 5 muscles in 2 patients compared with AChR + MG (2%) noted in only 1 muscle in 1 patient. Patients with MuSK + MG more often had myopathic appearing motor unit potentials (MUPs) (41% vs 30%) compared with AChR + MG. Myopathic appearing MUPs were found in milder cases of MuSK + MG (MGFA class I-IIB) compared with AChR + MG (MGFA Class IIB-V). Discussion: Patients with MuSK + MG may have a recognizable EDX profile from AchR + MG that includes (1) myotonic discharges, (2) greater occurrence of myopathic appearing MUPs in clinically mild disease, and (3) symptoms leading to earlier testing.

Electromyography Case Examples: Practical Approaches to Neuromuscular Symptoms.

Many neuromuscular complaints are evaluated with electrodiagnostic testing. In practice, physicians must plan the electrodiagnostic study to provide the most useful information addressing patients' symptoms. The approach to each study must be individualized based on the symptoms and findings of each previous result. This article reviews five real cases with common reasons for referral to the neurophysiology laboratory with discussion of the approach to testing, interpretation of the results, and practical decision-making points relevant to each case. The goal is to provide rationale for why specific studies were selected and how each was helpful in deriving the final diagnosis.

Yield of Head Imaging in Ambulatory and Hospitalized Patients With SARS-CoV-2: A Multi-Center Study of 8675 Patients.

BACKGROUND AND PURPOSE: To describe the neurological and cerebrovascular findings in patients who tested positive for SARS-CoV-2 and underwent head imaging in ambulatory and inpatient settings. METHODS: Consecutive patients aged ≥18 years with SARS-CoV-2 infection diagnosed or treated at Mayo Clinic sites from 3/11/2020 to 7/23/2020 with head CT or brain MRI within 30 days of SARS-CoV-2 diagnosis were included. Demographics, medical history, indication for SARS-CoV-2 testing, neurologic symptoms, indication for brain imaging, neuroimaging findings, etiology of cerebrovascular events, and hospital course were abstracted from medical records. RESULTS: Of 8,675 patients with SARS-CoV-2, 180 (2.07%) had head imaging. Mean age of the entire cohort was 42 ± 18 years, whereas mean age of those with head imaging was 62 ± 19 years. Common indications for imaging were headache (34.4%), encephalopathy (33.4%), focal neurologic symptom (16.7%), and trauma (13.9%). While 86.1% of patients who underwent head imaging had normal exams, cerebrovascular events occurred in 18 patients (0.21% of the total cohort). Of patients with cerebrovascular events, 8 (44.5%) had acute infarct; 6 (33.3%), acute intracranial hemorrhage; 5 (2.8%), subacute infarct; and 1 (0.6%) posterior reversible encephalopathy syndrome. In the thirteen patients with ischemic stroke, 6 (46.2%) had cryptogenic stroke; 3 (23.1%), other defined causes; 2 (15.4%), small vessel stroke; 1 (7.7%), large vessel stroke; and 1 (7.7%) cardioembolic stroke. CONCLUSION: In ambulatory and hospitalized patients with SARS-CoV-2 infection, the rate of head imaging is low, with common indications of encephalopathy and headache. Cerebrovascular events occurred rarely, and cryptogenic stroke was the most common stroke mechanism.

Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability.

BACKGROUND AND OBJECTIVES: There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. METHODS: Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). RESULTS: Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sjögren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications. DISCUSSION: Isolated SFN is uncommon but increasing in incidence. Most patients do not develop major neurologic impairments and disability but have multiple comorbid conditions, including cardiovascular ischemic events, and increased mortality from SFN onsets. Development of large fiber involvements and diabetes are common over time. Targeted testing facilitates interventional therapies for diabetes but also rheumatologic and rare genetic forms.

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary end point was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary end point was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.

Diagnostic modelling and therapeutic monitoring of immune-mediated necrotizing myopathy: role of electrical myotonia.

Delayed diagnosis of immune-mediated necrotizing myopathy leads to increased morbidity. Patients with the chronic course without 3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG or signal recognition particle-IgG are often challenging to diagnose. Immunotherapy response can also be difficult to assess. We created a statistical model to assist immune-mediated necrotizing myopathy diagnosis. Electrical myotonia versus fibrillations were reviewed as biomarkers for immunotherapy treatment response. Identified were 119 immune-mediated necrotizing myopathy cases and 938 other myopathy patients. Inclusion criteria included all having electrophysiological evaluations, muscle biopsies showing inflammatory/necrotizing myopathies, comprehensively recorded neurological examinations, and creatine kinase values. Electrical myotonia was recorded in 56% (67/119) of retrospective and 67% (20/30) of our validation immune-mediated necrotizing myopathy cohorts, and significantly (P < 0.001) favoured immune-mediated necrotizing myopathy over other myopathies: sporadic inclusion body myositis (odds ratio = 4.78); dermatomyositis (odds ratio = 10.61); non-specific inflammatory myopathies (odds ratio = 8.46); limb-girdle muscular dystrophies (odds ratio = 5.34) or mitochondrial myopathies (odds ratio = 14.17). Electrical myotonia occurred in immune-mediated necrotizing myopathy seropositive (3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG 70%, 37/53; signal recognition particle-IgG 29%, 5/17) and seronegative (51%, 25/49). Multivariate regression analysis of 20 variables identified 8 (including electrical myotonia) in combination accurately predicted immune-mediated necrotizing myopathy (97.1% area-under-curve). The model was validated in a separate cohort of 30 immune-mediated necrotizing myopathy cases. Delayed diagnosis of cases with electrical myotonia occurred in 24% (16/67, mean 8 months; range 0-194). Half (8/19) had a chronic course and were seronegative, with high model prediction (>86%) at the first visit. Inherited myopathies were commonly first suspected in them. Follow-up evaluation in patients with electrical myotonia on immunotherapy was available in 19 (median 21 months, range 2-124) which reduced from 36% (58/162) of muscles to 7% (8/121; P < 0.001). Reduced myotonia correlated with immunotherapy response in 64% (9/14) as well as with median creatine kinase reduction of 1779 U/l (range 401-9238, P < 0.001). Modelling clinical features with electrical myotonia is especially helpful in immune-mediated necrotizing myopathy diagnostic suspicion among chronic indolent and seronegative cases. Electrical myotonia favours immune-mediated necrotizing myopathy diagnosis and can serve as an adjuvant immunotherapy biomarker.