AANEM - IFCN Glossary of Terms in Neuromuscular Electrodiagnostic Medicine and Ultrasound.

Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide. HIGHLIGHTS: Optimal terminology in neuromuscular electrodiagnosis and ultrasound has been revisited. A team of international experts have revised and expanded a standardized glossary. This list of terms serves as standard reference for clinical practice, education and research.

A case of YY1-associated syndromic learning disability or Gabriele-de Vries syndrome with myasthenia gravis.

Exome sequencing is being used increasingly to evaluate patients with intellectual disability. YY1 is a ubiquitously distributed transcription factor belonging to the GLIKruppel class of zinc finger proteins recently recognized as the causative gene in 23 patients for the Gabriele-de Vries syndrome. We report a new case with similar features and a novel variant in YY1, in a region of the gene, which has not previously been reported. A 25 year old female was referred to clinical genetics with a diagnosis of autoimmune myasthenia gravis, facial dysmorphism and learning disability. Chromosomal microarray and gene panel test for congenital myasthenic syndrome was negative. Whole exome sequencing (WES) revealed a presumed pathogenic de novo novel, heterozygous, truncating variant in the YY1 gene, c.860_864delTTAAAA, p.Ile287Argfs*3. The Ile287 residue is conserved across species and is situated in the transcription repressor domain of the protein. This variant is novel and lies in a domain of the protein where no previously reported variants occur. The phenotypic features of our case closely match those of the reported patients. Autoimmune myasthenia gravis has not been reported in these patients and may constitute an expansion of this phenotypic spectrum or perhaps more likely a second unrelated diagnosis.

Complete dislocation of the ulnar nerve at the elbow: a protective effect against neuropathy?

INTRODUCTION: Recurrent complete ulnar nerve dislocation has been perceived as a risk factor for development of ulnar neuropathy at the elbow (UNE). However, the role of dislocation in the pathogenesis of UNE remains uncertain. METHODS: We studied 133 patients with complete ulnar nerve dislocation to determine whether this condition is a risk factor for UNE. In all, the nerve was palpated as it rolled over the medial epicondyle during elbow flexion. RESULTS: Of 56 elbows with unilateral dislocation, UNE localized contralaterally in 17 elbows (30.4%) and ipsilaterally in 10 elbows (17.9%). Of 154 elbows with bilateral dislocation, 26 had UNE (16.9%). Complete dislocation decreased the odds of having UNE by 44% (odds ratio = 0.475; P = 0.028), and was associated with less severe UNE (P = 0.045). CONCLUSIONS: UNE occurs less frequently and is less severe on the side of complete dislocation. Complete dislocation may have a protective effect on the ulnar nerve. Muscle Nerve 56: 242-246, 2017.

Hypoglossal nerve palsy: 245 cases.

INTRODUCTION: Apart from a case series of 100 subjects in 1996 and several small cohorts, there have been no large retrospective series of cranial nerve XII (CN XII) palsy. METHODS: From 1984 to 2014, 245 cases of CN XII palsy were identified via retrospective chart review using historical and exam findings that confirmed the diagnosis. In addition to clinical characteristics, univariate and multivariate models were investigated to predict neoplastic CN XII palsy. RESULTS: Major etiologic categories included: postoperative (29.3%), idiopathic (15.1%), primary neoplastic (14.2%), metastatic malignancy (13.0%), inflammatory (7.3%), radiation (6.1%), and traumatic (4.1%). A multivariate model revealed male gender and a personal history of cancer as predictive of neoplastic CN XII palsy. CONCLUSIONS: The most frequent etiologies and disease categories of CN XII palsy were identified, and male gender and personal history of cancer were found to be predictive of a neoplastic cause of CN XII palsy. Muscle Nerve 54: 1050-1054, 2016.

Electrodiagnostic reference values for upper and lower limb nerve conduction studies in adult populations.

INTRODUCTION: To address the need for greater standardization within the field of electrodiagnostic medicine, the Normative Data Task Force (NDTF) was formed to identify nerve conduction studies (NCS) in the literature, evaluate them using consensus-based methodological criteria derived by the NDTF, and identify those suitable as a resource for NCS metrics. METHODS: A comprehensive literature search was conducted of published peer-reviewed scientific articles for 11 routinely performed sensory and motor NCS from 1990 to 2012. RESULTS: Over 7,500 articles were found. After review using consensus-based methodological criteria, only 1 study each met all quality criteria for 10 nerves. CONCLUSION: The NDTF selected only those studies that met all quality criteria and were considered suitable as a clinical resource for NCS metrics. The literature is, however, limited and these findings should be confirmed by larger, multicenter collaborative efforts. Muscle Nerve 54: 371-377, 2016.

Establishing high-quality reference values for nerve conduction studies: A report from the normative data task force of the American Association Of Neuromuscular & Electrodiagnostic Medicine.

INTRODUCTION: There are not uniform standards for nerve conduction testing across the United States. The objective of this study is to present a set of methodologically sound criteria to evaluate the literature for the purpose of identifying high-quality normative nerve conduction studies (NCS) suitable for widespread use. METHODS: The Normative Data Task Force (NDTF) was formed to review published studies on methodological issues related to NCS. A set of criteria was then developed to evaluate the literature. These criteria and their rationale are described. RESULTS: We identified 7 key issues that reflect high quality in NCS. For each issue, specific review criteria were developed. CONCLUSION: Rigorous criteria enable identification of high-quality studies dealing with nerve conduction reference values. This represents the first step toward the overarching goal of recommending NCS techniques and reference values for electrodiagnostic medicine. Muscle Nerve 54: 366-370, 2016.

Reference values for jitter recorded by concentric needle electrodes in healthy controls: A multicenter study.

INTRODUCTION: The aim of this study was to create reference values for jitter measured with concentric needle electrodes. METHODS: Operators worldwide contributed recordings from orbicularis oculi (OO), frontalis (FR), and extensor digitorum (ED) muscles in healthy controls. Criteria for acceptable signal quality were agreed upon in advance. Fifteen or 20 recordings of acceptable quality from each muscle were required for voluntary and electrical stimulation recordings, respectively. RESULTS: Recordings from 59 to 92 subjects were obtained for each muscle and activation type. Outlier limits for mean consecutive difference and individual jitter data for voluntary activation were: OO, 31 and 45 µs; FR, 28 and 38 µs; ED, 30 and 43 µs; and for electrical stimulation they were: OO, 27 and 36 µs; FR, 21 and 28 µs; ED, 24 and 35 µs. CONCLUSION: Reference jitter values from concentric needle electrode recordings were developed from signals of defined quality while seeking to avoid creating supernormal values.

Feature selection for motor unit potential train characterization.

INTRODUCTION: Ten new features of motor unit potential (MUP) morphology and stability are proposed. These new features, along with 8 traditional features, are grouped into 5 aspects: size, shape, global complexity, local complexity, and stability. METHODS: We used sequential forward and backward search strategies to select subsets of these 18 features to discriminate accurately between muscles whose MUPs are predominantly neurogenic, myopathic, or normal. RESULTS AND CONCLUSIONS: Results based on 8102 motor unit potential trains (MUPTs) extracted from 4 different limb muscles (n = 336 total muscles) demonstrate the usefulness of these newly introduced features and support an aspect-based grouping of MUPT features.

Acute hypoxic hypoxia and isocapnic hypoxia effects on oculometric features.

INTRODUCTION: Visual performance impairment after hypoxia is well recognized in military and civilian aviation. The aims of this study were: 1) to assess oculometric features such as blink metrics, pupillary dynamics, fixations, and saccades as cognitive indicators of early signs of hypoxia; and 2) to analyze the impact of different hypoxic conditions ["hypoxic hypoxia" (HH) and "isocapnic hypoxia" (IH)] on specified oculometrics during mental workloads. METHODS: Oculometric data were collected on 25 subjects under 3 conditions: normoxia, HH (8% O2 + balance N2), and IH (7% O2 + 5% CO2 + balance N2). The mental workload task consisted of reading aloud linear arrays of numbers after exposure to gas mixtures. RESULTS: Blink rates were significantly increased under hypoxic conditions (by +100.7% in HH and by +92.8% in IH compared to normoxia). A faster recovery of blink rate was observed in transitioning from IH (23.6% vs. 76.3%) to normoxia. The percentage change in pupil size fluctuation was increased under HH more than under IH (29% vs. 4.4%). Under HH average fixation time and target area size were significantly higher than under IH. Total saccadic times under hypoxic conditions were significantly increased compared with normoxia. CONCLUSIONS: These results suggest that oculometric changes are indicators of hypoxia, which can be monitored using compact, portable, noninvasive eye-tracking devices in a cockpit analogous environment to detect hypoxia-induced physiological changes in aircrew. Comparative results between HH and IH support the potential role of carbon dioxide in augmenting cerebral perfusion and hence improved tissue oxygen delivery.

Early detection of hypoxia-lnduced cognitive impairment using the King-Devick test.

INTRODUCTION: Hypoxic incapacitation continues to be a significant threat to safety and operations at high altitude. Noninvasive neurocognitive performance testing is desirable to identify presymptomatic cognitive impairment, affording operators at altitude a tool to quantify their performance and safety. METHODS: There were 25 subjects enrolled in this study. Cognitive performance was assessed by using the King-Devick (K-D) test. The performance of the subjects on the K-D test was measured in normoxia followed by hypoxia (8% 02 equivalent to 7101 m) and then again in normoxia. RESULTS: K-D test completion time in hypoxia for 3 min was significantly longer than the Baseline Test (54.5 +/- 12.4 s hypoxic vs. 46.3 +/- 10.4 s baseline). Upon returning to normoxia the completion time was significantly shorter than in hypoxia (47.6 +/- 10.6 s post test vs. 54.5 +/- 12.4 s hypoxic). There was no statistically significant difference between baseline test and post test times, indicating that all subjects returned to their normoxic baseline levels. SpO2 decreased from 98 +/- 0.9% to 80 +/- 7.8% after 3 min on hypoxic gas. During the hypoxic K-D test, SpO2 decreased further to 75.8 +/- 8.3%. CONCLUSIONS: In this study the K-D test has been shown to be an effective neurocognitive test to detect hypoxic impairment at early presymptomatic stages. The K-D test may also be used to afford a reassessment of traditional measures used to determine hypoxic reserve time.

Electrodiagnostic Testing for Carpal Tunnel Syndrome When Routine Median Sensory and Thenar Motor Responses Are Absent.

PURPOSE: The cardinal symptoms of carpal tunnel syndrome (CTS) include pain in the affected hand(s). The median/second lumbrical nerve (Med2ndL) seems relatively preserved in severe CTS, with previous small studies suggesting its value in electromyogram to localize a median neuropathy to the wrist when both initial routine sensory and thenar motor responses are absent. METHODS: This is a retrospective analysis of 208 hands in 183 patients with electrophysiologically markedly severe CTS (absent routine sensory and thenar motor median responses) who underwent stimulation of both the Med2ndL and ulnar/second dorsal interosseous (Uln2ndDIn) motor nerves. A Med2ndL distal latency of ≥ 0.5 milliseconds when compared with the Uln2ndDIn supported the diagnosis of CTS. The presence or absence of hand pain was recorded if these data were available. RESULTS: Some 83.7% of hands (172/208) in 183 patients with markedly severe CTS had preservation of the Med2ndL meeting criteria for CTS. In those with pain data available, 77.1% (81/105) of hands had no pain. Of those 105 hands, 87 had preservation of the Med2ndL with 79.3% (69/87) demonstrating no pain. CONCLUSIONS: This is a large study that demonstrates the relative preservation of the Med2ndL response in markedly severe CTS. Assessment of the Med2ndL should be considered to electrophysiologically support CTS when routine sensory and thenar motor responses are absent. In addition, most patients with electrophysiologically markedly severe CTS had no pain.

Oculo-vestibular recoupling using galvanic vestibular stimulation to mitigate simulator sickness.

INTRODUCTION: Despite improvement in the computational capabilities of visual displays in flight simulators, intersensory visual-vestibular conflict remains the leading cause of simulator sickness (SS). By using galvanic vestibular stimulation (GVS), the vestibular system can be synchronized with a moving visual field in order to lessen the mismatch of sensory inputs thought to result in SS. METHODS: A multisite electrode array was used to deliver combinations of GVS in 21 normal subjects. Optimal electrode combinations were identified and used to establish GVS dose-response predictions for the perception of roll, pitch, and yaw. Based on these data, an algorithm was then implemented in flight simulator hardware in order to synchronize visual and GVS-induced vestibular sensations (oculo-vestibular-recoupled or OVR simulation). Subjects were then randomly exposed to flight simulation either with or without OVR simulation. A self-report SS checklist was administered to all subjects after each session. An overall SS score was calculated for each category of symptoms for both groups. RESULTS: The analysis of GVS stimulation data yielded six unique combinations of electrode positions inducing motion perceptions in the three rotational axes. This provided the algorithm used for OVR simulation. The overall SS scores for gastrointestinal, central, and peripheral categories were 17%, 22.4%, and 20% for the Control group and 6.3%, 20%, and 8% for the OVR group, respectively. CONCLUSIONS: When virtual head signals produced by GVS are synchronized to the speed and direction of a moving visual field, manifestations of induced SS in a cockpit flight simulator are significantly reduced.

AANEM - IFCN glossary of terms in neuromuscular electrodiagnostic medicine and ultrasound.

Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide.

Novel biallelic variants in MSTO1 associated with mitochondrial myopathy.

Mitochondrial disorders are caused by nuclear and mitochondrial pathogenic variants leading to defects in mitochondrial function and cellular respiration. Recently, the nuclear-encoded mitochondrial fusion gene MSTO1 (Misato 1) has been implicated in mitochondrial myopathy and ataxia. Here we report on a 30-yr-old man presenting with a maternally inherited NM_018116.3:c.651C>G, p.F217L missense variant as well as a paternally inherited arr[GRCh37] 1q22(155581773_155706887) × 1 deletion encompassing exons 7-14 of MSTO1 His phenotype included muscle weakness, hypotonia, early motor developmental delay, pectus excavatum, and scoliosis. Testing revealed elevated plasma creatine kinase, and electromyogram results were consistent with longstanding generalized myopathy. These phenotypic features overlap well with previously reported patients harboring biallelic MSTO1 variants. Additionally, our patient presents with dysphagia and restrictive lung disease, not previously reported for MSTO1-associated disorders. The majority of patients with disease-associated variants in MSTO1 present with biallelic variants suggesting autosomal recessive inheritance; however, one family has been reported with a single variant and presumed autosomal dominant inheritance. The pattern of inheritance we observed is consistent with the majority of previous reports suggesting an autosomal recessive disorder. We add to our knowledge of the syndrome caused by variants in MSTO1 and provide additional evidence supporting autosomal recessive inheritance. We also describe phenotypic features not reported in previous cases, although further research is needed to confirm they are associated with defects in MSTO1.

Neuromuscular disorders associated with paraproteinemia.

Neuromuscular disorders associated with monoclonal gammopathies are usually uncovered in approximately 10% of patients presenting with peripheral neuropathy complaints. This discovery should prompt further evaluation for underlying plasma cell dyscrasias. The most frequent monoclonal disorders associated with neuropathy are smoldering myeloma, multiple myeloma, Waldenström macroglobulinemia, solitary plasmacytoma, systemic immunoglobulin light chain (AL) amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), and cryoglobulinemia. If these are excluded by careful evaluation the patient is classified as having monoclonal gammopathy of undetermined significance. Diagnostic criteria, risk stratification to determine prognosis, and current management for these disorders are reviewed in this article.

Electrophysiology of Cranial Nerve Testing: Spinal Accessory and Hypoglossal Nerves.

Multiple techniques have been developed for the electrodiagnostic evaluation of cranial nerves XI and XII. Each of these carries both benefits and limitations, with more techniques and data being available in the literature for spinal accessory than hypoglossal nerve evaluation. Spinal accessory and hypoglossal neuropathy are relatively uncommon cranial mononeuropathies that may be evaluated in the outpatient electrodiagnostic laboratory setting. A review of available literature using PubMed was conducted regarding electrodiagnostic technique in the evaluation of spinal accessory and hypoglossal nerves searching for both routine nerve conduction studies and repetitive nerve conduction studies. The review provided herein provides a resource by which clinical neurophysiologists may develop and implement clinical and research protocols for the evaluation of both of these lower cranial nerves in the outpatient setting.

Vocal cord paralysis after vagus nerve stimulator battery replacement successfully treated with medialization thyroplasty.

The vagus nerve stimulator (VNS) has been used effectively for partial seizure disorders, however many patients suffer from side effects of alterations in voice. This case describes a new remediable adverse effect of the VNS. A patient with medically intractable epilepsy had improvement of his seizure control with VNS therapy after titrating him to a high output and rapid cycling paradigm with essentially no side effects. After a battery replacement, he was restarted on his previous settings and subsequently developed a hoarse voice. He was found to have complete left vocal cord paralysis, an adverse effect attributed to a rapid titration to his previous high output and rapid cycling paradigm. This side effect has not been previously described in the literature. The patient subsequently had a medialization thyroplasty with resolution of his hoarse voice.

Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy.

BACKGROUND: An underlying cause is found in only 7% to 30% of patients with chronic idiopathic axonal polyneuropathy (CIAP). Diabetes mellitus, inherited disorders, toxin exposure, and primary amyloidosis are the most common identified causes of sensory neuropathies affecting both large and small myelinated fibers. Undiagnosed impaired fasting glucose metabolism has been associated with CIAP at a higher frequency rate than in the general population. This increased prevalence rate was identified using the 2-hour oral glucose tolerance test (2h-OGTT) and a previous version of the American Diabetes Association (ADA) guidelines. OBJECTIVES: To determine the prevalence of abnormal fasting glucose metabolism in patients with CIAP and to compare the value of determining fasting plasma glucose levels using revised (2003) ADA criteria with the 2h-OGTT for predicting abnormal fasting glucose metabolism. PATIENTS: In this 24-month retrospective study, 100 consecutive patients were identified with no known cause for CIAP, including diabetes mellitus, between January 2003 and January 2005. All had both a fasting plasma glucose test and a 2h-OGTT in addition to a complete neurological examination. Neurophysiological studies, computer-assisted sensory examination, and quantitative sudomotor axonal reflex testing were used to classify CIAP into subtypes according to nerve fiber involvement. RESULTS: The prevalence of undiagnosed abnormal fasting glucose metabolism was found to be nearly 2-fold higher (62%) in patients with CIAP than in similar age-matched general population groups (33%). Using the 2003 revised ADA criteria, 39 patients (39%) had abnormal fasting plasma glucose metabolism (36 with impaired fasting glucose, 3 with diabetes mellitus), while the 2h-OGTT provided an even higher diagnostic rate of 62% (62 patients; P<.001) of impaired fasting glucose metabolism (38 with impaired glucose tolerance, 24 with diabetes mellitus). The abnormal glucose metabolism rates were found to be similar across the 3 subtypes (sensorimotor, pure sensory, and small-fiber neuropathy) of CIAP (P = .60, .72, and .61). CONCLUSIONS: This study adds to emerging evidence that abnormal glucose metabolism may be a risk factor for CIAP. Even with revised (2003) ADA criteria, the 2h-OGTT provides additional diagnostic information to the health care professional in the evaluation of CIAP. Subtypes of CIAP are equally likely to have abnormal glucose metabolism.

Normative data for Aδ contact heat evoked potentials in adult population: a multicenter study.

There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. Contact heat evoked potentials were recorded from 226 subjects (114 females), distributed per age decade between 20 and 79 years. Temperature stimuli were delivered by a thermode (32°C-51°C at a rate of 70°C/s). In phase I of the study, we investigated side-to-side differences and reported the maximum normal side-to-side difference in Aδ CHEP peak latency and amplitude for leg, forearm, and face. In phase II, we obtained normative data for 3 CHEP parameters (N2P2 amplitude, N2 latency, and P2 latency), stratified for gender and age decades from face, upper and lower limbs, and overlying cervical and lumbar spine. In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain.