A Late Diagnosis of Andersen-Tawil Syndrome in Teenage Siblings.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder characterized by a classic symptom triad, including periodic paralysis, ventricular arrhythmias with associated prolonged QT interval and U waves, and dysmorphic facial and skeletal features. Pathogenic variants of the KCNJ2 gene are linked to ATS. METHODS: We present two siblings with the same pathogenic mutation and facial characteristic of hypotelorism, yet with intrafamilial and sex-specific variability. RESULTS: The first patient is a 16-year-old male who presented from an outside hospital with subacute-onset weakness. The symptoms almost completely subsided the following day, with only mild proximal muscle weakness. Magnetic resonance imaging of the brain and cervical spine was unremarkable. He had one prior attack of self-resolving weakness without apparent triggering factors and a history of premature ventricular contractions and U waves seen on electrocardiogram without cardiac symptoms. On further evaluation his physical examination was significant for micrognathia, hypotelorism, and clinodactyly. Electrodiagnostic examination showed no clear evidence of polyneuropathy. Given his presentation of the typical triad of periodic weakness, dysmorphic features, and cardiac rhythm abnormalities, genetic testing was pursued revealing a pathogenic mutation of the KCNJ2 gene, indicative of ATS. Subsequent genetic testing of his older biological sister, with identical physical features but without a history of cardiac symptoms or episodic periodic paralysis, revealed the same pathogenic mutation. CONCLUSIONS: It is essential to note that ATS can manifest with a wide range of symptoms and some individuals may display only subtle or atypical signs, contributing to this challenging diagnosis.

Paradoxical thinning of the diaphragm on ultrasound is a risk factor for requiring non-invasive ventilation in patients with neuromuscular diaphragmatic dysfunction.

INTRODUCTION/AIMS: Point-of-care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with neuromuscular diaphragmatic dysfunction, paradoxical thinning of the diaphragm during inspiration is observed on ultrasound; however, its frequency, electrodiagnostic associations, and prognostic significance remain uncertain. METHODS: Medical records of patients presenting to two electrodiagnostic laboratories (Mayo Clinic, Rochester, Minnesota and University of Alberta, Edmonton, Alberta) from January 1, 2022 to December 31, 2022, for evaluation of suspected neuromuscular respiratory failure, were reviewed. RESULTS: 214 patients were referred and 19 patients excluded due to incomplete information. Of 195 patients (384 hemidiaphragms), 104 had phrenic neuropathy, 12 had myopathy, and 79 had no evidence of neuromuscular disease affecting the diaphragm. Paradoxical thinning occurred in 31 (27%) patients with neuromuscular diaphragmatic dysfunction and was unilateral in 30, the majority (83%) having normal contralateral ultrasound. Phrenic nerve conduction studies and diaphragm electromyography results did not distinguish patients with paradoxical thinning versus without. Most patients (71%) with paradoxical thinning required non-invasive ventilation (NIV), including 16 with unilateral paradoxical thinning. Paradoxical thinning and BMI ≥30 kg/m2 were risk factors for requiring NIV in multivariable logistic regression analysis, with odds ratios of 2.887 (95% CI:1.166, 7.151) and 2.561 (95% CI: 1.186, 5.532), respectively. DISCUSSION: Paradoxical thinning of the diaphragm occurs in patients with prominent neuromuscular diaphragmatic dysfunction, most commonly from phrenic neuropathy, and is a significant risk factor for requiring NIV. Unilateral paradoxical thinning is sufficient for needing NIV. BMI ≥30 kg/m2 additionally increases risk of requiring NIV in patients with neuromuscular diaphragmatic dysfunction.

Ultra high-frequency ultrasound of fascicles in the ulnar and radial nerves.

INTRODUCTION/AIMS: Ultra high-frequency ultrasound (UHFUS) has been demonstrated to allow easy visualization and quantification of median and digital nerve fascicles; however, there is a lack of normative data for other upper limb nerves. The purpose of this study was to use UHFUS to establish normative reference values and ranges for fascicle count and density within selected upper extremity nerves. METHODS: Twenty-one healthy volunteers underwent sonographic examination of the ulnar, superficial branch of the radial, and radial nerves on one upper limb using UHFUS with a 48 MHz linear transducer. The number of fascicles in each peripheral nerve and fascicle density were assessed. RESULTS: The mean fascicle number and fascicle density for each of the measured nerves was ulnar nerve at the wrist 11.7 and 2.0, ulnar nerve at the elbow 9.2 and 1.1, superficial branch of the radial nerve 7.3 and 2.5, and radial nerve at the spiral groove 4.2 and 0.8. A single significant association was observed between CSA and fascicle number in the ulnar nerve at the wrist (p = .023, r = 0.66). Neither fascicle number nor density could be predicted by age, sex, height, weight, or body mass index. DISCUSSION: UHFUS may help to establish a baseline of normative data on upper limb nerves that are not frequently biopsied due to their mixed motor and sensory functions and has the potential for increased understanding of nerve fascicular anatomy to improve diagnostic accuracy of focal nerve lesions, particularly those with selective fascicular involvement.

Clinical Utility and Diagnostic Yield of Genetic Testing for Inherited Neuromuscular Disorders in a Single, Large Neuromuscular Center.

Background and Objectives: Most published studies on the clinical utility of genetic testing for neuromuscular diseases (NMDs) focus on disease-specific cohorts and/or involve multiple centers. The aim of this study was to examine the clinical utility and diagnostic yield of genetic testing at a single, large neuromuscular center. Unlike previous studies, this study is unique in that it includes a broad array of patients at a single, large neuromuscular center, providing real-world data that may assist both neuromuscular specialists as well as general neurologists in decision-making regarding the need for genetic testing in patients with suspected NMDs. Methods: Genetic testing results were reviewed for all patients who underwent testing through a single genetic testing company for NMDs in this single laboratory at a large neuromuscular center from 2015 to 2020. Retrospective chart reviews were performed to determine whether genetic testing results conferred a specific NMD diagnosis, including cases where a variant of uncertain significance (VUS) was identified. Results: Genetic testing was pursued for 192 patients. A positive result, defined as a pathogenic mutation, a VUS, or both, was found in 77.1%. A definitive diagnosis was conferred in 35.9%. The most common testing indication was suspected neuropathy (53.3%), and the indication with the highest diagnostic yield was suspected myopathy (48.7%). Discussion: This study provides further evidence of the clinical utility of genetic testing for NMDs in a real-world setting with over one-third of patients tested receiving a definitive diagnosis. Over time, genetic testing will continue to become increasingly accessible, cost-effective, and sensitive, which will lead to even more utilization.

Diagnostic Neuromuscular Ultrasound to Confirm Clinical Significance of a Genetic Variant for Charcot-Marie-Tooth Type 4C: A Case Report.

ABSTRACT: Neuromuscular ultrasound has emerged as a beneficial, complementary tool to electromyography (EMG) in the diagnosis of neuromuscular diseases as it provides high-resolution anatomic imaging of peripheral nerves and muscles. It has been used previously as an adjunct to EMG to diagnose Charcot-Marie-Tooth disease. Here, we present a case of a 64-yr-old man with bilateral sensorineural hearing loss of 14 yrs who presented to an outpatient neuromuscular clinic at a tertiary medical center with very slow progressive paresthesias. This case highlights the application of neuromuscular ultrasound to help confirm the presence of a likely Charcot-Marie-Tooth disease type 4C despite indeterminate genetic testing results and challenging EMG results. He had genetic testing which revealed a normal PMP22 gene; however, he had a variant of uncertain significance in the SH3TC2 gene which has shown associations with autosomal recessive CMT4C. Neuromuscular ultrasound revealed mild median and significant tibial nerve uniform enlargement throughout their course. There may also be utility in performing neuromuscular ultrasound on similarly affected family members if the same variant of uncertain significance returns for SH3TC2 , with consideration of both peripheral nerve and nerve root assessment.

Ultrahigh-frequency ultrasound of fascicles in the common fibular, superficial fibular, and sural nerves.

INTRODUCTION/AIMS: While ultrasound assessment of cross-sectional area and echogenicity has gained popularity as a biomarker for various neuropathies, there is a scarcity of data regarding fascicle count and density in neuropathies or even healthy controls. The aim of this study was to determine whether fascicles within select lower limb nerves (common fibular, superficial fibular, and sural nerves) can be counted in healthy individuals using ultrahigh-frequency ultrasound (UHFUS). METHODS: Twenty healthy volunteers underwent sonographic examination of the common fibular, superficial fibular, and sural nerves on each lower limb using UHFUS with a 48 MHz linear transducer. Fascicle counts and density in each examined nerve were determined by a single rater. RESULTS: The mean fascicle number for each of the measured nerves included the following: common fibular nerve 9.85 (SD 2.29), superficial fibular nerve 5.35 (SD 1.59), and sural nerve 6.73 (SD 1.91). Multivariate linear regression analysis revealed a significant association between cross-sectional area and fascicle count for all three nerves. In addition, there was a significant association seen in the common fibular nerve between fascicle density and height, weight, and body mass index. Age and sex did not predict fascicle count or density (all p > .13). DISCUSSION: UHFUS enabled the identification and counting of fascicles and fascicle density in the common fibular, superficial fibular, and sural nerves. Knowledge about normal values and normal peripheral nerve architecture is needed in order to further understand and identify pathological changes that may occur within each nerve in different disease states.

Parsonage-Turner Syndrome and Hereditary Brachial Plexus Neuropathy.

Parsonage-Turner syndrome and hereditary brachial plexus neuropathy (HBPN) present with indistinguishable attacks of rapid-onset severe shoulder and arm pain, disabling weakness, and early muscle atrophy. Their combined incidence ranges from 3 to 100 in 100,000 persons per year. Dominant mutations of SEPT9 are the only known mutations responsible for HBPN. Parsonage and Turner termed the disorder "brachial neuralgic amyotrophy," highlighting neuropathic pain and muscle atrophy. Modern electrodiagnostic and imaging testing assists the diagnosis in distinction from mimicking disorders. Shoulder and upper limb nerves outside the brachial plexus are commonly affected including the phrenic nerve where diaphragm ultrasound improves diagnosis. Magnetic resonance imaging can show multifocal T2 nerve and muscle hyperintensities with nerve hourglass swellings and constrictions identifiable also by ultrasound. An inflammatory immune component is suggested by nerve biopsies and associated infectious, immunization, trauma, surgery, and childbirth triggers. High-dose pulsed steroids assist initial pain control; however, weakness and subsequent pain are not clearly responsive to steroids and instead benefit from time, physical therapy, and non-narcotic pain medications. Recurrent attacks in HBPN are common and prophylactic steroids or intravenous immunoglobulin may reduce surgical- or childbirth-induced attacks. Rehabilitation focusing on restoring functional scapular mechanics, energy conservation, contracture prevention, and pain management are critical. Lifetime residual pain and weakness are rare with most making dramatic functional recovery. Tendon transfers can be used when recovery does not occur after 18 months. Early neurolysis and nerve grafts are controversial. This review provides an update including new diagnostic tools, new associations, and new interventions crossing multiple medical disciplines.

A case series evaluating patient perceptions after switching from nusinersen to risdiplam for spinal muscular atrophy.

INTRODUCTION/AIMS: In 2016, nusinersen became the first disease-modifying medication approved by the U.S. Food and Drug Administration (FDA) for spinal muscular atrophy (SMA). With the later availability of risdiplam in 2020, individuals now have the option of switching from nusinersen to risdiplam. Limited published data exist to inform this decision. This study aims to evaluate the perceptions and experiences of adult participants and parents of minor participants who previously received nusinersen and switched to risdiplam for the treatment of SMA. METHODS: Institutional Review Board (IRB) approval was obtained from the Wake Forest IRB prior to the initiation of this study. A cross-sectional, observational study, with qualitative and quantitative data gathered via questionnaire and medical record review, was performed. Inclusion criteria included (1) prior diagnosis of SMA, (2) previous treatment with nusinersen, and (3) change to treatment with risdiplam. No participants were excluded based on age. RESULTS: Fourteen participants-eight adults and six children-were enrolled in the study. Respondents noted improvements in physical function with each medication. Overall, respondents reported worse satisfaction with the method of delivery of the intrathecally delivered nusinersen compared to the orally-delivered risdiplam, but no respondent reported negative overall satisfaction with either medication. A majority (78.6%) of respondents reported that switching from nusinersen to risdiplam was the correct decision. DISCUSSION: These results suggest that most patients are satisfied when switching from nusinersen to risdiplam, with the method of delivery being a primary factor.

Inpatient rehabilitation outcomes in patients with the new diagnosis of COVID-19 tractopathy: a case series.

STUDY DESIGN: Retrospective Case Series. OBJECTIVES: Describe the inpatient rehabilitation outcomes of four patients with COVID-19 tractopathy. SETTING: Olmsted County, Minnesota, United States of America. METHODS: Retrospective review of medical records was performed to collect patient data. RESULTS: Four individuals (n = 4, 3 men and 1 woman, mean age 58.25 years [range 56-61]) completed inpatient rehabilitation during the COVID-19 pandemic. All presented after COVID-19 infection and were admitted to acute care with progressive paraparesis. None were able to ambulate on admission to acute care. All received extensive evaluations which were largely negative except for mildly elevated CSF protein and MRI findings of longitudinally extensive T2 hyperintensity signal changes in the lateral (n = 3) and dorsal (n = 1) columns. All patients experienced incomplete spastic paraparesis. All patients experienced neurogenic bowel dysfunction; a majority experienced neuropathic pain (n = 3); half experienced impaired proprioception (n = 2); and a minority experienced neurogenic bladder dysfunction (n = 1). Between rehabilitation admission and discharge, the median improvement in lower extremity motor score was 5 (0-28). All patients were discharged home, but only one was a functional ambulator at time of discharge. CONCLUSION: While the underlying mechanism is yet to be elucidated, in rare cases a COVID-19 infection can lead to a tractopathy, presenting as weakness, sensory deficits, spasticity, neuropathic pain, and neurogenic bladder/bowel. Patients with COVID-19 tractopathy would benefit from inpatient rehabilitation to enhance their functional mobility and independence.

Posttraumatic Ruptured Axillary Mononeuropathy Without Shoulder Dislocation in an American Football Player: A Case Report and Review of the Literature.

ABSTRACT: A high school-aged right-handed adolescent boy presented with a 5-mo history of persistent proximal right arm weakness and numbness after an American football stinger injury without a documented history of a shoulder dislocation or humeral fracture. He developed diffuse deltoid muscle atrophy, persistent shoulder abduction weakness, and reduced pinprick sensation confined to the axillary distribution over 5 mos. Needle electromyography demonstrated dense fibrillation potentials and no voluntary activation in all three deltoid muscle heads, indicating a severe posttraumatic ruptured axillary mononeuropathy. The patient then underwent a complex three-cable sural nerve graft repair for attempted reinnervation of the axillary-innervated muscles. Isolated axillary nerve injuries are usually associated with anterior shoulder dislocations; however, a severe isolated persistent axillary mononeuropathy from a ruptured axillary nerve may occur in trauma patients without a clear history of shoulder dislocation. These patients may present with only mild persistent weakness of shoulder abduction. Electrodiagnostic testing to fully assess axillary nerve function should still be considered to identify patients with high-grade nerve injuries that may benefit from sural nerve grafting. The rapid recovery of our patient's initial symptoms with persistent severe axillary injury suggests a unique vulnerability of the nerve due to the neuroanatomy and possibly other factors.

Preoperative electrodiagnostic studies and postoperative outcomes for ulnar mononeuropathy at the elbow: A systematic review.

OBJECTIVE: To analyze the association between preoperative electrodiagnostic (EDX) studies and postoperative pain and functional outcomes following ulnar nerve decompression and/or transposition for ulnar neuropathy at the elbow (UNE). LITERATURE SURVEY: Protocol was submitted and database search was conducted by an experienced librarian of all available studies in the English language from 1990 to June 8, 2022. Databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Scopus. METHODOLOGY: Inclusion criteria consisted of randomized controlled trials, prospective and retrospective longitudinal studies, and studies involving adults ≥18 years of age who underwent ulnar nerve decompression and/or transposition for UNE. Study quality and risk of bias were assessed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality of Assessment Tool. Certainty in evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was not performed. SYNTHESIS: A total of 289 studies were screened, and 8 retrospective cohort studies met inclusion criteria comprising 762 patients. A decreased or absent preoperative sensory nerve action potential amplitude (SNAP) showed significance with worse postoperative outcomes. The presence of preoperative conduction block showed significance in higher quality studies. There was limited evidence for slow preoperative motor conduction velocities or preoperative electromyography (EMG) abnormalities and postoperative outcomes. Overall quality assessment demonstrated that two studies had "good," four "fair," and two "poor" quality of evidence. Certainty in evidence was "low" due to risk of bias. CONCLUSIONS: A decreased or absent preoperative ulnar SNAP may predict worse postoperative outcomes. Per higher quality studies, preoperative conduction block at the elbow may also predict worse postoperative outcomes. Careful interpretation is required with a full understanding of the limited evidence, risk of bias, and low certainty in evidence to support the use of preoperative EDX to predict postoperative outcomes in UNE.

Passive wrist deviation to increase the ultrasound identified procedural safe zone in carpal tunnel syndrome: A retrospective cohort study.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome. Although prior studies have explored the anatomic changes of the median nerve and carpal arch with different wrist deviations and positionings, the change in safe zone distance between the median nerve and ulnar artery with ulnar or radial wrist deviations has not been adequately investigated. OBJECTIVE: To identify the optimal wrist positioning that increases the safe zone distance between the median nerve and ulnar artery using ultrasound in patients with CTS. DESIGN: Retrospective cohort study. SETTING: Quaternary medical center multidisciplinary outpatient hand clinic. PARTICIPANTS: Twenty five patients (41 wrists) with clinical CTS who received an electrodiagnostic study (EDX) to evaluate CTS within 1 year prior to enrollment. INTERVENTIONS: Ultrasound-identified safe zone distance measurements were obtained in each patient between the ulnar aspect of the median nerve and the radial aspect of the ulnar artery with the wrist in neutral radial-ulnar deviation as well as in passive ulnar and radial deviation. MAIN OUTCOME MEASURE: The ultrasound-identified safe zone distance with the wrist in each of the three positions. RESULTS: The interstructural safe zone distance was significantly greater when measured in the ulnarly deviated position (1.08 cm) compared with either the neutral (0.61cm, p < .001) or radially deviated positions (0.52 cm, p < .001). Interstructural safe zone distance did not differ between those with normal, mild, moderate, or severe classifications of pathology, or between dominant and nondominant limbs. CONCLUSION: This study demonstrates that the ultrasound-measured interstructural safe zone distance was significantly greater in the ulnarly deviated position than in either the neutral position or radially deviated position. These findings may lead to improvement in the safety of ultrasound-guided injections.

Traumatic Brain Injury After Music-Associated Head Banging: A Scoping Review.

Objective: To examine the literature to understand the extent that music-associated head banging (MAHB), a common form of self-expression that involves rhythmically swinging one's head to music, is a risk factor for traumatic brain injury (TBI), to identify areas for further research, and to inform primary prevention strategies. Data Sources: A comprehensive search of several databases from database inception to June 30, 2021, was designed and conducted by an experienced librarian with input from study investigators. Study Selection: Study inclusion criteria encompassed all study designs evaluating TBI associated with MAHB. Two independent reviewers reviewed all titles, abstracts, and full texts. Data Extraction: Data were extracted by 2 independent reviewers, and results were summarized descriptively. Data Synthesis: Of 407 eligible studies, 13 met inclusion criteria. All included studies were case reports from multiple countries describing a case of moderate-severe TBI occurring as a direct consequence of MAHB. Of the individuals reported (n=13), they had 1 or more of the following: traumatic subdural hematoma (n=8), internal carotid artery dissection (n=2), basilar artery thrombosis (n=2), traumatic vertebral artery aneurism (n=1), or intracerebral hemorrhage (n=1). No studies were found involving mild TBI after MAHB. Conclusions: This scoping review suggests that MAHB is a risk factor for moderate-severe TBI, although the incidence of mild TBI after MAHB remains unknown. Additional research is needed to understand the association of TBI after MAHB through the spectrum of injury severity, including the potential sequelae of multiple subconcussive injuries.

Ultrasound-guided lumbar medial branch blocks and intra-articular facet joint injections: a systematic review and meta-analysis.

There is great interest in expanding the use of ultrasound (US), but new challenges exist with its application to lumbar facet-targeted procedures. The primary aim of this systematic review and meta-analysis was to determine the risk of incorrect needle placement associated with US-guided lumbar medial branch blocks (MBB) and facet joint injections (FJI) as confirmed by fluoroscopy or computerized tomography (CT). An a priori protocol was registered, and a database search was conducted. Inclusion criteria included all study types. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the National Heart, Lung, and Blood tool for assessing risk bias for observational cohort studies. Pooled analysis of the risk difference (RD) of incorrect needle placement was calculated. Pooled analysis of 7 studies demonstrated an 11% RD (P < 0.0009) of incorrect needle placement for US-guided MBB confirmed using fluoroscopy with and without contrast. Pooled analysis of 3 studies demonstrated a 13% RD (P < 0.0001) of incorrect needle placement for US-guided FJI confirmed using CT. The time to complete a single-level MBB ranged from 2.6 to 5.0 minutes. The certainty of evidence was low to very low. Ultrasound-guided lumbar MBB and FJI are associated with a significant risk of incorrect needle placement when confirmed by fluoroscopy or CT. The technical limitations of US and individual patient factors could contribute to the risk of incorrect needle placement.

Long-term clinical outcomes of genicular nerve radiofrequency ablation for chronic knee pain using a three-tined electrode for expanded nerve capture.

Objective: Genicular nerve radiofrequency ablation (GNRFA) is an effective treatment option for chronic knee pain in native knee osteoarthritis and total knee arthroplasty (TKA) patients. Recent dissections have revealed significant variability in typical genicular nerve targets and other sensory nerves not included in previous studies. Early, short-term results suggest that more complete sensory denervation with GNRFA may result in more significant pain reduction; however, no long-term clinical outcome exists. We aim to present long-term clinical outcomes after an expanded GNRFA technique with a three-tined radiofrequency cannula. Methods: Eleven consecutive patients with ≥6 months of knee pain underwent an expanded GNRFA protocol targeting the superomedial (SMGN), superolateral (SLGN), inferomedial genicular nerves (IMGN), in addition to the nerves to vastus medialis (NVM), lateralis (NVL), and intermedius (NVI). Long-term pain and impression of change outcomes were collected in a cross-sectional fashion. Results: At ≥18 months (mean 24 months) post-GNRFA, 91% (95% CI â€‹= â€‹59, 100%), 73% (95% CI â€‹= â€‹46, 99%), and 9% (95% CI â€‹= â€‹0, 26%) of patients reported ≥50%, ≥80%, and 100% pain relief, respectively. Additionally, 27% (95% CI â€‹= â€‹1, 54%) and 64% (95% CI â€‹= â€‹35, 92%) of individuals reported a PGIC score of 6 ("much improved") and 7 ("very much improved"), respectively. The proportion of individuals who reported the MCID for the PGIC (score of ≥6) was 91% (95% CI â€‹= â€‹59, 100%). There were no adverse events reported amongst the patients in this cohort. No patients progressed to surgery. Conclusion: This single-arm cohort suggests that an expanded GNRFA protocol targeting SMGN, SLGN, IMGN, NVM, NVL, and NVI nerves with a three-tined electrode, resulted in significant long-term (≥18 months) improvements in pain and patient-perceived global improvement. Large, head-to-head trials are needed to establish whether this GNRFA protocol is superior to those used in previous clinical studies and those currently used more commonly in practice.