Chronic Neurogenic Changes Research Articles

Heterozygous loss-of-function variants in SPTAN1 cause a novel early childhood onset distal myopathy with chronic neurogenic features.

Neurogenetic disorders caused by pathogenic variants in four genes encoding non-erythrocytic spectrins ( SPTAN1, SPTBN1, SPTBN2, SPTBN4) range from peripheral and central nervous system involvement to complex syndromic presentations. Heterozygous pathogenic variants in SPTAN1 are exemplary for this diversity with phenotypes spanning almost the entire spectrum. Through international collaboration we identified 14 families with genetically unsolved distal weakness and unreported heterozygous SPTAN1 loss-of-function variants including frameshift, nonsense and splice-acceptor variants. Clinical data, electrophysiology, muscle CT or MRI and muscle biopsy findings were collected and standardized. SPTAN1 protein, mRNA expression analysis and cDNA sequencing was performed on muscle tissue from two patients. All 20 patients presented with early childhood onset distal weakness. The severity varied both within families and between different families. Foot abnormalities ranged from hammer toes and pes cavus to distal arthrogryposis. Electrophysiology showed mixed myogenic and neurogenic features. Muscle MRI or CT in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes with mild dystrophic and chronic neurogenic changes in 7 patients. Finally, we provide proof for nonsense mediated decay in tissues derived from two patients. We provide evidence for the association of SPTAN1 loss-of-function variants with childhood onset distal myopathy in 14 families. This finding extends the phenotypic spectrum of SPTAN1 loss-of-function variants ranging from intellectual disability to distal weakness with a predominant myogenic cause. SPTAN1 loss-of-function variants, including frameshift, nonsense and splice site variants cause a novel childhood onset distal weakness syndrome with primarily skeletal muscle involvement. Hereditary motor neuropathies and distal myopathic disorders present a well-known diagnostic challenge as they demonstrate substantial clinical and genetic overlap. The emergence of SPTAN1 loss-of-function variants serves as a noteworthy example, highlighting a growing convergence in the spectrum of genotypes linked to both hereditary motor neuropathies and distal myopathies.

Mutations in alpha-B-crystallin cause autosomal dominant axonal Charcot-Marie-Tooth disease with congenital cataracts.

Mutations in the alpha-B-crystallin (CRYAB) gene have initially been associated with myofibrillar myopathy, dilated cardiomyopathy and cataracts. For the first time, peripheral neuropathy is reported here as a novel phenotype associated with CRYAB. Whole-exome sequencing was performed in two unrelated families with genetically unsolved axonal Charcot-Marie-Tooth disease (CMT2), assessing clinical, neurophysiological and radiological features. The pathogenic CRYAB variant c.358A>G;p.Arg120Gly was segregated in all affected patients from two unrelated families. The disease presented as late onset CMT2 (onset over 40 years) with distal sensory and motor impairment and congenital cataracts. Muscle involvement was probably associated in cases showing mild axial and diaphragmatic weakness. In all cases, nerve conduction studies demonstrated the presence of an axonal sensorimotor neuropathy along with chronic neurogenic changes on needle examination. In cases with late onset autosomal dominant CMT2 and congenital cataracts, it is recommended that CRYAB is considered for genetic testing. The identification of CRYAB mutations causing CMT2 further supports a continuous spectrum of expressivity, from myopathic to neuropathic and mixed forms, of a growing number of genes involved in protein degradation and chaperone-assisted autophagy.

A TRPV4 mutation caused Charcot-Marie-Tooth disease type 2C with scapuloperoneal muscular atrophy overlap syndrome and scapuloperoneal spinal muscular atrophy in one family: a case report and literature review

BackgroundCharcot-Marie-Tooth disease 2C (CMT2C) and scapuloperoneal spinal muscular atrophy (SPSMA) are different clinical phenotypes of TRPV4 mutation. The mutation of p.R316C has been reported to cause CMT2C and SPSMA separately.Case presentationHere, we reported a Chinese family harboring the same p.R316C variant, but with an overlap syndrome and different clinical manifestations. A 58-year-old man presented with severe scapula muscle atrophy, resulting in sloping shoulders. He also exhibited distinct muscle atrophy in his four limbs, particularly in the lower limbs. The sural nerve biopsy revealed severe loss of myelinated nerve fibers with scattered regenerating clusters and pseudo-onion bulbs. Nerve conduction study showed axon damage in both motor and sensory nerves. Sensory nerve action potentials could not be evoked in bilateral sural or superficial peroneal nerves. He was diagnosed with Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome, whereas his 27-year-old son was born with clubfoot and clinodactyly. Electromyogram examination indicated chronic neurogenic changes and anterior horn cells involvement. Although there was no obvious weakness or sensory symptoms, early SPSMA could be considered for him.ConclusionsA literature review of the clinical characteristics in CMT2C and SPSMA patients with TRPV4 mutation suggested that our case was distinct due to the overlap syndrome and phenotype variation. Altogether, this case broadened the phenotype spectrum and provided the nerve biopsy pathological details of TRPV4-related neuropathies.

Wasted leg syndrome: An atypical slowly-progressive form of lower motor neuron disease

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7–18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation.

P25 A complex case of mixed systemic sclerosis and myositis with severe multi-system involvement

P25 A complex case of mixed systemic sclerosis and myositis with severe multi-system involvement

A Young Man With Acute-Onset Bilateral Arm Weakness After Traumatic Sciatic Neuropathy: A Clinical Vignette.

A Young Man With Acute-Onset Bilateral Arm Weakness After Traumatic Sciatic Neuropathy: A Clinical Vignette.

Electrodiagnostic findings in facial onset sensory motor neuronopathy (FOSMN)

ObjectiveTo determine the electrodiagnostic characteristics of facial onset sensory and motor neuronopathy (FOSMN). MethodsElectrophysiological data from 10 FOSMN patients in Newcastle-upon-Tyne and Sydney were reviewed. Relevant literature was reviewed. ResultsFindings on standard electrophysiological assessment were in broad agreement with those published: blink reflexes were abnormal in all but one patient; sensory nerve action potentials were reduced but compound muscle action potentials preserved; mixed acute and chronic neurogenic change was identified on needle electromyography in bulbar and cervico-thoracic muscles in approximately 50% of patients.Upper limb somatosensory evoked potential (SEP) central conduction times were increased (n = 4) and progressed on repeat testing (n = 3). Upper motor neuron dysfunction was revealed by several measures [ipsilateral motor evoked potentials (MEPs) (n = 1); reduced short interval intra-cortical inhibition on threshold-tracking transcranial magnetic stimulation (n = 2); absent beta-band intermuscular coherence (n = 3)]. ConclusionsElectrodiagnostic investigation of FOSMN should include blink reflex testing, SEPs and tests of upper motor neuron function. The combination of progressive lower motor neuron disease and upper motor neuron disease on neurophysiological investigation provides further support for the contention that FOSMN is a rare variant of motor neurone disease. SignificanceThese findings will aid the neurologist and neurophysiologist in making a confident diagnosis of FOSMN, thus expediting appropriate care.

P047 An unusual case of dermatomyositis with co-existent anti-GAD and anti-NXP2 antibody positivity

Abstract Background/Aims Dermatomyositis (DM) is a rare disease. We present a case of DM with both anti-nuclear matrix protein 2 antibody (NXP2) as well as anti-glutamic acid decarboxylase antibody (GAD) positivity, the combination of which has yet not been documented in the current literature. Methods The case is described below. Results A 48 year old Caucasian male with no co-morbidities presented with a one-month history of sore throat and lethargy, followed 2 weeks later by muscular pain in his upper arms. On examination, there was erythema to the sun-exposed areas of the face and arms, hoarse voice and Gottron’s papules. He had proximal muscle weakness of 4/5 in his shoulder and hips. His creatinine kinase(CK) was elevated at 2914U/L. He was started on methylprednisolone 1 gram od for 3 days with improvement of his CK to 642U/L. His muscle biopsy showed mild chronic neurogenic changes and upregulation of C5b-9 but no evidence of inflammatory myopathy which was attributed to the steroid use prior to the biopsy. His myositis antibody screen was positive for Anti-Nuclear Matrix Protein antibody 2(NXP2). After 4 days he developed rapid onset dysphagia and a sudden drop in his spirometry readings with a fall in his FEV1from 94% to 85% and a fall in his FVC from 88% to 79%. He became acutely unwell, drowsy with difficulty completing sentences and global weakness. His CK had risen to 1567U/L despite the high dose intravenous methylprednisolone. He was diagnosed with Diabetic ketoacidosis(DKA) with a blood glucose of 32mmol/L , pH of 7.0, and transferred to ITU. Intravenous immunoglobulin (IVIG) was administered with subsequent improvement in all muscle groups. He was then commenced on a subcutaneous insulin regime and pulsed intravenous cyclophosphamide (Eurolupus) as his EMG showed a sensorimotor polyneuropathy as well as an inflammatory myopathy. His serology was negative for infectious aetiology. Malignancy screen including PET scan, oesophagogastroduodenoscopy and colonoscopy were normal however, he was found to be positive for anti-GAD antibody. Conclusion GAD antibodies are known to be associated with many disorders including diabetes and stiff person syndrome and can recognise different epitopes in various diseases. This is the first documented case of GAD occurring in a DM patient, in the presence of NXP2 antibodies. IVIG is used to treat both stiff man syndrome and refractory DM. It is possible that the combination of GAD and NXP2 contributed to the pathogenesis and severity of the clinical presentation in this case. Disclosure K. Beharry: None. G. Barminski: None. D. De Lord: None.

De Novo and Inherited Variants in GBF1 are Associated with Axonal Neuropathy Caused by Golgi Fragmentation

SummaryDistal hereditary motor neuropathies (HMNs) and axonal Charcot-Marie-Tooth neuropathy (CMT2) are clinically and genetically heterogeneous diseases characterized primarily by motor neuron degeneration and distal weakness. The genetic cause for about half of the individuals affected by HMN/CMT2 remains unknown. Here, we report the identification of pathogenic variants in GBF1 (Golgi brefeldin A-resistant guanine nucleotide exchange factor 1) in four unrelated families with individuals affected by sporadic or dominant HMN/CMT2. Genomic sequencing analyses in seven affected individuals uncovered four distinct heterozygous GBF1 variants, two of which occurred de novo. Other known HMN/CMT2-implicated genes were excluded. Affected individuals show HMN/CMT2 with slowly progressive distal muscle weakness and musculoskeletal deformities. Electrophysiological studies confirmed axonal damage with chronic neurogenic changes. Three individuals had additional distal sensory loss. GBF1 encodes a guanine-nucleotide exchange factor that facilitates the activation of members of the ARF (ADP-ribosylation factor) family of small GTPases. GBF1 is mainly involved in the formation of coatomer protein complex (COPI) vesicles, maintenance and function of the Golgi apparatus, and mitochondria migration and positioning. We demonstrate that GBF1 is present in mouse spinal cord and muscle tissues and is particularly abundant in neuropathologically relevant sites, such as the motor neuron and the growth cone. Consistent with the described role of GBF1 in Golgi function and maintenance, we observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals in this study. Our results not only reinforce the existing link between Golgi fragmentation and neurodegeneration but also demonstrate that pathogenic variants in GBF1 are associated with HMN/CMT2.

Taste disorder in facial onset sensory and motor neuronopathy: a case report

BackgroundTaste disorder is a common symptom in the general population. Several studies have shown that patients with neurological disorders, such as amyotrophic lateral sclerosis and Parkinson’s disease, develop taste disturbance. Facial onset sensory and motor neuronopathy (FOSMN) is a rare disease characterized by sensory disturbance and weakness spreading from the face to the limbs caudally. We describe a patient with FOSMN who showed taste disorder as the sole initial symptom.Case presentationA 49-year-old man who smoked cigarettes developed taste disturbance. Despite using zinc supplements, an herbal medication, and an ointment, his taste disorder worsened. 4 years later, a tingling feeling emerged at the tip of his tongue and gradually spread to his entire lips. At 55 years of age, he showed difficulty in swallowing, followed by facial paresthesia, muscle atrophy, and weakness in the face and upper limbs without apparent upper motor neuron sign. Cessation of smoking did not improve his taste disturbance, and he was unable to discriminate different tastes on the entire tongue. In an electrogustometric study, electrical stimulation did not induce any type of taste sensation. Blink reflex showed delayed or diminished R2 responses. Needle electromyography revealed severe chronic neurogenic changes in the tongue and masseter muscles. Mild chronic neurogenic changes were also observed in the limbs. In the thoracic paraspinal muscles, active neurogenic changes were detected. Findings of hematological and cerebrospinal fluid analyses, and magnetic resonance images of the brain and spinal cord were unremarkable. One cycle of intravenous immunoglobulin therapy did not improve his symptoms. We diagnosed him as having FOSMN with the sole initial symptom of taste disorder. Nine years after the onset of taste disorder, he developed impaired sensation of touch in the right upper limb and required tube feeding and ventilator support.ConclusionTaste disorder can be the initial manifestation of FOSMN and might involve the solitary nucleus.

A case of overlapping adult‐onset linear scleroderma and Parry‐Romberg syndrome presenting with widespread ipsilateral neurogenic involvement

Linear scleroderma is a variant of localized scleroderma. We report a 43-year-old woman who had developed left arm weakness and linear scleroderma on her back during pregnancy at 25 years of age, followed by left hemifacial atrophy and left leg weakness. She had multiple linear scleroderma lesions on her trunk and left limbs, left eyelid ptosis, impairment of vertical movement and abduction of the left eye, left hemifacial atrophy, and weakness and atrophy of the sternocleidomastoid, trapezius, and proximal limb muscles on the left side. On serology, antibodies to U1-ribonucleoprotein and Jo-1 were positive; anti-scleroderma-70 antibody was negative. Skin biopsy demonstrated increased hypertrophic collagen fibers without inflammatory infiltrates. Needle electromyography of left limb muscles revealed mild neurogenic patterns; left quadriceps muscle biopsy showed chronic neurogenic changes. Brain magnetic resonance imaging revealed mild left hemispheric atrophy. This is a rare case of linear scleroderma and Parry-Romberg syndrome presenting with widespread ipsilateral neurogenic manifestations.

5. All That glitters is not gold

IntroductionInflammatory muscle disease is a rare but well-recognised manifestation of systemic vasculitis. It can present as focal myositis or symmetrical proximal muscle involvement seen in polymyositis and dermatomyositis. Investigative findings in inflammatory myositis include raised creatine kinase, abnormal electromyography and muscle biopsy. MR scans can identify muscle abnormality, oedema, fibrosis and the extent of muscle involvement, and are routinely requested to evaluate patients with suspected or definite myositis. They also guide us to the appropriate muscles to biopsy. MR scans are not diagnostic of myositis and treating clinicians must be aware of its mimics. Our case demonstrates one such mimic.Case descriptionA 59-year-old male patient under care of the renal physicians for ANCA-associated vasculitis complained of bilateral thigh pain. He had completed IV cyclophosphamide therapy (CYCLOPs protocol) for vasculitis affecting lungs, kidneys, and ENT. He was taking 30mg prednisolone and 100mg azathioprine daily. He denied muscle weakness, paraesthesia, or sensory symptoms. There was no muscle wasting, fasciculation, or sensory loss. Deep tendon reflexes were normal.8-months prior, he was investigated for right hip pain and paraesthesia with MR spine and right hip, and neurophysiological studies. Investigations confirmed lumbar disc prolapse with neurophysiology in keeping with right L4 denervation changes. He had been treated with physiotherapy and daily pregabalin, duloxetine, and co-codamol.Renal physicians requested MR thigh, which was reported as muscle oedema over the long length of the right vastus medialis and lateralis, suggesting myositis. Rheumatology referral for myositis related to vasculitis was made. He was PR3+ve-3IU/ml (improved), ESR-2, CRP-4.6mg/L, CK-94U/L. EGFR remained stable at 66ml/min. Clinical features were not supportive of myositis and systemic vasculitis was in remission. The decision was made to discuss scans at the rheumatology- radiology meeting before considering a change in immunosuppression or muscle biopsy.Radiologists felt that findings of localised muscle group involvement suggested a neurogenic cause rather than primary muscle inflammation. They had reviewed MR lumbar spine done previously which had identified degenerative changes with right foraminal stenosis at L3-4 and L4-5 disc space. Electrophysiology showed chronic neurogenic changes of moderate severity in predominately L4 innervated muscles – vastus medialis and adductor magnus of the right lower limb. Findings were supportive of chronic right L4 radiculopathy and not a vasculitic neuropathy or myositis.Hence immunosuppression was left unchanged. He responded well to physiotherapy and did not require spinal surgical intervention.DiscussionOur patient developed bilateral thigh pain in the setting of vasculitis. MR imaging was suggestive of myositis. Differential diagnoses included myositis related to vasculitis, primary focal myositis followed by vasculitic neuropathy, or denervation changes due to nerve entrapment.MRI is an excellent imaging modality for skeletal muscle due to its soft tissue resolution. It helps in narrowing differentials in skeletal muscle pathology, clinicians are able to identify individually affected muscle or muscle groups, give information about active muscle inflammation and/or damage. They can assist clinicians in targeting muscle for biopsy. Pattern and extent of muscle involvement can provide valuable clue to peripheral nerve or root lesion.Though MR suggested myositis, clinical assessment was not typical of myositis. Our patient had no systemic features of active vasculitis, which are concurrently present in 80% of vasculitic neuropathies. Neurophysiology in vasculitic neuropathy typically shows evolving multifocal axonal neuropathy with reduced compound muscle action potential amplitudes. His electrophysiology was of chronic denervation in the L4 region and explained the patient’s clinical symptoms and MR findings.For skeletal muscle pathology, three key patterns of MRI signal intensity include mass lesions, fatty infiltration and muscular oedema. In this patient, recognising unilateral muscle oedema localised to the vastus medialis and lateralis (innervated by L4) was key to diagnosis. Other muscles innervated by L4 nerve root are iliopsoas, tibialis anterior and posterior. Neurophysiology did demonstrate changes in iliopsoas muscle. In this patient, the muscle atrophy common to lower motor neurone lesions was not present. This is possible when partial denervation or reinnervation occurs, changes noted on neurophysiological studies in this patient.Our case shows MR evidence of myositis may not always equate to inflammatory myositis. In this patient, awareness of the radiological mimics of myositis avoided a muscle biopsy or further immunosuppression.Key learning pointsMyositis is an uncommon but recognised manifestation of systemic vasculitis. Chronic denervation can cause muscle abnormalities that appears similar to myositis on MR scan of the affected muscle. As such Clinicians need to be aware of this similarity and in patients with localised or focal myositis. Knowledge of the muscles innervations may help to establish a neurogenic aetiology where muscles are solely affected. Muscle atrophy can be notably absent in denervated muscle if the nerve is partially denervated or regenerating.Conflict of interestThe authors declare no conflicts of interest.

F95. Laryngeal electromyography in patients with Amiotrophic Lateral Sclerosis (ALS): Preliminary results

Introduction Amyotrophic Lateral Sclerosis (ALS) is the most relevant motor neuron disease in adults and characterized by widespread weakness. Despite frequent bulbar involvement, little is known about clinical and electrophysiological changes in the larynx in patients with ALS. The objective of this study was to evaluate the frequency and pattern of involvement of laryngeal muscles in ALS and its functional relevance. In addition, we assessed whether laryngeal EMG (LEMG) would increase the diagnostic sensitivity for ALS. Methods Fourteen ALS patients, 13 with spinal onset and 1 with bulbar onset, underwent nasofibroscopy (NF) followed by LEMG, in which a concentric needle was used to evaluate the thyroid-arytenoid (TA), lateral crico-arytenoid (CAL), posterior crico-arytenoid (CAP) and crico-thyroid (CT) muscles, at rest and during activation. After LEMG, resting and activation of the genioglossus and masseter muscles were also studied using the same concentric needle. Results The mean age of the patients was 48.5 years and there were 6 women. The procedures were fast (30 min on average) and uneventful. Thirteen patients presented neurogenic changes in at least one laryngeal muscle. A single patient had entirely normal LEMG. We found a pattern compatible with chronic denervation (MUAPs remodeling and incomplete recruitment) with the following frequency: TA muscle in 11/14 patients (78.5%); CT in 10/14 patients (71.4%); CAP in 10/14 patients (71.4%) and CAL in 7/14 patients (50%). In 8 patients, there were fibrillations and/ or fasciculations associated with chronic neurogenic changes in the same muscle; of these, 4 had no alteration in the genioglossus muscle and 2 had only chronic alterations in the same muscle. NF revealed motor abnormalities in the larynx in 9 patients; in the remaining 5, NF was normal but LEMG identified signs of denervation in 4 of them. Conclusion LEMG is able to identify laryngeal denervation in patients with ALS. This procedure may increase diagnostic sensitivity for ALS by identifying bulbar involvement in patients without tongue denervation. Changes in LEMG may precede clinical involvement of the larynx in these patients.

It's Not the Lung! When a Neuromuscular Disease Presented as Recurrent Episodes of Shortness of Breath

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Recurrent episodes of shortness of breath and consequences of respiratory failure despite treatment requires reconsideration as such presentations may be due to a neuromuscular disease. CASE PRESENTATION: A 66yo male with a past medical history of hypertension and diastolic heart failure with EF 55% presents with progressively worsening dyspnea on exertion and multiple hospitalizations for hypoxic respiratory failure. CT chest revealed nonspecific bibasilar consolidations consistent with either atelectasis, aspiration, or pneumonia. Lung function demonstrated a mild restrictive defect, no obstruction, normal diffusion capacity, and no bronchodilator response. Patient improved with a trial of steroids but his clinical status continued to decline. Further history revealed loss of energy, generalized muscle weakness, joint pain, dysphagia with liquids but not solids, orthopnea, and dyspnea resulting in significant decrease in functional capacity to the point he was unable to use a sweeper around his house. Physical exam revealed central muscle wasting. Patient was urgently referred to Neurology and a motor nerve conduction study was obtained due to suspicion of a neuromuscular disorder. EMG of the upper and lower extremities showed abnormal activity and chronic neurogenic changes in multiple myotomes with decreased recruitment, consistent with an acute on chronic denervation process. After clinical evaluation, patient was formally diagnosed with ALS by Neurology. DISCUSSION: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular degenerative disease of the upper and lower motor neurons resulting in muscle weakness, fasciculations, atrophy, and hyper-reflexia. Presentation is variable but is most often either bulbar, with complaints of dysphagia or dysarthria, or spinal, with complaints of muscle weakness and gait instability. However, dyspnea is seldom the primary symptom at presentation. Diagnosis is multifaceted and individualized, requiring a thorough history and physical examination. Advanced studies such as electromyography are utilized to demonstrate denervation in the limbs. When left untreated, major morbidity and mortality in the form of chronic aspiration, secretion retention, or pneumonia may result. Despite the lack of a cure, various medications and assist devices may prolong and improve the overall quality of life and mortality. CONCLUSIONS: Shortness of breath, though a common symptom for an underlying intrinsic lung disease such as pneumonia or COPD, may actually be the result of a neuromuscular disorder. A careful history and physical exam from a pulmonary standpoint is crucial to the aid in diagnosis. Reference #1: Pavletic, Adriana J., and Oleh Hnatiuk. “Puzzling Dyspnea Caused by Respiratory Muscle Weakness.” Journal of the American Board of Family Medicine: JABFM (2012); 25.3:396-397. Reference #2: Rowland, Lewis, and Shneider, Neil. “Amyotrophic Lateral Sclerosis”. The New England Journal of Medicine: NEJM (2001); 344:1688-1700. DISCLOSURE: The following authors have nothing to disclose: Meilin Young, Tiffany Dumont, Anil Singh No Product/Research Disclosure Information

O21 Peak ratio and motor unit potential analyses in detection of chronic neurogenic changes in amyotrophic lateral sclerosis

Objectives Peak ratio analysis is a quantitative way of analyzing interference pattern by turns-amplitude analysis. We aimed in this study to compare the sensitivities of peak ratio analysis and quantitative motor unit potential (MUP) analysis in detecting chronic neurogenic changes in amyotrophic lateral sclerosis (ALS). Methods Twenty-two patients (1 definite, 7 probable, and 9 possible ALS according to Awaji criteria as reference standard, and 5 progressive muscular atrophy) were prospectively included. Quantitative MUP and peak ratio analyses were done in 22 biceps brachialis (BB), 22 tibialis anterior (TA) and 18 abductor pollicis brevis (APB) muscles on the least affected side. Results were compared to laboratory controls. The sensitivity of MUP duration and peak ratio was compared using the McNemar chi-square test. Results Peak ratio analysis was more frequently abnormal than MUP analysis in BB (59% vs. 23%), and TA (59% vs. 18%) muscles ( p Discussion Peak ratio analysis sampled at stronger effort detected more frequently chronic neurogenic changes than MUP analysis recruited at weak effort. Conclusions Peak ratio analysis may provide earlier detection of chronic neurogenic changes, thereby facilitating earlier diagnosis of ALS. Significance Peak ratio analysis which is available in commercial EMG machines should be considered in the electrodiagnostic investigation of ALS.

Recurrent stingers in an adolescent American football player: dilemmas of return to play. A case report and review of the literature

ABSTRACTWe present the case of a 16-year-old football linebacker with a history of recurrent stingers. Initial physical examination was normal as were cervical spine radiographs. MRI of the cervical spine revealed relative stenosis. Electrodiagnostic testing revealed chronic bilateral neurogenic changes of the superior trunk of the brachial plexus. A Kerr Collar was obtained to minimize head acceleration and force transmission through the neck. While there are return-to-play guidelines for recurrent stingers, there are inconsistencies with those recommendations. Our case highlights the challenges in contact sport athletes with recurrent stingers.

両下肢近位筋優位の筋力低下を呈した家族性アミロイドポリニューロパチー（FAP ATTR Ile107Val）の1例

Proximal dominant muscle weakness is rare in transthyretin (TTR)-related familial amyloid polyneuropathy (FAP). A 69-year-old Japanese man developed numbness and dysesthesia of the first, second and third digits of both hands since 2008. He presented to our hospital with one year history of progressive proximal muscle weakness in the lower extremities since 2013. Neurological examinations revealed predominant proximal muscle weakness and atrophy with areflexia in the lower extremities, decreased superficial sensation in the first, second and third fingers of both hands, and decreased superficial and deep sensation in the lower extremities. Nerve conduction studies revealed an axonal degeneration type of sensorimotor polyneuropathy and bilateral carpal tunnel syndrome. Electromyogram revealed acute and chronic neurogenic changes predominantly in proximal muscles. We performed biopsy of the left quadriceps muscle and observed neurogenic changes in the muscle tissue and an amyloid deposition in the adipose tissue. This amyloid deposition was not seen in endomysium, perimysium and blood vessels. Genetic analysis of the TTR gene revealed the patient was heterozygous for a single nucleotide substitution c.379 A>G, which resulted in the replacement of valine with isoleucine at position 107 of the mature protein. We diagnosed his condition as FAP with Amyloid Transthyretin (ATTR) Ile107Val.

Is suprascapular neuropathy common in high-performance beach volleyball players? A retrospective analysis.

Pain in the shoulder is a common problem in overhead sports and at times goes along with atrophy of the supra- and infraspinatus muscles. A neuropathy of the suprascapular nerve is one possible reason. The aim of the study was to examine the suprascapular nerve in Austrian high-performance beach volleyball players. In this cross-sectional study, 18 high-performance beach volleyball players were included. An electrophysiological examination was performed consecutively. Nerve conduction studies of the suprascapular nerve were performed bilaterally. Needle electromyography was done for the infraspinatus muscle of the dominant arm. Additionally, pain and muscle atrophy were evaluated. No acute or chronic neurogenic changes in the infraspinatus muscle were seen in any player, although atrophy of the suprascapularis innervated muscles was present in five players. A lesion of the suprascapular nerve could not be shown in any of the players. Therefore, a biomechanical cause has to be considered for the clinical symptoms in the present study population.

Anterior displacement of the spinal cord on flexion views in a patient with unilateral arm weakness

A 21-year-old man presented with a 1 year history of progressive right arm weakness and muscle wasting. The weakness was gradual in onset, initially beginning distally with weakness of wrist flexion; however it spread to involve the whole of the right arm. There was no weakness in the left arm or lower limbs and no other neurological symptoms. He took no regular medications, and did not have any significant past history. He worked in the freezer section of an abattoir. On examination, there was atrophy of the right pectoralis major, triceps, flexor and extensor muscle groups in the forearm, abductor pollicis brevis and all interossei muscles. There were fasciculations of the right triceps but also fasciculations evident in the left triceps muscle. There was moderate weakness across all muscle groups in the right arm, however the weakness and wasting was more marked in the hand and forearm muscles. Froment’s sign was positive in the right hand. Reflexes were normal and symmetrical. Sensation, proprioception and coordination were normal. Full blood count, electrolytes, serum protein electrophoresis and cerebrospinal fluid analysis were unremarkable. Nerve conduction and electromyography showed chronic partial denervation in the right C5 to T1 innervated muscles maximal in the lower myotomes, with minimal active denervation. These findings were consistent with chronic neurogenic changes in spinal roots or anterior segments. He underwent an MRI of his cervical spine in neutral and flexed positions (Fig. 1).

SLOWLY PROGRESSIVE UPPER LIMB WEAKNESS: TWO CASES OF HIRAYAMA DISEASE AND REVIEW OF LITERATURE

BackgroundWe present two cases of Hirayama disease. Hirayama disease (HD) is a rare, disabling, anterior horn disorder affecting predominantly young, males. HD presents with asymmetric or unilateral wasting and weakness...