Combined tendon reflex and motor evoked potential recordings in amyotrophic lateral sclerosis.

OBJECTIVE: This retrospective (case-control) collaborative study evaluates tendon reflex recordings combined with transcranial magnetic stimulation motor evoked potentials recordings (T-MEPs) at lower limbs in amyotrophic lateral sclerosis (ALS). METHODS: T-MEPs were recorded in 97 ALS patients distinguished according to their patellar reflex briskness. Patients' electrophysiological data were compared with values measured in 60 control patients matched for age and height. Correlations studies between parameters or with some patients' clinical characteristics were also performed. RESULTS: The central motor conduction time yields the highest sensitivity (82%) and specificity (93%), allowing twice more upper motor neuron (UMN) dysfunction detection than clinical examination, and being more altered in late stages of the disease. The T response to MEP response amplitude ratio (T/MEP ar) is nearly as sensitive to detect ALS and better identifies abnormal hyperreflexia. It is not correlated with evolutive stage, contrarily to conduction time-related parameters. In addition, T-MEPs detect asymmetries escaping clinical examination. CONCLUSIONS: The corticospinal conduction to lower limbs is slowed in ALS. The T/MEP ar helps deciding when patellar reflexes are abnormal in a given patient suspected of ALS. SIGNIFICANCE: The T-MEP technique provide powerful electrophysiological biomarkers of UMN involvement in ALS. This simple and painless procedure introduces the clinically useful concept of electrophysiological hyperreflexia and might be expanded to future exploration of proximal upper limbs and bulbar territories.

Motor-neuron-disease-like phenotype associated with IgLON5 disease.

A growing spectrum of neurological manifestations are being recognized in association with IgLON5 autoimmunity, including recent reports of motor-neuron-disease-like phenotype. Here we describe four cases of IgLON5 autoimmunity with motor neuron involvement and evaluate an additional 109 probable or definite amyotrophic lateral sclerosis cases seen in our neuromuscular clinic for IgLON5-IgG seropositivity. The presence of parasomnias, vocal cord dysfunction or hyperkinetic movements in a patient with motor-neuron-disease-like phenotype should prompt evaluation for IgLON5-IgG autoantibodies. Recognition and treatment of this autoimmune disease with immunosuppressive agents may bring about significant neurological improvement in a minority of cases.

Early advance care planning in amyotrophic lateral sclerosis patients: results of a systematic intervention by a palliative care team in a multidisciplinary management programme - a 4-year cohort study.

INTRODUCTION: Although recommended, the implementation of early advance care planning is suboptimal in amyotrophic lateral sclerosis (ALS) patients. Barriers to advance care planning include healthcare professionals’ and patients’ reluctance, and uncertainty about the right time to initiate a discussion. AIM OF THE STUDY: To determine how often advance care planning was initiated, and the content of the discussion in a first routine palliative care consultation integrated within a multidisciplinary management programme. METHODS: Between June 2012 and September 2016, a prospective cohort study was conducted in Geneva University Hospitals. Sixty-eight patients were seen every 3 months for a 1-day clinical evaluation in a day care centre. RESULTS: The patients’ mean ± standard deviation age was 68.6 ± 11.9 years, 50% were women. Four patients were excluded because of dementia. Advance care planning was initiated with 49 (77%) patients in the first palliative care consultation. Interventions most often addressed were cardiopulmonary resuscitation (49%), intubation and tracheostomy (47%) and palliative sedation (36.7%). Assisted suicide was discussed with 16 patients (36.6%). Functional disability was the only factor associated with initiation of advance care planning. Nearly half of the patients wrote advance directives (45%) or designated a healthcare surrogate (41%). Bulbar onset, functional disability and noninvasive ventilation were not associated with the completion of advance directives. CONCLUSION: Early initiation of advance care planning is feasible in most ALS patients during a routine consultation, and relevant treatment issues can be discussed. All ALS patients should be offered the opportunity to write advance directives as completion was not associated with disease severity. .

Sporadic late onset nemaline myopathy with monoclonal gammopathy of undetermined significance: two cases with long term stability.

Monoclonal gammopathy of undetermined significance (MGUS) associated to sporadic late onset nemaline myopathy (SLONM) is a rare and severely disabling condition of quickly progressive limb girdle acquired myopathy. It is believed by some authors to be due to myotoxicity of light chain deposits. Two female patients were diagnosed with MGUS associated SLONM. In the first case, diagnosis was delayed by 6 years thus giving time for a severe generalized myopathy and cardiomyopathy to develop. A single anti-myeloma chemotherapy with lenalidomide markedly improved and stabilized the patient's condition despite respiratory and cardiac insufficiency. In our second patient the condition was identified one year after onset of the first symptom and markedly improved after autologous bone marrow transplantation and lenalidomide. Clinicians should be aware of monoclonal gammopathy associated sporadic late onset nemaline myopathy as this acquired muscle disorder, although extremely rare, may be reversed by adequate management.

Impaired conduction of Ia sensory fibers in multifocal motor neuropathy: An electrophysiological demonstration.

OBJECTIVES: To report the clinical and electrophysiological findings in two patients with multifocal motor neuropathy (MMN) and bilateral absent patellar and Achilles tendon reflexes despite normal strength of quadriceps and calf muscles. METHODS: The medical history and clinical evaluation were completed by electrophysiological tests: sensory and motor nerve conduction studies, needle electromyography, motor-evoked potentials (MEPs) after transcranial magnetic stimulation, patellar T (tendon) responses, quadriceps and soleus H (Hoffman) reflex recordings. RESULTS: In the two patients, history, clinical evaluation, nerve conduction studies, favorable response to intravenous immunoglobulins, and positive anti-GM1 antibodies fulfilled the diagnosis of MMN. The lower limbs were asymptomatic, except for a unilateral weakness of foot dorsiflexion. The patellar and Achilles tendon reflexes disappeared during the course of the disease. The sensory nerve conduction studies were normal or minimally modified, M-wave and MEP/M amplitude ratio to the quadriceps were normal, patellar T (tendon) responses were virtually absent, and H-reflex to the quadriceps and soleus muscles were absent. CONCLUSIONS: These observations, which show the interruption of the reflex afferent pathway, raise the question of Ia afferent involvement in the lower limbs of these two patients with MMN. Further investigations should determine the frequency and significance of these findings in this disorder.

Multidisciplinary care in amyotrophic lateral sclerosis: a 4-year longitudinal observational study.

Over a four-year period, ALS patients complied with the modalities of the multidisciplinary management follow-up without any drop-outs. The multidisciplinary management structure also contributes to increasing the experience and knowledge of the clinicians involved in managing patients suffering from this rare disease.

Symptomatic tandem spinal stenosis: a clinical, diagnostic, and surgical challenge.

Tandem spinal stenosis (TSS) is an entity which refers to spinal canal diameter narrowing in at least two distinct regions of the spine. When symptomatic, management of TSS is controversial. In this study, we present a consecutive series of patients with symptomatic TSS and report diagnostic and surgical challenges. We retrospectively reviewed a consecutive series of N = 8 patients with symptomatic TSS who underwent surgical treatment in at least one region of the spine. Patients presented with multiple complaints, including neurogenic claudication, progressive gait disturbances, and signs of radiculopathy and/or myelopathy, among others. Modified Japanese Orthopedic Association (mJOA) and Oswestry Low Back Pain Disability Questionnaire (ODI) were obtained in pre- and postoperative period. Electroneurophysiological examinations were limited to patients whose clinical and radiological signs were not sufficient to determine which region was more affected. From 2015 to 2018, we included N = 8 consecutive patients with TSS who underwent surgery by a staged approach. The stenosis was localized in the cervical and lumbar region in six patients (75%) and in the cervical, dorsal, and lumbar level (triple TSS) in two patients (25%). Four patients (50%) underwent cervical and lumbar surgery, two (25%) underwent cervical surgery alone, and two (25%) were operated in all three involved regions. Surgical treatment allowed an improvement of the mean mJOA score (from 12.5/17 to 15/17) and mean ODI score (from 41 to 28%). TSS represents a clinical, diagnostic, and surgical challenge. We recommend to systematically obtain electrophysiological and radiological examinations and then to perform a staged surgery, beginning at the most symptomatic region.

A modern multidisciplinary approach to patients suffering from cervical spondylotic myelopathy.

BACKGROUND: The traditional approach to patients suffering from cervical spondylotic myelopathy (CSM) consists of mere assessment of radiological standard magnetic resonance (MR) images and evaluation of surgical indication, depending on clinical symptoms and degree of radiological stenosis. Identification of prognostic factors for surgery remains difficult. Surgery is thought to be able to stop the disease progression, while significant improvements of neurological symptoms are not predictable. METHODS: Authors present a modern approach to patients with CSM, that is comprehensive of clinical, electrophysiological and radiological findings, and that has been developed by a multidisciplinary team of experts (neurosurgeons, neurologists, neuroradiologists). Authors tried to identify the good responders to surgery, as those who really improved symptoms, by performing an integration of these data. This approach has been used in 11 consecutive patients suffering from and operated for CSM at our Institution. The multidisciplinary protocol included the complementary use of electrophysiological (motor and somatosensory evoked potentials), radiological (magnetic resonance, cervical plain and dynamic x-rays), and clinical (modified Japanese Orthopedic Association [mJOA] and Neck Disability Index [NDI] scores, Hirabayashi Recovery Ratio) values. These data were obtained at the preoperative period, and at 3 and 12 months follow-up. We defined as "good responders" those patients having had an improvement of the Hirabayashi Recovery Ratio of 50% and of the NDI of 30%. RESULTS: The mean preoperative mJOA was 12.79 (range 3-17), while the mean mJOA at 3 and 12 months was, respectively, 14.71 and 13.43. However, only the improvement at 3 months was statistically significant, while improvements from the preoperative assessment to 12 months and from 3 to 12 months were not significant. The mean preoperative NDI was 33.57%, while it was 32.43% and 24.36% at 3 and 12 months, respectively. None of these improvements was significant. Concerning response to surgery, we observed 7/11 (63.3%) good responders according to the Hirabayashi Recovery Ratio, and 6/11 (54.5%) good responders according to NDI results. CONCLUSIONS: A modern multidisciplinary approach to patients with CSM is mandatory to investigate the different aspects of the disease. Decompressive surgery was able, in our series, to improve or stabilize clinical symptoms. Further studies are necessary to allow for a proper selection of patients by cumulative analysis of multidisciplinary findings.

Contraction response to muscle percussion: A reappraisal of the mechanism of this bedside test.

OBJECTIVE: To study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders. METHODS: In 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide. In 3 additional healthy volunteers we searched for F-waves to disclose whether percussion excites axons within the muscle. RESULTS: Responses from 28 neurologically healthy patients (15 women) were analyzed after exclusion of 2 due to technical problems. Mean age (SD) was 28 (9) years. Maximal dorsiflexion of the ankle was not significantly modified by neuromuscular junction blockade (mean difference 0.01 mV [95%CI, -0.07 to 0.08], p=0.879). Muscle percussion evoked F-waves in the 3 healthy volunteers tested. CONCLUSIONS: Maximal contraction response to muscle percussion has a muscular rather than a neural origin. However, percussion also excites axons within the muscle. SIGNIFICANCE: These findings may provide clues to understand the changes observed in neuromuscular disorders.

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.

High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca(2+) release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca(2+) leak at rest, and depressed force production due to impaired SR Ca(2+) release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca(2+)-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.

Anti-TNF alpha medications and neuropathy.

We studied the clinical, electrophysiological, and pathological features, outcome, and frequency of anti-tumor necrosis factor alpha (a-TNF) medications-induced neuropathies (ATIN) in patients with inflammatory disorders. Of 2,017 patients treated with a-TNF medication, 12 patients met our inclusion criteria for a prevalence of 0.60% and an incidence of 0.4 cases per 1,000 person-years. The median time from a-TNF medication treatment to ATIN was 16.8 months (range 2-60 months). Six patients had focal or multifocal peripheral neuropathies. The other six had generalized neuropathies. For all, a-TNF medication was stopped. Seven patients received immunoglobulin infusions. ATIN outcome was favorable in all but one patient. ATINs are rare and heterogeneous neuropathies. In 10 patients, the neuropathy was "inflammatory", suggesting that it could be due to systemic pro-inflammatory effects of a-TNF agents.

Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy.

INTRODUCTION: Acute painful diabetic neuropathy (APDN) is a distinctive diabetic polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN) and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the small-fibre involvement, (2.) occurrence paradoxically after short-term achievement of good glycaemia control, (3.) intense pain sensation and (4.) eventual recovery. In the face of current recommendations to achieve quickly glycaemic targets, it appears necessary to recognise and understand this neuropathy. METHODS AND RESULTS: Over 2009 to 2012, we reported four cases of APDN. Four patients (three males and one female) were identified and had a mean age at onset of TIN of 47.7 years (±6.99 years). Mean baseline HbA1c was 14.2% (±1.42) and 7.0% (±3.60) after treatment. Mean estimated time to correct HbA1c was 4.5 months (±3.82 months). Three patients presented with a mean time to symptom resolution of 12.7 months (±1.15 months). One patient had an initial normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms, and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had a peroneal nerve biopsy showing loss of large myelinated fibres as well as unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS: According to the current recommendations of promptly achieving glycaemic targets, it appears necessary to recognise and understand this neuropathy. Based on our observations and data from the literature we propose an algorithmic approach for differential diagnosis and therapeutic management of APDN patients.

Multifocal motor neuropathy with high titers of anti-MAG antibodies.

Multifocal motor neuropathy (MMN) and anti-myelin-associated glycoprotein (anti-MAG)-associated neuropathy are clinically and electrophysiologically distinct entities. We describe a patient with characteristic features of both neuropathies, raising the possibility of an overlap syndrome. A 49-year-old patient reported a history of slowly progressive predominantly distal tetraparesis, with mild sensory deficits. Nerve conduction studies demonstrated persistent motor conduction blocks outside compression sites, typical of MMN. Laboratory findings revealed persistently high titers of anti-MAG immunoglobulin Mλ (IgMλ) paraprotein in the context of a monoclonal gammapathy of unknown significance. Skin biopsy of distal lower limb revealed IgM positive terminal nerve perineurium deposits. This case suggests that the distinction between subtypes of chronic inflammatory neuropathies may not be as clear as initially thought, and that the pattern of pathogenicity of anti-MAG antibodies may vary.

Experimental study of a late response recorded from the thoracic wall after phrenic nerve stimulation.

OBJECTIVES: The phrenic nerve cervical stimulation induces an early motor diaphragmatic M response that may be recorded from the 7th ipsilateral intercostal space (ICS). Some responses with prolonged latency and of unclear origin can be recorded from the same recording site. The aim of the study was to determine the electrophysiological characteristics and the neuroanatomical pathways underlying the long-latency responses (LLRs) recorded from the 7th ICS. METHODS: We studied seven healthy volunteers, five patients with spinal cord injury and five patients with diaphragmatic palsy. All underwent phrenic nerve conduction study. An LLR was sought for at different stimulation sites using various stimulus intensities. RESULTS: A polyphasic LLR was recorded from the 7th ICS in all healthy subjects. It was mainly elicited by nociceptive stimulations, not only of the phrenic, but also of the median nerves. Its latency was longer than 70ms, with a wide inter- and intra-individual variability. Amplitude was highly variable and some habituation phenomenon occurred. The LLR was retained in most tetraplegic patients after phrenic nerve stimulation, but absent otherwise. It was present in all patients with diaphragmatic palsy after phrenic nerve stimulation. CONCLUSION: The LLR is likely to be produced by both intercostal and diaphragm muscles. It is a polysynaptic and multisegmental spinal response, probably conveyed by small-diameter nociceptive A-delta and/or C fibres and modulated by a supraspinal control. SIGNIFICANCE: The LLR recorded from the chest wall may constitute, by analogy with the nociceptive component of the lower limb flexion reflex in humans, a protective and withdrawal spinal reflex response.

Peripheral autoimmune neuropathy assessed using corneal in vivo confocal microscopy.

BACKGROUND: Corneal nerves can be examined using in vivo confocal microscopy (IVCM). This new technique permits sequential observation of the corneal subbasal nerve plexus and detects early signs of diabetic peripheral neuropathy. OBJECTIVE: To describe a patient with autoimmune peripheral neuropathy followed up using corneal IVCM. DESIGN: Case report. SETTING: Clinic of neurology, Geneva, Switzerland. Patient A 56-year-old man with peripheral neuropathy diagnosed as anti-myelin-associated glycoprotein neuropathy. His symptoms initially worsened despite the administration of intravenous immunoglobulins and plasma exchange. Evolution was eventually favorable after rituximab and corticosteroids were given. At 1-year follow-up, clinical recovery was almost complete, and the patient was stable according to the results of clinical and electrophysiologic assessments. Main Outcome Measure Corneal nerve measurement by IVCM. RESULTS: Examination of corneal nerves using IVCM at 2 different times during the patient's clinical evolution (peak disease and recovery phase) demonstrated histologic signs that correlated with the results of clinical and electrophysiologic assessments. CONCLUSION: This observation supports the hypothesis that corneal IVCM could also be helpful for the early detection or follow-up of autoimmune peripheral neuropathy.

Mild clinical expression of Lambert-Eaton myasthenic syndrome in a patient with HIV infection.

Neuromuscular complications of HIV are related to immunodeficiency, direct cytotoxicity of the virus or side effect of the treatments. Autoimmune disorders involving the nervous system, including Guillain-Barre syndrome, myositis and vasculitis, have been described in association with HIV. Neuromuscular junction autoimmune diseases such as myasthenia gravis have been occasionally reported in patients with HIV, whereas the Lambert-Eaton myasthenic syndrome (LEMS) has never been described. We report an unusual case of paucisymptomatic LEMS in a patient with HIV infection.