Search

Hand weakness is a frequent chief concern in neurology practice. We report a case of a 55-year-old woman presenting with a chronic, gradually worsening right hand weakness and atrophy, selectively affecting the thenar muscles, without any sensory symptoms. She had a history of carpal tunnel syndrome and previously underwent surgical carpal tunnel release. This case delves into the differential diagnosis of hand weakness and atrophy, emphasizing the significance of myotomal innervation in intrinsic hand muscles. Furthermore, it outlines a systematic approach to diagnosing an uncommon cause for a common clinical presentation, offering a comprehensive differential diagnosis, and exploring various possible causes.

Objectives: To determine the relationship between the number of plasma exchanges and clinical outcome in patients experiencing myasthenic crisis., Methods: We retrospectively reviewed all episodes of myasthenia gravis exacerbation/crisis who received plasmapheresis in patients admitted to a single-center tertiary care referral center from July 2008 to July 2017. We performed statistical analyses to determine whether the increased number of plasma exchanges improves the primary outcome (hospital length of stay) and the secondary outcome (disposition to home, skilled nursing facility, long-term acute care hospital, or death)., Results: There is neither clinically observable nor statistically significant improvement in length of stay or disposition on discharge in patients who received 6 or greater sessions of plasmapheresis., Conclusions: This study provides class IV evidence that extending the number of plasma exchanges beyond 5 does not correlate with decreased hospital length of stay or improved discharge disposition in patients experiencing myasthenic crisis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction/aims: The purpose of this literature review is to develop an evidence-based guideline for the use of neuromuscular ultrasound in the diagnosis of ulnar neuropathy at the elbow (UNE). The proposed research question was: "In patients with suspected UNE, does ulnar nerve enlargement as measured with ultrasound accurately identify those patients with UNE?", Methods: A systematic review and meta-analysis was performed, and studies were classified according to American Academy of Neurology criteria for rating articles for diagnostic accuracy., Results: Based on Class I evidence in four studies, it is probable that neuromuscular ultrasound measurement of the ulnar nerve at the elbow, either of diameter or cross-sectional area (CSA), is accurate for the diagnosis of UNE., Recommendation: For patients with symptoms and signs suggestive of ulnar neuropathy, clinicians should offer ultrasonographic measurement of ulnar nerve cross-sectional area or diameter to confirm the diagnosis and localize the site of compression (Level B)., (Copyright © 2021 by the American Association of Neuromuscular & Electrodiagnostic Medicine, Inc. All rights reserved.)

Peripheral neuropathy is seen in 15% of patients with IgA monoclonal gammopathy. Treatment and prognosis of dysproteinemic neuropathy is usually guided by the underlying plasma cell disorders, which could be either benign or malignant. The true incidence of hematologic malignancy in patients with neuropathy associated with IgA monoclonal gammopathy is not known. However, patients with IgA M-protein are generally at increased risk for malignant transformation. Since neuropathy may be the first and only organ involvement, neurologists are key contributors in identifying each patient's plasma cell dyscrasia. We report two patients who presented with severe progressive polyneuropathy, had a detectable low-level IgA lambda paraproteinemia dismissed as incidental. Both were diagnosed later with a combination of malignant plasma cell dyscrasia and AL amyloidosis resulting in multiorgan failure and death. Both patients demonstrated red flags for malignant progression including abnormal serum free light chain, rapidly progressive debilitating neuropathy refractory to immunotherapy, prominent autonomic dysfunction, and weight loss. In summary, patients with IgA monoclonal gammopathy presenting with polyneuropathy can be at risk for malignant transformation. Failure to investigate for hematologic malignancy and AL amyloidosis may cause significant delays in treatment and result in fatal outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Diaphragm Pacing(DP) demonstrates benefits over mechanical ventilation(MV) for spinal cord injured(SCI) patients. The hypothesis of this report is that phrenic nerve conduction study(PNCS) results cannot differentiate success or failure in selection of patients for DP. Direct surgical evaluation of the diaphragm should be performed., Methods: Observational report of prospective databases of patients undergoing laparoscopic evaluation of their diaphragms to assess for ability to stimulate to cause contraction for ventilation., Results: In 50 SCI patients who could not be weaned from MV, PNCS results showed latencies in stimulated patients (n = 44) and non-stimulated(n = 6) overlapped (7.8 ± 2.5 ms vs 9.4 ± 2.8 ms) and the null hypothesis cannot be rejected (p-value>0.05). Amplitudes overlapped (0.4 ± 0.2 mV vs 0.2 ± 0.2 mV) and the null hypotheses cannot be rejected (P-value >0.05). In 125 non SCI patients with diaphragm paralysis, there were 78(62.4%) with false negative PNCS., Conclusion: PNCS are inadequate pre-operative studies. Direct laparoscopic evaluation should be offered for all SCI patients to receive the benefit of DP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal, neuromuscular disease with no cure. ALS incidence rates have not been assessed specifically in Ohio, yet the state contains both metropolitan and rural areas with a variety of environmental factors that could contribute to disease etiology. We report the incidence of ALS in Ohio residents diagnosed from October 2016 through September 2018., Methods: We engaged practitioners from 9 Ohio sites to identify newly diagnosed ALS patients and to complete case report forms with demographic and clinical information. ALS was diagnosed according to the Awaji criteria and classified as either definite, probable, or possible. We developed a method to estimate missing cases using a Poisson regression model to impute cases in counties with evidence of undercounting., Results: We identified 333 newly diagnosed ALS patients residing in Ohio during the 2-year index period and found incidence rates varied in the 88 state counties. After incorporating the estimated 27% of missing cases, the corrected crude annual incidence was 1.96/100,000 person-years, and the age- and gender-standardized incidence was 1.71/100,000 person-years (standardized to the 2010 US census)., Discussion/conclusion: The estimated Ohio incidence of ALS is overall similar to that reported in other states in the USA. This study reveals a geospatial variation in incidence within the state, and areas with higher rates warrant future investigation., (The Author(s). Published by S. Karger AG, Basel.)

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted odds ratio [OR] 1.60 95% confidence interval [CI] 1.04-2.45), with significantly greater effects for injuries occurring 10 or more years prior to symptom onset (P = .037). ALS risk was increased for those reporting severe electrical burns (adjusted OR 2.86, 95% CI 1.37-6.03), with odds ratios highest for burns after age 30 (OR 3.14), and for burns 10 or more years prior to symptom onset (OR 3.09). Hobbies involving lead were the most strongly associated with ALS risk (adjusted OR 2.92, 95% CI 1.45-5.91). Exposures to lead 20 or more years prior to diagnosis had larger effect sizes compared to those occurring more recently. Holding a job in mechanics, painting, or construction was associated with ALS. The identification of these specific environmental factors associated with ALS highlight the need for future prospective and laboratory studies to assess causality, biological mechanisms, and find prevention or treatment opportunities., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Objective: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG)., Methods: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups., Results: Patients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone., Conclusions: Thymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone., Clinicaltrialsgov Identifier: NCT00294658., Classification of Evidence: This study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone., (© 2020 American Academy of Neurology.)

Introduction: Chronic immune sensorimotor polyradiculopathy (CISMP) is a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant affecting both sensory and motor nerve roots without evidence of peripheral nerve demyelination., Methods: We report a case series of 9 patients with CISMP, identified from 2 tertiary centers. Clinical, electrodiagnostic, and neuroradiologic features, and treatment responses, were retrospectively reviewed., Results: Patients presented with sensorimotor deficits and hypo-/areflexia, predominantly involving lower extremities. Three had cranial nerve involvement. Electrodiagnostic findings in all patients localized to roots proximal to dorsal root ganglia, without evidence of peripheral nerve demyelination. Cerebrospinal fluid examination revealed an albuminocytologic association. Eight patients exhibited gadolinium enhancement and thickening of multiple spinal nerve roots and/or cranial nerves. All patients demonstrated good responses to immunotherapies., Discussion: CISMP is similar to CIDP in many aspects, but lacks typical electrodiagnostic findings of peripheral nerve demyelination. It is important to recognize this unusual and treatable entity. Muscle Nerve 59:658-664, 2019., (© 2019 Wiley Periodicals, Inc.)

Objectives: To evaluate the effectiveness of rescue treatment (intravenous immunoglobulin or plasma exchange) in patients with Guillain-Barre syndrome who did not respond or deteriorated after the initial management with intravenous immunoglobulin., Methods: We performed a retrospective review of the medical records of patients who responded poorly or did not respond to intravenous immunoglobulin treatment. The disability parameters of those who received second-line treatment with intravenous immunoglobulin or plasma exchange (20 patients) were compared with those who did not receive second-line treatment (19 patients)., Results: There was a statistically significant improvement in disability scores at 1 month in the patients who received the rescue treatment (p = 0.033). However, there was no significant difference in the disability scores at 3 and 6 months, or in length of intensive care unit stay., Conclusion: Our study showed that a second course of treatment to carefully selected patients may be beneficial., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events., Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50-0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed., Findings: Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase., Interpretation: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis., Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Neuromyotonic and myokymic discharges are abnormal electrical muscular discharges caused by ectopic discharges from motor axons and represent the hallmarks of peripheral nerve hyperexcitability. Neuromyotonic discharges are specific for peripheral nerve hyperexcitability syndromes, whereas myokymic discharges may occur either focally or in a more generalized fashion in many other peripheral nerve disorders. Isaacs syndrome and Morvan syndrome are rare acquired peripheral nerve hyperexcitability disorders that share common clinical features and are often associated with elevated voltage-gated potassium channel-complex antibodies. Central nervous system symptomatology is more common in Morvan syndrome, which also overlaps with limbic encephalitis. Cramp-fasciculation syndrome, a more common syndrome, may represent a milder form of peripheral nerve hyperexcitability. Peripheral nerve hyperexcitability syndromes should be distinguished from stiff person syndrome, myotonic disorders, and rippling muscle disease. When severe, Isaacs syndrome and Morvan syndrome may be disabling but often respond to membrane-stabilizing drugs and immunomodulatory treatments. The electrophysiologic features of these disorders are described., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cervical spinal cord injury can result in catastrophic respiratory failure requiring mechanical ventilation with high morbidity, mortality, and cost. Diaphragm pacing was developed to replace/decrease mechanical ventilation. We report the largest long-term results in traumatic cervical spinal cord injury., Methods: In this retrospective review of prospective institutional review board protocols, all patients underwent laparoscopic diaphragm mapping and implantation of electrodes for diaphragm strengthening and ventilator weaning., Results: From 2000 to 2017, 92 patients out of 486 diaphragm pacing implants met the criteria. The age at time of injury ranged from birth to 74 years (average: 27 years). Time on mechanical ventilation was an average of 47.5 months (range, 6 days to 25 years, median = 1.58 years). Eighty-eight percent of patients achieved the minimum of 4 hours of pacing. Fifty-six patients (60.8%) used diaphragm pacing 24 hours a day. Five patients had full recovery of breathing with subsequent diaphragm pacing removal. Median survival was 22.2 years (95% confidence interval: 14.0-not reached) with only 31 deaths. Subgroup analysis revealed that earlier diaphragm pacing implantation leads to greater 24-hour use of diaphragm pacing and no need for any mechanical ventilation., Conclusion: Diaphragm pacing can successfully decrease the need for mechanical ventilation in traumatic cervical spinal cord injury. Earlier implantation should be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Immunomodulating drugs are widely used in autoimmune, transplant, and cancer patients. However, these drugs are associated with various autoimmune neuromuscular diseases such as demyelinating polyneuropathy, myasthenia gravis, and myositis. Early recognition of these complications and immediately terminating these drugs are very essential since some are life-threatening conditions. This review provides a general overview of drug-induced autoimmunity and autoimmune neuromuscular diseases associated with tumor necrosis factor alpha (TNF-α) antagonists, immune checkpoint inhibitors, and interferon (IFN) type 1 (IFN-β and IFN-α).

Immune checkpoint inhibitors, used as immunotherapy in the treatment of melanoma and refractory cancer, may trigger autoimmune disorders. We describe a case of Guillain-Barré syndrome (GBS) after the treatment with ipilimumab and nivolumab and review 4 other reported cases. We confirmed the diagnosis of GBS by electrodiagnostic and cerebrospinal fluid studies. Electrodiagnostic results showed findings consistent with acquired demyelinating polyneuropathy and cerebrospinal fluid showed albuminocytologic dissociation. All patients were treated with intravenous immunoglobulin or other immunomodulating therapy. Among 5 cases which include our patient, 2 did well, 1 did not improve, and 2 died of respiratory insufficiency and multiorgan failure. Enhancing T-cell activation from immune checkpoint inhibitors may trigger GBS which should be suspected when progressive weakness and areflexia occur after treatment with immune checkpoint inhibitors.

Purpose of Review: This article provides a review of the clinical phenotypes and evaluation of peripheral nerve hyperexcitability syndromes. These rare diagnoses include cramp-fasciculation syndrome, Isaacs syndrome, and Morvan syndrome. Recent investigations have led to an understanding of the autoimmune underpinnings of these conditions and their specific associated antibodies. As the presentation of peripheral nerve hyperexcitability syndromes includes muscle stiffness, twitches, and spasms, which are also shared with certain central nervous system and myopathic conditions, the differential diagnosis of peripheral nerve hyperexcitability syndromes is reviewed., Recent Findings: Peripheral nerve hyperexcitability syndromes share clinical and electrodiagnostic evidence of motor nerve instability; however, their clinical presentations are varied. Case reviews have helped us understand the spectrum of symptoms associated with the three peripheral nerve hyperexcitability syndromes reviewed here: cramp-fasciculation syndrome, Isaacs syndrome, and Morvan syndrome. More recently, research has focused on understanding the voltage-gated potassium channel complex antibodies as well as neoplasms associated with these conditions., Summary: The diagnosis of peripheral nerve hyperexcitability syndromes requires a high index of suspicion, support from the physical examination, familiarity with the spectrum of symptoms associated with peripheral nerve hyperexcitability syndromes, and recognition of diagnostic EMG features. Voltage-gated potassium channel complex antibodies are associated with these conditions. Optimum treatment and autoimmune pathogenesis remain areas of active research.

Objective: To analyze the clinical characteristics of patients with POEMS presenting with polyneuropathy and discuss associated diagnostic challenges., Method: Retrospective analysis of 6 patients from 2 tertiary-care institutions., Results: Six patients presented with progressive sensorimotor deficits predominantly or exclusively in the lower extremities and were diagnosed with POEMS syndrome. In 4 patients, a diagnosis of chronic inflammatory demyelinating polyradiculopathy (CIDP) was mistakenly made. Low concentration of serum paraprotein and elevated vascular endothelial growth factor (VEGF) were detected in all 6 patients. Initial serum immunofixation and skeletal survey were normal in 2 patients each. On nerve conduction studies, motor and sensory responses were absent in the lower extremity in all 6 patients. Conduction velocity slowing and F-wave latency prolongation appear slightly more pronounced than distal motor latency prolongation in the upper extremity. Spinal MRI showed diffuse lumbosacral nerve root enhancement in all. In 3 patients, targeted bone marrow biopsy was needed for confirming the POEMS diagnosis. Treatment with corticosteroids, chemotherapy agent, focal radiation and/or autologous stem cell transplantation led to significant improvement in 5 of 6 patients., Conclusion: Diagnosis of POEMS should be considered in patients with progressive polyneuropathies of mixed demyelinating and axon loss features, including CIDP patients not responding to standard treatment. A polyradiculoneuropathy rather than a pure polyneuropathy seems to exist in POEMS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Paraspinous myopathy is a rare neuromuscular disorder characterized by selective involvement of the cervical, thoracic, or lumbar muscles. Leading clinical features include a bent spine or dropped head (antecollis). In myasthenia gravis (MG), patients may have camptocormia secondary to neuromuscular junction dysfunction of the paraspinal muscles, and this condition usually responds to acetylcholinesterase inhibitors or immunosuppressive treatments. However, concomitant MG and paraspinous myopathy with histologic and electrophysiologic evidence of myopathic changes of the paraspinal muscles has only been reported twice in the literature. In this case series, 5 patients with MG with paraspinous myopathy are reported. While neck and extension truncal weakness is not uncommon in MG, most often the weakness is due to neuromuscular junction dysfunction. Coexisting paraspinous myopathy and MG is under-recognized, is often resistant to mainstay treatments, and should be considered in patients presenting with neck or trunk extensor weakness.

Isolated unilateral abducens nerve palsy is usually due to ischemia, trauma or neoplasm. Dorello's canal is the space between the petrous apex and superolateral portion of the clivus, bound superiorly by Gruber's ligament. The abducens nerve travels with inferior petrosal sinus (IPS) though the Dorello's canal before entering the cavernous sinus. A 31-year-old man presented with neck pain, and binocular horizontal diplopia, worse looking towards left and at distance. He had a history of intravenous drug abuse but no history of hypertension or diabetes. On examination, he had complete left 6th nerve palsy with normal fundi, pupils, and other cranial nerves. Methicillin-resistant Staphylococcus aureus bacteremia was detected with naïve tricuspid valve endocarditis and multiple septic emboli to lungs with infarcts. His cerebrospinal fluid was normal. MRI of the brain was normal. MRV of head and neck showed thrombosis of the left internal jugular vein, left sigmoid sinus and left inferior petrosal sinus with normal cavernous sinus and no evidence of mastoiditis. He was treated with broad spectrum antibiotics. He was not anticoagulated for fear of pulmonary hemorrhage from pulmonary infarcts. Although cerebral venous sinus thrombosis commonly presents with elevated intracranial pressure, isolated ipsilateral 6th nerve palsy from its compression in Dorello's canal due to thrombosis of the ipsilateral inferior petrosal sinus is extremely rare. To our knowledge, only two patients have been reported with isolated abducens palsy due to IPS thrombosis; one caused by septic emboli and the other developed it during IPS cortisol level sampling., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

IgG4-related disease (IgG4-RD) is increasingly being recognized as an entity effecting the head and neck region. Although most commonly seen with salivary gland or paranasal sinus involvement, IgG4-RD may also involve the temporal bone and skull base. We report a rare care of a 61-year-old female with IgG4-RD presenting as synchronous lesions of the middle ear and middle cranial fossa with polyneuropathy of cranial nerves II, VI, and VII. Initial histopathological evaluation of her resected ear mass suggested a benign inflammatory process but no specific diagnosis. Her symptoms progressed over 10months prompting re-evaluation of the specimen and consideration of the IgG4-RD diagnosis. Key pathologic features included prominent lymphoplasmacytic population, storiform fibrosis, obliterative phlebitis, and IgG4 specific staining. The patient was treated with high-dose intravenous and oral steroids but was transitioned to azathioprine secondary to steroid-induced myopathy. Radiographic studies before and after treatment reveal marked improvement of the intracranial and extracranial disease. Correspondingly, her cranial neuropathies resolved. A high degree of clinical suspicion is necessary to diagnosis IgG4-RD. The diagnosis can be supported by elevated serum IgG, elevated IgG index, and pathognomonic histopathological findings. Primary treatment is with corticosteroids. However, immunotherapy using azathioprine or rituximab can be utilized in recurrent disease or patients with steroid intolerance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone., Methods: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period., Results: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003)., Conclusions: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

Introduction: Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an increasingly recognized CIDP subtype. Differentiating A-CIDP from Guillain-Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes., Methods: We report 3 patients with A-CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long-term treatment of these patients and review the literature on EDx studies in this syndrome., Results: Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy., Conclusion: Although several features may suggest the diagnosis of A-CIDP at initial presentation, close follow-up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A-CIDP from GBS patients., (© 2015 Wiley Periodicals, Inc.)

Background: Amyotrophic lateral sclerosis patients have significant respiratory abnormalities with incomplete understanding of respiratory control. This study analyzes electromyography (EMG) of the diaphragm (dEMG) using implanted diaphragm pacing (DP) electrodes., Methods: Retrospective analysis of dEMG data were obtained during Institutional Review Board and US Food and Drug Administration approved trials. The electrodes were used to analyze epochs of dEMG during multiple respiratory cycles., Results: Fifty-three patients were implanted. Thirty-six had bilateral dEMG assessments, 18 had continuous overnight readings with pulse oximetry, and 19 had serial analysis. Several findings revealed an alteration in the central respiratory drive including central apnea, hypoventilation, and hypercarbia. The electrodes showed unilateral dysfunction and demonstrated noninvasive ventilation suppression of diaphragm activity. DP can be used for serial monitoring, to decrease hypercarbia, improve sleep, and decrease atrophy., Conclusions: Multiple abnormalities of respiratory control can be seen in amyotrophic lateral sclerosis patients using dEMG through therapeutic DP electrodes. DP is used to overcome instability of respiratory control when there are intact diaphragm motor units leading to improved survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Despite being the most common entrapment neuropathy and the most common reason for referral to the electromyography (EMG) laboratory, the diagnosis of carpal tunnel syndrome (CTS) continues to be challenging due to a large number of electrodiagnostic (EDX) tests available. We present a flowchart and propose a practical approach to the diagnosis of CTS using the available literature and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) guidelines and the Practice Parameter for Electrodiagnostic Studies in Carpal Tunnel Syndrome.

Azathioprine is used for immunosuppression in myasthenia gravis (MG). We report a patient with seropositive MG who developed a brainstem lymphoma 4 years after being treated with azathioprine and review the literature on the occurrence of lymphoma in this patient population. An 82-year-old man with ocular MG who had been on azathioprine for 4 years developed subacute worsening of bulbar symptoms including diplopia, dysarthria and dysphagia mimicking MG exacerbation. Neuroimaging followed by biopsy showed brainstem diffuse large B-cell lymphoma (DLBCL). To our knowledge this is the first reported patient with brainstem DLBCL after azathioprine treatment in MG. Lymphoma has been reported in MG patients treated with azathioprine, although the incidence is unknown. We suggest reduction of azathioprine dose and subsequent discontinuation, if possible, in MG patients who are in remission. Special caution should be taken with elderly patients and Epstein-Barr virus serology prior to initiation may be useful in this population, but this requires further study., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Multifocal pyomyositis is a rare inflammatory myopathy caused by bacterial infection and abscess formation in multiple skeletal muscles. To date, electromyography (EMG) of pyomyositis has not been reported., Methods: We describe the EMG findings of a patient with pathologically proven multifocal pyomyositis., Results and Conclusions: Muscles affected by pyomyositis demonstrate EMG features similar to those of other inflammatory myopathies. Other features such as acute entrapment neuropathy may exist concomitantly due to nerve compression from muscle abscess formation., (© 2014 Wiley Periodicals, Inc.)

Objectives: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of central nervous system. We report a case of NMO spectrum disorder that developed acute cervical segmental denervation during an episode of transverse myelitis., Methods: Case report and a literature review., Results: A 69-year-old woman presented with right leg weakness, which improved in 2 weeks of intravenous methylprednisolone. Six weeks later, she returned with recurrent transverse myelitis followed by left hand weakness and atrophy. Electromyography showed active denervation on left C8/T1-innervated muscles. Magnetic resonance imaging of thoracic spine showed patchy T2-signal enhancement from T10 to lower cervical spine. NMO antibody was positive. Review of literature revealed 5 cases of cervical transverse myelitis that developed denervation on electromyography., Conclusions: Segmental denervation may occur in NMO and variants resulting from severe myelitis extending to involve gray and white matter leads to anterior horn cell loss.

Background: Diaphragm dysfunction (DD) can cause sleep abnormalities, dyspnea, atelectasis, and respiratory failure. Historical treatments, including positive pressure ventilation or diaphragm plication, may alleviate symptoms but do not restore physiologic diaphragm function. Diaphragm pacing (DP) is approved for spinal cord-injured patients and in amyotrophic lateral sclerosis. We report a series of DD patients undergoing use of DP outside of these initial indications., Methods: This report involves a prospective, nonrandomized, interventional trial under institutional review board approval at a single institution. DP involves laparoscopic motor point mapping with implantation of intramuscular electrodes in each hemidiaphragm. Postoperatively, diaphragm conditioning ensues., Results: Twenty-seven patients were evaluated; all patients had symptomatic and objective hypoventilation for an average of 36 months of symptoms. Causes included idiopathic (n = 13), chest surgery (n = 5), shoulder surgery or trauma (n = 6), and others (n = 3); 17 had bilateral involvement, 6 had nonstimulable diaphragms and were not implanted, and 21 were implanted. Thirteen (62%) had substantial clinically relevant respiratory improvements. Four ventilator patients were weaned completely. Four had partial improvement, 3 had no improvement, and 1 patient was lost to follow-up for objective analysis., Conclusion: This is the first report of DP being used to treat diverse causes of DD. Eighty-one percent of implanted patients experienced improvements. This success suggests a potential for a wider use of DP and areas for future research., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Respiratory insufficiency is the major cause of mortality in patients with amyotrophic lateral sclerosis or Lou Gehrig's disease. This is the final report of the diaphragm pacing (DP) pilot trial., Methods: Patients underwent laparoscopic diaphragm electrode implantations and subsequent conditioning of diaphragms. Serial respiratory function tests were performed in the initial year and followed until death., Results: Sixteen patients were implanted with no perioperative or unanticipated device-related adverse events. There were 452 implant-months of follow-up. DP allowed greater movement of the diaphragm under fluoroscopy, increased muscle thickness, and decreased the decline in forced vital capacity. Median survival from implant was 19.7 months with the cause of death respiratory in only 31%., Conclusions: Long-term analysis of DP in amyotrophic lateral sclerosis showed no safety issues and can positively influence diaphragm physiology and survival. This formed the initial basis for subsequent US Food and Drug Administration approval., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Myocardial pathology is rarely associated with myasthenia gravis (MG). We describe a case of newly diagnosed MG with decompensated heart failure [stress-induced cardiomyopathy (SICM)] that occurred during the crisis phase., Methods: Case report and review of literature., Results: A 42-year-old woman underwent chemotherapy followed by a transsternal resection of a malignant epithelioid thymoma invading the pericardium. A month after surgical resection, she developed progressive oropharyngeal symptoms with respiratory distress requiring tracheal intubation. Cardiac evaluation on the day of admission showed a normal ejection fraction, which rapidly decreased to 15% on the second hospital day and recovered to 45% after 1 week. Review of the literature revealed 4 myasthenic patients who developed SICM in the crisis phase; all improved with treatment., Conclusions: SICM may occur in MG crisis, especially in the presence of malignant thymoma. All previous cases including our patient had improved myocardial function and clinical outcomes.

Skeletal muscle from an encephalomyopathy was examined by morphological and biochemical modalities. Mitochondria displayed variability in size, numbers per myocyte, and morphology. Certain organelles had stacks of dense cristae, others contained variable numbers of crystalloids or several lipid droplets. In isolated skeletal muscle mitochondria, oxidative phosphorylation was reduced, but activities of the electron transport chain components were unaffected. This is the second case of adult onset encephalomyopathy with a phenotype overlapping MERRF and Kearns-Sayre syndrome associated with a heteroplasmic mtDNA 3255G > A mutation in the tRNA(UUR(LEU)). This study emphasizes the desirability of a multidisciplinary approach in the diagnosis of complex myopathies.

Introduction: We describe a patient with stable generalized myasthenia gravis who presented with new onset severe ophthalmoplegia and ptosis after initiation of voriconazole for aspergillosis., Methods: Ligand-protein docking software was used to simulate the interaction of voriconazole with the acetylcholine receptor (AChR). We tested voriconazole binding to AChR in comparison to high affinity and neutral compounds., Results: There was no clinical improvement after intravenous immunoglobulin infusion and plasmapheresis. However, the patient improved slowly after withdrawal of voriconazole. Based on our results, voriconazole binds favorably to AChR and may putatively block muscle nicotinic AChRs. Other theoretical explanations include blocking potassium channels and reducing their intracellular trafficking., Conclusions: The mechanisms involved in ocular exacerbation may be multi-factorial, reflecting the intricate dynamics of the neuromuscular junction. It is important to consider medications that harbor pyridine or pyrimidine moieties as potential causes of exacerbation in myasthenic patients, especially those who present with ocular symptoms., (Copyright © 2012 Wiley Periodicals, Inc.)

A woman with herpes simplex virus type 1 (HSV1) encephalitis had downbeat nystagmus. The nystagmus was robust in primary gaze but attenuated during upgaze, suggestive of the flocculus involvement. FLAIR and T2-sequences of the brain MRI revealed cerebral lesions typical of HSV1, but also patchy hyperintensities in bilateral flocculi. Cerebrospinal fluid polymerase chain reaction confirmed HSV1 infection. Encephalopathy and downbeat nystagmus gradually improved with acyclovir therapy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.

Mycophenolate mofetil (MMF) is used for immunosuppression in myasthenia gravis (MG). Although there are numerous data on associated infection and prophylaxis in transplant patients who are on MMF, data in MG remains lacking. We report two elderly seropositive MG patients who developed cytomegalovirus (CMV) enteritis and Epstein-Barr virus (EBV) encephalitis while on MMF for 5months and 1year, respectively. Chronic MMF therapy in MG patients may trigger life-threatening infections including CMV and EBV diseases, especially in the elderly. Similar to the practice in transplant patients, viral serology testing and appropriate prophylactic regimen with antiviral agents should be considered, particularly in older MG patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Recent epidemiological studies established extremely rare incidence of Guillain-Barre syndrome (GBS) after contemporary H1N1-influenza vaccine. We saw five patients with 'atypical' GBS variants that started within four weeks of 2010/2011 H1N1-influenza vaccine. There was no evidence for other etiologies of GBS. The patients presented with sensory ataxia, areflexia, extremity and oropharyngeal paresthesias, numbness, pain, weakness, sphincteric disturbances, and dysautonomia. One patient had Miller Fisher syndrome. All had elevated cerebrospinal fluid protein, and classic electrodiagnostic finding suggestive of GBS. All received the treatment with intravenous immunoglobulin with variable response. These pilot observations suggest that H1N1-influenza vaccine may be associated with rare and atypical variants of GBS. However, epidemiological studies with large cohorts are necessary to confirm excess cases of atypical GBS after H1N1-influenza vaccination., (Copyright © 2012. Published by Elsevier Ltd.)

Herpes zoster viral infection (shingles) frequently appears in the thoracic dermatomes with no detectable weakness. We describe three patients who exhibited classic symptoms of herpes zoster infection of the upper limb with various neuropathic findings, including multiple mononeuropathies, radiculopathy, and brachial plexopathy. The distribution of weakness and electrodiagnostic findings was not limited to the involved dermatomes. Furthermore, the electrodiagnostic studies in one patient show evidence of acquired demyelination; hence, the infectious process may include the axon and/or the myelin sheath of the peripheral nerves. In the upper limb, we suggest that a mismatch between the distribution of the vesicular herpetic rash and weakness, as corroborated by the clinical examination and the electrodiagnostic studies, may occur.

Objective: To compare clinical and economic outcomes following plasma exchange (PLEX) and intravenous immunoglobulin (IVIG) in U.S. patients with primary diagnoses of myasthenia gravis (MG)., Methods: Our cohort was identified from the Nationwide Inpatient Sample database for years 2000-2005 using codes from the International Classification of Diseases, 9th edition. Multivariate regression analyses were used to identify predictors of mortality, complications, length of stay, and total inpatient cost., Results: Among 1,606 hospitalized patients, the unadjusted mortality rate of MG crisis remained higher than those without crisis (0.44% vs 4.44%, p < 0.001), as well as the unadjusted complication rate (26.36% vs 11.23%, p < 0.001). MG crisis patients receiving PLEX had significantly more complications than those receiving IVIG (30.06% vs 14.79%, p < 0.001). Among the whole cohort, adjusted mortality and complication rates were not significantly different between the treatment groups (p > 0.05). Acute respiratory failure, major cardiac complications, and acute renal failure were associated with an increased mortality rate (p < 0.001). Age and respiratory failure were associated with an increased complication rate (p < 0.001). Length of stay was significantly longer for MG (6 vs 4 days, p < 0.001) and MG crisis (10 vs 5 days, p < 0.001) patients receiving PLEX. Inpatient costs were higher for MG ($26,662 vs $21,124, p < 0.01) and MG crisis ($53,801 vs $33,924, p < 0.001) patients receiving PLEX., Interpretation: Compared to PLEX, IVIG appears of similar clinical (mortality and complications) and perhaps of superior economic (length of stay and total inpatient charges) outcomes in the treatment of MG. Elderly and those with complex comorbid diseases including acute respiratory failure may be better treated with IVIG.