Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions.

OBJECTIVES: Plasmapheresis (PLEX) and intravenous immunoglobulin (IVIg) are commonly used to treat autoimmune neuromuscular disorders, including myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and other autoimmune neurological disorders. The side effect profiles of these therapies vary, and concern has been raised regarding the safety of PLEX in the elderly population. In this study, we have examined the pattern of PLEX and IVIg use for autoimmune neurological disorders at a single facility and in a national database, focusing on the complications in elderly patients. METHODS: We performed a retrospective chart review of adult patients at our institution receiving PLEX or IVIg for any autoimmune neuromuscular or neuro-immunological disease. Next, we analyzed the National Inpatient Sample database to confirm the trend in IVIg and PLEX use from 2012 to 2018 for a set of neuromuscular and neuro-immunological primary diagnoses. RESULTS: IVIg was overall favored over PLEX. The adverse effects were similar among elderly patients (age ≥65 years) compared with younger patients (<65 years) in our institution, even after adequate matching of patients based on age, sex, and medical history. We examined the National Inpatient Sample dataset and noted increasingly higher frequency of IVIg use, consistent with the findings from our institution or facility. CONCLUSIONS: Both PLEX and IVIg are safe therapeutic choices in adult patients with autoimmune neuromuscular disorders and other neuro-immunological diseases and can be safely administered in the appropriate clinical setting.

Veterans health administration information systems as a resource for rare disorders research: Creutzfeldt-Jakob disease as a paradigm.

OBJECTIVE: To illustrate the application of Veterans Health Administration (VHA) information systems in both clinical and epidemiologic investigations of a rare disease, our specific aims were: (1) to determine the number and incidence of Creutzfeldt-Jakob disease (CJD) diagnoses in the VHA from fiscal year (FY) 1997 through FY 2010 and (2) to describe the relevant clinical features associated with those diagnoses. METHODS: The VHA Medical SAS Datasets were queried for all unique, incident CJD diagnoses between FY 1997 and 2010. Electronic health records were then reviewed to validate diagnoses using modified criteria. RESULTS: During the study period, 115 CJD diagnoses (43 definite, 27 probable, 19 possible, and 26 suspected) were identified. Annual incidence ranged between 0.8 per million (95% CI, 0.3-1.7) in FY 2009 and 3.7 per million (95% CI, 2.1-6.4) in FY 1997. Dementia was documented in 111 cases (96.5%) and myoclonus in 73 (63.5%). Discharges consistent with CJD were noted in 31 of 78 patients (39.7%) with documented electroencephalography. CONCLUSIONS: For certain rare diseases, VHA information systems can be used to assemble a substantive case series for clinical study. However, the VHA's distinctive demographic characteristics and population dynamics may limit the external validity of epidemiologic investigations.

Neurogenic orthostatic hypotension after treatment with sorafenib.

A man in his 70s with a history of fatigue, abdominal pain, and a palpable abdominal mass was found to have a peritoneal desmoid tumour. One year after diagnosis, he was prescribed sorafenib to limit tumour growth. Two months later, he developed dyspnoea on exertion and lower extremity weakness and was reported to have supine hypertension and orthostatic hypotension. On formal autonomic testing, he was noted to have severely impaired sympathetic responses and marked orthostatic hypotension without appropriate chronotropic response. A decision to hold sorafenib was made, and treatment was started with graduated compression stockings, liberal fluid and sodium intake, and midodrine. The patient had a modest and gradual improvement in his symptoms. To our knowledge, this is the first reported case of orthostatic hypotension related to sorafenib or any vascular endothelial growth factor inhibitors.

Risperidone-induced bulbar palsy-like syndrome.

There have been several case reports of risperidone-associated dysphagia. Risperidone-induced bulbar palsy-like syndrome has not been previously described. We report on a 58-year-old gentleman with prior history of schizophrenia and remote chlorpromazine use with no history of extrapyramidal symptoms who experienced acute onset of dysphagia and facial diplegia with hyperprolactinemia while being treated with risperidone. To date there have been five reported cases of dysphagia associated with risperidone, occurring by such mechanisms as isolated pharyngeal dysfunction from pharyngeal constrictor palsy and dystonia, drug-induced parkinsonism, and acute dystonic reaction. These cases were associated either with initiation or up-titration of risperidone, with complete resolution of dysphagia after medication discontinuation or dose change. Our patient developed dysphagia within 2 weeks of taking risperidone and completely resolved 1 month after the medication was stopped. Unlike other reported cases, our patient also experienced symptomatic hyperprolactinemia, another known side effect of risperidone. Physicians should also be aware that risperidone can be associated with oropharyngeal dysphagia secondary to an acute bulbar palsy-like syndrome that places patients at increased risk of aspiration events and its associated morbidity and mortality.

Utility of intrathecal baclofen pump in primary lateral sclerosis.

Primary lateral sclerosis is a disorder categorized by insidious onset of progressive upper motor neuron dysfunction without lower motor neuron involvement. PLS often presents with gradual-onset, progressive lower extremity stiffness and pain due to muscle spasticity. Intrathecal Baclofen pumps (ITB) have been used to effectively treat spasticity in several neurologic conditions including MS and spinal cord injury. This study aimed at reviewing a cohort of PLS patients with spasticity requiring ITB to assess the clinical course, benefits, and complications in these patients. A series of 5 patients were identified who were diagnosed with PLS and received ITB as treatment for spasticity. The average age of the patients at the time of ITB insertion was 56.4 years. The average length of treatment was 10.4 years with a range of 4-15 years. All patients reported improvement in spasticity as measured by clinical examinations and Ashworth scores; 1/5 had complications with the pump related to migration of catheter. No patients required permanent removal of the ITB. ITB is a safe and effective treatment for spasticity in PLS and should be considered in other patients.

Funding the Educational Mission in Neurology.

Although it is self-evident that education in neurology is important and necessary, how to fund the educational mission is a frequent challenge for neurology departments and clinicians. Department chairs often resort to a piecemeal approach, cobbling together funding for educators from various sources, but frequently falling short. Here, we review the various sources available to fund the educational mission in neurology, understanding that not every department will have access to every source. We describe the multiple different teaching models and formats used by the modern student and educator and their associated costs, some of which are exorbitant. We discuss possible nonfinancial incentives, including pathways to promotion, educational research, and other awards and recognition. Neurological education is commonly underfunded, and departments and institutions must be nimble and creative in finding ways to fund the time and effort of educators.

Rituximab in the management of refractory myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disorder with a variable response to treatment. In this study, patients with refractory MG who were treated with rituximab were identified. A review of patients referred to the Yale Neuromuscular Clinic was performed. Patients with refractory MG who were treated with rituximab were reviewed for response to treatment. Patients who had muscle-specific kinase (MuSK(+)) or acetylcholine receptor (AChR(+)) antibodies were included. Six patients were identified who met the criteria described. All patients tolerated rituximab without side effects and had a reduced need for immunosuppressants and/or improvement in clinical function. Patients with refractory MG appeared to respond to rituximab in this small, retrospective study. This result suggests that a larger, prospective trial is indicated.

Multiple Cranial Neuropathies as the Presenting Sign in a Patient with Metastatic BRAF-Mutated Lung Adenocarcinoma with Leptomeningeal Involvement.

Leptomeningeal carcinomatosis accounts for only 4% of cases of multiple cranial neuropathies. Here, we report the case of a patient who presented with multiple synchronous cranial neuropathies. After treatment for neuroborreliosis and broad infectious workup, endobronchial ultrasound-guided mediastinal lymph node biopsy confirmed a diagnosis of metastatic BRAF-mutated lung adenocarcinoma with leptomeningeal involvement. To our knowledge, this is the first reported case of metastatic BRAF-driven lung adenocarcinoma with leptomeningeal disease at diagnosis. In this case, the presence of leptomeningeal carcinomatosis at diagnosis, not as a late manifestation of heavily pretreated disease, alludes to a possible association between leptomeningeal involvement and BRAF-mutated non-small cell lung cancer.

Teleneurology during the COVID-19 pandemic: A step forward in modernizing medical care.

BACKGROUND: The COVID-19 pandemic mandated rapid transition from face-to-face encounters to teleneurology visits. While teleneurology is regularly used in acute stroke care, its application in other branches of neurology was limited. Here we review how the recent pandemic has created a paradigm shift in caring for patients with chronic neurological disorders and how academic institutions have responded to the present need. METHOD: Literature review was performed to examine the recent changes in health policies. Number of outpatient visits and televisits in the Department of Neurology was reviewed from Yale University School of Medicine and Johns Hopkins School of Medicine to examine the road to transition to televisit. RESULTS: The federal government and the insurance providers extended their supports during the COVID-19 pandemic. Several rules and regulations regarding teleneurology were revised and relaxed to address the current need. New technologies for video conferencing were incorporated. The transition to televisits went smoothly in both the institutions and number of face-to-face encounters decreased dramatically along with a rapid rise in televisits within 2 weeks of the declaration of national emergency. CONCLUSION AND RELEVANCE: The need for "social distancing" during the COVID-19 pandemic has created a major surge in the number of teleneurology visits, which will probably continue for the next few months. It may have initiated a more permanent transition to virtual technology incorporated medical care.

Amyotrophic Lateral Sclerosis Among Veterans Deployed in Support of Post-9/11 U.S. Conflicts.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a recognized military service-connected condition. Prior prevalence studies of ALS among U.S. war Veterans were not able to address concerns related to neurodegenerative sequelae of traumatic brain injury (TBI) and disregarded risk heterogeneity from occupational categories within service branches. MATERIALS AND METHODS: We identified the prevalence of definite and possible ALS and cumulative incidence of definite ALS among Post-9/11 U.S. Veterans deployed in support of Post-9/11 conflicts (mean age 36.3) who received care in the Veterans Health Administration during fiscal years 2002-2015. Using a case-control study design, we also evaluated the association of TBI and major military occupation groups with ALS adjusting for demographics and comorbidities. RESULTS: The prevalence of ALS was 19.7 per 100,000 over 14 years. Both prevalence and cumulative incidence of definite ALS were significantly higher among Air Force personnel compared to other service branches and among tactical operation officers and health care workers compared to general and administrative officers. Neither TBI nor younger age (<45 years) was associated with ALS. Depression, cardiac disease, cerebrovascular disease, high blood pressure, and obstructive sleep apnea were clinical comorbidities significantly associated with ALS in this population of Veterans. CONCLUSION: This study among a cohort of relatively young Veterans showed a high ALS prevalence, suggesting an early onset of ALS among deployed military service members. The higher prevalence among some military specific occupations highlights the need to determine which occupational exposures specific to these occupations (particularly, Air Force personnel, tactical operations officers, and health care workers) might be associated with early onset ALS.

Is needle electromyography safe in patients on anticoagulation or antiplatelet therapy?

Needle electromyography (EMG) is a valuable diagnostic tool in the evaluation of the PNS and yet the risk of complications with this procedure in patients on anticoagulant or antiplatelet medications is unknown. Guidelines recommend caution when performing needle EMG in patients with disturbances of hemostasis because of the risks of intramuscular hemorrhage or other bleeding. This commentary reviews a study by Lynch et al. that investigated the risk of hematoma formation following needle EMG of the tibialis anterior muscle in 158 patients on antiplatelet or anticoagulant medications. The authors used a standardized approach to the needle examination, followed by application of direct pressure to the insertion site after removal of the needle. Three hematomas were detected--two in patients on warfarin, and one in a patient taking clopidogrel. None of the patients had symptomatic bleeding. These results indicate that the risk of hematoma formation is low following needle EMG when direct pressure is applied after removal of the needle.

Neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis.

OBJECTIVE: To explore the association of peripheral neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) use in patients with cancer. METHODS: Published data search up to November 2018 reporting peripheral neuropathy in patients with cancer treated with VEGFR-TKIs was performed. The primary outcome was presence of peripheral neuropathy at the end of the trial. Random-effects meta-analysis was performed to estimate relative risk (RR) of individual treatment. RESULTS: Thirty randomized clinical trials (RCTs) including 12,490 patients with cancer were included in this analysis. Eight studies compared VEGFR-TKIs with placebo and the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. When compared against placebo, VEGFR-TKIs were associated with a higher risk of peripheral neuropathy (RR 1.76; 95% confidence interval [CI] 1.13-2.75, p = 0.01). Similarly, a stronger association was noted for sensory neuropathy with VEGFR-TKIs monotherapy (RR 1.61; 95% CI 1.09-2.37, p = 0.02). Risk of peripheral neuropathy with VEGFR-TKIs was higher even when they were compared against control (either placebo or standard chemotherapeutic agents) (RR 1.08; 95% CI 1.01-1.15, p = 0.03). High-grade neuropathy (RR 1.28; 95% CI 1.06-1.54, p <0.01) and high-grade sensory neuropathy (RR 1.38; 95% CI 1.09-1.74, p < 0.01) were noted more frequently with VEGFR-TKIs treatment compared against control. CONCLUSIONS: VEGFR-TKIs therapy appeared to be associated with an increased risk of neuropathy.

Independent home use of a brain-computer interface by people with amyotrophic lateral sclerosis.

OBJECTIVE: To assess the reliability and usefulness of an EEG-based brain-computer interface (BCI) for patients with advanced amyotrophic lateral sclerosis (ALS) who used it independently at home for up to 18 months. METHODS: Of 42 patients consented, 39 (93%) met the study criteria, and 37 (88%) were assessed for use of the Wadsworth BCI. Nine (21%) could not use the BCI. Of the other 28, 27 (men, age 28-79 years) (64%) had the BCI placed in their homes, and they and their caregivers were trained to use it. Use data were collected by Internet. Periodic visits evaluated BCI benefit and burden and quality of life. RESULTS: Over subsequent months, 12 (29% of the original 42) left the study because of death or rapid disease progression and 6 (14%) left because of decreased interest. Fourteen (33%) completed training and used the BCI independently, mainly for communication. Technical problems were rare. Patient and caregiver ratings indicated that BCI benefit exceeded burden. Quality of life remained stable. Of those not lost to the disease, half completed the study; all but 1 patient kept the BCI for further use. CONCLUSION: The Wadsworth BCI home system can function reliably and usefully when operated by patients in their homes. BCIs that support communication are at present most suitable for people who are severely disabled but are otherwise in stable health. Improvements in BCI convenience and performance, including some now underway, should increase the number of people who find them useful and the extent to which they are used.

Immunoglobulin therapy in the treatment of multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a chronic immune-mediated disorder leading to slowly progressive muscle weakness and wasting. Current treatments are aimed at modulating the immune system in order to avoid further decline and to maintain functional status. Intravenous immunoglobulin (IVIg) is widely used in the treatment of immune-mediated disorders and is the only treatment approved for MMN. While patients do remain stable with maintenance IVIg treatment, most patients will slowly deteriorate over many years. The use of subcutaneous immunoglobulin (ScIg) is also gaining acceptance in this disease. The amount of axonal loss and the number of years without immunoglobulin (Ig) treatment appear to be associated with the permanence of weakness. We summarize the key literature to date that supports Ig use in the treatment of MMN.

Durability of the Rituximab Response in Acetylcholine Receptor Autoantibody-Positive Myasthenia Gravis.

IMPORTANCE: Myasthenia gravis (MG), an autoimmune disorder of neuromuscular transmission, is treated by an array of immunotherapeutics, many of which are nonspecific. Even with current therapies, a subset of patients has medically refractory MG. The benefits of B-cell-targeted therapy with rituximab have been observed in MG; however, the duration of these benefits after treatment is unclear. OBJECTIVE: To evaluate the durability of response to rituximab in the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG. DESIGN, SETTING AND PARTICIPANTS: This retrospective case series study included 16 patients with AChR+ MG referred to an MG clinic from January 1, 2007, to December 31, 2015. The patients were treated with rituximab and followed up for 18 to 84 months after treatment. MAIN OUTCOMES AND MEASURES: Assessment of long-term clinical response, durability of response and/or relapse rate, AChR autoantibody levels, adverse effects, and inflammatory markers. RESULTS: In the 16 patients (6 men and 10 women; median age, 42 [range, 18-69] years), clinical improvement was observed in parallel with complete withdrawal or reduction of other immunotherapies, with all patients achieving complete stable remission, pharmacologic remission, or minimal manifestations based on the Myasthenia Gravis Foundation of America postintervention status criteria. Nine patients (56%) had a relapse during a mean follow-up of 36 (range, 24-47) months. Seven patients (44%) remained relapse free with a mean follow-up of 47 (range, 18-81) months since the last rituximab treatment. All values were normalized to a pretreatment anti-AChR antibody level of 100% and the mean levels after each rituximab cycle were calculated. A 33% decrease was seen after cycle 1 of rituximab treatment (100% vs 67%; P = .004); 20% after cycle 2 (compared with cycle 1) (67% vs 47%; P = .008); and 17% after cycle 3 (compared with cycle 2) (47% vs 30%; P = .02). However, the serum cytokine levels measured were found to be unchanged. CONCLUSIONS AND RELEVANCE: Rituximab therapy appears to be an effective option in patients with refractory AChR+ MG, who were observed to have a durable response after treatment. Identification of markers of disease relapse and sustained remission are critical next steps in the development of pathophysiology-relevant, evidence-based practice parameters for rituximab in the treatment of MG.

Relationship Between Cerebrospinal Fluid Protein Levels and Electrophysiologic Abnormalities in Guillain-Barré Syndrome.

OBJECTIVES: The cerebrospinal fluid (CSF) protein level is known to be elevated in patients with Guillain-Barré syndrome (GBS). This report correlates the degree of CSF protein elevation with the number of electrophysiologic abnormalities on nerve conduction study (NCS). METHODS: We reviewed 38 patients admitted to our institution with a diagnosis of GBS and had both a measured CSF protein level and a NCS within 24 hours of each other. RESULTS: CSF protein level correlates with the number of NCS demyelination criteria, as described by Cornblath, in patients with GBS. CONCLUSIONS: This retrospective study is the first to demonstrate a relationship between the CSF protein level and the electrophysiologic abnormalities that accompany GBS.

The effect of prednisone on the progression from ocular to generalized myasthenia gravis.

Fifty percent of ocular myasthenia gravis (OMG) patients will progress to generalized myasthenia, 90% within 3 years from the onset of ocular symptoms. This study was performed to determine whether treatment with oral prednisone initiated and completed within 2 years from the onset of ocular symptoms would affect the progression of ocular myasthenia to generalized myasthenia gravis (GMG). Fifty-six patients were included in this review, with 27 patients in the prednisone-treated group and 29 patients in the untreated group. The treated group was initiated on 60 mg of prednisone daily with a slow taper over 3-6 months. At 2 years, significantly fewer patients in the treated group (3 of 27) progressed to generalized myasthenia when compared to the untreated group (10 of 29) (chi(2), p=0.04). Our results suggest that the early use of steroids may decrease progression of ocular to generalized myasthenia gravis. The decision to use steroids should be considered early in the course of patients diagnosed with ocular myasthenia gravis. This study should be considered preliminary and a prospective trial is warranted to confirm our observations.

Puerto Rican founder mutation G787A in the SGCG gene: a case report of 2 siblings with LGMD 2C.

We describe 2 siblings who are homozygous for the G787A mutation in the γ-sarcoglycan gene (SGCG), who presented with a severe childhood onset limb-girdle muscular dystrophy, and share a similar clinical phenotype and disease course consistent with LGMD 2C. The siblings' mother is asymptomatic and is heterozygous for the same mutation. The father is estranged but presumably was also an asymptomatic heterozygous carrier as the father's sister (siblings' aunt) died of complications related to a muscular dystrophy at the age of 14. The paternal grandparents of these siblings were first cousins. All members of the family are of Puerto Rican ancestry supporting the theory that this is a founder mutation, as has been previously suggested by Duncan et al The clinical presentation, workup, and course of our patients are described in detail. These 2 cases effectively double the reported cases of this founder mutation.