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Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0–10) was 7 (interquartile range, 6–7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722–1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Introduction Postural tachycardia syndrome is a form of orthostatic intolerance that often leads to functional impairment. Methods This survey explored functional status and impact of symptoms in adults ( n = 958) ages 18 to 60 (M = 32.63 ± 10.52 years, 96.7% female) with postural tachycardia syndrome. Results Individuals reported an average of 11 daily life activities impacted by postural tachycardia syndrome with high levels of self-perceived disability. Additionally, 93.4% reported some degree of cognitive impairment and falls occurred in 55.3% of participants annually. Despite frequent falls and functional impairment, participants infrequently (26.9%) utilized therapy services. Conclusion Individuals with postural tachycardia syndrome are at an increased risk of experiencing disability and often require assistance with daily activities. Further research is necessary to understand the potential role of therapy in improving function and quality of life.

The neuromuscular junction (NMJ) is a critical component of the motor unit that is made up of the distal, unmyelinated nerve terminal, synaptic space, and end-plate region of the muscle fiber. Contraction of muscle fiber involves a coordinated series of steps that ultimately generates an action potential at the muscle end plate (also known as an end-plate potential). Normally the end-plate potential substantially exceeds the threshold necessary to trigger an action potential in the muscle fiber, and this difference is termed the safety factor of neuromuscular transmission. Disorders that affect the NMJ reduce this safety factor, a change that results in fatigable weakness.

A number of medical and neurologic conditions may result from inadequate ingestion, absorption, transport, or storage of critical vitamins and micronutrients. Individuals at risk for inadequate dietary intake include those who are receiving prolonged parenteral nutrition for various chronic medical conditions, those who have eating disorders or chronic alcoholism, and those who are part of a resource-limited population. Malabsorption may result from several conditions, including chronic gastrointestinal disorders and gastrointestinal surgeries. Excessive intake of vitamins such as vitamin B6 may directly cause neurotoxicity, and copper deficiency myeloneuropathy may result from excessive ingestion of zinc (often in the form of denture cream aggressively used for loose-fitting dentures), which competes with copper for absorption within the gastrointestinal tract.

Usually used in emergency settings, bedside sonographic measurement of optic nerve sheath diameter can aid in diagnosing elevated intracranial pressure. We report a case of a 26-year-old male hospitalized for CAR T-cell therapy with Axicabtagene Ciloleucel for treatment of relapsed diffuse large B-cell lymphoma, who developed progressive symptoms of immune effector cell-associated neurotoxicity syndrome. Fundoscopic examination suggested the presence of blurred optic disc margins. Bedside ocular ultrasound revealed wide optic nerve sheath diameters and bulging optic discs bilaterally. The patient had a ventriculostomy placed for monitoring and received treatment with steroids and mannitol, as well as tocilizumab. After 7 days in the ICU, the patient recovered with no evidence of long-term neurological deficits.

ObjectiveTo describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester.MethodsWe performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests).ResultsA total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group (p < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period.ConclusionsABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.

Background and Purpose: Due to the potential for high mortality and neurologic complications of rheumatoid meningitis (RM), awaiting biopsy confirmation may delay vital treatment intervention. Our aim was to describe the clinical presentations of RM in our population and determine whether meningeal biopsy impacted diagnosis, treatment, and outcomes. Methods: A retrospective chart review was completed for patients at Mayo Clinic with a diagnosis of RM within the last 28 years. Those with identified alternative inflammatory, infectious, or neoplastic causes of pachymeningitis or leptomeningitis were excluded. Results: Fourteen patients meeting inclusion/exclusion criteria were identified. All patients were positive for rheumatoid factor or cyclic citrullinated peptide. All patients had magnetic resonance imaging abnormalities characterized by pachymeningeal and/or leptomeningeal enhancement. Of the 10 patients who underwent biopsy, nonspecific findings were seen in 74%. All patients except one were treated with corticosteroids with subsequent symptomatic improvement. Radiographic improvement or resolution was seen in 10 (83%) of 12. Patients improved with corticosteroid treatment, including those who were diagnosed with RM on clinical basis without undergoing a biopsy as well. Conclusions: This retrospective review displays the myriad of clinical presentations of RM. It also suggests that with appropriate exclusion of infectious, neoplastic, and other autoimmune etiologies, biopsy may not be necessary to initiate treatment.

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic–clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. To our knowledge, there are no previously reported cases describing non-convulsive status epilepticus (NCSE) with electroencephalogram (EEG) documentation in the setting of acute porphyria crisis. We report a unique presentation of NCSE, which resolved after administering levetiracetam in a patient with variegate porphyria, without a known seizure disorder., Highlights • Seizures among acute intermittent porphyria (AIP) patients are not uncommon with prevalence being as high as 10%–20%. • Non-convulsive status epilepticus (NCSE) in variegate porphyria (VP) patients should be considered in patients with altered mental status and acute porphyric crisis. • Recognition and avoidance of prophyrogenic anti-seizure medications is important in the treatment of these patients. • Levetiracetam and hemin are potential treatment combinations for nonconvulsive status epilepticus in acute porphyria crisis patients.

Background Sjogren syndrome (SS) is one of the most common autoimmune disorders that classically affects exocrine glands, resulting in keratoconjunctivitis sicca and xerostomia, and frequently is associated with other systemic symptoms. SS appears to have a particular predilection for involving the autonomic nervous system. Study question Does immunotherapy improve signs and symptoms of autonomic nervous system impairment in SS? Study design This is a retrospective review of patients seen in the autonomic clinic at our institution who underwent an evaluation for a suspected autonomic disorder that ultimately was attributed to SS. SS patients who were treated with immunotherapy and completed autonomic testing before and after treatment were included in this review. Results A total of 4 patients were identified who were treated for SS-related autonomic dysfunction with immunotherapy and underwent repeat autonomic testing after treatment. Marked clinical and functional improvement was seen after treatment with intravenous immunoglobulin in all patients and adjunctive rituximab therapy in 1 patient. The clinical improvement with immunotherapy in these patients correlated with markedly improved findings on autonomic testing in all. Measures and outcomes Clinical symptoms and results of autonomic testing prior to and following immunotherapy were assessed. Conclusions Autonomic signs and symptoms in SS are potentially immunoresponsive, but immunotherapy in these patients may require repeated, ongoing, or adjunctive therapy for optimal and sustained improvement.

Introduction Granulomatosis with polyangiitis (GPA) is a vasculitic process that can cause neurological dysfunction in addition to characteristic sinus and pulmonary manifestations. This case report highlights the spectrum of nervous system manifestations and includes rarely reported autonomic and pituitary involvement. Case report A 62-year-old woman presented with orthostatic intolerance, tachycardia, dry mouth, and temperature sensitivity; subsequent autonomic reflex study demonstrated widespread postganglionic sympathetic sudomotor, cardiovagal, and cardiovascular adrenergic impairment reflective of autonomic neuropathy and overall autonomic failure. Additional progressive symptoms included dysarthria, dysphagia, bilateral hearing loss, voice hoarseness, and right-sided facial numbness with multiple cranial neuropathies identified on neurological examination. The diagnosis of central diabetes insipidus was also confirmed. Pachymeningitis was present on brain magnetic resonance imaging. Pathologic review of the dural biopsy specimen revealed necrotizing granulomatous vasculitis consistent with GPA. She was treated with intravenous methylprednisolone and rituximab. Over the next 2 months, she had near-complete resolution of her symptoms with normalization on repeat autonomic testing. Conclusions This is a unique GPA case presenting with autonomic failure and pituitary dysfunction with conclusive objective findings of autonomic dysfunction. Autonomic dysfunction and other disease manifestations were responsive to immunosuppressive therapy.

The electrodiagnostic (EDX) evaluation of suspected neuromuscular conditions in the intensive care unit (ICU) requires a thoughtful approach, with particular attention to technical factors that can impact testing in this setting and knowledge of how the various neuromuscular conditions translate into EDX findings for these patients. Electrodiagnostic testing is typically performed in the ICU in order to identify a neuromuscular cause for respiratory failure and weakness. An approach to EDX testing and typical findings in ICU- acquired weakness and primary neuromuscular conditions such as Guillain-Barré syndrome, myasthenic crisis, West Nile poliomyelitis, amyotrophic lateral sclerosis, and other neuromuscular conditions encountered in ICU patients are discussed.

Objective: To report a case series of dysautonomia associated with COVID-19 infection.Methods: This is a retrospective review of patients evaluated in the autonomic clinic at our institution with suspected signs and symptoms of dysautonomia who underwent formal evaluation, including autonomic testing.Results: Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. All patients had symptoms typical of COVID-19 infection, though none were hospitalized for these or other symptoms. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity intolerance. Five patients reported the onset of autonomic symptoms concomitant with other COVID-19 symptoms, with the other patient reporting symptom onset 6 weeks following initial COVID-19 symptoms. Autonomic testing demonstrated an excessive postural tachycardia in 4 patients, a hypertensive response with head-up tilt in 3 patients, orthostatic hypotension in 1 patient, and sudomotor impairment in 1 of the patients with excessive postural tachycardia.Conclusions: We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.

Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

Postural tachycardia syndrome is a common condition characterized by the presence of orthostatic intolerance in conjunction with excessive postural tachycardia. This review will focus on treatment updates in postural tachycardia syndrome and will include a discussion of rehabilitative, vasopressor, heart rate modulation, volume expansion, and immunomodulatory treatment strategies. A recent study added to existing literature the benefits of exercise retraining in postural tachycardia syndrome (POTS) patients who were able to successfully complete a 3-month exercise regimen. Another recent, novel study reported the benefits of respiratory retraining in POTS patients reporting breathlessness. The benefits of volume expansion in the treatment of POTS were strengthened by 2 recent studies, including a study demonstrating the value of oral rehydration salts in improving hemodynamic parameters in POTS patients and another prospective study demonstrating the value of IV saline infusions in POTS patients. A recent meta-analysis reviewed the efficacy of ivabradine in the treatment of POTS, while another systematic review and meta-analysis reviewed the benefits of metoprolol in the treatment of childhood and adolescent POTS. Also included in this review is that of a large clinical trial comparing propranolol and bisoprolol alone and with pyridostigmine, demonstrating efficacy of beta blockers and an absence of any clear additive benefit with pyridostigmine. A retrospective review of droxidopa in a large POTS cohort reported improvement in only 27% of POTS patients. Recent approaches to the pharmacologic and non-pharmacologic treatment of cognitive dysfunction and fatigue in POTS patients were reviewed. Finally, a retrospective series of the benefits of intravenous immunoglobulin in POTS suspected of being autoimmune is reviewed. The treatment of postural tachycardia syndrome is complex and nuanced, requiring a combination of lifestyle and pharmacologic treatments in most patients. This review provides treatment updates for this enigmatic condition.

Background: West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms. The dominant hypothesis is that antiviral inflammatory responses triggered initially to clear WNV may persist to promote a post-infectious proinflammatory state. Methods: In 4 serologically-confirmed WNV patients with persistent post-infectious symptoms (3 WNV fever, 1 neuroinvasive disease), we ordered a comprehensive cytokine panel at weeks 8, 10, 12, and 36 months post-onset of illness, respectively, to better understand the pathophysiology of the protracted symptoms. Results: All patients had abnormally elevated tumor necrosis factor alpha (TNF-α), a major molecule triggering antiviral cytokines and chronic inflammation in many human autoimmune diseases, but heretofore not reported to be upregulated in human WNV infection. Three patients also had elevations of other proinflammatory proteins. Major symptoms included fatigue, arthralgias, myalgias, generalized or multifocal pain or weakness, imbalance, headaches, cognitive problems, and symptoms of dysautonomia. Conclusion: The findings provide support for an extended post-infectious proinflammatory state that may contribute to chronic inflammation and long-term morbidity in some WNV survivors and further suggest that TNF-α may play a pathogenic role in initiating this inflammatory environment. Clinical trials may be warranted to determine if TNF-α inhibitors or other immunosuppressive agents can improve patient outcomes.

Background Patients with postural tachycardia syndrome (POTS) often have gastrointestinal (GI) symptoms. Occasionally, these symptoms can be so severe that nonoral nutrition/hydration support (NONHS), including intravenous fluids (IVFs), enteral nutrition (EN), and parenteral nutrition (PN), becomes necessary. Methods This is a retrospective cohort study of adult patients diagnosed with POTS at the Mayo Clinic Arizona from January 2010 to January 2017 with a minimum of 6 months of follow up. Demographic information, symptomatology, medications, GI testing, autonomic and autoantibody testing, and healthcare utilization data were abstracted from the electronic medical record. Results Three-hundred thirty-two patients with POTS were included, of which 32 required NONHS. Patients receiving NONHS were more likely to be female; have lower body mass index; have GI symptoms including nausea, vomiting, diarrhea, and constipation; have abdominal pain; use opiates; have delayed gastric emptying; see more specialists; and be seen in an emergency room or be hospitalized for symptoms. Of these patients, 21 (66%) required IVF, 19 (59%) required EN, and 9 (28%) required PN. Six (19%) patients required all 3 NONHS modalities at some point during their follow-up period. Conclusions NONHS may be required in a subset of patients with POTS. Those receiving NONHS have more severe symptoms and abnormal GI motility and autonomic testing and exhibit greater healthcare utilization. Management of these patients is complex and challenging and requires a multidisciplinary approach. Further prospective studies are needed to identify optimal management strategies.

Postural tachycardia syndrome (POTS) is one of the most common causes of orthostatic intolerance and is being increasingly recognized in clinical practice. Gastrointestinal (GI) symptoms are reported commonly in patients with POTS and pose a considerable management challenge, making it imperative that gastroenterologists be aware of this condition and its GI comorbidities. Although the evidence presented herein does not prove causation, it does support an association between GI symptoms, GI dysmotility, and POTS. At present, the evaluation and treatment of GI symptoms in patients with POTS remains largely empirical. General measures to treat POTS may lead to improvement in both GI and non-GI symptoms. GI symptoms refractory to these measures should prompt further diagnostic evaluation of gastrointestinal dysmotility and appropriate dietary and pharmacologic management. This review focuses its attention on the involvement of the GI tract in POTS including a discussion of GI symptoms and conditions associated with POTS, followed by an analysis of abnormalities in gut physiology described in POTS, and concluding with an overview of management and suggestions for research directions.

Background: We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Methods: Fifty-eight patients with CINM seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Results: Mean CMAP durations were prolonged and mean CMAP amplitudes were severely reduced, both proximally and distally, in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than one nerve. Discussion: Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy, and are highly specific for the diagnosis of CINM. This article is protected by copyright. All rights reserved.

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis (RA) and has a high mortality rate. It can present as a first diagnosis of RA, in long-standing disease, or in active or well-controlled disease. Neurological manifestations vary widely.A patient with a 30-year history of RA, well controlled with methotrexate therapy, presented with new-onset seizures. Magnetic resonance imaging showed leptomeningeal and pachymeningeal enhancement. A de novo workup resulted in diagnosis of RM.Cerebrospinal fluid findings for RM are nonspecific, typically lymphocytic pleocytosis; however, they can be neutrophilic, as in this case. Magnetic resonance imaging findings consist of leptomeningeal and pachymeningeal enhancement but can also involve the parenchyma. The diagnosis is typically confirmed with meningeal biopsy. Treatment involves high-dose corticosteroids or immunomodulatory therapy, or both. Long-term follow-up with radiologic surveillance typically ranges from improvement to resolution.

Purpose of review Conditions that affect the cauda equina are a diverse group of disorders that require timely recognition and management. This article reviews cauda equina anatomy, the diagnostic approach to disorders of the cauda equina, features of cauda equina syndrome, and diskogenic and nondiskogenic disorders of the cauda equina. Recent findings Establishing clinical criteria for cauda equina syndrome has been a focus of a number of reviews, although the clinician must maintain a low threshold for emergent imaging in cases of suspected cauda equina syndrome because of the suboptimal reliability of various signs and symptoms in identifying this condition clinically. The timing of surgical intervention for compressive causes of cauda equina dysfunction remains a point of contention, although urgent decompression remains standard practice. A recent review that focused on outcomes in patients with cauda equina compression who underwent surgical decompression identified significant residual deficits in patients despite appropriate and timely intervention. Autoimmune conditions targeting the cauda equina have been increasingly recognized, including chronic immune sensory polyradiculopathy and chronic immune sensorimotor polyradiculopathy. Summary Disorders that affect the cauda equina require thoughtful and timely clinical examination and diagnostic testing to establish a definitive cause and an appropriate treatment approach.

The diagnostic evaluation of a patient with suspected postural tachycardia syndrome (POTS) requires a thoughtful diagnostic approach utilizing a careful clinical history and examination, laboratory, and autonomic testing. This article outlines the importance of a thorough history in identifying mechanism of symptom onset, clinical features, associated clinical conditions or disorders, and factors that may result in symptom exacerbation. The clinical examination involves an assessment of pupillary responses, an evaluation for sudomotor and vasomotor signs, and an assessment for joint hypermobility. Laboratory testing helps to exclude mimics of autonomic dysfunction, recognize conditions that may exacerbate symptoms, and to identify conditions that may cause or be associated with autonomic nervous system disease. The purpose of autonomic testing is to confirm a POTS diagnosis, exclude other causes of orthostatic intolerance, and may provide for characterization of POTS into neuropathic and hyperadrenergic subtypes. Other diagnostic studies, such as epidermal skin punch biopsy, exercise testing, radiographic studies, sleep studies, gastrointestinal motility studies, and urodynamic studies should be considered when clinically appropriate.

Immune therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are first line in the treatment of worsening myasthenia gravis. Although PLEX is favored in myasthenic crisis, IVIG is increasingly used in exacerbations due to cost and ease of administration.To review and critically assess current evidence on the effects of IVIG and PLEX on functional outcomes in patients with worsening myasthenia gravis.A structured critical appraisal was conducted on the objective topic. This included a creation of a structured question based on a clinical scenario, comprehensive literature search, selection of evidence for review, and critical appraisal of selected evidence. Evidence was summarized and commentary provided. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology.A single-blinded, randomized-controlled trial that compared IVIG and PLEX in 84 patients with worsening myasthenia gravis was selected for review. Primary outcome measure was functional status at 14 days after treatment, as assessed by the Quantitative Myasthenia Gravis Score. Change in Quantitative Myasthenia Gravis Score at day 14 for all subjects was 4.0, without statistically significant differences between IVIG and PLEX groups.IVIG and PLEX are equally effective in worsening myasthenia gravis. Treatment decisions may depend on several variables, including presence of respiratory distress, medical comorbidities, access to medication, and cost. PLEX will likely remain the treatment of choice in true myasthenic crisis.

Background Nonspecific symptoms such as fatigue and dizziness are common in multiple sclerosis (MS), even in patients with normal exams. Little is known about the relationship of autonomic dysfunction with these symptoms and quality of life. Objective Assess the association of autonomic symptom burden with fatigue, clinical status and quality of life. Methods Subjects completed an autonomic symptom (COMPASS-31), quality of life (MSQOL-54) and fatigue (FSS) questionnaire at their routine MS clinic follow-up. Demographic and clinical data were collected from the medical record. Pearson correlations were assessed between autonomic symptoms and fatigue, quality of life, disability and disease duration. Results One-hundred subjects completed the study (mean age 48 years; 78% female; 84% relapsing-remitting), mean disease duration was 14.7 years and mean EDSS 2.5. MSQOL-54 composite scores were 58 physical and 65 mental. COMPASS-31 correlated with MSQOL-54 (Physical R = −0.60; Mental −0.54; p R =0.51; p R =0, p =0.97) or disease duration ( R = −0.02, p =0.84). Conclusions Autonomic symptom burden is correlated with decreased quality of life and increased fatigue. Autonomic symptoms are present early in the disease and at low disability and may reflect aspects of disease burden that are not well-captured by current disability measures.

To describe the spectrum of autonomic dysfunction in a uniformly evaluated cohort of patients with Sjögren syndrome.A series of 13 patients underwent a comprehensive evaluation for suspected autonomic impairment, including a neurological examination, autonomic testing, and laboratory studies. A diagnosis of Sjögren syndrome was established as the cause of autonomic dysfunction in all. Clinical features, findings on autonomic testing, and laboratory results are described.All patients in this series reported postural lightheadedness and syncope or near-syncope. Autonomic testing confirmed the presence of orthostatic hypotension on tilt-table testing in 5 patients and an excessive postural tachycardia and/or hypertensive response in 8 patients. Only 2 of the patients with orthostatic hypotension had a significant sensory neuropathy. Symptoms suggestive of gastrointestinal and genitourinary impairment were seen in nearly all patients, with abnormal motility testing (most frequently esophageal dysmotility) in 5 of 6 patients who underwent formal testing. Patients in this series treated with immune-modulating therapy experienced significant improvement.A diagnosis of Sjögren syndrome should be aggressively pursued in patients with signs and symptoms suggestive of autonomic nervous system impairment. Although the spectrum of adrenergic failure is variable, ranging from orthostatic hypotension to an excessive postural tachycardia, most patients do have symptoms of more generalized autonomic failure. Patients who were treated with immune-modulating therapy did improve.

We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions.Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes.Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve.Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018.

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised.To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy.Patients with simultaneous copper deficiency (0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified.34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation.An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance.

Alexander disease (AxD) is an astrogliopathy, resulting from a mutation in the glial fibrillary astrocytic protein gene. Different clinical subtypes have been described, including infantile, juvenile, and adult onset, based upon the age at which symptoms begin. Patients with the adult-onset form, develop a progressive, spastic paraparesis, palatal myoclonus, ataxia, and bulbar weakness. Autonomic nervous system (ANS) dysfunction has been reported as a potential manifestation of adult-onset AxD, but has not been well characterized. We report a case of adult-onset AxD with symptomatic orthostatic hypotension (OH) and heat intolerance that underwent formal autonomic testing. In addition, a comprehensive literature search was conducted to review the frequency and pattern of autonomic dysfunction in this patient population. A 51-year-old patient was diagnosed with AxD at the age of 47, following an 8-year history of vertigo, intermittent diplopia, and sleep disturbance. The patient developed symptoms of OH, erectile dysfunction, and heat intolerance soon after his diagnosis. Autonomic testing demonstrated OH on tilt-table testing (47 mmHg decrease in BP with 18 BPM heart rate increment) with absent late phase II and IV responses during the Valsalva maneuver, severe cardiovagal impairment, and preserved postganglionic sympathetic sudomotor function. These findings were interpreted as being consistent with central autonomic failure. The most common autonomic symptoms reported in other AxD cases include constipation, urinary incontinence, and sphincter dysfunction. To our knowledge, this is the first report of formal autonomic testing in AxD. Signs and symptoms of ANS impairment can occur in patients with AxD, and can include orthostatic hypotension and bowel/bladder dysfunction. Autonomic testing in our patient suggests impairment in central autonomic pathways.

Objective To describe the postural orthostatic tachycardia syndrome (POTS), including clinical presentation, pathophysiology, diagnostic methods, and current management models. Data Sources PubMed, Cochrane Library were searched for articles available prior to October 30, 2015. Methods Review of the available English-language literature. Results Postural orthostatic tachycardia syndrome presentation is discussed, along with underlying associated physiology for POTS and recommended nonpharmacologic and pharmacologic management strategies. Conclusion Postural orthostatic tachycardia syndrome patients commonly present with complaints of postural lightheadedness, or dizziness, which can be associated with various other conditions. Nonpharmacologic and pharmacologic treatment methods are available to improve the underlying pathophysiology of the disorder. Laryngoscope, 2016

Camptocormia is a debilitating gait disorder characterized by the hyperflexion of the thoracolumbar spine during the upright position. Its etiologies are heterogenous, including parkinsonism and various neuromuscular disorders. Here, we report a camptocormia patient due to a late-onset axial myopathy with numerous lobulated fibers. The patient's father reportedly had similar symptoms. Myriad lobulated fibers are common among patients with an autosomal recessive muscular dystrophy due to calpain-3 gene (CAPN3) mutations or calpainopathy. CAPN3 sequencing revealed a single c.759-761delGAA mutation. Calpainopathy carriers are generally asymptomatic. The presence of lobulated fibers in this patient suggests that camptocormia could be a manifestation of calpainopathy carrier, although the possibility of a coexisting undiagnosed myopathy cannot be excluded. The current patient should spur the evaluation of camptocormia among calpainopathy carriers.

Introduction Rippling muscle disease (RMD) is a rare disorder of muscle hyperexcitability clinically characterized by painful muscle stiffness, rippling phenomenon, percussion-induced muscle mounding, and rapid contraction. RMD is typically considered to be electrically silent, but electrical activity during the muscle rippling has been occasionally described. RMD could be genetically determined or immune-mediated (iRMD). The association between cancer and iRMD is extremely rare. Case report We present here a patient with electrically active iRMD preceding the diagnosis of breast cancer. The patient had acetylcholine receptor binding antibodies but no clinical or electrophysiological signs of myasthenia. Muscle biopsy revealed inflammatory changes and a mosaic distribution of sarcolemmal caveolin-3 deficiency. Sequencing of caveolin-3 gene detected no mutation. Immunotherapy led to the resolution of the RMD and disappearance of the serum acetylcholine receptor antibodies. Conclusions The abnormal electrical activity in this patient suggests that an acquired neuromuscular hyperexcitability syndrome represents a continuum of disorders. The close temporal relationship between the onset of iRMD and the diagnosis of breast cancer raises the possibility that iRMD might be paraneoplastic.

BackgroundAutonomic nervous system dysfunction has been identified in patients following traumatic brain injury (TBI), including concussion. Abnormal postural heart rate and blood pressure instability have been identified in post-concussive patients. Recently, we have identified abnormal respiratory patterns during autonomic testing for post-concussive symptoms. Tachypnea is a clinical feature of autonomic instability in paroxysmal sympathetic hyperactivity following severe TBI and the purpose of this study is to identify abnormal respiratory patterns in patients with autonomic nervous system impairment following mild TBI.MethodsA retrospective review of patients in the Mayo Clinic Arizona Concussion Program from October 2017 to March of 2018 was performed. Clinical features and autonomic testing were reviewed. Autonomic testing included blood pressure and heart rate responses to Valsalva, heart rate variability during deep breathing, blood pressure and heart rate responses to head-up tilt, sudomotor testing, and respiratory responses using respiratory inductive plethysmography. Patients with co-morbidities or medications with potential to influence autonomic testing were excluded.ResultsFifteen patients with a history of concussion were studied. Nine of 15 patients had abnormal cardiovascular responses on autonomic testing, typically excessive postural tachycardia with head-up tilt. Abnormal respiratory patterns were identified in 8 of 9 patients with abnormal autonomic testing and in 3 of 6 patients without other abnormalities on autonomic testing. A number of different respiratory patterns were identified including tachypnea, prolonged apneic episodes, Cheyne-Stokes, and other unusual respiratory patterns.ConclusionWe have identified abnormal respiratory patterns in a series of concussion patients with or without other signs of dysautonomia. Tachypnea has been previously reported as a clinical feature of paroxysmal sympathetic hyperactivity following severe TBI and was present in some patients in this series. The clinical significance and mechanisms involved in the generation of respiratory dysrhythmia require further study, but may be another manifestation of post-concussive dysautonomia.

We report a case of superficial siderosis erroneously diagnosed as amyotrophic lateral sclerosis. The patient's symptoms began 18 years prior with unilateral upper extremity weakness, fasciculations, and hyperreflexia. The patient then developed ataxia and hearing loss 15 years after his original symptoms. The magnetic resonance images revealed superficial siderosis involving the spinal cord and brain. We want to attract attention to superficial siderosis as a rare amyotrophic lateral sclerosis mimic disorder.

Critical illness myopathy, neuropathy, and neuromyopathy are frequently encountered in the intensive care unit, particularly in the setting of sepsis and the systemic inflammatory response syndrome. A multidisciplinary approach is important to optimize management and minimize debility associated with these neuromuscular disorders. This article reviews the underlying pathophysiology, risk factors, clinical presentation, electrodiagnostic evaluation, management, and prognosis of these disorders.