Search

We treated a patient who developed transient multifocal encephalopathy with extrapyramidal symptoms (oromandibular dystonia, oculogyric crisis, and limb dystonia) in temporal proximity to ondansetron administration on emergence from general anesthesia. No other medications known to cause extrapyramidal reactions were administered. Although these symptoms resolved fully, the presentation was dramatic and resembled the symptoms of structural brain injury. Ondansetron is used frequently as an antiemetic agent in many clinical settings and is not limited to surgical patients. Therefore, the entire medical community should be cognizant of this potential adverse reaction. [ABSTRACT FROM AUTHOR]

Purpose: Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO 2PEAK ), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC)., Methods: Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO 2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions., Results: The ET group demonstrated a greater improvement in VO 2PEAK , higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO 2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09)., Conclusion: Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC., (© 2023. The Author(s).)

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.

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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To 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., Methods: We 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)., Results: A 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., Conclusions: ABF 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., (© 2021 American Academy of Neurology.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goodman, Khoury, Blair and Grill.)

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., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

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., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Diverse acute neurological injuries may cause acute cardiopulmonary events including neurogenic pulmonary edema (NPE) and neurogenic stunned myocardium (NSM). The mechanism is probably mediated by sympathetic nervous system activation. Focal central nervous system (CNS) lesions, such as demyelinating lesions in multiple sclerosis (MS), may also cause cardiopulmonary disturbances. We aim to review the acute cardiopulmonary events associated with MS relapses. We performed a literature search using PubMed, and selected case reports of acute cardiac and/or pulmonary events related to MS exacerbations. We grouped these events into three categories: 1) NPE with normal cardiac function; 2) NSM and Takotsubo cardiomyopathy (TTC); 3) coexisting myocardial dysfunction and pulmonary edema. In some cases, cardiac and pulmonary symptoms preceded the onset of neurological symptoms. The majority of cases were associated with acute demyelinating lesions located in the medulla. Acute brainstem MS relapses, with demyelinating lesions affecting the medulla, may cause acute cardiac and pulmonary events presumably secondary to sympathetic hyperstimulation. Specific regions in the medulla that regulate cardiac function, systemic blood pressure and pulmonary hydrostatic pressure seem to be responsible for these events.

Background: Sjögren 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.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: 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., Case Report: 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., Conclusions: 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.

Introduction: 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 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., 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 1 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. Muscle Nerve 57: 395-400, 2018., (© 2017 Wiley Periodicals, Inc.)

Objective: To describe the spectrum of autonomic dysfunction in a uniformly evaluated cohort of patients with Sjögren syndrome., Methods: 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., Results: 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., Conclusions: 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.

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, 127:1195-1198, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: 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., Objectives: To review and critically assess current evidence on the effects of IVIG and PLEX on functional outcomes in patients with worsening myasthenia gravis., Methods: 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., Results: 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., Conclusions: 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.

Purpose of Review: This article provides an update on the various metabolic and toxic causes of myelopathy. The clinical features, laboratory findings, characteristic imaging and electrodiagnostic patterns, and approach to treatment are reviewed in depth., Recent Findings: Vitamin B12 deficiency is a common condition, with prevalence rates that increase with age, and is particularly common in the elderly and in certain geographic areas. Nutritional surveys from the United States have suggested prevalence rates of approximately 6% in those 70 years of age or older, and prevalence rates were reported to be 10% in those older than 75 in the United Kingdom. Copper deficiency is a less common cause of myelopathy, but may result in clinical signs and symptoms indistinguishable from those of vitamin B12 deficiency. Recent reports highlight the importance of excessive zinc in the pathogenesis of copper deficiency and the importance of exogenous zinc cessation in the treatment of copper deficiency. A recent study reviewed previously reported cases of zinc myelopathy in zinc-smelter workers in the 1870s. These workers developed symptoms identical to those reported in the modern descriptive series of copper deficiency myeloneuropathy., Summary: Deficiencies of vitamin B12, folate, copper, and vitamin E may result in characteristic clinical, electrodiagnostic, and imaging features. Prompt recognition and treatment is critical to limit permanent neurologic impairment. Recognition of the toxic causes of myelopathy, including nitrous oxide exposure, heroin, radiation, various chemotherapeutic agents, liver disease, konzo, lathyrism, and zinc excess, is aided by understanding the typical clinical and imaging features associated with these agents.

A 36-year-old healthy woman developed a postinfectious autonomic neuropathy with adrenergic failure and symptoms of orthostatic intolerance. Treatment with immunomodulating therapy, including corticosteroids and immunoglobulin, resulted in marked improvement in clinical symptoms and findings on autonomic testing.

Background: 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., Objective: 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., Results: 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., Conclusion: 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.

Inclusion body myositis is the most common idiopathic inflammatory myopathy in elderly individuals. It typically causes proximal and distal limb weakness with forearm flexors and quadriceps being the most severely affected muscles. Axial musculature is infrequently involved. Here, we report an 80-year-old man who presented with an 18-month history of progressive truncal weakness causing stooped posture while standing and walking. Neurologic examination revealed no limb weakness. magnetic resonance imaging studies showed atrophy and findings, suggesting fatty replacement of paraspinal muscles. Needle electromyography confirmed the presence of an axial myopathy. Thoracic paraspinal muscle biopsy showed canonical features of inclusion body myositis. The current patient broadens the clinical presentation of inclusion body myositis.

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.

Disorders that concomitantly affect the spinal cord and peripheral nerves can be characterized as myeloneuropathies. Such conditions can be broadly categorized as metabolic, inflammatory, infectious, or hereditary disorders. Because these disorders may present with predominantly myelopathic or peripheral neuropathic signs and symptoms, a careful neurologic examination and a thoughtful diagnostic evaluation are necessary to establish a diagnosis of myeloneuropathy. This article outlines an approach to the identification, evaluation, and treatment of myeloneuropathy.

Introduction: Carisoprodol is a centrally acting muscle relaxant used in the treatment of various musculoskeletal disorders whose main metabolite, meprobamate, is a controlled substance in the United States due to its sedative properties and potential for abuse., Case Description: We report a case of a 51-year-old man with cognitive impairment and tremor who developed worsening tremor, anxiety, myoclonus, ataxia, and psychosis on abrupt cessation of carisoprodol. At hospital discharge, his cognitive function significantly improved compared with when he was on carisoprodol., Conclusion: Carisoprodol withdrawal is an important and under-recognized syndrome that should be considered in patients presenting with neurologic symptoms who are taking the medication. Carisoprodol withdrawal can be successfully treated with the use of benzodiazepines, although further studies are needed to identify the most appropriate treatment protocol.

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 (CIM) is a frequent cause of generalized weakness in the intensive care unit. Prolonged compound muscle action potential (CMAP) durations have been described in this patient population, and this study presents further data on CMAP duration in normal controls and patients with CIM. The findings highlight the importance of testing multiple nerve muscle combinations in weak, critically ill patients. Recognition of this pattern, which has not been widely described, can facilitate the diagnosis of CIM.

Introduction: Copper deficiency is an increasingly recognized cause of gait unsteadiness. Recognized causes of copper deficiency include excess zinc ingestion, and malabsorption. Although hematologic abnormalities have been attributed to copper deficiency in patients with celiac disease, myeloneuropathy due to copper deficiency has not been well described in patients with celiac disease., Case Report: A 69-year-old woman was evaluated for a 5-year history of progressive gait unsteadiness and weight loss. She had no other gastrointestinal symptoms. Her neurologic examination revealed a sensory ataxia, and electrodiagnostic testing confirmed a myeloneuropathy. She had decreased serum copper levels and markedly elevated gliadin and tissue transglutaminase antibodies. Subsequent duodenal biopsy showed findings consistent with celiac disease. The patient was diagnosed with copper deficiency myeloneuropathy due to celiac disease. Adoption of a gluten-free diet along with copper supplementation resulted in significant clinical improvement, including improvement on electrodiagnostic testing., Conclusions: Celiac disease should be considered in patients found to have copper deficiency, even in patients without gastrointestinal symptoms. Furthermore, the authors suggest that some cases of ataxia associated with celiac disease are likely due to copper deficiency myeloneuropathy.

Introduction: Copper deficiency is an increasingly recognised cause of neurological impairment. This retrospective review highlights clinical and electrodiagnostic findings in patients diagnosed at our institution with copper deficiency., Methods: Clinical, radiographic and electrodiagnostic findings were reviewed in patients with evidence of copper deficiency. Patients with other potential causes of myelopathy or neuropathy were excluded., Results: The predominant clinical feature in all six patients was a sensory ataxia, resulting in marked gait unsteadiness. Nerve conduction studies and needle EMG were performed in all patients and revealed a mild to moderate distal, axonal, sensorimotor peripheral neuropathy. Median and tibial somatosensory evoked potentials were abnormal in all five patients in which it was performed, showing impaired conduction in central or proximal peripheral somatosensory pathways., Conclusions: This pattern of electrodiagnostic findings suggests that impairment in somatosensory pathways demonstrated by somatosensory evoked potential testing is the main cause of the sensory ataxia in patients with copper deficiency.

Introduction: Baroreflex failure and bulbar palsy have been rarely reported as potential complications of radiotherapy for head and neck tumors. However, the occurrence of both disorders in the same patient has not been well described. We present a unique patient with radiation-induced cranial neuropathies, resulting in bulbar palsy and baroreflex failure., Case Report: A 67-year-old man underwent surgical resection of tonsillar squamous cell carcinoma and postoperative radiation therapy. Six years later, he developed severe orthostatic hypotension with syncope, followed later by progressive bulbar impairment. EMG showed myokymic discharges in the tongue, and marked orthostatic hypotension was noted on tilt-table testing., Conclusion: Progressive bulbar impairment and baroreflex failure can occur following radiotherapy for head and neck cancers. Furthermore, these manifestations of radiation injury can occur in the same patient.

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.

Small fiber peripheral neuropathy is a frequently encountered neurological disorder, which can be difficult to diagnose. In this article, the differential diagnosis of small fiber neuropathy is discussed, along with role of autonomic testing, skin biopsy, and quantitative sensory testing, in establishing a definitive diagnosis of small fiber peripheral neuropathy. Disorders of orthostatic intolerance, including postural orthostatic tachycardia syndrome (POTS), are also discussed, emphasizing diagnostic evaluation and a treatment approach to these disorders.

Copper deficiency has been associated with a clinical syndrome, myeloneuropathy. Radiographic changes resembling B(12) deficiency in the cervical spinal cord have been described. We present a case of copper deficiency myeloneuropathy, with cervical MR imaging findings resembling B(12) deficiency, which partially reversed following copper supplementation. This is, to our knowledge, the first described case of radiographic improvement with copper supplementation.

Background: Pregnancy may be a risk factor for aggressive behavior in cavernous malformations. Relatively few cases exist in the literature and management is unclear., Methods: This unique case report describes a 28-year-old female 27 weeks pregnant who presented with 2 hemorrhages from a pontine cavernous malformation within 1 week. Morbidity increased with the second hemorrhage., Results: The patient underwent a suboccipital craniotomy and excision of the cavernous malformation. She successfully delivered a normal child at 36 weeks gestation and is ambulatory and independent 3 months postoperatively., Conclusions: Pregnancy and prior hemorrhage may be risk factors for repeated hemorrhages. Management decisions can be difficult during pregnancy, but successful excision during pregnancy is possible. The behavior of cavernous malformations and management decisions for this patient are discussed.

The effect of oxygen tension on cellular growth and metabolism was studied in actively growing WI-38 cells [greater than 90% labeled nuclei (LN)] grown under atmospheres containing 5% CO2 and various combinations of O2 and N2. Cells grown under a partial pressure of oxygen (PO2) of 7.8 +/- 3.5 mm Hg had a significantly slower growth rate, lower saturation densities and higher rates of glucose consumption and lactate production than did cells grown under a PO2 of 44 +/- 7 mm Hg. There were no significant differences in saturation density or the rates of glucose consumption or lactate production between cells grown under PO2 26 +/- 4 mm Hg, 44 +/- 7 mm Hg, or 134 +/- 11 mm Hg. Population doubling time was slightly prolonged at a PO2 of 134 mm Hg compared to a PO2 of 44 mm Hg. Cells grown under a PO2 of 291 +/- 25 mm Hg showed only 20-30% of the growth rate and 10-20% of the saturation density of cells grown under a PO2 of 134 mm Hg. Despite this reduced growth, cells grown under a PO2 of 291 mm Hg consumed four to six times as much glucose and produced four to six times as much lactate per cell as cells grown at a PO2 of 134 mm Hg. Cells grown under a PO2 of 560 +/- 38 mm Hg attached but did not proliferate. This toxic effect of oxygen on cell proliferation was reversible and was not due to an effect of oxygen on the media.