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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.

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.

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.

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: 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.

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.

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.

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.

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.

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.

Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke).

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.

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.

We reviewed electrodiagnostic findings in patients whose electromyograph pointed toward a disorder of the central nervous system. Of the 34 patients identified, 17 did not have a clinical diagnosis of a central nervous system disorder before electromyogram. Signs suggesting a central nervous system disorder included poor activation, poor relaxation, extensor plantar responses, and flexor spasms on needle electromyogram. Ultimate central nervous system diagnoses included myelopathy, demyelinating disease, parkinsonism, tumor, and stroke.

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.

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.

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: 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 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.

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.

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.

Objective: We report clinical, electrophysiologic and pathologic features of five new cases of facial onset sensory and motor neuronopathy or FOSMN syndrome. An autopsy performed in one case identified TDP-43 cytoplasmic inclusions. Background Vucic et al. described four adult males in 2006 with facial sensory loss gradually spreading to cervical and brachial dermatomes associated with LMN weakness of cranio-bulbar and upper extremity (UE) distribution. Autopsy in one case suggested a neurodegenerative process affecting motoneurons and sensory ganglia. Design/Methods: A retrospective review of patients referred to Mayo Clinic from 2004 to 2011 identified five males who met the clinical features of FOSMN. Results: The age of onset ranged from 55 to 63 years. The presenting symptoms often years after onset, were facial numbness (5), associated with loss of taste (1), dysphagia (3), and masseter weakness (2). Sensory loss spread to scalp, neck, upper torso and distal UEs. Patients developed facial, masseter, bulbar, neck flexor/extensor and LMN weakness of UEs. Two patients died of respiratory failure 6 and 9 years after onset. Electrodiagnostic studies revealed prolonged to absent trigeminal blink R1 responses, reduced sensory nerve action potentials in UEs, and chronic denervation mainly in cranial and cervical regions. CSF protein elevation (4) ranged from 46 to 96 mg/dL. Brain and cervical MR images were normal. Biopsies of greater auricular and transverse cervical nerves revealed low grade axonal degeneration. A patient aged 65 who died 6 years after onset, came to autopsy. Neuronal loss and gliosis with TDP-43 positive cytoplasmic neuronal and glial inclusions were present in hyploglossal nucleus and cervical motoneurons. Alpha-synuclein positive inclusions were found in substantia nigra, pigmented brainstem nuclei and mesial temporal lobe suggestive of incidental Lewy body disease. Conclusions: FOSMN syndrome joins sporadic ALS, frontotemporal lobar degeneration (FTLD-U) and other neurodegenerative disorders as a TDP-43 proteinopathy. Disclosure: Dr. Bosch has nothing to disclose. Dr. Tracy has nothing to disclose. Dr. Goodman has nothing to disclose. Dr. Dyck has nothing to disclose. Dr. Toro has nothing to disclose. Dr. Giannini has nothing to disclose.

Objective: To compare the rates of abnormality in CHEPS and other diagnostic tests used to detect sensory neuropathy or small fiber neuropathy in consecutive patients with clinical evidence of pure sensory or small fiber peripheral neuropathy. Background Sensory neuropathy and small fiber neuropathy are more difficult to diagnose than polyneuropathy. In recent years a number of physiological and pathology tests have arisen to help diagnosing these conditions. Contact Heat Evoked Potential Stimulation (CHEPS) provides objective evidence of spinothalamic pathway dysfunction from skin to cerebral cortex. Design/Methods: Patients with symptoms and signs suggesting sensory neuropathy or small fiber neuropathy (exclusions: symptoms or signs of weakness) were consecutively recruited over an 18 month period to an IRB approved protocol. Sixteen signed consent and underwent neurologic examination, CHEPS, NCS, EMG, autonomic testing, quantitative sensory testing, and distal as well as proximal epidermal nerve fiber density. Rates of abnormality were determined based on laboratory or published normal values. Results: Among all 16 sensory neuropathy patients objective tests showed the following rates of abnormality: CHEPS 69%, distal epidermal skin biopsy 63%, EMG 63%, sural NCS 31%, QSART 19%, heart rate variation 6%, and proximal epidermal skin biopsy 6%. Among 7 patients with clinical evidence of small fiber neuropathy objective tests showed the following rates of abnormality: CHEPS 71%, distal epidermal skin biopsy 57%, EMG 57%, sural NCS 43%, QSART 19%, heart rate variation 0%, and proximal epidermal skin biopsy 0%. Conclusions: In patients with clinical sensory neuropathy or small fiber neuropathy: 1) objective tests show CHEPS to have the highest rates of abnormality, exceeding epidermal skin biopsy, QSART, heart rate variation, NCS, and EMG; 2) subjective quantitative sensory testing shows high rates of abnormality in heat pain VAS and cooling detection threshold values; 3) combinations of physiology and pathology tests yield higher rates of abnormality than single tests alone. Disclosure: Dr. Smith has nothing to disclose. Dr. Bosch has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Goodman has nothing to disclose. Dr. Jones has nothing to disclose.