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Objective/Background: Neurological complications occur at a high frequency after hematopoietic cell transplantation (HCT). However, an absence is noted in the published literature as regards the quantification of the exact burden and the outcomes thereof. In this systematic review, we endeavored to detail if the recipients of HCT developed any noninfectious neurological events/complications. Methods According to the PICO criteria, medical literature was searched. Complications that were evaluated included: stroke, peripheral neuropathy, myasthenia gravis, seizures, and posterior reversible encephalopathy syndrome. After strictly defining relevant variables and parameters, data from 173 eligible articles were then extracted accordingly, from the full text for each, for quantitative analysis; additionally, two American Society of Hematology conference abstracts were also subject to data extraction. Results As is evident from the results of the data analysis, an increased frequency of these complications was seen in the HCT recipient population in comparison to the general population. The relative risk ranged from 1.33× to 142× depending on the complication studied. Conclusion These findings demonstrate that the recipients of HCT had a significantly higher risk of neurological complications and that their early recognition can enhance the monitoring of HCT survivors for the early developmental signs of neurological toxicity. This would facilitate timely interventions, thus ensuring a better quality of life.

ObjectiveTo determine whether MRI gadolinium enhancement patterns in myelopathies with longitudinally extensive T2 lesions can be reliably distinguished and assist in diagnosis.MethodsWe retrospectively identified 74 Mayo Clinic patients (January 1, 1996–December 31, 2019) fulfilling the following criteria: (1) clinical myelopathy; (2) MRI spine available; (3) longitudinally extensive T2 hyperintensity (≥3 vertebral segments); and (4) characteristic gadolinium enhancement pattern associated with a specific myelopathy etiology. Thirty-nine cases with alternative myelopathy etiologies, without previously described enhancement patterns, were included as controls. Two independent readers, educated on enhancement patterns, reviewed T2-weighted and postgadolinium T1-weighted images and selected the diagnosis based on this knowledge. These were compared with the true diagnoses, and agreement was measured with Kappa coefficient.ResultsAmong all cases and controls (n = 113), there was excellent agreement for diagnosis using postgadolinium images (kappa, 0.76) but poor agreement with T2-weighted characteristics alone (kappa, 0.25). A correct diagnosis was more likely when assessing postgadolinium image characteristics than with T2-weighted images alone (rater 1: 100/113 [88%] vs 61/113 [54%] correct, p < 0.0001; rater 2: 95/113 [84%] vs 68/113 [60%] correct, p < 0.0001). Of the 74 with characteristic enhancement patterns, 55 (74%) were assigned an alternative incorrect or nonspecific diagnosis when originally evaluated in clinical practice, 12 (16%) received immunotherapy for noninflammatory myelopathies, and 2 (3%) underwent unnecessary spinal cord biopsy.ConclusionsMisdiagnosis of myelopathies is common. The gadolinium enhancement patterns characteristic of specific diagnoses can be identified with excellent agreement between raters educated on this topic. This study highlights the potential diagnostic utility of enhancement patterns in myelopathies with longitudinally extensive T2 lesions.

Objectives To describe CSF‐defined neuronal intermediate filament (NIF) autoimmunity. Methods NIF‐IgG CSF‐positive patients (41, 0.03% of 118599 tested, 1996–2019) were included (serum was neither sensitive nor specific). Criteria‐based patient NIF‐IgG staining of brain and myenteric NIFs was detected by indirect immunofluorescence assay (IFA); NIF‐specificity was confirmed by cell‐based assays (CBAs, alpha internexin, neurofilament light [NF‐L]), heavy‐[NF‐H] chain). Results Sixty‐one percent of 41 patients were men, median age, 61 years (range, 21–88). Syndromes were encephalopathy predominant (23), cerebellar ataxia predominant (11), or myeloradiculoneuropathies (7). MRI abnormalities (T2 hyperintensities of brain, spinal cord white matter tracts. and peripheral nerve axons) and neurophysiologic testing (EEG, EMG, evoked potentials) co‐localized with clinical neurological phenotypes (multifocal in 29%). Thirty patients (73%) had ≥ 1 immunological perturbation: cancer (paraneoplastic), 22; systemic infection (parainfectious [including ehrlichosis, 3] or HIV), 7; checkpoint‐inhibitor cancer immunotherapy, 4; other, 5. Cancers were as follows: neuroendocrine‐lineage carcinomas, 12 (small cell, 6; Merkel cell, 5; pancreatic, 1 [11/12 had NF‐L‐IgG detected, versus 8/29 others, P = 0.0005]) and other, 11. Onset was predominantly subacute (92%) and accompanied by inflammatory CSF (75%), and immunotherapy response (77%). In contrast, CSF controls (15684 total) demonstrated NIF‐IgG negativity (100% of test validation controls), and low frequencies of autoimmune diagnoses (20% of consecutively referred clinical specimens) and neuroendocrine‐lineage carcinoma diagnosis (3.1% vs. 30% of NIF cases), P

A 77-year-old man presented with 1 week of back pain, night sweats, confusion, jaundice, and pruritus with patchy, blanchable erythematous lesions over his trunk (figure 1). Neurologic examination was normal, but a lumbar spine MRI showed diminished bone marrow signal. He was thrombocytopenic (13 × 109/L) and anemic (7.2 g/dL) with an immunoglobulin M (IgM) kappa monoclonal gammopathy and bone marrow biopsy consistent with Waldenstrom macroglobulinemia (WM). He was initiated on 60 mg prednisone daily and rituximab. Skin biopsy revealed nonspecific dermal edema with perivascular inflammation. Two weeks into admission, he developed left lower motor neuron facial droop, and was kept on the prednisone started 2 days prior for his WM. Shortly after that, it was noted that his Borrelia burgdorferi enzyme immunoassay (EIA) screen and supplemental B burgdorferi IgM immunoblot were positive, while the immunoglobulin G immunoblot was negative. Three weeks later, his facial palsy had resolved, but given extensive tick exposure history, he was treated with 3 weeks of doxycycline. CSF collection was deferred due to thrombocytopenia.

BACKGROUND Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA. METHODS Charts of adult patients with SE from St. Mary's Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic. RESULTS There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P

Bacterial infections of the nervous system manifest themselves in several ways, most of which are neurologic emergencies. This chapter reviews the classic syndromes of meningoencephalitis and focal infection (cerebritis or abscess) and the syndromes of neurosyphilis, tuberculosis, botulism, leprosy, Lyme disease, Whipple disease, rickettsiosis, diphtheria, and ventricular shunt infections.

A 52-year-old man is admitted to a neurosciences intensive care unit during winter for management of seizures requiring mechanical ventilation. Two days earlier he reported cough and myalgia. He was found seated on the couch with altered mental state and was minimally responsive. Upon arrival to the emergency department he was febrile at 38.8 °C and tachycardic. Complete blood cell count showed leukocytosis (11.1×109 cells/L, neutrophilic predominance). Computed tomography of the head showed an area of hypodensity in the left temporal lobe. During computed tomography, the patient had generalized convulsions requiring lorazepam, fosphenytoin, and levetiracetam, followed by initiation of a continuous midazolam infusion before seizures were controlled. He was started on broad-spectrum antimicrobials, including acyclovir, and a lumbar puncture was performed. Cerebrospinal fluid protein concentration was 196 mg/dL, and he had 10 white blood cells/µL with lymphocyte predominance. There was no hypoglycorrhachia. After 24 hours, the patient was weaned from the midazolam infusion and maintained on levetiracetam monotherapy. He was extubated but remained encephalopathic. Magnetic resonance imaging performed the day after admission demonstrated numerous T2 hyperintense lesions throughout both cerebral hemispheres including both mesial temporal lobes and right thalamus. Nasopharyngeal polymerase chain reaction was positive for influenza virus A, which was later typed further and identified as pandemic 2009 H1N1 virus. A diagnosis of influenza-associated encephalopathy/encephalitis was made. The patient was treated with oseltamivir, as well as high-dose intravenous methylprednisolone. His encephalopathy gradually improved. Repeated imaging at 3-month follow-up showed resolution of the previously seen abnormalities. His neurologic examination was normal. Postinfectious or parainfectious autoimmunity syndromes refer to neurologic signs and symptoms that develop during or after an infection but are not thought to be caused by direct infection of the nervous system.

Parasitic infections make up a small but important subset of central nervous system (CNS) infections. Although necessary to be considered in the comprehensive differential diagnosis for patients presenting with suspected neurologic infections, these conditions are particularly important in regions where parasitic infections are endemic and for immunocompromised patients. Among the most common parasitic infections of the CNS are neurocysticercosis, echinococcosis (hydatid cyst), toxoplasmosis, amebic meningoencephalitis, and cerebral malaria.

ObjectiveTo compare acute treatment responses and long-term outcome in leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis.MethodsRetrospective case series of 118 patients with LGI1 antibody encephalitis evaluated at Mayo Clinic across all US sites from 1 May 2008 to 31 March 2019. Patient clinical data were identified and analysed through the neuroimmunology laboratory and electronic medical record. LGI1 antibody detection was by cell-based indirect immunofluorescence assay of serum, cerebrospinal fluid or both. Clinical outcomes were faciobrachial dystonic seizure (FBDS) resolution, modified Rankin Scale (mRS) score, Kokmen Short Test of Mental Status (STMS) score (0–38 point scale) and neuropsychometric testing results.ResultsCompared with intravenous immunoglobulin (IVIg) (n=21), patients treated with single-agent acute corticosteroids (intravenous, oral or both) (n=49) were more likely to experience resolution of FBDS (61% vs 7%, p=0.002) and improvements in mRS score (ΔmRS score 2 vs 0, p=0.008) and median Kokmen STMS scores (ΔKokmen STMS score 5 points vs 0 points, p=0.01). In 54 patients with long-term follow-up (≥2 years), the median mRS score was 1 (range 0–6) and the median Kokmen STMS score was 36 (range 24–38) after all combinations of immunotherapy. Neuropsychometric testing in 32 patients with long-term follow-up (≥2 years) demonstrated short-term memory impairments in 37%.ConclusionsCorticosteroids appeared more effective acutely than IVIg in improving LGI1 antibody encephalitis in this retrospective comparison of immunotherapies. While improvement with immunotherapy is typical and long-term outcome is favourable, short-term memory deficits are noted in approximately a third of the patients.

Background and ObjectiveSevere attacks of myelin oligodendrocyte glycoprotein (MOG) antibody–associated disorder (MOGAD) and aquaporin-4 (AQP4) antibody–positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) may require ventilatory support, but data on episodes are limited, particularly for MOGAD. We sought to compare the frequency, characteristics, and outcomes of MOGAD and AQP4-NMOSD attacks requiring ventilatory support.MethodsThis retrospective descriptive study identified Mayo Clinic patients (January 1, 1996–December 1, 2020) with MOGAD or AQP4-NMOSD and an attack requiring noninvasive or invasive ventilation at Mayo Clinic or an outside facility by searching for relevant terms in their electronic medical record. Inclusion criteria were (1) attack-related requirement for noninvasive (bilevel positive airway pressure or continuous positive airway pressure) or invasive respiratory support (mechanical ventilation); (2) MOG or AQP4 antibody positivity with fulfillment of MOGAD and AQP4-NMOSD clinical diagnostic criteria, respectively; and (3) sufficient clinical details. We collected data on demographics, comorbid conditions, indication for and duration of respiratory support, MRI findings, treatments, and outcomes. The races of those with attacks requiring respiratory support were compared to those without such attacks in MOGAD and AQP4-NMOSD.ResultsAttacks requiring ventilatory support were similarly rare in patients with MOGAD (8 of 279, 2.9%) and AQP4-NMOSD (11 of 503 [2.2%]) (p= 0.63). The age at attack (median years [range]) (MOGAD 31.5 [5–47] vs AQP4-NMOSD 43 [14–65];p= 0.01) and percentage of female sex (MOGAD 3 of 8 [38%] vs AQP4-NMOSD 10 of 11 [91%];p= 0.04) differed. The reasons for ventilation differed between MOGAD (inability to protect airway from seizure, encephalitis or encephalomyelitis with attacks of acute disseminated encephalomyelitis 5 [62.5%] or unilateral cortical encephalitis 3 [37.5%]) and AQP4-NMOSD (inability to protect airway from cervical myelitis 9 [82%], rhombencephalitis 1 [9%], or combinations of both 1 [9%]). Median ventilation duration for MOGAD was 2 days (range 1–7 days) vs 19 days (range 6–330 days) for AQP4-NMOSD (p= 0.01). All patients with MOGAD recovered, but 2 of 11 (18%) patients with AQP4-NMOSD died of the attack. For AQP4-NMOSD, Black race was overrepresented for attacks requiring ventilatory support vs those without these episodes (5 of 11 [45%] vs 88 of 457 [19%];p= 0.045).DiscussionVentilatory support is rarely required for MOGAD and AQP4-NMOSD attacks, and the indications differ. Compared to MOGAD, these attacks in AQP4-NMOSD may have higher morbidity and mortality, and those of Black race were more predisposed, which we suspect may relate to socially mediated health inequality.

Peripheral neuropathies secondary to neurotoxicants are frequently considered but can be difficult to diagnose. Accurate diagnosis is important to avoid unnecessary testing, prevent further exposure, and initiate treatment when available. This article reviews key features of some of the more common or representative toxic neuropathies, including those caused by occupational and environmental exposure, medications, and chemotherapeutic agents.

Shotgun metagenomic sequencing can detect nucleic acids from bacteria, fungi, viruses, and/or parasites in clinical specimens; however, little data exist to guide its optimal application to clinical practice. We retrospectively reviewed results of shotgun metagenomic sequencing testing requested on cerebrospinal fluid samples submitted to an outside reference laboratory from December 2017 through December 2019. Of the 53 samples from Mayo Clinic patients, 47 were requested by neurologists, with infectious diseases consultation in 23 cases. The majority of patients presented with difficult-to-diagnose subacute or chronic conditions. Positive results were reported for 9 (17%) Mayo Clinic patient samples, with 6 interpreted as likely contamination. Potential pathogens reported included bunyavirus, human herpesvirus 7, and enterovirus D-68, ultimately impacting care in two cases. Twenty-seven additional samples were submitted from Mayo Clinic Laboratories reference clients, with positive results reported for three (11%): two with potential pathogens (West Nile virus and Toxoplasma gondii) and one with Streptococcus species with other bacteria below the reporting threshold (considered to represent contamination). Of 68 negative results, 10 included comments on decreased sensitivity due to high DNA background (n = 5), high RNA background (n = 1), insufficient RNA read depth (n = 3), or quality control (QC) failure with an external RNA control (n = 1). The overall positive-result rate was 15% (12/80), with 58% (7/12) of these interpreted as being inconsistent with the patient’s clinical presentation. Overall, potential pathogens were found in a low percentage of cases, and positive results were often of unclear clinical significance. Testing was commonly employed in cases of diagnostic uncertainty and when immunotherapy was being considered.

BACKGROUND: Inappropriate use of diagnostic tests contributes to rising healthcare expenditures, and improving appropriate utilization rates is important for high-value patient care. The Venereal Disease Research Laboratory (VDRL) test performed in cerebrospinal fluid (CSF) has historically been improperly utilized, although there is no recent evaluation of its use in clinical practice. OBJECTIVES: Quantify the rates of appropriate CSF-VDRL testing, determine the CSF-VDRL false-positivity rate, and describe the causes of false-positive CSF-VDRL reactivity. DESIGN: Retrospective cohort study PATIENTS: A total of 32,626 patients with CSF-VDRL testing at one of three Mayo Clinic sites (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ) from January 1, 1994, to February 28, 2018. MAIN MEASURES: Rate of appropriate CSF-VDRL test utilization from January 1, 2011, to December 31, 2017, and CSF-VDRL true- and false-positivity rates from January 1, 1994, to February 28, 2018. KEY RESULTS: Among 8553 persons with negative CSF-VDRL results, testing was inappropriately ordered for 8399 (98.2%) of these patients. The word “syphilis” or “neurosyphilis” appeared in the notes of 1184 (13.8%) individuals with a negative CSF-VDRL result. From January 1994 through February 2018, 33,933 CSF-VDRL tests were performed on 32,626 individual patients. Among the 60 positive CSF-VDRL results, 43 (71.7%) were true-positives and 17 (28.3%) were false-positives. All patients with false-positive CSF-VDRL results were tested unnecessarily. Neoplastic meningitis was a common cause of false-positive CSF-VDRL results. CONCLUSIONS: Inappropriate use of CSF-VDRL testing for the diagnosis of neurosyphilis remains problematic in clinical practice. Following recommended testing algorithms would prevent unnecessary testing and minimize false-positive results.

Background: Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The putative mechanism is impairment of thermoregulation due to a presumed demyelinating hypothalamic lesion. Objective: To describe a cohort of patients with MS, who developed EH. Methods: Patients were identified through review of the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within any field. We reviewed records for accuracy of diagnoses and abstracted relevant data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic lesions. Results: Of 156 patients, 34 had concurrent MS and hypothermia. Thirty-two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years, and median expanded disability status scale (EDSS) was 8.0. Most patients presented with alterations in consciousness. Infection was suspected as the precipitating factor in 19 (56%), but clinically/laboratory supported in only 9 (28%). MRI lesions were evident within the hypothalamus in only 4 (14%). Conclusion: EH occurs predominantly in patients with advanced secondary progressive MS. The major manifestation is altered consciousness. Infection is often suspected as causal, but infrequently confirmed. Although commonly implicated, hypothalamic lesions were rarely evident on MRI and were absent in two post-mortem evaluations.

Objectives We evaluate incidence and prevalence of autoimmune encephalitis and compare the epidemiology of autoimmune and infectious encephalitis.

Background The Venereal Disease Research Laboratory (VDRL) test performed in cerebrospinal fluid (CSF) is considered highly specific for the diagnosis of neurosyphilis, but algorithms to diagnose neurosyphilis require positive syphilis serologic testing prior to obtaining CSF-VDRL. Inappropriate use of diagnostic tests depletes healthcare resources, and contributes to rising healthcare expenditures. CSF-VDRL has historically been improperly utilized; however there is no recent evaluation of its use in clinical practice. We aimed to quantify rates of appropriate CSF-VDRL testing, determine the CSF-VDRL false-positivity rate and describe causes of false-positive CSF-VDRL reactivity. Methods In this retrospective cohort study of three Mayo Clinic sites (Rochester, MN, Jacksonville, FL, and Scottsdale, AZ), we measured the rate of appropriate CSF-VDRL test utilization in patients with negative testing from January 1, 2011 to December 31, 2017. We then identified all patients with positive CSF-VDRL testing from January 1, 1994 to February 28, 2018, characterized true- and false-positive rates and described causes of CSF-VDRL false-positivity. Results Among 8,553 persons with negative CSF-VDRL results, testing was unnecessarily ordered in 8,399 (98.2%). The word “syphilis” or “neurosyphilis” appeared in the notes of only 1,184 (13.8%) individuals with a negative CSF-VDRL result. From January 1994 through February 2018, 33,933 CSF-VDRL tests were performed on 32,626 individual patients. Among 60 positive CSF-VDRL results, 41 (68.3%) were true-positives, 2 (3.3%) were indeterminate, and 17 (28.3%) were false-positives. Every patient with true-positive CSF-VDRL had positive serologic syphilis testing prior to CSF testing. All patients with false-positive CSF-VDRL results were inappropriately tested. Neoplastic meningitis was a common cause of false-positive CSF-VDRL results. Conclusion This is the first study in decades to review CSF-VDRL utilization for the diagnosis of neurosyphilis. Inappropriate use of CSF-VDRL testing for diagnosis of neurosyphilis remains problematic in clinical practice. Following recommended testing algorithms would prevent unnecessary testing, preserve resources, and minimize false-positive results. Disclosures All Authors: No reported disclosures

Early recognition of an infectious syndrome and initiation of appropriate treatment improves outcome. Yet, in spite of advances in diagnosis and treatment, infections of the central nervous system (CNS) still result in significant morbidity and mortality. Choosing appropriate diagnostic studies can expedite diagnosis, avoid exposure to unnecessary invasive testing, and reduce costs of care. Awareness and early detection of known complications of CNS infections can decrease morbidity. Here we review common and rare infections that can result in severe neurologic compromise. We use a syndromic approach, emphasizing practical aspects of diagnosis and management.

Click here to listen to the Podcast 'Query encephalitis' is a common neurological consultation in hospitalised patients. Identifying the syndrome is only part of the puzzle. Although historically encephalitis has been almost synonymous with infection, we increasingly recognise parainfectious or postinfectious as well as other immune-mediated causes. We must also distinguish encephalitis from other causes of encephalopathy, including systemic infection, metabolic derangements, toxins, inherited metabolic disorders, hypoxia, trauma and vasculopathies. Here, we review the most important differential diagnoses (mimics) of patients presenting with an encephalitic syndrome and highlight some unusual presentations (chameleons) of infectious encephalitis.

Background GFAP (glial fibrillary acidic protein)-IgG is predominantly associated with meningoencephalomyelitis, and neuropathy presentations are rare. Methods We reviewed clinical, electrodiagnostic and histopathological presentations of GFAP-IgG associated peripheral neuropathy. Results We identified six cases, five of whom had peripheral neuropathy as the initial presentation. Acute/subacute polyradicluoneuropathy or proximal nerve involvement was a common presentation. Three had demyelinating neuropathies on electrophysiological studies. Nerve biopsies (n = 2) demonstrated T-cell predominant perivascular inflammatory collections, and all patients with clinical follow up responded favorably to immunotherapy. Conclusion GFAP neuropathy represents a potentially treatable immune-mediated neuropathy and can occur with or without co-existing meningoencephalomyelitis.

Introduction Elsberg syndrome (ES) is a rarely recognized cause of cauda equina syndrome and lower thoracic myelitis, mainly linked to reactivation, or occasionally primary, infection with herpes simplex virus type 2. West Nile virus neuroinvasive disease is rarely considered in the differential diagnosis of patients with ES. Case report A 63-year-old man with pancreatic cancer in remission and polymyalgia rheumatica on low-dose prednisone presented with a 10-day history of low-back pain and a viral-type illness with low-grade fever, nausea, and vomiting. Days later, he developed left leg monoparesis, neurogenic bladder, and bowel. Magnetic resonance imaging of the lumbar spine revealed a hyperintense signal abnormality within the central spinal cord and conus medullaris with mild swelling of the conus. Cells, proteins, and glucose in cerebrospinal fluid were 67/mm, 70 mg/dL, and 58 mg/dL, respectively. Serology was positive for West Nile virus IgM. Nerve conduction studies and electromyography showed an acute motor neurogenic process affecting left lumbosacral segments. Conclusions West Nile virus neuroinvasive disease is an uncommon condition that should be considered in patients with ES. Determining the etiology of ES in the acute setting may avoid unnecessary diagnostic investigations and treatments.

ObjectiveTo determine the persistence of no evident disease activity (NEDA) in a population-based relapsing-remitting MS (RRMS) cohort.MethodsAll incident cases of RRMS in Olmsted County between 2000 and 2011 were identified using a medical records linkage system. Persistence of NEDA after RRMS diagnosis was determined by retrospective chart review. MRI activity, relapse, or Expanded Disability Status Scale (EDSS) worsening resulted in failure of NEDA.ResultsWe identified 93 incident cases of RRMS including 82 individuals with sufficient follow-up to determine the persistence of NEDA. There were 44 individuals not on disease-modifying therapy (DMT), whereas 37 individuals were prescribed an injectable DMT and 1 received mitoxantrone during the interval over which NEDA was maintained. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years according to routine care assessment. At 10 years, there was no difference in EDSS disability among patients who maintained NEDA vs those who failed NEDA at 1 year (p = 0.3).ConclusionsNEDA infrequently persists beyond 2 years in a population-based cohort of newly diagnosed patients with RRMS.

We describe clinical and diagnostic features of various autoimmune and viral encephalitis subtypes.Population-based studies have demonstrated both autoimmune and viral causes have similar prevalence and incident rates. Repertoire of autoimmune biomarkers has considerably increased with discovery of many novel neural antibodies including glial fibrillary acidic proteinα-immunoglobulin G. Similarly, with use of next generation sequencing and DNA libraries, many viral causes are being detected which would have been categorized as encephalitis of unknown cause a decade ago.Autoimmune and viral encephalitides can resemble one another and sometimes autoimmune encephalitis may be triggered by viral infections. Early diagnosis and treatment is the key to both causes, which emphasizes the importance of clinical diagnosis before laboratory confirmation.

Objective:Elsberg syndrome (ES) is an established but often unrecognized cause of acute lumbosacral radiculitis with myelitis related to recent herpes virus infection. We defined ES, determined its frequency in patients with cauda equina syndrome (CES) with myelitis, and evaluated its clinical, radiologic, and microbiologic features and outcomes.Methods:We searched the Mayo Clinic medical records for ES and subsequently for combinations of index terms to identify patients with suspected CES and myelitis.Results:Our search yielded 30 patients, 2 diagnosed with ES and an additional 28 with clinical or radiologic evidence of CES retrospectively suspected of having ES. We classified patients in 5 groups according to diagnostic certainty. MRI and EMG confirmed that 2 had only myelitis, 5 only radiculitis, and 16 both. Two had preceding sacral herpes infection and 1 oral herpes simplex. Spinal cord lesions were commonly multiple, discontinuous, not expansile, and centrally or ventrally positioned. Lesions generally spared the distal conus. Nerve root enhancement was occasionally prominent and was smooth rather than nodular. Lymphocytic CSF pleocytosis was common. Thirteen patients (43%) had viral isolation studies, which were commonly delayed; the delay may have accounted for the low rate of viral detection. Acyclovir was administered to 6 patients. Most patients recovered with sequelae; 1 patient experienced encephalomyelitis and died.Conclusion:ES is a definable condition likely responsible for 10% of patients with combined CES and myelitis. Radiologic findings are not entirely specific but may help in differentiating ES from some competing diagnostic considerations. We propose criteria to facilitate diagnosis.

Objective: To characterize patients misdiagnosed with multiple sclerosis (MS). Methods: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Results: Of 110 misdiagnosed patients, 51 (46%) were classified as “definite” and 59 (54%) “probable” misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Conclusions: Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.

Retroviruses are a family of RNA viruses that replicate by reverse transcription. The family includes HIV and human T-lymphotropic virus. This chapter reviews neurologic manifestations of these retroviruses. A retrovirus in the genus Lentivirus, HIV has 2 forms, HIV-1 and HIV-2. HIV-1 is associated with the global AIDS pandemic, whereas HIV-2 causes an AIDS-like illness primarily in West Africa, although pockets of infection exist globally.

The diagnostic criteria for multiple sclerosis (MS) rely on clinical, paraclinical, and radiographic findings of limited specificity. Many disorders mimic MS, and the decision of when to investigate an alternative diagnosis can be challenging. Reliance on extensive ancillary testing to exclude potential mimics, however, is unnecessary in most cases. Rather, recognition and rigorous interpretation of "classic" clinical and radiographic features of MS are often sufficient to establish the diagnosis. Misinterpretation of the clinical and radiographic diagnostic criteria for MS in the setting of more common diseases and syndromes and a lack of vigilance for "red flags" are important contributors to misdiagnosis. A clinical framework for the differential diagnosis of MS that emphasizes phenotypes atypical for MS and suggests diseases or syndromes in which they more commonly occur may be an important diagnostic guide for clinicians in contemporary practice.

Objective: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy. Method: We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of ≥1 neural autoantibody (n = 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6- to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency. Results: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p = 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%). Conclusions: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy. Classification of evidence: This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control.

The differential of cervical spondylotic myelopathy (CSM) is broad and includes multiple conditions that can cause and mimic myelopathy. In adults older than 55 years of age, CSM is the most common cause of myelopathy. This article summarizes the pathophysiology, clinical presentation, differential diagnosis, diagnostic evaluation, and natural history of CSM. Available treatment options and their complications are reviewed.

Background A high index of suspicion is required to make the diagnosis of constrictive pericarditis (CP) in patients presenting with cirrhosis and volume overload, as they can otherwise go misdiagnosed for years. Methods Case report. Findings A 51 year-old man with a history of presumed alcoholic cirrhosis presented to the emergency department with anasarca. Abdominal ultrasound with Doppler demonstrated a nodular cirrhotic liver, but no evidence of portal hypertension or ascites. The chest x-ray, however, was significant for a right-sided pleural effusion and pericardial calcification, suggestive of (CP). Transthoracic echocardiogram and ECG-gated computerized tomography scan of the chest without IV contrast confirmed the diagnosis. The patient was referred to thoracic surgery for definitive pericardiectomy. Conclusion The diagnosis of CP is often neglected by admitting physicians, who usually attribute the symptoms to another disease process. Although a multimodality approach is necessary for the diagnosis of CP, this case highlights the utility of chest x-ray, a relatively non-invasive and inexpensive test, in expediting the diagnosis.

A 64-year-old woman developed sudden onset of diplopia, headache, and bilateral abducens palsy. MRI revealed no intracranial mass, ischemia, or intraorbital pathology. Magnetic resonance angiography suggested bilateral carotid cavernous fistulas (CCFs, figure 1). Digital substraction angiogram revealed an intercavernous sinus dural arteriovenous fistula (DAVF), which was successfully embolized (figure 2). By 3-month follow-up, her …

A 70-year-old woman with a history of non-Hodgkin lymphoma presented with left-sided facial pain. MRI of the face, orbit, and neck was negative (figure). A week later, she developed hypesthesia in a V3 distribution. Repeat MRI was again nondiagnostic but fluorodeoxyglucose (FDG)-PET showed increased uptake along the left V3 branch of the trigeminal nerve, as well as in the parotid gland. Biopsy of the left parotid confirmed recurrent lymphoma.

A 58-year-old man presented with daily hour-long spells of hypothermia, hyperhidrosis, and hypotension. Results of laboratory studies, including thyroid-stimulating hormone, free thyroxine, total/bioavailable testosterone, morning cortisol, and urine osmolality, were normal. MRI of the brain

Objective: To highlight the utility of magnetic resonance gradient echo (MR GRE) in the early diagnosis of primary angiitis of the central nervous system (PACNS) through a case report. Background PACNS is a rare form of vasculitis. The presenting symptoms of PACNS are often nonspecific, including encephalopathy, headaches, stroke, seizures, and cranial nerve palsies. Currently, biopsy is the gold standard for diagnosing PACNS. The sensitivity and specificity of less invasive testing, including conventional MRI, magnetic resonance angiography (MRA), CSF analysis, and four vessel angiography, are not as robust. Design/Methods: Case-report and literature review. Results: : A 52 year old gentleman presented for workup of episodic vertigo, dysphasia, and headaches. MRI brain revealed confluent subcortical T2 signal hyperintensities in the right frontotemporal and left temporal regions, corresponding small punctuate and linear zones of contrast enhancement, and a subacute left cerebellar hemorrhage. His MR GRE imaging revealed subcortical microhemorrhages and a left cerebellar hemorrhage. Serologic workup revealed normal CBC, electrolytes, INR, sedimentation rate, lactate dehydrogenase, angiotensin-converting enzyme level, myeloperoxidase, proteinase, antiphospholipid, and paraneoplastic antibodies. CSF examination revealed prominent lymphocytosis and negative cytology. MRA and conventional angiography were unrevealing. A cortical biopsy revealed chronic perivascular lymphocytic inflammation with focal granulomatous features and negative beta amyloid stain suggestive of PACNS. The patient was treated with a five day course of intravenous methylprednisolone (1 gram daily), followed by an oral prednisone taper. He reported no further episodes of vertigo or semantic paraphasia following initiation of steroids. Conclusions: Our case demonstrates the utility of GRE in the early diagnosis of PACNS. The presence of cortical and/or subcortical signal hypointensities on GRE (consistent with petechial hemorrhages) can help to distinguish PACNS from many of its mimickers. Such an imaging modality may be useful for promptly establishing the diagnosis and treating with immunosuppression, which is needed to avoid significant morbidity and mortality. Disclosure: Dr. Toledano has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Dhamija has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Moseley has nothing to disclose.