Michel Toledano

Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy.

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.

Cervical Spondylotic Myelopathy

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.

The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study

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.

Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis

To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.

A Clinical Approach to the Differential Diagnosis of Multiple Sclerosis

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.

Teaching NeuroImages: Diagnostic utility of FDG-PET in neurolymphomatosis

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.

Teaching NeuroImages: Hypothermia and corpus callosum agenesis in Shapiro syndrome Too cold, even for a Viking

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 brainA 58-year-old man presented with daily hour-long spells of hypothermia, hyperhidrosis, and hypotension. Results of laboratory studies, including thyroidstimulating hormone, free thyroxine, total/bioavailable testosterone, morning cortisol, and urine osmolality, were normal. MRI of the brain revealed corpus callosum agenesis (figure, A and B) consistent with Shapiro syndrome. Shapiro syndrome is a rare disorder described in fewer than 60 patients. It consists of periodic hypothermia, hyperhidrosis, and corpus callosum agenesis.1,2 Any condition with corpus callosum agenesis can cause the lateral ventricles to assume a Viking helmet appearance (figure, C). The hypothermia in Shapiro syndrome is probably due to hypothalamic dysfunction and may be responsive to clonidine.2

Elsberg syndrome A rarely recognized cause of cauda equina syndrome and lower thoracic myelitis

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.

Teaching NeuroImages: Seeing double Intercavernous sinus dural arteriovenous fistula causing bilateral abducens palsy

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 …

Population-based study of “no evident disease activity” in MS

Objective To determine the persistence of no evident disease activity (NEDA) in a population-based relapsing-remitting MS (RRMS) cohort. Methods All 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. Results We 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). Conclusions NEDA infrequently persists beyond 2 years in a population-based cohort of newly diagnosed patients with RRMS.