ImportanceAutoimmune encephalitis misdiagnosis can lead to harm.ObjectiveTo determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis.Design, Setting, and ParticipantsThis retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), University of Washington in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded.Main Outcomes and MeasuresData were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions.ResultsA total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (>3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).Conclusions and RelevanceWhen evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

Background and PurposeSmartphone applications have been increasingly identified as a novel platform for dissemination of healthcare related information. However, there have been no studies done to evaluate the availability and content of stroke related apps. Purpose: This study aims to identify and analyze stroke-related applications available on the Apple iTunes and Android Google Play Store.MethodsThe Apple iTunes store and Android Google Play Store were searched for stroke-related applications on July 27, 2013 using keywords: stroke, brain attack, intracranial hemorrhage, subarachnoid hemorrhage, cerebral infarction. The content of the applications was analyzed by two independent investigators.ResultsA total of 93 relevant applications (46.2% android and 53.8% iPhone) were identified of which 47.3% were available free of cost. 92% of apps were identified as useful by users and over 60% had scientifically valid information. There is a significant participation of healthcare agencies in dissemination of stroke related information through apps with 47.3% apps being uploaded by them. Over half of all stroke related apps were aimed towards health care workers (51.6%), 75% of which could be utilized as bedside tools for patient care and remainder had information related to recent research advances. The difference in scientific validity between the apps aimed at general population versus healthcare professionals was statistically significant (P<0.01). There was no statistical association between cost of app and scientific validity or usefulness.ConclusionsSmartphone apps are a significant source of information related to stroke. An increasing participation of healthcare agencies should be encouraged to promote dissemination of scientifically valid information.

YouTube may be a significant resource for dissemination of information on public health issues like West Nile virus infection and should be targeted by healthcare agencies for this use. The major drawback of this medium is lack of verification by authorized healthcare professionals before these videos are made available for viewing by the community. Hence, a strict caution should be exercised in obtaining the information from unauthorized videos posted on YouTube.

Objective:To determine risk factors associated with clinical relapses and development of chronic epilepsy in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) IgG encephalitis.Methods:Patients with seizures related to LGI1-antibody encephalitis with ≥ 24 months of follow-up from disease onset were identified in the Mayo Clinic electronic medical record and Neuroimmunology lab records. Charts were reviewed to determine clinical factors, seizure types, imaging, treatment, occurrence of relapse, and outcome. Binary logistic regression analysis was performed to identify predictors of the development of chronic epilepsy. Univariate Cox proportional hazards regression was used to examine the influence of baseline characteristics on relapse risk.Results:Forty-nine patients with LGI1-antibody encephalitis and acute symptomatic seizures were identified. Almost all patients (n=48, 98%) were treated with immunotherapy. Eight had definite, and two had possible chronic epilepsy at last follow-up (10/49, 20.4%). Female sex (P=0.048) and younger age at disease onset (P=0.02) were associated with development of chronic epilepsy. Relapses occurred in 20 (40.8%), with a median time to first relapse of 7.5 months (range 3-94 months). Initial treatment with chronic steroid sparing immunotherapy was associated with reduced risk of relapse (hazards ratio=0.28, 95% CI 0.11-0.73, P=0.009).Conclusions:Chronic epilepsy occurred in 20.4% of our patients with LGI1-antibody encephalitis despite aggressive immunotherapy. Risk factors for chronic epilepsy were female sex and earlier age of onset. Relapses occurred in 40.8% of patients with prolonged follow-up, and chronic steroid sparing immunotherapy was associated with a lower relapse rate.

Background and ObjectivesTo assess the clinical practice applicability of autoimmune encephalitis (AE) criteria (2016).MethodsMedical records of 538 adults diagnosed with AE or related autoimmune encephalopathy at Mayo Clinic (not including pure movement disorders) were reviewed and AE guideline criteria applied.ResultsOf 538 patients, 288 were male (52%). The median symptom onset age was 55 years (range, 11–97 years; 16 had onset as children). All had other non-AE diagnoses reasonably excluded. Of 538 patients, 361 (67%) met at least possible criteria, having all 3 of subacute onset; memory deficits, altered mental status or psychiatric symptoms, and ≥1 supportive feature (new focal objective CNS finding, N = 285; new-onset seizures, N = 283; supportive MRI findings, N = 251; or CSF pleocytosis, N = 160). Of 361 patients, AE subgroups were as follows: definite AE (N = 221, 61%, [87% AE-specific IgG positive]), probable seronegative AE (N = 18, 5%), Hashimoto encephalopathy (N = 20, 6%), or possible AE not otherwise categorizable (N = 102, 28%). The 221 patients with definite AE had limbic encephalitis (N = 127, 57%), anti–NMDA-R encephalitis (N = 32, 15%), ADEM (N = 8, 4%), or other AE-specific IgG defined (N = 54, 24%). The 3 most common definite AE-IgGs detected were as follows: LGI1 (76, 34%), NMDA-R (32, 16%), and high-titer GAD65 (23, 12%). The remaining 177 patients (33%) not meeting possible AE criteria had the following: seizures only (65, 12% of all 538 patients), brainstem encephalitis without supratentorial findings (55, 10%; none had Bickerstaff encephalitis), or other (57, 11%). Those 57 “others” lacked sufficient supportive clinical, radiologic, or CSF findings (N = 26), had insidious or initially episodic onset of otherwise typical disorders (N = 21), or had atypical syndromes without clearcut memory deficits, altered mental status, or psychiatric symptoms (N = 10). Fifteen of 57 were AE-specific IgG positive (26%). Among the remaining 42, evidence of other organ-specific autoimmunity (mostly thyroid) was encountered in 31 (74%, ≥1 coexisting autoimmune disease [21, 50%] or ≥1 non–AE-specific antibodies detected [23, 53%]), and all but 1 had an objective immunotherapy response (97%).DiscussionThe 2016 AE guidelines permit autoimmune causation assessment in subacute encephalopathy and are highly specific. Inclusion could be improved by incorporating AE-IgG–positive patients with isolated seizures or brainstem disorders. Some patients with atypical presentations but with findings supportive of autoimmunity may be immune therapy responsive.