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Abstract
Thomas Pollak explores the emergence of a new worldview which attempts to explain
all manner of ills as the result of inflammation or immune dysfunction. He argues
that while this view is rooted in science, it neglects the true complexity of most
health conditions, and risks undermining the more holistic concepts of illness favoured
by psychiatry.
This case series assesses the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis. Question What diseases are misdiagnosed as autoimmune encephalitis and which factors contribute to misdiagnosis? Findings In this case series of 107 outpatients misdiagnosed with autoimmune encephalitis, approximately half had functional neurologic or psychiatric disorders. An insidious rather than subacute onset and lack of magnetic resonance imaging or cerebrospinal fluid findings suggestive of inflammation were clues to misdiagnosis; overinterpretation of serum nonspecific antibodies was a major contributor to misdiagnosis. Meaning A broad range of disorders are misdiagnosed as autoimmune encephalitis and misdiagnosis occurs in many settings including at specialized centers participating in this study. Importance Autoimmune encephalitis misdiagnosis can lead to harm. Objective To determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis. Design, Setting, and Participants This 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 Measures Data were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions. Results A 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 Relevance When 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.
Physical symptoms account for more than half of all outpatient visits, yet the predominant disease-focused model of care is inadequate for many of these symptom-prompted encounters. Moreover, the amount of clinician training dedicated to understanding, evaluating, and managing common symptoms is disproportionally small relative to their prevalence, impairment, and health care costs. This narrative review regarding physical symptoms addresses 4 common epidemiologic questions: cause, diagnosis, prognosis, and therapy. Important findings include the following: First, at least one third of common symptoms do not have a clear-cut, disease-based explanation (5 studies in primary care, 1 in specialty clinics, and 2 in the general population). Second, the history and physical examination alone contribute 73% to 94% of the diagnostic information, with costly testing and procedures contributing much less (5 studies of multiple types of symptoms and 4 of specific symptoms). Third, physical and psychological symptoms commonly co-occur, making a dualistic approach impractical. Fourth, because most patients have multiple symptoms rather than a single symptom, focusing on 1 symptom and ignoring the others is unwise. Fifth, symptoms improve in weeks to several months in most patients but become chronic or recur in 20% to 25%. Sixth, serious causes that are not apparent after initial evaluation seldom emerge during long-term follow-up. Seventh, certain pharmacologic and behavioral treatments are effective across multiple types of symptoms. Eighth, measuring treatment response with valid scales can be helpful. Finally, communication has therapeutic value, including providing an explanation and probable prognosis without "normalizing" the symptom.
In our article, we reconstruct how the patient-made term “long COVID” was able to become a widely accepted concept in public discourses. While the condition was initially invisible to the public eye, we show how the mobilization of subjective evidence online, i.e., the dissemination of reports on the different experiences of lasting symptoms, was able to transform the condition into a crucial feature of the coronavirus pandemic. We explore how stakeholders used the term “long COVID” in online media and in other channels to create their illness and group identity, but also to demarcate the personal experience and experiential knowledge of long COVID from that of other sources. Our exploratory study addresses two questions. Firstly, how the mobilization of subjective evidence leads to the recognition of long COVID and the development of treatment interventions in medicine; and secondly, what distinguishes these developments from other examples of subjective evidence mobilization. We argue that the long COVID movement was able to fill crucial knowledge gaps in the pandemic discourses, making long COVID a legitimate concern of official measures to counter the pandemic. By first showing how illness experiences were gathered that defied official classifications of COVID-19, we show how patients made the “long COVID” term. Then we compare the clinical and social identity of long COVID to that of chronic fatigue syndrome (ME/CFS), before we examine the social and epistemic processes at work in the digital and medial discourses that have transformed how the pandemic is perceived through the lens of long COVID. Building on this, we finally demonstrate how the alignment of medical professionals as patients with the movement has challenged the normative role of clinical evidence, leading to new forms of medical action to tackle the pandemic.
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