Autoimmune Encephalitis Resembling Dementia Syndromes

Abstract

ObjectiveAs autoimmune encephalitis (AIE) can resemble neurodegenerative dementia syndromes, and patients do not always present as encephalitis, this study evaluates how frequently AIE mimics dementia and provides red flags for AIE in middle-aged and older patients.MethodsIn this nationwide observational cohort study, patients with anti–leucine-rich glioma-inactivated 1 (LGI1), anti–NMDA receptor (NMDAR), anti–gamma-aminobutyric acid B receptor (GABABR), or anti–contactin-associated protein-like 2 (CASPR2) encephalitis were included. They had to meet 3 additional criteria: age ≥45 years, fulfillment of dementia criteria, and no prominent seizures early in the disease course (≤4 weeks).ResultsTwo-hundred ninety patients had AIE, of whom 175 were 45 years or older. Sixty-seven patients (38%) fulfilled criteria for dementia without prominent seizures early in the disease course. Of them, 42 had anti-LGI1 (48%), 13 anti-NMDAR (52%), 8 anti-GABABR (22%), and 4 anti-CASPR2 (15%) encephalitis. Rapidly progressive cognitive deterioration was seen in 48 patients (76%), whereas a neurodegenerative dementia syndrome was suspected in half (n = 33). In 17 patients (27%; 16/17 anti-LGI1), subtle seizures had been overlooked. Sixteen patients (25%) had neither inflammatory changes on brain MRI nor CSF pleocytosis. At least 1 CSF biomarker, often requested when dementia was suspected, was abnormal in 27 of 44 tested patients (61%), whereas 8 had positive 14-3-3 results (19%). Most patients (84%) improved after immunotherapy.ConclusionsRed flags for AIE in patients with suspected dementia are: (1) rapidly progressive cognitive decline, (2) subtle seizures, and (3) abnormalities in ancillary testing atypical for neurodegeneration. Physicians should be aware that inflammatory changes are not always present in AIE, and that biomarkers often requested when dementia was suspected (including 14-3-3) can show abnormal results. Diagnosis is essential as most patients profit from immunotherapy.

Clinical Features and Therapeutic Effects of Anti-leucine-rich Glioma Inactivated 1 Encephalitis: A Systematic Review

“…A quarter of patients with anti-LGI1 encephalitis suffered from cognitive decline in orientation, while fewer patients had impairment in visuospatial skills and executive function. Contrary to our results, Bastiaansen et al ( 84 ) discovered that patients with anti-LGI1 encephalitis showed similarities in frequency and severity of visuospatial and executive function impairment as those with anti-GABA B R encephalitis (~70% in anti-LGI1 encephalitis and 55% in anti-GABA B R encephalitis). We drew the controversial conclusion that this was possibly because some cases we included did not contain complete information on cognitive disorders, which could serve as a reminder for clinicians to pay more attention to cognitive impairments in patients with anti-LGI1 encephalitis.…”

“…As AE can affect any brain network involving initiating and regulating sleep, all types of sleep disorders can occur, with distinct association, frequency, and intensity ( 85 ). Compared to other research ( 84 ), the rate of sleep disorders in anti-LGI1 encephalitis was lower based on our results, thus it reminded us to pay more attention to patients' sleep problems especially for clinicians.…”

“…This review described clinical features and therapeutic effects of anti-LGI1 encephalitis comprehensively. According to our results, the most common symptom of anti-LGI1 encephalitis was short-term memory loss, which is a common characteristic in other AE (84). A quarter of patients with anti-LGI1 encephalitis suffered from cognitive decline in orientation, while fewer patients had impairment in visuospatial skills and executive function.…”

“…According to previous research ( 74 ), FBDS was considered as pathognomonic for anti-LGI1 encephalitis, in which EEG typically showed prominent muscle artifacts (lasting 0.5–1.6 s). Meanwhile, FBDS was also reported to be the most common seizure type in anti-LGI1 encephalitis, as well as a distinction among anti-LGI1 encephalitis and other AE ( 84 ).…”

Antibody Therapies in Autoimmune Encephalitis

“…The relapse risk in anti-NMDAR encephalitis is estimated to be 12% within 2 years, and the large majority of the relapses will be milder than previous episodes [15]. Two other retrospective cohorts showed relapse rates of 16% and 17% after a median follow-up of 30 and 24 months, respectively [22,37]. The chance of relapses after second-line immunotherapy, including rituximab, is however much smaller [15].…”