Cardiopulmonary Coupling Spectrogram as an Ambulatory Method for Assessing Sleep Disorders in Patients With Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: Sleep disorders are a common and important clinical feature in patients with autoimmune encephalitis (AE); however, they are poorly understood. We aimed to evaluate whether cardiopulmonary coupling (CPC), an electrocardiogram-based portable sleep monitoring technology, can be used to assess sleep disorders in patients with AE. METHODS: Patients fulfilling the diagnostic criteria of AE were age- and sex-matched with recruited healthy control subjects. All patients and subjects received CPC testing between August 2020 and December 2022. Demographic data, clinical information, and Pittsburgh Sleep Quality Index (PSQI) scores were collected from the medical records. Data analysis was performed using R language programming software. RESULTS: There were 60 patients with AE (age 26.0 [19.8-37.5] years, male 55%) and 66 healthy control subjects (age 30.0 [25.8-32.0] years, male 53%) included in this study. Compared with healthy subjects, patients with AE had higher PSQI scores (7.00 [6.00-8.00] vs 3.00 [2.00-4.00], p < 0.001), lower sleep efficiency (SE 80% [71%-87%] vs 92% [84%-95%], p < 0.001), lower percentage of high-frequency coupling (25% [14%-43%] vs 45% [38%-53%], p < 0.001), higher percentage of REM sleep (19% ± 9% vs 15% ± 7%, p < 0.001), higher percentage of wakefulness (W% 16% [11%-25%] vs 8% [5%-16%], p = 0.074), higher low-frequency to high-frequency ratio (LF/HF 1.29 [0.82-2.40] vs 0.91 [0.67-1.29], p = 0.001), and a higher CPC-derived respiratory disturbance index (9.78 [0.50-22.2] vs 2.95 [0.40-6.53], p < 0.001). Follow-up evaluation of 14 patients showed a decrease in the PSQI score (8.00 [6.00-9.00] vs 6.00 [5.00-7.00], p = 0.008), an increased SE (79% [69%-86%] vs 89% [76%-91%], p = 0.030), and a decreased W% (20% [11%-30%] vs 11% [8%-24], p = 0.035). Multiple linear regression indicated that SE (-7.49 [-9.77 to -5.21], p < 0.001) and LF/HF ratio (0.37 [0.13-0.6], p = 0.004) were independent factors affecting PSQI scores in patients with AE. DISCUSSION: Sleep disorders with autonomic dysfunction are common in patients with AE. Improvements in the PSQI score and SE precede the restoration of sleep microstructural disruption in the remission stage. CPC parameters may be useful in predicting sleep disorders in patients with AE.

[The diagnostic challenge of autoimmune encephalitis]. / Le défi diagnostique des encéphalites auto-immunes.

Autoimmune encephalitis encompasses a spectrum of neurological disorders characterized by an autoimmune response directed against neurons and glia. Around two-thirds of cases exhibit autoantibodies targeting neuronal or glial antigens in the cerebrospinal fluid and/or serum. The diagnosis is based on specific criteria combining a subacute clinical presentation and complementary test results. However, approximately one-quarter of patients do not present any paraclinical abnormalities, making the diagnosis complex. Testing for anti-antibodies is pivotal for diagnosis, and their interpretation should be contextual. Best practices for anti-neural antibody detection involve appropriate sample collection and confirmation of positive results in relation to the clinical picture.

L'encéphalite auto-immune comprend un spectre de troubles neurologiques caractérisés par une réponse auto-immunitaire dirigée contre les neurones et les cellules gliales. Environ deux tiers des cas présentent des autoanticorps dirigés contre des antigènes neuronaux et gliaux dans le liquide céphalorachidien et/ou le sérum. Le diagnostic repose sur des critères spécifiques combinant une présentation clinique subaiguë et des résultats d'examens complémentaires. Environ un quart des patients ne présente pas d'anomalie paraclinique, rendant le diagnostic complexe. La recherche des autoanticorps est cruciale pour le diagnostic de certitude et son interprétation doit être contextuelle. Les bonnes pratiques pour leur dosage impliquent le prélèvement d'échantillons appropriés et la confirmation des résultats positifs par rapport au tableau clinique.

Case report: Shingles-associated probable Bickerstaff brainstem encephalitis with IgM anti-sulfatide positivity.

Background: Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity. Case presentation: We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is the most appropriate diagnosis. Conclusions: We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles.

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. METHODS: Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. RESULTS: A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. DISCUSSION: Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

B-cell targeted therapies in autoimmune encephalitis: mechanisms, clinical applications, and therapeutic potential.

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.

Predictors and Clinical Characteristics of Relapses in LGI1-Antibody Encephalitis.

BACKGROUND AND OBJECTIVES: Relapses occur in 15%-25% of patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) autoimmune encephalitis and may cause additional disability. In this study, we clinically characterized the relapses and identified factors predicting their occurrence. METHODS: This is a retrospective chart review of patients with LGI1-Ab encephalitis diagnosed at our center between 2005 and 2022. Relapse was defined as worsening of previous or appearance of new symptoms after at least 3 months of clinical stabilization. RESULTS: Among 210 patients, 30 (14%) experienced a total of 33 relapses. The median time to first relapse was 23.9 months (range: 4.9-110.1, interquartile range [IQR]: 17.8). The CSF was inflammatory in 11/25 (44%) relapses, while LGI1-Abs were found in the serum in 16/24 (67%) and in the CSF in 12/26 (46%); brain MRI was abnormal in 16/26 (62%) relapses. Compared with the initial episode, relapses manifested less frequently with 3 or more symptoms (4/30 patients, 13% vs 28/30, 93%; p < 0.001) and had lower maximal modified Rankin scale (mRS) score (median 3, range: 2-5, IQR: 1 vs 3, range: 2-5, IQR: 0; p = 0.001). The median mRS at last follow-up after relapse (2, range: 0-4, IQR: 2) was significantly higher than after the initial episode (1, range: 0-4, IQR: 1; p = 0.005). Relapsing patients did not differ in their initial clinical and diagnostic features from 85 patients without relapse. Nevertheless, residual cognitive dysfunction after the initial episode (hazard ratio:13.8, 95% confidence interval [1.5; 129.5]; p = 0.022) and no administration of corticosteroids at the initial episode (hazard ratio: 4.8, 95% confidence interval [1.1; 21.1]; p = 0.036) were significantly associated with an increased risk of relapse. DISCUSSION: Relapses may occur years after the initial encephalitis episode and are usually milder but cause additional disability. Corticosteroid treatment reduces the risk of future relapses, while patients with residual cognitive dysfunction after the initial episode have an increased relapse risk.

Suspected autoimmune encephalitis: A retrospective study of patients referred for therapeutic plasma exchange.

INTRODUCTION: Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE. METHODS: A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for "suspected AE." The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete. RESULTS: A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology. CONCLUSION: Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

Seroprevalence of neuronal antibodies in diseases mimicking autoimmune encephalitis.

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti-titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions.

Autoimmune and inflammatory neurological disorders in the intensive care unit.

PURPOSE OF REVIEW: The present review summarizes the diagnostic approach to autoimmune encephalitis (AE) in the intensive care unit (ICU) and provides practical guidance on therapeutic management. RECENT FINDINGS: Autoimmune encephalitis represents a group of immune-mediated brain diseases associated with antibodies that are pathogenic against central nervous system proteins. Recent findings suggests that the diagnosis of AE requires a multidisciplinary approach including appropriate recognition of common clinical syndromes, brain imaging and electroencephalography to confirm focal pathology, and cerebrospinal fluid and serum tests to rule out common brain infections, and to detect autoantibodies. ICU admission may be necessary at AE onset because of altered mental status, refractory seizures, and/or dysautonomia. Early management in ICU includes prompt initiation of immunotherapy, detection and treatment of seizures, and supportive care with neuromonitoring. In parallel, screening for neoplasm should be systematically performed. Despite severe presentation, epidemiological studies suggest that functional recovery is likely under appropriate therapy, even after prolonged ICU stays. CONCLUSION: AE and related disorders are increasingly recognized in the ICU population. Critical care physicians should be aware of these conditions and consider them early in the differential diagnosis of patients presenting with unexplained encephalopathy. A multidisciplinary approach is mandatory for diagnosis, ICU management, specific therapy, and prognostication.

Status epilepticus: what's new for the intensivist.

PURPOSE OF REVIEW: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review. RECENT FINDINGS: Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures. SUMMARY: Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.

Cerebral baylisascariosis in a rainbow lorikeet (Trichoglossus moluccanus) in a German Zoo.

BACKGROUND: The raccoon roundworm, Baylisascaris procyonis, can cause a meningoencephalitis as neural larva migrans which is known in avian species, including rainbow lorikeets in North America, but has not been described in Old World parrots in Germany yet. CASE PRESENTATION: A 2-month-old, male rainbow lorikeet from a zoo in Germany was submitted for necropsy. Prior to death the animal had progressive neurological signs like apathy and torticollis. In the cerebrum a focally extensive severe granulomatous to necrotizing encephalitis with an intralesional larval nematode was diagnosed. Based on the clinical and pathological findings, the larval morphology and the epidemiological background, the larva was identified as Baylisascaris procyonis. CONCLUSIONS: Cerebral baylisascariosis should be considered as a differential diagnosis in zoo and pet birds with neurological signs having contact to racoons or rather racoon faeces in Germany due to the high prevalence of Baylisascaris procyonis in the German raccoon population.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

BACKGROUND: Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. METHODS: The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. RESULTS: Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. CONCLUSIONS: In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.

Clinical Spectrum, Treatment and Outcome of Children with Autoimmune Encephalitis.

OBJECTIVE: To assess the clinical spectrum, treatment, and outcome of children with autoimmune encephalitis (AE). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Paediatrics, The Aga Khan University Hospital, Karachi, Pakistan, from January 2017 to December 2021. METHODOLOGY: Medical records of children with a diagnosis of AE were reviewed for clinical features, treatment details, and outcomes. Outcome was defined as good (0-2) or poor (3-6) based on a modified Rankin Scale (mRS) score at 3-month follow-up. Descriptive statistics were reported and logistic regression was used to assess the prognostic factors associated with outcome. RESULTS: Thirty-three patients were identified with AE. Thirteen (39.3%) were antibody positive. Anti-N-methyl-D-aspartate receptor (NMDAR) antibody was seen in 92% of positive cases. Behavioural abnormalities (87.8%), seizures (81.8%), movement disorders (66.6%), psychiatric symptoms (63.6%), and mutism (33.3%) were the prominent symptoms. Thirty (91%) patients received first-line immunotherapy. Good outcome was seen in 14 (48.2%) patients. Univariable analysis showed that the odds of having poor outcome were 2.5 (95% confidence interval [CI] 0.37-16.88, p=0.34) in patients with chorea. In addition, an elevated cerebrospinal fluid (CSF) protein had an odds ratio (OR) of 8.6 (CI 0.88-84.83, p=0.064) and positive CSF antibodies had an OR of 3.7 (CI 0.79-17.72, p=0.095) for a poor outcome. Mortality was seen in 4 (12.1%) patients. CONCLUSION: A very low threshold is needed for the diagnosis of AE in children presenting with behavioural symptoms and chorea. Although the odds for poor prognosis were higher in patients with chorea, elevated CSF protein and positive CSF antibodies, the p-value did not come out significant. KEY WORDS: Autoimmune encephalitis, Antibodies, NMDAR, Immunotherapies, mRS score, Outcome.

Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice.

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disorders (MOGAD) is an autoimmune central nervous system disease. Antigen-specific immune tolerance using nanoparticles such as Polylactic-co-glycolic acid (PLGA) have recently been used as a new therapeutic tolerization approach for CNS autoimmune diseases. We examined whether MOG1-125 conjugated with PLGA could induce MOG-specific immune tolerance in an experimental autoimmune encephalitis (EAE) mouse model. EAE was induced in sixty C57BL/6 J wild-type mice using MOG1-125 peptide with complete Freund's Adjuvant. The mice were divided into 12 groups (n = 5 each) to test the ability of MOG1-125 conjugated PLGA intervention to mitigate the severity or improve the outcomes from EAE with and without rapamycin compared to antigen alone or PLGA alone. EAE score and serum MOG-IgG titers were compared among the interventions.Kindly check and confirm the processed Affiliation “4” is appropriate.I confirmed the Aff 4.Affiliation: Corresponding author information have been changed to present affiliation. Kindly check and confirm.I checked and confirmed the Corresponding author's information. RESULTS: Mice with EAE that were injected intraperitoneally with MOG1-125 conjugated PLGA + rapamycin complex showed dose-dependent mitigation of EAE score. Intraperitoneal and intravenous administration resulted in similar clinical outcomes, whereas 80% of mice treated with subcutaneous injection had a recurrence of clinical score worsening after approximately 1 week. Although there was no significant difference in EAE scores between unconjugated-PLGA and MOG-conjugated PLGA, serum MOG-IgG tended to decrease in the MOG-conjugated PLGA group compared to controls. CONCLUSION: Intraperitoneal administration of PLGA resulted in dose-dependent and longer-lasting immune tolerance than subcutaneous administration. The induction of immune tolerance using PLGA may represent a future therapeutic option for patients with MOGAD.