[Cognitive impairment? Don't forget neurolues]. / Geheugenklachten? Vergeet neurolues niet.

BACKGROUND: Cognitive disorders usually develop slowly over years and are mainly caused by untreatable neurodegenerative disorders. Rapidly progressive cognitive disorders should raise suspicion of an underlying and treatable psychiatric, internal or neurological condition. Timely recognition of these conditions is important. CASE: We present the case of a 68-year old man, presenting on the emergency department with a history of progressive cognitive impairment since several weeks. Cerebral MRI showed T2-hyperintensities in the left hippocampal, mesotemporal and insular regions; lesser so in the right mesotemporal region. After initial treatment for herpesencephalitis and autoimmune encephalitis, we diagnosed neurolues and started treatment with benzylpenicillin. CONCLUSION: It may be difficult to diagnose neurolues because the vast variety of clinical symptoms and radiological signs. This case shows that neurolues should be considered in a patient with rapidly progressive cognitive disorders and that neurolues can mimic a herpesencephalitis or an autoimmune encephalitis. Timely recognition is important to prevent irreversible damage.

Exploring seizure characteristics in individuals with autoimmune encephalitis: A comprehensive retrospective study in a low-middle-income country setting.

INTRODUCTION: Seizures and epilepsy are well-documented in association with autoimmune encephalitis. Despite this, a notable gap exists in understanding the persistence of seizures beyond the acute phase, particularly within the context of low- and low-middle-income settings. OBJECTIVE: To evaluate the frequency, clinical characteristics, diagnosis, and potential factors associated with the occurrence and persistence of seizures in autoimmune encephalitis patients. METHODS: This was a retrospective, cross-sectional study. Patients diagnosed with possible, probable or confirmed autoimmune encephalitis according to the Graus criteria at the "Instituto Nacional de Ciencias Neurológicas" in Lima, Peru, were included between January 2018 and April 2023. Demographic, clinical, diagnosis, and management information was recorded. A bivariate analysis was performed considering the persistence of seizures at one-year follow-up and a second analysis was performed to compare the groups according to the anti N-methyl-D-aspartate receptor (NMDAR) antibody results. RESULTS: Sixty patients predominantly male (40; 66.7 %) were included. Only 36 (60 %) patients were tested for antibodies, 16 (44.4 %) were NMDAR positive. 46 (76.7 %) patients had at least one seizure and 13 (37.1 %) had seizures after 1 year of follow-up. Patients with seizure relapse were younger, 20 (IQR: 18-28) versus 29.5 years (IQR: 21-48), p=0.049. Four (44.4 %) patients with persistent seizures had positive NMDAR results. Similar sex distributions, no differences in seizure characteristics, and higher CSF cell count in the NMDAR-positive group were observed. Neuroimaging, EEG findings, and follow-up times were comparable between the groups. CONCLUSIONS: We found a 37.1 % seizures rate after one year of follow-up, predominantly in younger patients.

[Auditory hallucinations in a pregnant patient caused by autoimmune encephalitis]. / Auditieve hallucinaties bij een zwangere pa­-tiënte op basis van auto-immuunencefalitis.

In this case report we describe a pregnant woman with newly developed auditory hallucinations, initially seen by a psychiatrist of the psychiatric emergency service. The day after assessment , the patient developed epileptic seizures and was referred to the hospital. After additional blood and liquor tests and an MRI scan, an autoimmune encephalitis was diagnosed. She was treated with prednisolone and immunoglobulins. She made a full recovery and gave birth to a healthy son at term. In this article we describe the diagnostic considerations, the course and treatment, the importance of being alert to a somatic cause of psychiatric symptoms and of multidisciplinary collaboration.

Postoperative brainstem cavernous malformations complicated with LGI1 encephalitis and hypertrophic olivary degeneration: A case report and literature review.

We presented a case of a 34-year-old male with postoperative brainstem cavernous malformations complicated with LGI1 encephalitis and secondary hypertrophic olivary degeneration (HOD). Due to recurrent dizziness and headache, the patient was diagnosed as brainstem cavernous malformations with recurrent hemorrhage and underwent resection. He subsequently developed unexplained abnormal mental behavior 1 month after the surgery, and diagnosed with LGI1 encephalitis. Six months later, cranial MRI showed HOD. This condition is rare in clinical practice,and a complex mechanism underlies the occurrence.

Identification of etiologies according to baseline clinical features of pediatric new-onset refractory status epilepticus in single center retrospective study.

PURPOSE: New-onset refractory status epilepticus (NORSE) is defined as a state of prolonged seizure activity that does not improve despite the appropriate administration of medications, with underlying causes unknown after the initial diagnosis of status epilepticus. Because episodes of NORSE are accompanied by severe complications and a high risk of mortality, the prompt identification of the underlying cause is crucial for effective treatment and outcome prediction. This study assessed the relationship of NORSE etiologies with baseline clinical features in pediatric population. METHODS: Seventy-one pediatric patients, under 18 years of age at the initial diagnosis (4.50 ± 4.04, mean ± standard deviation), who experienced at least one episode of NORSE and underwent a comprehensive diagnostic evaluation between January 2005 and June 2020 at our center, were retrospectively selected. We reviewed clinical features at disease onset and long-term follow-up data. Uniform manifold approximation and projection (UMAP) was used to distinguish etiological clusters according to baseline clinical characteristics, and further analysis was performed based on underlying etiologies. RESULTS: Two distinct etiological groups-genetic and non-genetic-were identified based on the UMAP of clinical characteristics. Dravet syndrome (12/15, 80%) was more predominant in patients with a genetic diagnosis, whereas cryptogenic NORSE and encephalitis were prevalent in patients without a genetic diagnosis. The analysis of etiological categories revealed that age at the onset of status epilepticus (P=0.021) and progression to super refractory status epilepticus (SRSE) (P=0.038) were independently associated with differences in etiologies. CONCLUSION: Several clinical features in patients with NORSE, including the age of onset and the development of SRSE, can help identify underlying causes, which necessitate prompt and adequate treatment.

Memory function in autoimmune encephalitis: a cross-sectional prospective study utilising multiple memory paradigms.

BACKGROUND AND OBJECTIVE: Autoimmune encephalitis (AE) is often associated with clinically significant memory impairment. This study aimed to evaluate memory in a cross-sectional prospective AE cohort using multiple memory paradigms. METHODS: 52 patients (50% seropositive) meeting Graus criteria for possible AE were prospectively recruited between October 2019 and August 202. A comprehensive examination of memory was performed, including tests of supraspan verbal memory (list learning), logicosemantic memory (story learning), figural memory (learning of geometric designs), and verbal associative learning (verbal paired associates). Memory scores were compared to demographically adjusted normative data. Pattern analysis was conducted to assist in the identification of patterns in memory performances. RESULTS: Mean memory scores were not significantly below the normative mean. At an individual patient level, over 20% of the cohort exhibited impaired delayed figural memory, supraspan verbal memory learning and recall. Observed performances were significantly below expected performance for story learning (p = 0.017) and recall (p = 0.003), figural recall (p < 0.0001), initial acquisition (p < 0.001) and final acquisition of a list (p < 0.001) and all delayed recall measures of the list (p < 0.00001). 54.76% of patients exhibited intact psychometrics, and 16 distinct patterns of impairment emerged, indicating variability in memory outcomes. DISCUSSION: While statistical evidence for memory impairment did not emerge at an aggregate level, a proportion of patients present with evidence of abnormal memory performance on psychometrics. Variability in impaired memory measures argues for an individualised patient-focused approach to clinical assessment in AE. Future research should validate these findings with a larger sample size and explore the relationships between memory profiles and other cognitive functions.

Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes.

Kleine-Levin syndrome (KLS) is a rare, recurring sleep disorder that easily ignored. Episodic upward-gaze palsy is an uncommon manifestation observed in patients of KLS, which further complicates this disorder. Although peripheral microbial infection have been recognized as most common triggers for KLS, the underlying pathophysiology of this disorder remains unclear. We reported a unique case of KLS elicited by acute encephalitis, which was confirmed by pleocytosis of cerebrospinal fluid at the early stage. The cerebrospinal fluid returned to normal over time while the attacks continued to recur frequently. Episodic upward-gaze palsy was observed during attacks and clinical symptoms were exacerbated following a subsequent COVID-19 infection. This report presents a classic KLS case with distinctive characteristics, which should facilitate more accurate and earlier diagnosis for clinicians. Furthermore, it provides a new perspective for understanding the pathogenesis of this rare disease. CITATION: Lv H, Long X, Lv Y, Zhou J. Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes. J Clin Sleep Med. 2024;20(9):1555-1556.

Prognostic factors underlying the development of drug-resistant epilepsy in patients with autoimmune encephalitis: a retrospective cohort study.

OBJECTIVE: The aim of our study was to analyze the characteristics of patients with autoimmune encephalitis (AE) to identify prognostic factors associated with the development of drug-resistant epilepsy (DRE). METHODS: In this retrospective observational cohort study, we enrolled adult patients with AE between January 2016 and December 2022. The patients were categorized into two groups based on the presence or absence of DRE at the last follow-up. The predictors of the development of DRE were investigated using logistic regression analysis. RESULTS: Among 121 AE patients, 75.2% (n = 91) experienced acute symptomatic seizures, and 29.8% (n = 36) developed DRE at the last follow-up. On multivariate regression analysis, the factors associated with DRE were antibody negativity (OR 3.628, 95% CI 1.092-12.050, p = 0.035), focal seizure (OR 6.431, 95% CI 1.838-22.508, p = 0.004), refractory status epilepticus (OR 8.802, 95% CI 2.445-31.689, p = 0.001), interictal epileptiform discharges on EEG (OR 6.773, 95% CI 2.206-20.790, p = 0.001), and T2/FLAIR hyperintensity in the limbic system (OR 3.286, 95% CI 1.060-10.183, p = 0.039). CONCLUSIONS: In this study, the risk of developing DRE was mainly observed among AE patients who were negative for antibodies or had focal seizures, refractory status epilepticus, interictal epileptiform discharges on EEG, and T2/FLAIR hyperintensity in the limbic system.

Autoimmune-associated seizure disorders.

With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders.

Reversible encephalitis-like episodes in fragile X-associated tremor/ataxia syndrome: a case report.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. CASE PRESENTATION: A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. CONCLUSIONS: This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Cerebellar syndrome as the presenting feature of Hashimoto encephalopathy.

Hashimoto encephalopathy presents with a myriad of neuropsychiatric features in the background of elevated antithyroid antibodies and it may or may not be associated with Hashimoto thyroiditis. It is a diagnosis of exclusion. Here, we present the case of a hypothyroid woman in her 30s, with a 5-year history of chronic progressive gait ataxia along with hand and head tremor, inattention and electroencephalogram (EEG) suggestive of interictal epileptiform discharges without any clinical seizures. The patient had very high titres of anti-thyroid peroxidase antibodies >2000 IU/mL and was on very high-dose levothyroxine replacement therapy. She responded to intravenous pulse corticosteroids. Improvement was noted both clinically and on subsequent EEGs. Pure cerebellar syndrome without frank encephalopathy can also be a rare presentation of Hashimoto encephalopathy. This highlights the importance of antithyroid antibodies testing even in cases of pure cerebellar syndrome to rule out Hashimoto encephalopathy associated ataxia.

Reversible dementia and insomnia in ABGA related encephalitis.

BACKGROUND: ABGAs are historically associated with Encephalitis Lethargica (EL). Typically ABGAs are also found in children resulting in a variety of neuropsychiatric and extrapyramidal disorders, rare cases are reported in adults with atypical movement disorders. No description of basal ganglia reversible lesions related to ABGAs are reported and these antibodies are not included in the list of autoimmune encephalitis. METHODS AND RESULTS: A 55 years old female presented sub-acute onset of an anxious-depressive disorder and obsessive-compulsive behavior associated with intractable insomnia affecting sleep onset and sleep maintenance. Brain-MRI showed diffuse hyperintensities on FLAIR sequences in the basal ganglia. A therapy with IV-immunoglobulin was started and the clinical condition improved dramatically and insomnia and psychiatric symptoms resolved completely. CONCLUSION: Our case highlights the importance of making a fast diagnosis. When caught early ABGAs-related encephalitis is susceptible of a good outcome and response to treatment. Reversible insomnia and dementia in our case expand ABGA clinical presentation in adults and favors the hypothesis of an immune pathogenesis for Encephalitis Lethargica, especially in the hyperkinetic form as previously suggested, as in our case.