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.

Combined Treatment of Progressive Encephalitis in an X-linked Agammaglobulinemia Patient.

Most patients with X-linked agammaglobulinemia are susceptible to infections, while some cases also suffer from inflammatory or autoimmune complications. We describe a patient with progressive encephalitis who improved after the use of immunomodulatory treatment with corticosteroids, fluoxetine, and nitazoxanide. In most of the cases the evolution of the progressive encephalitis is complicated and catastrophic. Based on our experience and the review of the literature, we propose the use of this combined treatment to control this devastating complication.

Long-term seizure outcome and mobility after surgical treatment for Rasmussen encephalitis in children: A single-center experience.

OBJECTIVE: Rasmussen Encephalitis (RE) is a rare inflammatory neurodegenerative disease associated with refractory seizures, hemiparesis, and cognitive deterioration, due to lateralized cortical atrophy. Hemispheric surgery (hemispherotomy) is the mainstay of treatment, but its unavoidable motor deficits and lack of long-term data regarding seizure outcomes can make patients and families apprehensive to undergo this procedure. The present study aimed at analyzing the results of surgical treatment for RE from a motor and epilepsy standpoint, and mitigate such concerns. METHODS: Clinical and operative data were retrospectively collected from medical records of pharmacoresistant patients treated with functional hemispherectomy at a tertiary reference center for epilepsy surgery, during a 24-year period (1996-2020). Variables such as age of epilepsy onset, seizure semiology, seizure frequency, immunomodulatory therapy, age at surgery, duration of epilepsy, surgical procedures and complications, number of medications used preoperatively and postoperatively were described and statistically analyzed. RESULTS: Forty-three (43) patients were included in this study. Mean age of epilepsy onset was 6.14 years, the average interval between epilepsy onset and hemispherotomy was 2.21 years. and the mean age at surgery was 8.28 years. Thirty patients (69.7%) were Engel I at their last follow-up, of whom 23 (56.4%) were Engel Ia, within a mean follow-up of 11.3 years. Duration of epilepsy, seizure frequency, and age at surgery, among others, did not correlate with seizure outcome, except the use of immunotherapy which led to worse outcomes (p < .05). Also, after surgery, motor functionality was significantly recovered (i.e., most patients returned to their previous status) with time. SIGNIFICANCE: This study tackled some issues regarding the surgical treatment of this disease, particularly showing that hemispherotomy is safe and leads to potentially recoverable disability of motor functions while providing high rates of effective and long-lasting seizure control; therefore, early surgical indication should be warranted once medical refractoriness has been established.

Rabies, the cause of fatal encephalitis.

To describe the clinical progression and medical protocols applied in a 41 year old man who was bited by a bat three months before. The patient did not ask for medical care until acute tremor and pain in the right thoracic limb and hydro-phobia started. For a history of a wild animal bite associated with a unique clinical condition, we suspected of rabies encephalitis, confirming the diagnostic by pathology after his death. This case ocurred in Guadalajara, Jalisco, México, in April, 2022. The last case of human rabies reported in Jalisco secondary to bat bite was almost 30 years ago. As an uncomon disease, medical personnel and facilities should be prepared to attend this sort of cases after clinical suspicion. For the present case, the medical history was the key for diagnosis. Rabies is a disease caused by the neurotropic virus belonging to the Rhabdoviridae family whose prognosis is bleak, with mortality close to 100% and therapeutic options limited. This case emphasizes the high mortality of rabies virus infection and the importance of increasing awareness and education to the public in general, with regard to applying the vaccine as post-exposure prophylaxis.

Viral, Bacterial, Metabolic, and Autoimmune Causes of Severe Acute Encephalopathy in Sub-Saharan Africa: A Multicenter Cohort Study.

OBJECTIVES: To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa. STUDY DESIGN: One hundred thirty-four children (6 months to 18 years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical referral centers in Uganda, Malawi, and Rwanda were enrolled between 2015 and 2016. Locally available diagnostic tests could be supplemented in 117 patients by viral, bacterial, and 16s quantitative polymerase chain reaction testing, metagenomics, untargeted metabolomics, and autoimmune immunohistochemistry screening. RESULTS: Fourteen (12%) cases of viral encephalopathies, 8 (7%) cases of bacterial central nervous system (CNS) infections, and 4 (4%) cases of inherited metabolic disorders (IMDs) were newly identified by additional diagnostic testing as the most likely cause of encephalopathy. No confirmed cases of autoimmune encephalitis were found. Patients for whom additional diagnostic testing aided causal evaluation (aOR 3.59, 90% CI 1.57-8.36), patients with a viral CNS infection (aOR 7.91, 90% CI 2.49-30.07), and patients with an IMD (aOR 9.10, 90% CI 1.37-110.45) were at increased risk for poor outcome of disease. CONCLUSIONS: Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute encephalopathy in children in Uganda, Malawi, and Rwanda that are missed by conventional diagnostics and are associated with poor outcome of disease. Improved diagnostic capacity may increase diagnostic yield and might improve outcome of disease.

Neurological sequelae after encephalitis associated with herpes simplex virus in children: systematic review and meta-analysis.

BACKGROUND: Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. OBJECTIVE: To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. METHODS: This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. RESULTS: Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2-62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30-55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2-14.6). The included studies presented regular quality and substantial heterogeneity. CONCLUSION: Even with antiviral therapy, half of patients will develop some type of disability.

[Encephalitis as neurological complication due dengue]. / Encefalitis como complicación neurológica por dengue.

We present the case of a 32-year-old male, previously healthy, with a 5-day history of fever, frontal-occipital headache, retro-ocular pain, rash, petechiae, myalgia, arthralgia, and abdominal pain. Blood tests with leukopenia, severe thrombocytopenia, transaminitis, long clotting times. Severe dengue with associated coagulopathy was diagnosed, indicating transfer to ICU. Presents torpid evolution, altered state of consciousness, psychomotor agitation, and aggressiveness. Structural, ischemic-hemorrhagic alterations, bacterial and fungal infections were ruled out. Finally diagnosing dengue encephalitis, confirmed by DENV PCR in CSF. Support measures are provided with favorable evolution. Encephalitis is the most serious neurological complication after dengue virus infection.

Encefalitis como complicación neurológica por dengue / Encephalitis as neurological complication due dengue

Resumen Se presenta el caso de un varón de 32 años, previamente sano, que consultó por fiebre de cinco días, cefalea, dolor retro-ocular, rash, petequias, mialgias, artralgias y dolor abdominal. Presentaba leucopenia, trombocitopenia intensa, transaminitis y tiempo de coagulación prolongado. Se diagnosticó un dengue grave con coagulopatía que requirió manejo en Unidad de Cuidados Intensivos. Evolucionó con alteración del estado de conciencia, agitación psicomotora y agresividad. Se descartaron alteraciones estructurales, isquémicohemorrágicas, infecciones bacterianas y micóticas. Se confirmó finalmente una encefalitis por dengue por una RPC para virus dengue positiva en LCR. Se brindaron medidas de soporte con una evolución favorable. La encefalitis es la complicación neurológica más grave tras la infección por virus del dengue.

Abstract We present the case of a 32-year-old male, previously healthy, with a 5-day history of fever, frontal-occipital headache, retro-ocular pain, rash, petechiae, myalgia, arthralgia, and abdominal pain. Blood tests with leukopenia, severe thrombocytopenia, transaminitis, long clotting times. Severe dengue with associated coagulopathy was diagnosed, indicating transfer to ICU. Presents torpid evolution, altered state of consciousness, psychomotor agitation, and aggressiveness. Structural, ischemic-hemorrhagic alterations, bacterial and fungal infections were ruled out. Finally diagnosing dengue encephalitis, confirmed by DENV PCR in CSF. Support measures are provided with favorable evolution. Encephalitis is the most serious neurological complication after dengue virus infection.

Benefits of multi-day supplementation with probiotic kefir in Rasmussen encephalitis: the first case report.

INTRODUCTION: Rasmussen encephalitis (RE) is a rare inflammatory disease, characterized by unilateral hemispheric atrophy, focal intractable seizures, progressive hemiparesis, and neurological deficits. CASE REPORT: The patient is a young man under pharmacotherapy for epilepsy, exhibiting classical abnormal movements, which are consider typical hallmarks of RE. During clinical care sessions, he presented many episodes of tonic-clonic seizures involving sudden loss of consciousness followed by a post-ictal phase with weakness and interaction difficulty. During the kefir supplementation, the patient presented only short-term absence seizures, quickly returning to activities. Additionally, he presented cognitive and language improvement, being more responsive to commands. The daily diary control of patient's mother and caregiver at school reported an impressive reduction in number and severity of seizures, becoming less aggressive and more involved in school activities. The serum biochemical markers showed that kefir administration caused a significant decrease of pro-inflammatory and a simultaneous increase of anti-inflammatory cytokine levels. In parallel, after treatment, this probiotic reduced reactive oxygen species levels, increased NO bioavailability, revealing antiapoptotic and antigenotoxic effects. Regarding the microbiological analysis, kefir increased Lactobacillus and Bifidobacterium species. CONCLUSION: To our knowledge, this is the first case reporting remarkable beneficial effects of the probiotic kefir in RE. This case report strongly suggests kefir supplementation as a potential and safe-effective adjuvant therapeutic strategy in the control and treatment of RE.

Human Herpesvirus 6 Detection during the Evaluation of Sepsis in Infants Using the FilmArray Meningitis/Encephalitis Panel.

We used the FilmArray meningitis/encephalitis panel for evaluation of sepsis in febrile neonates. We detected human herpesvirus 6, a virus we did not routinely test for previously, in the cerebrospinal fluid of 7 neonates. In all 7 cases, detection of the virus did not warrant antiviral treatment.

The neuroprotective effect of Riparin IV on oxidative stress and neuroinflammation related to chronic stress-induced cognitive impairment.

BACKGROUND: Cognitive impairment is identified as one of the diagnostic criteria for major depressive disorder and can extensively affect the quality of life of patients. Based on these findings, this study aimed to investigate the possible effects of Riparin IV (Rip IV) on cognitive impairment induced by chronic administration of corticosterone in mice. METHODS: Female Swiss mice were divided into four groups: control (Control), corticosterone (Cort), Riparin IV (Cort + Rip IV), and Fluvoxamine (Cort + Flu). Three groups were administered corticosterone (20 mg/kg) subcutaneously during the 22-day study, while the control group received only vehicle. After the 14th day, the groups were administered medications: Riparin IV (Rip IV), fluvoxamine (Flu), or distilled water, by gavage, 1 h after the subcutaneous injections. After treatment, mice underwent behavioral testing, and brain areas were removed for oxidative stress and cytokine content assays. RESULTS: The results revealed that Cort-treated mice developed a cognitive impairment and exhibited a neuroinflammatory profile with an oxidative load and Th1/Th2 cytokine imbalance. Rip IV treatment significantly ameliorated the cognitive deficit induced by Cort and displayed a neuroprotective effect. CONCLUSION: The antidepressant-like ability of Rip IV treatment against chronic Cort-induced stress may be due to its potential to mitigate inflammatory damage and oxidative stress. The antioxidant and anti-inflammatory effect observed indicates Rip IV as a possible drug for antidepressant treatment of non-responsive patients with severe and cognitive symptoms.

The Neuroprotective Effect of Doxycycline on Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are a group of chronic, progressive disorders characterized by the gradual loss of neurons that affect specific regions of the brain, which leads to deficits in specific functions (e.g., memory, movement, cognition). The mechanism that drives chronic progression of NDs remains elusive. Among the proposed underlying pathophysiological mechanisms, aggregation and accumulation of misfolded proteins and neuroinflammation have been credited to contribute to extensive neural loss. Therapeutic agents that confer neuroprotection by downregulating these shared characteristics could therefore have beneficial effects on a wide range of NDs. In this regard, a commonly used antibiotic, doxycycline (Doxy), has been shown to reduce the progression and severity of disease in different experimental models of neurodegeneration by counteracting these common features. This review will focus on the effects reported for Doxy regarding its neuroprotective properties, the "off-target" effects, thereby supporting its evaluation as a new therapeutic approach for diseases associated with a neurodegeneration.

NDP-MSH reduces oxidative damage induced by palmitic acid in primary astrocytes.

Recent findings relate obesity to inflammation in key hypothalamic areas for body weight control. Hypothalamic inflammation has also been related to oxidative stress. Palmitic acid (PA) is the most abundant free fatty acid found in food, and in vitro studies indicate that it triggers a pro-inflammatory response in the brain. Melanocortins are neuropeptides with proven anti-inflammatory and neuroprotective action mediated by melanocortin receptor 4 (MC4R), but little is known about the effect of melanocortins on oxidative stress. The aim of this study was to investigate whether melanocortins could alleviate oxidative stress induced by a high fat diet (HFD) model. We found that NDP-MSH treatment decreased PA-induced reactive oxygen species production in astrocytes, an effect blocked by the MC4R inhibitor JKC363. NDP-MSH abolished nuclear translocation of Nrf2 induced by PA and blocked the inhibitory effect of PA on superoxide dismutase (SOD) activity and glutathione levels while it also per se increased activity of SOD and γ-glutamate cysteine ligase (γ-GCL) antioxidant enzymes. However, HFD reduced hypothalamic MC4R and brain derived neurotrophic factor mRNA levels, thereby preventing the neuroprotective mechanism induced by melanocortins.

[Encephalitis lethargica. The epidemic at the dawn of neurology]. / Encefalitis letargica. La epidemia en los albores de la neurologia.

Lethargic encephalitis is a neurological illness that shows a wide range of symptoms and signs, including neurological and psychiatric spectrum. It presented in an epidemic way, following influaenza relapses. The last relapse started at the beginning of 20th century and it was deeply described by Constantin von Economo. The illness described first in Europe and North America, was described in many others countries including Chile. There were beautiful descriptions by Chilean physicians like Lea-Plaza, Tello, Iturra and Cienfuegos. Their works showed the complexity of the illness like European physicians did too. The etiology is still unknown; however growing evidence about autoinmune aetiology is gaining force with the use of actual medical technology. In this work, we show encephalitis lethargica, focusing in clinical picture, the beauty of medical descriptions that physicians did at this date.

TITLE: Encefalitis letargica. La epidemia en los albores de la neurologia.La encefalitis letargica es un cuadro neurologico con una variada gama de manifestaciones clinicas en el ambito neurologico y tambien en el psiquiatrico. El cuadro se ha presentado de manera epidemica en brotes que han seguido a los de la gripe. El ultimo brote acaecido a comienzos del siglo XX lo describio en profundidad Constantin von Economo. La epidemia notificada inicialmente en Europa y luego en Norteamerica se presento tambien en otras latitudes, incluyendo Chile. Asi, las descripciones de Lea-Plaza, Tello, Iturra, Cienfuegos y otros medicos chilenos dieron cuenta del cuadro en Chile con toda la complejidad que tambien tuvo en Europa. El origen sigue siendo un misterio, aunque la evidencia creciente de que fuera autoinmune gana fuerza con los hallazgos de la tecnologia medica actual. En este trabajo presentamos el cuadro, privilegiando la riqueza clinica y la belleza de las descripciones realizada por los medicos de la epoca en que esta enfermedad se presento.

Updates in the Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes.

The disorders of the central nervous system associated with cancer by remote immune-mediated mechanisms are a heterogeneous group. These disorders encompass the classic paraneoplastic disorders and the recently recognized autoimmune encephalitis associated with antibodies against neuronal cell surface or synaptic proteins that occur with or without cancer association. In the last decade, the new surge of interest in neuronal diseases associated with anti-neuronal antibodies led to the rapid discovery of new forms of disease that have different manifestations and were not previously suspected to be immune mediated. The recognition of these syndromes is important because it may lead to early detection of an underlying malignancy and prompt initiation of treatment, improving chances for a better outcome.