Encephalitis Patients Research Articles

P-OT027. Approach and management of suspected encephalitic patients in omdurman teaching hospital

Introduction . The aim of this study was to assess the approach and management of suspected encephalitic patients in Omdurman teaching hospital. Methods . This was a cross-sectional descriptive study, conducted on 84 patients who are suspected of encephalitis in neurology department. The data was analyzed using SPSS. Results . The commonest group of age affected (21–40) representing about 66.7% with 84.5% female predominant and most of the patients from Khartoum state (58.3%). Regarding the main presenting symptoms, 100% presented with fever and headache, 36.9% with seizure and 28.6% with agitation, other symptoms like abnormal behavior, memory disturbance, photophobia, neck stiffness and nausea / vomiting ranging from (22.6–8.3%). 1.2% has a history of SLE and also 1.2% presented with bilateral 6th cranial nerve lesion. 28.6% presented with unconsciousness and disoriented. 13.1% comatose with 20.2% had personality changes and memory disturbance. Regarding upper and lower limbs examination 13.1% hemiparesis, 4.8% quadriparesis and 1.2% paraparesis. 100% did a CBC showed lymphocyte predominant about 70.2%, 100% elevation in ESR. 71 patients did a CSF analysis with 83.1% showed abnormality, increasing lymphocyte cells, others were normal. MRI/CT scan was done in 50 patients;, in 63.2% MRI showed temporal hyperintense lesion, whereas CT scan was normal in majority of cases (71%). EEG was abnormal in 3.6% of cases. Most of the cases were managed empirically with antiviral and antibiotics, 100% and 94% respectively. About 85.7% received antiepileptic. The most common complication was seizure (85.7%). 26.2% ended up with motor deficit. Fortunately, most of the cases completely recovered (65.5%). Conclusion . The diagnostic approach to patients with encephalitis must include CSF, neuroimaging (MRI) plus or minus EEG. Empirical antimicrobial therapy for patients with suspected encephalitis should include rapid administration of intravenous acyclovir at appropriate dosages if clinically suspected despite unobtainable CSF result. We must identify the exact etiology and once an etiologic agent of encephalitis is identified, antimicrobial therapy should be targeted to that infectious agent, or therapy should be discontinued if treatment directed against the etiologic agent is not available.

Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder which often presents with neuropsychiatric symptoms. A large proportion of cases are associated with an identifiable tumor, most commonly ovarian teratoma. However, recent literature has also described an overlap of anti-NMDAR encephalitis and demyelinating syndromes. Cases have been reported of anti-NMDAR encephalitis in patients with ADEM, optic neuritis, myelitis and multiple sclerosis. This link is considered rare, however has important clinical implications as treatments and prognosis may differ.Case presentationA 33-year-old female with a history of multiple sclerosis presented with new-onset neuropsychiatric symptoms. After substance-induced psychosis was ruled out, she was admitted to the medical ward for work up of psychosis secondary to multiple sclerosis. However, the consultation-liaison psychiatry service noted atypical symptoms which were concerning for autoimmune encephalitis. Admission to a psychiatric inpatient ward was deferred. Anti-NMDAR encephalitis was diagnosed with CSF analysis demonstrating lymphocytic pleocytosis and anti-NMDAR antibodies. In addition to first-line treatment of encephalitis with steroids, second-line immunotherapies were also implemented given the patient’s underlining demyelinating syndrome. The patient’s neurologic and psychiatric symptoms began to improve.ConclusionsThere is literature to demonstrate a possible connection between anti-NMDAR encephalitis and demyelinating syndromes. As such, autoimmune encephalitis should be considered in patients with multiple sclerosis presenting with atypical symptoms. Determining the correct diagnosis is crucial to inform the appropriate treatment protocol, and to improve prognosis.

Extreme Delta Brush in Anti-NMDAR Encephalitis Correlates With Poor Functional Outcome and Death.

Objective: To characterize EEG findings in anti-NMDAR encephalitis patients looking for the proportion of EEGs that were abnormal, presence of extreme delta brush (EDB), and to relate EEG findings to clinical outcomes (Glasgow Outcome Scale (GOS) at 6 months, need for ICU admission, and death).Methods: This retrospective cohort single center study included patients with anti-NMDAR encephalitis who had ≥1 EEGs obtained from 2014 to 2021. EEGs were retrospectively analyzed by 2 reviewers. Clinical outcomes of interest were extracted through hospital and clinic chart review.Results: Twenty-one patients with anti-NMDAR encephalitis were included. Sixty-four EEGs were analyzed. Four EEGs (6.3%) were within normal limits. Focal or generalized slowing (without EDB) was seen on 44 EEGs (68.8%). EDB was seen on 16 EEGs (25.0%) in 9 of 21 patients (42.9%). The presence of EDB was significantly associated with need for ICU admission (p = 0.02), poorer outcome at 6 months as per the GOS (p = 0.002), and with death (p=0.02). EDB was present on ≥1 EEG of every patient who died.Conclusions: The presence of EDB on EEG in anti-NMDAR encephalitis patients is associated with increased need for ICU admission, worse functional outcomes at 6 months, and risk of death.

Temporal rank of clinical characteristics and prognosis of anti-N-methyl-d-aspartate receptor encephalitis.

ObjectivesEarly recognition and intervention of patients with the anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis are important to achieve a better prognosis. The study aims to summarize the real‐world perspectives of anti‐NMDAR encephalitis patients in China via electronic medical records (EMRs).MethodsUsing EMRs of patients from 2013 to 2019 from West China Hospital in China, a retrospective research was conducted to demonstrate the temporary rank of clinical characteristics and disease prognosis of anti‐NMDAR encephalitis. The modified Rankin Scale (mRS) scores were used to divide the anti‐NMDAR‐encephalitis into two groups (poor prognosis vs. good prognosis). Chi‐square test and logistic regression were used to analyze factors associated with prognosis.ResultsHere, 78 patients were included. The most common clinical characteristics are cognitive dysfunction (86.0%) and thought disorder (86.0%). Cognitive dysfunction, thought disorder, and seizures tended to appear soon after prodrome symptoms. Logistics analysis results showed that cognitive dysfunction (OR = 4.48, 95% CI = 1.09–18.47), the score of (GCS ≤ 8) (OR = 4.52, 95% CI = 1.18–17.32), positive antibodies in serum (OR = 4.89, 95% CI = 1.19–20.13) and delay immunotherapy (OR = 4.76, 95% CI = 1.79–12.60) were risk factors of poor clinical outcomes.ConclusionsThere are two peaks in the development of autoimmune encephalitis (AE). The first peak is cognitive dysfunction, and the second peak is autonomic dysfunction. Cognitive dysfunction and GCS score ≤8 at admission, antibodies positive in serum, and delay immunotherapy were risk factors for a poor prognosis at discharge.

Two decades of one health surveillance of Nipah virus in Thailand

BackgroundNipah virus (NiV) infection causes encephalitis and has > 75% mortality rate, making it a WHO priority pathogen due to its pandemic potential. There have been NiV outbreak(s) in Malaysia, India, Bangladesh, and southern Philippines. NiV naturally circulates among fruit bats of the genus Pteropus and has been detected widely across Southeast and South Asia. Both Malaysian and Bangladeshi NiV strains have been found in fruit bats in Thailand. This study summarizes 20 years of pre-emptive One Health surveillance of NiV in Thailand, including triangulated surveillance of bats, and humans and pigs in the vicinity of roosts inhabited by NiV-infected bats.MethodsSamples were collected periodically and tested for NiV from bats, pigs and healthy human volunteers from Wat Luang village, Chonburi province, home to the biggest P. lylei roosts in Thailand, and other provinces since 2001. Archived cerebrospinal fluid specimens from encephalitis patients between 2001 and 2012 were also tested for NiV. NiV RNA was detected using nested reverse transcription polymerase chain reaction (RT-PCR). NiV antibodies were detected using enzyme-linked immunosorbent assay or multiplex microsphere immunoassay.ResultsNiV RNA (mainly Bangladesh strain) was detected every year in fruit bats by RT-PCR from 2002 to 2020. The whole genome sequence of NiV directly sequenced from bat urine in 2017 shared 99.17% identity to NiV from a Bangladeshi patient in 2004. No NiV-specific IgG antibodies or RNA have been found in healthy volunteers, encephalitis patients, or pigs to date. During the sample collection trips, 100 community members were trained on how to live safely with bats.ConclusionsHigh identity shared between the NiV genome from Thai bats and the Bangladeshi patient highlights the outbreak potential of NiV in Thailand. Results from NiV cross-sectoral surveillance were conveyed to national authorities and villagers which led to preventive control measures, increased surveillance of pigs and humans in vicinity of known NiV-infected roosts, and increased vigilance and reduced risk behaviors at the community level. This proactive One Health approach to NiV surveillance is a success story; that increased collaboration between the human, animal, and wildlife sectors is imperative to staying ahead of a zoonotic disease outbreak.

Anti-GABA-B receptor encephalitis with small cell lung cancer presenting with septic shock during immunotherapy

Abstract Introduction: Most patients with anti-γ-aminobutyric acid-B (anti-GABA-B) receptor encephalitis present with cancer and have a poor response to immunotherapy. Moreover, septic shock, a subset of sepsis, is rarely reported in these patients during immunotherapy. Patient concerns: A 55-year-old man presented with epileptic seizure and cognitive impairment. He was previously healthy and had no family history of psychiatric disorders but had a history of smoking and emphysema. Diagnoses: Combined with the symptoms and antibody testing, anti-GABA-B encephalitis with anti-Hu antibody was diagnosed. During immunotherapy, he presented with septic shock. Further investigations and pathological examination confirmed the diagnosis of small cell lung cancer. Interventions: The patient was treated with five days of intravenous immunoglobulin (0.4/kg/d), ten days of methylprednisolone (1.0 g once a day and half the dose every three days), plus ten days of oxycarbazepine (0.3 g b.i.d.) and magnesium valproate (0.25 g b.i.d.). He received nine days of conventional treatment for septic shock in addition to meropenem (1 g intravenously every 8 hours) and etimicin (0.3 g intravenously per day). After that, he received one month of prednisone 30 mg with dose reduction 5 mg every two weeks, oxcarbazepine 0.3 g b.i.d. and valproic acid 0.25 g b.i.d. for antiepileptic treatment, olanzapine 5 mg qd + qn for antipsychotic symptoms. Outcomes: He was able to communicate with others normally and also had improved memory and clear thinking. Mini-Mental State Examination and Modified Rankin Scale were 23/30 and 1. At discharge, the titer of anti-GABA-B receptor antibody in serum (1:10) was significantly lower than the titer in serum on the day of admission (1: 100). Conclusion: Anti-GABA-B receptor encephalitis patients with cancer can respond well to immunotherapy. Personalized treatment should be considered to avoid complications like septic shock in anti-GABA-B receptor encephalitis with cancer during immunotherapy.

ОСОБЛИВОСТІ КЛІНІЧНОГО ПЕРЕБІГУ ПІСЛЯКОРОВИХ ЕНЦЕФАЛІТІВ У ІМУНОСУПРЕСОВАНИХ ОСІБ

Primary acute measles encephalitis and acute postmeasles encephalitis are the most common neurological complications of measles. It is important to detect encephalitis, which develops a month or more after the manifestations of measles infection. These encephalitis are rare and occur mainly in people with immunodefi ciency. Multiple sclerosis is a chronic disease of the central nervous system for the treatment of which diseasemodifying therapy is used, namely monoclonal antibodies, that can lead to immunosuppression and immunodefi ciency. Nowadays, there is insuffi cient information about the course of postcortical encephalitis in patients with multiple sclerosis who are taking immunosuppressive drugs. The article presents data on the clinical classifi cation, diagnosis and treatment of measles encephalitis. A clinical case of measles inclusion body encephalitis in a thirty-threeyear-old patient with multiple sclerosis on the background of annual intake of monoclonal antibodies is presented. She also had viral-bacterial pneumonia and developed disseminated intravascular coagulation in the brain and lungs. These complications of measles infection led to the death of the person after a month and a half of intensive care. Thus, patients with multiple sclerosis who are taking drugs with immunosuppressive eff ects are among the risk group for measles inclusion body encephalitis. Measles inclusion body encephalitis in such patients can be severe, which complicates timely diagnosis, proper treatment and leads to death.

Title: Poor Long-Term Outcomes of Patients with Human Herpesvirus 6 Encephalitis

Background:Human herpesviruses 6 (HHV-6) A and B cause encephalitis in patients with hematologic malignancies especially those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data on the long-term outcomes of patients with HHV-6 encephalitis is limited.Methods:To assess the clinical and diagnostic characteristics, and outcomes of patients with HHV-6 encephalitis, we performed a retrospective review of all patients with positive HHV-6 in plasma or CSF between Nov 2011 and Jun 2017. Cases were categorized based on pre-defined criteria for possible, probable and definite HHV-6 encephalitis.Results:Ten patients with leukemia (n=5), lymphoma (n=2), and other hematologic cancers (n=3) met the criteria for definite (n=8), probable (n=1) and possible (n=1) HHV-6 encephalitis (Table 1). All except one were allogeneic HSCT recipients (three umbilical cord and six matched unrelated donors). Among 9 cases, the median time to onset of illness was early at 23 days (IQR: 20.5-29.5) after transplantation. The clinical symptoms were confusion (80%), retrograde amnesia (60%), fever (50%), rash (50%) and seizures (20%). Before or at the time of illness, patients had GVHD (55%), pre-engraftment syndrome (44%) and CMV (22%). CSF showed mild pleocytosis (WBC 5-22; n=6) and elevated protein (n=8). Plasma HHV-6 PCR was negative in 2 cases, while brain MRI was normal in one definitive case. The most common MRI abnormality was increased T2 signal in the bilateral hippocampal (40%) and mesial temporal lobes (50%). All patients received intravenous ganciclovir for a median duration of 27 days (range: 10-48). Follow-up MRI at 4-40 weeks in 6 patients showed moderate to severe bilateral hippocampal atrophy (50%) or no interval improvement (33%). Five patients died; none were due to HHV-6 encephalitis.One patient developed possible HHV-6 encephalitis with retinitis at post-transplant day +429; despite clinical improvement, the HHV-6 load remained at >2x106 copies/ml suggesting this case as reactivated chromosomally integrated-HHV-6.Conclusions:HHV-6 infection among patients with hematologic malignancies and transplantation is associated with significant long-term morbidity and all-cause mortality. A negative plasma HHV-6 PCR does not rule out the diagnosis. Despite prolonged treatment, persistent neurologic deficits associated with moderate to severe bilateral hippocampal atrophy are characteristic long-term findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prospective Study of High Dose Foscarnet Prophylaxis for HHV-6 Related CNS Diseases in Cord Blood Transplantation for Adult Patients

Background: Umbilical cord blood transplant (UCBT) recipients showed higher incidence of HHV-6 related CNS diseases (HHV-6 RCD) than those of bone marrow (BM) or peripheral blood (PB). It causes short-term memory impairment or disorientation, which sometimes become irreversible, and convulsions in severe cases, resulted in high non-relapse mortality. We reported previously that in the group given higher doses of prophylactic Foscarnet (FCV) (≥60mg/kg), the incidence of HHV-6 RCD was reduced (Asano-Mori Y, et al. ASH 2013). We thus conducted a prospective study to assess efficacy of higher dose (120mg/kg) of prophylactic FCV to further reduce the incidence and to improve outcome of HHV-6 RCD.Patients and Methods: The study was started since May 2014 and was finished on September 2015. The protocol was approved by local IRB and UCBT recipients who gave written informed consent were included. FCV 120 mg/kg was administered prophylactically from day 7 to day 50 post UCBT.. FCV dose was adjusted according to renal function. The incidence of HHV-6 RCD, types of manifestation and severity of the symptoms, treatment response, and prognosis were evaluated.Results: Among 113 who were included in this study, 9 failed to start FCV from day 7 due to early death or renal impairment, 37 were switched to other drugs at some point before day 50 for reasons such as renal impairment or viral infections other than HHV-6 (23 changed to GCV, 10 to ACV, and 4 to CDV), and 67 received planned dose of FCV. Fifteen developed HHV-6 RCD (12 HHV-6 limbic encephalitis (LE) and 3 myelitis). The cumulative incidence of HHV-6 RCD was 11.5%. No significant risk factors before transplant associated with the development of HHV-6 RCD were identified. Six out of 22 who developed severe pre-engraftment immune reactions (PIR) developed HHV-6 RCD. PIR was shown to be a significant risk factor for HHV-6 RCD development when it was treated as a time-dependent covariate. The median onset day was day 40, and 4 out of 15 patients developed after the cessation of FCV. Only one of 12 encephalitis patients developed convulsions. The median number of copies of HHV-6 in the cerebrospinal fluid at onset was 40,400/µL. HHV-6 viral load in peripheral blood was examined on the same day of CSF examination in 13 and was not detected in 7. Six patients were treated with FCV and GCV in combination, 4 received increased dose of FCV, and 1 was switched from FCV to GCV. Two out of 4 patients who developed after the prophylactic administration of FCV resumed FCV, and the remaining 2 resumed GCV. The virus became undetectable in all 13 evaluable patients by follow-up CSF examination after treatment. The median day of viral disappearance from CSF was 19 days (8-34 days) after diagnosis. All but 2 who were unevaluable due to other complications, had their symptoms improved without sequalae. The median time from treatment intervention to symptomatic improvement was 28 days. The OS after 1 year from HHV6 encephalitis myelitis group was 46.2%, and there was no significant difference in the prognosis as 47.3% OS after 1 year from non-onset group when time-dependent co-analysis was performed (HR 1.88, 95%CI;0.49-2.84, p=0.69). Analysis of OS for 67 patients who were able to undergo preventative FCV administration and other group showed 53.2% and 38.3% respectively in 1 year, revealing a trend in which OS appeared to become higher as a result of continued prophylaxis.Conclusion: There was no difference in the incidence of HHV-6 RCD compared to the previous report even after prophylactic administration of high dose 120 mg/kg of FCV. However, there were few severely ill individuals, most of their symptoms improved due to antiviral treatment without significant sequalae. DisclosuresNo relevant conflicts of interest to declare.

Short- and Long-Lived Autoantibody-Secreting Cells in Autoimmune Neurological Disorders.

As B cells differentiate into antibody-secreting cells (ASCs), short-lived plasmablasts (SLPBs) are produced by a primary extrafollicular response, followed by the generation of memory B cells and long-lived plasma cells (LLPCs) in germinal centers (GCs). Generation of IgG4 antibodies is T helper type 2 (Th2) and IL-4, -13, and -10-driven and can occur parallel to IgE, in response to chronic stimulation by allergens and helminths. Although IgG4 antibodies are non-crosslinking and have limited ability to mobilize complement and cellular cytotoxicity, when self-tolerance is lost, they can disrupt ligand-receptor binding and cause a wide range of autoimmune disorders including neurological autoimmunity. In myasthenia gravis with predominantly IgG4 autoantibodies against muscle-specific kinase (MuSK), it has been observed that one-time CD20+ B cell depletion with rituximab commonly leads to long-term remission and a marked reduction in autoantibody titer, pointing to a short-lived nature of autoantibody-secreting cells. This is also observed in other predominantly IgG4 autoantibody-mediated neurological disorders, such as chronic inflammatory demyelinating polyneuropathy and autoimmune encephalitis with autoantibodies against the Ranvier paranode and juxtaparanode, respectively, and extends beyond neurological autoimmunity as well. Although IgG1 autoantibody-mediated neurological disorders can also respond well to rituximab induction therapy in combination with an autoantibody titer drop, remission tends to be less long-lasting and cases where titers are refractory tend to occur more often than in IgG4 autoimmunity. Moreover, presence of GC-like structures in the thymus of myasthenic patients with predominantly IgG1 autoantibodies against the acetylcholine receptor and in ovarian teratomas of autoimmune encephalitis patients with predominantly IgG1 autoantibodies against the N‐methyl‐d‐aspartate receptor (NMDAR) confers increased the ability to generate LLPCs. Here, we review available information on the short-and long-lived nature of ASCs in IgG1 and IgG4 autoantibody-mediated neurological disorders and highlight common mechanisms as well as differences, all of which can inform therapeutic strategies and personalized medical approaches.

High Level of Soluble CD146 In Cerebrospinal Fluid Might be a Biomarker of Severity of Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BackgroundDisruption of the blood–brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis.MethodTwenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge.ResultssCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls.ConclusionOur data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis.

Clinical Characteristics and Long-Term Prognosis of Anti-LGI1 Encephalitis: A Single-Center Cohort Study in Beijing, China.

Background: This study aimed to analyze the clinical characteristics of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis patients and investigate prognostic factors by using a large-sample and long-term follow-up cohort.Methods: The clinical data of 45 patients (29 males; mean age, 57.0 years) from May 2014 to August 2019 were collected. All patients were followed up by face-to-face interviews in the third month after discharge and then by telephone and/or face-to-face interviews every 6 months until November 2020. We evaluated each patient's response to the initial treatments at the first interview and divided them into “responders” and “nonresponders.” Relapses were recorded. At the end of follow-up, each patient was evaluated and reclassified into “complete recovery” or “unhealed” groups. Intergroup differences were assessed.Results: All patients presented with seizures at the initial consultation. Other common manifestations included cognitive dysfunction (82.2%), psychiatric disturbance (66.7%), sleep disorder (54.5%), and hyponatremia (66.7%). During the follow-up period (32.8 ± 13.5 months), six patients experienced relapse within 6–37 months. We observed that the patients who did not respond to the initial treatments and those who relapsed all had a poor long-term prognosis. The patients in the “unhealed” group were older (p = 0.009), had a lower incidence of generalized tonic–clonic seizures (p = 0.041), and had a higher probability of cerebrospinal fluid (CSF) abnormalities (p = 0.024) than those in the “complete recovery” group.Conclusion: Anti-LGI1 encephalitis was characterized by seizures, cognitive impairment, psychiatric disturbance, and sleep disorders and was often accompanied by hyponatremia. Patients who responded poorly to the initial treatments and those patients who relapsed had dismal long-term prognoses. Advanced age and CSF abnormalities may be risk factors for poor prognosis, but these still need to be verified.

Core cerebrospinal fluid biomarker profile in anti-LGI1 encephalitis.

To compare CSF biomarkers' levels in patients suffering from anti-Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis to neurodegenerative [Alzheimer's disease (AD), Creutzfeldt-Jakob's disease (CJD)] and primary psychiatric (PSY) disorders. Patients with LGI1 encephalitis were retrospectively selected from the French Reference Centre database between 2010 and 2019 and enrolled if CSF was available for biomarkers analysis including total tau (T-tau), phosphorylated tau (P-tau), amyloid-beta Aβ1-42, and neurofilaments light chains (NfL). Samples sent for biomarker determination as part of routine practice, and formally diagnosed as AD, CJD, and PSY, were used as comparators. Twenty-four patients with LGI1 encephalitis were compared to 39 AD, 20 CJD and 20 PSY. No significant difference was observed in T-tau, P-tau, and Aβ1-42 levels between LGI1 encephalitis and PSY patients. T-Tau and P-Tau levels were significantly lower in LGI1 encephalitis (231 and 43ng/L) than in AD (621 and 90ng/L, p < 0.001) and CJD patients (4327 and 55ng/L, p < 0.001 and p < 0.01). NfL concentrations of LGI1 encephalitis (2039ng/L) were similar to AD (2,765ng/L) and significantly higher compared to PSY (1223ng/L, p < 0.005), but significantly lower than those of CJD (13,457ng/L, p < 0.001). Higher levels of NfL were observed in LGI1 encephalitis presenting with epilepsy (3855ng/L) compared to LGI1 without epilepsy (1490ng/L, p = 0.02). No correlation between CSF biomarkers' levels and clinical outcome could be drawn. LGI encephalitis patients showed higher NfL levels than PSY, comparable to AD, and even higher when presenting epilepsy suggesting axonal or synaptic damage linked to epileptic seizures.

The Neurological and Neurosurgical Presentations of SARSCoV2 Affected Patients: A Systematic Review.

Presentation with neurological complaint is not very uncommon. Few patients report with intracerebral hemorrhage which are considered as cases of neurosurgical intervention, on the other hand respiratory depression and encephalitis patients need care in Neurosurgical intensive care unit (Neurosurgical ICU) for treating or measuring intracranial pressure (ICP). This systematic review includes 2683 COVID- 19 patients of 17 articles who had neurological manifestations. Out of these 17 studies 8 articles were retrospective case series, 3 were prospective case series, 3 were case reports, 2 were cross-sectional and 1 cohort study. Headache was commonest neurological feature presented in 7 studies. Cerebro-vascular problem, loss of smell and impaired conscious level was present in four studies each. Seizure was presenting feature in 3 studies. There were series where patients reported with loss of taste. Other presenting features were dizziness and ataxia. Previous studies supported that Corona virus can cause encephalitis, multiple sclerosis or cerebral hemorrhage. Respiratory failure due to damage of cardiorespiratory center of brainstem by COVID- 19 virus has not been ruled out. Bang. J Neurosurgery 2021; 10(2): 169-174

Exposure to tick-borne encephalitis virus among nature management workers in the Netherlands

Tick-borne encephalitis virus (TBEV) has only recently been detected in the Netherlands. With still few autochthonous tick-borne encephalitis (TBE) patients, human exposure to TBEV is expected to be very low among the general population. We aimed to assess the exposure to TBEV among persons with an occupationally high risk of tick bites in the Netherlands.In our cross-sectional serological survey, employees and volunteers of nature management organizations provided a single blood sample and completed an online questionnaire in 2017. The sera were screened in the anti-TBEV IgG Enzyme-Linked Immunosorbent Assay (ELISA), after which a TBEV-specific virus neutralization test (VNT) was applied to confirm positive ELISA outcomes.Ten sera tested positive for IgG antibodies in the TBEV ELISA, among 556 participants who did not report vaccination against TBEV. Through confirmation in VNT, TBEV-specific IgG antibodies were detected among 0.5% (3/556, 95%CI 0.1%–1.6%). During the five years prior to the questionnaire, 87% reported tick bites. Half of the participants considered that most of their tick bites (75% to 100%) had been acquired while being at work.A very low seroprevalence of TBEV exposure was observed among these nature management workers, even though they report a six times higher exposure to tick bites, compared to our general population. Nonetheless, the emergence of TBEV in the Netherlands reaffirms the need for education and preventative measures against tick bites and tick-borne diseases.

Paraneoplastic encephalitis associated with renal cell carcinoma.

Paraneoplastic encephalitis is autoimmune encephalitis accompanied by tumors. Renal cell carcinoma (RCC) is a kidney cancer originating from various types of renal cells and rarely has been associated with paraneoplastic neurologic manifestation. We identified a case series of paraneoplastic encephalitis-associated RCC. From a prospective institutional cohort, we identified autoimmune encephalitis patients with RCC. The association between RCC and encephalitis was determined by the following criteria: (1) possible autoimmune encephalitis according to the operational autoimmune encephalitis diagnostic criteria and (2) RCC simultaneously diagnosed with neurological manifestation of encephalitis. A total of three patients presented encephalitis accompanied by RCC. Two patients had clear cell RCC, and one had chromophobe RCC. All patients showed limbic encephalitis with cognitive decline, memory impairment, or seizure. Brain magnetic resonance imaging showed T2 hyperintensities at the mesial temporal lobe in two patients with clear cell RCC but no remarkable findings in one patient with chromophobe RCC. While one patient who had early surgery within one month of RCC onset had a favorable response to the treatment, the other two patients showed a partial response and a detrimental result. Paraneoplastic encephalitis associated with RCC presented as limbic encephalitis and was responsive to immunotherapy combined with tumor resection. As our cases identified, RCC should be considered as a cause of seronegative autoimmune encephalitis.

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti-GABABR encephalitis.

To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrinreleasingpeptide (ProGRP) levels were found in 70% of patients with a median value of 490.10pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p>.05). The value between SCLC and non-SCLC subgroup was significantly different (p<.05). Ten patients received immunotherapy (three patients refused treatment). After immunotherapy, the frequency of seizures was significantly reduced. There was a significant difference in mRS between admission and after treatment (p<.05). The average survival time after onset was 27.7months. Epilepsy is the most common clinical manifestation of Anti-GABABR encephalitis. The prognosis of anti-GABABR encephalitis is poor. Section of anti-GABABR encephalitis patients have higher level of serum ProGRP and positive GSF oligoclonal bands. Elevated ProGRP or positive CSF oligoclonal bands with classic clinical features can potentially help to improve early recognition of anti-GABABR encephalitis.

Prevalence and clinical manifestations of herpes simplex virus infection among suspected patients of herpes simplex encephalitis in Shiraz, Iran.

Encephalitis has infectious and noninfectious etiology. Among infectious agents, viruses are the main causes of encephalitis; Herpes simplex virus (HSV) is known as the most common causative agent of viral encephalitis. In this current cross-sectional investigation, we aimed to assess the prevalence of HSV in the cerebrospinal fluid (CSF) specimens of Herpes Simplex Encephalitis (HSE) suspected patients and also determining the clinical symptoms and laboratory findings of this viral complication. Two hundred consecutive HSE suspected patients with clinical diagnosis of encephalitis were included in the study and then the presence of HSV DNA in their CSF was applied by Polymerase Chain Reaction (PCR) assay. Molecular detection of two hundred (117 males with mean age: 43years, 83 females with mean age: 39years) CSF samples showed that 22 (11.11%) cases were positive for HSV infection. 15(68.18%) of the positive samples were more than 50years old, however, there was no significant correlation between age distribution, gender and HSE clinical manifestations. Fever (91%), headache (72.7%), seizer (59%), and weakness (59%) were the most common symptoms in positive patients and also mortality rate was (18.18%). CSF laboratory abnormalities of HSE cases were as follows; lymphocytic pleocytosis 19 (86.3%), leukocytosis 19 (86.3%), elevated protein level 16 (72.7%), and hypoglycorrhachia 3(13.6%). Screening of HSE suspected patients is crucial in the treatment of patients and reduce the mobility and morbidity of patients. Qualitative PCR as an available method in most developing countries could be a reliable method to monitor consecutive HSE suspected patients.

Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

ObjectiveTo report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings.MethodsWe retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry.ResultsThree patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity.ConclusionAMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.

Electrophysiological Evaluation in Identifying Unique Sleep Features Among Anti-LGI1 Encephalitis Patients During Active and Recovery Phase.

ObjectiveThe purpose of this study was to illustrate the electrophysiological features of sleep disturbances in patients with anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis in both active and recovery stages.MethodsRetrospectively filed video electroencephalogram (VEEG) and polysomnography (PSG) data in 24 patients with anti-LGI1 encephalitis were analyzed in comparison with that in 20 individuals without sleep disorders as control group.ResultsSleep efficiency (SE) and total sleep time involving REM and NREM sleep were significantly decreased in patients with anti-LGI1 encephalitis during the active stage compared to that during the recovery stage and in the control group. Imbalanced sleep structure was found, demonstrated by elevated N1, decreased N3 and REM components, as well as abnormal N2 structure characterized with significantly lower spindle duration and density during the active stage. These findings were independent of the presence of nocturnal episodic events or sleep hyperkinetic movements (HMs). HMs were present in 11/23 patients throughout NREM and REM sleep (nonspecific in sleep stages) during the active stage. During the recovery stage, SE and sleep structures were dramatically improved, including the percentage of N3 and REM sleep, spindle duration and density. Ten of 11 patients with HMs were followed up. HMs were totally remitted in 3 patients and still persistent in 1, while evolved into REM sleep behavior disorder (RBD) in 4 with comorbid periodic limb movement syndrome (PLMS) in 3/4, and only PLMS in 2.ConclusionSleep disturbances were remarkable and intrinsic features in active anti-LGI1 encephalitis, marked by overall disruptions of both NREM and REM sleep, as well as the presence of HMs, which tend to evolve into RBD or PLMS during the recovery stage. Long-term follow-up with PSG is needed, especially for those patients with severe sleep disturbances during the active phase.