Encephalopathy In Adults Research Articles

Therapeutic potential of phytocompounds of Bacopa monnieri (L.) Wettst (literature review)

The aim of the work was to evaluate the pharmacological effects and therapeutic potential of individual compounds and extracts of B. monnieri based on the analysis of data from scientific periodicals regarding chemical composition and biological action. Theoretically significant were the studies of the materials of the scientific-metric database PubMed and Google Scholar over the last five years regarding the chemical composition and biological action of extracts based on B. monnieri and their individual components. The search query was carried out by the Latin name of the plant, with the exception of publications related to botanical research. In separate PubChem searches, names of individual phytocompounds were used to establish structure and distribution in plants. The SuperPred web server was used to predict therapeutic potential. The authors analyzed the chemical composition of the extracts, presented the structural and pharmacological characteristics of bacosides and their aglycones: bacosin and juubogenin, cucurbitacin E, loliolide, betulinic and asiatic acids and the flavonoid oroxindin. The mechanism of action of bacoside on β-amyloid is characterized and illustrated. Using machine learning, the prospects for using the main compounds of bacopa to create drugs were calculated taking into account the ATC classification, their biological effects and alternative plant sources were given. Experimental animal studies of whole aqueous or ethanolic extracts of B. monnieri have been found to support a cognitive enhancement effect. The extract was not toxic to humans. Numerous clinical trials show the effectiveness of the use of extracts in the treatment of anhedonia, depression, Alzheimer's disease, Parkinson's disease, dementia and hyperactivity. An analysis of clinical studies in Ukraine shows that drugs based on B. monnieri can be used in the complex treatment of cognitive impairment associated with dyscirculatory encephalopathy in adults and perinatal CNS damage in children. Considering the amphiphilicity of bacosides and the non-toxicity of extracts, they can be involved in the development of various dosage forms with a wide range of therapeutic applications. Further study of the pharmacological action of B. monnieri and the development of drug technology for solid and liquid dosage forms based on it are promising.

Predictors of Wernicke Encephalopathy in Adults Admitted for Acute Alcohol Induced Pancreatitis in the United States (P8-4.005)

Predictors of Wernicke Encephalopathy in Adults Admitted for Acute Alcohol Induced Pancreatitis in the United States (P8-4.005)

Identification of a panel of plasma protein biomarkers for determining Chronic Traumatic Encephalopathy in adults

Importance: Chronic Traumatic Encephalopathy (CTE) which results from trauma to the head can be a debilitating condition. If the patient luckily has no complications immediately, the long-term effects like gradually progressing tauopathy can seriously affect the individual's quality of life. This review aims to identify a panel of plasma neurobiomarkers that can be used to screen CTE in adults. Observations: This is a scoping review based on the methodological framework presented by Arksey & O'Malley, in 2005. Keywords were used to search the literature and articles were screened to identify the plasma biomarkers involved in chronic brain injury. A total of 38 plasma protein biomarkers were identified. A rubric was designed keeping in view the characteristics highlighted in the literature. The biomarkers were then scored on the basis of the rubric devised. The biomarkers which obtained the highest scores were Neurofilament Light chain (NfL), Phosphorylated forms of tau (P-Tau), and Neuron specific enolase (NSE) with 12, 12, and 11 scores respectively. Both NfL and p-Tau are present in serum and Cerebrospinal fluid (CSF) with equal sensitivity. Both originate mainly from the brain, are present at the pico level of quantification, and represent chronic brain injury. NSE on the other hand is detected with higher sensitivity in CSF than in blood. The rest of its qualities equate with those of NfL and p-Tau. Conclusion and relevance: In conclusion, NfL, p-Tau, and NSE have the optimum characteristics that are the best fit for diagnosing CTE as compared to other biomarkers. The specificity in terms of origin from the brain, representation of chronic brain trauma, and detecting the smallest amount present in plasma with almost the same detection sensitivity as CSF, are the qualities that make these biomarkers the most suitable ones. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evidence-based approach to management of hepatic encephalopathy in adults.

Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.

Cerebrospinal Fluid Extracellular Vesicles with Distinct Properties in Autoimmune Encephalitis and Herpes Simplex Encephalitis

Encephalitis mediated by autoantibodies against neuronal antigens and herpes simplex encephalitis (HSE) are seemingly separate causes of encephalopathy in adults. Autoimmune encephalitis (AE) is autoimmune in origin, and herpes simplex encephalitis is infectious. The purpose of this study was to examine the role of cerebrospinal fluid (CSF) exosomes from patients with antibody-positive AE and HSE. Towards this, exosomes were isolated from CSF from 13 patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, 11 patients with anti-gamma-aminobutyric acid-B (GABAB) receptor encephalitis, 9 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and 8 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, and 12 control individuals negative of antibodies against neuronal autoantigens. There were ten miRNAs highly expressed in patients with anti-NMDAR encephalitis compared to those in control subjects. Eight miRNAs were found to be lower expressed in anti-NMDAR encephalitis CSF-derived exosomes. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by AE differential expressed exosomic miRNAs demonstrated that AE-related exosomic miRNAs may participate as a feedback regulation in cancer development. In addition, the exosome concentration in CSF of 9 HSE patients was significantly higher compared to those from 9 HSV( −) patients. This observation was consistent with the results that exosome concentration was found to be higher in the animal model which was inoculated intranasally with HSV-1 compared to controls. Furthermore, western blot demonstrated that the subunits of NMDAR, GABABR, and AMPAR were detected highly expressed in exosomes derived from sera of HSV-1-treated animal model compared to controls. More importantly, exosomes isolated from CSF of HSE patients contained higher expression levels of two miRNAs encoded by HSV, miR-H2-3p, and miR-H4-3p compared to those from HSV( −) patients. In summary, HSV may trigger brain autoimmunity in HSE by presentation of surface autoantigens via exosomes.

Genetic causes of acute encephalopathy in adults: beyond inherited metabolic and epileptic disorders.

Acute encephalopathy is a widely used term, implying a rapidly progressive multifocal or diffuse brain dysfunction, caused by acute structural disturbance or a myriad of metabolic, toxic, epileptic, or infection-related factors. Apart from the more common acquired causes, a broad range of rare inherited disorders may produce spells of encephalopathy in adulthood, posing diagnostic challenges to clinicians. Among the latter, neurometabolic disorders and epileptic syndromes constitute typical examples. Interestingly, certain genetic entities have the potential to provoke episodic changes of cognition, via alternative, neither metabolic nor epileptic, mechanisms. Our aim is to provide a short and focused overview of their clinicoradiological features and potential pathophysiology. As the neurogenetic landscape is rapidly evolving, it is important to be familiar with these chameleons, in order to provide swift diagnosis and proper genetic counselling.

Risk Factor and Long-Term Outcome Analyses for Acute Limbic Encephalitis and Calcineurin Inhibitor-Induced Encephalopathy in Adults following Allogeneic Hematopoietic Cell Transplantation

Post-transplantation acute limbic encephalitis (PALE) is a rare, severe inflammatory disorder in the bilateral limbic system, including the hippocampus. To date, only a few studies have reported details, including risk factors for PALE; however, further clinical evidence of PALE, especially in cerebrospinal fluid human herpesvirus 6-negative cases, is warranted. In addition, data are sparse regarding the risk factors for calcineurin inhibitor (CNI)-induced encephalopathy (CNIE) following allogeneic hematopoietic cell transplantation (allo-HCT) in adults. Therefore, we examined the risk factors for and clinical details of PALE and CNIE. We retrospectively analyzed consecutive patients who underwent allo-HCT between January 2005 and November 2017. A total of 485 patients age 46 years (median) were eligible. In total, 14 PALE cases and 11 CNIE cases were identified. Multivariable analyses identified older age, use of an HLA-mismatched unrelated donor (URD), graft-versus-host disease (GVHD) prophylaxis with CNI and mycophenolate mofetil, and grade II-IV acute GVHD as significantly associated with an increased risk of PALE. In 13 patients who received high-dose methylprednisolone (mPSL) therapy, 6 (46%) responded to mPSL therapy, and 3 (23%) achieved complete remission at day 90 after mPSL administration. Furthermore, myelodysplastic syndrome (MDS), HLA-mismatched URD, and grade II-IV acute GVHD were significantly associated with an increased risk of CNIE. The 5-year nonrelapse mortality rate was 50% in PALE and 63% in CNIE, suggesting a very poor prognosis. In conclusion, this study provides evidence that HLA-mismatched URD and acute GVHD may independently contribute to the development of PALE, possibly in part through HLA-mismatch-derived alloimmune responses. Other than acute GVHD, we have identified MDS and HLA-mismatched URD as novel predictors of CNIE after allo-HCT.

Aminoglycosides and metronidazole for the treatment of hepatic encephalopathy in adults with cirrhosis

Aminoglycosides and metronidazole for the treatment of hepatic encephalopathy in adults with cirrhosis

P: 9 Pharmacotherapies that Specifically Target Ammonia for the Prevention and Treatment of Hepatic Encephalopathy in Adults With Crrhosis

BACKGROUND: Ammonia plays a key role in the genesis of hepatic encephalopathy (HE). Recent interest has focused on drugs which specifically target ammonia, e.g. sodium benzoate (SB), glycerol phenylbutyrate (GPB), ornithine phenylacetate (OP), AST-120, and polyethylene glycol (PEG). This study aims to evaluate the utility of these pharmacotherapies vs. placebo or non-absorbable disaccharides (NAD), for the management of HE in people with cirrhosis. L-ornithine L-aspartate is not included. METHODS: Electronic/manual searches of the literature were undertaken for relevant RCTs. The results of the meta-analyses are presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CIs). Bias control was assessed using the CHBG domains and the certainty of the evidence using GRADE. RESULTS: Eleven RCTs were identified involving SB (n = 1), GPB (n = 1), OA (n = 2), AST-120 (n = 2) and PEG (n = 3). Treatment periods ranged from five days to 16 weeks. All but one trial was at “high risk of bias”; the certainty of the evidence was very low for all outcomes. Nine trials, with 733 participants, reported blood ammonia concentrations. Significant reductions were observed in placebo-controlled trials evaluating SB (MD −32.00, 95% CI −46.85 to −17.15); GPB (MD −12.00, 95% CI −23.37 to −0.63); OP (MD −27.10, 95% CI −48.55 to −5.65) and AST-120 (MD −22.00, 95% CI −26.75 to −17.25). No significant differences in blood ammonia concentrations were observed when compared to NADs. Eleven trials, with 943 participants, reported mortality data, although there were no events in five trials. No beneficial or harmful effects were found in any of the trials. Seven trials, with 521 participants reported data on HE. Beneficial effects were identified for GPB vs. placebo (RR 0.57, 95% CI 0.36 to 0.90; 178 participants; 1 trial; NNTB = 6) and for PEG vs. lactulose (RR 0.19, 95% CI 0.08 to 0.44; 190 participants; 3 trials; NNTB = 4); no beneficial effects were observed in the remaining three trials with extractable data (Figure 1). Ten trials, with 790 participants, reported a total of 130 serious adverse events. There was no evidence of beneficial or harmful effects of the five agents when compared to placebo or NADs. CONCLUSIONS: These agents generally reduce blood ammonia concentrations, when compared to placebo, but not when compared to NADs. Their overall effects on clinical outcomes of interest and the potential harms associated with their use remain uncertain. Further evidence is needed to fully evaluate their utility in this clinical setting.

P: 51 Aminoglycosides and Metronidazole for the Prevention and Treatment of Hepatic Encephalopathy in Adults With Cirrhosis

BACKGROUND: The EASL/AASLD guidelines stipulate that both neomycin and metronidazole may be used as alternatives for the treatment of overt HE, whereas the Italian guidelines state that these antibiotics are currently not recommended, mainly because of their potential systemic toxicity. This study aims to evaluate the utility of aminoglycosides and metronidazole vs. placebo, non-absorbable disaccharides (NAD) and other active treatment, for the management of HE in adults with cirrhosis. METHODS: Electronic/manual searches of the literature were undertaken for relevant RCTs. The results of the meta-analyses are presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CIs). Bias control was assessed using the CHBG domains and the certainty of the evidence using GRADE. RESULTS: Twenty RCTs evaluated aminoglycosides including neomycin (n = 15) paromomycin (n = 4), and ribostamycin (n = 1). Treatment periods ranged from 3 to 168 days. Comparators included: placebo (n = 2), NADs (n = 7), other antibiotics viz. rifaximin, erythromycin and ciproxin (n = 9) and BCAAs (n = 2). All but one trial was at 'high risk of bias'; the certainty of the evidence was low or very low for all outcomes. Twenty trials, with 1110 participants, reported mortality data, although there were no events in 12 trials. No differential beneficial or harmful effects were found in any of the trials (RR 1.10, 95% CI 0.89 to 1.42, I2 6%, P = 0.39). Seventeen trials, with 1025 participants reported data on HE. No differential beneficial or harmful effects were found in any of the trials (RR 0.89, 95% CI 0.57 to 1.39, I2 69%, P = 0.62). Twenty trials, with 1110 participants, reported 778 serious adverse events (SAEs), although there were no events in eight trials. Use of the aminoglycosides was associated with more SAEs including pneumonia and renal failure (RR 1.46, 95% CI 0.99 to 2.16, I2 0%, P = 0.06) (Figure 1). One RCT evaluated metronidazole vs. rifaximin. Treatment was administered for three days as an adjunct to oral lactulose, LOLA and thrice daily enemata. Both regimens were equally as effective; no adverse events were reported. CONCLUSIONS: Although no significant differences were observed between the effects of aminoglycosides and other interventions, in relation to death and HE, in patients with cirrhosis, their use may be associated with an increased risk of serous adverse events. The utility of metronidazole for the management of HE can not be evaluated on the basis of the available literature. Neither drug should be used routinely in this setting.

Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.

Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.

Medical interventions for prevention and treatment of hepatic encephalopathy in adults with cirrhosis: a network meta-analysis

Medical interventions for prevention and treatment of hepatic encephalopathy in adults with cirrhosis: a network meta-analysis

57-Year-Old Woman With Fever and Confusion

57-Year-Old Woman With Fever and Confusion

WHEN PIGS FLY: THROMBOEMBOLIC EVENTS IN A CASE OF SEVERE H1N1 INFLUENZA TYPE A

SESSION TITLE: Critical Care 4 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: H1N1 Subtype Influenza Type A, strain responsible for the 2009 pandemic, is primary regarded as a disease affecting lung parenchyma, yet it is its ability to infiltrate and cause system wide complications which has made it such a deadly virus. It is hypothesized the disease process may cause a propensity for thromboembolic events through activation of platelets, alterations of coagulation factors, or endothelial dysfunction. There have been multiple documented cases of pulmonary embolism and myocardial infarctions in prior reports in H1N1 infected individuals, but few of cerebral events. We present a unique case of a previously healthy 47 year old male with severe H1N1-influenza whose hospital course was complicated by multiple cerebral infarcts and R-femoral DVT. CASE PRESENTATION: 47 year old caucasian male without a significant PMHx presented initially for fevers, myalgias, and respiratory distress requiring intubation at an outside facility. The patient’s condition worsened and was transferred to our facility for higher level of care. He was initially found to to have septic shock and started on empiric antibiotics. PCR was positive for H1N1 flu, oseltamivir was initiated. The pt underwent a bronchoscopy with washings. He continue to have fevers although multiple cultures of blood, bronchial washings, sputum were negative for any growth bacterial or fungal growth. On day 4, the patient was found to have a DVT of R-femoral vein and started on a heparin drip; of note, chemical DVT prophylaxis was initiated at time of admission. The pt had difficulty with arousability off sedation and underwent extensive neurological workup including CSF studies which were negative. MRI was significant for multiple small bilateral cerebral infarcts. Repeat echos were negative for signs of endocarditis or PFO on bubble study. Pt improved following tracheostomy placement and was discharged to LTAC on day 17th of hospitalization. DISCUSSION: The clinical course of this case was particularly challenging due to the severity of illness and continual negative initial workup of the pt. The pt continued to have poor neurological improvement. Although multiple strokes were seen on head MRI, the territories were small and unlikely to have accounted for the pt’s decreased arousability. One possibility could have been influenza-associated encephalitis which is a rare complication and likely under-diagnosed given lack of distinctive clinical symptoms and diagnostic criteria. CSF studies were unremarkable but difficulty in obtaining influenza PCR on CSF limited our results. CONCLUSIONS: This case serves to illustrate the widespread effects of Influenza Type A H1N1, even in healthy individuals. In this particular case, the pt had both venous and arterial thromboembolic events which is unique. It is important to keep in mind the extent of the disease process in this disease, especially in critically-ill patients. Reference #1: Dimitroulis, I. A., Katsaras, M., & Toumbis, M. (2016). H1N1 infection and embolic events: A multifaceted disease. Pneumon, 29(3), 230-235. Reference #2: Coorevits, L., Demuynck, H., Boone, E., Roelens, J., & Surmont, I. (2011). Trombo-embolic complications in influenza A(H1N1)2009: A forgotten and fatal danger, also in so-called "mild” flu? [Trombo-embolische Reference #3: Meijer, W. J., Linn, F. H. H., Wensing, A. M. J., Leavis, H. L., van Riel, D., GeurtsvanKessel, C. H., … Murk, J.-L. (2016). Acute influenza virus-associated encephalitis and encephalopathy in adults: a challenging diagnosis. JMM Case Reports, 3(6), e005076. http://doi.org/10.1099/jmmcr.0.005076 DISCLOSURES: No relevant relationships by Donna Cota, source=Web Response No relevant relationships by Luna Liu, source=Web Response No relevant relationships by Robyn Moran, source=Web Response

Probiotics in Disease Prevention and Treatment.

Few treatments for human diseases have received as much investigation in the past 20years as probiotics. In 2017, English-language meta-analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, and hepatic encephalopathy in adults. The strongest evidence in favor of probiotics lies in the prevention or treatment of 5 disorders: necrotizing enterocolitis, acute infectious diarrhea, acute respiratory tract infections, antibiotic-associated diarrhea, and infant colic. Probiotic mechanisms of action include the inhibition of bacterial adhesion; enhanced mucosal barrier function; modulation of the innate and adaptive immune systems (including induction of tolerogenic dendritic cells and regulatory T cells); secretion of bioactive metabolites; and regulation of the enteric and central nervous systems. Future research is needed to identify the optimal probiotic and dose for specific diseases, to address whether the addition of prebiotics (to form synbiotics) would enhance activity, and to determine if defined microbial communities would provide benefit exceeding that of single-species probiotics.

Acute Febrile Encephalopathy in Adults; a Review of 3 Prospective Trials

Introduction: Acute Febrile Encephalopathy (AFE) is a heterogeneous clinical syndrome that refers to fever associated or followed by mental deterioration with or without other neurologic manifestations, including seizure and sensory motor deficits. The emergency nature of AFE necessitates high levels of knowledge and skill for the physician to provide correct diagnostic plan(s) among a wide range of etiologies. Fever accompanying shortens the list of differential diagnosis to mainly infectious agents. Materials and Methods: Based on a digital search in Pubmed looking for the terms mental alteration, fever, adult, elderly and topical countries, and infectious diseases, three prospective trials which met the inclusive criteria were selected and reviewed. Results:A total of 430 adult and elderly patients with a mean age of 30 years old admitted to different hospitals of India and diagnosed with AFE were investigated for the most common causes of AFE and other clinical outcomes. In this review, primary CNS infections including pyogenic meningitis (PM) and viral encephalitis various in the most common viral agent in different studies were the main causes responsible for AFE in adults, followed by sepsis associated encephalopathy (SAE) and cerebral malaria (CM). Poor prognostic and protective factors were listed based on the findings and by considering other studies. Viral encephalitis is associated with the most mortality rate and physical disabling, compared to other etiologies. Conclusion: Primary CNS infections including bacterial meningitis and viral meningoencephalitis account for the most causes of AFE in adult and elderly patients with the most fatality for viral agents.

Acute influenza virus-associated encephalitis and encephalopathy in adults: a challenging diagnosis

Background: Acute influenza-associated encephalopathy/encephalitis (IAE) in adults is a rare but well-known complication of influenza virus infection. The diagnosis is difficult to make due to the absence of distinctive clinical symptoms and validated diagnostic criteria. We present an illustrative case and a case review on acute IAE in adults.Methods: We performed a Medline search of the English literature using the terms influenz*, encephal* and adult, and constructed a database of detailed descriptions of patients with influenza virus infection with influenza-like symptoms at the onset of neurological symptoms.Results: A total of 44 patients were included. Confusion and seizures were the most prevalent neurological symptoms, present in 12 (27 %) and 10 (23 %) patients, respectively. Magnetic resonance imaging (MRI) was performed in 21 patients and anomalies were found in 13 (62 %), with lesions located throughout the brain. Influenza virus RNA was detected in cerebrospinal fluid (CSF) in 5 (16 %) of 32 patients. Eight (18 %) of the forty-four patients died. The benefits of antiviral and immunomodulatory therapy have not been well studied.Discussion: Our results show that many different neurological symptoms can be present in patients with acute onset IAE. Therefore, the diagnosis should be considered in patients with fever and neurological symptoms, especially during the influenza season. Laboratory diagnosis consists of demonstration of influenza virus RNA in brain tissue, CSF or respiratory samples, and demonstration of intrathecal antibody production against influenza virus. The presence of brain lesions in MRI and influenza virus in CSF appear to be of prognostic value.

Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults

Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days...

Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment.

BackgroundX-linked Ornithine Transcarbamylase deficiency (OTCD) is often unrecognized in adults, as clinical manifestations are non-specific, often episodic and unmasked by precipitants, and laboratory findings can be normal outside the acute phase. It may thus be associated with significant mortality if not promptly recognized and treated. The aim of this study was to provide clues for recognition of OTCD in adults and analyze the environmental factors that, interacting with OTC gene mutations, might have triggered acute clinical manifestations.MethodsWe carried out a clinical, biochemical and molecular study on five unrelated adult patients (one female and four males) with late onset OTCD, who presented to the Emergency Department (ED) with initial fatal encephalopathy. The molecular study consisted of OTC gene sequencing in the probands and family members and in silico characterization of the newly detected mutations.ResultsWe identified two new, c.119G>T (p.Arg40Leu) and c.314G>A (p.Gly105Glu), and three known OTC mutations. Both new mutations were predicted to cause a structural destabilization, correlating with late onset OTCD. We also identified, among the family members, 8 heterozygous females and 2 hemizygous asymptomatic males. Patients' histories revealed potential environmental triggering factors, including steroid treatment, chemotherapy, diet changes and hormone therapy for in vitro fertilization.ConclusionsThis report raises awareness of the ED medical staff in considering OTCD in the differential diagnosis of sudden neurological and behavioural disorders associated with hyperammonemia at any age and in both genders. It also widens the knowledge about combined effect of genetic and environmental factors in determining the phenotypic expression of OTCD.

Herpes Simplex Encephalitis as a Potential Cause of Anti–N-Methyl-d-Aspartate Receptor Antibody Encephalitis

Encephalitis mediated by anti-N-methyl-D-aspartate (NMDA) receptor antibodies and herpes simplex (HS) encephalitis are seemingly separate causes of encephalopathy in adults and children. Herpes simplex encephalitis is infectious, and anti-NMDA receptor antibody encephalitis is autoimmune in origin. Both can cause seizures and encephalopathy, although the latter can also cause psychiatric symptoms and movement disorders. Owing to the rarity of these 2 diseases, patients with co-occurrence are important because they alert clinicians to possible links between 2 seemingly separate processes. In a case series of 2 patients observed at our center, we describe an infant and an adult who had confirmed HS encephalitis and then developed confirmed anti-NMDA receptor antibody encephalitis. Polymerase chain reaction testing for HS virus was performed. Testing for NMDA receptor antibodies was performed by Associated Regional and University Pathologists Laboratory in Salt Lake City, Utah. We conclude that atypical cases of HS or other viral encephalitides should be investigated for concomitance of an autoimmune encephalitis. We suspect that the pathophysiologic mechanisms by which HS virus infects neurons produce a higher likelihood of contracting anti-NMDA receptor antibody encephalitis.