Non-Polio Enteroviruses Isolated by Acute Flaccid Paralysis Surveillance Laboratories in the Russian Federation in 1998-2021: Distinct Epidemiological Features of Types.

More than 100 types of non-polio enteroviruses (NPEVs) are ubiquitous in the human population and cause a variety of symptoms ranging from very mild to meningitis and acute flaccid paralysis (AFP). Much of the information regarding diverse pathogenic properties of NPEVs comes from the surveillance of poliovirus, which also yields NPEV. The analysis of 265 NPEV isolations from 10,433 AFP cases over 24 years of surveillance and more than 2500 NPEV findings in patients without severe neurological lesions suggests that types EV-A71, E13, and E25 were significantly associated with AFP. EV-A71 was also significantly more common among AFP patients who had fever at the onset and residual paralysis compared to all AFP cases. In addition, a significant disparity was noticed between types that were common in humans (CV-A2, CVA9, EV-A71, E9, and E30) or in sewage (CVA7, E3, E7, E11, E12, and E19). Therefore, there is significant evidence of non-polio viruses being implicated in severe neurological lesions, but further multicenter studies using uniform methodology are needed for a definitive conclusion.

Neurological and neuromuscular manifestations in patients with West Nile neuroinvasive disease, Belgrade area, Serbia, season 2022.

INTRODUCTION: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease. METHODS: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale. RESULTS: Among the 135 analyzed patients, encephalitis, meningitis and acute flaccid paralysis (AFP) were present in 114 (84.6%), 20 (14.8%), and 21 (15.6%), respectively. Quadriparesis/quadriplegia and monoparesis were the most frequent forms of AFP, present in 9 (6.7%) and 6 (4.4%) patients, respectively. Fourty-five (33.3%) patients had cerebellitis, 80 (59.3%) had rhombencephalitis, and 5 (3.7%) exhibited Parkinsonism. Ataxia and wide-based gait were present in 79 (58.5%) patients each. Fifty-one (37.8%) patients had tremor (41 (30.3%) had postural and/or kinetic tremor, 10 (7.4%) had resting tremor). Glasgow coma score (GCS) ≤ 8 and respiratory failure requiring mechanical ventilation developed in 39 (28.9%), and 33 (24.4%) patients, respectively. Quadriparesis was a risk factor for prolonged ventilator support (29.5 ± 16.8 vs. 12.4 ± 8.7 days, p = 0.001). At discharge, one patient with monoparesis recovered full muscle strength, whereas 8 patients with AFP were functionally dependent. Twenty-nine (21.5%) patients died. All of the succumbed had encephalitis, and 7 had quadriparesis. Ataxia, tremor and cognitive deficit persisted in 18 (16.9%), 15 (14.2%), and 22 (16.3%) patients at discharge, respectively. Age, malignancy, coronary disease, quadriparesis, mechanical ventilation, GCS ≤ 8 and healthcare-associated infections were risk factors for death (p = 0.001; p = 0.019; p = 0.004; p = 0.001; p < 0.001; p < 0.001, and p < 0.001, respectively).

Comparison of acute flaccid myelitis and transverse myelitis in children and evaluation of diagnostic criteria.

BACKGROUND AND PURPOSE: Acute flaccid myelitis (AFM) and transverse myelitis (TM) are serious conditions that may be difficult to differentiate, especially at onset of disease. In this study, we compared clinical features of pediatric AFM and TM and evaluated current diagnostic criteria, aiming to improve early and accurate diagnosis. METHODS: Two cohorts of children with enterovirus D68-associated AFM and clinically diagnosed TM were compared regarding presenting clinical features, additional investigations, and outcome. Current diagnostic criteria for AFM and TM were applied to evaluate their specificity. RESULTS: Children with AFM (n = 21) compared to those with TM (n = 36) were younger (median 3 vs. 10 years), more often had a prodromal illness (100% vs. 39%), predominant proximal weakness (69% vs. 17%), and hyporeflexia (100% vs. 44%), and less often had sensory deficits (0% vs. 81%), bowel and/or bladder dysfunction (12% vs. 69%), and hyperreflexia (0% vs. 44%). On magnetic resonance imaging, brainstem involvement was more common in AFM (74% vs. 21%), whereas supratentorial abnormalities were only seen in TM (0% vs. 40%). When omitting the criterion of a sensory level, 11 of 15 (73%) children with AFM fulfilled the diagnostic criteria for TM. Of children with TM, four of 33 (12%) fulfilled the diagnostic criteria for probable/definite AFM. CONCLUSIONS: Although there is considerable overlap between AFM and TM in children, we found important early differentiating clinical and diagnostic features. Meeting diagnostic criteria for AFM in children with TM and vice versa underlines the importance of thorough clinical examination and early and accurate diagnostic studies.

High-dose chemotherapy and autologous stem cell transplantation in primary lymphomatoid granulomatosis of the central nervous system.

Primary lymphomatoid granulomatosis of the CNS (CNS-LG) is a rare lymphoid neoplasia associated Epstein-Barr Virus (EBV) and often accompanied by immunodeficiencies. No treatment standards have been defined yet. However, due to often devastating neurologic sequelae and based on similarities to diffuse large B-cell lymphoma, curative treatment requires intensive therapy protocols resembling protocols applied in CNS lymphoma. Here, the clinical courses and treatments of four primary CNS-LG patients in analogy to aggressive CNS-lymphomas including methotrexate, thiotepa, cytarabine, carmustine, and rituximab are presented. This is the first report on high-dose chemotherapy with CNS-directed drugs and autologous blood stem cell transplantation in primary CNS-LG.

Acute flaccid paralysis of a new surfer: A case report.

RATIONALE: Surfer's myelopathy is a rare atraumatic spinal cord injury most frequently experienced by novice surfers. Patients often experience back pain, followed by motor, sensory, bowel, and bladder involvement. Here, we report a case of surfer's myelopathy. PATIENT CONCERNS: The patient presented with acute low back pain associated with lower limb weakness, sensory loss, urinary retention, and perineal paraesthesia 1 hour after her first surf lesson. DIAGNOSIS: On arrival at the emergency department, she was noted to have flaccid paralysis with flickers in both lower limbs, reduced sensation in the midthoracic region, reduced anal tone, and saddle anesthesia. Magnetic resonance imaging of the spine revealed evidence of restricted diffusion from T6 to the level of the conus. Extensive investigations, including cerebrospinal fluid analysis, vasculitides/paraneoplastic screening, and further imaging, were unremarkable. She was diagnosed with complete T7 spinal cord injury secondary to surfer's myelopathy. INTERVENTIONS: She subsequently received methylprednisolone and was transferred to the spinal injury unit for rehabilitation. As she experienced persistent neuropathic pain at the level of the injury, she received input from the local pain team. One month after the injury, the patient developed swelling of the right thigh associated with reduced internal and external rotation of the right hip, impacting rehabilitation. The patient was diagnosed with heterotopic ossification following a triple-phase bone scan. She then received intravenous zolendronic acid, which had a good effect. OUTCOMES: Four months after the initial presentation, she was discharged to the community. Despite no improvement in her neurological status, she was independent of transfers and mobility with a wheelchair. In addition, she managed her neurogenic bowel and bladder independently with intermittent self-catheterization and a transanal irrigation system. At 6 months, she engaged well with returning to drive program and vocational rehabilitation. LESSONS: Neurological recovery from surfer's myelopathy has been shown to vary from complete recovery to minimal recovery. With a spinal-specific rehabilitation program, this patient remains independent of her activities of daily living. Surfer's myelopathy often occurs in inexperienced surfers; therefore, it is crucial to provide education to surfers and instructors.

Description of Bone Health Changes in a Cohort of Children With Acute Flaccid Myelitis (AFM).

OBJECTIVES: To qualitatively describe bone health changes in children with acute flaccid myelitis (AFM) and assess relationships with muscle mass and strength and functional performance. METHODS: Retrospective analysis of a cohort of 79 children with AFM seen consecutively in one specialized academic center between January 1, 2007, and December 31, 2019. RESULTS: Of the 79 participants who were aged 4 months to 21 years old, 41 (52%) had bone density measured by dual energy absorptiometry (DXA) and 32 of them (78%) were diagnosed with low bone mass (LBM). We recorded 25 fractures that occurred after onset of neurologic deficit in 14 of the children in the cohort (18%). Lean muscle mass correlated with bone mass and functional performance as assessed by Physical Abilities and Mobility Scale (PAMS) but not with muscle strength as assessed by manual muscle testing (MMT). Bone density in the lower limbs was associated with ambulatory status. CONCLUSION: Children with AFM have a high likelihood of muscle and bone loss and frequently sustain pathologic fractures. Bone health in children with AFM should be carefully monitored, and efforts should be made to preserve bone mass and maximize muscle mass.

[Infection of the central nervous system by Epstein-Barr virus: clinical manifestations and prognosis]. / Infección del sistema nervioso central por el virus de Epstein-Barr: manifestaciones clínicas y pronóstico.

INTRODUCTION: The role of Epstein-Barr virus (EBV) in central nervous system (CNS) infections is not fully resolved. We wanted to describe the clinical manifestations of patients with EBV infection in cerebrospinal fluid. PATIENTS AND METHODS: We reviewed the clinical records of all adult patients EBV PCR-positive in cerebrospinal fluid, without lymphoproliferative disease, during 2004 to 2020. RESULTS: We identified 27 patients, 22 (81.5%) were men, and median age was 54 years. Twenty-three (82.1%) patients were immunosuppressed, 16 HIV-positive. In 15 (55.6%) patients coinfection with another microorganism was diagnosed and in 12 (44.4%) patients it was detected as the only pathogen. Of the 12 patients, three (25%) was immunocompetent patients, one had Guillain Barre syndrome (GBS), another had disseminated multiphasic encephalitis, and another had lymphocytic meningitis; 9 (75%) immunosuppressed, 7 HIV-positive, 4 had encephalitis that resolved without sequelae and 4 had encephalopathy, two HIH-positive had moderate cognitive impairment as a sequela. CONCLUSIONS: In our study, EBV produced encephalitis, meningitis, polyradiculomyelitis and GBS, mainly in immunosuppressed patients. In more than half of the cases, it is associated with other pathogens where the role of EBV is unclear. In immunocompetent patient, the infection can be serious and leave sequelae and in HIV-positive patients with encephalopatic involvement without encephalitis, the neurological damage could be greater, so we consider it of interest to carry out studies to evaluate the prognosis as well as the role of antivirals in the evolucion of these clinical pictures.

TITLE: Infección del sistema nervioso central por el virus de Epstein-Barr: manifestaciones clínicas y pronóstico.Introducción. El papel del virus de Epstein-Barr (VEB) en las infecciones del sistema nervioso central no siempre está claro. Nuestro objetivo fue describir las manifestaciones clínicas y la evolución de los pacientes con detección del VEB en el líquido cefalorraquídeo (LCR). Pacientes y métodos. Se revisaron las historias clínicas de todos los pacientes adultos con detección del VEB en el LCR por reacción en cadena de la polimerasa diagnosticados desde 2004 hasta 2020 sin enfermedad linfoproliferativa. Resultados. Se diagnosticó a 27 pacientes, 22 (81,5%) hombres, con una mediana de 54 años; 23 (82,1%) pacientes eran inmunodeprimidos, 16 positivos para el virus de la inmunodeficiencia humana (VIH). En 15 (55,6%) pacientes, el VEB se detectó en coinfección con otro microorganismo, y en 12, como único patógeno. De los 12 pacientes, tres (25%) eran inmunocompetentes, uno presentó un síndrome de Guillain-Barré, otro una encefalitis diseminada multifásica y otro una meningitis linfocitaria; y nueve (75%) inmunodeprimidos, de los que cuatro presentaron encefalitis que se resolvieron sin secuelas, y cuatro encefalopatía, dos de ellos positivos para el VIH, que presentaron secuelas (deterioro cognitivo moderado). Conclusiones. En nuestro estudio, el VEB produjo cuadros de encefalitis, meningitis, polirradiculomielitis y SGB, principalmente en inmunodeprimidos. En más de la mitad de los casos se asocia a otros patógenos, en donde el papel del VEB no está claro. En inmunocompetentes, las infecciones pueden ser graves y dejar secuelas, y en pacientes con VIH con encefalopatía sin encefalitis, el daño neurológico podría ser mayor, por lo que consideramos de interés realizar estudios que evalúen el pronóstico y el papel de los antivirales en la evolución de estos cuadros clínicos.

Upper extremity nerve transfers for acute flaccid myelitis: a systematic literature review.

BACKGROUND: Acute flaccid myelitis (AFM) is a rare disease that commonly affects young children. AFM's pathophysiology involves loss of lower motor neurons following a viral infection and induces acute asymmetric flaccid paralysis most commonly in the upper extremities. Nerve transfers have emerged as a treatment option for these patients with permanent motor deficits. OBJECTIVE: To summarize the literature and report safety and efficacy outcomes following nerve transfers for recovery of shoulder abduction and external rotation, and elbow flexion and extension in pediatric patients with AFM. Recovery of at least antigravity function was defined as a successful outcome. This systematic review was performed according to the PRISMA guidelines. The PubMed, Embase and Cochrane databases were utilized. RESULTS: Five studies comprising 44 patients (median age 2.95 years; 71% male), and 93 upper extremity nerve transfers were included. Thirty-eight patients received 65 nerve transfer procedures aiming for recovery of shoulder abduction and/or external rotation with a transfer to the axillary and/or suprascapular nerve. The recovery of shoulder abduction and external rotation was achieved in 40.7% (n = 11/27) and 60% (n = 6/10) of patients, respectively. Time from injury to surgery showed an inverse relationship with the odds for successful recovery (OR: 0.81; 95% CI: 0.64-1.02; p = 0.07); however, statistical significance was not reached. Successful recovery of elbow flexion with a transfer to the musculocutaneous was reported at a rate of 92.3% (n = 12/13). Successful re-innervation of the radial nerve with recovery of elbow extension was found in 75% (n = 6/8) of patients. No complications were reported. CONCLUSIONS: Upper extremity nerve transfers appear to be promising and safe for AFM patients. Shoulder abduction is the most challenging upper extremity function to recover. Further studies are warranted to identify whether nerve transfers are associated with superior outcomes when performed earlier.

Isolation and molecular characterization of Adenovirus in suspected acute flaccid paralysis patients: A preliminary report from Pakistan.

Human adenoviruses (HAdVs) usually cause asymptomatic or mild infection, but infrequently, they are responsible for various severe syndromes including neurological disorders. Various research studies have investigated the association of HAdVs with acute flaccid paralysis (AFP). The purpose of this study was to investigate the genetic diversity of HAdVs and their association with AFP. Stool samples from patients ≤ 12 years of age with suspected AFP were collected from all over Pakistan within the framework of poliovirus surveillance. Poliovirus- and enterovirus-negative samples were screened for HAdVs. For virus isolation, the human epithelial cell line HEp-2c was used, culture-positive samples were screened by nested PCR assay, and partial hexon gene sequences were used for genotype identification. Out of 172 samples, 94 were positive by virus isolation, 89 were positive by PCR, and 32 isolates were genotyped successfully. Phylogenetic analysis showed that the HAdVs belonged to species A (HAdV-A12 and A31), B (HAdV-B3 and B7), C (HAdV-C1 and C6), D (HAdV-D19 and D93), and F (HAdV-F41), showing 99-100% nucleotide sequence identity and 98.3-100% amino acid sequence identity). Most of these genotypes have been reported previously in AFP cases, but this is the first report of the detection of HAdV-D93 in stool samples from AFP cases. The detection of a significant fraction of the HAdVs genotypes indicates that these genetically distinct genotypes are circulating in Pakistan and suggests their possible role in the pathogenesis of AFP.

Nerve Transfers for Restoration of Elbow Flexion in Patients With Acute Flaccid Myelitis.

PURPOSE: The purpose of this study was to evaluate short- to midterm outcomes of patients with acute flaccid myelitis who underwent nerve transfers for restoration of elbow flexion. METHODS: Patients with a minimum of 10 months of follow up after undergoing nerve transfers to restore elbow flexion were clinically assessed using the Active Movement Scale (AMS). They were evaluated for any postoperative complications, particularly weakness in the distribution of the donor nerve(s). Fifteen of 25 consecutive patients who were treated using this surgical technique were included in the final analysis. RESULTS: All patients exhibited poor elbow flexion preoperatively (AMS 0 to 3). At a mean follow up of 17.3 months, 80% (15/25) of patients achieved excellent elbow flexion (AMS 6 or 7); 9 of these 15 had full active range of motion. Two patients achieved good elbow flexion (AMS 5) with antigravity movement to less than 50% of the passive range of motion. No cases of superficial or deep infection were reported, and all patients maintained identical motor function, relative to preoperative status, of the muscles innervated by the donor nerves. CONCLUSIONS: Nerve transfer surgery has shown promising short- to midterm results for recovery of nerve and muscle function, particularly for the restoration of elbow flexion. We recommend this treatment option for patients not demonstrating clinical improvement after 6 to 9 months of incomplete recovery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Involvement of RIG-I Pathway in Neurotropic Virus-Induced Acute Flaccid Paralysis and Subsequent Spinal Motor Neuron Death.

Poliomyelitis-like illness is a common clinical manifestation of neurotropic viral infections. Functional loss and death of motor neurons often lead to reduced muscle tone and paralysis, causing persistent motor sequelae among disease survivors. Despite several reports demonstrating the molecular basis of encephalopathy, the pathogenesis behind virus-induced flaccid paralysis remained largely unknown. The present study for the first time aims to elucidate the mechanism responsible for limb paralysis by studying clinical isolates of Japanese encephalitis virus (JEV) and Chandipura virus (CHPV) responsible for causing acute flaccid paralysis (AFP) in vast regions of Southeast Asia and the Indian subcontinent. An experimental model for studying virus-induced AFP was generated by intraperitoneal injection of 10-day-old BALB/c mice. Progressive decline in motor performance of infected animals was observed, with paralysis being correlated with death of motor neurons (MNs). Furthermore, we demonstrated that upon infection, MNs undergo an extrinsic apoptotic pathway in a RIG-I-dependent fashion via transcription factors pIRF-3 and pIRF-7. Both gene-silencing experiments using specific RIG-I-short interfering RNA and in vivo morpholino abrogated cellular apoptosis, validating the important role of pattern recognition receptor (PRR) RIG-I in MN death. Hence, from our experimental observations, we hypothesize that host innate response plays a significant role in deterioration of motor functioning upon neurotropic virus infections. IMPORTANCE Neurotropic viral infections are an increasingly common cause of immediate or delayed neuropsychiatric sequelae, cognitive impairment, and movement disorders or, in severe cases, death. Given the highest reported disability-adjusted life years and mortality rate worldwide, a better understanding of molecular mechanisms for underlying clinical manifestations like AFP will help in development of more effective tools for therapeutic solutions.

Infections of the Spine and Spinal Cord.

PURPOSE OF REVIEW: Infections of the spine and spinal cord are associated with a high risk of morbidity and mortality and, therefore, require prompt clinical recognition, efficient diagnostic evaluation, and interdisciplinary treatment. This article reviews the pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment of infections of the spine and spinal cord to help practicing clinicians recognize, evaluate, and manage patients with such infections. RECENT FINDINGS: Aging of the population, increasing use of immunosuppressive medications, and other factors have contributed to increasing rates of spinal infections. Although the most common agents responsible for spinal infections remain bacteria and viruses, fungal infections occur in individuals who are immunocompromised, and parasitic infections are common in endemic regions, but patterns are in evolution with migration and climate change. Recent outbreaks of acute flaccid myelitis in children have been associated with enteroviruses A71 and D68. SUMMARY: Infections of the spine and spinal cord can be challenging to diagnose, requiring a thorough history and neurologic examination, laboratory studies of serum and CSF, neuroimaging (particularly MRI), and, in some instances, biopsy, to establish a diagnosis and treatment regimen. Interdisciplinary management including collaboration with experts in internal medicine, infectious disease, and neurosurgery is important to improve clinical outcomes.

Meningoencephalitis caused by Bovine alphaherpesvirus 5 in Pernambuco, Brazil / [Meningoencefalite causada pelo Bovine alphaherpesvirus 5 em Pernambuco, Brasil]

Objetivou-se descrever a ocorrência do Bovine alphaherpesvirus 5 (BoHV5) como causa de meningoencefalite não supurativa em bovinos do estado de Pernambuco, Brasil. Para tanto, 32 amostras de sistema nervoso embebidas em parafina foram obtidas de animais acometidos por doenças neurológicas atendidos na Clínica de Bovinos de Garanhuns da Universidade Federal Rural de Pernambuco (CBG-UFRPE), entre 2012 e 2016. As amostras foram analisadas quanto à presença do gene da glicoproteína C do BoHV5 por reação em cadeia da polimerase (PCR). Dois animais (6,25%) tiveram resultado positivo à PCR, e sua análise de sequenciamento indicou 100% de similaridade para o BoHV5. Os resultados histopatológicos desses dois animais revelaram lesões multifocais de meningoencefalite não supurativa associada à polioencefalomalácia, presença de corpúsculos de inclusão basofílicos, infiltração de células de Gitter e presença de manguitos perivasculares. A PCR se mostra uma importante ferramenta para diferenciação das infecções por BoHV5 de outras enfermidades neurológicas de bovinos, especialmente a raiva.(AU)

Infectious Myelopathies.

In the setting of both globalization and increasing use of immunosuppressive therapy, infectious myelopathies are an important cause of morbidity worldwide. Clinical spinal cord syndromes related to infection are varied, including transverse myelitis, acute flaccid paralysis related to anterior horn cell involvement, spinal cord compression, chronic spastic paraparesis, and myeloradiculitis. Causative pathogens include viruses, parasites, pyogenic and atypical bacteria, and fungi. The epidemiology, clinical characteristics, diagnosis, and treatment of selected organisms will be discussed in this article.

Dementia and cognitive impairment in adults as sequels of HSV-1-related encephalitis: a review / Demência e déficit cognitivo em adultos como sequelas de encefalite relacionada ao HSV-1: uma revisão

ABSTRACT. Considering the variety of mechanisms of Herpes simplex virus (HSV-1) contamination and its broad invasive potential of the nervous system, a life-long latent infection is established. Infected adult individuals may be susceptible to viral reactivation when under the influence of multiple stressors, especially regarding immunocompromised patients. This guides a series of neuroinflammatory events on the cerebral cortex, culminating, rarely, in encephalitis and cytotoxic / vasogenic brain edema. A sum of studies of such processes provides an explanation, even though not yet completely clarified, on how the clinical evolution to cognitive impairment and dementia might be enabled. In addition, it is of extreme importance to recognize the current dementia and cognitive deficit worldwide panorama. The aim of this literature review is to elucidate the available data upon the pathophysiology of HSV-1 infection as well as to describe the clinical panorama of the referred afflictions.

RESUMO. Considerando a variedade de mecanismos de contaminação pelo vírus Herpes simplex (HSV-1) e seu amplo potencial invasivo do sistema nervoso, uma infecção latente por toda a vida é estabelecida. Indivíduos adultos infectados podem ser suscetíveis à reativação viral quando estão sob a influência de múltiplos estressores, principalmente em pacientes imunocomprometidos. Esse fator orienta uma série de eventos neuroinflamatórios no córtex cerebral, culminando, raramente, em encefalite e edema cerebral citotóxico/vasogênico. Um somatório de estudos desses processos fornece uma explanação, embora ainda não totalmente esclarecida, de como a evolução clínica para déficit cognitivo e demência pode ser possibilitada. Além disso, é de extrema importância reconhecer o panorama mundial atual da demência e do déficit cognitivo. O objetivo da presente revisão de literatura é elucidar os dados disponíveis sobre a fisiopatologia da infecção pelo HSV-1, assim como descrever o panorama clínico das referidas afecções.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.