Case report of meningoencephalitis associated with SARS-CoV-2 infection showing a decrease in idiopathic focal cerebral blood flow.

Some neurological complications are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A 74-year-old man was diagnosed with infection by SARS-CoV-2. Eighteen days after SARS-CoV-2 infection, he developed disturbed consciousness and aseptic meningoencephalitis. An analysis of cerebrospinal flood revealed an elevated cell count (184/µL) and protein level (260 mg/dL). Cranial magnetic resonance imaging showed no abnormalities. By contrast, 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed a significant decrease in cerebral blood flow (CBF) in the left parietal and occipital lobes. He died suddenly 3 months after being transferred to a rehabilitation clinic without any clear cause of death. The SARS-CoV-2 infection can cause aseptic meningoencephalitis with a distinctive decrease in CBF pattern without magnetic resonance image abnormality or intracranial artery stenosis.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Initially Presenting as Septic Meningoencephalitis in a 16-Year-Old Male.

Background: We describe a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in a 16-year-old patient who initially presented with clinical features of septic meningoencephalitis. This case outlines the importance of considering a diagnosis of MOGAD in patients who fail to improve with appropriate antimicrobial therapy or show a positive clinical response to glucocorticoids (often used in treatment of meningococcal meningitis). We emphasise the importance of recognising that an infectious prodrome can precede MOGAD. Case description: A 16-year-old male was admitted with vomiting, fever, headache, photophobia and altered mental state. He was treated for meningoencephalitis with initial clinical improvement. Lumbar puncture findings were suggestive of viral meningoencephalitis. During admission the patient went through several periods of transient clinical and biochemical improvement, alternating with periods of symptomatic relapse. On day 17 of admission, he was transferred to a tertiary centre for suspected autoimmune disseminated meningoencephalitis (ADEM) and two days later, he suffered a catastrophic neurological decline with new dysarthria, dysphagia, aphasia, horizontal nystagmus and facial paralysis. He made a remarkable neurological recovery after commencing treatment with IV immunoglobulin, IV methylprednisolone and plasma exchange, with complete resolution of symptoms. Conclusion: MOGAD can run a variable course and present soon after a central nervous system infection, making the diagnosis more challenging. Nonetheless, patients can achieve a full neurological recovery with early recognition, diagnosis and treatment of this rare entity. LEARNING POINTS: Autoimmune encephalitis can be preceded by an infectious prodrome which makes the diagnosis more challenging.Autoimmune encephalitis can run a subacute and fluctuating course with transient periods of symptomatic improvement preceding a rapid neurological decline.Glucocorticoids often used in treatment of patients with meningococcal meningitis may lead to transient symptomatic improvement in patients with autoimmune encephalitis, masking the diagnosis.MRI findings of demyelination in autoimmune encephalitis may lag behind clinical symptoms by days to weeks.

Neuroprotective effects of CysLT2R antagonist on Angiostrongylus cantonensis-induced edema and meningoencephalitis.

Cysteinyl leukotrienes (CysLTs) can induce a disruption of the blood-brain barrier (BBB), and this reaction is mediated by cysteinyl-leukotriene receptors. In this study, we used A. cantonensis-induced eosinophilic meningoencephalitis as a model to investigate whether the CysLT2 receptor involved in the pathogenesis of angiostrongyliasis meningoencephalitis. The present study provides evidence that the CysLT2 receptor antagonist HAMI3379 reduced the number of infiltrated eosinophils and brain edema in eosinophilic meningoencephalitis. Additionally, we found that HAMI3379 significantly decreased the protein levels of M1 polarisation markers (CD80, iNOS, IL-5 and TNF-α), increased the expression of M2 polarisation markers (CD206, IL-10 and TGF-ß) both in vivo and in vitro. Matrix metalloproteinase-9, S100B, GFAP, fibronectin, and claudin-5 were markedly lower after HAMI3379 treatment. Therefore, HAMI3379 reduced the BBB dysfunction in angiostrongyliasis meningoencephalitis. We have identified microRNA-155 as a BBB dysfunction marker in eosinophilic meningoencephalitis. The results showed that microRNA-155 was 15-fold upregulated in eosinophilic meningoencephalitis and 20-fold upregulated after HAMI3379 treatment. Our results suggest that CysLT2R may be involved in A. cantonensis-induced brain edema and eosinophilic meningoencephalitis and that down-regulation of CysLT2R could be a novel and potential therapeutic strategy for the treatment of angiostrongyliasis meningoencephalitis.

Meningoencephalomyelitis and brachial plexitis in a dog infected with louping ill virus.

A foxhound from a hunting kennel in the United Kingdom was euthanized after being hospitalized with progressive neurologic signs, including tremors, seizures, and obtunded mentation. No abnormalities were appreciated on gross postmortem examination. Histologically, severe meningoencephalomyelitis and mild neuritis of the brachial plexus were present. Molecular analysis of brain tissue detected louping ill virus. In addition, louping ill virus-specific antigens were detected in neurons within the brainstem, the entire length of the spinal cord, as well as in rare cells in the brachial plexus using immunohistochemistry. The genetic sequence of the virus appears most closely related to a previously detected virus in a dog from a similar geographic location in 2015. This is the first characterization of the inflammatory lesions and viral distribution of louping ill virus in a naturally infected dog within the spinal cord and brachial plexus.

Cryptococcal meningoencephalitis and pneumonia in a HIV positive patient: A case report.

Key Clinical Messages: Early diagnosis of cryptococcal infection is the key to improving outcomes, any newly diagnosed HIV patient presenting with subacute or chronic headache, particularly those who are CD4-deplete, should be investigated for cryptococcal meningitis. We had some delay in our patient management, including delay in HIV diagnosis, delay in doing LP and delay in initiation of anti-cryptococcal treatment and also early start of ART before specific cryptococcal treatment exacerbated IRIS in the patient. So, paying attention to these points can improve the prognosis of such patients. Abstract: Cryptocccus is a fungal pathogen and the causative agent of Cryptococcosis among human immunodeficiency virus (HIV) positive people. Meningoencephalitis is the most common manifestation of cryptococcal infection, while pulmonary cryptococcosis is often neglected due to nonspecific clinical and radiological presentation leading to a delay in diagnosis and disseminated disease. Here, we reported a 67-year-old man with newly diagnosed HIV who presented with concurrent cryptococcal meningoencephalitis and pulmonary cryptococcosis that admitted with the complaint of dyspnea and productive cough for 1.5 months, worsening shortness of breath, fever and weight loss since 15 days prior to admission. He also had severe oral candidiasis. Lung computed tomography (CT) revealed ill-defined subpleural cavitary lesion in left lower zone with bilateral diffuse ground glass opacity and air bronchogram. His HIV PCR test was positive with absolute CD4 count less than 50 cells/mm3. After starting antiretroviral therapy (ART), he gradually developed a headache and decreased level of consciousness. Cerebrospinal fluid (CSF) analysis revealed 450 cells, predominantly lymphocytes, with protein of 343 mg/dL and glucose of 98 mg/dL (corresponding blood glucose 284 mg/dL). CSF India ink staining was positive for crypococcus spp. Liposomal amphotericin B in combination with fluconazole (due to the unavailability of flucytosin) was stated. He was intubated because of hypoxia and his bronchoalveolar lavage was positive for Cryptococcus spp. too. He died 2 weeks after starting antifungal therapy based on this study it should be mentioned that neurologic and respiratory symptoms may be the first presentation of acquired immunodeficiency syndrome.

A Report of Two Cases of Meningoencephalitis Caused by Streptococcus intermedius.

Objective: In this paper, we analyzed the clinical data of patients with meningoencephalitis caused by Streptococcus intermedius to understand better the clinical characteristics of the disease and recommend auxiliary diagnostic mode as well as treatment experience. Methods: We reviewed the clinical data of two patients admitted to our department in 2019 with meningoencephalitis caused by S. intermedius. Results: Two female patients were examined, one of whom had a history of radiotherapy for nasopharyngeal carcinoma while the other had no underlying disease. These two patients were admitted with symptoms of meningoencephalitis. Cerebrospinal fluid examinations revealed elevated levels of leukocytes and protein. After treatment with meropenem, the condition improved for a brief time, but then worsened with a decline in mental status and limb movement. Blood and cerebrospinal fluid cultures demonstrated the absence of pathogenic bacteria, while genome sequencing of cerebrospinal fluids revealed the presence of S. intermedius. Cranial magnetic resonance imaging revealed multiple cerebral abscesses (CAs). After coadministration of linezolid as an anti-infective, clinical symptoms gradually improved, and the CAs shrank on follow-up imaging. The condition exhibited a pattern of improvement-deterioration-improvement. Conclusion: Meningoencephalitis caused by S. intermedius is complex and prone to fluctuation and formation of multiple CAs. The definitive clinical diagnosis of this disease can be aided by genome sequencing technology, and early clarification of the etiology combined with the use of potent antibiotics is effective.

Allele frequency of a genetic risk variant for necrotizing meningoencephalitis in pug dogs from Europe and association with the clinical phenotype.

Introduction: Necrotizing meningoencephalitis (NME) in pugs is a potentially fatal disease, which needs lifelong treatment with immunosuppressive or immunomodulatory drugs and shares parallels with acute fulminating multiple sclerosis. Genetic variants of the DLA class II gene are associated with an increased risk for NME. Genetic testing is recommended prior to breeding. The aim of this study was to describe the current allele frequency of a previously identified NME risk variant in the European pug population. A secondary aim was to investigate the association of the NME risk variant with the clinical phenotype in pugs. Methods: Results of genetic testing for the CFA12:2605517delC variant in European pugs between 2012 and 2020 were retrieved (n = 5,974). A validated questionnaire was mailed to all submitters of samples for further information on neurological signs, diagnostic tests, and disease course. Results: The allele frequency of the CFA12 NME risk variant was 25.7% in the European pug population dogs; 7.4% of the dogs were homozygous and 36.7% were heterozygous for the NME risk variant on CFA12. Completed questionnaires were available in 203 dogs including 25 dogs with epileptic seizures or other neurological signs. The clinical phenotype was consistent with NME in 3.9% with a median age of onset of 1.0 years, and indicative of idiopathic epilepsy in 2.9% with a median onset of 2.5 years. Eleven dogs remained unclassified. Pugs with the NME phenotype were significantly more frequently homozygous for the NME risk variant on CFA12 compared to pugs ≥6 years without neurological signs or seizures (p = 0.008). Discussion: The CFA12:2605517delC genetic risk variant is widely distributed in the European pug population and frequently homozygous in pugs with a NME phenotype. The data support the clinical relevance of the CFA12:2605517delC genetic risk variant.

A Case in which Eosinophilic Meningoencephalitis Occurred during Oral Corticosteroid Tapering and after Switching from Anti-IL-5 to Anti-IgE Treatment.

A 49-year-old man with severe eosinophilic asthma, sinusitis, and esophagitis was admitted with a sudden severe headache. The patient was diagnosed with eosinophilic meningoencephalitis based on frontotemporal abnormalities on brain magnetic resonance imaging and high eosinophil counts in the cerebrospinal fluid. His allergic-disease control levels were poor, requiring regular oral corticosteroid (OCS) use. He was switched from anti-interleukin (IL)-5 to anti-IgE therapy because of worsening urticaria and asthma symptoms during OCS tapering. We suspect this was a case of complex eosinophilic meningoencephalitis caused by the combination of OCS tapering and anti-IL-5 therapy cessation that acquired anti-IgE antibody sensitization based on positive drug-induced lymphocyte stimulation test results.

Curative effects and mechanisms of AG1296 and LY294002 co-therapy in Angiostrongylus cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis.

BACKGROUND: Co-therapy with albendazole and steroid is commonly used in patients with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis infections. However, anthelminthics often worsen symptoms, possibly due to the inflammatory reaction to antigens released by dying worms. Therefore, the present study was to investigate the curative effects and probable mechanisms of the platelet-derived growth factor receptor-beta (PDGFR-ß) inhibitor AG1296 (AG) and the phosphoinositide 3-kinase inhibitor (PI3K) LY294002 (LY) in A. cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis. METHODS: Western blots were used to detect matrix protein degradation and the expressions of PDGFR-ß/PI3K signaling pathway. The co-localization of PDGFR-ß and vascular smooth muscle cells (VSMCs), and metalloproteinase-9 (MMP-9) and VSMCs on the blood vessels were measured by confocal laser scanning immunofluorescence microscopy. Sandwich enzyme-linked immunosorbent assays were used to test S100B, interleukin (IL)-6, and transforming growth factor beta in the cerebrospinal fluid to determine their possible roles in mouse resistance to A. cantonensis. RESULTS: The results showed that AG and LY cotherapy decreased the MMP-9 activity and inflammatory reaction. Furthermore, S100B, IL-6 and eosinophil counts were reduced by inhibitor treatment. The localization of PDGFR-ß and MMP-9 was observed in VSMCs. Furthermore, we showed that the degradation of the neurovascular matrix and blood-brain barrier permeability were reduced in the mouse brain. CONCLUSIONS: These findings demonstrate the potential of PDGFR-ß inhibitor AG and PI3K inhibitor LY co-therapy as anti-A. cantonensis drug candidates through improved neurovascular unit dysfunction and reduced inflammatory response.

Chronic Cerebellar Meningoencephalitis in Adulthood: A Report of a Rare Case.

The development of meningoencephalitis is a result of an inflammation of the meninges and the brain, which can cause neurological sequelae. Cerebellar meningoencephalitis in adult patients is extremely rare and requires special diagnostic approaches. The aim of this report is to present a rare case of meningoencephalitis and evaluate the diagnostic and therapeutic techniques. We present a 45-year-old male patient who has entered the neurosurgery clinic with a severe headache lasting for a month. Neurological status determines intracranial hypertension. Magnetic resonance tomography (MRT) showed evidence of hyperintense lesions with homogenous enhancement in the right hemisphere of the cerebellum. The patient underwent a suboccipital paramedian craniotomy to excise the lesions and for the pathohistological examination of the biopsy material. Biopsy examination found sections expressing an infection process causing chronic meningoencephalitis in the right hemisphere of the cerebellum. The patient was treated postoperatively with cephalothin 2 g every 12 hours for 14 days. Follow-up examinations proved a relief of the symptoms. Meningoencephalitis of the cerebellum and the meninges is a complication that may occur in adulthood, and surgical excision, biopsy examination, and antibiotic therapy are promising methods for managing the disease.

Card9 Broadly Regulates Host Immunity against Experimental Pulmonary Cryptococcus neoformans 52D Infection.

The ubiquitous soil-associated fungus Cryptococcus neoformans causes pneumonia that may progress to fatal meningitis. Recognition of fungal cell walls by C-type lectin receptors (CLRs) has been shown to trigger the host immune response. Caspase recruitment domain-containing protein 9 (Card9) is an intracellular adaptor that is downstream of several CLRs. Experimental studies have implicated Card9 in host resistance against C. neoformans; however, the mechanisms that are associated with susceptibility to progressive infection are not well defined. To further characterize the role of Card9 in cryptococcal infection, Card9em1Sq mutant mice that lack exon 2 of the Card9 gene on the Balb/c genetic background were created using CRISPR-Cas9 genome editing technology and intratracheally infected with C. neoformans 52D. Card9em1Sq mice had significantly higher lung and brain fungal burdens and shorter survival after C. neoformans 52D infection. Susceptibility of Card9em1Sq mice was associated with lower pulmonary cytokine and chemokine production, as well as reduced numbers of CD4+ lymphocytes, neutrophils, monocytes, and dendritic cells in the lungs. Histological analysis and intracellular cytokine staining of CD4+ T cells demonstrated a Th2 pattern of immunity in Card9em1Sq mice. These findings demonstrate that Card9 broadly regulates the host inflammatory and immune response to experimental pulmonary infection with a moderately virulent strain of C. neoformans.

A practical guide to necropsy of the elasmobranch chondrocranium and causes of mortality in wild and aquarium-housed California elasmobranchs.

Elasmobranchs are common, iconic species in public aquaria; their wild counterparts are key members of marine ecosystems. Post-mortem examination is a critical tool for disease monitoring of wild elasmobranchs and for management of those under human care. Careful necropsy of the head, with a focus on clinically relevant anatomy, can ensure that proper samples are collected, increasing the chance of presumptive diagnoses prior to slower diagnostic workup. Immediate feedback from a thorough head necropsy allows for faster management decisions, often identifying pathogens, routes of pathogen entry, and pathogenesis, which are current shortcomings in published literature. This article proposes a protocol for necropsy of the elasmobranch chondrocranium, emphasizing unique anatomy and careful dissection, evaluation, and sampling of the endolymphatic pores and ducts, inner ears, brain, and olfactory system as part of a complete, whole-body necropsy. Extensive use of cytology and microbiology, along with thorough sample collection for histology and molecular biology, has proven effective in identifying a wide range of pathogens and assisting with characterization of pathogenesis. The cause of mortality is often identified from a head necropsy alone, but does not replace a thorough whole-body dissection. This protocol for necropsy and ancillary diagnostic sample collection and evaluation was developed and implemented in the necropsy of 189 wild and aquarium-housed elasmobranchs across 18 species over 13 years (2011-2023) in California. Using this chondrocranial approach, meningoencephalitis was determined to be the primary cause of mortality in 70% (118/168) of stranded wild and aquarium-housed elasmobranchs. Etiology was largely bacterial or protozoal. Carnobacterium maltaromaticum bacterial meningoencephalitis occurred in salmon sharks (Lamna ditropis), shortfin mako sharks (Isurus oxyrinchus), common thresher sharks (Alopias vulpinus), and one Pacific electric ray (Tetronarce californica). Miamiensis avidus was the most common cause of protozoal meningoencephalitis and found almost exclusively in leopard sharks (Triakis semifasciata) and bat rays (Myliobatis californica) that stranded in San Francisco Bay. Bacterial pathogens were found to use an endolymphatic route of entry, while protozoa entered via the nares and olfactory lamellae. Trauma was the second most common cause of mortality and responsible for 14% (24/168) of wild shark strandings and deaths of aquarium-housed animals.

Acute Meningoencephalitis Associated with Borrelia miyamotoi, Minnesota, USA.

Borrelia miyamotoi is an emerging tickborne pathogen that has been associated with central nervous system infections in immunocompromised patients, albeit infrequently. We describe a case-patient in Minnesota, USA, who had meningeal symptoms of 1 month duration. B. miyamotoi infection was diagnosed by Gram staining on cerebrospinal fluid and confirmed by sequencing.

A rare case report of meningoencephalitis caused by Streptococcus porcinus.

Acute pyogenic meningitis is a medical emergency. Bacteria are the major causative agents of pyogenic meningitis with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis being the most common. Here, we describe a case of bacterial meningoencephalitis caused by Streptococcus porcinus. To our knowledge this is the first case described in literature. The patient was treated with ceftriaxone and supportive treatment.

IL-33 Enhances the Total Production of IgG, IgG1, and IgG3 in Angiostrongylus cantonensis-Infected Mice.

The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching. In our experiment, C57BL/6 mice were each infected with 35 infectious larvae and were divided into groups that received an intraperitoneal injection of IL-33, anti-IL-33 monoclonal antibody (mAb), or anti-ST2 mAb 3 days post-infection (dpi) and were subsequently administered booster shots at 5-day intervals with the same dose. Serum samples from each group were collected weekly for ELISA assays. The levels of total IgG, IgG1, and IgG3 were significantly increased in A. cantonensis-infected mice that were treated with IL-33, and the levels decreased significantly in infected groups treated with anti-IL-33 or anti-ST2 mAb. These results suggest that IL-33 may play a critical role in the pathogenesis of human angiostrongyliasis and could be useful for understanding protective immunity against this parasitic infection.

Successful Management of Acute Streptococcal Meningoencephalitis Complicated by Bilateral Third-Nerve Palsies, Wall-Eyed Bilateral Internuclear Ophthalmoplegia, Blindness, and Deafness: Case Report.

Introduction: Streptococcal meningoencephalitis (SME) is a rare, and frequently lethal, acute infection, and inflammation of the central nervous system parenchyma, with associated meningeal involvement. Bacterial meningoencephalitis is generally associated with high rates of morbidity and mortality, despite available antimicrobial and corticosteroid treatments. While Streptococcus pneumoniae is well recognised to cause bacterial meningitis, direct extension into the central nervous system parenchyma is rare. Case Presentation: A previously well 49-year-old man presented with sudden onset severe headache, fevers, neck stiffness, and reduced consciousness. The manifestations of SME in this patient were bilateral pupil-involving third-nerve palsies, wall-eyed bilateral internuclear ophthalmoplegia (WEBINO), bilateral blindness, bilateral deafness, a right lower motor neuron facial palsy, and upper motor neuron signs in his limbs. Initially, a partial response to high dose intravenous antibiotics occurred, but with administration of intravenous corticosteroids, further substantial resolution of the patient's neurological and neuro-ophthalmological deficits occurred. Conclusion: This case highlights the benefit of multidisciplinary diagnostic and therapeutic interventions in a case of SME complicated by bilateral pupil-involving third-nerve palsies, WEBINO, bilateral blindness, bilateral deafness, a right lower motor neuron facial palsy, and upper motor neuron signs. It appears to be the first reported case of SME with this rare collection of neuro-ophthalmological abnormalities.

Exploring the extrachromosomal plasmid rDNA of Naegleria fowleri AY27 genotype II: A human brain-eating amoeba via high-throughput sequencing.

Naegleria fowleri, also known as brain-earing amoeba, causes severe and rapidly fatal CNS infection in humans called primary amebic meningoencephalitis (PAM). The DNA from the N. fowleri clinical isolate was sequenced for circular extrachromosomal ribosomal DNA (CERE - rDNA). The CERE contains 18 S, 5.8 S, and 28 S ribosomal subunits separated by internal transcribed spacers, 5 open reading frames (ORFs), and mostly repeat elements comprising 7268 bp out of 15,786 bp (46%). A wide variety of variations and recombination events were observed. Finally, the ORFs that comprised only 4 hypothetical proteins were modeled and screened against Zinc drug-like compounds. Two compounds [ZINC77564275 (ethyl 2-(((4-isopropyl-4 H-1,2,4-triazol-3-yl) methyl) (methyl)amino) oxazole-4-carboxylate) and ZINC15022129 (5-(2-methoxyphenoxy)-[2,2'-bipyrimidine]-4,6(1 H,5 H)-dione)] were finalized as potential druggable compounds based on ADME toxicity analysis. We propose that the compounds showing the least toxicity would be potential drug candidates after laboratory experimental validation is performed.

Clinical Spectrum and Epidemiology of Human Parechovirus Infections in Infants: A Retrospective Study in the Western Part of Sweden.

Background: Human parechovirus (HPeV) infections can cause sepsis and meningoencephalitis in infants. To improve our knowledge of the consequences of HPeV infections in young children, the incidence, clinical spectrum, and short-term outcome among infants infected with HPeV were investigated retrospectively. Methods: The presence of HPeV RNA was investigated by polymerase chain reaction in cerebrospinal fluid from 327 children aged 0 to 12 months sampled between 2014 and 2017. Eighty-one were infected with HPeV and included in the study. These infants were divided into 3 groups based on clinical assessment: HPeV was the presumed cause of disease (n = 35); HPeV could have contributed to or been considered the cause of disease (n = 24); and HPeV was not considered the cause of disease (n = 22). Results: Infection with HPeV type 3 was common in all groups (n = 54), and most children were younger than 3 months (n = 63). The children in the first group (HPeV as presumed cause) had meningoencephalitis (n = 20), viral sepsis (n = 9), or non-severe viral infection (n = 6). The youngest were more prone to develop meningoencephalitis, while the slightly older children had symptoms of viral sepsis or nonsevere viral infection (P < .05). Eleven had symptom onset within 2 days after birth. Two infants diagnosed with sudden infant death syndrome were HPeV infected when tested postmortem. Conclusions: HPeV infections were identified in 25% of children with suspected central nervous system infection. The clinical presentation of those infected with HPeV varied with age. HPeV infections may be associated with sudden infant death syndrome, although this is not well studied. The results suggest that HPeV infections may be underdiagnosed in young infants.

Exploring therapeutic approaches against Naegleria fowleri infections through the COVID box.

Naegleria fowleri, known as the brain-eating amoeba, is the pathogen that causes the primary amoebic meningoencephalitis (PAM), a severe neurodegenerative disease with a fatality rate exceeding 95%. Moreover, PAM cases commonly involved previous activities in warm freshwater bodies that allow amoebae-containing water through the nasal passages. Hence, awareness among healthcare professionals and the general public are the key to contribute to a higher and faster number of diagnoses worldwide. Current treatment options for PAM, such as amphotericin B and miltefosine, are limited by potential cytotoxic effects. In this context, the repurposing of existing compounds has emerged as a promising strategy. In this study, the evaluation of the COVID Box which contains 160 compounds demonstrated significant in vitro amoebicidal activity against two type strains of N. fowleri. From these compounds, terconazole, clemastine, ABT-239 and PD-144418 showed a higher selectivity against the parasite compared to the remaining products. In addition, programmed cell death assays were conducted with these four compounds, unveiling compatible metabolic events in treated amoebae. These compounds exhibited chromatin condensation and alterations in cell membrane permeability, indicating their potential to induce programmed cell death. Assessment of mitochondrial membrane potential disruption and a significant reduction in ATP production emphasized the impact of these compounds on the mitochondria, with the identification of increased ROS production underscoring their potential as effective treatment options. This study emphasizes the potential of the mentioned COVID Box compounds against N. fowleri, providing a path for enhanced PAM therapies.