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Frontiers in Public Health 2023The outbreak of in Pakistan presents a significant public health concern due to its high fatality rate and limited treatment options. This review explores the impact of... (Review)
Review
The outbreak of in Pakistan presents a significant public health concern due to its high fatality rate and limited treatment options. This review explores the impact of the outbreak on communities and the challenges faced in combating the disease. It evaluates available treatment options and highlights the need for early diagnosis and intervention. The study proposes recommendations to improve public health preparedness, including public awareness campaigns, enhanced healthcare infrastructure, and robust water surveillance systems. Collaboration between research institutions and public health organizations is emphasized to develop effective outbreak response strategies.
Topics: Humans; Naegleria fowleri; Pakistan; Central Nervous System Protozoal Infections; Water; Disease Outbreaks
PubMed: 37927850
DOI: 10.3389/fpubh.2023.1266400 -
Molecules (Basel, Switzerland) Feb 2024Systemic lupus erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect any organ in the body, including the neurological system. Multiple... (Review)
Review
Systemic lupus erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect any organ in the body, including the neurological system. Multiple factors, such as environmental (infections), genetic (many HLA alleles including DR2 and DR3, and genes including C4), and immunological influences on self-antigens, such as nuclear antigens, lead to the formation of multiple autoantibodies that cause deleterious damage to bodily tissues and organs. The production of autoantibodies, such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of this disease. This autoimmune disease results from a failure of the mechanisms responsible for maintaining self-tolerance in T cells, B cells, or both. Immune complexes, circulating antibodies, cytokines, and autoreactive T lymphocytes are responsible for tissue injury in this autoimmune disease. The diagnosis of SLE is a rheumatological challenge despite the availability of clinical criteria. NPSLE was previously referred to as lupus cerebritis or lupus sclerosis. However, these terms are no longer recommended because there is no definitive pathological cause for the neuropsychiatric manifestations of SLE. Currently, the treatment options are primarily based on symptomatic presentations. These include the use of antipsychotics, antidepressants, and anxiolytic medications for the treatment of psychiatric and mood disorders. Antiepileptic drugs to treat seizures, and immunosuppressants (e.g., corticosteroids, azathioprine, and mycophenolate mofetil), are directed against inflammatory responses along with non-pharmacological interventions.
Topics: Humans; Lupus Vasculitis, Central Nervous System; Lupus Erythematosus, Systemic; Autoantibodies; Immunosuppressive Agents; Seizures
PubMed: 38398500
DOI: 10.3390/molecules29040747 -
Brain and Behavior Nov 2023We have commonly observed prominent cerebral veins on susceptibility-weighted angiography (SWAN) in acute meningoencephalitis. This study aimed to investigate the...
BACKGROUND AND PURPOSE
We have commonly observed prominent cerebral veins on susceptibility-weighted angiography (SWAN) in acute meningoencephalitis. This study aimed to investigate the clinical significance of these findings.
METHODS
Cerebral veins on SWAN of 98 patients with acute meningoencephalitis diagnosed from February 2016 through October 2020 were classified into three groups according to the degree of venous prominence (mild, 23; moderate, 53; and prominent, 22). Clinical variables and laboratory findings were compared between these groups. The influence of variables on the prediction of prominent cerebral veins was measured by random forest (RF) and gradient boosting machine (GBM).
RESULTS
As cerebral veins became more prominent, cerebrospinal fluid (CSF) glucose level decreased (69.61 ± 29.05 vs. 59.72 ± 22.57 vs. 48.36 ± 20.29 mg/dL, p = .01) and CSF protein level increased (100.73 ± 82.98 vs. 104.73 ± 70.99 vs. 159.12 ± 118.15 mg/dL, p = .03). The etiology of meningoencephalitis, neurological symptoms, and increased intracranial pressure (ICP) signs differed between groups (p < .05). RF and GBM demonstrated that CSF protein level was the variable with the highest power to predict the prominent cerebral vein (mean decrease in node impurity: 4.19, relative influence: 50.66).
CONCLUSION
The presence of prominent cerebral veins on SWAN in acute meningoencephalitis was significantly associated with a low CSF glucose level and a high CSF protein level, as well as ICP. Thus, the visual grade of the cerebral veins on SWAN may be utilized for the management of patients with acute meningoencephalitis.
Topics: Humans; Cerebral Veins; Magnetic Resonance Angiography; Intracranial Hypertension; Meningoencephalitis; Glucose
PubMed: 37721542
DOI: 10.1002/brb3.3255 -
Journal of Cellular and Molecular... Apr 2024Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus...
Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus (NPSLE). Microglial activation is observed in NPSLE patients. However, the mechanisms regulating microglia-mediated neurotoxicity in NPSLE remain elusive. Here, we showed that M1-like proinflammatory cytokine levels were increased in the cerebrospinal fluid (CSF) of SLE patients, especially those with neuropsychiatric symptoms. We also demonstrated that MRL/lpr lupus mice developed anxiety-like behaviours and cognitive deficits in the early and active phases of lupus, respectively. An increase in microglial number was associated with upregulation of proinflammatory cytokines in the MRL/lpr mouse brain. RNA sequencing revealed that genes associated with phagocytosis and M1 polarization were upregulated in microglia from lupus mice. Functionally, activated microglia induced synaptic stripping in vivo and promoted neuronal death in vitro. Finally, tofacitinib ameliorated neuropsychiatric disorders in MRL/lpr mice, as evidenced by reductions in microglial number and synaptic/neuronal loss and alleviation of behavioural abnormalities. Thus, our results indicated that classically activated (M1) microglia play a crucial role in NPSLE pathogenesis. Minocycline and tofacitinib were found to alleviate NPSLE by inhibiting micrglial activation, providing a promising therapeutic strategy.
Topics: Humans; Mice; Animals; Microglia; Lupus Vasculitis, Central Nervous System; Depression; Mice, Inbred MRL lpr; Brain; Lupus Erythematosus, Systemic; Cytokines
PubMed: 38494844
DOI: 10.1111/jcmm.18190 -
Cytokine Oct 2023Bacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by...
BACKGROUND
Bacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections. We aimed to examine correlations of interleukin (IL)-6, IL-8, IL-10, IL-12(p40), and tumor necrosis factor (TNF)-α levels with disease severity, complications, and outcome in patients with acute bacterial meningitis.
METHODS
The study involved 30 patients with bacterial meningitis/meningoencephalitis admitted to the University Hospital St. George, Plovdiv over a period of 4 years. Patients were selected based on clinical presentation and laboratory abnormalities, consistent with a neuroinfection. Enzyme-linked immunosorbent assay was used to measure the studied cytokines in both cerebrospinal fluid (CSF) and serum in parallel. For microbiological diagnosis multiplex, polymerase chain reaction, and CSF culture were used.
RESULTS
In patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum. CSF TNF-α, CSF IL-8, and CSF IL-10 had a moderate negative correlation to CSF glucose. It was found that serum IL-8 is significantly elevated in patients who experienced neurological complications, have severe clinical course, and in deceased patients. CSF IL-10 is increased only in patients with severe acute bacterial meningitis.
CONCLUSION
Among patients with acute bacterial meningitis serum IL-8 could delineate these with increased risk of neurological complications, severe clinical course, and fatal outcome. Serum IL-8 and CSF IL-10 could be used as indicators of disease severity.
Topics: Humans; Interleukin-10; Tumor Necrosis Factor-alpha; Interleukin-8; Meningitis, Bacterial; Cytokines; Interleukin-6; Nervous System Diseases; Disease Progression
PubMed: 37544134
DOI: 10.1016/j.cyto.2023.156315 -
Infection Feb 2024We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN)...
PURPOSE
We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN) results, as well as the predictive values of the technique, regarding the cerebrospinal fluid (CSF) characteristics.
METHODS
FA is a multiplex real-time PCR detecting 14 of the most common ME pathogens in CSF. All FA performed at our hospital (2018-2022) were retrospectively reviewed. FA was compared to conventional techniques and its performance was assessed based on the final diagnosis of the episode.
RESULTS
FA was performed in 313 patients with suspicion of ME. Most patients had altered mental status (65.2%) and fever (61%). Regarding CSF characteristics, 49.8% and 53.7% presented high CSF proteins and pleocytosis, respectively. There were 84 (26.8%) positive FA results, mainly for HSV-1 (10.9%), VZV (5.1%), Enterovirus (2.6%), and S. pneumoniae (1.9%). In the 136 cases where both FA and routine methods were performed, there was a 25.7% lack of agreement. We identified 6.6% FN results, but 28.6% FP, mainly due to HSV-1. This resulted in a high negative predictive value (NPV) of 93.4%, but a positive predictive value (PPV) of 73%. Remarkably, PPV as low as 36.9%, and 70.2%, were found in cases without pleocytosis, or lack of high CSF protein levels, respectively.
CONCLUSION
FA was associated with high NPV, but frequent FP results and low PPV, particularly for HSV-1, and especially in patients without high CSF protein levels or pleocytosis.
Topics: Humans; Meningitis; Encephalitis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Leukocytosis; Meningoencephalitis; Multiplex Polymerase Chain Reaction
PubMed: 37515691
DOI: 10.1007/s15010-023-02076-x -
Neurology(R) Neuroimmunology &... Sep 2023The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple...
OBJECTIVES
The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS).
METHODS
This is a case series study.
RESULTS
In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies.
DISCUSSION
Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.
Topics: Humans; Female; Male; West Nile Fever; West Nile virus; Multiple Sclerosis; Antibodies, Viral; Immunoglobulin M
PubMed: 37562975
DOI: 10.1212/NXI.0000000000200154 -
Emerging Microbes & Infections Dec 2023Avian influenza H5N1 is a highly pathogenic virus that primarily affects birds. However, it can also infect other animal species, including mammals. We report the...
Avian influenza H5N1 is a highly pathogenic virus that primarily affects birds. However, it can also infect other animal species, including mammals. We report the infection of nine juvenile red foxes () with Highly Pathogenic Avian Influenza A type H5N1 (Clade 2.3.4.4b) in the spring of 2022 in the central, western, and northern regions of New York, USA. The foxes displayed neurologic signs, and examination of brain and lung tissue revealed lesions, with brain lesions ranging from moderate to severe meningoencephalitis. Analysis of tissue tropism using RT-PCR methods showed a comparatively lower Ct value in the brain, which was confirmed by hybridization targeting Influenza A RNA. The viral RNA labelling was highly clustered and overlapped the brain lesions, observed in neurons, and grey matter. Whole viral genome sequences obtained from the affected foxes were subjected to phylogenetic and mutation analysis to determine influenza A clade, host specificity, and potential occurrence of viral reassortment. Infections in red foxes likely occurred due to preying on infected wild birds and are unlikely due to transmission between foxes or other mammals.
Topics: Animals; Humans; Influenza in Birds; Foxes; Influenza, Human; Influenza A Virus, H5N1 Subtype; Tissue Distribution; Phylogeny
PubMed: 37589241
DOI: 10.1080/22221751.2023.2249554 -
Cureus May 2024The development of meningoencephalitis is a result of an inflammation of the meninges and the brain, which can cause neurological sequelae. Cerebellar...
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.
PubMed: 38846185
DOI: 10.7759/cureus.59782 -
Journal of Veterinary Internal Medicine 2023Although idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT).
BACKGROUND
Although idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT).
HYPOTHESIS/OBJECTIVES
Describe semiology, magnetic resonance imaging (MRI) findings and outcome of dogs with IEHT or SEHT. We hypothesized that structural lesions affecting the middle cranial fossa or mesencephalic aqueduct could lead to SEHT.
ANIMALS
One hundred dogs with IEHT (n = 71) or SEHT (n = 29).
METHODS
Retrospective, multicenter, study of dogs with episodic (nonintentional) head tremor and brain MRI between 2004 and 2022.
RESULTS
Lesions on MRI in SEHT dogs were localized to the middle cranial fossa (15/29), cerebrocortex (3/29), brainstem (2/29), fourth ventricle (1/29) or multifocal (8/29) with thalamus involvement (6/8). Secondary compression of the mesencephalic aqueduct (19/29), third ventricle or interthalamic adhesion or both (14/29) was common. The most common underlying condition in dogs with SEHT was a pituitary mass. Dogs with SEHT were older, had additional neurological signs and were more likely to be euthanized after diagnosis (P < .001 for all) compared to IEHT dogs. Two SEHT dogs had only tremor. In IEHT dogs, 8/10 owners reported that the tremor decreased or abated over time (range, 106-2315 days) without treatment. Tremor remission occurred in SEHT dogs treated for underlying meningoencephalitis.
CONCLUSIONS AND CLINICAL IMPORTANCE
Presence of additional neurological signs and older age may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these. An intracranial structural abnormality cannot be excluded in dogs with normal neurological examination.
Topics: Dogs; Animals; Tremor; Retrospective Studies; Third Ventricle; Brain; Head; Magnetic Resonance Imaging; Dog Diseases
PubMed: 37850712
DOI: 10.1111/jvim.16880