Neurological Conundrum: A Case of Cerebellar Hemispheric Enlargement and Atypical Symptoms.

Cerebellar hemispheric enlargement with atypical neurological symptoms poses diagnostic challenges in clinical practice. We present the case of a 57-year-old female with persistent headache, left facial paraesthesia, dysarthria, gait ataxia, and longstanding neck swelling. Imaging studies revealed enlargement of the left cerebellar hemisphere with associated mass effect and compression of adjacent structures. The underlying etiology remained uncertain despite extensive evaluation, including magnetic resonance imaging and angiography. Differential diagnoses included neoplastic, vascular, inflammatory, and metabolic etiologies, but none fully accounted for the clinical findings. Management strategies focused on symptomatic relief and close monitoring. This case underscores the complexity of diagnosing and managing patients with rare neurological manifestations and highlights the need for continued research and collaborative approaches in optimising patient care.

A Case of MRI-Negative Leptomeningeal Disease From Non-small Cell Lung Cancer.

Leptomeningeal disease (LMD) is a rare complication of advanced non-small cell lung cancer (NSCLC), associated with a poor prognosis. We report the case of a 55-year-old man, who presented with a metastatic NSCLC with limited brain and abdominal metastases. He was treated with both chemoimmunotherapy and stereotactic radiotherapy (SRT) to the brain. Despite treatment, the patient experienced progressive neurological symptoms not in keeping with the extent of disease seen on imaging of the brain. Due to this incongruence between symptoms and radiologic findings, he underwent a lumbar puncture, which had positive cytology for LMD. He had a rapid progression of symptoms and died six days after the discovery of LMD. We review the available literature regarding the prevalence of MRI-negative LMD from a solid primary malignancy.

Increased MCHC*RDW-SD interaction values: indicators of neurological impairment in lead-poisoned children.

Background: The neurotoxic effects of lead in children can have long-lasting and profound impacts on the developing nervous system. This study aimed to identify a reliable and easily accessible biomarker to monitor neurological impairment in lead-poisoned children. Methods: We analyzed hematological data from 356 lead-poisoned children, comparing them with age and gender-matched healthy controls. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were employed to identify and evaluate potential biomarkers for neurological damage. Results: Significant changes in erythrocyte parameters were observed in lead-poisoned children. Upon further analysis, increased mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD) interaction values were found to be significantly associated with neurological impairment. The MCHC*RDW-SD interaction model demonstrated an AUC of 0.76, indicating its effectiveness in reflecting neurological damage. Additionally, the MCHC*RDW-SD Interaction value showed weak or no correlation with other erythrocyte parameters, suggesting its independence as an indicator. Conclusion: Our findings propose the increased MCHC*RDW-SD interaction value as a robust and independent biomarker for detecting neurological impairment in lead-poisoned children. This underscores the potential of utilizing specific erythrocyte parameters for screening the neurotoxic effects of lead exposure in pediatric populations.

Forensic assessment of somatoform and functional neurological disorders.

Functional neurological disorders (FND) and somatization are common in clinical practice and medicolegal settings. These conditions are frequently disabling and, if arising following an accident, may lead to claims for legal compensation or occupational disability (such as social security disability insurance). However, distinguishing FND and somatization from symptoms that are intentionally produced (i.e., malingered or factitious) may pose a major forensic psychiatric challenge. In this article, we describe how somatoform disorders and FND lie along a spectrum of abnormal illness-related behaviors, including factitious disorder, compensation neurosis, and malingering. We provide a systematic approach to the forensic assessment of FND and conclude by describing common litigation scenarios in which FND may be at issue. Forensic testimony may play an important role in the resolution of such cases.

A case of Parkinsonian symptoms secondary to chronic subdural hematoma.

Chronic subdural hematoma is a known neurosurgical entity often associated with a spectrum of neurological manifestations. While primarily recognized for its characteristic accumulation of blood between the dura mater and arachnoid membrane, emerging literature suggests a rare association between chronic subdural hematoma and Parkinsonian symptoms. This report aims to underscore this unique neurological relationship by presenting a case of a 70-year-old male who developed Parkinsonism following chronic subdural hematoma post-head trauma. This case underscores the rare association between chronic subdural hematoma and Parkinsonian symptoms, emphasizing the importance of timely diagnosis and intervention in managing such cases.

Unraveling Neurological Shades: Vitamin D Toxication and Central Pontine Myelinolysis Exposed.

This case report is about a middle-aged female who presented with complaints of pain in the abdomen with intractable vomiting for three months, pain and weakness in bilateral lower limbs for two months, and irritability for three days. She was previously treated for lumbar disc bulge and severe narrowing of the spinal cord whose treatment also included vitamin D supplements. After taking high doses of a vitamin D supplement daily for approximately four months, it resulted in vitamin D toxicity. The sodium level of the patient was in the normal range throughout the treatment. Her magnetic resonance imaging brain revealed features of central pontine myelinolysis. The development of central pontine myelinolysis due to vitamin D toxicity, with normal sodium levels, makes this a rare case for discussion.

A new perspective on positive symptoms: expression of damage or self-defence mechanism of the brain?

Usually, positive neurological symptoms are considered as the consequence of a mere, afinalistic and abnormal increase in function of specific brain areas. However, according to the Theory of Active Inference, which argues that action and perception constitute a loop that updates expectations according to a Bayesian model, the brain is rather an explorer that formulates hypotheses and tests them to assess the correspondence between internal models and reality. Moreover, the cerebral cortex is characterised by a continuous "conflict" between different brain areas, which constantly attempt to expand in order to acquire more of the limited available computational resources, by means of their dopamine-induced neuroplasticity. Thus, it has recently been suggested that dreams, during rapid eye movement sleep (REMS), protect visual brain areas (deprived of their stimuli during rest) from being conquered by other normally stimulated ones. It is therefore conceivable that positive symptoms also have a functional importance for the brain. We evaluate supporting literature data of a 'defensive' role of positive symptoms and the relevance of dopamine-induced neuroplasticity in the context of neurodegenerative and psychiatric diseases. Furthermore, the possible functional significance of idiopathic REMS-related behavioural disorder as well as phantom limb syndrome is examined. We suggest that positive neurological symptoms are not merely a passive expression of a damage, but active efforts, related to dopamine-induced plasticity, to maintain a correct relationship between the external world and its brain representation, thus preventing healthy cortical areas from ousting injured ones.

Superinfected COVID-19 in a young patient with posterior reversible encephalopathy syndrome: A case report.

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with central nervous system (CNS) symptoms usually related to autoregulatory cerebral failure and high blood pressure. Neuroimaging is critical to diagnosis. Neurological presentations of COVID-19 disease are categorized into CNS symptoms and peripheral nervous system (PNS) symptoms. The patient was a 15-year-old female with SARS-CoV-2 pneumonia who developed PRES with a typical clinical and radiological appearance. She was treated with dexamethasone, phenytoin, sodium valproate and remdesivir. The patient was discharged after recovery of symptoms and was in good general condition. It is recommended that in patients affected by COVID-19 with neurological symptoms, the PRES can be considered in the differential diagnosis.

Late-onset Myoclonic Seizure in a 78-year-old Woman with Gaucher Disease.

We herein report a 78-year-old woman with Gaucher disease (GD) who was initially diagnosed with GD type 1, had been receiving long-term enzyme replacement therapy since 58 years old, and developed neurological manifestations in her 70s. The neurological manifestations included myoclonic seizures and progressive cognitive decline. Although it is rare for GD patients to first develop neurologic manifestations at such an advanced age, physicians engaged in long-term care for GD patients should be alert for this possibility.

eHealth tools to assess the neurological function for research, in absence of the neurologist - a systematic review, part I (software).

BACKGROUND: Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. METHODS: Four search engines (PubMed, Web of Science, Scopus & EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. FINDINGS: A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. INTERPRETATION: The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. FUNDING: The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired.

Extracellular vesicles in plasma and cerebrospinal fluid in patients with COVID-19 and neurological symptoms.

INTRODUCTION: Increased levels of extracellular vesicles (EVs) are associated with haemostatic disturbances in various clinical settings. However, their role in COVID-19 patients is still not fully clear. In the present study we investigated EVs in plasma from patients with COVID-19 and neurological symptoms in relation to the activation of coagulation. METHODS: Nineteen COVID-19 patients with neurological symptoms and twenty-three aged-matched healthy individuals were included. Global coagulation assays were performed and levels of EVs were determined by flow-cytometry in plasma and cerebrospinal fluid (CSF). RESULTS: A procoagulant state characterized by significantly increased overall coagulation- (OCP) and overall haemostatic potential (OHP), diminished overall fibrinolytic potential (OFP) together with a denser fibrin structure was found in patients with COVID-19. Flow cytometry revealed elevated levels of plasma circulating EVs derived from neutrophils (MPO+) and platelets (CD61+), as well as EVs expressing phosphatidylserine (PS+) and complement component C5b-9 (TCC+) in patients with COVID-19 compared with controls. The concentrations of PS+, CD61+ and TCC+ EVs were positively correlated with OCP and OHP in COVID-19 patients. Moreover, we identified CD61+, MPO+ and endothelial cell-derived EVs, as well as EVs exposing PS and TCC in the CSF of patients suffering from neurological symptoms during COVID-19. CONCLUSION: The unique finding in this study was the presence of EVs in the CSF of COVID-19 patients with neurologic manifestations as well as higher expression of complement protein on circulating plasma EVs. EVs may indicate blood-brain barrier damage during SARS-COV-2 infection.

Encephalopathy in hospitalized patients with Coronavirus disease 2019: A single-center study

Objective@#This study aimed to determine the incidence of encephalopathy among hospitalized patients with COVID-19. @*Methods@#This was a retrospective observational study conducted in a tertiary hospital in Cebu City, Philippines. This study is a complete enumeration of all records of adult patients admitted for COVID-19 detected through polymerase chain reaction from March 1, 2020 to September 30, 2021. The cases were then classified as to the presence or absence of encephalopathy. @*Results@#The study determined that 6 in every 1000 admitted COVID-19 patients developed encephalopathy. The clinico-demographic profile of patients with encephalopathy were mostly elderly with a mean age of 67, males (55.7%), and obese stage I (61.1%). Encephalopathy was more likely to develop in patients with type 2 diabetes mellitus (80.1%) and coronary artery disease (40.0%). Most patients who did not have encephalopathy however had a history of CVD. Most patients (66.7%) who developed encephalopathy were dyspneic on presentation. Laboratory examination results showed an increase in fasting blood sugar and elevated levels of LDH, CRP, serum ferritin, procalcitonin, and D-dimer. Majority of patients (66.7%) with encephalopathy were intubated. Taking into consideration the stage of infection and the incidence of encephalopathy, most patients (66.6%) were in the hyperinflammatory stage. The number of hospitalization days and severity of illness did not have any association with developing encephalopathy. Dichotomous categorization of outcomes into deceased and discharged showed that clinical outcomes and the development of encephalopathy were significantly associated, with 66.7% of patients with encephalopathy expiring during their course of hospitalization.@*Conclusion@#The incidence of encephalopathy among admitted COVID-19 patients was 6 in every 1000 patients. Encephalopathy was more common in elderly males who were obese with type 2 diabetes mellitus and coronary artery disease. The most common presentation of patients who developed encephalopathy was dyspnea. Collated laboratory results showed an increase in fasting blood sugar and elevated levels of LDH, CRP, serum ferritin, procalcitonin, and D-dimer. Majority of patients with encephalopathy were intubated and were in the hyperinflammatory stage of COVID-19 infection. Dichotomous categorization of outcomes into deceased and discharged showed that clinical outcomes and the development of encephalopathy were significantly associated, with most patients with encephalopathy expiring during their course of hospitalization.

Association of SARS-CoV-2 infection with neurological impairments in pediatric population: A systematic review.

Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged <18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. A total of 843 no-duplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6985 individuals were included, where 12.8% (n = 892) of hospitalized patients experienced neurocognitive impairments which includes: 1) neurological symptoms (n = 294 of 892, 33.0%), 2) neurological syndromes and neuroimaging abnormalities (n = 223 of 892, 25.0%), and 3) other phenomena (n = 233 of 892, 26.1%). Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

Identification of Prototheca from the Cerebrospinal Fluid of a Cat with Neurological Signs.

Prototheca infections are rare in cats, and they are usually associated with cutaneous or subcutaneous infections by P. wickerhamii, with no evidence of neurological signs or systemic disease. In this study, we report the identification of prototheca in the cerebrospinal fluid (CSF) of a cat with neurological symptoms. Fourteen CSF samples were gathered from cats presented with neurological disease between 2012 and 2014. The inclusion criteria for the samples were an increase in CSF protein and cell number (pleocytosis), suggestive of an infectious inflammatory status of the central nervous system (CNS). Nine samples fulfilled the inclusion criteria (inflammatory samples), while five samples, used as control, did not (non-inflammatory samples). All the samples were screened molecularly for different pathogens associated with CNS disease in cats, including prototheca. Out of 14 CSF samples, only one inflammatory sample tested positive for prototheca. Upon sequence and phylogenetic analysis of the amplicon, the strain was characterized as P. bovis. This report is the first documented evidence of prototheca in the cerebrospinal fluid of a cat with neurological signs. Prototheca should be considered in the diagnostics procedures on the CNS of cats presented with infectious diseases.

Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) for non-epileptic seizures: a consecutive case series.

BACKGROUND: Research has demonstrated that implementation of Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) achieved full symptom remission in 93% of people with Functional Neurological Symptoms Disorder (FNSD), most of them exhibiting motor symptoms. The basis for NH-CBT is consistent with a predictive coding aetiological model of FNSD. This idea is transparently shared with people with FNSD in the form of telling them that their symptoms are caused by a nocebo effect, usually followed by some physical activity that aims to change the person's belief about their body. AIMS: To demonstrate that a version of NH-CBT can also be effective in eliminating or reducing non-epileptic seizures (assumed to be a sub-type of FNSD). METHOD: A consecutive case series design was employed. Participants were treated with NH-CBT over a 12-week period. The primary outcome measure was seizure frequency. Numerous secondary measures were employed, as well as a brief qualitative interview to explore participants' subjective experience of treatment. RESULTS: Seven out of the 10 participants became seizure free at least 2 weeks before their post-treatment assessment, and all stayed seizure-free for at least 5 months. Six of those seven remained seizure free at 6-month follow-up. There were large positive effect sizes for the majority of secondary measures assessed. CONCLUSIONS: This case series provides evidence of feasibility and likely utility of NH-CBT in reducing the frequency of non-epileptic seizures.

[Subtle and subclinical neurological findings in patients with SARS-CoV-2]. / Hallazgos sutiles y subclínicos neurológicos en pacientes con SARS-CoV-2.

Background: There are severe neurological conditions in patients with COVID-19, such as: cerebrovascular disease, Guillain-Barré syndrome, encephalitis, acute hemorrhagic necrotizing encephalopathy and myelitis. Objective: We describe that the patient with SARS-CoV 2 with respiratory symptoms has subtle or subclinical neurological manifestations. Material and methods: Observational, cross-sectional, analytical study, which included patients aged 18-65 years with respiratory symptoms and a confirmed diagnosis of COVID-19. Intubated patients with chronic neurodegenerative diseases or pre-existing neurological compromise were excluded. Semiology of the headache and neurological examination were performed; Serum levels of glucose, protein, electrolytes, lactate, C-reactive protein, lactic dehydrogenase, and D-dimer were measured. Cerebrospinal fluid (CSF) analysis and electroencephalogram (EEG) were also performed in patients who accepted the risks. Results: A high prevalence of subtle neurological manifestations was found in patients with COVID-19 with only a respiratory clinical picture. Headache, anosmia, dysgeusia, and hypopalesthesia predominated in the early stages, with frequent abnormal findings in the CSF (>70%) and less frequently in the EEG (<20%). Conclusions: Headache, anosmia, dysgeusia and hypoesthesia were frequent at the beginning of the infection, together with abnormal findings in CSF and EEG, without other neurological symptoms or neurological disease.

Introducción: existen condiciones neurológicas severas en pacientes con COVID-19, como: enfermedad cerebrovascular, síndrome de Guillain-Barré, encefalitis, encefalopatía necrotizante hemorrágica aguda y mielitis. Objetivo: describimos que el paciente con SARS-CoV-2 con síntomas respiratorios tiene manifestaciones neurológicas sutiles o subclínicas. Material y métodos: estudio observacional, transversal, analítico, que incluyó pacientes de 18-65 años con síntomas respiratorios y diagnóstico de COVID-19 confirmado. Se excluyeron pacientes intubados, con enfermedades neurodegenerativas crónicas o compromiso neurológico preexistente. Se realizó semiología de la cefalea y exploración neurológica; Se midieron los niveles séricos de glucosa, proteínas, electrolitos, lactato, proteína C reactiva, deshidrogenasa láctica y dímero D. También se realizaron análisis de líquido cefalorraquídeo (LCR) y un electroencefalograma (EEG) en los pacientes que aceptaron los riesgos. Resultados: se encontró alta prevalencia de manifestaciones neurológicas sutiles en pacientes con COVID-19 con solo cuadro clínico respiratorio. Cefalea, anosmia, disgeusia e hipopalestesia predominaron en las primeras etapas, con hallazgos anormales frecuentes en el LCR (>70%) y con menos frecuencia en el EEG (<20%). Conclusiones: la cefalea, anosmia, disgeusia e hipoestesia fueron frecuentes al inicio de la infección, junto con hallazgos anormales en LCR y EEG, sin otros síntomas neurológicos ni enfermedad neurológica.

Self-Reported Neurological Symptoms Two Years After Hospital Discharge Among COVID-19 Survivors.

Background: The acute stage of COVID-19 often presents with neurological manifestations. Objective: This study aims to investigate the long-term neurological effects on survivors. Methods: This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19. Results: Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms. Conclusion: Neurological symptoms are common among COVID-19 survivors, especially in severe cases.

Neuroprotective Agents with Therapeutic Potential for COVID-19.

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.

APOE Polymorphism Is Associated with Changes in the Kynurenine Pathway.

BACKGROUND: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between APOE polymorphism and the KP. This study explored the associations between the KP and APOE polymorphism in disorders associated with APOE polymorphism and changes in the KP. METHODS: Subjects with morbid obesity before and after bariatric surgery (numbers 139 and 95, respectively), depression (number 49), and unspecified neurological symptoms (number 39) were included. The following grouping of the APOE genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 = ɛ3ɛ3 + ɛ2ɛ4, and E4 = ɛ3ɛ4 + ɛ4ɛ4. The KP metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, and Xanthurenic acid were quantified in serum. RESULTS: The main findings were a significant positive association between E3 and Quinolinic acid (difference between E3 and E2E4: 12.0 (3.5; 18.6) ng/mL); p = 0.005), and a negative association between E4 and Kynurenine (difference between E4 and E2E3: -31.3 (-54.2; -3.2) ng/mL; p = 0.008). Quinolinic acid has been ascribed neurotoxic and inflammatory effects, and Kynurenine is a marker of inflammation. CONCLUSIONS: The findings indicate that APOE polymorphism might cause changes in the KP that contribute to the disease. Inflammation could be the link between APOE and the KP.