Cerebrospinal Fluid Studies Research Articles

A Case Report of Systemic Lupus Erythematosus Presenting as Isolated Mononeuropathy Multiplex

Mononeuropathy multiplex is a pattern of progressive sensory and motor deficits in the distribution of two or more peripheral nerves. The differential for mononeuropathy multiplex includes vasculitis, autoimmune disorders, infectious diseases, sarcoidosis, amyloidosis, cryoglobulinemia, and paraneoplastic disease. We present a case of a 42-year-old woman with hypothyroidism who presented with 1 week of ascending numbness and weakness, persistent fevers, and 3 months of constant burning pain in both feet. Her neurologic exam was notable for asymmetric weakness, loss of sensation, and diminished reflexes of her lower extremities. Other than mild fever and tachycardia, there were no systemic exam findings. Her laboratory workup was significant for elevated inflammatory markers, positive ANA, anti-ribonucleoprotein, smooth muscle antibody, and lupus anticoagulant, high anti-dsDNA titers, and low complement levels. An MRI of her lumbar spine was negative for lumbosacral nerve root pathology. Cerebrospinal fluid studies demonstrated normal cell counts, glucose, and protein and no evidence of infection. An electromyography (EMG) and nerve conduction studies (NCS) demonstrated asymmetric involvement of multiple individual peripheral nerves. Given the patient’s symptoms, asymmetric exam findings, laboratory results, and EMG/NCS findings, she was diagnosed with mononeuropathy multiplex secondary to systemic lupus erythematosus (SLE) and started on steroid and immunosuppressant therapy with symptomatic improvement. Overall, this case illustrates the unique presentation of mononeuropathy multiplex as the initial manifestation of SLE. The identification of this specific type of neuropathy may play a crucial role in the prompt diagnosis of SLE and timely initiation of treatment, preventing further complications of the disease.

Stroke and Guillain-Barre syndrome secondary to spotted fever –A case report

Rickettsial infection is an important differential diagnosis in prolonged febrile illness and in returned travellers.We report a 44-year-old male from Deraniyagala, Sri Lanka, with spotted fever Rickettsiosis presenting with stroke and Guillain-Barre syndrome. He presented with dysarthria, reduced sensorium, and acute renal failure on the background of a prolonged febrile illness over two weeks. Following admission there was rapid deterioration of consciousness due to renal failure requiring intubation and repeated haemodialysis. On brain imaging, there were bilateral basal ganglia and internal and external capsule infarctions. His serology was positive for spotted fever Rickettsial infection and there was rapid improvement following treatment with doxycycline. However, difficulty in weaning off from the ventilator due to poor respiratory effort and symmetrical flaccid quadriparesis with areflexia raised concerns of concomitant Guillain-Barre syndrome. Serial cerebrospinal fluid (CSF) studies showed the development of elevated CSF protein with cytoalbuminologic dissociation during his stay in the intensive care unit (ICU). A diagnosis of co-existing Guillain-Barre syndrome was supported by the neuro-physiological findings and marked motor improvement following therapeutic plasmapheresis. This unmasked the right-sided mild residual hemiparesis he suffered due to stroke.

Case Report: New-onset relapsing-remitting multiple sclerosis with positive Uhthoff phenomenon after second BNT162b2 dose

Objectives new-onset relapsing-remitting multiple sclerosis (RRMS) has rarely been communicated as a side effect of SARS-CoV-2 vaccination (SC2V). Here we report a patient with new-onset RRMS shortly after the second BNT162b2 vaccine dose, which was diagnosed only after a relapse after the third vaccine dose. Case report the patient is a 31 year-old male who developed eye problems 48 days after the second dose of BNT162b2. The symptoms were attributed to eye strain and gradually disappeared without treatment. Further workup was negative. Three months after the third BNT162b2 dose, urinary urgency developed. Eleven months after the third BNT162b2 dose, he developed sensory and visual disturbances that were noticeable post-exercise and progressed and worsened with alcohol and heat. MRI showed typical lesions that met the Barkhof/Tintore criteria for RRMS. Cerebrospinal fluid (CSF) studies revealed elevated kappa free light chains and positive oligoclonal bands. Because the revised McDonalds criteria were met, RRMS was diagnosed and ocrelizumab was started. Conclusions this case shows that SARS-CoV-2 vaccination can trigger new-onset RRMS, the clinical presentation of SC2V-induced multiple sclerosis is similar to multiple sclerosis due to other triggers, and the severity of the relapses may increase with the number of boosters given. Although, rare, a neurologist should be aware of the presumably rare event in which SC2V triggers new-onset multiple sclerosis.

Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer’s disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.

An Interesting Case of COPD Exacerbation Presenting with Mixed Features of Intracranial Hypertension and Hypercapnic Encephalopathy

Background: Idiopathic intracranial hypertension (IIH or pseudotumor cerebri) has two major morbidities: papilledema with visual loss and disabling headache. Intracranial Venous Hypertension (IVH) is a fundamental mechanism of IIH. Although traditionally considered limiting to the central nervous system, evidence suggests IIH as a systemic disease associated with cardiorespiratory disorders, which has been far less comprehended. Case Report: A 60-year-old female with Chronic Obstructive Pulmonary Disease (COPD) was admitted for dyspnea and developed a coma with a pH of 7.01 and pCO2 of 158 mmHg. She was intubated and had persistent nuchal rigidity, a brief myoclonus episode with a negative electroencephalogram, and negative CT head studies. A Lumbar Puncture (LP) revealed elevated opening pressure (35 cmH2O) with normal Cerebral Spinal Fluid (CSF) studies. Her nuchal rigidity improved after the removal of 40 mL CSF. The ophthalmology examination the next day after her the large volume LP didn’t show visual loss or papilledema. The patient improved clinically and was extubated two days later. Her echocardiogram showed a dilated right ventricle with pulmonary hypertension. The patient was discharged home. Discussion: IIH is different from hypercapnic encephalopathy and characterized by increased intracranial pressure with papilledema, vision loss, and debilitating headache. Hypercapnia-induced increased intracranial venous flow and pulmonary hypertension-caused elevated central venous pressure with consequent outflow resistance lead to IVH. In hypercapnic encephalopathy, the presentation is mostly cognitive changes. In this case, nuchal rigidity with a negative CT head scan triggered the investigation of IIH. Conclusion: A deep understanding of the relationship between COPD and IIH is vital. There is insufficient evidence to recommend routine eye examinations in COPD patients for papilledema and to conduct a pulmonary function test for a newly diagnosed IIH patient. However, we highly suggest a timely ophthalmology exam prior to performing an LP in COPD patients with suspecting IIH to avoid unnecessary procedures and meanwhile improve clinical outcomes.

Cryptococcal meningitis in a diabetic

A 75-year-old male, a known case of hypertension and diabetes, from Bihar, India, had presented to the medicine department with a complaint of fever for the last 1 month and drowsiness for the last 5 days. In view of drowsiness, a cerebrospinal fluid study was done which was suggestive of cryptococcosis (budding yeast in India Ink Preparation). Cryptococcal meningitis is usually found in cases of immunocompromised states like HIV and it is quite less in non-HIV patients like diabetics. Liposomal amphotericin B was started as per protocol. The patient, however, developed anuria and septic shock and succumbed to his illness. Therefore, clinicians should suspect cryptococcal meningitis in nonimmunocompromised patients also because timely treatment may be given as it has a potential cure.

EPEN-06. IDENTIFICATION OF CSF MIRNA BIOMARKERS FOR THE EARLY DETECTION OF MEASURABLE RESIDUAL DISEASE IN PAEDIATRIC EPENDYMOMA: A BIOMECA STUDY

Abstract BACKGROUND Ependymoma (EPN) is the second most common malignant paediatric brain tumour. 50% of children relapse. Detection of Measurable Residual Disease (MRD) via MRI is difficult and lacks sensitivity for very early recurrence, necessitating an urgent need for identifying new, robust biomarkers for the early diagnosis, prognosis, and clinical management of disease progression in EPN. We hypothesise that microRNA (miRNA) quantification in the cerebrospinal fluid (CSF) will have clinical utility in the early detection of MRD in these patients. PATIENTS/METHODS A discovery cohort of EPN CSF samples (n=12) from patients enrolled on the SIOP Ependymoma II clinical trial (trials.gov identifier: NCT02265770) and control leukaemia CSF samples (n=8) underwent RNA-sequencing (QIAGEN) after total RNA extraction using QIAGEN miRNeasy Serum/Plasma kit. The EPN cohort consisted of infratentorial (IT; n=9), supratentorial (ST; n=1) and spinal (SP; n=2) cases taken prior to, or at, resection (primary/relapse). RESULTS Raw sequencing data entered a quality-control pipeline (Tally/Cutadapt), followed by alignment to miRBase-v22 (https://mirbase.org/) using Chimira (PMID:26093149). Two outlying (infratentorial) EPN samples were removed, leaving a 10 (IT+ST+SP) versus 8 comparison. Extracted raw counts were normalised across samples using DESeq2 (PMID:25516281) and 87 differentially-expressed miRNAs identified (adj-p<0.05). EPN samples completely segregated from controls on clustering/heatmap analysis. From these 87 miRNAs, a core set of 53 were overlapping in comparisons removing spinal (IT+ST remaining) and supratentorial (IT alone) samples. These miRNAs underwent combined ranking by adjusted-p and abundance (normalised count) values, and top-ranking candidates taken forward for confirmation using highly-sensitive Taqman PCR, prior to validation in additional samples. CONCLUSION Circulating miRNA quantification offers promise for EPN diagnosis and MRD detection. Further CSF study in larger patient cohorts, and serum/plasma analysis, are now warranted.

Clinical, Radiological, and Etiological Aspects of Pachymeningitis: A Study of 24 Cases.

Introduction and importance Hypertrophic pachymeningitis (HP) is an uncommon disorder with varied etiological origins and heterogeneous clinical presentation. Establishing the etiological diagnosis poses a challenge, but prompt identification provides a treatment window, potentially leading to a reversal of symptoms.MRI is the reference examination, allowingnot onlythe early diagnosis of pachymeningitisbut alsothe assessment of its extent and importance, detection of possible complications, and suggestion of etiology. Case presentation We conducted a retrospective study involving 24 patients recruited over 5 years for who brain imaginghad revealed the presence ofpachymeningitis.The average age of the patients was 40 years, with a male-to-female ratio of 0.6. Clinical discussion Headache was present in 54.17% of patients. All the patients underwent MRI examinations utilizing different sequences, with subsequent Gadolinium injection showing localized and asymmetrical meningeal thickening in 13cases,and diffuse in the rest. The cerebrospinal fluid study unveiled an inflammatory fluid characterized by a lymphocytic predominance and hyperproteinorrhea, noted in 50% of the patients. The histopathological analysis of a stereotactic biopsyconductedon an individual patient revealed non-diagnostic results. The etiological investigationwas dominatedby tuberculosis, which was detectedin 33.3% of cases.Idiopathic origin was identifiedin 16.7% of patients. Conclusion Meningeal thickening is rare, and the multitude of potential causes makes the etiological investigation challenging unless they fall within the scope of secondary meningeal disorders; otherwise, a dural biopsy becomes necessary, and the prompt initiation of treatment, along with determining the etiology influences the prognosis.

Potential diagnostic and distinguishing roles of microneedle‐based biosensors in bacterial and aseptic meningitis

AbstractMeningitis, which is defined by inflammation of the meninges, is a major cause of death and morbidity worldwide. Traditional diagnostic approaches, such as imaging procedures and the study of cerebrospinal fluid, are intrusive, time consuming and sometimes non‐specific. The suggested approach entails creating a biosensor based on microneedles that can detect in real time without the requirement for labels. The biosensor uses highly sensitive detection techniques to detect changes in ionic current and modulation of impedance in response to biomolecules that are of interest, such as proteins and nucleic acids, which are linked to meningitis infections. Initial studies have shown that the microneedle‐based biosensor for meningitis diagnosis is both feasible and effective. When it comes to identifying bacterial and aseptic meningitis biomarkers from blood and cerebrospinal fluid (CSF) samples, the biosensor showed excellent sensitivity and specificity. This novel technique has the potential to enhance patient outcomes by facilitating prompt intervention and tailored therapy by offering a quick, safe and accurate way to distinguish between bacterial and aseptic meningitis. To maximise the biosensor's performance and confirm its therapeutic usefulness in various contexts, more investigations and advancements are necessary.

Efficacy of next-generation genomic sequencing (NGS) applied to cerebrospinal fluid (CSF) in the identification of actionable mutations in Mexican patients.

e14000 Background: Among the benefits offered by NGS from liquid biopsy are the molecular classification of neoplasms as well as the identification of therapeutic targets, without the need to obtain a biopsy of the tumor when it is not feasible. Since 2016, the World Health Organization has included these biomarkers as part of its classification for better management. Additionally, in the case of metastatic tumors, it allows the identification of therapeutic targets as well as resistance mutations and even driver mutations to better understand their biology. In this study, we evaluated the efficacy of CSF NGS in the identification of actionable mutations in patients with CNS neoplasms, and its potential impact on the personalization of cancer treatments for patients in our center. Methods: A retrospective analysis of nine cases was performed in which CSF was used to identify NGS-actionable mutations, collecting, and descriptively analyzing clinical and molecular data from these patients. Results: Mean age was 51.89 years; 55.56% were men and 44.44% women; 66.67% had family history of cancer, of which 83.33% were first-degree relatives; 88.89% had neurological symptoms prior to the study; 33.33% were primary CNS tumors; 55.56% were secondary tumors metastatic to the CNS; 11.11% were indicated due to suspected CNS metastasis. At least 1 genomic alteration was found in 89% of the cases; the most frequently altered gene in primary tumors was TP53 (66.67%). In secondary tumors, the most frequently altered genes were AR and EGFR with 40% incidence each; Approved therapies were found in 55.56% of the cases, therapies approved in other neoplasms in 44.44%, and phase 2 or 3 clinical trials were available in 88.89%. Specific alterations found in are listed in the table. Survival rate at 6-month follow-up was 55.56%. Conclusions: In our patients, the study of CSF through NGS effectively identified actionable mutations with approved treatment in the analyzed neoplasms, other neoplasms, or clinical trials available for enrollment in most cases. In one case, it was possible to rule out the presence of metastasis in CNS, avoiding unnecessary toxicity. To our knowledge, this is the first study in our country that reports the findings of this technique in medical practice, however, more research is needed in bigger populations to optimize and validate the implementation of this study as part of the approach to patients with CNS tumors. [Table: see text]

Meningitis in Children: Still a Can't-Miss Diagnosis.

Although vaccination and antimicrobial treatment have significantly impacted the frequency and outcomes of meningitis in children, meningitis remains a critical can't-miss diagnosis for children, where early recognition and appropriate treatment can improve survival and neurologic outcomes. Signs and symptoms may be nonspecific, particularly in infants, and require a high index of suspicion to recognize potential meningitis and obtain the cerebrospinal fluid studies necessary for diagnosis. Understanding the pathogens associated with each age group and specific risk factors informs optimal empirical antimicrobial therapy. Early treatment and developmental support can significantly improve the survival rates and lifelong neurodevelopment of children with central nervous system infections.

Flow cytometry for meningeal infiltration in B acute lymphoblastic leukemia in a low middle income country.

Meningeal infiltration in children with B acute lymphoblastic leukemia is one of the most serious complications. Timely diagnosis not only significantly enhances treatment efficacy but also leads to improve patient outcome and reduce risk of relapse. This is particularly crucial in low to middle income countries facing health constraints, where optimizing resources is essential. Conventional cytology (CC) study of cerebrospinal fluid (CSF) is considered in different countries to be the Gold-standard despite its low sensitivity (< 50%). The study of CSF by multiparametric flow cytometry (MFC) appears to be an alternative. The aim of our study was to assess MFC analytical performance compared with CC. Our cross sectional study was conducted over a six-month period in the biological hematology department. CSF samples underwent analysis for the presence of blasts using both CC and MFC. Cytological slides of the CSF were prepared by cytocentrifugation in a Shandon Cytospin 4™. Flow cytometric analysis was performed on the BD FACSLyric™ flow cytometer. All statistical analyses were performed using SPSS version 21.0 (SPSS Inc.). Agreement between the two methods was made using the Kappa index and χ2 test. This study was approved by the local ethics committee. Sixty CSF samples from 39 children with B acute lymphoblastic leukemia were analyzed. Meningeal infiltration was detected respectively in 20% of cases by MFC and 5% of cases by CC, with a significant difference p = 0.006. Comparing the two methods, the Kappa coefficient was 0.35, indicating weak agreement between the two methods. Moreover, MFC positivity was higher even for hypocellular samples. Of the 51 hypocellular samples, eight were positive by MFC while they were negative by CC. MFC shows better sensitivity while retaining good specificity for the detection of meningeal involvement. MFC could therefore be a complementary method to CC for detecting blast cells in the central nervous system.

Abstract PO5-20-06: Paraneoplastic cerebellar degeneration in anti-Yo antibody and HER2-positive metastatic breast carcinoma

Abstract Paraneoplastic cerebellar degeneration (PCD) in the context of breast carcinoma affects less than 1% of patients. In most cases, breast cancer diagnosis follows several months or even years after the onset of neurological symptoms. The first association between PCD and occult gynecologic cancers (breast or ovarian) was identified in 1938 with the discovery of antibodies directed against cytoplasmic antigens of Purkinje cells (“anti-Yo antibodies”). Since then, evidence has grown significantly to support anti-Yo antibodies as excellent diagnostic markers of PCD with underlying gynecologic and breast carcinoma. This case study evaluates a 57-year-old female who initially presented with headache and subacute cerebellar ataxia. Her symptoms progressed over a period of three months with multiple falls, onset of speech difficulties, and diplopia. She also reported 30-pound weight loss, which she attributed to dieting and starting semaglutide. Magnetic resonance imaging (MRI) of the brain and spine were unremarkable and autoimmune workup was normal. Cerebral spinal fluid (CSF) and serum studies demonstrated positive anti-Yo antibodies. Computed tomography (CT) of the abdomen and pelvis showed an enlarged left axillary lymph node concerning for metastatic disease with a 1.2cm focus of asymmetric density in the central inferior left breast parenchyma. Diagnostic mammogram one year prior was reportedly normal. Ataxia symptoms improved after a course of empiric intravenous immunoglobulins and steroids. Ultrasound-guided biopsy of the left axillary lymph node revealed metastatic mammary carcinoma: estrogen and progesterone receptor negative and human epidermal growth factor receptor 2 (HER2)-positive, cT0N2aM0, ypTxN1aM0, stage IIIa (AJCC 8th edition). She underwent further metastatic workup, including repeat CSF studies and MRI. MRI of the spine was remarkable for multiple hemangiomas throughout the cervical, thoracic, and lumbar spine, with subsequent unremarkable bone scan. MRI of the abdomen was remarkable for right hepatic lobe hemangioma and a right adrenal nodule. CSF studies showed no sign of metastases. After multidisciplinary discussion, TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) neoadjuvant therapy was initiated and repeat imaging demonstrated favorable treatment response with a shrinking axillary mass; no primary breast mass was identified. The patient underwent left sentinel lymph node biopsy with a positive frozen section intraoperative for invasive cancer, therefore proceeded with left axillary lymph node dissection. She was offered a mastectomy but elected for only axillary surgery. Pathology revealed 1 of 14 lymph nodes were positive for metastatic ductal carcinoma. She remains in a rehabilitation center and her ataxia is improving, but her functional status remains below baseline. She is undergoing radiation to whole breast and regional lymph nodes. With this case, we aim to continue to build upon the limited base of the exceedingly rare presentation of breast cancer-associated paraneoplastic syndrome. In addition, several studies and case reports have demonstrated a strong correlation between HER2 overexpression and anti-Yo associated PCD. As we continue to diagnose and monitor breast cancer patients, we could consider starting to screen for anti-Yo antibodies in HER2-positive patients to gain insight into a patient’s prognosis and development of PCD. Citation Format: You Kim, Alison Coogan, Andrea Madrigrano. Paraneoplastic cerebellar degeneration in anti-Yo antibody and HER2-positive metastatic breast carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-06.

Clinical, Laboratory and Radiological Correlates of Xpert MTB/RIF Assay Study in Cerebrospinal Fluid in CNS Tuberculosis

Background: Cerebrospinal fluid (CSF) Xpert MTB/RIF assay is an initial test for the diagnosis of tuberculous meningitis (TBM). Nevertheless, it is not very clear which of the factors govern CSF-Gene Xpert/MTB positivity. Objective: Hence, we aimed to assess the relationship, if any, between the clinical, laboratory and radiological parameters of the central nervous system (CNS) tuberculosis patients and the Gene Xpert study in CSF in such patients. Methods and Material: First, we studied 200 patients with CNS tuberculosis according to the case definition, and subsequently, we performed a Gene Xpert study on the CSF of these patients. Then, we correlated the clinical, radiological, and CSF criteria with the Gene Xpert positivity using the univariate binary logistic regression method via SPSS 20 (P-value &lt;0.05). Results: Seventy-five (37.5%) patients (57.3% females) of median 24 years of age, were CSF-Gene Xpert/MTB-positive and 125 (62.5%) patients were negative. The mean duration of illness (P = 0.017), weight loss or failure to thrive (P &lt; 0.001), loss of consciousness or seizure (P = 0.001), signs of meningeal irritation (P = 0.027), stage III of TBM (P &lt; 0.001), evidence of dissemination (P = 0.003), basal exudates (P = 0.004), hydrocephalus (P = 0.018), CSF lymphocytic predominance (P &lt; 0.001), and reduced CSF glucose (P = 0.011) correlated significantly with positive the Gene Xpert/MTB results. Also, Gene Xpert had a sensitivity of 80% and a specificity of 74.84% against culture Xpert. Conclusions: Xpert MTB/RIF might be more useful in the later stages of the disease and those with more severe disease.

Tolosa Hunt Syndrome: An Atypical Presentation of a Rare Condition

Abstract Purpose: Tolosa-Hunt Syndrome (THS) is a rare disorder with signs and symptoms that mimic various other diseases. Diagnosis of THS, especially in atypical cases, can be challenging due to the need to exclude other diseases. Observations: A 59-year-old-male presented with acute vision loss of his left eye preceded by acute worsening of chronic headaches. Additionally, he had near complete ophthalmoplegia of this eye. He underwent extensive workup including numerous hematologic studies, cerebrospinal fluid studies, and neuro-radiological imaging studies. All tests had normal results except for an elevated ESR of 92 mm/hour and an abnormal MRI of the brain and orbits. The MRI revealed the left orbit as abnormal with proptosis and intraconal inflammatory change. It also showed abnormal enhancement of the left orbital apex and adjacent lateral aspect of the left sphenoid sinus. He was diagnosed with THS and rapidly responded to corticosteroid treatment. Conclusions and Importance: THS can be challenging to diagnose because it is a diagnosis of exclusion. An added difficulty with THS is the need to quickly recognize and diagnose it since early treatment with corticosteroids can produce a rapid treatment response and decreases the chance of severe residual symptoms. THS does not usually affect the optic nerve, but optic nerve damage can occur and involvement of the optic nerve further increases the urgency of diagnosing it and promptly initiating treatment.

Approaching an undetermined diagnosis in the aftermath of rhombencephalitis: A case report

A 49-year-old male patient manifested acute onset increased imbalance, quadriparesis, and speech impairment 1 month after undergoing ventricular-peritoneal shunt for normal pressure hydrocephalus (although magnetic resonance imaging [MRI] of the brain with contrast was otherwise normal), which showed improvement afterward. He had hypercalcemia and elevated erythrocyte sedimentation rate. Repeat brain MRI revealed pachymeningitis coupled with rhombencephalitis, while cerebrospinal fluid study unveiled only increased protein level without evidence of active infection. Given these findings, neurosarcoidosis was preliminarily considered a plausible cause of the recent clinical manifestations, and the patient was prescribed methylprednisolone, which led to significant improvement. However, the steroid treatment was discontinued on the revelation that the patient grappled with severe sepsis. Despite an initial improvement following a post-management of sepsis, his condition deteriorated, and he became lost to follow-up after 4 months of initial presentation. An infective etiology was ruled out since his condition improved with steroid. Precluding vasculitis or demyelinating disorder left the physicians with primary central nervous system (CNS) lymphoma or sarcoidosis as a proper diagnosis based on the fact that the patient experienced deterioration when steroid was excluded from the treatment regimen. This case study portrays a need to conduct a more specific and elaborate investigation, driven by a strong perception to both primary CNS lymphoma and sarcoidosis, to optimize clinical diagnosis, which facilitates the formulation of an appropriate treatment regimen.

Cryptococcus Infection in an Immunocompetent Patient

A case of a 26-year-old female who was apparently healthy without any comorbidities presented with a history of headache, which was gradually progressive over 2 months with features suggestive of raised intracranial pressure. Cerebrospinal fluid (CSF) study was done, which revealed chronic meningitis. Indian ink staining of CSF showed Cryptococcus, and the species was identified as Cryptococcus gattii. She did not have any respiratory symptoms, but the chest radiography showed a consolidative patch caused by growing yeasts mimicking a mass. Cryptococcal infection is rarely seen in immunocompetent individuals. Among the two species of Cryptococcus, C. gattii is known to cause infections in immunocompetent. It is imperative to have a high index of suspicion and early diagnosis of such a condition to avoid unwanted complications in patients.

Cytotoxic Lesion of Corpus Callosum after COVID-19 Vaccination: Case Report

Purpose: Cytotoxic lesions of corpus callosum (CLOCCs) are associated with many disease entities. Serious neurological complications after coronavirus disease 2019 (COVID-19) vaccination are rare. Case report: A 20-year-old man presented with severe headache for 2 days. He had received the first dose of ChAdOx1nCoV-19 COVID-19 vaccine 5 days ago. Persistent dull headache occurred on the third day after vaccination and intensified gradually to awaken him from sleep at night. No neck stiffness was observed. Brain magnetic resonance angiography (MRA) 9 days after vaccination revealed an oval-shaped diffusion-weighted restriction lesion at the splenium of corpus callosum with a mildly high signal intensity on T2-weighted images (T2WI) and low signal intensity on apparent diffusion coefficient (ADC) imaging but without enhancement after contrast injection. A COVID-19 polymerase chain reaction test was negative. A blood test revealed slight leukocytopenia, thrombocytopenia, and hyponatremia. Further autoimmune and hematological studies were normal. A cerebrospinal fluid study revealed normal intracranial pressure. The patient’s headache improved gradually. Follow-up brain MRA 5 weeks after vaccination revealed complete disappearance of the diffusion-weighted restriction lesion of the splenium. Conclusion: CLOCCs are rare transient adverse effect of COVID-19 vaccination possibly related to a cytokine storm. The splenic lesion might disappear spontaneously with a good prognosis.

Is foramen magnum decompression for acquired Chiari I malformation like putting a finger in the dyke? - A simplistic overview of artificial intelligence in assessing critical upstream and downstream etiologies.

Missed diagnosis of evolving or coexisting idiopathic (IIH) and spontaneous intracranial hypotension (SIH) is often the reason for persistent or worsening symptoms after foramen magnum decompression for Chiari malformation (CM) I. We explore the role of artificial intelligence (AI)/convolutional neural networks (CNN) in Chiari I malformation in a combinatorial role for the first time in literature, exploring both upstream and downstream magnetic resonance findings as initial screening profilers in CM-1. We have also put together a review of all existing subtypes of CM and discuss the role of upright (gravity-aided) magnetic resonance imaging (MRI) in evaluating equivocal tonsillar descent on a lying-down MRI. We have formulated a workflow algorithm MaChiP 1.0 (Manjila Chiari Protocol 1.0) using upstream and downstream profilers, that cause de novo or worsening Chiari I malformation, which we plan to implement using AI. The PRISMA guidelines were used for "CM and machine learning and CNN" on PubMed database articles, and four articles specific to the topic were encountered. The radiologic criteria for IIH and SIH were applied from neurosurgical literature, and they were applied between primary and secondary (acquired) Chiari I malformations. An upstream etiology such as IIH or SIH and an isolated downstream etiology in the spine were characterized using the existing body of literature. We propose the utility of using four selected criteria for IIH and SIH each, over MRI T2 images of the brain and spine, predominantly sagittal sequences in upstream etiology in the brain and multiplanar MRI in spinal lesions. Using MaChiP 1.0 (patent/ copyright pending) concepts, we have proposed the upstream and downstream profilers implicated in progressive Chiari I malformation. The upstream profilers included findings of brain sagging, slope of the third ventricular floor, pontomesencephalic angle, mamillopontine distance, lateral ventricular angle, internal cerebral vein-vein of Galen angle, and displacement of iter, clivus length, tonsillar descent, etc., suggestive of SIH. The IIH features noted in upstream pathologies were posterior flattening of globe of the eye, partial empty sella, optic nerve sheath distortion, and optic nerve tortuosity in MRI. The downstream etiologies involved spinal cerebrospinal fluid (CSF) leak from dural tear, meningeal diverticula, CSF-venous fistulae, etc. AI would help offer predictive analysis along the spectrum of upstream and downstream etiologies, ensuring safety and efficacy in treating secondary (acquired) Chiari I malformation, especially with coexisting IIH and SIH. The MaChiP 1.0 algorithm can help document worsening of a previously diagnosed CM-1 and find the exact etiology of a secondary CM-I. However, the role of posterior fossa morphometry and cine-flow MRI data for intracranial CSF flow dynamics, along with advanced spinal CSF studies using dynamic myelo-CT scanning in the formation of secondary CM-I is still being evaluated.

Be Alert to ALERD: Acute Leukoencephalopathy with Restricted Diffusion—Atypical Presentation of a Rare Case

AbstractAcute leukoencephalopathy with restricted diffusion (ALERD) is a novel entity observed in children with acute encephalopathy. It is characterized by diffusion restriction on magnetic resonance imaging (MRI), which can be the distinctive and sometimes the only imaging finding. Other routine MRI sequences may appear normal. ALERD can have infectious or noninfectious causes. In this case, we present a patient with infectious ALERD associated with influenza B virus. A 10-year-old boy presented to the emergency room with a brief history of fever and cough, followed by altered sensorium. He was irritable and ataxic. Neck stiffness was elicited upon examination. An MRI of the brain showed extensive symmetric diffusion restriction in the periventricular and deep white matter, corpus callosum, posterior limb of the internal capsule, and cerebral peduncles of both cerebral hemispheres. Cerebrospinal fluid study, blood and urine toxicology panels were noncontributory. The respiratory panel test was positive for influenza B. A diagnosis of infectious ALERD was made. Following treatment with steroids, intravenous immunoglobulin, antiglutamate agents, and supportive measures, he showed clinical and radiological improvement. The reporting of ALERD has risen in recent years due to its increased detection using MRI. Diffusion-weighted image plays the key role in the final diagnosis. Supportive care and prompt treatment of seizures are very important for better outcome. Follow-up imaging is also required to assess reappearance of white matter edema and development of cerebral atrophy or gliosis.