Rheumatoid meningitis: a case series report and review of modern therapeutic schemes and outcome.

INTRODUCTION: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. METHODS: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. RESULTS: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. CONCLUSIONS: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended.

Leptomeningeal enhancement in multiple sclerosis: a focus on patients treated with hematopoietic stem cell transplantation.

Background: Leptomeningeal enhancement (LME) is considered an MRI marker of leptomeningeal inflammation in inflammatory neurological disorders, including multiple sclerosis (MS). To our knowledge, no disease-modifying therapies (DMTs) have been demonstrated to affect LME number or morphology so far. Methods: Monocentric study investigating the frequency and number of LME in a cohort of people with (pw)MS who performed a 3 T brain MRI with a standardized protocol (including a post-contrast FLAIR sequence), and exploring the impact of autologous hematopoietic stem cell transplantation (AHSCT) on this marker. In a longitudinal pilot study, consecutive MRIs were also analyzed in a subgroup of pwMS, including patients evaluated both pre- and post-AHSCT. Results: Fifty-five pwMS were included: 24/55 (44%) had received AHSCT (AHSCT group) and 31 other treatments (CTRL group). At least one LME was identified in 19/55 (35%) cases (42 and 29% in the AHSCT and CTRL groups, respectively; p = 0.405). In the AHSCT group, LME number correlated with age at AHSCT (R = 0.50; p = 0.014), but not with age at post-treatment MRI. In the longitudinal pilot study (n = 8), one LME disappeared following AHSCT in 1/4 patients, whereas LME number was unchanged in the remaining four pwMS from the CTRL group. Discussion: These results suggest that AHSCT may affect development and persistence of LME, strengthening the indication for early use of effective therapies bioavailable within the central nervous system (CNS), and therefore potentially targeting compartmentalized inflammation.

Cerebellar leptomeningeal enhancement: An imaging finding of rapidly progressive Purkinje cell cytoplasmic autoantibody type 1 paraneoplastic cerebellar syndrome.

Purkinje cell cytoplasmic autoantibody type 1 (PCA1), also known as anti-Yo, is a 'high-risk' paraneoplastic antibody, associated with rapidly progressive cerebellar syndrome. In patients with this syndrome, various MRI abnormalities have been documented, including atrophy in the cerebellum and brainstem, T2 hyperintensity in the brainstem and spinal cord, and cranial nerve enhancement. This report introduces an imaging finding, cerebellar leptomeningeal enhancement, which was observed in all three cases at early stages. Despite neurological deterioration, all patients underwent immunotherapy, and subsequent follow-up MRI revealed resolution of the leptomeningeal enhancement, suggesting that this feature is distinct from meningeal carcinomatosis.

Postoperative disappearance of leptomeningeal enhancement around the brainstem in glioblastoma.

PURPOSE: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. METHODS: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. RESULTS: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. CONCLUSIONS: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.

Persistent Headaches in an Avid Hiker: A Case of Chronic Coccidioidal Meningitis.

The clinical presentation, diagnosis, treatment, and complications of coccidioidal meningitis caused by the dimorphic pathogenic fungus Coccidioides (Coccidioides immitis and Coccidioides posadasii) have been well documented in the literature. Despite the abundance of literature concerning this disease manifestation, it is not very commonly seen in clinical practice, delaying its diagnosis and treatment and leading to devastating neurological sequelae. Therefore, considering this disease process as a potential diagnosis in endemic areas is important for appropriate and timely treatment. We present the case of a 26-year-old male who was found to have chronic coccidioidal meningitis on further investigation. The patient presented as a transfer for an abnormal head MRI with a three-month history of progressive occipital headaches and shortness of breath. Associated symptoms included transit vision loss, upper extremity numbness, night sweats, decreased appetite, and weight loss. Relevant risk factors were being a hiker and living in the southwest of Texas. The patient was started on empiric ceftriaxone and vancomycin. A repeat MRI showed leptomeningeal enhancement and acute infarcts in the left temporal lobe and lentiform nucleus. Cerebrospinal fluid (CSF) analysis showed pleocytosis with lymphocytic predominance, the presence of eosinophils, elevated protein level, and an extremely low glucose level. Further workup ruled out syphilis and tuberculosis. Therefore, considering his clinical presentation, risk factors, and workup results, ceftriaxone and vancomycin were discontinued, and high-dose oral fluconazole was started, which produced a marked clinical response within the next 48 hours. A CT thorax showed findings suggestive of pulmonary coccidioidomycosis, and Coccidioides serology in both serum and CSF specimens returned positive.

Association of MRI leptomeningeal enhancement with disability worsening in progressive multiple sclerosis: A clinical and post-mortem study.

BACKGROUND: Leptomeningeal enhancement (LME) has been described as a biomarker of meningeal inflammation in multiple sclerosis (MS). OBJECTIVE: The aim of this study was to (1) assess if LME is predictive of disability worsening in progressive MS (pMS) patients and (2) investigate the pathological substrates of LME in an independent post-mortem MS series. METHODS: In total, 115 pMS patients were imaged yearly with 1.5T MRI, using post-contrast CUBE 3D FLAIR for LME detection. Endpoint: to identify the baseline variables predictive of confirmed disability worsening (CDW) at 24 months follow-up. Post-mortem, inflammation, and structural changes of the leptomeninges were assessed in 12 MS/8 control brains. RESULTS: LME (27% of patients at baseline) was associated with higher EDSS and lower brain volume (nBV). LME was unchanged in most patients over follow-up. LME at baseline MRI was independently associated with higher risk of 24 months CDW (HR 3.05, 95% CI 1.36-6.84, p = 0.007) in a Cox regression, including age, nBV, T2 lesion volume, high-efficacy treatments, and MRI disease activity. Post-mortem, focal structural changes (fibrosis) of the leptomeninges were observed in MS, usually associated with inflammation (Kendall's Tau 0.315, p < 0.0001). CONCLUSIONS: LME is frequently detected in pMS patients using 1.5T MRI and is independently predictive of disability progression. LME could result from both focal leptomeningeal post-inflammatory fibrosis and inflammation.

Neurosarcoidosis With Multi-Organ Involvement: A Case Report and Literature Review.

Sarcoidosis is a multisystemic disease that, in rare cases, can involve the central nervous system (CNS). We present a case of sarcoidosis with intracranial and multi-organ involvement. The patient presented with a one-month history of headaches. Imaging revealed leptomeningeal nodular enhancement (LNE), and a PET/CT scan of the chest and abdomen showed bilateral hilar, retroperitoneal, and inguinal lymphadenopathy. The diagnosis of sarcoidosis was confirmed by an ultrasound-guided inguinal lymph node biopsy. The patient was started on a combination of corticosteroids and immunosuppressive drugs, with a gradual improvement in symptoms and radiological findings over several months.

Case report: 3D intracranial vessel wall MRI in Susac syndrome: potential relevance for diagnosis and therapeutic management.

Background: Susac syndrome (SS) is a rare immune-mediated vasculitis affecting retina, inner ear and brain. Assessment of central nervous system (CNS) involvement is currently based on standard brain magnetic resonance imaging (MRI) sequences. Accuracy of three dimensional (3D)-vessel wall imaging (VWI) was compared to standard sequences and contrast-enhanced-3D T2-fluid attenuated inversion recovery (CE-FLAIR) to assess CNS disease activity in two cases of definite SS. Methods: Brain MRI scan and retinal fluorescein angiogram (RFA) were performed at disease onset and at 1, 3, and 6 months after induction therapy start. CE-FLAIR and VWI based on 3D black-blood proton density weighted (PDW) with and without gadolinium were added to standard sequences on a 3 Tesla MRI scanner. Results: Contrast enhanced-VWI (CE-VWI) detected an abnormal diffuse leptomeningeal enhancement (LME) in both cases at onset and during follow-up. Pathological enhancement on CE-VWI persisted at 6-month brain MRI, despite absence of new lesions and disappearance of LME on CE-FLAIR. Follow-up RFA revealed new arterial wall hyperfluorescence in both cases. Conclusions: VWI may represent a useful tool for diagnosing and monitoring CNS disease activity in SS patients, as confirmed by concordance with RFA, leading treatment's choice and timing. Moreover, CE-VWI seemed at least as sensitive as CE-FLAIR in detecting LME, possibly being superior to the latter in posterior fossa. LME remission might be not accurate in predicting suppression of CNS inflammation in SS.

Neurosarcoidosis Presenting With Confusion and Speech Alteration.

Neurosarcoidosis (NS) is a rare manifestation of sarcoidosis, a multisystem inflammatory granulomatous disease. We describe a unique case of NS with confusion and speech alteration as presenting symptoms. A 65-year-old male with a history of Ramsay Hunt syndrome and Lyme infection presented to the emergency room after an acute episode of disorientation, garbled speech, and left facial droop, along with months of worsening generalized fatigue, gait ataxia, left-sided periorbital headaches, bilateral peripheral neuropathy, and bladder disturbance. A recent CT scan of his chest showed mediastinal lymphadenopathy, and a lymph node biopsy revealed non-necrotizing granulomas, Langhans giant cells, and focal Schaumann bodies. A brain MRI revealed a mildly enlarged anterior pituitary gland, mild prominent enhancement of the trigeminal nerves bilaterally, and right frontal, parietal, and superior temporal leptomeningeal enhancement. Lumbar puncture cerebrospinal fluid analyses were consistent with aseptic meningitis. A diagnosis of probable NS was made. The patient received IV methylprednisolone 1 g for three days, followed by a prednisone taper with clinical improvement. NS is a diagnostic challenge due to the variability of clinical presentations of the disease. This case demonstrates how vague chronic neurologic symptoms preceding an unusual acute clinical presentation delayed the diagnosis of NS in a patient with sarcoidosis.

Neurosarcoidosis: A Rare Presentation as a Seizure.

Neurosarcoidosis is a rare disorder that can develop in patients with a history of sarcoidosis or can develop even when sarcoidosis is not diagnosed. It is a granulomatous disease of the nervous system that causes different neurological disorders based on its location. However, diagnosing neurosarcoidosis remains a challenge as it mimics many other neurological disorders and does not have any biochemical markers of high specificity. A tissue-proven biopsy is the gold standard but is difficult to obtain in neurological illnesses. Thus, diagnosis is established based on the clinical syndrome and imaging, which mostly show meningeal/parenchymal lesion enhancement, in addition to the exclusion of other causes. Glucocorticoids, immunosuppressants, and anti-tumour necrosis factor (TNF) drugs are the mainstays of treatment. We discuss a case of neurosarcoidosis in a 52-year-old woman with a known history of sarcoidosis.

A Perplexing Case of Bladder Mass Biopsy-Proven Neurosarcoidosis.

Sarcoidosis is a multi-organ systemic disease that presents with several clinical manifestations, and patients can develop neurologic complications. Neurosarcoidosis may be life-threatening; therefore, early recognition and treatment are key. Here, we present a case of a 55-year-old African American male who presented with a complaint of dizziness and left-sided weakness; he ultimately received a diagnosis of neurosarcoidosis after elaborate radiographic investigations and bladder mass biopsy. Neurosarcoidosis remains a diagnostic dilemma as it can clinically and radiographically mimic multiple conditions including multiple sclerosis, central nervous system lymphoma, multiple myeloma, and progressive multifocal leukoencephalopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy coexistent with reversible splenial lesion syndrome: A case report and literature review.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disorder. Reversible splenial lesion syndrome (RESLES) is a transient clinical-imaging syndrome characterized by specific magnetic resonance imaging (MRI) pattern. A 58-year-old man was admitted with a fever, headache, and confusion for 1 week. Brain MRI showed abnormal leptomeningeal enhancement in the brainstem and high signal intensity on diffusion-weighted MRI of the corpus callosum. Anti-GFAP antibody was positive in the serum and cerebrospinal fluid analysis. This patient significantly improved and had no relapse after glucocorticoid and immune suppressant therapy. A repeated brain MRI revealed the lesion in the corpus callosum and abnormal leptomeningeal enhancement in the brainstem disappeared. Linear perivascular radial enhancement is the characteristic pattern of autoimmune GFAP astrocytopathy which is rarely coexistent with RESLES.

Does sevoflurane sedation in pediatric patients lead to "pseudo" leptomeningeal enhancement in the brain on 3 Tesla magnetic resonance imaging?

BACKGROUND: Prominent leptomeningeal contrast enhancement (LMCE) in the brain is observed in some pediatric patients during sedation for imaging. However, based on clinical history and cerebrospinal fluid analysis, the patients are not acutely ill and do not exhibit meningeal signs. Our study determined whether sevoflurane inhalation in pediatric patients led to this pattern of 'pseudo' LMCE (pLMCE) on 3 Tesla magnetic resonance imaging (MRI). AIM: To highlight the significance of pLMCE in pediatric patients undergoing enhanced brain MRI under sedation to avoid misinterpretation in reports. METHODS: A retrospective cross-sectional evaluation of pediatric patients between 0-8 years of age was conducted. The patients underwent enhanced brain MRI under inhaled sevoflurane. The LMCE grade was determined by two radiologists, and interobserver variability of the grade was calculated using Cohen's kappa. The LMCE grade was correlated with duration of sedation, age and weight using the Spearman rho rank correlation. RESULTS: A total of 63 patients were included. Fourteen (22.2%) cases showed mild LMCE, 48 (76.1%) cases showed moderate LMCE, and 1 case (1.6%) showed severe LMCE. We found substantial agreement between the two radiologists in detection of pLMCE on post-contrast T1 imaging (kappa value = 0.61; P < 0.001). Additionally, we found statistically significant inverse and moderate correlations between patient weight and age. There was no correlation between duration of sedation and pLMCE. CONCLUSION: pLMCE is relatively common on post-contrast spin echo T1-weighted MRI of pediatric patients sedated by sevoflurane due to their fragile and immature vasculature. It should not be misinterpreted for meningeal pathology. Knowing pertinent clinical history of the child is an essential prerequisite to avoid radiological overcalling and the subsequent burden of additional investigations.

Meningitis as a complication of Sjögren's syndrome.

Sjögren's syndrome can be complicated by several neurological manifestations, including aseptic meningitis, which can be manifested with headache, flu-like symptoms, confusion, fever, signs of meningeal irritation, with or without focal neurological symptoms and cranial nerve palsy. Neuroimaging can reveal contrast enhancement in the lepto- or pachymeninges. Therefore, Sjögren's syndrome should be considered in the differential diagnosis of lepto- or pachymeningeal enhancement.

Subdural Empyema in Pediatric Bacterial Meningitis: A Case Report.

Bacterial meningitis in pediatric populations presents a formidable challenge, necessitating careful evaluation and swift intervention. The clinical spectrum of pediatric bacterial meningitis requires a clear understanding, considering its diverse presentations, risk factors, and evolving diagnostic and therapeutic approaches. We present the case of an eight-year-old male who presented with an acute onset of fever, severe headache, and vomiting following an upper respiratory tract infection. A physical examination revealed meningeal irritation signs, altered consciousness, and focal seizures. Laboratory results showed elevated inflammatory markers, and cerebrospinal fluid analysis indicated abnormalities. Initial imaging displayed sinus involvement, but the patient's condition deteriorated. Subsequent magnetic resonance imaging revealed subdural empyema and meningoencephalitis. Streptococcus pneumoniae was identified as the causative agent. Subsequently, tailored antibiotic therapy and urgent neurosurgical interventions were initiated. The patient recovered with the resolution of neurological deficits. This case underscores the complexity of pediatric bacterial meningitis and its potential complications, emphasizing the relationship between upper respiratory tract infections, sinus involvement, and meningitis development. A multidisciplinary approach, combining targeted antimicrobial therapy with neurosurgical intervention, proved crucial for optimal management and favorable outcomes. This detailed case report highlights the importance of early diagnosis and comprehensive management in pediatric bacterial meningitis cases.

Cerebral developmental venous anomalies in children with mismatch repair deficiency.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is one of the rare cancer predisposition syndromes. The aim of this study was to evaluate the cerebral developmental venous anomalies in children with central nervous system tumors associated with CMMRD, an area in which there is extremely little experience. METHODS: Data from children diagnosed with medulloblastoma and high grade central nervous sytem tumor were retrospectively collected. According to the European CMMRD criteria, nine patients were diagnosed as CMMRD syndrome and the others consisted of the group without CMMRD. All radiological examinations of these children were retrospectively reviewed. Whole exome sequencing was performed to index cases` germline DNA. RESULTS: Nine children from four families, six females and three males, were studied. The median age at the first tumor diagnosis was 4.5 years (range, 9 months to 14 years). All CMMRD patients had café au lait spots, but none fulfilled the diagnostic criteria for neurofibromatosis. The patients developed high-grade glial tumor (n: 7) and medulloblastoma (n: 2). The affected genes in the three families were MSH6 [c.478C > T (p.Gln160Ter)], MSH6 [c.2871dupC (p.Phe958LeufsTer5)] and MLH1 [c.236G > A(p.Arg79Lys)], respectively. Seven patients had multiple developmental venous anomalies; six patients had leptomeningeal enhancement; and five patients had cavernomas. None of these findings were present in the group without CMMRD. CONCLUSIONS: Constitutional mismatch repair deficiency should be considered when multiple developmental venous anomalies, cavernomas, and leptomeningeal enhancement are detected, especially in patients with café au lait spots.

Tumor glioneuronal leptomeníngeo difuso: diagnóstico y tratamiento con un caso ilustrativo / Diffuse leptomeningeal glioneuronal tumor: A review of diagnosis and management with an illustrative case

El tumor glioneuronal leptomeníngeo difuso es una entidad infrecuente, con un curso indolente; fue descrito en la clasificación de los tumores del sistema del sistema nervioso central de la OMS 2016. Presentamos el caso de un varón de 11 años que comienza con un cuadro clínico inespecífico de cefalea, dolor lumbosacro e hidrocefalia comunicante. En el curso clínico aparecen crisis epilépticas con lesiones nodulares en RM craneal; fue diagnosticado de meningitis tuberculosa y tratado con tuberclostáticos. Ante un deterioro clínico progresivo, a pesar del tratamiento, y empeoramiento de los hallazgos en RM craneoespinal, se le realiza biopsia cerebral y de leptomeninges que confirma el diagnóstico de tumor glioneuronal leptomeníngeo difuso. El tumor glioneuronal leptomeníngeo difuso debe incluirse en el diagnóstico diferencial de los cuadros que se presentan con hidrocefalia comunicante y lesiones leptomeníngeas. Se precisa un diagnóstico histológico precoz mediante biopsia para establecer un tratamiento adecuado (AU)

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are a rare indolent neoplasm described in the 2016 WHO classification of tumors of the central nervous system (CNS). We describe a case of an 11 year old boy who initially presented intermittent headache, low back pain and communicating hydrocephalus, misdiagnosed as having tuberculous meningitis. Further clinical deterioration with seizures was observed and follow-up MRI showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain and leptomeninges revealed a diffuse leptomeningeal glioneuronal tumor. DLGNT should be considered in the differential diagnosis of conditions presenting as communicating hydrocephalus with nodular lesions and leptomeningeal enhancement. A timely histologic diagnosis through a biopsy of the brain is necessary to confirm the diagnosis (AU)

COVID-19 Encephalopathy Presenting As New-Onset Seizure: A Case Report.

Since its outbreak, it's been well-documented that coronavirus disease 2019 (COVID-19) can present with wide variety of neurological manifestations in absence of the usual respiratory symptoms. We report one such severe neurological manifestation of SARS-CoV-2 infection. To our knowledge, this is the first reported case of COVID-19 encephalopathy with CSF and MRI findings in the United Arab Emirates. We present a case of a 52-year-old female who presented with complaints of altered mentation, anosmia, headache, dizziness, weakness, lethargy, and vomiting. While in the emergency department she developed two generalized tonic-clonic seizure episodes, a more pronounced delirium, and tachypnea which required intubation. She was then admitted to the intensive care unit (ICU). She was COVID-19 positive and subsequent MRI revealed encephalopathy. She was discharged from ICU and was under long-term care at the time of case documentation.

Medulloblastoma Presenting As Isolated Leptomeningeal Enhancement With No Primary Mass.

Medulloblastoma presenting with diffuse leptomeningeal enhancement and no identified intra-parenchymal primary mass is extremely rare. A 14-year-old previously healthy boy presented with a three-week history of symptoms consistent with increased intracranial pressure (ICP). Magnetic resonance imaging (MRI) revealed diffuse leptomeningeal enhancement which prompted consideration of infectious, inflammatory, and neoplastic etiologies. The patient became rapidly unstable requiring the placement of an external ventricular drain (EVD) and induction of a phenobarbital coma for refractory seizures. The "sugar-coated" appearance of the abnormal enhancement and thickened tissues raised concern specifically for malignancy. The patient remained extremely unstable and ultimately required surgical decompression for increased ICP at which time a biopsy was obtained. Despite attempting bridging intra-ventricular chemotherapy, the patient, unfortunately, passed away, just 14 days from the initial presentation. Final pathology later confirmed the diagnosis of medulloblastoma. Awareness of medulloblastoma in the differential of diffuse leptomeningeal enhancement is crucial for early identification and treatment of this rare presentation. This case is the first pediatric report of primary leptomeningeal medulloblastoma without a primary mass involving the large cell/anaplastic variant.