Clinicoradiological features of probable chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described chronic inflammatory central nervous system disease. This case report describes a young female patient presenting with weakness in bilateral upper and lower limbs and tinnitus for 2 months. A neurological examination revealed signs of brainstem and cerebellar involvement. MRI brain showed characteristic features of CLIPPERS, with punctate and nodular enhancement in the pons and cerebellum. Differential diagnoses were systematically considered and excluded. The patient showed significant clinical and radiological improvement with steroid therapy. No clinical or radiological red flags occurred during the follow-up. This case underscores the critical role of integrating clinical and radiological findings to effectively diagnose and manage CLIPPERS. It emphasises the importance of ruling out alternative diagnoses through a thorough evaluation.

[Translated article] Specific Cutaneous Lesions in Patients With Neurosarcoidosis.

Neurosarcoidosis is an uncommon but potentially serious disease of the central nervous system that can cause major sequelae. We analyzed the presence and diagnostic usefulness of specific cutaneous lesions in 58 patients with neurosarcoidosis. Sixteen patients (27.6%) had specific cutaneous lesions (14 men and 2 women; mean age, 50 years [range, 20-84 years]). Twenty-four types of neurological lesions were observed: cranial neuropathy (n=7), parenchymal lesions (n=4), meningeal lesions (n=3), myelopathy (n=3), pituitary lesions (n=1), hydrocephalus (n=2), and peripheral neuropathy (n=4). Twenty types of specific cutaneous lesions were observed: maculopapular lesions (n=6), plaques (n=9), lupus pernio (n=1), and scar sarcoidosis (n=4). These last lesions coexisted with maculopapular lesions in 2 patients and plaques in another 2. Specific cutaneous lesions were present at diagnosis of neurosarcoidosis in 13 patients. Recognition of specific cutaneous lesions in a patient with suspected neurosarcoidosis is important as biopsy can accelerate diagnosis.

Corticosteroid treatment for acute hydrocephalus in neurosarcoidosis: a case report.

BACKGROUND: Neurosarcoidosis occurs symptomatically in 5-10% of patients with sarcoidosis, and hydrocephalus is a rare complication of neurosarcoidosis, with either acute or subacute onset and presenting symptoms related to increased intracranial pressure. It represents a potentially fatal manifestation with a mortality rate of 22% (increased to 75% in case of coexistence of seizures) that requires a prompt initiation of treatment. High-dose intravenous corticosteroid treatment and neurosurgical treatment must be considered in all cases of neurosarcoidosis hydrocephalus. CASE PRESENTATION: Here we present a case of hydrocephalus in neurosarcoidosis, complicated by generalized seizures, in a 29-year-old Caucasian male patient treated with medical treatment only, with optimal response. CONCLUSION: Since neurosurgery treatment can lead to severe complications, this case report underlines the possibility to undergo only medical treatment in selected cases. Further studies are needed to stratify patients and better identify those eligible for only medical approach.

Neurosarcoidosis: Frozen section rescue for a big mimicker - A case report.

Neurosarcoidosis is an uncommon but potentially serious manifestation of sarcoidosis. Diagnosis may be particularly challenging especially when neurosarcoidosis occurs in isolation or is the initial presentation of the systemic disease. The authors take this opportunity to report a case of neurosarcoidosis, presenting as the first manifestation of the disease, diagnosed on frozen section, occurring in a 43-year-old male patient with no past history or manifestation of sarcoidosis.

Neurosarcoidosis and Neurologic Complications of Sarcoidosis Treatment.

Sarcoidosis is an immune-mediated multisystem granulomatous disorder. Neurosarcoidosis (NS) accounts for 5% to 35% of cases. The diagnostic evaluation of NS can be a clinical challenge. Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard to evaluate central nervous system NS. In almost all cases treatment is warranted. Although glucocorticoids remain the first-line therapy in patients with sarcoidosis, in NS timely initiation of second- or third-line treatment is strongly recommended. Of these, tumor necrosis factor-alpha inhibitors are the most promising. However, the treatment itself may be responsible for/associated with developing neurologic symptoms mimicking NS. Thus, it is important to consider the possibility of drug-induced neurologic symptoms in sarcoidosis.

Current progression in application of extracellular vesicles in central nervous system diseases.

Early diagnosis and pharmacological treatment of central nervous system (CNS) diseases has been a long-standing challenge for clinical research due to the presence of the blood-brain barrier. Specific proteins and RNAs in brain-derived extracellular vesicles (EVs) usually reflect the corresponding state of brain disease, and therefore, EVs can be used as diagnostic biomarkers for CNS diseases. In addition, EVs can be engineered and fused to target cells for delivery of cargo, demonstrating the great potential of EVs as a nanocarrier platform. We review the progress of EVs as markers and drug carriers in the diagnosis and treatment of neurological diseases. The main areas include visual imaging, biomarker diagnosis and drug loading therapy for different types of CNS diseases. It is hoped that increased knowledge of EVs will facilitate their clinical translation in CNS diseases.

Cardiac Involvement in Neurosarcoidosis: A Single-Center Investigation

BACKGROUND AND OBJECTIVES: Sarcoidosis is a multisystem inflammatory granulomatous disease. Among systemic sarcoidosis manifestations, cardiac or nervous system involvement can result in significant morbidity and mortality. We describe the overlapping incidence of cardiac sarcoidosis (CS) within a neurosarcoidosis (NS) cohort and determine the frequency of other nonsarcoid cardiac diseases in these patients. METHODS: We performed a retrospective chart review of patients evaluated at the University of Utah from 2010 to 2022. Patients were included if they had (1) at least one instance of a diagnostic code for sarcoidosis in their medical record-International Classification of Diseases (ICD) 9 code 135 or ICD 10 code D86; (2) at least one outpatient visit in the Neurology Department within the University of Utah electronic health record with a diagnosis of definite, probable, or possible NS based on 2018 consensus criteria; (3) at least one outpatient visit in the Cardiology Department within the University of Utah electronic health record; and (4) ECG available in their medical record for review. Of 64 definite, probable, or possible patients with NS in the University of Utah cohort, 52 met our inclusion criteria and were included in this study. RESULTS: Of 52 patients with NS who met our inclusion criteria, 65.38% were female, with an average age of 60.9 years (range 38-84). More than half (58%) were obese (BMI ≥ 30). CS was diagnosed in 6 patients with NS (12%). Symptoms suggestive of possible cardiac dysfunction included lower extremity edema (50%), palpitations (46%), chest pain (44%), and shortness of breath (27%). ECG abnormalities included nonspecific T-wave change (40%) and right bundle branch block (17%). Three patients experienced ventricular tachycardia: sustained in one patient and nonsustained in 2 patients. Cardiac MRI was performed in 17 patients (32.7%) and in 3 patients (17.6%), which revealed diffuse myocardial enhancement suggesting CS. DISCUSSION: In this cohort, 12% of patients with NS also had confirmed CS. In addition, these patients had a high burden of cardiovascular disease not directly attributed to sarcoidosis. Our data suggest that patients with NS require comprehensive cardiac evaluation. Future studies are needed to clarify the extent of the direct contribution of granulomatous inflammation on the cardiovascular system from the indirect contribution of treatments such as glucocorticoids that lead to increased risk of cardiovascular disease in sarcoidosis.

Brain-derived extracellular vesicles: Potential diagnostic biomarkers for central nervous system diseases.

Extracellular vesicles (EVs) are membrane-enclosed nanovesicles secreted by cells into the extracellular space and contain functional biomolecules, e.g. signaling receptors, bioactive lipids, nucleic acids, and proteins, which can serve as biomarkers. Neurons and glial cells secrete EVs, contributing to various physiological and pathological aspects of brain diseases. EVs confer their role in the bidirectional crosstalk between the central nervous system (CNS) and the periphery owing to their distinctive ability to cross the unique blood-brain barrier (BBB). Thus, EVs in the blood, cerebrospinal fluid (CSF), and urine can be intriguing biomarkers, enabling the minimally invasive diagnosis of CNS diseases. Although there has been an enormous interest in evaluating EVs as promising biomarkers, the lack of ultra-sensitive approaches for isolating and detecting brain-derived EVs (BDEVs) has hindered the development of efficient biomarkers. This review presents the recent salient findings of exosomal biomarkers, focusing on brain disorders. We summarize highly sensitive sensors for EV detection and state-of-the-art methods for single EV detection. Finally, the prospect of developing advanced EV analysis approaches for the non-invasive diagnosis of brain diseases is presented.

Neurosarcoidosis.

Sarcoidosis affects the nervous system in 5% of cases. 60% of cases involve the cranial and peripheral nerves, the remainder the central nervous system, in which a leptomeningitis, a pachymeningitis and a vasculitis may arise. Stroke and cerebral haemorrhage may occur, and certain infections in the brain are more likely with sarcoidosis. Patients respond well to treatment but oftentimes with residual neurological impairments which may be severe. A greater understanding of the disease and the need for early treatment and use of biological therapies have improved treatment outcome in recent times.

Tuberculous Meningitis or Neurosarcoidosis-a Diagnostic Quandary. From the National Multiple Sclerosis Society Case Conference Proceedings

Distinguishing granulomatous diseases remains diagnostically challenging. Clinical phenotypes and neuroimaging findings resemble many infectious and noninfectious disorders. We describe a Hispanic/Latino man diagnosed with tuberculous meningitis who deteriorated neurologically after treatments. Additional workup revealed a pathology more consistent with neurosarcoidosis. Care access delays and social circumstances likely complicated his diagnosis.

Sarcoidosis with myelitis and autonomic neuropathy treated with infliximab.

In this case report, a 55-year-old man presented with back pain, urinary retention, sensory disturbances, erectile dysfunction, leg paresis and orthostatism. Spinal MRI showed longitudinal extensive myelitis. Lymph node biopsy was compatible with sarcoidosis and a diagnosis of probable neurosarcoidosis (NS) was made. The patient benefited from prednisolone but relapsed during withdrawal. Infliximab resulted in almost complete remission. In conclusion, relapse is often seen when phasing out prednisolone, whereas infliximab appears to have a lasting effect and should be considered in the early stages of severe NS.

Complications of the Central Nervous System in Pediatric Patients With Common Cold Coronavirus Infection During 2014-2019.

BACKGROUND: In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection. METHODS: From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis. RESULTS: A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised. The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients). Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection. CONCLUSION: ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.

Isolated neurosarcoidosis with a primary lesion in the cauda equina.

A man in his late 50s without notable medical background was admitted with subacute onset of bilateral lower extremity weakness. Blood and physiological examinations revealed no significant abnormalities. Cerebrospinal fluid (CSF) examination revealed elevated cell count and protein levels and an immunoglobulin G index of 2.01. T1-weighted MRI showed swelling and enhancement of the cauda equina. After admission, the patient developed bowel and bladder incontinence, deteriorated to manual muscle test 0 and developed right trochlear, trigeminal and facial nerve palsy. He underwent a cauda equina biopsy and was diagnosed with neurosarcoidosis. After methylprednisolone pulse therapy and corticosteroid treatment, cauda equina syndrome including lower extremity weakness and cerebral nerve palsy improved. The patient's daily activities improved to the baseline level over 2 months after discharge. Serum and CSF soluble interleukin-2 receptor levels were within the reference range and decreased with the improvement of neurological and imaging findings.

Circular RNAs: Diagnostic and Therapeutic Perspectives in CNS Diseases.

Circular RNAs (circRNAs) are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends. A growing body of evidence suggests that circRNAs play important roles in physiology and pathology. In particular, accumulating data on circRNA functions in various central nervous system (CNS) diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders. In this review, we focus on the regulatory and functional roles of circRNAs in CNS diseases, highlighting their diagnostic and therapeutic potential, with the aim of providing new insights into CNS diseases.

Cell membrane-based nanomaterials for theranostics of central nervous system diseases.

Central nervous system (CNS) diseases have been widely acknowledged as one of the major healthy concerns globally, which lead to serious impacts on human health. There will be about 135 million CNS diseases cases worldwide by mid-century, and CNS diseases will become the second leading cause of death after the cardiovascular disease by 2040. Most CNS diseases lack of effective diagnostic and therapeutic strategies with one of the reasons that the biological barrier extremely hampers the delivery of theranostic agents. In recent years, nanotechnology-based drug delivery is a quite promising way for CNS diseases due to excellent properties. Among them, cell membrane-based nanomaterials with natural bio-surface, high biocompatibility and biosafety, are of great significance in both the diagnosis and treatment of different CNS diseases. In this review, the state of art of the fabrication of cell membranes-based nanomaterials is introduced. The characteristics of different CNS diseases, and the application of cell membranes-based nanomaterials in the theranostics are summarized. In addition, the future prospects and limitations of cell membrane nanotechnology are anticipated. Through summarizing the state of art of the fabrication, giving examples of CNS diseases, and highlighting the applications in theranostics, the current review provides designing methods and ideas for subsequent cell membrane nanomaterials.

Common Clinical and Molecular Pathways between Migraine and Sarcoidosis.

Migraine and sarcoidosis are two distinct medical conditions that may have some common biological and clinical pathways. Sarcoidosis is a chronic granulomatous disease characterized by the formation of granulomas in various organs, including the lungs, skin, cardiovascular system, lymph nodes, and brain. Migraine is a common comorbidity in sarcoidosis patients and a common neurological disorder characterized by recurrent headaches that can be accompanied by other symptoms, such as nausea, vomiting, and sensitivity to light and sound. There have been several reports of individuals with neurosarcoidosis experiencing migraines, though the exact relationship between the two disorders is not well understood. Both conditions have been associated with inflammation and the activation of the immune system. In sarcoidosis, the formation of granulomas is thought to be an immune response to the presence of an unknown antigen. Similarly, the pain and other symptoms associated with migraines are thought to be caused by inflammation in the brain and the surrounding blood vessels. There is also evidence to suggest an interplay of environmental and genetic factors playing a role in both conditions, but evidence is inconsistent with the hypothesis of shared genetic susceptibility. This review aims to illustrate common clinical and biological pathways between migraine and sarcoidosis, including inflammation and dysregulation of the immune system, with a focus on the cumulative burden of concurrent disorders and therapeutic implications.

Neurosarcoidosis: Diagnostic Challenges and Mimics A Review.

PURPOSE OF REVIEW: Neurosarcoidosis is a rare manifestation of sarcoidosis that is challenging to diagnose. Biopsy confirmation of granulomas is not sufficient, as other granulomatous diseases can present similarly. This review is intended to guide the clinician in identifying key conditions to exclude prior to concluding a diagnosis of neurosarcoidosis. RECENT FINDINGS: Although new biomarkers are being studied, there are no reliable tests for neurosarcoidosis. Advances in serum testing and imaging have improved the diagnosis for key mimics of neurosarcoidosis in certain clinical scenarios, but biopsy remains an important method of differentiation. Key mimics of neurosarcoidosis in all cases include infections (tuberculosis, fungal), autoimmune disease (vasculitis, IgG4-related disease), and lymphoma. As neurosarcoidosis can affect any part of the nervous system, patients should have a unique differential diagnosis tailored to their clinical presentation. Although biopsy can assist with excluding mimics, diagnosis is ultimately clinical.

Free light chains as a reliable biomarker of intrathecal synthesis in the diagnosis of CNS inflammatory diseases.

OBJECTIVE: To address the diagnostic performances of cerebrospinal fluid (CSF) free light chains (FLC) measurements compared to oligoclonal bands (OCB) to support multiple sclerosis (MS) diagnosis. RESULTS: kFLC index showed the highest diagnostic accuracy to detect MS patients with the highest AUC compared to OCB, IgG index, IF kFLC R, kFLC H, λFLC index and IF λFLC. CONCLUSIONS: FLC indices are biomarkers of intrathecal Immunoglobulin synthesis and central nervous system (CNS) inflammation. kFLC index can discriminate between MS and other CNS inflammatory disorders, while λFLC index is less informative for MS but can play a role to support the diagnosis of other inflammatory CNS disorders.

Diagnostic Dilemma of Central Nervous System Tuberculosis with Neurocysticercosis and Neurosarcoidosis: A Case Report.

Multiple ring-enhancing lesions are commonly encountered abnormalities in neuroimaging. There are many differentials for such lesions as infections, neoplasms, vascular lesions, inflammatory and demyelinating conditions, and granulomatous diseases. In developing countries, tuberculoma and neurocysticercosis are the two important etiologies to be considered. This case report illustrates how multiple ring-enhancing lesions can lead to our management in one direction while the true diagnosis remains elusive. A 53-year-old male who presented with a headache was initially diagnosed and treated as neurocysticercosis, then neurosarcoidosis ultimately turned out to be a case of Central Nervous System Tuberculosis on further evaluation. Consideration of only clinical scenarios and neurological imaging can lead to diagnostic inaccuracy, mismanagement and poor outcome, therefore, other supporting lab investigations should be considered for making a correct diagnosis. Keywords: brain; case reports; neurocysticercosis; sarcoidosis; tuberculoma.