Neurosarcoidosis: Current Perspectives on Diagnosis, Management, and Future Directions.

Neurosarcoidosis, a manifestation of sarcoidosis affecting the central or peripheral nervous system, presents unique challenges in diagnosis and management. Neurosarcoidosis can manifest with a wide range of symptoms, including cranial neuropathies, seizures, meningitis, and cognitive impairments. The heterogeneity of presentations often leads to diagnostic delays and complications. Diagnosis relies on a combination of clinical features, neuroimaging, cerebrospinal fluid analysis, and evidence of systemic sarcoidosis. Recent advances in imaging techniques, including high-resolution MRI, positron emission tomography (PET) scans, and novel biomarkers, have improved diagnostic accuracy. However, distinguishing neurosarcoidosis from mimicking conditions such as multiple sclerosis remains challenging. Treatment typically begins with corticosteroids, often requiring long-term immunosuppression. Second-line agents such as methotrexate and mycophenolate mofetil are frequently used as steroid-sparing options. Biologic therapies, particularly Tumor necrosis factor-alpha (TNF-α) inhibitors like infliximab, have shown promise in refractory cases. The long-term management of neurosarcoidosis necessitates a multidisciplinary approach with regular monitoring of disease activity and treatment response. Despite advancements, significant knowledge gaps persist in understanding the etiology, pathophysiology, and optimal management of neurosarcoidosis. Future research directions include identifying specific biomarkers, developing targeted therapies, and exploring novel imaging techniques. The rarity and heterogeneity of neurosarcoidosis underscore the importance of multicenter studies and international collaborations to advance our understanding and improve patient outcomes. Emerging technologies and innovative therapeutic approaches offer promising avenues for enhancing diagnosis and treatment in the coming years.

Extrapulmonary sarcoidosis.

Sarcoidosis is a chronic disease of unknown origin that develops when a genetically susceptible host is exposed to an antigen, leading to an exuberant immune response characterized by granulomatous inflammation. Although lung involvement is almost universal as well as the leading cause of morbidity and mortality, virtually any organ can be affected. In particular, sarcoidosis of the heart, nervous system, and eyes can be devastating, leading to death, debilitation and blindness, and a multidisciplinary approach involving expert specialists is required for prompt diagnosis and appropriate treatment. Sarcoidosis of the skin can be disfiguring, thus posing a substantial psychologic and social impact on the patients. The diagnosis is often straightforward in the presence of compatible clinical manifestations in patients with biopsy-proven sarcoidosis, but is challenging when extrapulmonary signs/symptoms occur in isolation. Corticosteroids remain the first line therapy, with immunosuppressive or biologic agents being reserved to patients failing or experiencing side effects from steroids or developing refractory disease.

Neurosarcoidosis in a 67-Year-Old Male Without Pulmonary Involvement: A Case Report.

Neurosarcoidosis is a rare and complex form of sarcoidosis that affects the nervous system, presenting significant diagnostic and therapeutic challenges due to its varied neurological symptoms and potential complications. We present a case of a 67-year-old immunocompetent male who presented with altered sensorium, prompting a thorough evaluation. His medical history revealed intermittent low-grade fevers, progressive weight loss, and frailty, rendering him bedridden for over a year. Previous blood tests had ruled out specific etiologies, with normal serum calcium and angiotensin-converting enzyme (ACE) levels. Upon presentation, further diagnostic workup included imaging and laboratory tests. Results showed elevated serum calcium, increased ACE levels, and depressed intact parathyroid hormone levels. MRI of the brain with contrast revealed lobulated mucosal thickening in the right sphenoid sinus and adjacent anterior cavernous sinus. A CT scan of the chest was unremarkable. Additionally, a splenic biopsy revealed hypoechoic foci with neutrophilic, lymphocytic, and histiocytic granulomas. Based on imaging and histopathological findings, the patient was diagnosed with neurosarcoidosis. The patient was treated with prednisolone and methotrexate, leading to a prompt improvement in consciousness and symptoms. Follow-up demonstrated continued improvement and stabilization of his condition. This case highlights the importance of considering neurosarcoidosis in patients with unexplained neurological symptoms and underscores the value of a multidisciplinary approach in managing this challenging condition.

An Atypical Presentation of a Patient With Neurosarcoidosis: A Case Report.

Neurosarcoidosis is a disease in which noncaseating granulomas, characteristic of sarcoidosis, are found within organs of the nervous system such as the brain and spinal cord. This case report highlights a 57-year-old male with worsening bilateral lower extremity weakness and numbness in addition to ptosis and oculomotor nerve palsy of the right eye. Computed tomography (CT) imaging showed mediastinal and hilar lymphadenopathy, which raised suspicion for neurosarcoidosis. Multiple biopsies were taken from lymph nodes in the mediastinal region, which resulted in non-necrotizing epithelioid cell granulomas, consistent with the suspected neurosarcoidosis. Medical providers must include neurosarcoidosis within a much broader differential diagnosis when encountering patients that present with a similar presentation shown in this case report so that treatment can be promptly initiated as soon as possible.

Neurosarcoidosis: Clinical, biological, and MRI presentation of central nervous system disease in a national multicenter cohort.

INTRODUCTION: Neurosarcoidosis (NS) is a systemic inflammatory granulomatous disease affecting of patients with sarcoidosis. Its diagnosis is difficult as there is no specific test for it. Because of its rarity, the management of NS has so far only been described in case series and short retrospective cohorts. The objective of this study is description of the clinical, paraclinical presentation and the therapeutic management of central nervous system (CNS) involvement in NS patients in France. METHODS: This multicenter, retrospective, observational study involved patients hospitalized between 2010 and 2019 with a diagnosis of sarcoidosis and CNS involvement. RESULTS: We included 118 patients (38 with isolated NS, 80 with NS associated with systemic sarcoidosis). NS was the initial presentation in 78% of patients, with cranial nerve involvement (36%), medullary symptoms (23%), and seizures (21%). Twenty-one percent of the patients had already been diagnosed with systemic sarcoidosis. The most frequent biological abnormality was lymphopenia (62.5%), while angiotensin-converting enzyme was increased in 21%. Meningitis was present in 45% and hyperproteinorachia in 69.5% of cases. MRI mainly revealed white matter abnormalities and leptomeningeal enhancement (34%). Corticosteroids were the most useful treatment, and immunosuppressive agents were used in steroid-resistant patients and to limit side effects. Methotrexate, cyclophosphamide, and anti-TNFα were also used, exhibiting good efficacy. CONCLUSIONS: This cohort contributes to a better understanding of the clinical phenotype and associated imaging and biological abnormalities. Sharing of clinical, biological, and imaging data, as well as the therapeutic responses, of patients with NS helps to better understand and manage this disease that affects a small number of patients per center. A database project could be implemented in the future to enable this.

Neurosarcoidosis complicated by systemic vasculitis.

A 62-year-old woman with medical history of hypertension, diabetes mellitus, coronaropathy, neurosarcoidosis, s/p craniotomy (brain mass resection) presented with worsening headaches, generalized weakness, vomiting, and hyporexia over two weeks. Brain MRI showed worsening of the known right cavernous sinus mass, vasculitis panel was negative. Patient received IV steroids; during hospitalization, she had a syncopal episode, CT Head was normal, EKG showed new T-wave inversion with troponin elevation. She experienced worsening mentation, left-sided hemiparesis; CT head showed acute hypodensity in the right MCA territory, CTA revealed bilateral distal M1 segment stenosis. Ineligible for thrombolysis/thrombectomy, she was started on aspirin. Echocardiograms were normal. Ischemic signs in her right toes prompted an aortogram showing arterial obstructions in the RLE, necessitating SFA stent placement, and clopidogrel. IV cyclophosphamide was added without additional vascular complications. This case illustrates neurosarcoidosis complicated by systemic vasculitis of medium-large vessels, responding to aggressive immunosuppression with glucocorticoids and cytotoxic agents.

Neurosarcoidosis of the trigeminal nerve: clinical accompaniments, radiographic findings, and association with neuralgia.

BACKGROUND: Cranial neuropathy is a principal disease manifestation of neurosarcoidosis, but many forms remain poorly described, including trigeminal nerve disease despite its frequency in reported cohorts (5-12%). Herein, we characterize the clinical course of patients with neurosarcoidosis involving the trigeminal nerve. METHODS: A single-center retrospective cohort analysis of patients with biopsy-proven sarcoidosis involving the trigeminal nerve was conducted between 1/1/2000-3/7/2023. RESULTS: The trigeminal nerve was affected in 14/245 (5.7%) patients, being clinically symptomatic in 5/245 (2.0%) and asymptomatic with radiographic involvement in 9/245 (3.7%). 14/14 (100.0%) patients had systemic sarcoidosis. In the symptomatic group, trigeminal neuropathy was an inaugural feature in 4/5 (80.0%), unilateral in 5/5 (100.0%) with the V1 subdivision most affected (4/5, 80.0%), and associated with neuralgia in 2/5 (40.0%). On MRI, the cisternal nerve roots (9/14, 64.3%), Meckel's cave (7/14, 50.0%), and cavernous sinus (5/14, 35.7%) were most commonly affected, and 14/14 (100.0%) patients had extra-trigeminal neuroinflammation on cranial MRI. CSF was abnormal in at least one dimension in 11/12 (91.7%) tested. All three treated patients with symptomatic trigeminal neuropathy responded to immunomodulatory treatment, and symptomatic treatments for trigeminal neuralgia were helpful in two patients. After a median follow-up period of 63 months, the median modified Rankin scale score was 1 for both subgroups. CONCLUSION: Neurosarcoidosis may involve any portion of the trigeminal apparatus, and when affected, it frequently demonstrates a mismatch in radiographic involvement from its clinical manifestations of facial numbness and pain, and typically occurs in association with other clinical or radiographic manifestations of neurosarcoidosis.

A Comprehensive Characterization of Patients with Spinal Cord Neurosarcoidosis: A Single Center Cross-Sectional Study of Clinical Outcomes.

Background/Objective: To describe the clinical features and radiological outcomes of patients with spinal cord neurosarcoidosis, treatments, and long-term follow-up for this rare disorder. Methods: A cross-sectional, retrospective medical chart review was performed for all patients with spinal cord neurosarcoidosis treated at a single center between 01/1995 and 12/2020. Radiological imaging, laboratory test results, the type of immunosuppressive therapy, and function test scores were reviewed. Results: We assessed 39 patients with spinal cord neurosarcoidosis (23 men, 16 women, mean age at presentation 46.4 years, SD 10.2 years). The mean (SD) duration of spinal cord neurosarcoidosis at data abstraction was 9.8 (6.3) years. There were 24 patients (62%) with extensive intramedullary lesions, 8 (21%) with multiple patchy intramedullary lesions, 12 (31%) with leptomeningeal involvement, and 7 (18%) with nerve root enhancement. The cervical spine was the most commonly affected region in 33 patients (85%). The most common presenting symptoms were paresthesia/neuropathic pain in 20 (51%) and weakness of extremities in 15 (38%) patients. Most patients (n = 37; 95%) had been treated with corticosteroids at symptom onset, and methotrexate was the most used immunosuppressive therapy (n = 19; 49%). Of 34 patients with follow-up magnetic resonance imaging (MRI) available, the median time to improvement per MRI was 10.8 months (95% CI, 6.1-17.0 months). Of 31 patients with MRI enhancement at presentation, 18 (58%) had complete enhancement resolution at follow-up, with a median time to resolution of 51.8 months (95% CI, 24.9-83.4 months). Patients had significantly lower pyramidal (p = 0.004) and sensory functional (p = 0.031) systems scores from presentation to the last clinic visit. Conclusions: Because spinal cord neurosarcoidosis is challenging to diagnose and no set treatment guidelines exist, clarifying patients' clinical parameters and responses to various treatments is needed to improve timely and efficient care. The incidence of spinal cord involvement in sarcoidosis in our cohort was higher than intracranial involvement and most patients had a long extensive intramedullary lesion. We also observed that most patients with spinal cord neurosarcoidosis improved clinically and radiologically after treatment; however, the resolution of MRI enhancement after immunosuppressive therapy may take years. Prospective studies of neurosarcoidosis will be crucial to address questions about effective treatment and long-term prognosis.

Systemic Sarcoidosis With Neurosarcoidosis Features as a Risk Factor for Multifocal Osteonecrosis.

Sarcoidosis is a systemic inflammatory disease that affects diverse organs such as the lungs, skin, eyes, and brain. Osseous involvement in sarcoidosis usually affects bones of the appendages with direct infiltration of non-caseating granulomas without bony infarcts. Symptoms of sarcoid bone lesions respond well to corticosteroid therapy. In contrast, corticosteroids act as a risk factor for the development of osteonecrosis resulting in pain and disability. Osteonecrosis that involves three or more different anatomic sites, defined as multifocal osteonecrosis (MFON), is rare. MFON has not been documented in the setting of sarcoidosis. We report a systemic sarcoidosis patient with predominant neuropsychiatric manifestations, who progressively developed MFON. Despite the limited use of corticosteroid treatment, the high burden of systemic sarcoidosis and its related neuropsychiatric involvementmay have collectively contributed to the development of MFON. This case highlights the rare association of MFON with systemic sarcoidosis and the need for further investigation into the underlying pathogenesis of MFON to prevent disability and morbidity.

Neurosarcoidosis Complicated by Noncommunicating Hydrocephalus with Atypical Presentation, Diagnosed and Treated with Endoscopic Surgery: A Case Report.

Neurosarcoidosis is a condition that is characterized by the occurrence of noncaseating epithelioid granulomas in various organs throughout the body, including the lungs, heart, and central nervous system. It is particularly prevalent in cases of noncommunicating hydrocephalus. While its clinical presentations may vary, neurological deficits such as hemiparesis are extremely uncommon. We herein present a case of unilateral hydrocephalus resulting from neurosarcoidosis presenting with hemiparesis. A 58-year-old woman exhibited right hemiparesis, altered mental status, and aphasia persisting for 1 month. Magnetic resonance imaging showed unilateral hydrocephalus of uncertain etiology. The patient underwent external ventricular drainage, endoscopic fenestration of the septum pellucidum (septostomy), and lesion biopsy, which led to a histopathological diagnosis. Hemiparesis can accompany unilateral hydrocephalus caused by neurosarcoidosis. Endoscopic procedures provide an effective option for the diagnosis and treatment of noncommunicating hydrocephalus caused by neurosarcoidosis.

Aseptic meningitis with recurrent headache episodes, vomiting, and central fever as first manifestation of isolated neurosarcoidosis: a case report.

BACKGROUND: Neurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity. CASE REPORT: A 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in ß2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found. CONCLUSIONS: This case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits.

Diagnostic value of soluble Interleukin-2 receptor in patients suffering neurosarcoidosis: A systematic review.

Background: Neurosarcoidosis is an inflammatory granulomatous disease. Up to 25% of occult sarcoidosis affecting the nervous system are only detected by autopsy. In addition, in recent years the suspicion arose that the soluble Interleukin-2 Receptor (sIL-2R) might be useful in differentiating between neurosarcoidosis and neurosarcoidosis-like diseases such as neurotuberculosis, multiple sclerosis, or cerebral lymphoma. Objectives: Therefore, we aimed to systematically review randomized controlled trials (RCT), observational studies, and case-control studies evaluating sIL-2R levels in neurosarcoidosis patients. Design: For this systematic review, a comprehensive literature search of electronic databases including EMBASE, The Web Of Science, The Cochrane Library, MEDLINE, and Google Scholar was conducted. The search was limited to the English language and publication date up to January 08th, 2024. Data Sources and Methods: As part of the search strategy conducted, 6 articles met the inclusion criteria. Two independent reviewers extracted the relevant data from each article. In addition, 2 independent reviewers assessed the quality of each study using the Newcastle-Ottawa Scale (NOS). Results: We included 6 studies comprising 98 patients suffering from neurosarcoidosis, 525 non-sarcoidosis patients, and 118 healthy controls. Included studies were published between 2010 and 2023. Cerebrospinal fluid (CSF) sIL-2R levels differed significantly between neurosarcoidosis patients and multiple sclerosis, vasculitis, and healthy controls whereas serum sIL-2R levels did not reveal sufficient discriminative power. sIL-2R index was able to discriminate neurosarcoidosis from neurotuberculosis, bacterial/viral meningitis, and healthy controls. Conclusions: In this systematic review, we found indications that sIL-2R may be a useful biomarker for the diagnosis of neurosarcoidosis. To determine an additional diagnostic value of sIL-2R, large prospective studies are needed that not only examine absolute sIL-2R levels in serum or CSF but also the dynamic changes as well as the implications of renal function on sIL-2R levels.

Neurosarcoidosis as a rapidly progressive dementia associated with normal pressure hydrocephalus.

Neurosarcoidosis (NS) is a rare subtype of sarcoidosis with a poor prognosis and diverse clinical presentations that often poses a diagnostic and therapeutic challenge. We describe the case of a 53-year-old male with an initial diagnosis of lingual sarcoidosis, who subsequently developed ataxia and rapidly progressive cognitive impairment. A lumbar puncture revealed hypoglycorrhachia, hyperproteinorrachia, lymphocytic pleocytosis, and elevated IL-6 levels (600 pg/ml). Cerebrospinal fluid flow cytometry showed an elevated CD4 lymphocyte concentration and a CD4+/CD8+ ratio of 3.91, indicative of NS. Brain MRI showed hyperintense periventricular and subcortical lesions on FLAIR/T2 resembling progressive multifocal leukoencephalopathy (PML), although negative PCR for JC virus ruled out the differential diagnosis. Following a favorable evolutionary course with corticosteroid pulses, the patient relapsed with normotensive hydrocephalus, treated with immunosuppressants and ventriculoperitoneal shunting with a good response to date. This case underscores the importance of maintaining a high index of suspicion for NS in individuals with sarcoidosis and neurologic symptoms. In these cases, cerebrospinal fluid biomarkers such as IL-6 and CD4+/CD8+ ratio are essential to guide the diagnosis. Furthermore, it highlights that hydrocephalus is a rare complication and requires a multidisciplinary approach, including medical and neurosurgical treatment.

La neurosarcoidosis es un subtipo raro de sarcoidosis con mal pronóstico y diversas presentaciones clínicas que a menudo plantea un reto diagnóstico y terapéutico. Describimos el caso de un varón de 53 años con diagnóstico inicial de sarcoidosis lingual, que posteriormente desarrolló ataxia y deterioro cognitivo de rápida evolución. Una punción lumbar reveló hipoglucorraquia, hiperproteinorraquia, pleocitosis linfocítica y niveles elevados de IL-6 (600 pg/ml). La citometría de flujo del líquido cefalorraquídeo mostró una concentración elevada de linfocitos CD4 y un cociente CD4+/CD8+ de 3.91, indicativo de neurosarcoidosis. La RM cerebral evidenció lesiones hiperintensas periventriculares y subcorticales en FLAIR/T2 que se asemejaban a una leucoencefalopatía multifocal progresiva (LMP), aunque la PCR negativa para el virus JC descartó el diagnóstico diferencial. Tras un curso evolutivo favorable con pulsos de corticoides, el paciente recayó con hidrocefalia normotensiva, tratada con inmunosupresores y derivación ventriculoperitoneal con buena respuesta hasta la fecha. Este caso subraya la importancia de mantener un alto índice de sospecha de neurosarcoidosis en individuos con sarcoidosis y síntomas neurológicos. En estos casos, los biomarcadores del líquido cefalorraquídeo tales como la IL-6 y el cociente CD4+/CD8+ son esenciales para orientar el diagnóstico. Además, destaca que la hidrocefalia es una complicación poco frecuente y requiere un abordaje multidisciplinario, que incluya tratamiento médico y neuroquirúrgico.

Neurosarcoidosis With Panhypopituitarism: Two Cases and Literature Review.

Neurosarcoidosis (NS) with hypothalamic-pituitary (HP) involvement (HP-NS) is a rare clinical condition, conferring variable hormonal deficits that are typically irreversible. Here, we present 2 cases of NS with panhypopituitarism. The first patient presented with cauda equina syndrome and arginine vasopressin deficiency, while the second developed recurrent optic neuritis and vision loss in the setting of a sellar mass. In the first case, neurological symptoms resolved after therapy with high-dose glucocorticoids, infliximab, and methotrexate; while in the second, visual restoration followed resection of the granulomatous tissue and immunosuppressive therapy. In both cases, pituitary dysfunction persisted despite neurological improvement. We contextualized the presentations and outcomes through a literature review of HP-NS case reports and case series. This revealed high rates of extraneurologic sarcoidosis in HP-NS patients with panhypopituitarism, while underscoring the need for hormonal replacement-as endocrinopathies rarely respond to sarcoidosis-directed immunosuppression.

Neurosarcoidosis: An under-diagnosed cause of myelopathy.

Sarcoidosis is a granulomatous disorder with multi-organ involvement, and etiology still remains unknown. Neurosarcoidosis is the involvement of the nervous system in sarcoidosis. Spinal cord involvement is usually intra-dural, but extra-dural involvement can also occur. Here, we report a case of 30 years old lady presenting with subacute onset paraparesis with bladder and bowel involvement, which was finally diagnosed as sarcoidosis-associated myelopathy with the longitudinally extensive transverse myelitis (LETM) phenotype.

Longitudinally extensive transverse myelitis as an initial manifestation of sarcoidosis: A rare case and its management.

Key Clinical Message: Sarcoidosis-induced LETM represents a rare but life-threatening neurological manifestation of sarcoidosis, characterized by spinal cord inflammation, and associated neurological deficits. Sarcoidosis should be included in the differential diagnosis of LETM, particularly in patients with no lung involvement. Prompt recognition and management are obligatory to optimize outcomes and prevent long-term disability. Abstract: Sarcoidosis is a multisystem inflammatory granulomatous disorder characterized by the formation of noncaseating granulomas. Although sarcoidosis commonly affects the skin, lymph nodes, and lungs, neurological involvement of sarcoidosis has also been reported. Longitudinally extensive transverse myelitis (LETM) is a rare but well-documented serious manifestation of neuroscoidosis. We report a case of LETM caused by sarcoidosis in a 53-year-old male who presented with progressive bilateral lower extremity weakness, urinary retention, and paresthesia. Laboratory evaluations revealed elevated inflammatory markers. Magnetic resonance imaging of the spine showed hyperintense signals consistent with transverse myelitis. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and elevated protein levels. Chest computed tomography showed hilar lymphadenopathy. A biopsy of the intrathoracic lymph node showed noncaseating granulomas consistent with sarcoidosis. A diagnosis of sarcoidosis-induced LETM was made after ruling out all other possible etiologies. His condition improved gradually after starting high-dose prednisone, mycophenolate, and rehabilitation strategies. Our case underscores the importance of prompt diagnosis and management of sarcoidosis-induced LETM and highlights that sarcoidosis must be included among differential diagnoses of LETM, especially in cases with no lung involvement.

A Case of Suspected Neurosarcoidosis Evading Diagnosis With Cervical Biopsy.

Neurosarcoidosis is a rare manifestation of sarcoidosis, posing diagnostic challenges due to its varied clinical presentation and the lack of definitive diagnostic tests. We present a case of a 46-year-old African American female with progressive ascending bilateral sensory loss, weakness, and a bifrontal headache. Despite undergoing extensive diagnostic workup including cerebrospinal fluid analysis, neuroimaging, and bronchoscopic evaluation, a definitive diagnosis remained elusive. The patient underwent an open cervical spinal cord biopsy, which did not yield conclusive evidence of neurosarcoidosis. Subsequent complications included suspicion of an epidural abscess and post-operative cervical kyphosis. This case underscores the diagnostic dilemma and potential complications associated with the evaluation and management of neurosarcoidosis, highlighting the importance of a multidisciplinary approach in such cases.

Sarcoidosis Presenting as Longitudinally Extensive Transverse Myelitis: A Case Report.

Spinal cord sarcoidosis is a rare condition that can present as a longitudinally extensive transverse myelitis. Current imaging may suggest this pathology, but the final diagnosis relies on the histologic findings. Teaching point: Considering neurosarcoidosis in the differential diagnosis of longitudinally extensive transverse myelitis.

Stroke associated with sarcoidosis: A systematic review of reported cases.

BACKGROUND: Sarcoidosis can be associated with stroke. Whether granulomatous vasculitis directly causes stroke in patients with sarcoidosis remains unclear. This systematic review aims to consolidate reports of concurrent sarcoidosis and stroke. METHODS: Medline and Embase were searched for terms encompassing sarcoidosis and stroke with a censoring date of March 25, 2023. Cases were reviewed by two authors, with the inclusion criteria: biopsy-confirmed systemic sarcoidosis, stroke confirmed by imaging or pathology, clinical description of individual patient history, and English language publications. RESULTS: Of 1628 articles screened, 51 patients from 49 articles were included (65% male, mean age 41 years). Seventy-one percent of strokes were ischemic and 29% were hemorrhagic. Lesions were supratentorial in 78% of cases, infratentorial in 34%, and multifocal in 45%. Presenting symptoms were variable, with the most common being headache (38%) followed by weakness (35%). 10 patients had recurrent strokes. Stroke was the presenting symptom of sarcoidosis in 65%. 21 patients had brain biopsies. The most common neuropathologic findings were perivascular (33%) or intramural (33%) non-caseating granulomas. On imaging, 32 patients had findings suggestive of neurosarcoidosis, including 35% with evidence of meningeal enhancement. 63% of patients were treated with corticosteroids and/or other immunomodulatory therapy, with varying clinical improvement. CONCLUSIONS: Stroke associated with sarcoidosis generally follows trends in stroke incidence, with infarction being more common than hemorrhage and male sex carrying a higher risk. Most patients were diagnosed with sarcoidosis during or following their stroke episode. Brain biopsy infrequently shows clear granulomatous vasculitis.

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.