Neurosarcoidosis …

Neuroimmunology

Updated 04.26.2026
Released 05.08.1995
Expires For CME 04.26.2029

Neurosarcoidosis

Authors: Munther M Queisi MD MPH, Daniel P Kurz Jr MD

See Contributor Disclosures

Editor: Anthony T Reder MD

Cite this article

Neurosarcoidosis

In This Article

Quick Link

Introduction

Overview

Sarcoidosis is a rare, multisystem inflammatory disorder characterized by noncaseating granulomatous inflammation, most commonly affecting the lungs, followed by lymph nodes, skin, and eyes (22; 49). Neurologic involvement, referred to as neurosarcoidosis, occurs in approximately 5% to 26% of patients with systemic sarcoidosis and represents one of the most challenging manifestations of the disease (06).

Neurosarcoidosis is defined by granulomatous involvement of the central and/or peripheral nervous systems and is notable for its marked clinical heterogeneity (97; 06). It may present in the context of established systemic sarcoidosis or as an isolated neurologic syndrome without evident systemic disease, often contributing to diagnostic delay or misdiagnosis (14). The condition can affect virtually any part of the nervous system, with phenotypes including parenchymal (encephalitic) disease, cerebrovascular disease, cranial neuropathies (isolated or multiple), leptomeningeal or pachymeningeal involvement, spinal cord disease, neuroendocrine dysfunction, and peripheral nervous system manifestations, such as large fiber neuropathy, small fiber neuropathy, autonomic neuropathy, and myopathy (103). These manifestations may occur in isolation or concurrently, further complicating clinical recognition and management (24).

The diagnosis of neurosarcoidosis remains challenging due to its protean presentations, lack of specific biomarkers, and frequent overlap with infectious, neoplastic, and other inflammatory conditions (97; 90; 94). If left untreated, neurosarcoidosis can lead to substantial and potentially irreversible morbidity and, in some cases, mortality (105). Recent advances in understanding disease immunopathogenesis, along with increasing evidence supporting the use of targeted biological therapies—including tumor necrosis factor inhibitors and interleukin-6 (IL-6) inhibitors—have begun to shape evolving diagnostic frameworks and therapeutic strategies (89; 36).

Key points

	• Neurosarcoidosis occurs in a minority of patients with systemic sarcoidosis but carries a disproportionate risk of morbidity and diagnostic complexity.
	• Clinical presentations are highly heterogeneous and may involve any part of the central or peripheral nervous system, often mimicking infectious, neoplastic, or other inflammatory disorders.
	• Neurosarcoidosis may present as an isolated neurologic syndrome without evidence of systemic disease, contributing to frequent diagnostic delay or misdiagnosis.
	• No single diagnostic test is definitive; diagnosis typically relies on a combination of clinical, radiographic, and histopathologic findings, often requiring exclusion of alternative etiologies.
	• Early recognition and treatment are critical, as untreated disease can result in irreversible neurologic injury and increased mortality.
	• Emerging biological therapies, particularly tumor necrosis factor inhibitors, are increasingly being used in refractory disease and are reshaping management strategies.

Historical note and terminology

The history of sarcoidosis spans approximately 150 years. The first clinical description was provided in 1869 by Jonathan Hutchinson, a London-based surgeon and dermatologist who noted unusual skin lesions (96; 25). The term “sarcoidosis” was later coined by Caesar Boeck in 1899 to describe his histopathological findings of “epithelioid cells with large pale nuclei and a few giant cells” on skin biopsy. Initially considered primarily a dermatologic condition, sarcoidosis gradually came to be recognized as a multisystem disorder, most commonly affecting the lungs (43; 95).

Neurosarcoidosis evolved from early reports of uveoparotid fever to encompass involvement of virtually any region of the neuroaxis (44). Despite its recognition, a standardized definition for neurosarcoidosis was not established until 2018, when the Neurosarcoidosis Consortium Consensus Group proposed formal diagnostic criteria (97). However, the timeline for neurosarcoidosis as a distinct clinical entity remains incompletely documented.

Despite the work of multiple generations of researchers, fundamental questions remain regarding the pathogenesis of neurosarcoidosis, including the precise triggers and whether an infectious origin plays a role. The underlying cause of the disease continues to be elusive, underscoring ongoing challenges in diagnosis and management (95; 96).

Clinical manifestations

Presentation and course

Meningeal involvement. Meningeal involvement in neurosarcoidosis can manifest as subacute, chronic, or relapsing aseptic meningitis, as well as pachymeningitis (35). These patients typically present with headaches, neck stiffness, or altered mental status. The temporal pattern of symptoms, whether persistent, recurrent, or relapsing, is a key clue for clinical suspicion in consideration of whether to apply a treatment strategy (57; 77).

Gadolinium-enhanced MRI is critical for evaluation, typically revealing diffuse and nodular leptomeningeal enhancement. In pachymeningeal disease, imaging may demonstrate focal dural-based masses that mimic tumors or cavernous sinus lesions, or diffuse dural thickening and enhancement. Common sites of dural involvement include the falx cerebri, anterior and middle cranial fossae, and the tentorium cerebelli. Leptomeningeal disease may extend along the dorsal subpial region of the spinal cord, occasionally reaching the cauda equina (18; 07).

Diagnosis requires careful exclusion of alternative causes. CSF analysis and clinical assessment help rule out infectious etiologies (tuberculosis, viral, or fungal meningitis), neoplastic meningitis, and other inflammatory disorders, such as myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Aseptic meningitis is defined by recurrent or persistent meningeal symptoms without evidence of infection (57; 77).

Meningeal involvement often coexists with other neurosarcoidosis phenotypes, including cranial neuropathies, parenchymal/encephalitic lesions, and can lead to complications such as hydrocephalus. Pachymeningeal disease, particularly when diffuse or multifocal, is frequently refractory to oral therapies and often requires escalation to biological agents, including tumor necrosis factor (TNF) inhibitors (66).

Cranial neuropathies. Cranial neuropathies in neurosarcoidosis often present acutely, either as a single episode or in a recurrent pattern. Cranial nerve VII (facial nerve) is the most commonly affected cranial nerve, manifesting as unilateral or bilateral facial weakness. Optic nerve involvement, including optic neuritis or perineuritis, is the next most frequent, followed by trigeminal and vestibulocochlear nerves. Symptoms include facial numbness or pain, tinnitus, hearing loss, or vertigo. Less commonly, cranial nerves IX, X, and XII may be involved, resulting in dysphagia, dysphonia, or tongue dysfunction. Bilateral sensorineural hearing loss should prompt consideration of neurosarcoidosis (14; 06; 10).

Pathophysiologically, cranial nerves may be affected by direct granulomatous infiltration, adjacent meningeal disease, cavernous sinus involvement, or secondary effects of raised intracranial pressure. Approximately 44% of patients present with involvement of more than one cranial nerve, which may occur simultaneously or sequentially and may be bilateral (06).

Evaluation includes high-resolution MRI of the brain, with orbital or skull base sequences as indicated. MRI findings often demonstrate optic nerve or sheath enhancement consistent with optic neuritis or perineuritis (inflammation of the nerve sheath), and other affected cranial nerves may show focal enhancement. Thorough neuro-ophthalmologic assessment is recommended for patients with visual symptoms to evaluate for ocular manifestations of sarcoidosis, including uveitis, iridocyclitis, or other eye involvement (18; 40).

It is essential to exclude mimics, such as multiple sclerosis, neuromyelitis optica, or myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Prognostically, patients with isolated cranial neuropathy generally have a favorable course, with low risk of progression, except in cases of optic neuropathy (52; 106; 68). Cranial neuropathies typically respond to corticosteroids; however, optic nerve and vestibulocochlear involvement may follow a relapsing-remitting or chronic course, sometimes necessitating more aggressive immunotherapy, including biological agents (68).

Encephalitic or parenchymal involvement. Encephalitic or parenchymal involvement is a common and often severe manifestation of neurosarcoidosis, reported in approximately 30% to 50% of cases. Clinical presentation is highly variable but frequently includes seizures, encephalopathy with cognitive or behavioral changes, headaches, focal neurologic deficits, and signs of increased intracranial pressure. The disease course is typically subacute but may follow a relapsing-remitting or chronic trajectory (32; 58).

Neuroimaging demonstrates diverse patterns. Lesions most commonly involve the hypothalamus, brainstem, and cerebral hemispheres and often show persistent or heterogeneous contrast enhancement, sometimes with surrounding edema. These imaging features can closely mimic malignancy, including gliomas or lymphomas. In some cases, non-enhancing periventricular lesions are observed; these may remain stable over time, and their clinical significance is uncertain. Parenchymal lesions may occur in isolation or in conjunction with leptomeningeal involvement (105; 73).

The differential diagnosis is broad and includes demyelinating disorders, such as multiple sclerosis, neuromyelitis optica, and MOG antibody–associated disease, as well as inflammatory conditions, such as neuro-Behçet disease and primary or secondary CNS malignancies. In patients presenting with atypical demyelinating features or suspected neoplasm, neurosarcoidosis should be carefully considered and excluded (73).

Parenchymal neurosarcoidosis can follow an aggressive course and may be less responsive to corticosteroids compared to other phenotypes, frequently necessitating escalation to second-line or biological immunotherapies (73).

Myelopathic involvement. Myelopathic involvement in neurosarcoidosis represents a diagnostically challenging phenotype, particularly in patients without a known history of systemic sarcoidosis, in whom it may be the initial manifestation of disease. The presentation is often nonspecific and may be mistaken for neoplastic, infectious, inflammatory, or degenerative conditions, including spinal cord tumors or spondylotic myelopathy. Misdiagnosis can lead to unnecessary surgical interventions with potential for permanent neurologic disability (66; 74; 53).

Clinically, patients typically present with subacute to chronic progressive myelopathy characterized by limb weakness, sensory disturbances, gait imbalance, and bowel or bladder dysfunction. Examination often reveals a sensory level, hyperreflexia, and other upper motor neuron signs. There is a notable predilection for dorsal column involvement, leading to impaired vibration and proprioception, which contributes to sensory ataxia and recurrent falls (66).

MRI of the spine with and without contrast is essential for evaluation. Imaging findings are variable but most commonly demonstrate longitudinally extensive spinal cord lesions (involving three or more vertebral segments), typically in the cervical or thoracic cord. Other patterns include short-segment lesions or tumefactive-appearing masses, particularly involving the dorsal subpial region on axial imaging. Enhancement patterns may vary, and associated findings can include spinal leptomeningeal involvement, meningitis, or meningoradiculitis (66; 67; 81).

The differential diagnosis is broad and includes inflammatory myelopathies, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and MOG antibody–associated disease, as well as infectious etiologies and neoplastic processes. Careful evaluation is required to avoid misdiagnosis and inappropriate management (78).

Myelopathic neurosarcoidosis often follows a progressive course and may require early and aggressive immunosuppressive therapy. Many patients ultimately require escalation to biological agents, including tumor necrosis factor (TNF) inhibitors. Delayed diagnosis and treatment are associated with a higher risk of irreversible spinal cord injury and long-term disability (30).

Cerebrovascular manifestations. Cerebrovascular manifestations of neurosarcoidosis are uncommon but clinically significant and may present acutely with focal neurologic deficits, including motor weakness, sensory disturbances, visual changes, or cognitive and behavioral alterations. These events may be the initial manifestation of disease or occur in patients with known systemic sarcoidosis (41; 79; 109).

The underlying mechanisms are multifactorial and include granulomatous vasculitis with perivascular and intramural inflammation, meningeal inflammation, vascular compression from adjacent mass lesions, and cardioembolism in the setting of cardiac sarcoidosis. Granulomatous vasculitis leads to vessel wall thickening, luminal narrowing, and subsequent ischemic or hemorrhagic events. Small perforating vessels are most affected, resulting in lesions within deep brain structures, such as the brainstem, thalamus, and basal ganglia. Large territorial infarcts and transient ischemic attacks are less frequent but may occur. Cerebral venous sinus thrombosis is another recognized manifestation (45; 41; 109).

A key diagnostic challenge lies in distinguishing cerebrovascular events related to neurosarcoidosis from those due to conventional vascular risk factors, as many patients also have comorbidities, such as diabetes, hyperlipidemia, obesity, or cardiomyopathy. This distinction is critical, as inflammatory vasculopathy requires immunosuppressive therapy rather than standard stroke management alone (75).

Neuroimaging plays a central role in evaluation. Contrast-enhanced MRI of the brain, along with vascular imaging, such as magnetic resonance angiography or venography, may identify small infarcts, microhemorrhages, or venous thrombosis. However, conventional imaging may be limited in detecting small-vessel involvement. Advanced vessel wall imaging techniques, including black-blood MRI, can demonstrate intracranial vessel wall enhancement and are increasingly valuable in identifying inflammatory vasculopathy and potential biopsy targets (112; 26).

Although historically considered rare, cerebrovascular involvement in neurosarcoidosis may be underrecognized and should be routinely considered in the evaluation of patients with compatible clinical and radiographic features.

A subset of patients with neurosarcoidosis demonstrates involvement of the hypothalamic–pituitary axis, including the pituitary stalk and surrounding suprasellar structures. This results from granulomatous inflammation of the infundibular or pre-infundibular regions and may lead to hypophysitis or hypothalamic dysfunction, which can be irreversible despite treatment (11). Notably, MRI findings may be normal in some cases, further complicating diagnosis (54).

Clinical manifestations. Clinical manifestations are often dominated by endocrine dysfunction, including central diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypogonadism, and thyroid abnormalities, as well as systemic features, such as sleep disturbances, bradycardia, and hypothermia. These patients frequently require long-term hormonal replacement and close multidisciplinary monitoring (54; 03).

Although uncommon, neuroendocrine involvement can progress to life-threatening complications. Patients are at risk for acute adrenal crisis, which may present with hypotension, altered mental status, and hypoglycemia, necessitating intensive care management. Tuberculosis can infect adrenals, often bilaterally, and should be excluded. Treatment requires prompt administration of intravenous corticosteroids along with supportive measures, including fluid and electrolyte correction, initiation of desmopressin when indicated, and stress-dose hydrocortisone (46; 61).

Peripheral nervous system involvement. Peripheral nervous system involvement in sarcoidosis remains underrecognized despite its significant impact on patient function and quality of life. Patients most commonly present with pain and paresthesia in a length-dependent, glove-and-stocking distribution, although asymmetric polyradiculoneuropathy can also occur. Less frequently, presentations include mononeuritis multiplex, plexopathy, or isolated sensory or motor neuropathies. Electrodiagnostic studies typically demonstrate a distal axonal sensorimotor polyneuropathy, which is the most common pattern, although demyelinating features may also be observed. In select cases, nerve and muscle biopsy may aid in diagnosis (06). Small fiber neuropathy is increasingly recognized as a para-neurosarcoidosis phenomenon, as its pathogenesis is not directly related to granulomatous infiltration. Clinically, small fiber neuropathy presents with neuropathic pain and paresthesia followed by numbness, with involvement that may extend beyond distal extremities to include the face (particularly the trigeminal distribution), torso, and proximal limbs. Autonomic dysfunction is also common and may manifest as early satiety, orthostatic intolerance, palpitations, erectile dysfunction, or abnormalities in sweating. Diagnosis is established with a skin biopsy demonstrating reduced intraepidermal nerve fiber density as well as decreased sweat gland innervation supporting autonomic involvement. Importantly, alternative causes of small fiber neuropathy, particularly diabetes mellitus, should always be carefully excluded (104).

Prognosis and complications

Neurosarcoidosis is a potentially life-threatening condition with a highly variable clinical course, often resulting in significant morbidity and, in severe cases, mortality. Its diverse manifestations can lead to acute neurologic deterioration requiring intensive care unit (ICU) admission and prolonged hospitalization. The most serious complications include status epilepticus, acute hydrocephalus, severe metabolic and endocrine disturbances, adrenal crisis, spinal cord injury, and cerebrovascular events (10; 27).

Meningeal involvement may result in acute or subacute hydrocephalus, presenting with altered mental status and reduced level of consciousness. Hydrocephalus may be communicating, due to impaired CSF absorption at the arachnoid villi, or noncommunicating, resulting from obstruction of CSF pathways by granulomatous masses. Progressive elevation in intracranial pressure can lead to cerebral herniation syndromes and seizures. These patients require urgent multidisciplinary management involving neurology, neurosurgery, and critical care, including emergent neuroimaging, CSF diversion with external ventricular drain or ventriculoperitoneal shunting, high-dose corticosteroids, seizure control, and escalation to immunosuppressive or biological therapies (80).

Cranial neuropathies may result in permanent neurologic deficits, particularly with optic nerve involvement, which can lead to irreversible vision loss. Involvement of lower cranial nerves may impair swallowing and airway protection, increasing the risk of aspiration, respiratory compromise, and acute hypoxic respiratory failure, sometimes necessitating intubation and ventilatory support (20).

Parenchymal or encephalitic disease may precipitate severe complications, such as status epilepticus, acute encephalopathy, and cerebral edema, with risk of herniation. These presentations require rapid recognition and aggressive management, often in an ICU setting, with close collaboration between neurology and neurosurgical teams (12).

Myelopathic involvement may lead to profound and potentially irreversible disability, including paralysis, sensory loss, and bowel or bladder dysfunction. In severe cases, involvement of the cervical spinal cord can result in respiratory compromise. Cauda equina involvement and dysautonomia may further complicate the clinical course. Early diagnosis and prompt initiation of therapy are critical to prevent permanent neurologic injury (13; 02).

Neuroendocrine complications, particularly hypothalamic–pituitary involvement, may result in acute adrenal crisis, a frequently underrecognized but life-threatening condition characterized by hypotension, altered mental status, and hypoglycemia. These patients require immediate ICU-level care with intravenous corticosteroids, fluid and electrolyte resuscitation, desmopressin when indicated, and stress-dose hydrocortisone. Associated features may include bradycardia and hypothermia (54; 03).

Cerebrovascular involvement can present with acute focal neurologic deficits, including motor weakness or visual disturbances. It is essential to distinguish sarcoidosis-related inflammatory vasculopathy from cerebrovascular events due to traditional vascular risk factors as management differs substantially. Inflammatory mechanisms require prompt immunosuppressive therapy, whereas standard stroke protocols alone may be insufficient or inappropriate (75).

Overall prognosis in neurosarcoidosis is highly variable and depends on the pattern and severity of organ involvement, timeliness of diagnosis, and response to therapy. Although some patients experience a monophasic or steroid-responsive course, others develop chronic, relapsing disease requiring long-term immunosuppression. Delayed recognition and treatment are associated with increased risk of irreversible neurologic damage and long-term disability.

Epidemiology

The epidemiology of neurosarcoidosis is not well defined and largely reflects that of systemic sarcoidosis, with significant variability across geographic regions and populations. In the United States, sarcoidosis occurs more frequently among African Americans and individuals of Northern European ancestry, groups in which neurosarcoidosis is consequently more often observed. In Europe, certain countries have reported regional clustering and higher incidence rates, suggesting potential environmental or genetic influences (62; 16; 84).

Data from low- and middle-income countries remain limited and likely underestimate the true burden of disease. This is partly due to diagnostic challenges, as neurosarcoidosis can be difficult to distinguish from other conditions with overlapping clinical and radiographic features, particularly infectious granulomatous diseases, such as tuberculosis. Variability in access to advanced imaging, histopathological confirmation, and specialist care further contributes to underrecognition and reporting differences worldwide (94).

Overall, the global distribution of neurosarcoidosis remains incompletely characterized, underscoring the need for improved diagnostic frameworks and epidemiological surveillance.

Noncaseating granulomas are the pathological hallmark of sarcoidosis. These granulomas consist of tightly organized aggregates of activated macrophages, epithelioid cells, and multinucleated giant cells, surrounded by CD4+ T lymphocytes and, to a lesser extent, B cells (05; 65; 107). A central feature of granuloma formation is a Th1-predominant immune response, with key cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), which are produced by activated macrophages and T cells, respectively, to drive persistent inflammation. Dysregulation of immune homeostasis includes abnormalities in naive and regulatory CD4+ T cells, along with paradoxical peripheral T-cell anergy despite heightened local immune activation (55; 38; 83).

In neurosarcoidosis, granulomatous inflammation can involve both the central and peripheral nervous systems, resulting in focal or multifocal neuronal injury through direct tissue infiltration, mass effect, or secondary inflammation. Despite advances in understanding immune pathways, the precise etiology of sarcoidosis remains incompletely defined (14).

Multiple lines of evidence support a multifactorial pathogenesis involving environmental exposures, infectious triggers, and genetic susceptibility (80). Infectious agents, particularly mycobacteria, have been proposed as contributors due to shared immunopathologic features. Mycobacterial antigens, including heat shock proteins and antigen 85 (Ag85) complexes, elicit T-cell responses and cytokine profiles similar to those observed in sarcoidosis, raising the possibility of antigen-driven immune activation (17; 76; 21).

Environmental and occupational exposures have been implicated. Risk factors include exposure to mold, insecticides, metalworking fluids, and inorganic dusts, such as silica and beryllium. Increased risk has been observed with certain occupations, including healthcare, construction, and building materials industries. Notably, there was a higher incidence of sarcoidosis among World Trade Center responders, particularly firefighters, highlighting the potential role of inhaled particulate matter in disease pathogenesis (71; 39; 25).

Genetic susceptibility further contributes to disease risk. Familial clustering and increased incidence among first- and second-degree relatives support a heritable component. Described HLA and non-HLA genetic associations remain heterogeneous. Candidate genes implicated in susceptibility include variants in ZNF592, BLOC1S1, and loci within the 15q25 chromosomal region (102; 85; 01; 38).

Overall, sarcoidosis is best understood as a complex immune-mediated disorder arising from an interplay between genetic predisposition and environmental or antigenic exposures, leading to dysregulated granulomatous inflammation in affected tissues.

Differential diagnosis

Confusing conditions

Neurosarcoidosis presents with a wide range of neurologic manifestations, which often overlap with other neuroinflammatory, autoimmune, infectious, and neoplastic disorders. Accurate differentiation is critical for guiding appropriate therapy.

Neuroinflammatory and autoimmune mimics include multiple sclerosis, neuromyelitis optica, MOG antibody-associated disease (MOGAD), neuro-Behcet disease, ANCA-associated vasculitis, secondary CNS vasculitis, and IgG4-related disorders.

Multiple sclerosis may present with optic neuritis, myelitis, cranial neuropathies, and ovoid CNS lesions; differentiation relies on periventricular or juxtacortical MRI lesions, oligoclonal bands in CSF, and absence of systemic sarcoidosis features, such as hilar lymphadenopathy or granulomas on biopsy (82; 28; 29).

Neuromyelitis optica typically manifests with longitudinally extensive spinal cord lesions, severe optic neuritis, or area postrema syndrome and is distinguished by serum aquaporin-4 (AQP4) antibody positivity and lack of systemic sarcoidosis features (108; 29; 87).

MOGAD can present with tumefactive white matter lesions, meningitis, or short-segment myelitis but is identified by MOG-IgG seropositivity and predilection for cortical/subcortical lesions without systemic sarcoidosis features (04; 29; 101).

Neuro-Behcet disease often involves brainstem lesions, meningoencephalitis, or cranial nerve palsies; a history of oral or genital ulcers, positive pathergy testing, HLA-B51 positivity, and neutrophilic CSF pleocytosis support the diagnosis (51). ANCA-associated vasculitis may mimic pachymeningitis or cranial neuropathies but is associated with ear-nose-throat disease, pulmonary cavitations, necrotizing granulomas on biopsy, and positive c-ANCA (PR3) serology (70; 91).

Secondary CNS vasculitis can arise from infectious, autoimmune, or neoplastic etiologies, producing multifocal infarcts or meningeal enhancement, with diagnosis guided by angiography and evaluation for systemic disease (70). IgG4-related disease can present with cranial neuropathies or dural involvement, often accompanied by systemic manifestations such as retroperitoneal fibrosis or pancreatitis, with biopsy showing IgG4-positive plasma cells (98; 99).

Neuroinfectious mimics include CNS tuberculosis, fungal infections, subacute or chronic meningitis, and neurosyphilis. CNS tuberculosis often presents with basal leptomeningeal enhancement, cranial neuropathies, and longitudinally extensive myelitis; differentiation relies on caseating granulomas, positive CSF cultures or PCR, and epidemiological exposure (64; 33). Fungal infections (eg, histoplasmosis, blastomycosis) and chronic meningitides, such as cryptococcal or herpes simplex virus–associated disease, may produce basilar meningitis, hydrocephalus, or cranial neuropathies, with CSF testing and imaging aiding diagnosis (69). Neurosyphilis can present with meningitis, cranial neuropathies, or myelopathy, confirmed via serum RPR/VDRL and CSF-VDRL testing (37).

Neoplastic and cancer-associated CNS disorders also can mimic neurosarcoidosis. Primary or secondary CNS lymphoma may present with enhancing brain lesions, leptomeningeal disease, and cranial neuropathies; diagnosis is established through CSF cytology or flow cytometry, FDG-PET demonstrating hypermetabolic masses, and biopsy showing malignant lymphoid cells (86). Meningiomas often appear as well-circumscribed dural or meningeal-based mass lesions, sometimes affecting skull-based cranial nerves, but typically lack systemic involvement or CSF abnormalities (111). Leptomeningeal spread from metastatic tumors can produce multiple cranial neuropathies, leptomeningeal enhancement, and cauda equina involvement; a history of known primary malignancy (eg, lung, breast, melanoma, lymphoma) along with positive CSF cytology, flow cytometry, and FDG-PET findings aids diagnosis (72).

Overall, distinguishing neurosarcoidosis from these mimics requires careful integration of clinical features, systemic findings, neuroimaging, laboratory testing, and, when necessary, histopathological confirmation. Recognition of characteristic patterns of CNS and systemic involvement is essential to avoid misdiagnosis and ensure timely initiation of immunosuppressive therapy.

Diagnostic workup

The evaluation of neurosarcoidosis should be tailored according to whether the patient has a known history of systemic sarcoidosis or presents without prior diagnosis, as the diagnostic approach differs significantly between these two cohorts. Historically, the Kveim test was an important early tool in the diagnosis of sarcoidosis wherein validated aseptically acquired sarcoidal tissue suspensions produced granuloma formation at the injection site within 4 to 6 weeks for 84% of biopsy-confirmed sarcoidosis participants (92). Sensitivity and specificity of the Kveim test vary depending on the spleen source used, and the suspension itself lacks approval by the U.S. Food and Drug Administration. Currently, there are no reliable biomarkers for identifying or monitoring disease activity in sarcoidosis or in neurosarcoidosis. Specifically, serum angiotensin converting enzyme (ACE) levels are elevated in 40% to 60% of patients with pulmonary sarcoidosis but are neither sensitive nor specific and are variably used in clinical practice (14). Similarly, data are limited regarding the diagnostic utility of CSF ACE and soluble interleukin-2 receptors for neurosarcoidosis.

Patients with known systemic sarcoidosis. For patients with a confirmed history of sarcoidosis, the diagnostic workup begins with a thorough neurologic assessment, including detailed history and physical examination. Key objectives include defining the temporal profile of neurologic symptoms, differentiating central versus peripheral nervous system involvement, and identifying upper and lower motor neuron findings. A detailed sensory examination is critical to characterize neuropathic involvement and assess for subtle deficits (22; 93; 49).

If clinical suspicion is high, neuroimaging should be performed. Brain and spinal MRI with and without gadolinium contrast are preferred as contrast enhancement often indicates active inflammation, and T2 hyperintensity indicates prior neurologic injury. In patients unable to undergo MRI due to contraindications (eg, pacemakers, metal implants), CT head with and without contrast is an alternative. Vascular imaging via CT or MR angiography can evaluate venous sinus thrombosis, ischemic strokes, or hemorrhagic events (14).

CSF analysis is valuable, particularly when imaging is inconclusive. Typical findings include lymphocytic predominant pleocytosis, elevated protein, hypoglycorrhachia, or, in some cases, restricted oligoclonal bands. CSF evaluation also provides an opportunity to exclude mimics, including AQP4 and MOG antibody-associated disorders, infectious etiologies (eg, tuberculosis), and other inflammatory or autoimmune diseases. CNS biopsy is generally not required in this cohort if imaging and CSF findings support the diagnosis, typically meeting criteria for probable neurosarcoidosis (06; 80).

Patients without known systemic sarcoidosis. In patients whose neurologic presentation precedes systemic symptoms, or in those with isolated CNS or peripheral nervous system disease, a more comprehensive systemic evaluation is essential.

Pulmonary assessment. Inquiry regarding cough, dyspnea, and exercise intolerance should be performed, with a low threshold for pulmonary function tests or chest CT to identify parenchymal disease or hilar/mediastinal lymphadenopathy.

Dermatologic evaluation. Skin manifestations, such as erythema nodosum or lupus pernio, provide an accessible biopsy target.

Cardiovascular assessment. Evaluate for orthopnea, chest pain, syncope, palpitations, or other signs of cardiac involvement. Investigations may include ECG, echocardiography, or cardiac MRI to detect sarcoid-related cardiomyopathy or conduction abnormalities.

Ophthalmologic evaluation. A comprehensive eye exam detects uveitis, optic neuritis, or other ocular sarcoidosis manifestations (22; 93; 49).

If systemic findings or imaging suggest biopsy sites, extra-neural tissue sampling lowers procedural risk compared to CNS biopsy. Common biopsy targets include hilar or mediastinal lymph nodes, skin, liver, muscle, or bone marrow. Histopathological confirmation establishes the diagnosis of probable neurosarcoidosis (97).

In cases in which no biopsy target is identified and alternative etiologies have been reasonably excluded, a diagnosis of possible neurosarcoidosis may be considered. Rarely, a CNS biopsy may be necessary, particularly if imaging reveals accessible meningeal or cortical disease, allowing for histopathological confirmation and a diagnosis of definite neurosarcoidosis (97).

Key principles of workup

	• Stratify patients based on prior systemic sarcoidosis.
	• Perform comprehensive neurologic and systemic assessments.
	• Use MRI (with/without contrast) as the primary imaging modality; CT is an alternative when MRI is contraindicated.
	• CSF analysis aids in detecting inflammation and excluding mimics.
	• Pursue extra-neural biopsy whenever feasible; CNS biopsy is reserved for cases in which no alternative tissue is available and diagnosis is uncertain.
	• Always exclude mimics—including neuroinflammatory, infectious, autoimmune, and neoplastic disorders—before establishing the diagnosis.

Management

Management of neurosarcoidosis is guided by expert consensus and observational data, as randomized controlled trials remain limited. Consensus recommendations emphasize early recognition and treatment of active disease to prevent irreversible neurologic injury. There is broad agreement that corticosteroids are the first-line therapy, particularly in acute or severe presentations. However, important areas of variability remain, including the optimal duration of therapy, timing of escalation to steroid-sparing or biological agents, and the role and frequency of surveillance imaging. Not all patients require a uniform stepwise escalation strategy; treatment should be individualized based on disease severity, phenotype, and response to therapy. Increasingly, MRI surveillance is utilized to monitor disease activity, although standardized intervals and protocols are not universally defined (60).

Corticosteroids remain the cornerstone of initial treatment. In acute or severe presentations—such as encephalopathy, myelopathy, or vision-threatening disease—patients are typically treated with intravenous methylprednisolone (eg, 1 g daily for 3–5 days), followed by transition to oral prednisone (approximately 0.5 mg/kg/day). A gradual taper is recommended to minimize long-term corticosteroid toxicity, including weight gain, diabetes, osteoporosis, hypertension, mood disturbances, and increased infection risk. Although some patients respond adequately to corticosteroids alone, many require additional immunosuppressive therapy to achieve sustained disease control and facilitate steroid tapering (08; 50; 80).

Steroid-sparing immunosuppressive agents are commonly introduced early in the disease course. Among these, methotrexate and mycophenolate mofetil have greater efficacy and tolerability compared to azathioprine in observational studies. These agents reduce relapse risk and allow reduction of corticosteroid dose, thereby limiting cumulative toxicity. Methotrexate is typically administered weekly and requires monitoring for hepatotoxicity, cytopenias, and pulmonary toxicity. Mycophenolate is associated with gastrointestinal side effects, leukopenia, and increased infection risk. Azathioprine, although used, carries risks of myelosuppression, hepatotoxicity, and hypersensitivity reactions. Importantly, concomitant use of these agents may also reduce the formation of anti-drug antibodies when biological therapies are introduced (32).

Tumor necrosis factor (TNF) inhibitors have emerged as key therapies for moderate to severe neurosarcoidosis and are to be used for at least 1 year. Agents such as infliximab (typically 5–10 mg/kg intravenously every 4–8 weeks) and adalimumab (subcutaneous injections every 1–2 weeks) target TNF-alpha, a central cytokine in granuloma formation and maintenance. These agents have substantial efficacy in controlling disease activity across CNS and peripheral nervous system manifestations. Observational studies suggest that infliximab is superior to cyclophosphamide in achieving clinical and radiographic improvement, with high relapse-free survival rates beyond 12 months. However, TNF inhibitors carry risks of serious infections (including reactivation of tuberculosis), infusion reactions, and the development of anti-drug antibodies, which may reduce therapeutic efficacy over time. Pre-treatment screening for latent infections and ongoing laboratory monitoring is essential. A subset of patients develops neutralizing antibodies to TNF inhibitors, resulting in diminished response. In such cases, switching to an alternative biological class is often necessary (48; 42; 19; 09).

Interleukin-6 (IL-6) inhibitors, such as tocilizumab (administered intravenously or subcutaneously), are an emerging therapeutic option. IL-6 plays a key role in inflammatory signaling. CSF IL-6 levels are elevated in neurosarcoidosis compared to other neuroinflammatory disorders, such as neuromyelitis optica spectrum disorder (59). Tocilizumab has shown efficacy in systemic sarcoidosis and may be beneficial in neurosarcoidosis, particularly in patients who are refractory to or intolerant of TNF inhibitors. Adverse effects include infection risk, hepatotoxicity, cytopenias, and lipid abnormalities, necessitating regular monitoring (89).

Based on case reports and small series, Janus kinase (JAK) inhibitors suggest benefit in refractory sarcoidosis through modulation of cytokine signaling pathways. However, their role in neurosarcoidosis remains investigational. Known risks include infections, cytopenias, thromboembolic events, and lipid abnormalities (31; 23).

Across all treatment modalities, close clinical follow-up and radiographic monitoring are essential. MRI of the brain and/or spine with and without contrast is typically performed 3 to 6 months after initiation or escalation of therapy to assess treatment response. Clinical improvement, radiographic stability, or resolution of enhancement and the ability to taper corticosteroids are key markers of therapeutic success. These therapeutic strategies apply to both central and peripheral nervous system involvement (60).

Overall, the management of neurosarcoidosis requires a multidisciplinary, individualized approach that balances disease control with treatment-related risks. Despite advances in immunotherapy, significant gaps remain in evidence-based guidance, highlighting the need for prospective studies to better define optimal treatment strategies.

Outcomes

Management of neurosarcoidosis frequently requires prolonged immunosuppression, which carries a substantial risk of treatment-related complications. Adverse effects must be anticipated, monitored, and managed proactively and often require multidisciplinary coordination.

Opportunistic and serious infections. All classes of immunosuppressive therapies, including corticosteroids, steroid-sparing agents (eg, methotrexate, mycophenolate, azathioprine), and biological therapies (eg, TNF inhibitors, IL-6 inhibitors), increase susceptibility to opportunistic and systemic infections. These include fungal infections, such as cryptococcal meningitis, histoplasmosis, blastomycosis, and aspergillosis, as well as reactivation of latent infections, such as tuberculosis. Progressive multifocal leukoencephalopathy has been reported rarely (47; 63; 100).

Cryptococcal meningitis is a particularly important consideration. It may present subacutely with headaches, fever, altered mental status, cranial neuropathies, and signs of increased intracranial pressure. Additional infections include bacterial sepsis, urinary tract infections, and upper respiratory tract infections, ranging from mild to life-threatening (47).

A major clinical challenge arises when serious infection occurs in patients receiving immunosuppressive therapy. In such cases, temporary discontinuation or reduction of immunosuppressive agents is often necessary to allow for infection control. This must be balanced against the risk of neurosarcoidosis relapse or progression. Shared decision-making involving the patient will determine when and how to safely resume individualized therapy and should be collaborative among neurology, infectious disease, and other relevant specialties.

Corticosteroid-related complications. Corticosteroids are associated with a broad range of adverse effects, particularly with prolonged use. Steroid-induced hyperglycemia is common and may be especially challenging in patients with pre-existing diabetes mellitus. Management may require intensification of antihyperglycemic therapy and early initiation of steroid-sparing or biological agents to facilitate corticosteroid tapering. During high-dose intravenous methylprednisolone therapy, close inpatient glucose monitoring is essential, often necessitating endocrinology consultation.

Additional corticosteroid-related complications include weight gain, hypertension, osteoporosis, mood and psychiatric disturbances, cataracts, increased infection risk, and myopathy. Gastrointestinal complications, including peptic ulcer disease, bleeding, and, rarely, perforation, may occur, especially with concomitant NSAIDS; prophylaxis with H2 blockers or proton pump inhibitors is often recommended in high-risk patients (110; 56).

Adrenal insufficiency and adrenal crisis. Prolonged corticosteroid therapy can suppress the hypothalamic–pituitary–adrenal axis, leading to secondary adrenal insufficiency. This may progress to adrenal crisis, a life-threatening condition characterized by hypotension, tachycardia, hypoglycemia, and electrolyte abnormalities, such as hyponatremia and hyperkalemia. Clinical features include profound fatigue, severe muscle weakness, altered mental status, nausea, vomiting, abdominal pain, and, in severe cases, shock.

Patients with underlying sarcoidosis on chronic corticosteroid therapy with acute illness should be promptly evaluated for adrenal insufficiency. Administration of stress-dose corticosteroids should not be delayed while awaiting confirmatory testing (15).

Hematologic toxicity and bone marrow suppression. Long-term use of immunosuppressive and cytotoxic agents, including methotrexate, mycophenolate mofetil, azathioprine, and cyclophosphamide, is associated with bone marrow suppression and hematologic abnormalities, such as leukopenia, neutropenia, anemia, and thrombocytopenia. These abnormalities increase the risk of opportunistic infections, sepsis, septic shock, and, in severe cases, mortality.

Regular laboratory monitoring, including complete blood count with differential, is essential for early detection of cytopenias. Dose adjustments or discontinuation of the offending agent may be required if significant hematologic toxicity develops. Emerging data suggest that inflammatory markers, such as the neutrophil-to-lymphocyte ratio, may have prognostic value in sarcoidosis, with higher ratios associated with more severe or progressive disease, although their role in routine clinical practice remains to be fully defined (34).

References

01: Adrianto I, Lin CP, Hale JJ, et al. Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. PloS One 2012;7(8):e43907. PMID 22952805
02: Al-Hader R, Nofar J, Mohamedelkhair A, Affan M, Schultz LR, Cerghet M. A comprehensive characterization of patients with spinal cord neurosarcoidosis: a single center cross-sectional study of clinical outcomes. J Clin Med 2024;13(17):5069. PMID 39274281
03: Anthony J, Esper GJ, Ioachimescu A. Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. Pituitary 2016;19(1):19-29. PMID 26267304
04: Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol 2023;22(3):268-82. PMID 36706773
05: Barna BP, Judson MA, Thomassen MJ. Inflammatory pathways in sarcoidosis. Adv Exp Med Biol 2021;1304:39-52. PMID 34019262
06: Barreras P, Stern BJ. Clinical features and diagnosis of neurosarcoidosis – review article. J Neuroimmunol 2022;368:577871. PMID 35523055
07: Bathla G, Freeman CW, Moritani T, et al. Retrospective, dual-centre review of imaging findings in neurosarcoidosis at presentation: prevalence and imaging sub-types. Clin Radiol 2020;75(10):796.e1-796.e9. PMID 32703543
08: Baughman RP, Valeyre D, Korsten P, et al. ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J 2021;58(6):2004079. PMID 34140301
09: Bechman K, Biddle K, Miracle A, et al. Systematic review and meta-analysis of the efficacy of biologic and targeted synthetic therapies in sarcoidosis. Thorax 2025;80(10):702-10. PMID 40393718
10: Berntsson SG, Elmgren A, Gudjonsson O, Grabowska A, Landtblom AM, Moraes-Fontes MF. A comprehensive diagnostic approach in suspected neurosarcoidosis. Sci Rep 2023;13(1):6539. PMID 37085608
11: Blazin T, Prajapati D, Mohammed LLM, et al. Hypothalamic-pituitary axis dysfunction, central diabetes insipidus, and syndrome of inappropriate antidiuretic hormone secretion as the first clinical presentation of neurosarcoidosis: why early diagnosis and treatment is important? Cureus 2020;12(11):e11481. PMID 33329977
12: Bou GA, El Sammak S, Chien LC, Cavanagh JJ, Hutto SK. Tumefactive brain parenchymal neurosarcoidosis. J Neurol 2023;270(9):4368-76. PMID 37219604
13: Bou GA, Garcia-Santibanez R, Castilho AJ, Hutto SK. Neurosarcoidosis of the cauda equina: clinical course, radiographic and electrodiagnostic findings, response to treatment, and outcomes. Neurol Neuroimmunol Neuroinflamm 2022;9(4):e1170. PMID 35487693
14: Bradshaw MJ, Pawate S, Koth LL, Cho TA, Gelfand JM. Neurosarcoidosis: pathophysiology, diagnosis, and treatment. Neurol Neuroimmunol Neuroinflamm 2021;8(6):e1084. PMID 34607912
15: Bridwell RE, April MD. Adrenal emergencies. Emerg Med Clin North Am 2023;41(4):795-808. PMID 37758424
16: Brito-Zeron P, Kostov B, Superville D, Baughman RP, Ramos-Casals M; Autoimmune Big Data Study Group. Geoepidemiological big data approach to sarcoidosis: geographical and ethnic determinants. Clin Exp Rheumatol 2019;37(6):1052-64. PMID 31498063
17: Carlisle J, Evans W, Hajizadeh R, et al. Multiple Mycobacterium antigens induce interferon-gamma production from sarcoidosis peripheral blood mononuclear cells. Clin Exp Immunol 2007;150(3):460-8. PMID 17924974
18: Carlson ML, White JR, Espahbodi M, et al. Cranial base manifestations of neurosarcoidosis: a review of 305 patients. Otol Neurotol 2015;36(1):156-66. PMID 25029595
19: Chaiyanarm S, Satiraphan P, Apiraksattaykul N, et al. Infliximab in neurosarcoidosis: a systematic review and meta-analysis. Ann Clin Transl Neurol 2024;11(2):466-76. PMID 38087813
20: Chakales PA, Herman MC, Chien LC, Hutto SK. Pachymeningitis in biopsy-proven sarcoidosis: clinical course, radiographic findings, response to treatment, and long-term outcomes. Neurol Neuroimmunol Neuroinflamm 2022;9(6):e200028. PMID 36163175
21: Chioma OS, Wiggins Z, Rea S, Drake WP. Infectious and non-infectious precipitants of sarcoidosis. J Autoimmun 2024;149:103239. PMID 38821769
22: Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis. An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2020;201(8):e26-51. PMID 32293205
23: de Melo Bandeira MCF, Van Pesch V, Onofrj V, Lawson TM, Yildiz H. Tofacitinib as maintenance therapy for refractory neurosarcoidosis. Acta Neurol Belg 2025;125(3):829-31. PMID 39503837
24: Dos Santos A, Courtin E, Ruet A, et al. Neurosarcoidosis: clinical, biological, and MRI presentation of central nervous system disease in a national multicenter cohort. Brain Behav 2024;14(9):e3443. PMID 39279263
25: Drent M, Crouser ED, Grunewald J. Challenges of sarcoidosis and its management. N Engl J Med 2021;385(11):1018-32. PMID 34496176
26: Edjlali M, Qiao Y, Boulouis G, et al. Vessel wall MR imaging for the detection of intracranial inflammatory vasculopathies. Cardiovasc Digan Ther 2020;10(4):1108-19. PMID 32968663
27: El Sammak S, Lec BM, Bou GA, Wagstaff WV, Lawson EC, Hutto SK. Hydrocephalus in neurosarcoidosis: clinical course, radiographic accompaniments, and experience with shunting. Mult Scler Relat Disord 2023;79:105040. PMID 37783195
28: Filippi M, Preziosa P, Arnold DL, et al. Present and future of the diagnostic work-up of multiple sclerosis: the imaging perspective. J Neurol 2023;270(3)1286-99. PMID 36427168
29: Filippi M, Preziosa P, Margoni M, Rocca MA. Diagnostic criteria for multiple sclerosis, neuromyelitis optica spectrum disorders, and myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease. Neuroimaging Clin N Am 2024;34(3):293-316. PMID 38942518
30: Flanagan EP, Kaufmann TJ, Krecke KN, et al. Discriminating long myelitis of neuromyelitis optica from sarcoidosis. Ann Neurol 2016;79(3):437-47. PMID 26677112
31: Friedman MA, Le B, Stevens J, et al. Tofacitinib as a steroid-sparing therapy in pulmonary sarcoidosis, an open-label prospective proof-of-concept study. Lung 2021;199(2):147-53. PMID 33825964
32: Fritz D, van de Beek D, Brouwer MC. Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis. BMC Neurol 2016;16(1):220. PMID 27846819
33: Garg RK. Tuberculosis of the central nervous system: current concepts in diagnosis and treatment. Curr Opin Neurol 2025;38(4):406-13. PMID 40047235
34: Ghasempour Alamdari M, Kalami N, Shojaan H, et al. Systematic review of the diagnostic role of neutrophil to lymphocyte ratio in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2023;40(1):e2023008. PMID 36975052
35: Gombolay GY, Gadde JA. Aseptic meningitis and leptomeningeal enhancement associated with anti-MOG antibodies: a review. J Neuroimmunol 2021;358:577653. PMID 34229204
36: Gomez H, Noel N, Schmidt J, et al. Comparing the efficacy and safety of cyclophosphamide, infliximab and methotrexate in neurosarcoidosis: a multicenter retrospective study. J Neurol 2025;272(8):531. PMID 40702280
37: Hamill MM, Ghanem KG, Tuddenham S. State-of-the-art review: neurosyphilis. Clin Infect Dis 2024;78(5):e57-68. PMID 37593890
38: Hardin A, Dawkins B, Pezant N, Rasmussen A, Montgomery C. Genetics of neurosarcoidosis. J Neuroimmunol 2022;372:577957. PMID 36054933
39: Hena KM, Yip J, Jaber N, et al. Clinical course of sarcoidosis in World Trade Center-exposed firefighters. Chest 2018;153(1):114-23. PMID 29066387
40: Henderson AD, Tian J, Carey AR. Neuro-ophthalmic manifestations of sarcoidosis. J Neuroophtahlmol 2021;41(4):e591-7. PMID 33110001
41: Hutto SK, Kyle K, Balaban DT, Martinez-Lage M, Venna N. Ischemic stroke in neurosarcoidosis: a retrospective cohort analysis. Mult Scler Relat Disord 2022a;68:104227. PMID 36240703
42: Hutto SK, Kyle K, Cavanagh JJ, Reda H, Venna N. Adalimumab for CNS sarcoidosis: single-center experience and literature review. J Neurol 2022b;269(4):2064-72. PMID 34487233
43: Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357(21):2153-65. PMID 18032765
44: Ibitoye RT, Wilkins A, Scolding NJ. Neurosarcoidosis: a clinical approach to diagnosis and management. J Neurol 2017;264(5):1023-8. PMID 27878437
45: Jachiet V, Lhote R, Rufat P, et al. Clinical, imaging, and histological presentations and outcomes of stroke related to sarcoidosis. J Neurol 2018;265(10):2333-41. PMID 30109479
46: Jacobi J. Management of endocrine emergencies in the ICU. J Pharm Pract 2019;32(3):314-26. PMID 30852927
47: Jamilloux Y, Valeyre D, Lortholary O, et al. The spectrum of opportunistic diseases complicating sarcoidosis. Autoimmun Rev 2015;14(1):64-74. PMID 25305373
48: Joubert B, Chapelon-Abric C, Biard L, et al. Association of prognostic factors and immunosuppressive treatment with long-term outcomes in neurosarcoidosis. JAMA Neurol 2017;74(11):1336-44. PMID 29052709
49: Judson MA. A primer on the clinical aspects of sarcoidosis for the basic and translational scientist. J Clin Med 2021;10(13):2857. PMID 34203188
50: Judson MA. The treatment of sarcoidosis: translating the European respiratory guidelines into clinical practice. Curr Opin Pulm Med 2022;28(5):451-60. PMID 35838355
51: Kidd DP. Neurological involvement by Behçet’s syndrome: clinical features, diagnosis, treatment and outcome. Pract Neurol 2023;23(5):386-400. PMID 37775123
52: Kidd DP, Burton BJ, Graham EM, Plant GT. Optic neuropathy associated with systemic sarcoidosis. Neurol Neuroimmunol Neuroinflamm 2016;3(5):e270. PMID 27536707
53: Kurtz RM, Babatunde VD, Schmitt JE, Berger JR, Mohan S. Spinal cord sarcoidosis occurring at sites of spondylotic stenosis, mimicking spondylotic myelopathy: a case series and review of the literature. AJNR Am J Neuroradiol 2023;44(1):105-10. PMID 36521966
54: Langrand C, Bihan H, Raverot G, et al. Hypothalamo-pituitary sarcoidosis: a multicenter study of 24 patients. QJM 2012;105(10):981-95. PMID 22753675
55: Lepzien R, Liu S, Czarnewski P, et al. Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome. Eur Respir J 2021;58(1):2003468. PMID 33446605
56: Li JX, Cummins CL. Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions. Nat Rev Endocrinol 2022;18(9):540-57. PMID 35585199
57: Lin J, Pulst-Korenberg J, Zamvil SS, Graves J, Newsome SD, Amezcua L. Tuberculous meningitis or neurosarcoidosis-a diagnostic quandary. From the National Multiple Sclerosis Society Case Conference Proceedings. Neurol Neuroimmunol Neuroinflamm 2024;11(1):e200184. PMID 38118077
58: Lord J, Paz Soldan MM, Galli J, et al. Neurosarcoidosis: longitudinal experience in a single-center, academic healthcare system. Neurol Neuroimmunol Neuroinflamm 2020;7(4):e743. PMID 32404428
59: Mangioris G, Pittock SJ, Yang B, et al. Cerebrospinal fluid cytokine and chemokine profiles in central nervous system sarcoidosis: diagnostic and immunopathologic insights. Ann Neurol 2024;96(4):704-14. PMID 39031103
60: Manzano GS, Eaton J, Levy M, et al. Consensus recommendations for the management of neurosarcoidosis: a Delphi survey of experts across the United States. Neurol Clin Pract 2025;15(2):e200429. PMID 39830676
61: Martucci G, Bonicolini E, Parekh D, Thein OS, Scherkl M, Amrein K. Metabolic and endocrine challenges. Semin Respir Crit Care Med 2021;42(1):78-97. PMID 32882734
62: Mateyo K, Thomeer M. Sarcoidosis around the globe. Semin Respir Crit Care Med 2017;38(4):393-403. PMID 38750456
63: McEntire CRS, Fletcher A, Toledano M, et al. Characteristics of progressive multifocal leukoencephalopathy associated with sarcoidosis without therapeutic immune suppression. JAMA Neurol 2023;80(6):624-33. PMID 37093609
64: Mertiri L, Freiling JT, Desai NK, Kralik SF, Huisman TAGM. Pediatric and adult meningeal, parenchymal, and spinal tuberculosis: A neuroimaging review. J Neuroimaging 2024;34(2):179-94. PMID 38073450
65: Miedema J, Cinetto F, Smed-Sörensen A, Spagnolo P. The immunopathogenesis of sarcoidosis. J Autoimmun 2024;149:103247. PMID 38734536
66: Murphy OC, Salazar-Camelo A, Jimenez JA, et al. Clinical and MRI phenotypes of sarcoidosis-associated myelopathy. Neurol Neuroimmunol Neuroinflamm 2020;7(4):e722. PMID 32269072
67: Mustafa R, Passe TJ, Lopez-Chiriboga AS, et al. Utility of MRI enhancement pattern in myelopathies with longitudinally extensive T2 lesions. Neurol Clin Pract 2021;11(5):e601-11. PMID 34824894
68: Nakirikanti AS, El Sammak S, Tyor W, Hutto SK. Predictors of visual outcome in optic neuropathy of sarcoidosis. J Neuroimmunol 2025;400:578529. PMID 40023555
69: Nathan CL, Emmert BE, Nelson E, Berger JR. CNS fungal infections: a review. J Neurol Sci 2021;422:117325. PMID 33516057
70: Nehme A, Boulanger M, Aouba A, et al. Diagnostic and therapeutic approach to adult central nervous system vasculitis. Rev Neurol (Paris) 2022;178(10):1041-54. PMID 36156251
71: Newman KL, Newman LS. Occupational causes of sarcoidosis. Curr Opin Allergy Clin Immunol 2012;12(2):145-50. PMID 22314258
72: Nguyen A, Nguyen A, Dada OT, et al. Leptomeningeal metastasis: a review of the pathophysiology, diagnostic methodology, and therapeutic landscape. Curr Oncol 2023;30(6):5906-31. PMID 37366925
73: Nitsch L, Skowasch D, Courtin E, et al. Factors associated with relapse in patients with neurosarcoidosis. Neurology 2025;104(11):e213705. PMID 40373242
74: Nolte JYC, Ten Dam L, van de Beek D, Brouwer MC. Clinical characteristics and outcome of neurosarcoidosis-associated myelitis: a retrospective cohort study and review of the literature. Eur J Neurol 2022;29(6):1763-70. PMID 35189010
75: Noroozi Gilandehi S, Wong KH, Francis T, et al. Cardiac involvement in neurosarcoidosis: a single-center investigation. Neurol Neuroimmunol Neuroinflamm 2024;11(2):e200196. PMID 38181319
76: Oswald-Richter KA, Drake WP. The etiologic role of infectious antigens in sarcoidosis pathogenesis. Semin Respir Crit Care Med 2010;31(4):375-9. PMID 20665387
77: Ozair A, Wilding H, Bhanja D, et al. Leptomeningeal metastatic disease: new frontiers and future directions. Nat Rev Clin Oncol 2025;22(2):134-54. PMID 39653782
78: Pardo CA. Clinical approach to myelopathy diagnosis. Continuum (Minneap Minn 2024;30(1):14-52. PMID 38330471
79: Pua DKA, Anand P, Bhattacharyya S. Stroke associated with sarcoidosis: a systematic review of reported cases. J Neurol Sci 2024;462:123080. PMID 38850770
80: Queisi MM, Pardo CA. (2025). Neurosarcoidosis in critical care, internal, and pulmonary medicine: a practical approach. Semin Respir Crit Care Med 2025;46(6):622-40. PMID 41371265
81: Ramos-Casals M, Pérez-Alvarez R, Kostov B, et al. Clinical characterization and outcomes of 85 patients with neurosarcoidosis. Sci Rep 2021;11(1):13735. PMID 34215779
82: Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med 2018;378(2), 169-80. PMID 29320652
83: Robert M, Yatim N, Sacré K, Duffy D. Sarcoidosis immunopathogenesis—a new concept of maladaptive trained immunity. Trends Immunol 2024;45(6):406-18. PMID 38796404
84: Rossides M, Darlington P, Kullberg S, Arkema EV. (2023). Sarcoidosis: epidemiology and clinical insights. J Intern Med 2023;293(6):668-80. PMID 36872840
85: Sato H, Woodhead FA, Ahmad T, et al. Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups. Hum Mol Genet 2010;19(20):4100-11. PMID 20685690
86: Schaff L. Central nervous system lymphoma. Continuum (Minneap Minn) 2023;29(6):1710-26. PMID 38085895
87: Sechi E. NMOSD and MOGAD. Continuum (Minneap Minn) 2024;30(4):1052-87. PMID 39088288
88: Sharma OP. Sarcoidosis. Dis Mon 1990;39(9):472-535. PMID 2201509
89: Sharp M, Donnelly SC, Moller DR. Tocilizumab in sarcoidosis patients failing steroid sparing therapies and anti-TNF agents. Respir Med X 2019;1:100004. PMID 31187094
90: Shen J, Lackey E, Shah S. Neurosarcoidosis: diagnostic challenges and mimics a review. Curr Allergy Asthma Rep 2023;23(7):399-410. PMID 37256482
91: Sherri A, Mortada MM, Makowska J, Lewandowska-Polak A. Primary angiitis of the CNS and ANCA-associated vasculitis: from pathology to treatment. Rheumatol Int 2024;44(2):211-22. PMID 37777632
92: Siltzbach LE. The Kveim test in Sarcoidosis: a study of 750 patients. JAMA 1961;178(5):476-82. PMID 13912868
93: Singha A, Liao SY, Herman DD, et al. Summary for clinicians: clinical practice guideline for the diagnosis and detection of sarcoidosis. Ann Am Thorac Soc 2020;17(12):1510-5. PMID 32970953
94: Sodsri T, Baughman RP, Sriprasart T. Diagnosis of pulmonary sarcoidosis in tuberculosis endemic area-a narrative review. J Thorac Dis 2023;15(10):5760-72. PMID 37969315
95: Spagnolo P. Sarcoidosis: a critical review of history and milestones. Clin Rev Allergy Immunol 2015;49(1):1-5. PMID 25737246
96: Spagnolo P, Rossi G, Trisolini R, Sverzellati N, Baughman RP, Wells AU. Pulmonary sarcoidosis. Lancet Respir Med 2018;6(5):389-402. PMID 29625772
97: Stern BJ, Royal W, Gelfand JM, et al. Definition and consensus diagnostic criteria for neurosarcoidosis: from the Neurosarcoidosis Consortium Consensus Group. JAMA Neurol 2018;75(12):1546-53. PMID 30167654
98: Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366(6):539-51. PMID 22316447
99: Terrim S, Mahler JV, Filho FVM, et al. Clinical presentation, investigation findings, and outcomes of IgG4-related pachymeningitis: a systematic review. JAMA Neurol 2025;82(2):193-9. PMID 39556369
100: Valeyre D, Bernaudin JF, Brauner M, Nunes H, Jeny F. Infectious complications of pulmonary sarcoidosis. J Clin Med 2024;13(2):342. PMID 38256476
101: Varley JA, Champsas D, Prossor T, et al. Validation of the 2023 International Diagnostic Criteria for MOGAD in a selected cohort of adults and children. Neurology 2024;103(1):e209321. PMID 38870448
102: Voorter CEM, Drent M, van den Berg-Loonen EM. Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA-DQB1*0602-DRB1*150101. Hum Immunol 2005;66(7):826-35. PMID 16112030
103: Voortman M, Drent M, Stern BJ. Neurosarcoidosis and neurologic complications of sarcoidosis treatment. Clin Chest Med 2024;45(1):91-103. PMID 38245373
104: Voortman M, Raasing L, Burggraaff J, Wieske L, Veltkamp M. Small fiber neuropathy in sarcoidosis. Semin Respir Crit Care Med 2025;46(6):557-63. PMID 41218636
105: Voortman M, Stern BJ, Saketkoo LA, Drent M. The burden of neurosarcoidosis: essential approaches to early diagnosis and treatment. Semin Respir Crit Care Med 2020;41(5):641-51. PMID 32777849
106: Webb LM, Chen JJ, Aksamit AJ, et al. A multi-center case series of sarcoid optic neuropathy. J Neurol Sci 2021;420:117282. PMID 33358503
107: Weeratunga P, Moller DR, Ho LP. Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis. J Clin Invest 2024;134(1):e175264. PMID 38165044
108: Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85(2):177-89. PMID 26092914
109: Winter Y, Groppa S, Uphaus T, et al. Cerebral vasculitis as a clinical manifestation of neurosarcoidosis: a scoping review. Autoimmun Rev 2024;23(4):103528. PMID 38492907
110: Yao TC, Huang YW, Chang SM, Tsai SY, Wu AC, Tsai HJ. Association between oral corticosteroid bursts and severe adverse events: a nationwide population-based cohort study. Ann Intern Med 2020;173(5):325-30. PMID 32628532
111: Yuen CA, Zheng M, Saint-Germain MA, Kamson DO. Meningioma: novel diagnostic and therapeutic approaches. Biomedicines 2025;13(3):659. PMID 40149634
112: Zeiler SR, Qiao Y, Pardo CA, Lim M, Wasserman BA. Vessel wall MRI for targeting biopsies of intracranial vasculitis. AJNR Am J Neuroradiol 2018;39(11):2034-6. PMID 30262647

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Munther M Queisi MD MPH

Dr. Queisi of The Johns Hopkins Hospital has no relevant financial relationships to disclose.
See Profile
Daniel P Kurz Jr MD

Dr. Kurz of The University of Chicago Medicine received a grant from Biogen as a clinical trial investigator.
See Profile

Editor

Anthony T Reder MD

Dr. Reder of the University of Chicago received honorariums from Genentech, Genzyme, and TG Therapeutics for service on advisory boards and as a consultant and stock options from NKMax America for advisory work and an unrestricted lab research grant from BMS.
See Profile

Former Authors

Kelley Nicholas MD PhD
Anna M Delios MD
Chelsea Gloeckner MD
Amy Espinal MD
Widad Abou Chaar MD
Deric M Park MD FACP

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: female>male
Heredity: heredity may be a contributing factor
Population groups selectively affected: African Americans

Japanese

Northern Europeans
Occupation groups selectively affected: Post 9/11 firefighters and rescue workers

Automobile manufacturers

ICD & OMIM codes

ICD-10: Sarcoidosis, unspecified: D86.9
ICD-11: Sarcoidosis, unspecified: 4B20.Z
OMIM: Sarcoidosis: #181000

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Neurosarcoidosis

Associated Disorders

Blau syndrome

Differential Diagnosis

multiple sclerosis
neuromyelitis optica
MOG antibody-associated disease (MOGAD)
neuro-Behcet disease
ANCA-associated vasculitis
- secondary CNS vasculitis
- IgG4-related disorders
- CNS tuberculosis
- fungal infections
- subacute or chronic meningitis
- neurosyphilis
- neoplastic and cancer-associated CNS disorders

Also Relevant

Acute inflammatory demyelinating polyradiculoneuropathy
Autoimmune sensorineural hearing loss
Azathioprine
Diagnosis of childhood immune-mediated CNS vasculitides
Mycophenolate
- Neuromuscular pathology: overview
- Prednisone
- Recurrent meningitis
- Sarcoidosis neuropathy

Neurosarcoidosis …

Neurosarcoidosis

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Epidemiology

Differential diagnosis

Confusing conditions

Diagnostic workup

Key principles of workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Balo concentric sclerosis

Mental status examination

Viral and retroviral myositis

Mitochondrial disorders

Drug-induced myasthenic syndromes

Younger-onset (early-onset) Alzheimer disease

Upadacitinib

Reducing body myopathy

Neurosarcoidosis

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Epidemiology

Differential diagnosis

Confusing conditions

Diagnostic workup

Key principles of workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Balo concentric sclerosis

Mental status examination

Viral and retroviral myositis

Mitochondrial disorders

Drug-induced myasthenic syndromes

Younger-onset (early-onset) Alzheimer disease

Upadacitinib

Reducing body myopathy

This is an article preview.
Start a Free Account
to access the full version.