Clinical and magnetic resonance imaging manifestations of neurosarcoidosis

doi:10.1016/j.semarthrit.2004.07.011

Seminars in Arthritis and Rheumatism

Volume 34, Issue 4, February 2005, Pages 649-661

https://doi.org/10.1016/j.semarthrit.2004.07.011 Get rights and content

Objectives

To describe clinical and neuroimaging manifestations of neurosarcoidosis in a cohort of 21 patients.

Patients and methods

We reviewed records of 21 patients with sarcoidosis and central nervous system (CNS) manifestations referred to Cooper University Hospital, with emphasis on neuroimaging findings and associated clinical and laboratory evidence of sarcoidosis. Nineteen patients were categorized as having “definite,” “probable,” or “possible” neurosarcoidosis, while 1 had associated CNS vasculitis and another had Hodgkin’s lymphoma with cauda equina syndrome.

Results

The most common manifestations included myelopathy, cranial neuropathies, and encephalopathy. In 6 patients, CNS biopsy showed sterile, noncaseating granuloma (NCG), while in the remainder, the diagnosis was established through a combination of clinical, radiographic, and laboratory findings. Notably, 10 patients developed acute neurological emergencies, including seizures, spinal cord compression, and increased intracranial pressure. Findings on magnetic resonance imaging (MRI) included a variety of manifestations, including isolated mass lesion, diffuse intraparenchymal inflammatory lesions in the brain and spinal cord, leptomeningeal enhancement, hydrocephalus, and intracranial hemorrhage.

Conclusions

Sarcoidosis is associated with diverse neurological manifestations and neuroimaging findings. The diagnosis of isolated CNS sarcoidosis requires a biopsy to document the presence of sterile NCG and to exclude neoplasms and other granulomatous diseases. When a biopsy of the CNS is not possible, a diagnosis of neurosarcoidosis can reasonably be supported in many patients by MRI findings and exclusion of other disorders.

Relevance

Optimum management of patients with neurosarcoidosis relies on the ability of clinicians to recognize the broad spectrum of clinical and neuroimaging manifestations of the disorder.

Section snippets

Patients and methods

We performed a retrospective chart review of 69 patients meeting criteria for sarcoidosis (7) seen at our institution from 1988 through 2003. Records were examined with particular attention to the presence of neurological symptoms, neuroimaging studies, and cerebral spinal fluid (CSF) analysis. Relevant serological studies and concurrent systemic involvement were also noted. After the exclusion of alternate diagnoses, patients were classified as having “definite,” “probable,” or “possible”

Results

A total of 21 patients (6 definite, 11 probable, and 4 possible) were diagnosed with neurosarcoidosis in accordance with our criteria (Table 1). Seventeen were black (81%), three were white (14%), and one was Hispanic, with an average age of 41 years (range 20–65). In 11 patients, a diagnosis of sarcoidosis was not made until after neurological symptoms developed. In the remaining patients, the diagnosis of sarcoidosis preceded neurological disorders by 5 months to 20 years (average = 93

Discussion

Neurological involvement preceded a diagnosis of sarcoidosis in 11 patients (52%), consistent with prior observations of 31 to 74% (3, 4, 9, 10, 11, 12, 13). Neurosarcoidosis occurs in 5 to 10% of patients with systemic sarcoidosis, typically within 2 years of initial diagnosis (1, 2, 4, 14) and with a mean age from 33 to 44 years (4, 9). Although most patients with neurosarcoidosis eventually demonstrate extra-neurological manifestations (11), neurological involvement remains isolated in 10 to

Acknowledgment

The authors greatly appreciate the assistance of Debra Donato in the preparation of this manuscript.

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The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes.
We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis.
Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17–70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/μL; range: 1–643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up.
Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.
Retrospective, dual-centre review of imaging findings in neurosarcoidosis at presentation: prevalence and imaging sub-types
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To assess the prevalence of various imaging manifestations in neurosarcoidosis (NS) patients at presentation and to explore if specific imaging findings may cluster in different sub-groups.
A retrospective, dual-institution, systematic imaging review was undertaken of the magnetic resonance imaging (MRI) findings in 100 consecutive NS patients who presented over a 15-year period. Clustering analysis (k-mode) was performed to evaluate co-occurrence of imaging findings.
Non-enhancing white matter (NEWM) lesions were the most common imaging abnormality (56%), followed by leptomeningeal (47%) and pachymeningeal (32%) involvement. Other common manifestations included cranial nerve involvement (30%), parenchymal granulomas (27%), hypothalamic–pituitary–adrenal axis involvement (26%), and hydrocephalus (14%). Additionally, a higher prevalence of perivascular enhancement (23%), cerebrovascular events (including ischaemic and haemorrhagic events; 17%), and ependymal involvement (20%) were noted than recognised previously. Additional k-mode analysis was performed to explore underlying disease sub-clusters. This was evaluated for clusters varying between two though five (k=2–5). For k=4, the analysis revealed that the imaging findings may possibly be divided into disease sub-sets of four groups, each with varying distribution of imaging manifestations and clinical manifestations.
Overall, NEWM lesions and meningeal involvement are the most common imaging manifestations of NS. The prevalence of perivascular enhancement, cerebrovascular events, and ependymal involvement is likely higher than reported previously. Additionally, different imaging findings in NS may cluster together and imaging subtypes in NS possibly exist.
Leukocyte profiles in blood and CSF distinguish neurosarcoidosis from multiple sclerosis
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Distinguishing neurosarcoidosis (NS) from multiple sclerosis (MS) remains challenging and available parameters lack discriminatory power. Comprehensive flow cytometry data of blood and CSF leukocytes of patients with NS (n = 24), MS (n = 49) and idiopathic intracranial hypertension (IIH, n = 52) were analyzed by machine learning algorithms. NS featured a specific immune cell pattern with increased activated CD4+ T cells in CSF and increased plasma cells in blood. Combining blood and CSF parameters improved the differentiation. We thereby identify and independently validate a multi-dimensional model of blood and CSF supporting the difficult differential diagnosis between NS and MS.
Cerebrovascular manifestations in neurosarcoidosis: how common are they and does perivascular enhancement matter?
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Citation Excerpt :
Again, Oaksaken reported two cases of ICH in their series of 50 patients.21 Similarly, Spencer et al., reported one such case in their series of 21 patients.28 Notably, none of these three patients had an MRI study and all of them were clinically symptomatic.
To determine the occurrence of ischaemic and haemorrhagic events in patients with neurosarcoidosis at presentation and follow-up and to evaluate its association with perivascular enhancement.
The MRI findings in patients with neurosarcoidosis who presented to our institute from 2002–2017 were retrospectively reviewed, with emphasis on cerebrovascular events. A chi-squared test was used to evaluate the statistical association with presence of perivascular enhancement.
A total of 49 patients (32 females and 17 males) were analysed. Ischaemic events were noted in four patients at presentation while parenchymal haemorrhages occurred in three patients. The combined occurrence of cerebrovascular events (CVEs) at presentation was 14%. On follow-up, three additional patients developed ischaemic infarcts, of which, one patient had parenchymal haemorrhage at presentation. Additionally, one patient also developed new parenchymal haemorrhages. In total, 10 patients in current cohort developed CVEs, either at presentation or on follow-up. Perivascular enhancement was seen in 50% of patients with cerebrovascular events and 18% of patients with neurosarcoidosis, but no CVEs. This was statistically significant (p<0.05).
CVEs in patients with neurosarcoidosis are more common than previously reported and appear to be significantly related to the presence of perivascular enhancement on imaging.
Neurosarcoidosis
2018, Sarcoidosis: A Clinician's Guide
Neurosarcoidosis refers to central or peripheral nervous system involvement during sarcoidosis, linked to granulomatous invasion of various area of the nervous system. Clinical manifestations are heterogeneous, ranging from psychiatric or cognitive disturbances to motor or sensory deficits. Brain and medullar magnetic resonance imaging and cerebrospinal fluid analyses are crucial for neurosarcoidosis diagnosis and help to rule out other causes of nervous system involvement. Electroneuromyogram is useful for plexic, radicular, nerve, and muscle localizations. Infections and hematologic or solid malignancies are the more frequent differential diagnoses of neurosarcoidosis. Treatments rely on corticosteroids. Immunosuppressive drugs are frequently added because of the protracted course of neurosarcoidosis. Tumor necrosis factor alpha inhibitors have demonstrated efficacy in neurosarcoidosis, in addition to other treatments.

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View full text

Clinical and magnetic resonance imaging manifestations of neurosarcoidosis

Objectives

Patients and methods

Results

Conclusions

Relevance

Section snippets

Patients and methods

Results

Discussion

Acknowledgment

Chest

Mayo Clin Proc

Am J Med

Surg Neurol

Comput Med Imaging Graph

Clin Neurol Neurosurg

Surg Neurol

Clin Imaging

Comput Med Imaging Graph

Chest

Chest

Neurological complications of sarcoidosis

Clin Exp Neurol

Neurologic manifestations in sarcoidosisreview of the literature, with a report of 23 cases

Ann Intern Med

Sarcoidosis and its neurological manifestations

Arch Neurol

The spectrum of central nervous system sarcoidosis

A clinical and pathologic study. Mt Sinai J Med

Central nervous system sarcoidosis-diagnosis and management

QJM February

ATS/ERS/WASOG statement on sarcoidosis

American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis

Life-threatening vasculitis associated with sarcoidosis

J Clin Rheumatology

Systemic manifestations and enzyme studies in sarcoidosis with neurologic involvement

Acta Med Scand

Central nervous system sarcoidosis

Q J Med

Long-term follow-up of neurosarcoidosis

Neurology

Neurosarcoidosisa review of its intracranial manifestation

J Neurol

Neurosarcoidosissigns, course and treatment in 35 confirmed cases

Medicine (Baltimore)

Therapeutic considerations in patients with refractory neurosarcoidosis

Arch Neurol

Neurosarcoidosisclinical presentations and course in 50 patients

Acta Neurol Scand

Spinal cord sarcoidosis

Ann Neurol

Intraspinal sarcoidosisdiagnosis and management

Surg Neurol

Spinal cord sarcoidosis

Neuroradiology

Sarcoidosis mimicking gliomacase report and review of intracranial sarcoid mass lesions

Neurology

Neurosarcoidosisthe long-term clinical course

Neurology

Shunt-responsive dementia in sarcoid meningitisrole of magnetic resonance imaging and cisternography

J Neuroimaging

Neurosarcoidosis resembling meningiomaMRI characteristics and pathologic correlation

J Neuroimag