This site is targeted at medical and radiology professionals, contains user contributed content, and material that may be confusing to a lay audience. Use of this site implies acceptance of our Terms of Use.

Neurosarcoidosis

Central nervous system involvement by sarcoidosis (also termed neurosarcoidosis) is relatively common among patients with systemic sarcoidosis and has a bewildering variety of manifestations, often making diagnosis difficult. 

For a general discussion of the underlying condition, please refer to the article sarcoidosis

Epidemiology

The demographics of affected patients is not different to that of systemic sarcoidosis, typically affecting patients 30-40 years of age with a female predilection 2. Histologically, central nervous system involvement is seen in 14-27% of patients with systemic sarcoidosis, although only 3-15% are symptomatic 1-3. Interestingly up to 10% of patients with systemic disease will demonstrate imaging findings; thus not all patients with demonstrable imaging findings of neurosarcoidosis are symptomatic. 

Disease limited to the central nervous system (e.g. isolated neurosarcoidosis) is rare, with incidence ranging between series from 1-17% 1,6

Clinical presentation

Central nervous system involvement by sarcoidosis is very variable, with lesions potentially involving the leptomeninges, pituitary and parenchyma of all parts of the intracranial compartment. Thus clinical presentation is also vary variable and non-specific. It includes:

  • signs and symptoms of raised ICP due to hydrocephalus
  • cranial nerve palsies
    • optic nerve involvement (particularly common) 5
    • facial nerve palsy
  • diabetes insipidus from pituitary involvement
  • seizures
  • variable weakness, paresthesias and dysarthria/dysphasia
  • spinal cord involvement presenting as myelopathy 5

Although it is very rare to have isolated neurosarcoidosis (e.g. without systemic disease), central nervous system symptoms are not uncommonly the first manifestation, and as such patients are often imaged without the diagnosis of systemic sarcoidosis having yet been made. 

Radiographic features

The radiographic features of neurosarcoidosis can be thought of as occurring in one or more of five compartments. From superficial to deep they are:

  • skull vault involvement (refer to musculoskeletal manifestations of sarcoidosis)
  • pachymeningeal involvement
  • leptomeningeal involvement (seen in up to 40% of cases 1
    • pituitary and hypothalamic involvement
    • cranial nerve involvement
  • parenchymal involvement (most common)
CT

Although CT is usually the first modality used in the work-up of patients with neurosarcoidosis, it is not as sensitive or specific as MRI, with up to 60% of patients with subsequently proven neurosarcoidosis having negative CT scans 2. The features will be similar and regions that demonstrate enhancement on MRI may also be seen to enhance on CT, although often less dramatically. 

On non-contrast scanning lesions, be they pachymeningeal, leptomeningeal or parenchymal, can appear hyperdense 2

Often the only finding is hydrocephalus due to unseen leptomeningeal disease 2

MRI

MRI with contrast is the modality of choice for investigating suspected neurosarcoidosis.  In general lesions follow a standard signal intensity 1-2:

  • T1: iso- or hypointense with respect to adjacent grey matter
  • T2
    • variable
    • most are hyperintense
    • some lesions can be iso or hypointense
  • T1 C+: homogenous enhancement
Pachymeningeal involvement

Pachymeningeal disease often takes the form of pachymeningeal thickening with homogenous enhancement. In some cases the masses can be low on T2 weighted images, which although a helpful clue, is not pathognomonic. 

Leptomeningeal involvement

The most important sequence is T1 weighted with contrast, as quite prominent changes may be inapparent on other sequences. There may be focal or generalised leptomeningeal enhancement: 3

  • particularly around the basal aspects of the brain and circle of Willis
  • nodular or smooth 
  • may follow perforating vessels up into the brain (via the perivascular spaces
    • sometimes referred to as tongues of fire sign 2
    • can mimic parenchymal lesions
    • can result in a CNS vasculitis picture, especially if leptomeningeal disease is subtle elsewhere 1-2
  • may result in hydrocephalus
Pituitary and hypothalamic involvement

Although pituitary and hypothalamic involvement is frequently seen as part of more extensive leptomeningeal disease, it may also be encountered in isolation, sometimes with limited disease confined to the infundibulum. 

Cranial nerve involvement

Cranial nerves may be involved either as part of more widespread leptomeningeal disease, or in isolation. Although any nerve can be involved, the facial nerve and optic nerve are most commonly affected:

  • facial nerve involvement is usually symptomatic, but is often normal on imaging
  • optic nerve involvement can be anywhere along its course from the globe to the optic chiasm

Also see orbital manifestations of sarcoidosis for a discussion of the non-optic nerve orbital disease spectrum.  

Parenchymal involvement

Parenchymal involvement is the most common finding and can be in a number of forms 1,5:

  • extension of leptomeningeal disease up perivascular spaces
  • periventricular high T2 white matter lesions
    • often indistinguishable from MS or chronic small vessel ischaemic change
    • may have low T2 components (without haemorrhage) due to high cellularity
  • enhancing masses/nodules
Nuclear medicine

Gallium-67 citrate scan is insensitive to central nervous system involvement, positive in only 5% of cases. It is however helpful in confirming the presence of systemic disease when neurological manifestations are the presenting complaint. In this setting, gallium scan is positive in approximately 45% 1. Care should be taken however in interpreting results as other inflammatory/white cell abundant diseases may also be positive, some of which are on the differential for neurosarcoidosis (e.g. tuberculosis and lymphoma). 

Treatment and prognosis

Treatment of neurosarcoidosis remains poorly established. Corticosteroids are the mainstay of treatment with methotrexate sometimes used as a second line agent 1

It is important to note that imaging correlates poorly with treatment response. Recurrence of symptoms and/or imaging evidence of disease progression is common. 

Differential diagnosis

The differential is broad and depends on the pattern of involvement. 

For pachymeningeal involvement consider
For leptomeningeal involvement consider
For pituitary and hypothalamic involvement consider
For cranial nerve involvement consider

in addition to all causes of leptomeningeal disease (see above), specific entities to be considered include 1:

For parenchymal involvement consider

Related articles

Updating… Please wait.
Loadinganimation

Alert_accept

Error Unable to process the form. Check for errors and try again.

Alert_accept Thank you for updating your details.