Description
Neurosarcoidosis refers to the involvement of the central nervous system (CNS) in sarcoidosis, a systemic non-caseating granulomatous disease of unknown aetiology that primarily affects the lungs (pulmonary sarcoidosis) and lymphatic system.
Pathogenesis
Although the exact cause is unknown, sarcoidosis is thought to be a result of an exaggerated cellular immune response to various antigens or self-antigens. This immune response leads to the formation of non-caseating granulomas, the hallmark of the disease. In neurosarcoidosis, these granulomas primarily affect the CNS, including the brain, spinal cord, and cranial and peripheral nerves.
Epidemiology, Risk Factors & Associations
Neurosarcoidosis is a relatively rare manifestation of sarcoidosis, affecting approximately 5-15% of individuals with sarcoidosis. It can occur at any age but is more common in adults between 20 and 40 years old. Both sexes are equally affected, and it occurs worldwide, with no particular geographic predisposition. It has been found to be more prevalent in people of African descent.
Associations:
- Löfgren syndrome (a.k.a. acute pulmonary sarcoid): Fever, malaise, bilateral hilar adenopathy. Erythema nodosum and large joint arthralgia. May have uveitis, parotitis
- Heerfordt syndrome (a.k.a. salivary gland sarcoidosis): Fever, parotitis, uveitis, and facial nerve paralysis
Clinical Features
Clinical manifestations of neurosarcoidosis are highly variable and depend on the areas of the nervous system affected. Features may include:
- Cranial neuropathies, with the facial nerve being the most commonly involved, resulting in facial palsy.
- Headaches and seizures
- Hydrocephalus and increased intracranial pressure due to granulomas affecting the base of the brain.
- Neuroendocrine abnormalities due to hypothalamic or pituitary involvement, including diabetes insipidus or hypopituitarism.
- Myelopathy or radiculopathy if the spinal cord or nerve roots are involved.
Pathological Features
Histopathology
- Characterised by non-caseating granulomas, consisting of tightly packed mononuclear cells, primarily macrophages and T lymphocytes, often surrounded by a rim of lymphocytes.
- Special stains for fungi and mycobacteria are typically negative, helping to distinguish sarcoid granulomas from those caused by infectious agents.
Radiological Features
General Features
- Solitary or multifocal CNS masses with an abnormal chest x-ray
MRI
- Leptomeningeal diffuse or nodule thickening and enhancement is a common finding, especially at the base of the brain.
- Leptomeningeal involvement around the hypothalamus and pituitary infundibulum can also be seen
- Parenchymal lesions which can be solitary or multiple, typically demonstrating T2 hyperintensity and enhancement after gadolinium administration.
- Myelopathy or radiculopathy if the spinal cord or nerve roots are involved.
- Any cranial nerve can be involved – most commonly the facial nerve.
CT
- Less sensitive than MRI but may reveal parenchymal lesions or calcifications.
- Can identify thoracic manifestations of sarcoidosis, which can support the diagnosis.
NM
FDG-PET can show hypermetabolic activity in areas of active inflammation and granuloma formation, and can be useful in identifying sites for biopsy.
Staging
There is no specific staging system for neurosarcoidosis. The severity and progression of the disease are generally assessed based on clinical manifestations, neurological deficits, and imaging findings.
Differential Diagnosis
- Multiple sclerosis: Typically presents with white matter lesions disseminated in time and space, and is a common mimic of neurosarcoidosis. However, the granulomas typical of sarcoidosis are not seen in MS.
- Lymphoma or metastatic disease: Can also cause multiple enhancing lesions in the CNS. The patient’s age, clinical history, and pattern of lesions can help distinguish these conditions.
- Tuberculosis or fungal infections: These infections can also cause granulomas and may mimic neurosarcoidosis. The presence of caseation in the granulomas, positive cultures or molecular diagnostic tests can help distinguish these infections.
- Vasculitis: Conditions such as CNS vasculitis or Behçet’s disease can present with similar findings to neurosarcoidosis. However, they often have distinguishing clinical and imaging features.