Clinical syndromes of neurosarcoidosis
Cranial neuropathy
Cranial neuropathy is the most common manifestation of the neurological complications of systemic sarcoidosis. It tends not to be severe and recovery usually occurs. Facial neuropathy is the most common manifestation of this at a frequency of 12-64%. Frequently bilateral, the lesion may arise in the nerve within an enlarged parotid gland or at the skull base or brainstem.
Double vision due to ophthalmoloplegia (when the nerves which make the eyes move are affected) has been noted in several reports, but is very rare as is isolated trigeminal neuropathy which causes facial numbness. The eighth cranial nerve may be involved in a number of ways; subacute unilateral hearing loss due to involvement of the nerve or the cochlea itself, and sometimes also the brain stem. This may or may not be associated with vertigo leading to a feeling of giddiness and imbalance. Lower cranial neuropathies also occur with involvement of the ninth, tenth and twelfth nerves leading to difficulty with speech and swallowing, but this is relatively less frequent than other cranial neuropathies.
Involvement of the optic nerve leading to visual loss has been noted in some 5% of cases in which the nervous system is involved and can be due to pressure on the optic nerve by an inflammatory mass within the brain, to inflammation of the nerve itself or to inflammation within the eye (uveitis). Patients may present with a subacute painful reduction in vision indistinguishable on clinical grounds from optic neuritis, or with a progressive painless decline in vision, but it affects both eyes more commonly. In general the visual loss is worse than that which is seen in optic neuritis, but it also tends to improve with adequate treatment.
Hemisphere involvement
Involvement of the brain itself may arise either due to the development of inflammation of the lining of the brain spreading in or to a mass of inflammatory tissue forming within the brain. The former may present with psychiatric symptoms with abnormal mental states including psychosis. Others present with what is known as encephalopathy, with a fluctuating level of consciousness and often the signs of the condition vary from day to day.
Focal mass lesions may cause weakness or numbness down one side, headaches are extremely common and epileptic seizures may also occur. These problems are often the most difficult to treat of all cases of neurosarcoidosis. Mass lesions may be mistaken for tumours, and sometimes doctors recommend an operation or biopsy to find out what the problem is due to before sarcoidosis is diagnosed. Involvement of the cerebellum and brain stem and the development of an akinetic rigid syndrome similar to Parkinsonism have been reported but are rare.
Hypothalmic and pituitary involvement
Autopsy series have shown that the development of inflammation in and around the hypothalamus, the pituitary gland and around the third ventricle is the most common site of neurological involvement. 10-35% in some series have symptoms related to disease in this region, so it may occur without causing obvious symptoms during life. The most common presenting symptom is of thirst and a need to drink more than usual. Obesity, sleep disturbance and temperature fluctuation have also been reported. Patients with lesions in this area may have visual field defects.
Meningitis and its complications
Acute meningitis is not common but a chronic and indolent basal granulomatous leptomeningitis or arachnoiditis is a common autopsy finding and may seemingly be asymptomatic or unrecognised. Cranial neuropathies may or may not occur and hydrocephalus may arise, in which the ventricles enlarge due to an increase in pressure around the brain, which may necessitate an operation to drain excess fluid from the brain. Treatment of this is often extremely difficult owing to shunt blockage. The condition known as hypertrophic pachymeningitis can occur in sarcoidosis and in other diseases like rheumatoid arthritis, and causes chronic headache, visual symptoms and hearing problems. These occur when the nerves passing out through the meninges become inflamed.
Spinal cord involvement
All parts of the spinal cord may be affected. Most commonly patients present with a cervical cord or conus medullaris involvement, which may be painful. The clinical syndrome varies between mild involvement with numbness, and severe, with evidence for transverse myelitis leading to difficulty walking and bladder problems. MRI scans show inflammation of the spinal cord and sometimes, like in the brain, it is thought to be a tumour before the diagnosis is made.
Involvement of the cauda equina has also been reported. This presents with an ascending, often bilateral, predominantly sensory disturbance with bladder and bowel problems. It tends not to be painful.
Peripheral neuropathy
Neuropathy reflects involvement of the nerves underneath the skin and outside of the brain and spinal cord.
- A symmetrical neuropathy involving the nerves of sensation and muscle control progressing over months or years is most typical.
- A purely sensory neuropathy has also been described and mononeuritis multiplex, when lots of different nerves are affected, may also occur.
- A subacute radiculoneuropathy resembling Guillain Barré syndrome has also been noted, in which patients develop an ascending numbness and weakness which can sometimes become sufficiently severe to require hospitalisation. Involvement of this part of the nervous system may occur unnoticed without any symptoms.
- Granulomatous masses underneath the skin or around joints may cause compressive neuropathies such as carpal tunnel syndrome.
- Recently a severe painful neuropathy known as a small fibre neuropathy has been shown, and is often not quickly diagnosed.
Muscle involvement
Muscle involvement is frequently asymptomatic and there are two forms:
- The nodular form involves the development of nodules of inflammation which may be single or multiple within limb muscles, sometimes associated with mild tenderness, but often not causing symptoms. Nodules are readily seen on MRI scans of the affected tissue and these lesions show contrast enhancement. Gallium scans often show uptake within the nodules.
- The myopathic form presents with a slowly progressive painful weakness and loss of muscle tissue in which MRI shows no nodules, but Gallium scans may show increased uptake. Muscle blood tests are sometimes elevated but are usually normal. Granulomas are seen on muscle biopsy, and response to treatment with immunosuppression and corticosteroids is poor, with the majority of patients continuing to deteriorate.