Neurosarcoidosis 1851370 224718164 2008-07-10T02:51:23Z Jfdwolff 46555 not actually free '''Neurosarcoidosis''' (sometimes shortened to '''neurosarcoid''') refers to [[sarcoidosis]], a condition of unknown cause featuring [[granuloma]]s in various tissues, involving the [[central nervous system]] (brain and spinal cord). It can have many manifestations, but abnormalities of the [[cranial nerves]] (a group of twelve nerves supplying the head and neck area) are the most common. It may develop acutely, subacutely, and chronically. Approximately 5-10% of people with sarcoidosis of other organs (e.g. [[lung]]) develop central nervous system involvement. Only 1% of people with sarcoidosis will have neurosarcoidosis alone without involvement of any other organs. Diagnosis can be difficult, with no test apart from [[biopsy]] being completely reliable. Treatment is with [[immunosuppression]].<ref name=Joseph2007>{{cite journal |author=Joseph FG, Scolding NJ |title=Sarcoidosis of the nervous system |journal=Practical neurology |volume=7 |issue=4 |pages=234–44 |year=2007 |pmid=17636138 |doi=10.1136/jnnp.2007.124263 |doi_brokendate=2008-06-23}}</ref> The first cases of sarcoidosis involving the nervous system was reported in 1948.<ref name="pmid18124739">{{cite journal |author=Colover J |title=Sarcoidosis with involvement of the nervous system |journal=Brain |volume=71 |issue=Pt. 4 |pages=451–75 |year=1948 |pmid=18124739 |doi=10.1093/brain/71.4.451}}</ref><ref>{{cite journal |doi=10.1001/archneur.60.8.1166 |year=2003 |month=Aug |author=Burns TM |title=Neurosarcoidosis |volume=60 |issue=8 |pages=1166–8 |pmid=12925378 |journal=Archives of neurology}}</ref> ==Signs and symptoms== ===Neurological=== Abnormalities of the cranial nerves are present 50-70% of cases. The most common abnormality is involvement of the [[facial nerve]], which may lead to reduced power on one or both sides of the face (65% resp 35% of all cranial nerve cases), followed by reduction in [[visual perception]] due to [[optic nerve]] involvement. Rarer symptoms are [[diplopia|double vision]] ([[oculomotor nerve]], [[trochlear nerve]] or [[abducens nerve]]), decreased sensation of the face ([[trigeminal nerve]]), [[hearing loss]] or [[Vertigo (medical)|vertigo]] ([[vestibulocochlear nerve]]), [[dysphagia|swallowing problems]] ([[glossopharyngeal nerve]]) and weakness of the shoulder muscles ([[accessory nerve]]) or the [[tongue]] ([[hypoglossal nerve]]). Visual problems may also be the result of [[papilledema]] (swelling of the [[optic disc]]) due to obstruction by granulomas of the normal [[cerebrospinal fluid]] (CSF) circulation.<ref name=Joseph2007/> [[Seizure]]s (mostly of the [[Tonic-clonic seizure|tonic-clonic]]/"grand mal" type) are present in about 15%, and may be the presenting phenomenon in 10%.<ref name=Joseph2007/> [[Meningitis]] (inflammation of the lining of the brain) occurs in 3-26% of cases. Symptoms may include [[headache]] and [[meningism|nuchal rigidity]] (being unable to bend the head forward). It may be acute or chronic.<ref name=Joseph2007/> Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the [[internal capsule]] would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause [[headache]] and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised [[intracranial pressure]] and [[hydrocephalus]]<ref name=Joseph2007/> Involvement of the [[spinal cord]] is rare, but can lead to abnormal sensation or weakness in one or more limbs, or [[cauda equina]] symptoms ([[incontinence]] to urine or stool, decreased sensation in the [[buttock]]s).<ref name=Joseph2007/> ===Endocrine=== Granulomas in the [[pituitary gland]], which produces numerous [[hormone]]s, is rare but leads to any of the symptoms of [[hypopituitarism]]: [[amenorrhoea]] (cessation of the [[menstrual cycle]]), [[diabetes insipidus]] (dehydration due to inability to concentrate the urine), [[hypothyroidism]] (decreased activity of the [[thyroid]]) or [[hypocortisolism]] (deficiency of [[cortisol]]).<ref name=Joseph2007/> ===Mental and other=== [[Psychiatry|Psychiatric problems]] occur in 20% of cases; many different disorders have been reported, e.g. [[Clinical depression|depression]] and [[psychosis]]. [[Peripheral neuropathy]] has been reported in up to 15% of cases of neurosarcoidosis.<ref name=Joseph2007/> Other symptoms due to sarcoidosis of other organs may be [[uveitis]] (inflammation of the [[uvea|uveal layer]] in the eye), [[dyspnoea]] (shortness of breath), [[arthralgia]] (joint pains), [[lupus pernio]] (a red skin rash, usually of the face), [[erythema nodosum]] (red skin lumps, usually on the shins), and symptoms of [[liver]] involvement ([[jaundice]]) or [[heart]] involvement ([[heart failure]]).<ref name=Joseph2007/> ==Diagnosis== The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by [[biopsy]] (surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are [[computed tomography]] (CT) or [[magnetic resonance imaging]] (MRI) of the brain, [[lumbar puncture]], [[electroencephalography]] (EEG) and [[evoked potential]] (EP) studies. If the diagnosis of sarcoidosis is suspected, typical [[chest X-ray|X-ray]] or CT appearances of the chest may make the diagnosis more likely; elevations in [[angiotensin-converting enzyme]] and [[calcium in biology|calcium]] in the blood, too, make sarcoidosis more likely. In the past, the [[Kveim test]] was used to diagnose sarcoidosis. This now obsolete test had a high (85%) sensitivity, but required [[spleen]] tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.<ref name=Joseph2007/> Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate [[granuloma]]s (collections of inflammatory cells) rich in [[epithelioid]] cells and surrounded by other immune system cells (e.g [[plasma cell]]s, [[mast cell]]s). Biopsy may be performed to distinguish mass lesions from [[tumour]]s (e.g. [[glioma]]s).<ref name=Joseph2007/> MRI with [[gadolinium]] enhancement is the most useful neuroimaging test. This may show enhancement of the [[pia mater]] or [[white matter]] lesions that may resemble the lesions seen in [[multiple sclerosis]].<ref name=Joseph2007/> Lumbar puncture may demonstrate raised [[protein]] level, pleiocytosis (i.e. increased presence of both [[lymphocyte]]s and [[neutrophil granulocyte]]s) and [[oligoclonal band]]s. Various other tests (e.g. ACE level in CSF) have little added value.<ref name=Joseph2007/> ==Criteria== Some recent papers propose to classify neurosarcoidosis by likelihood:<ref name=Joseph2007/> * ''Definite'' neurosarcoidosis can only be diagnosed by plausible symptoms, a positive biopsy and no other possible causes for the symptoms * ''Probable'' neurosarcoidosis can be diagnosed if the symptoms are suggestive, there is evidence of central nervous system inflammation (e.g. CSF and MRI), and other diagnoses have been excluded. A diagnosis of systemic sarcoidosis is not essential. * ''Possible'' neurosarcoidosis may be diagnosed if there are symptoms not due to other conditions but other criteria are not fulfilled. ==Pathophysiology== {{main|Sarcoidosis#Causes and pathophysiology}} Sarcoidosis is a disease of unknown cause that leads to the development of granulomas in various organs. While the lungs are typically involved, other organs may equally be affected. Some subforms of sarcoidosis, such as [[Löfgren syndrome]], may have a particular precipitant and have a specific course. It is unknown which characteristics predispose sarcoidosis patients to brain or spinal cord involvement.<ref name=Joseph2007/> ==Treatment== Neurosarcoidosis, once confirmed, is generally treated with [[glucocorticoid]]s such as [[prednisolone]]. If this is effective, the dose may gradually be reduced (although many patients need to remain on steroids long-term, frequently leading to side-effects such as [[diabetes mellitus|diabetes]] or [[osteoporosis]]). [[Methotrexate]], [[hydroxychloroquine]], [[cyclophosphamide]], [[pentoxifylline]], [[thalidomide]] and [[infliximab]] have been reported to be effective in small studies. In patients unresponsive to medical treatment, [[radiation therapy|radiotherapy]] may be required. If the granulomatous tissue causes obstruction or mass effect, [[neurosurgery|neurosurgical]] intervention is sometimes necessary. Seizures can be prevented with [[anticonvulsant]]s, and psychiatric phenomena may be treated with medication usually employed in these situations.<ref name=Joseph2007/> ==Prognosis== Of the phenomena occurring in neurosarcoid, only [[facial nerve]] involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena.<ref name=Joseph2007/> ==Epidemiology== Sarcoidosis has a prevalence of 40 per 100,000. Given that less than 10% of these will have neurological involvement, and possibly later on in their disease course, neurosarcoidosis has a prevalence of less than 4 per 100,000.<ref name=Joseph2007/> ==Notable cases== The American television personality and actress [[Karen Duffy]] wrote "Model Patient: My Life As an Incurable Wise-Ass" on her experiences with neurosarcoidosis.<ref>{{cite book |author=Duffy, Karen Grover |title=Model Patient : My Life As an Incurable Wise-Ass |publisher=Perennial |location=New York, NY |year= |pages= |isbn=0-06-095727-1 |oclc= |doi=}}</ref> ==References== <references/> ==External links== * [http://www.emedicine.com/NEURO/topic649.htm eMedicine] [[Category:Neurological disorders]]