Neurosarcoidosis Clinical Presentation
- Author: Gabriel Bucurescu, MD, MS; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS more...
Onset of neurosarcoidosis is most often in the fourth or fifth decade of life, but the disease affects children and the elderly as well. Neuropathy is rarely the presenting feature of sarcoidosis; commonly it reflects a neurologic extension of existing sarcoidosis, usually occurring within 2 years of onset of systemic illness (eg, fatigue, malaise, arthralgia, fever, and weight loss).
In patients known to have sarcoid, the appearance of neurologic symptoms usually poses no diagnostic problems. However, the possibility of unrelated disease, especially infections, must be kept in mind. The symptoms can be acute, subacute, or chronic.
Clinical presentations are diverse and include the following:
Diffuse sensorimotor neuropathy
Distal-to-proximal slowly progressive weakness
Distal numbness and dysesthesia
Multifocal neuropathies that mimic mononeuritis multiplex
An acute generalized demyelinating motor neuropathy similar to Guillain-Barré syndrome
Generalized or localized muscle weakness or soreness
Most of the neuropathies associated with sarcoidosis are initially multifocal and eventually become confluent; thus, the initial presentation may be that of mononeuritis multiplex. This is seen most frequently in the cranial nerves: lower motor neuron neuropathy of the facial nerve (the nerve most frequently involved) may present along with other cranial neuropathies or as bilateral facial neuropathies, sometimes in a sequential manner mimicking Lyme disease.
When neuropathy is associated with fever, uveitis, and parotid gland enlargement, some patients may be thought to have Heerfordt syndrome. Carpal tunnel syndrome may be more common in patients with sarcoidosis than in the general population.[10, 11, 12] Audiovestibular manifestations of sarcoidosis (especially sensory hearing loss) are likely to be primarily a result of vestibulocochlear nerve neuropathy.
In a series of 57 patients with biopsy-proven sarcoidosis causing limb neuropathy, most patients noted a definite date of clinical onset. Positive neuropathic sensory symptoms—especially pain—were prominent, overshadowing weakness and sensory loss. The pattern was almost always asymmetric and not length-dependent (unlike distal polyneuropathy). The pathologic process was focal or multifocal, involving most classes of nerve fibers and variable levels of proximal to distal levels of roots and peripheral nerves.
A case of neurosarcoidosis presenting as complicated sinusitis has been reported, but the incidence of sinonasal cases is rare, ranging from 1-4% of patients. Head and neck manifestations occur in approximately 10-15% of patients with sarcoid.
Cranial nerve mononeuropathy
The facial nerve is the most commonly affected cranial nerve in neurosarcoidosis. Either unilateral or bilateral involvement may occur.
Heerfordt syndrome is a rare manifestation characterized by fever, uveitis, swelling of the parotid gland, and facial nerve palsy. It represents a type of neurosarcoidosis. The lesion site has been controversial, but direct nerve compression by parotid gland swelling or by a lesion within the facial canal has been assumed, in light of observations of accompanying taste disturbance.
A rare case of gingival sarcoidosis has been described in a patient with cranial nerve involvement.
Cranial nerve mononeuropathies may produce the following manifestations:
Impaired taste and smell
Blindness, blurry vision, double vision, visual field defects, pupillary abnormalities, dry and sore eyes
Slurred speech, impaired swallowing, hoarseness
Vertigo, sensorineural deafness, tinnitus
Weakness of trapezius and sternocleidomastoid muscles
Tongue deviation and atrophy
Peripheral nerve involvement may result in sensory or motor mononeuropathy, mononeuropathy multiplex, or polyneuropathy. Sensory neuropathy is characterized by loss of sensation and abnormal sensation (eg, tingling, numbness, extremity pain, low back pain, painful patches over the thorax, stocking/glove deficits) Motor neuropathy is characterized by weakness, leading to immobility and joint stiffness. Bell-shaped truncal tightening and pain with sensory disturbance of superficial and deep sensations has also been described.
Patients may present with more focal findings referable to the nerve involved. Thus, polyradiculopathy involving the cauda equina may present as progressive lower extremity weakness with or without sphincter involvement. Mononeuropathies present as symptoms reflecting impairment of function in the particular nerve distribution.
Central nervous system involvement
Central nervous system involvement may affect the hypothalamus/pituitary gland, cerebral cortex, cerebellum, and spinal cord (rarely), resulting in the following:
Changes in appetite
Changes in sleep cycle (somnolence, hypersomnia  )
Impaired temperature regulation (hyperthermia, hypothermia)
Change in menstrual period
Amnesia, both short term and long term
Loss of judgment
Cerebral infarct or transient ischemic attack
Kleine-Levine-Critchley syndrome (rare) 
Parkinsonism (with basal ganglia infiltration) 
Sudden death 
Seizures may be the first manifestation of neurosarcoidosis. Generally, seizures indicate a chronic course with poor prognosis. Patients with isolated mass lesions and simple partial or complex partial seizures (with or without secondary generalization) may have better outcomes than patients with generalized tonic-clonic seizures only.
Some patients with neurosarcoidosis may have small-fiber neuropathy with autonomic involvement. This may manifest as unexplained pain and dysesthesia, reduced warm and cold sensitivity, or even cardiac autonomic disturbances. Recognition of cardiac autonomic disturbances may be of clinical relevance because of their associated morbidity.
Sudden death from systemic sarcoidosis is highly unusual. Rare cases of sudden death have been reported. The mechanism of action in one case was suspected to be involvement of the nucleus of the solitary tract in the brainstem, and the cause of death was attributed to central hypoventilation. Another report describes a case of a woman aged 24 years who was found unconscious and subsequnetly died. No neurological symptoms were observed prior to this. Autopsy showed obstructive hydrocephalus.
Patient may have signs of the following:
Clinical findings depend on the type and the nature of the peripheral nerve involvement. In diffuse polyneuropathy, patients experience weakness with a distal predominance. Deep tendon reflexes are attenuated or absent.
Sensory modalities are impaired in a stocking-and-glove distribution, with large-fiber modalities (eg, proprioception, vibration) more commonly and more severely affected than small-fiber functions (eg, pain, temperature). However, the prevalence of small-fiber neuropathy with pain as a symptom may be more frequent than previously recognized. Pure sensory neuropathy has been reported.
Myopathy is characterized by tenderness, muscles feeling "hard" on palpation, and weakness. Distal atrophy may be noted, depending on the duration of the neuropathy.
Focal neuropathies result in dysfunction in the distribution of that nerve. The most common of these neuropathies is that of unilateral lower motor neuron facial nerve, and patients often are thought to have Bell palsy at presentation. Facial nerve neuropathy also can be bilateral.
Polyradiculopathy commonly affects the cauda equina. Patients present with asymmetrical weakness of the lower extremities, with loss of the deep tendon reflexes and patchy sensory loss, including the perianal region.
Eye involvement may be evident on examination; vision may be affected. Neurosarcoidosis may produce optic neuritis leading to optic atrophy. See the images below.
Hebel R, Dubaniewicz-Wybieralska M, Dubaniewicz A. Overview of neurosarcoidosis: recent advances. J Neurol. 2015 Feb. 262 (2):258-67. [Medline].
Voorter CE, Drent M, Hoitsma E, Faber KG, van den Berg-Loonen EM. Association of HLA DQB1 0602 in sarcoidosis patients with small fiber neuropathy. Sarcoidosis Vasc Diffuse Lung Dis. 2005 Jun. 22(2):129-32. [Medline].
Desestret V, Didelot A, Meyronet D, Bruyas A, Jouvet A, Honnorat J. Neurosarcoidosis with diencephalitis and anti-Ma2 antibodies. Neurology. 2010 Mar 2. 74(9):772-4. [Medline].
Kobayashi D, Rouster-Stevens K, Harper A. La crosse virus encephalitis preceding neurosarcoidosis diagnosed by brain biopsy. Pediatrics. 2011 Apr. 127(4):e1091-6. [Medline].
Motta M, Alongi F, Bolognesi A, Cozzarini C, Di Muzio N, Fazio F. Remission of refractory neurosarcoidosis treated with brain radiotherapy: a case report and a literature review. Neurologist. 2008 Mar. 14(2):120-4. [Medline].
Joseph FG, Scolding NJ. Neurosarcoidosis: a study of 30 new cases. J Neurol Neurosurg Psychiatry. 2009 Mar. 80(3):297-304. [Medline].
Allen RK, Sellars RE, Sandstrom PA. A prospective study of 32 patients with neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2003 Jun. 20(2):118-25. [Medline].
Byard RW, Manton N, Tsokos M. Sarcoidosis and mechanisms of unexpected death. J Forensic Sci. 2008 Mar. 53(2):460-4. [Medline].
Petropoulos IK, Zuber JP, Guex-Crosier Y. Heerfordt syndrome with unilateral facial nerve palsy: a rare presentation of sarcoidosis. Klin Monbl Augenheilkd. 2008 May. 225(5):453-6. [Medline].
Niemer GW, Bolster MB, Buxbaum L, Judson MA. Carpal tunnel syndrome in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2001 Oct. 18(3):296-300. [Medline].
SHAMBAUGH GE, CIRKSENA WJ, NEWCOMER KL. CARPAL TUNNEL SYNDROME AS MANIFESTATION OF SARCOIDOSIS. Arch Intern Med. 1964 Dec. 114:830-3. [Medline].
Nakatani-Enomoto S, Aizawa H, Koyama S, Kuroda K, Kimura T, Kikuchi K. Transient swelling of peripheral nerves in a case of neurosarcoidosis. Intern Med. 2004 Nov. 43(11):1078-81. [Medline].
Colvin IB. Audiovestibular manifestations of sarcoidosis: a review of the literature. Laryngoscope. 2006 Jan. 116(1):75-82. [Medline].
Burns TM, Dyck PJ, Aksamit AJ, Dyck PJ. The natural history and long-term outcome of 57 limb sarcoidosis neuropathy cases. J Neurol Sci. 2006 May 15. 244(1-2):77-87. [Medline].
Brigger MT, McLeod IK, Sorensen MP. Neurosarcoidosis presenting as complicated sinusitis: a case report and review. Ear Nose Throat J. 2008 Feb. 87(2):93-5. [Medline].
Parthasarathy K, Wu J, Vigneswaran N. Oral and maxillofacial pathology case of the month. Neurosarcoidosis. Tex Dent J. 2010 Aug. 127(8):786-9. [Medline].
Miura S, Kusumoto M, Noda K, Azuma K, Toda R, Honda S, et al. Bell-shaped sensory impairments of all modalities in a neurosarcoidosis patient. Clin Neurol Neurosurg. 2007 Nov. 109(9):794-8. [Medline].
Nakazato Y, Kondo S, Ohkuma A, Ito Y, Tamura N, Araki N. Neurosarcoidosis presenting as spontaneously remitting hypersomnia. J Neurol. 2009 Nov. 256(11):1929-31. [Medline].
Afshar K, Engelfried K, Sharma OP. Sarcoidosis: a rare cause of Kleine-Levine-Critchley syndrome. Sarcoidosis Vasc Diffuse Lung Dis. 2008 Sep. 25(1):60-3. [Medline].
D'Errico S, Bello S, Cantatore S, Neri M, Riezzo I, Turillazzi E, et al. Immunohistochemical characterisation and TNF-a expression of the granulomatous infiltration of the brainstem in a case of sudden death due to neurosarcoidosis. Forensic Sci Int. 2011 May 20. 208(1-3):e1-5. [Medline].
Hoitsma E, Faber CG, van Kroonenburgh MJ, Gorgels AP, Halders SG, Heidendal GA, et al. Association of small fiber neuropathy with cardiac sympathetic dysfunction in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005 Mar. 22(1):43-50. [Medline].
Zoja R, Andreola S, Gentile G, Rancati A. Sudden death from systemic sarcoidosis: a case of legal medicine. Sarcoidosis Vasc Diffuse Lung Dis. 2012 Mar. 29(1):62-8. [Medline].
Uzawa A, Kojima S, Yonezu T, Kanesaka T. Truncal polyradiculopathy due to sarcoidosis. J Neurol Sci. 2009 Jun 15. 281(1-2):108-9. [Medline].
Mañá J, Gámez C. Molecular imaging in sarcoidosis. Curr Opin Pulm Med. 2011 Sep. 17(5):325-31. [Medline].
Kim SK, Im HJ, Kim W, Kim TS, Hwangbo B, Kim HJ. F-18 fluorodeoxyglucose and F-18 fluorothymidine positron emission tomography/computed tomography imaging in a case of neurosarcoidosis. Clin Nucl Med. 2010 Feb. 35(2):67-70. [Medline].
Petereit HF, Reske D, Tumani H, et al. Soluble CSF interleukin 2 receptor as indicator of neurosarcoidosis. J Neurol. 2010 Nov. 257(11):1855-63. [Medline].
Eckstein C, Saidha S, Sotirchos ES, Byraiah G, Seigo M, Stankiewicz A, et al. Detection of clinical and subclinical retinal abnormalities in neurosarcoidosis with optical coherence tomography. J Neurol. 2012 Jul. 259(7):1390-8. [Medline].
Bos MM, Overeem S, van Engelen BG, Scheffer H, van den Elzen C, Ter Laak H, et al. A case of neuromuscular mimicry. Neuromuscul Disord. 2006 Aug. 16(8):510-3. [Medline].
Nemni R, Galassi G, Cohen M, Hays AP, Gould R, Singh N, et al. Symmetric sarcoid polyneuropathy: analysis of a sural nerve biopsy. Neurology. 1981 Oct. 31(10):1217-23. [Medline].
Vital A, Lagueny A, Ferrer X, Louiset P, Canron MH, Vital C. Sarcoid neuropathy: clinico-pathological study of 4 new cases and review of the literature. Clin Neuropathol. 2008 Mar-Apr. 27(2):96-105. [Medline].
Said G, Lacroix C, Planté-Bordeneuve V, Le Page L, Pico F, Presles O, et al. Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a clinicopathological study of 11 patients. Brain. 2002 Feb. 125:264-75. [Medline].
Levy Y, Uziel Y, Zandman G, Rotman P, Amital H, Sherer Y, et al. Response of vasculitic peripheral neuropathy to intravenous immunoglobulin. Ann N Y Acad Sci. 2005 Jun. 1051:779-86. [Medline].
Santos E, Shaunak S, Renowden S, Scolding NJ. Treatment of refractory neurosarcoidosis with Infliximab. J Neurol Neurosurg Psychiatry. 2010 Mar. 81(3):241-6. [Medline].
Pereira J, Anderson NE, McAuley D, Bergin P, Kilfoyle D, Fink J. Medically refractory neurosarcoidosis treated with infliximab. Intern Med J. 2011 Apr. 41(4):354-7. [Medline].
Bomprezzi R, Pati S, Chansakul C, Vollmer T. A case of neurosarcoidosis successfully treated with rituximab. Neurology. 2010 Aug 10. 75(6):568-70. [Medline].
Androdias G, Maillet D, Marignier R, et al. Mycophenolate mofetil may be effective in CNS sarcoidosis but not in sarcoid myopathy. Neurology. 2011 Mar 29. 76(13):1168-72. [Medline].
Hammond ER, Kaplin AI, Kerr DA. Thalidomide for acute treatment of neurosarcoidosis. Spinal Cord. 2007 Dec. 45(12):802-3. [Medline].
Hoitsma E, Faber CG, van Santen-Hoeufft M, De Vries J, Reulen JP, Drent M. Improvement of small fiber neuropathy in a sarcoidosis patient after treatment with infliximab. Sarcoidosis Vasc Diffuse Lung Dis. 2006 Mar. 23(1):73-7. [Medline].
Hostettler KE, Studler U, Tamm M, Brutsche MH. Long-Term Treatment with Infliximab in Patients with Sarcoidosis. Respiration. 2011 Jul 29. [Medline].
Sundaresan P, Jayamohan J. Stereotactic radiotherapy for the treatment of neurosarcoidosis involving the pituitary gland and hypothalamus. J Med Imaging Radiat Oncol. 2008 Dec. 52(6):622-6. [Medline].