eMedicine Specialties > Neurology > Neuromuscular Diseases

Sarcoidosis and Neuropathy

Author: N K Nikhar, MD, Assistant Professor, Department of Neurology, George Washington University School of Medicine
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Updated: Mar 8, 2007

Introduction

Background

In its most common form, the idiopathic multisystem disorder sarcoidosis is characterized by pulmonary, lymphoreticular system, and skin involvement. Histologically, noncaseating granulomas are prominent in biopsies from lymph nodes or affected organs. Neurological involvement occurs in 5-15% of cases. Among those with neurosarcoidosis, a subset has predominantly neuromuscular involvement.

Pathophysiology

Sarcoidosis is idiopathic, and the trigger antigen inciting granuloma formation is unknown. The prominent involvement of the pulmonary system has raised the possibility of inciting airborne agents, but to date no infectious organism has been linked.

The lymphoreticular system is affected with prominent cervical and mediastinal lymphadenopathy (eg, perihilar and peritracheal nodes) and involvement of the smaller scattered lymphatic collections in solid organs (eg, spleen, liver) and in lymphatic tissue surrounding glandular organs such as the parotid and lacrimal glands.

Debate continues as to whether sarcoidosis results from a dysfunctional immune system or a secondary response to environmental antigens. Sarcoid granulomas may be seen in solid organs such as liver, kidney, and spleen. Neurosarcoidosis results from nervous system involvement by sarcoid granulomas.

The clinical features of neurosarcoidosis depend on the site of neuraxis involved. While neurosarcoidosis most commonly affects the central nervous system, a subset of patients demonstrate predominantly peripheral nervous system involvement. This may manifest as a myopathy and/or a peripheral neuropathy depending on the distribution of the granulomas.

The true incidence of peripheral neuropathy in sarcoidosis is unknown, as a significant number of asymptomatic patients with sarcoidosis have subclinical peripheral nerve involvement.

Neuropathy occurs via 2 mechanisms. The tissue can be involved directly: in muscle, a slow and indolent myositis results, and in the nerve, a neuropathy results. Granulomas in the nerve are seen most often in the perineurium and the epineurium, with local effects leading to axonal damage.

Some studies reveal sparing of the endoneurium, but others show prominent infiltration of the endoneurium, suggesting that all 3 nerve layers may be involved. Occasionally, myelin loss is prominent, with appearance of myelin ovoids. Whether the latter are due to compression from the granulomas, a result of regional toxic effects, or a result of specific targeting of the myelin sheath is unclear.

Tajima suggested a predominance of helper T cells in the sarcoid granulomas. Inflammation of the vasa nervorum or the arterioles to the muscles can result in ischemic injury. Peripheral nerve injury from these mechanisms may result in a diffuse polyneuropathy, mononeuritis multiplex, focal mononeuropathies, or polyradiculopathy from involvement of spinal root sheaths. The spinal root sheaths are an extension of the pachymeninges and a tissue for which sarcoid granulomas have a particular predilection.

Frequency

United States

Neurosarcoidosis occurs in approximately 5% of patients with sarcoidosis. Peripheral neuropathy is seen in 5-15% of those with neurosarcoidosis. In a series from Johns Hopkins University, 2 of 33 patients with neurosarcoidosis had peripheral neuropathy. Eighty-five percent of this patient population was African American and 15% was white.

International

Forty percent of 35 patients with neurosarcoidosis in a French series had peripheral neuropathy. Ninety-one percent of these patients were Caucasian, and 9% were black. The large discrepancy between the 2 groups may exist because the white population with neurosarcoidosis is more predisposed to peripheral neuropathy than the black population. The term "black" is used rather than African American because it refers to members of the African race and is less restrictive in its description of different nationalities.

Mortality/Morbidity

• The mortality rate is difficult to assess.
• Most patients with peripheral neuropathy from sarcoidosis also exhibit other systemic or CNS manifestations of the disease. These manifestations pose greater morbidity and mortality risks than polyneuropathy alone.
• The proportion of patients who have exclusively sarcoid polyneuropathy is unknown.

Race

• Neurosarcoidosis is far more prevalent in the black population than in Caucasians: as many as 85% of patients with neurosarcoidosis are black. While sarcoidosis in general is more common in blacks than in other races, it is also seen in Caucasians, as shown in numerous studies from Europe. Whether the percentage of patients with peripheral neuropathy from sarcoidosis is higher in blacks than in whites is not clear.
• No racial predilection for the development of sarcoid neuropathy is known.

Sex

The female-to-male ratio ranges from 55:45 to 63:37.

Age

All ages are affected, but young adults are especially susceptible.

Clinical

History

Neuropathy can be the presenting feature of sarcoidosis, but this is rare; more commonly, neuropathy reflects a neurological extension of existing sarcoidosis.

• Some patients present with a diffuse sensorimotor neuropathy, whereas others present with distal to proximal slowly progressive weakness or distal numbness and dysesthesia. Occasionally they may present with multifocal neuropathies that mimic mononeuritis multiplex. Studies investigating the involvement of small diameter unmyelinated fibers have revealed a higher prevalence of small-fiber neuropathy than previously recognized.
• More focal findings present with symptoms referable to the nerve involved. Thus, in polyradiculopathy involving the cauda equina, patients may have progressive lower extremity weakness with or without sphincteric involvement.
• Mononeuropathies present with symptoms reflecting impairment of function in the particular nerve distribution.
• Numerous studies suggest that 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, where lower motor neuron neuropathy of the facial nerve (which is the nerve most frequently involved) may present along with other cranial neuropathies or as bilateral facial neuropathies.

Physical

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 severely affected than small-fiber functions (eg, pain, temperature). Recent findings suggest a higher prevalence of small-fiber neuropathy with pain as a symptom than hitherto recognized.
• Pure sensory neuropathy has been reported.
• 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 and presents as an asymmetrical weakness of the lower extremities, with loss of the deep tendon reflexes and patchy sensory loss, including the perianal region.

Causes

The causes of sarcoidosis are unknown.

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