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Sarcoidosis is a granulomatous disease with the potential to affect many different organ systems. Approximately 5% of patients with systemic sarcoidosis have neurological involvement.1 Peripheral neuropathy occurs in up to 20% of these patients and is usually asymptomatic. Neurophysiological findings are consistent with primary axonal polyneuropathy.1 We report an unusual case of neurosarcoidosis, presenting with multiple painful sensory mononeuropathies (MPSM) and progressing to a symmetric confluent sensory neuropathy.
A patient in her 4th decade of life presented with a history of multiple sensory deficits. She first developed acute onset pain and numbness of the right little finger, followed by a change in taste over the anterior two thirds of the tongue, without facial weakness. Two months later, the patient developed numbness in the palmar aspect of all fingers with dysesthesia, intermittent burning, and throbbing pain. Three months later, the pain spread to involve the dorsal aspect of the forearms. Seven months after the initial onset of symptoms, the patient developed a burning sensation in the distribution of the right sural nerve, and numbness in the right posterior leg and over the left side of the trunk. The patient denied muscle weakness, painful radicular symptoms, or systemic features.
Physical examination was remarkable for the absence of sweet taste sensation over the anterior tongue bilaterally. Sensory examination demonstrated reduced pinprick sensation in the fingers of both hands and in the right sural nerve distribution. Muscle strength was preserved throughout. Tendon reflexes were absent in the arms and ankles, and asymmetric at the knees. Gait, cognitive functions, and cranial nerve examination were unremarkable.
Laboratory investigations included a polyclonal increase in IgGM component, with a low concentration band in the slow γ region. Serum immunofixation confirmed the presence of IgG λ. Serum antineutrophil antibodies were positive, with a homogeneous pattern (1/640), and the serum angiotensin converting enzyme (ACE) concentration was raised (69 U/litre; normal range, 8–52). Other laboratory investigations were normal or absent, including serum chemistry, complete blood count, erythrocyte sedimentation rate, serum vitamin B12 concentration, antinuclear antibodies, anti-SSA/SSB antibodies, rheumatoid factor, cryoglobulins, serum complement, and serology testing for Epstein-Barr virus, herpes simplex virus types 1 and 2, and human immunodeficiency virus types 1 and 2. Cerebrospinal fluid (CSF) examination revealed an increased concentration of protein (980 mg/litre; normal range, 150–450), with oligoclonal bands. The CSF cell count, bacterial culture, Gram stain, Lyme antibody titre, and myelin basic protein were unremarkable. Nerve conduction studies (NCSs) revealed absent right sural, right superficial peroneal, and bilateral ulnar and median sensory nerve action potentials (SNAPs). The remainder of the motor and sensory NCSs and needle electromyography, in the upper and lower extremities, were unremarkable. Blink reflexes were normal. Median nerve somatosensory evoked potential study revealed absent Erb’s point potentials, bilaterally. Follow up NCSs, three months after the initial study, showed deterioration in the sensory NCSs, as demonstrated by the loss of left sural, left superficial peroneal, and both radial SNAPs. The sensory neuropathy had now become confluent and symmetrical. Motor NCSs remained normal. Non-contrast brain magnetic resonance imaging demonstrated three small subcortical white matter signal changes. Chest x ray was normal. A chest computerised tomography scan demonstrated scattered centrilobular nodules, with thickening of the interlobular septa, and no hilar lymphadenopathy, which was consistent with lung sarcoidosis. Pulmonary function tests were normal. Abdominal fat pad aspiration biopsy was negative for amyloid. A right sural nerve biopsy revealed non-caseating granulomas admixed with chronic inflammatory cells in the epineurium (fig 1A, B). Immunohistochemistry of the lymphoid infiltrate was not possible because of technical difficulties. Sural nerve teased fibre preparations revealed myelin ovoids in numerous fascicles. Vasculitis was not seen. Biopsy of the right gastrocnemius muscle was normal. The patient was treated with prednisone, starting at 60 mg/day. At last follow up, 12 months after treatment onset, the patient continued to experience pain, but had not developed new neurological deficits. The patient was eventually lost to follow up.
We report a case of sarcoid neuropathy presenting as MPSM and progressing to a symmetric confluent sensory polyneuropathy. This case was particularly challenging because the patient was not known to have sarcoidosis at presentation. The findings of a raised serum ACE concentration and lung computerised tomography imaging suggested a diagnosis of sarcoidosis. This was confirmed by demonstrating non-caseating granulomas in the epineurium of the right sural nerve. Although previous cases of pure sensory sarcoid neuropathy have been reported, they were distinct from our case in that the patients were already diagnosed with systemic sarcoidosis,2 or the symptom of pain was unreported.2 To our knowledge, our case is the first description of systemic sarcoidosis presenting as MPSM.
Sensorimotor and pure motor polyneuropathies have been reported in systemic sarcoidosis.1,2 The relative frequency of different subtypes of sarcoid neuropathies is uncertain. In a detailed clinical description of 10 cases, chronic sensorimotor peripheral neuropathy was the most common form of non-cranial neuropathy.1 Other patterns included small fibre neuropathy,3 acute ascending paralysis similar to Guillain-Barré syndrome,1 polyradiculopathy,4 and lumbosacral plexopathy.1
A potential mechanism of nerve damage in sarcoid neuropathy includes the local effects of tissue inflammation through release of noxious secretory products by activated inflammatory cells.5 Alternatively, ischaemia induced by necrotising vasculitis5 and direct mechanical compression of nerve fibres may lead to primary axonal degeneration,2 as supported by pathological findings of non-caseating granulomas in the epineurium and perineurium with periangiitis, panangiitis, perineuritis, and axonal loss.5 Furthermore, most neurophysiological findings were consistent with an axonal form of nerve injury.1,2 In our case, the neurophysiological and pathological findings were consistent with primary axonal degeneration. We hypothesise that peripheral nerve injury may have resulted from mechanical compression of nerve fibres, because there was no evidence of vasculitis in our case. Moreover, the effects of local tissue inflammation could not be ruled out in this case.
The authors acknowledge Dr T Hedley-Whyte for assistance with the figure.
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