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Hilar adenopathy is often but not always appreciated on chest radiographs MRI scans may demonstrate enhancement of the meninges in the brain, particularly in the posterior fossa, and of affected spinal roots in patients with radiculopathy (Fig 14 3) Angiotensin converting enzyme (ACE) levels may be elevated in those with lung disease but it is not a very sensitive test In patients with subclinical neuropathy, the most common nding is an absence or reduction in SNAP amplitudes in a mononeuropathy multiplex pattern52,57 In patients with the symmetric sensorimotor peripheral neuropathy, the SNAPs may be absent or reduced in amplitude52,58 Motor NCS also reveal reduced or absent compound muscle action potential (CMAP) amplitudes in the lower limbs, with decreased or borderline normal CMAPs in the upper limbs Patients may also show EMG changes suggestive of a
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MIXED CONNECTIVE TISSUE DISEASE
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Mixed connective tissue disease represents an overlap syndrome of SLE, scleroderma, and myositis A mild distal axonal sensorimotor polyneuropathy reportedly occurs in approximately 10% of patients12,48
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NEUROPATHIES ASSOCIATED WITH SYSTEMIC DISEASE
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Figure 14 3 Sarcoidosis MRI scan of the brain with contrast demonstrates enhancement of the meninges around the cerebellum (A) and of the cauda equina (B) in a patient who presented with multiple cranial neuropathies and a polyradiculopathy
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radiculopathy or polyradiculopathy50 Quantitative sensory testing often reveals abnormal thermal thresholds, and autonomic testing may be abnormal as well indicative of small ber involvement56
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Treatment
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Neurosarcoidosis, particularly of the cranial nerves, may respond well to corticosteroid treatment50 If patients are resistant to corticosteroids, other immunosuppressive agents can be tried (eg, cyclosporine, methotrexate, and IVIG)59 Unfortunately, following cessation of treatment, the patients appear to return to a
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Histopathology
Nerve biopsies can reveal noncaseating granulomas in ltrating the endoneurium, perineurium, and epineurium along with lymphocytic necrotizing angiitis (Fig 14 4)52 There is a combination of axonal loss as well as demyelination Muscle biopsies likewise can demonstrate noncaseating granulomas in the endomysium even in patients without an underlying myopathy52 Skin biopsies may reveal reduced intraepidermal nerve ber suggestive of a small ber in some patients55
Pathogenesis
Sarcoidosis is an autoimmune disorder, although the etiology and pathogenic mechanism of the disorder is unclear Peripheral neuropathy may result from direct compression, ischemia, a combination of these two insults, or other ill-de ned factors The cranial nerves and mononeuropathies of the peripheral nervous system are likely to result from direct neural invasion and compression The AIDP- and CIDP-like neuropathies may be the result of diffuse in ltration of nerve and nerve roots or the result of poorly de ned immunologic compromise related to the sarcoidosis itself
Figure 14 4 Sarcoidosis Super cial peroneal nerve biopsies reveal a noncaseating granuloma in the epineurium and perivascular in ammation Paraf n section stained with H&E
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SECTION II
SPECIFIC DISORDERS
propensity for developing compromise of their nervous system
tracts, cortical atrophy and loss of neurons in the thalamus, basal ganglia, and brainstem64
Pathogenesis CELIAC DISEASE (GLUTEN-INDUCED ENTEROPATHY OR NONTROPICAL SPRUE) Clinical Features
Intolerance to gluten, which is a protein found in wheat and wheat products, results in a malabsorption syndrome (weight loss, abdominal distention, and steatorrhea) Diagnosis of celiac disease is based on the documentation of (1) malabsorption, (2) demonstration of blunting and attening of jejunal villi, and (3) clinical and histologic improvement following the institution of a gluten-free diet60 Neurologic complications are estimated to occur in 10% of patients who are affected, with ataxia and peripheral neuropathy being the most common problems61,62 The neuropathy associated with celiac disease usually manifests as distal sensory loss, paresthesias, and imbalance60,61,63 68 Generalized sensorimotor polyneuropathy, motor neuropathy, multiple mononeuropathies, autonomic neuropathy, and neuromyotonia also have all been reported in association with celiac disease or antigliadin/antiendomysial antibodies Neurological examination often demonstrates loss of large ber sensory modalities, mild distal muscle weakness, reduced or absent muscle stretch re exes, and an ataxic gait Signs of a small ber neuropathy or autonomic neuropathy may be evident67,68 The neuropathy may be secondary to malabsorption of vitamins B12 and E However, some patients have no appreciable vitamin de ciencies The pathogenic basis for the neuropathy in these patients is unclear but may be autoimmune in etiology61,69
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