Drug-Induced Neurologic Manifestations of RA
Medications used for the treatment of RA are another cause of neurologic symptoms. Glucocorticoids can cause myopathy, psychosis, and benign intracranial hypertension.  Methotrexate can cause headaches and impair concentration; leflunomide has been associated with peripheral neuropathy; and gold salt therapy has been implicated in the development of peripheral neuropathy, cranial nerve palsies, and Guillain-Barré syndrome.  Taking a full drug history remains an essential component of the diagnosis and management of neurologic symptoms associated with RA.
CNS Cervical Subluxation
Cervical joint destruction in patients with RA may lead to vertebral subluxation, which can cause neurologic deficits from spinal cord injury.  A possible mechanism for cervical subluxation includes intervertebral joint destruction resulting in chronic cervical instability.
Neuromuscular disorders include myopathy and myositis. Muscle weakness with or without atrophy has been observed in patients with RA. In a study of myopathy in juvenile idiopathic arthritis, muscle fibers from leg biopsies contained inflammatory cells and expressed the major histocompatibility complex (MHC) class II, which researchers conclude is evidence of inflammatory myopathy.  Myopathy can also be seen in the context of glucocorticoid treatment.
CNS Progressive Multifocal Leukoencephalopathy
PML, which is associated with the polyoma JC virus, has been diagnosed in patients treated with rituximab for RA.  However, to date no direct causal relationship has been shown to exist between RA and PML. 
PNS Other Neuropathies
Neuropathic abnormalities are detected more frequently by nerve conduction studies (NCS) and electromyography (EMG) in patients with RA vs controls. 
Disorders of the central nervous system (CNS) associated with RA include CNS vasculitis, meningitis, CNS rheumatoid nodules, progressive multifocal leukoencephalopathy (PML), and cervical subluxation causing spinal cord injury.  CNS vasculitis is a rare extra-articular manifestation of RA; however, case reports detailing the high morbidity associated with intracerebral arteritis have been published in the literature.  Presenting symptoms can include headaches, seizures, stroke, encephalopathy, relapsing focal neurologic deficits, and other neuropsychiatric symptoms.  The diagnosis of CNS vasculitis is complex, requiring magnetic resonance imaging (MRI) coupled with magnetic resonance angiography (MRA) to examine specific vascular territories associated with segmental vascular stenosis. 
Rheumatoid meningitis is a rare extra-articular manifestation of RA consisting of an inflammatory infiltration of the meninges, usually diagnosed by spinal tap. Most patients later diagnosed with CNS meningitis tended to have long-standing, seropositive RA; a majority of these patients present with altered mental status. 
CNS Rheumatoid Nodules
Rheumatoid nodules have been reported rarely in the CNS, where nodular presence in the dura mater or choroid plexus can cause neurologic dysfunction.  Nerve root compression can also result from extradural nodules located in the spinal canal. Patients presenting with CNS nodules are more likely to have severe erosive joint disease and high titers of rheumatoid factor. 
PNS Compression Neuropathies
Sensory and motor dysfunction can occur secondary to compressive neuropathies. Carpal tunnel syndrome (CTS) is a common neurologic extra-articular manifestation of RA. Presenting symptoms, findings on physical examination, and diagnostic testing for CTS in RA are similar to assessment for suspected CTS in patients without RA.  Nonsurgical management involves treatment of the underlying disease process. Symptomatic treatments include splints, anti-inflammatory medications, and local corticosteroid injections. 
PNS Noncompressive Neuropathies
Noncompressive neuropathies associated with extra-articular RA include mononeuritis multiplex and distal symmetry neuropathy. Necrotizing vasculitis has been implicated in the pathogenesis of the ensuing axonal degeneration.  The presence of noncompressive neuropathies increases the morbidity associated with RA. 
Rheumatoid arthritis (RA) is an inflammatory disease that may be associated with extra-articular manifestations. Although these manifestations may reflect a more active disease course, no direct correlation between the extent of joint involvement and severity of extra-articular disease has been proven.  Reported incidence rates for severe extra-articular manifestations of RA have varied widely, partly due to a lack of clinical consensus despite previous efforts to define them.  However, the incidence rate of certain extra-articular manifestations of RA, such as vasculitis, appears to be declining. 
Early diagnosis and aggressive treatment of RA has been postulated to reduce the risk of developing severe extra-articular manifestations. Independent risk factors for extra-articular manifestations of RA have since been identified, including smoking and history of early disease disability.  Individual extra-articular manifestations of RA may have distinct disease mechanisms.  Conclusive data on the effects of specific treatment regimens on their prevalence and severity are pending and currently under investigation.