CNS Lupus Clinical Presentation

Updated: Aug 22, 2017
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Niranjan N Singh, MD, DM  more...
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Presentation

History

Among the neurologic manifestations of systemic lupus erythematosus (SLE), the most common are the organic encephalopathies (35-75% of case series), which basically comprise all potential variations of acute confusion, lethargy, or coma; chronic dementias; depression, mania, or other affective disturbances; or psychosis.

Mental status changes

Acute or subacute mental status changes may be secondary to diffuse cerebritis but should be differentiated from focal cortical dysfunction resulting from thromboembolic cerebrovascular accident (CVA) or from diffuse changes resulting from electrolyte or metabolic derangements (accentuated by concomitant renal failure); medication effects including steroid psychosis (most problematic with high dosages and long durations); aseptic meningitis (seen especially with nonsteroidal anti-inflammatory drugs [NSAIDs]); or opportunistic infections that result in meningitis, encephalitis, brain abscess, or systemic infection with a secondary toxic encephalopathy.

Posterior reversible encephalopathy syndrome

Posterior reversible encephalopathy syndrome (PRES) has been described in SLE. Patients are generally on immunosuppressive drugs, have had episodes of relative hypertension, and have renal involvement. Magnetic resonance image (MRI) findings are characteristic, involving the occipital lobes in particular, which differentiates PRES from other central nervous system (CNS) complications of SLE. Clinical and radiographic resolution of abnormalities within 1-4 weeks is typically seen. In spite of this, patients with PRES might present with dramatic signs and symptoms. [13]

Seizures

Seizures are already known to occur in 14-25% of patients with lupus compared with 0.5-1% in the general population. [14] Seizures may result from cerebral vasculitis (ischemic or hemorrhagic manifestations), cardiac embolism, opportunistic infection, drug intoxication, or associated metabolic derangements. A seizure focus may result from an acute insult or from the development of a seizure focus in an area of previous brain insult. Partial or secondarily generalized seizures are most common, but all seizure types have been reported.

Electrolyte disturbance and medication effects should be excluded, especially those resulting from antidepressants, stimulant medications used to treat fatigue, or withdrawal from sedatives or alcohol. Opportunistic infections should be considered in patients receiving immunosuppressive therapy. Steroid therapy, especially high-dose pulse therapy, has been associated with status epilepticus.

Joseph et al identified that primary neurologic presentation of SLE was more common than anticipated (10/41 patients) and included both seizures (4 cases) and movement disorders such as parkinsonism and myoclonus (4 cases). [15] The investigators found a higher overall frequency of seizures (42%), as an early manifestation in 27% of patients, and, in 10%, seizures were the first SLE symptom. Previous to this, there had been no case reports of myoclonus in SLE as a presenting feature. [15]

Cranial nerve involvement

Cranial nerve involvement is also relatively uncommon and usually transient, [16] occurring in 10% of patients with SLE. Oculomotor nerve palsies and all other cranial neuropathies have been reported. Visual disturbances tend to be bilateral (80%) and to occur late in the disease course (77%); these include optic neuritis, retinopathy, and concurrent migrainous features. Anterior segment findings include keratoconjunctivitis sicca, keratitis, and scleritis. Retinopathy can be associated with cotton wool exudates (indicative of local retinal ischemia) and hemorrhages. [15, 17, 18]

Lee et al reported a case of SLE with recurrent laryngeal palsy resulting in vocal cord paresis. Laryngeal electromyography (LEMG) on both cricothyroid and thyroarytenoid muscles confirmed a left recurrent laryngeal neuropathy with ongoing processes of denervation and reinnervation. [19]

Stroke

Stroke is clinically evident in 5-10% of most series and may involve small, medium, or large vessels by a variety of mechanisms as discussed earlier. Subacute evolution or any premonitory symptoms suggest a thrombotic or vasculitic mechanism, whereas an abrupt onset with maximum deficit initially supports an embolic mechanism.

Vasculitis is often seen with SLE but is usually limited to small vessels alone. The primary pathology in SLE-related vasculitis is leukocytoclastic vasculitis. Medium- and large-vessel vasculitis in association with SLE is distinctly uncommon.

Ischemic stroke should be differentiated from brain hemorrhage, brain abscess, and other structural lesions. Parenchymal brain hemorrhage may result from bleeding into an ischemic vascular bed, particularly following cardiac emboli or dural sinus thrombosis.

Peripheral neuropathy

Peripheral neuropathy occurs in as many as 18% of patients with SLE. A sensory or sensorimotor predominantly distal polyneuropathy is most common; however, the patchy deficits and subacute time course of mononeuritis multiplex and the rapidly progressive course of acute demyelinating polyneuropathy have been reported. The neuromuscular junction may be affected, mimicking the weakness patterns (and physiology) of myasthenia gravis or myasthenic syndrome. Myositis is clinically apparent as proximal weakness and myalgias in 3-5% of patients but, if assiduously sought, may be found in as many as 50%.

Myopathy

Autoimmune-mediated myopathy must be differentiated from myopathy induced by steroid or antimalarial therapy as well as arthralgias and other musculoskeletal sequelae of SLE. Distinction from arthralgias and other musculoskeletal conditions is based on symmetrical, proximal muscle weakness (in excess of that weakness explained by painful give way), elevated creatine kinase, and absence of other musculoskeletal findings. Distinguishing SLE-induced myopathy from medication-induced myopathy is dependent on the time course of the weakness in relation to changes in medical therapy. In difficult cases, clinical response to increasing or decreasing the suspected medication may settle the issue.

Spinal cord involvement

Spinal cord involvement is rare but devastating. Transverse myelitis, subacute-to-chronic demyelinating syndromes, and abrupt vascular occlusive events (e.g., spinal artery thrombosis) have been described. Slowly progressive lesions may result from demyelination or compression by tumor or central disc herniation. Rapid onset suggests transverse myelitis, infarction, or compression by a rapidly expanding lesion (e.g., epidural abscess).

Fatigue

Chronic fatigue is a common symptom in SLE and usually does not relate to objective muscular effort (i.e., walking up stairs may seem no harder than walking on level ground). [20] Fatigue may contribute to both self-perceived and to measurable cognitive impairment, chiefly by impairing frontal lobe attentional functions. This may relate to metabolic dysfunction of brain parenchyma, as discussed in Organic Encephalopathies.

Depression, myopathy, excessive daytime fatigue due to nocturnal sleep disorder, and systemic conditions (e.g., electrolyte disturbance, fluid overload, pulmonary insufficiency) remain in the differential diagnosis. Many patients with mild orthostatic hypotension present with symptoms resembling chronic fatigue and may not complain of the usual presyncopal symptoms.

Other neurologic syndromes

Less common neurologic syndromes presenting in the patient known to have SLE include movement disorders (chorea, ataxia, parkinsonism), pseudotumor cerebri, and venous sinus thrombosis. Movement disorders were not included in the American College of Rheumatology (ACR) criteria. Chorea has been seen in fewer 4% of patients. [21]

Acute aseptic meningitis is rarely described in association with NSAID therapy, but this condition must be differentiated from infectious etiologies, especially in immunosuppressed patients.

Neurologic syndromes are often present at SLE presentation, and SLE should be considered in the following individuals:

  • Young patients with new-onset confusional or psychiatric states, stroke, or parkinsonism
  • Patients presenting with a multifocal process affecting the CNS, especially if both CNS (e.g., patients carrying the presumptive diagnosis of multiple sclerosis) and peripheral nervous systems (PNS) are affected
  • Patients with cranial neuropathies
  • Patients with noncompressive myelopathies
  • Patients with chorea, unexplained ataxia, myopathy, or polyneuropathy

Microembolic signals have been well recognized in SLE with CNS involvement. Azarpazhooh et al reported microembolic signals in patients with SLE at risk for neuropsychiatric syndromes. [22] Cerebral embolism is further speculated to be implicated in the pathophysiology of SLE with neuropsychiatric syndrome.

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Physical Examination

Abrupt or subacute onset of any focal neurologic deficit in systemic lupus erythematosus (SLE) may result from local vasculitis with thrombosis, distant artery-to-artery embolization, or cardiac emboli. Mass lesions (e.g., subdural or parenchymal hemorrhages) or brain abscess remain in the differential diagnosis.

Paraparesis implicates cauda equina, thoracic-lumbar spinal cord, partial lesions of the cervical cord, brainstem lesions, or parasagittal cerebral lesions. Extensor toe signs localize to the cord or above, excluding cauda equina. Acute lesions at either cauda or cord levels may be associated with hyporeflexia, areflexia, or sphincter disturbances. If an areflexic paraparesis is unaccompanied by a sensory level or spreads to the arms, acute demyelinating polyneuropathy (Guillain-Barré syndrome) should be considered. Sensory loss to pain and temperature with sparing of posterior column function (position sense, graphesthesia with or without vibration sense) suggests an anterior spinal artery syndrome.

Clinically involved cord levels require immediate imaging (ie, myelography or magnetic resonance imaging [MRI]) to exclude compressive lesions. If myelography is performed, spinal fluid should be collected for analysis before introducing contrast media.

Cranial neuropathies most commonly result from lupus vasculitis affecting the vasa nervorum supplying the involved nerve. Although optic neuritis (painful or painless subacute loss of visual acuity, usually accompanied by visible inflammation of the optic nerve head) and retrobulbar neuritis are most common, any cranial nerve may be affected. Imaging studies can exclude compressive lesions that result from opportunistic infection, tumor, or aneurysm.

Diffuse weakness may result from polyneuropathy, myopathy, neuromuscular junction disease, or systemic fatigue.

Examination findings of objective, symmetric proximal muscle weakness (with or without concomitant pain) support myopathy, whereas distal symmetric weakness (with distal sensory loss) implicates a peripheral polyneuropathy. Myopathy should never be accompanied by sensory loss, but it may at times be asymmetric.

Mononeuritis multiplex results in patchy, asymmetric weakness, sensory loss, or both in the distribution of multiple peripheral nerves or roots. Clinical distinction between proximal myopathy and polyradiculopathy or proximal mononeuritis multiplex may be difficult, requiring electromyogram (EMG) or nerve conduction velocity (NCV) studies or even nerve and muscle biopsies for an accurate diagnosis.

Weakness that improves or worsens with repetitive testing suggests a neuromuscular junction defect. Painful give way weakness without organic muscle weakness supports arthralgia or other musculoskeletal etiology.

Fatigue from autoimmune disorder is rarely accompanied by objective muscular weakness. Orthostatic hypotension should be excluded.

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