Neurological Manifestations Of Sjögren's Syndrome
Steven Mandel, M.D.
Clinical Professor of Neurology
Jefferson Medical College
Reprinted with permission of the author, entire and unedited.
Neurological complications of Sjogren's Syndrome can be divided into neuromuscular manifestations occurring in 10-20% of patients; central nervous system complications in 25% of patients, and subclinical disease that may be present on laboratory or histological studies, the extent of which is undetermined and may not be predicted in any single individual.
The criteria for diagnosis of Sjogren's disease would be the following:
Primary Sjogren's symptoms and objective signs of ocular dryness with positive Schirmer's test and positive Rose-Bengal or fluorescein staining of cornea and conjunctiva.
Symptoms of objective signs of dry mouth with decreased parotid flow rate and abnormal biopsy of salivary gland and systemic autoimmune disorder, with elevated rheumatoid factor and presence of anti-SSA (Ro) or anti-SSB (La).
In secondary Sjogren's syndrome, one would have signs and symptoms of Sjogren's disease plus clinical features sufficient to allow a diagnosis of rheumatoid arthritis, systemic lupus erythematosus, polymyositis, or scleroderma. Exclusions would be sarcoidosis, pre- existing lymphoma, acquired immunodeficiency disease, and other known causes of keratitis sicca or salivary gland enlargement.
There are many causes of keratitis and salivary gland enlargement other than Sjogren's. For example, keratitis can be caused by herpes virus, trauma from contact lens, environmental irritants, ultraviolet lights, x- rays, neuropathies, or vitamin-A deficiency. Salivary gland enlargement can be caused by bacterial infections (including gonorrhea and syphilis), viral illnesses (such as infectious mononucleosis, TB, leprosy), excessive alcohol intake, and HIV.
There are many extraglandular manifestations in addition to neurological signs: gastrointestinal (dysphagia), respiratory (bronchitis), endocrine (thyroiditis), skin (vaginal dryness), hematological (anemia), and renal (vasculitis and glomerulonephritis).
Twenty-five per cent of patients with rheumatoid arthritis have Sjogren's syndrome; 50% of patients with Sjogren's have rheumatoid arthritis. There can be associations with thyroiditis and myasthenia gravis.
HIV infection can occur in combination with sicca syndrome which would be prominent in young males. In the HIV group there would be a lack of autoantibodies against SSA and SSB, and a positive test should be found for HIV.
Myopathy is defined as injury to muscle and myalgia as pain in muscle.
Individuals with muscle problems may have pain on palpation or spontaneous pain (myalgias). They may be unable to climb stairs or carry things (weakness). Individuals may or may not have symptoms. Individuals may have fever, fatigue, arthralgias, myalgias, or lymphadenopathy. Weakness is more prominent proximally than distally. The course is generally mild and insidious. Weakness can occur in those with renal involvement, renal tubular acidosis, and hypokalemia. Muscle biopsy may show myositis, but positive biopsy can be found in the absence of clinical symptoms in 17-74% of patients.
When Sjogren's syndrome is suspected in muscle, a sed rate and electromyography should be performed, and muscle and nerve biopsy should be considered. Muscle involvement has been reported to include myositis, muscle fiber necrosis, and elevated muscle enzymes.
Neuropathies are characterized by paresthesias, which can be numbness and tingling or painful dysesthesias such as burning. The neurological examination may be normal, despite clinical complaints because of involvement of small fibers. The lower extremities are more involved than the upper extremities.
Types of possible neuropathies include sensory neuropathy or dorsal root ganglioneuropathy. Individuals may present with ataxia, loss of vibration and position sense, or hyperalgesia (hypersensitivity to noxious stimuli). There also may be alterations in appreciation of pain and temperature with burning. Reflexes may be absent.
Motor involvement can occur along with sensory involvement. Weakness may be subacute and symmetrical. There also can be a rapidly progressive course of weakness to include a mononeuritis multiplex. Asymmetrical findings as well as stocking glove distribution of findings have also been reported.
Polyradiculoneuropathy may be present. This would be characterized by findings mimicking disc abnormalities with nerve root pain and weakness in a radicular distribution.
Trigeminal sensory neuropathy can occur and may be characterized by progressive sensory complaints on the face. They are generally spontaneous and nonlancinating. They could start on one side and subsequently become bilateral. They may be progressive over months to years. Motor involvement of the fifth nerve (affecting chewing and jaw movements) is uncommon. There can be tissue destruction around the nostrils because of picking and scratching, corneal ulcerations, lingual ulcerations, and alteration of taste and smell. The lesion would be at the trigeminal ganglion. Other cranial nerves could be involved such as the second nerve which would cause optic neuritis.
Multiple mononeuropathies such as carpal tunnel syndrome, ulnar neuropathy, or tarsal tunnel syndrome can occur. There can be autonomic neuropathy with anhydrosis (inability to sweat) and postural hypotension leading to light-headedness and dizziness with change of body position.
In general, individuals who develop sensory complaints do so before they develop the sicca syndrome. Individuals who develop a sensory or motor problem generally will have sicca symptoms preceding the sensory or motor disorder.
Motor neuron disease has recently been reported in a number of patients who turn out to have sicca syndrome.
Central nervous system involvement can include disorders involving the brain (focal and nonfocal) and the spinal cord.
Those focal deficit disorders in the brain can include motor and sensory loss with hemiparesis, aphasia, dysarthria, seizures, movement disorders, and cerebellar syndrome. Nonfocal diffuse disorders can be subacute or acute and can include encephalopathy, aseptic meningitis, cognitive function, dementia, or psychiatric abnormalities. Spinal cord disorders can include transverse myelitis, chronic progressive myelitis, Brown-Séquard syndrome, neurogenic bladder, and lower motor neuron disease.
Neurodiagnostic studies of the central nervous system in Sjogren's syndrome can include CAT scan, cerebral angiography, or magnetic resonance imaging. Electrophysiological studies can include electroencephalogram, evoked response testing, brainstem visual and somatosensory evoked potential studies, and cerebrospinal fluid analysis, including elevated IgG index, oligoclonal banding, and cytology showing reactive lymphoid cells.
In regards to immunopathogenesis of central nervous system disease in Sjogren's syndrome, those with serious focal symptoms are more likely to be SSA positive.
Neuropsychological abnormalities have included deficits of attention; concentration; verbal intelligence greater than nonverbal intelligence, signifying a subcortical dementia; or dysnomia. Alzheimer's multi-infarct dementia must be excluded.
Affective disorders include hysteria, hypochondriasis, somatization, depression, dysphoria, anxiety, and panic disorders.
MRI abnormalities have been reported to be both
focal and nonfocal, but may also be absent in a number of
individuals. It appears that focal deficits are seen on MRI
more prominently in patients younger than 35.
The pathology of findings in the central nervous system in primary Sjogren's syndrome include lymph mononuclear lymphocytic infiltration in the meninges and parenchyma, microinfarcts and microhemorrhages in the parenchyma, and the presence of vasculopathy. In the peripheral nerves, there can be involvement of mononuclear lymphocytic infiltration in dorsal root ganglia, nerve and muscle, as well as an inflammatory vascular response also affecting dorsal root ganglia, nerve and muscle.
Sjogren's syndrome has been confused with multiple sclerosis, especially because of the similar features that could include focal and diffuse deficits of brain and spinal cord. There can be peripheral nervous system disease, and this would be rare in multiple sclerosis.
Systemic lupus erythematosus and central nervous system involvement have shared many characteristics similar to patients with central nervous system Sjogren's disease. This would include multifocal neurological manifestations. Focal deficits appear to be more common in Sjogren's, but seizures more common in lupus. Concentration and cognitive disorders are common to both. In addition, the presence of vasculopathy and microinfarcts in both brain and spinal cord may be difficult to distinguish between Sjogren's and systemic lupus erythematosus.
Other central nervous system disorders that can be present in patients with Sjogren's that may mimic other neurological disease include multiple sclerosis, Parkinson's disease, Guillain Barré syndrome, or Alzheimer's multi-infarct dementia.
Therapy is directed towards the vasculopathy associated with the neurological manifestations. These can include corticosteroids, azathioprine, cyclophosphamide, and IVIG.
The true incidence and prevalence or neurological manifestations vary in various series reported in the literature. The neurological manifestations must be recognized early and aggressively treated so as to avoid long-term complications that would reduce the probability of success with treatment.
Steven Mandel, M.D.
Clinical Professor of Neurology
Jefferson Medical College
We extend our heartfelt gratitude to Dr. Stephen Mandel, MD for his contribution to Sjogren's World.