Wegener's Granulomatosis involving the Central Nervous System
Wegener's granulomatosis is a systemic disease that is recognized as a necrotizing granulomatous vasculitis that predominately affects small to medium sized vessels. It is also associated with positive ANCA serology and anti-protease 3 antibodies. C- ANCA testing has a specificity of >95% and has varying sensitivities with the lowest being 33% in patients with inactive Wegener's and the highest being 90% in active generalized Wegener's (1). It was first described to involve the upper and lower respiratory tracts and the kidneys (3). It is now known to be a widely systemic process that could potentially involve any organ.
Wegner's commonly affects the nervous system in 22-54% of patients (3). This, however, largely represents cases that involve the peripheral nervous system. Central Nervous System involvement is rather uncommon and is seen in only 7-11% of patients (3). There are three recognized mechanisms of how Wegener's can involve the central nervous system.
The most common cause of neurological complications is a result of vasculitis while the least common is due to remote granulomatous formation (2). However, 30% of cases are actually due to a combination of the above mechanisms (3).
Diagnosing different Categories of Wegner's granulomatosis related CNS disease:
Diagnosing whether neurological symptoms are related to Wegner's is difficult as there are no specific diagnostic hallmarks. "Chronic hypertrophic pachymeningitis (CHP), pituitary gland involvement, and cerebral vasculitis" are the three major clinical patterns (3). Different diagnostic tests are useful in each pattern.
The pathophysiology of CHP is due to the thickening of the dura mater from inflammation. These patients usually present with severe analgesic-resistant headaches. They may also have cranial nerve palsies involving CN III, V, VI, VII, and VIII. Performing a lumbar puncture can help diagnosis this entity, as the fluid can reveal a "pleocytosis with lymphocyte predominance and/or high protein concentrations" (3). MRI, however, is the best diagnostic tool, as it will show thickening of the dura but this must be differentiated from other disorders that can cause a thickening of the dura such as sarcoidosis or tuberculosis (3).
Patients who have granulomatous inflammatory involvement of the pituitary gland usually present with diabetes insipidus which can be confirmed by a 24-hour water deprivation test. About 50% of these patients may also have hyperprolactinemia as a result of pressure on the pituitary stalk. MRI is again a useful diagnostic test in this pattern as it can show an "enlarged and gladolinium-enhanced pituitary gland" (3).
Vasculitic involvement is the toughest pattern to diagnose because it is often difficult to differentiate from atherosclerotic disease involving the vessels of the nervous system. MRI can identify vasculitis but these findings are often nonspecific and angiography cannot often identify disease affecting small vessels, making this test less useful. Most often the diagnosis of this pattern of CNS involvement is made when there is active disease outside of the nervous system and the patients clinically improve with immunosuppression (3).
Take Home Points
Although Wegener's granulomatosis most frequently involves the respiratory tract and kidneys, it can potentially involve any organ system even the central nervous system. Wegener's affects the nervous system by direct granulomatous extension, remote granulomatous formation, and vasculitis (2). A number of tests can aide in the diagnosis including a MRI, lumbar puncture, and angiography, but the clinical presence of extracranial involvement and response to steroids is often the best way to diagnosis Wegener's related CNS involvement.
Contributed by Kelly Garner, MD and Bruce Rabin, MD