WASHINGTON — Vague presenting symptoms in combination with lack of accurate tests hamper the diagnosis of central nervous system vasculitis, while likely contributing to its overdiagnosis, according to Dr. David B. Hellmann, chairman of the department of medicine and the vice dean at the Johns Hopkins Bayview Medical Center in Baltimore.
Speaking at the annual meeting of the American Neurological Association, Dr. Hellmann discussed a few common myths about CNS vasculitis—also known as primary angiitis of the central nervous system (PACNS)—and offered clinical pearls.
Myths
▸ CNS vasculitis is common. In fact, CNS vasculitis accounts for only 1% all biopsy-proven cases of vasculitis. “CNS vasculitis is one of the greatest diagnostic challenges that any of us can face,” said Dr. Hellmann, who is also the executive director of the Johns Hopkins Vasculitis Center. Most of the common presenting features of CNS vasculitis are shared by a variety of other conditions. While there is a cluster of symptoms that is highly suggestive of this disease, a full range of CNS abnormalities is possible. No imaging tests are specific and even brain biopsy can be falsely negative.
▸ Angiograms are sensitive and specific. The sensitivity of magnetic resonance (MR) angiography ranges from 40% to 80%, and the specificity is quite low at around 25%. The main abnormality apparent on MR angiography is a beading pattern of alternating constriction and dilatation. Posterior circulation is less likely to be affected.
▸ Stroke presentation is common. While focal abnormalities are seen in about 50% of CNS vasculitis cases, very rarely do they present as stroke. “Focal [cerebral] abnormalities are pretty common by the time that you make the diagnosis but in retrospect, very few patients describe a strokelike presentation,” said Dr. Hellmann.
▸ Systemic signs are common. “Systemic symptoms are overrated. One of the myths of CNS vasculitis is that people have fevers and many other symptoms. They may, but it's actually the minority of patients who have systemic signs,” said Dr. Hellmann.
Pearls
▸ Definitive diagnosis takes biopsy. The criterion for making a possible diagnosis of CNS vasculitis is a newly acquired neurologic deficit, exclusive of other causes. A positive biopsy allows for definitive diagnosis. The diagnosis of possible CNS vasculitis is made when there is no biopsy but the clinical picture and imaging, along with the exclusion of other causes, is suggestive.
Brain biopsy is falsely negative about 25%-40% of the time. “More atrophy is biopsied in the nondominant temporal lobe,” said Dr. Hellmann.
Biopsy specimens should be taken from of the leptomeninges or parenchyma to produce a greater yield. Studies suggest that biopsy is positive in 9%-36% of suspected cases. “It seems to be worth doing, as another diagnosis is often found,” said Dr. Hellmann. However in 25%-35% of patients, biopsy produces no diagnosis.
▸ Prescribe no cyclophosphamide without a definitive diagnosis. “In the absence of biopsy-proven case, I get nervous about using cyclophosphamide,” said Dr. Hellmann. “For someone who has biopsy-proven disease, I think that … most rheumatologists would use prednisone and cyclophosphamide,” said Dr. Hellmann. For a patient who is rapidly deteriorating, 1 g/day Solu-Medrol (methylprednisolone sodium succinate) should be given intravenously for the first few days, followed by 60 mg/day for a month, then taper the dose over the next 2–6 months. Oral cyclophosphamide can be used for 3–12 months.
▸ The most common presentation is insidious cognitive decline with headache. Studies have shown that the two most common presenting symptoms are diffuse cortical dysfunction (in an estimated 95% of cases) and headache (seen in roughly 70% of cases). Associated headaches are marked by an insidious rather than thunderclap onset. Seizures are also common.
▸ Lumbar puncture and MRI are sensitive but not specific. In terms of diagnostic testing, lumbar puncture and MRI are very sensitive but sensitivity is very low. In fact, patients with CNS vasculitis may have perfectly normal-appearing MRIs. Cerebral spinal fluid (CSF) findings are abnormal in 85%-90% of cases. This includes modestly elevated protein levels and modest mononuclear pleocytosis.
In terms of imaging, MRI is much more sensitive than CT. However, there is no specific pattern to look for on MRI.
Speed of Onset Key to Differential
The differential diagnosis of CNS vasculitis or PACNS includes rheumatic diseases, infections, drugs, and vasculopathies, said Dr. Hellmann. In particular, consider reversible cerebral vasoconstriction (RCVS), lupus, HIV, histoplasmosis, tuberculosis, intravascular lymphoma, and cerebral amyloid angiopathy (distinguished by an average age of onset that is 30 years greater than for PACNS).