A 64-year-old man with a history of bipolar disorder presented to the hospital with six weeks of visual hallucinations, cognitive changes, and what he described as a “dull” bi-frontal headache. Per his family, these behavioral changes were different from his bipolar disorder. Physical examination was normal except for agitation and visual hallucinations. Vital signs were stable. Laboratory work showed normal complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone level, rapid plasma reagin results, and vitamin B12 levels. A CT of the head showed a small subarachnoid hemorrhage in the left frontal lobe. Lumbar puncture yielded normal cerebrospinal fluid studies. An MRI of the head with contrast showed acute hemorrhagic infarcts in the bilateral parietal lobes (Figure 1), multiple punctate acute cortical infarcts, and chronic cortical and lacunar infarcts. Transthoracic echocardiogram was normal. Routine electroencephalography showed no epileptiform activity.
A detailed rheumatologic history and physical examination did not suggest connective tissue disorder or systemic vasculitis. Autoimmune work-up (anti-nuclear antibody, anti-double stranded DNA, anti-SSA, anti-SSB, anti-neutrophilic cytoplasmic antibodies, C3, C4, cryoglobulins, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein) was not revealing. A cerebral angiogram demonstrated scattered focal areas of irregularity and narrowing in both intracranial internal carotid arteries and posterior circulations (Figure 2). Biopsy of the parietal dura and cortex was performed and revealed lymphocytic vasculitis. He was started on oral prednisone and cyclophosphamide. At two-week follow-up, he noted significant improvement in his symptoms.
The patient's diagnosis is primary angiitis of the central nervous system (PACNS). PACNS is a rare form of vasculitis, restricted to the blood vessels of the brain, spinal cord, and leptomeninges. It has an annual incidence of 2.4 cases per 1 million person-years, with median age of onset at approximately 50 years. The exact cause of PACNS is unknown. Histologically, three patterns of vasculitis are described: granulomatous (58%), lymphocytic (28%), and necrotizing (14%).
The most common symptoms associated with PACNS are headache and confusion, typically insidious in nature. Other potential clinical features include focal neurological deficits, seizures, cranial neuropathies, and radiculopathy. Constitutional symptoms are not typical, and if present warrant a search for other causes. No specific lab or radiological test is diagnostic of PACNS. An MRI of the brain is abnormal in 90% to 100% cases and commonly shows multi-territorial infarcts, hemorrhages, and/or leptomeningeal enhancement. Angiography has a low diagnostic yield, and when abnormal shows scattered areas of stenosis. Brain biopsy is often considered in spite of its poor sensitivity (50%) due to the need to rule out common masqueraders, including infection, malignancy, or degenerative disease. Diagnostic criteria for PACNS include 1) unexplained neurologic deficit after thorough evaluation; 2) angiographic or biopsy-proven central nervous system vasculitis; and 3) exclusion of mimicking conditions. Immunosuppression with high-dose glucocorticoids alone or in combination with cyclophosphamide is the mainstay of therapy.
- PACNS is a rare but increasingly recognized entity with nonspecific clinical, laboratory, and radiological features.
- PACNS is a diagnosis of exclusion with additional information typically obtained from imaging or biopsy; immunosuppressants are the mainstay of therapy.