Primary Angiitis of the Central Nervous System (PACNS), commonly known as CNS vasculitis, is a rare autoimmune disease defined by inflammation of the blood vessel walls specifically within the brain and spinal cord. The condition is considered “primary” because the inflammation is confined to the central nervous system, with no evidence of a more widespread, systemic vasculitis affecting other parts of the body. This inflammation causes the walls of small and medium-sized arteries to swell, which narrows, obstructs, or weakens the vessels, restricting blood flow and potentially damaging brain or spinal cord tissue.
Presenting Symptoms Leading to Suspicion
The initial signs of CNS vasculitis are varied and not specific to the disease. A new, severe, or persistent headache is the most common symptom, often developing over weeks or months rather than appearing as a sudden “thunderclap” headache. The slow and often progressive nature of these diverse symptoms is a feature that can lead a physician to consider CNS vasculitis.
Many individuals also experience cognitive changes, such as memory difficulties, confusion, or shifts in personality. Focal neurological deficits, which are problems linked to specific brain areas, are also common. These can manifest as stroke-like events, muscle weakness, numbness or tingling sensations on one side of the body, vision loss, or issues with balance and coordination. Seizures may also occur as a primary symptom.
The Diagnostic Evaluation Process
The diagnostic process begins with blood work to check for general markers of inflammation, like an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). These tests help investigate if a systemic autoimmune disease or infection is causing the symptoms.
A lumbar puncture (spinal tap) is performed to collect a small sample of cerebrospinal fluid (CSF) from the lower back. This fluid is analyzed for signs of inflammation, such as an increased white blood cell count or elevated protein levels. However, a normal CSF result does not rule out CNS vasculitis.
Neuroimaging is a primary component of the evaluation. A Magnetic Resonance Imaging (MRI) scan of the brain is performed to look for signs like multiple small strokes, white matter changes, or a mass-like lesion. To visualize blood vessels directly, cerebral angiography is used. Catheter-based digital subtraction angiography (DSA) is the most accurate method, though less invasive CT or MR angiography are also options. These scans search for a pattern of alternating vessel narrowing and dilation.
If other tests are inconclusive, a brain biopsy is the definitive method for diagnosis. This surgical procedure involves removing a very small piece of brain tissue and the associated blood vessels from an affected area identified on imaging. A pathologist then examines this tissue under a microscope to look for direct evidence of inflammation within the vessel walls, confirming the diagnosis.
Challenges in Reaching a Diagnosis
Diagnosing CNS vasculitis is challenging due to its rarity, which can lead to delays in consideration. Its symptoms overlap with many more common neurological disorders.
Diagnostic tests have limitations, as neuroimaging and CSF analysis can be normal in some individuals or show non-specific abnormalities. Cerebral angiography can also be misleading, producing false-negative results if only the smallest vessels are affected or false-positive results from conditions that mimic vasculitis.
The brain biopsy also presents challenges. It is an invasive procedure with inherent risks, and because the inflammation can be patchy, a biopsy might be taken from an unaffected area. This “sampling error” can lead to a false-negative result, where the disease is present but the tissue sample does not show it.
Establishing a Differential Diagnosis
A primary part of the diagnosis involves ruling out other conditions that can mimic CNS vasculitis. One of the most important is Reversible Cerebral Vasoconstriction Syndrome (RCVS), which can have similar angiographic findings. RCVS is distinguished by a sudden “thunderclap” headache at onset and vessel narrowing that resolves on its own within about three months.
Physicians must also exclude a number of other conditions that can cause similar symptoms or imaging results. These include:
- Systemic autoimmune diseases like lupus (SLE), Sjögren’s syndrome, or Behçet’s disease, which are identified through antibody tests and disease activity outside the nervous system.
- Central nervous system infections from bacteria or fungi, which can also cause inflammation of cerebral blood vessels and are often ruled out through CSF analysis.
- Demyelinating diseases such as Multiple Sclerosis (MS), which can cause white matter lesions on an MRI that appear similar to those in vasculitis.
- Non-inflammatory vasculopathies like intracranial atherosclerosis or Moyamoya disease, which cause vessel narrowing and require specific imaging to differentiate.