Primary Angiitis of the Central Nervous System

Introduction:

Primary central nervous system (PACNS) angiitis emerges as a complex neurological disorder characterized by inflammatory processes targeting the blood vessels surrounding the brain and spinal cord. Clinical presentation commonly includes seizures (when the brain experiences chaotic electrical activity, leading to shifts in behavior, movement, or levels of consciousness), headaches, encephalopathy (brain dysfunction), and stroke (the interruption of blood flow to a specific region of the brain), necessitating a comprehensive diagnostic approach. The diagnostic process includes the evaluation of symptoms, brain biopsy, imaging studies, and analysis of cerebral spinal fluid (CSF) values. However, due to the scarcity of cases, navigating the diagnosis and subsequent management poses persistent challenges.

What Is Primary Angiitis of the Central Nervous System?

Primary angiitis of the central nervous system, known as isolated angiitis of the CNS or isolated vasculitis of the central nervous system, is a debilitating condition that targets the blood vessels within the spinal cord and brain. This inflammation arises from the infiltration of immune cells into the vessel walls, triggering their deterioration and resulting in thickening, and obstruction of blood flow. Moreover, these inflammatory processes heighten the risk of blood vessel rupture, leading to potentially life-threatening intracranial hemorrhage.

What Are the Symptoms of Primary Angiitis of the Central Nervous System?

The onset of PACNS unfolds gradually for most, characterized by a slow progression, yet for some individuals, it may manifest suddenly, defying expectations. Symptoms of PACNS lack specificity and exhibit remarkable variability, making diagnosis challenging. The array of major symptoms encompasses:

1. Headaches.

2. Visual alterations.

3. Behavioral shifts.

4. Altered cognition (fluctuations in consciousness, memory, perception, and awareness).

5. Seizures.

6. Encephalopathy (cluster of brain disorders marked by a deterioration in cognitive function).

7. Stroke (interruption in cerebral blood supply).

8. Focal neurologic deficits, pinpointing anomalies in brain or spinal cord function at discrete locations.

9. Transient ischemic attacks (brief episodes of stroke-like symptoms lasting mere minutes).

10. Myelopathy (dysfunction within the spinal cord).

11. Ataxia (impaired coordination).

12. Cranial neuropathies (damage to the cranial nerves governing sensory and motor functions of the head and neck).

13. Radiculopathy (compression or irritation of spinal nerve roots).

How to Diagnose Primary Angiitis of the Central Nervous System?

The comprehensive evaluation of PACNS encompasses an array of factors, including the patient's medical background, clinical manifestations, laboratory analyses, and imaging assessments.

1. Imaging Findings:

• Cerebral Angiography: The cornerstone in PACNS diagnosis lies in conventional cerebral angiography, an X-ray technique specifically targeting blood vessels. This method illuminates regions of vessel constriction, dilation, or multi-site obstruction. Additional observations may reveal arterial widening, emergence of collateral vessels to offset blockages, and a delayed contrast dye presence. Frequently, the affliction predominantly impacts larger or proximal vessels.

• Magnetic Resonance Angiography: To ensure adequate visualization, a blend of magnetic resonance angiography (MRA) and traditional angiography is employed for assessment. However, when inflammatory alterations affect arteries with diameters less than 500 µm (micrometer), necessitating precise scrutiny, a brain biopsy becomes imperative.

• Magnetic Resonance Imaging: Introducing another modality, MRI (magnetic resonance imaging) reveals abnormalities in 90 percent of patients, often indicating diminished cerebral blood flow alongside concurrent constriction and dilation of various large and small vessels bilaterally within the brain. Instances of bleeding can accompany such presentations, while additional findings may include the presence of mass lesions. Furthermore, utilizing high-resolution contrast-enhanced MRI (HR-MRI) can prove valuable in discerning pathological changes within intracranial vessels.

2. Biopsy: Given the scattered nature of the disease, diagnostic sensitivity typically falls within the range of 53 to 74 percent. However, using imaging technology can significantly enhance sensitivity. Findings often encompass transmural inflammation, indicating inflammation across all layers of blood vessels, alongside evident vessel wall damage. Additionally, granulomatous inflammation, characterized by immune cells within blood vessels, lymphocytic cellular infiltrates, and acute necrotizing vasculitis, which results in blood vessel damage leading to its demise, is commonly observed. Moreover, neointimal proliferation, indicative of cell growth within blood vessels, and thromboses, forming blood clots within vessels, contribute to the diagnostic profile.

3. CSF Findings: These scans depict inflammatory alterations, accompanied by a mild increase in lymphocytic pleocytosis (elevated lymphocyte count) and heightened protein levels.

4. Laboratory Findings: Elevated erythrocyte sedimentation rate and serum C-reactive protein levels are commonly observed, although they may remain unaltered in certain instances.

How to Manage Primary Angiitis of the Central Nervous System?

The management of PACNS includes:

1. Induction Therapy: This involves employing corticosteroids like oral Prednisone in conjunction with Cyclophosphamide, which, when used together, can lead to fewer relapses. Before initiating treatment, it is crucial to address any existing infectious diseases.

• Corticosteroids: This involves high-dose intravenous corticosteroids administered at 1000 mg per day for three to five days or oral Prednisone at 1 mg per kilogram of body weight per day. Simultaneously, managing gastritis or ulcers and preventing blood clots is crucial in the treatment strategy.

• Cyclophosphamide: This medication is commonly administered in two forms:

1. As an oral pill, prescribed at a dosage of 2 milligrams per kilogram of body weight per day for three to six months.

2. An intravenous infusion is typically dosed at 750 milligrams per square meter of body surface area per month over six months.

Potential side effects encompass infections, infertility, and an increased risk of cancer. Notably, pregnant patients should refrain from its use due to associated risks. When patients exhibit intolerance to immunosuppressive therapies, tumor necrosis factor-α blockers like Infliximab and Etanercept, or Rituximab, which are biological agents, are considered.

2. Maintenance Therapy: Maintenance therapies play a crucial role in reducing relapses and preventing long-term disabilities, typically initiated four to six months following the start of induction therapy. Immunomodulating agents like Azathioprine (at a daily dosage of 1 to 2 mg per kg), Methotrexate (given weekly at 20 to 25 mg), and Mycophenolate mofetil (administered daily at 1 to 2 grams) are commonly employed. Azathioprine's potential side effects can be managed with oral Prednisolone.

Additionally, calcium and vitamin D supplementation is recommended for osteoporosis (a bone disorder in which its density is reduced) prevention. At the same time, prophylactic measures against pneumocystis infection (a fungal infection) and gastric ulcers should be considered. Supportive therapies involving antipsychotics and anticonvulsants may also be necessary.

Conclusion:

PACNS, while uncommon, leaves a significant impact as it affects both the spinal cord and brain. Despite its rarity, understanding the immunopathogenesis driving it and developing effective treatments remain formidable challenges. The elusive nature of diagnosis stems from the lack of specificity in symptoms, laboratory tests, and imaging results for PACNS. Consequently, the pursuit of optimal treatment strategies and long-lasting management approaches continues to be impeded by the limited grasp of PACNS pathogenesis and the absence of comprehensive randomized controlled trials.