What is Primary Central Nervous System Vasculitis?
Primary angiitis of the central nervous system (PACNS) is a rare condition that causes inflammation in the blood vessels of the brain and spinal cord. What’s unique about this disease is that it doesn’t show any signs of affecting other blood vessels in the body. This condition was first identified as distinct in 1959, and since then, we’ve learned that it can manifest itself in many different ways.
When diagnosing PACNS, things can be a little vague because the symptoms are fairly common and can resemble those of other conditions. For instance, the most common symptom is a headache – something many of us experience from time to time. However, other more specific symptoms can include one-sided weakness (hemiparesis), difficulty speaking (aphasia), numbness, vision problems, lack of coordination (ataxia), and others.
What Causes Primary Central Nervous System Vasculitis?
We’re not entirely sure what causes PACNS (a disease where blood vessels in the brain swell), but one possibility is infection from the varicella zoster virus (VZV), which causes chickenpox and shingles. Some other causes could be:
* Bacteria including Mycoplasma, Rickettsia, and Treponema
* Viral infections like HIV or Hepatitis C
* Conditions that alter the body’s immune systems like systemic lupus erythematosus (SLE; an immune system disorder that causes joint pain and swelling), Churg-Strauss syndrome (a condition that causes inflammation in blood vessels), Behcet syndrome (a rare disorder that causes blood vessel inflammation), and Sjogren syndrome (a disorder of the immune system characterized by dry eyes and mouth), among others.
Some research also shows a connection between PACNS and cerebral amyloid angiopathy, a condition where a protein called amyloid builds up in the walls of the arteries in the brain. In animal studies, the buildup of amyloid protein is thought to possibly trigger PACNS.
Risk Factors and Frequency for Primary Central Nervous System Vasculitis
This uncommon health issue hasn’t had many studies tracking exactly how common it is. However, the data available suggests that each year, there are about 2.4 cases for every million people. It affects males and females equally and is typically diagnosed when a person is around 50 years old.
Signs and Symptoms of Primary Central Nervous System Vasculitis
PACNS is a condition that typically begins gradually and worsens over time. However, it can occasionally start suddenly. The symptoms vary from person to person and usually several occur at the same time. They can include common symptoms like headaches, cognitive problems, and strokes as well as less common signs like visual issues, seizures, trouble speaking, and memory loss.
It’s important to note that PACNS should always be considered a potential cause in cases where there’s a rapid decline in cognitive abilities or personality changes that can’t be otherwise explained.
- Headache
- Cognitive dysfunction
- Stroke
- Transient ischemic attack (TIA)
- Difficulty speaking (Aphasia)
- Visual symptoms, including trouble seeing, blurred vision, & double vision
- Seizures
- Ataxia (lack of muscle control)
- Papilledema (swelling of the optic nerve)
- Intracranial bleeding (bleeding inside the skull)
- Amnestic syndrome (memory loss)
Testing for Primary Central Nervous System Vasculitis
Diagnosing Primary Angiitis of Central Nervous System (PACNS) can be tricky, mainly because we do not have a clear biological indicator or ‘biomarker’ and this condition often shows a range of non-specific signs. Blood tests such as the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and anti-neutrophil cytoplasm antibody (ANCA) are not particularly helpful in diagnosing PACNS as they don’t consistently or specifically point to the condition.
However, the examination of cerebrospinal fluid (CSF) – the fluid that surrounds the brain and spinal cord – is helpful in most cases. This is because over 90% of PACNS patients show a slight increase in white blood cells or total protein, or both, in their CSF. Radiographic imaging, like MRI, is also highly beneficial; over 90% of PACNS cases show abnormal MRI results, with ischemia (restricted blood supply) being the most commonly observed problem.
For an official PACNS diagnosis, doctors use set criteria formulated by the researchers Calabrese and Mallek. A patient will be diagnosed with PACNS if they show an unexplained neurological deficit (after exploring other possible causes), display signs of inflammation within the central nervous system (confirmed by either angiography – a medical imaging technique to visualize blood vessels, or histopathological examination – a microscopic examination of tissue), and show no signs of vasculitis (inflammation of blood vessels) elsewhere in the body or any other condition that could explain the observed features.
Therefore, the main tools for diagnosing PACNS are angiography and a biopsy of the central nervous system. Angiography can show unusual features like alternating narrow and normal or wide sections in vessels, and blocked arteries. Magnetic Resonance Angiography (MRA) could be used as an alternative to conventional angiography, although conventional angiography is more sensitive in picking up the changes. Biopsy could also be used for diagnosing PACNS, but its sensitivity is lower compared to angiography, meaning there might be less chance of picking up the condition. However, its specificity is higher, meaning if it does pick up the condition, it is very likely to be accurate.
Finally, an approach combining clinical, laboratory, and imaging findings with angiography, and if needed, a biopsy, is the most sensible strategy for diagnosing PACNS.
Treatment Options for Primary Central Nervous System Vasculitis
Primary CNS vasculitis is a disease that affects the blood vessels in the brain. Treatment strategies for this disease are mainly based on case studies, where doctors observe how individual patients respond to different treatments. In many cases, relief from symptoms and disease control can be achieved through the use of drugs called glucocorticoids, either on their own or combined with another drug called cyclophosphamide. These treatments have been found to be successful in approximately 80% of cases.
Where these drugs don’t effectively control the disease, the tumor necrosis factor-alpha blockers (like infliximab or etanercept) and mycophenolate mofetil can be used. These drugs are meant to be used in addition with the standard therapy, not as replacements.
In addition to the direct treatment of the disease, preventative treatment against disease complications like Pneumocystis jirovecii, a type of pneumonia, and osteoporosis, is recommended for all patients undergoing standard therapy.
To monitor how well the treatment is working, regular brain scans (MRI and MRA) are usually ordered every 4 to 6 weeks after starting treatment, and then every 3 to 4 months during the first year. Regular neurological exams, where the doctor assesses the patient’s nervous system function, are also required.
What else can Primary Central Nervous System Vasculitis be?
When doctors are trying to diagnose a condition called PACNS, there are a group of other conditions there they must first rule out because they have similar symptoms. These conditions are divided into two main groups.
The first group, referred to as reversible cerebral vasoconstriction syndromes (RCVS), include conditions like Call-Fleming syndrome, migrainous vasospasm, and post-partum angiopathy. These conditions are similar to primary CNS angiitis. They generally begin suddenly and tests of the fluid that surrounds the brain and spinal cord (CSF) are usually normal. Additional tests, like angiography, can show abnormal results but a biopsy doesn’t show any signs of inflammation in the blood vessels.
The second group of conditions that can appear similar to PACNS are those that cause inflammation of the blood vessels in the brain due to another disease. This includes a variety of different causes such as:
- Infections caused by bacteria like tuberculosis or syphilis, viruses like Epstein-Barr virus or VZV, and fungi like Candida or Aspergillus.
- Conditions related to the body’s immune system such as Churg-Strauss disease, SLE, and Behcet syndrome.
- Other conditions that can result in inflammation of the blood vessels in the brain include Moyamoya disease, fibromuscular dysplasia, and radiation-induced vascular disease.
Doctors will do a complete examination for these conditions before confirming a diagnosis of PACNS.
What to expect with Primary Central Nervous System Vasculitis
There aren’t enough cases of PACNS, or primary angiitis of the central nervous system, in controlled medical studies to determine key indicators that could predict the outcome. However, data from retrospective observational studies (that look back in time and examine past events) show that patients generally have better health outcomes when treated with either glucocorticoids (a type of anti-inflammatory medication) or a combination of glucocorticoids and cyclophosphamide (a type of chemotherapy medication).
Individuals with PACNS may have a slightly shorter life expectancy when compared to the general population. And the prognosis tends to be less favourable for those who have the disease in larger blood vessels.
Possible Complications When Diagnosed with Primary Central Nervous System Vasculitis
Patients may experience a prolonged period of symptoms that can last several years, and additional episodes can lead to worsening of neurological conditions. Some studies note that the chance of these episodes recurring is around 27%. If patients are prescribed steroids or other medications to suppress their immune system for long-term treatment, they might face significant health risks. These include an elevated risk for high blood pressure, type 2 diabetes, and a greater likelihood of contracting opportunistic infections, which are infections that occur more frequently or are more severe in people with weakened immune systems.
Common Risks:
- Prolonged period of symptoms lasting several years
- Worsening of neurological conditions due to recurring episodes
- Elevated risk of high blood pressure with long-term use of steroids or other immunosuppressant medications
- Increase in the chances of developing type 2 diabetes with prolonged use of such medications
- Greater susceptibility to opportunistic infections due to a weakened immune system
Preventing Primary Central Nervous System Vasculitis
Patients should know that their condition might be long-lasting or recurring. They should be aware of the side effects of medications such as cyclophosphamide and steroids. It’s important to remember that these medications need to be closely monitored. They might need to make lifestyle changes and take steps to treat other health conditions they may have, like diabetes, high blood pressure, or osteoporosis.
If a patient is on long-term steroid treatment, it’s advised to take medication that helps prevent Pneumocystis pneumonia, a type of lung infection. Also, those on cyclophosphamide treatment should have frequent Complete Blood Count (CBC) tests, which measures the cells that make up your blood. These precautions help ensure that the treatment is effective and safe.
