Graft vs. host disease (GVHD) of the nervous system — meaning GVHD that affects either the central nervous system (CNS-GVHD) or peripheral nervous system (PNS-GVHD) — is a serious manifestation of the disease.
Because our nervous systems control so many different functions throughout our bodies, symptoms can be wide ranging in both type and severity. Seizures, cognitive impairment, trouble speaking or walking, peripheral neuropathy, and more can result, depending on whether the central nervous system or peripheral nervous system is the target of the attack.
What is our body’s nervous system?
Our nervous system is our body’s information super highway — it’s how electrical signals travel to and from our brains. These “messages” are both sent and received…the brain sends signals down the spinal cord throughout the body to peripheral nerves, and those nerves send signals back to the brain. This two-way system not only controls bodily functions — like breathing, heart rate and blood pressure, and digestion — it also allows us to experience thoughts, feelings, and emotions, as well as move and experience the world through our senses.
Our central nervous system is comprised of our brain and spinal cord; our peripheral nervous system encompasses all the nerves throughout our body that are not in our brain or spinal cord.
Within our peripheral nervous system are two sub-segments: the somatic nervous system — which controls our voluntary body movements, like raising your hand in class or typing on a computer — and our autonomic nervous system, which controls our unconscious bodily functions…things like breathing, digestion, and heart rate/blood pressure. If you drill down even further there are two additional classifications within the autonomic nervous system — the parasympathetic system (responsible for all “resting” and “digesting” functions in the body) and the sympathetic nervous system (responsible for our “fight or flight” response in moments of stress).
Different nerve cells — or neurons — control different things in our bodies: motor neurons control muscle movement; sensory neurons allow us to feel everything from touch to temperature through our skin; and nerve cells in our autonomic system control all the automatic functions within our body that we just discussed.
When GVHD attacks nerves, symptoms depend on which type of nerves are targeted by the disease.
Symptoms of Nervous System GVHD
When GVHD attacks the central nervous system, the brain and spinal cord are affected. This often leads to encephalitis, or swelling of the brain and its blood vessels. When this happens, symptoms like seizures, loss of consciousness, difficulty thinking, speaking, or hearing, hallucinations, personality changes, and other stroke-like symptoms can occur. Demyelination — or damage to the protective coverings of nerves, called the myelin sheath — can result from CNS-GVHD as well. This is called encephalomyelitis, and it can cause symptoms that mimic multiple sclerosis (which also damages the myelin sheath). CNS-GVHD can lead to medical emergencies that need to be treated immediately. Thankfully, it’s incredibly rare.
When GVHD attacks the peripheral nervous system, the nerves outside of the brain and spinal cord are affected which leads to peripheral neuropathy, or damage and dysfunction in the body’s nerves.
Peripheral neuropathy is often associated with tingling hands and feet, something diabetics often experience — and while that’s a common manifestation, people can experience a wide range of other symptoms, too, depending on which peripheral nerves are affected.
When sensory nerves are affected, symptoms of peripheral neuropathy are often felt in the hands and feet, as well as the arms and legs. The discomfort ranges from feelings of “pins and needles” to extreme, stabbing pain. Numbness, burning, and tingling are common ways patients describe the discomfort.
Some additional symptoms may include:
- A sensitivity to anything touching your skin
- Pain when a sheet or blanket touches your skin, or pain when putting weight on your feet
- Feeling like you have socks or gloves on even when you don’t
If your motor nerves are affected, you might find that it’s difficult to move, because your muscles are compromised.
You may experience:
- Weakness
- Lack of coordination and falling
- Muscle cramping, or muscle wasting
- A heavy feeling in your arms or legs
When autonomic nerves are affected, symptoms related to blood pressure control, digestion, or temperature regulation may occur.
Things like:
- Lightheadedness or dizziness
- Intolerance to heat (which can make you sweat too much or not enough)
- Digestive or bowel problems
- Urinary incontinence
- Sexual dysfunction (like erectile dysfunction)
Tests to Diagnose Nervous System GVHD
Your doctor will conduct thorough testing and eliminate other potential causes of your symptoms (like infections, diabetes, vitamin deficiencies, etc.) before diagnosing you with nervous system GVHD.
To diagnose CNS-GVHD doctors will conduct thorough neurologic testing, order imaging studies (like MRIs or CT scans), and potentially biopsy brain matter or cerebral spinal fluid.
Many tests are used to diagnose peripheral neuropathy, including:
- Nerve conduction tests
- Strength tests
- Blood tests to check organ function and vitamin levels (vitamin deficiencies can sometimes cause peripheral neuropathy, especially B12 deficiency)
- X-rays and other imaging tests
Treatments for CNS-GVHD
Like all other kinds of GVHD, steroids play an extremely important role in getting the symptoms of nervous system GVHD under control, regardless of whether the central or peripheral nervous system is affected. Several immunosuppressive agents are typically used in combination, including corticosteroids, IV immunoglobulin, plasmapheresis, or cyclophosphamide.
If you suffered encephalitis (swelling of the brain) as a result of GVHD, you might need various kinds of rehabilitation to regain brain and bodily function, too, depending on how much damage occurred. Cognitive shortcomings — like difficulty thinking, concentrating, remembering, or learning new things — are common, as are emotional and physical problems.
People may find that it’s hard to regulate their feelings, motivate themselves, or practice self-control. They may also be left with weak muscles or trouble with coordination. Trouble sleeping can happen, too.
Physical therapists will help you regain physical strength through exercise; occupational therapists can help you regain independence in your activities of daily living — things like showering, getting dressed, or preparing food — and counseling, cognitive, and behavioral therapy can help people overcome anxiety, anger, and depression, “retrain” the brain to perform tasks and learn new ways of doing things, and think in different ways than before.
Music and art therapy are incredibly helpful, too, as they allow avenues for emotional expression; speech and language therapy can also help with speaking, swallowing, writing, and reading.
Exercising Your Brain
Did you know that our brains can “rewire” themselves? It’s an amazing phenomenon called neuroplasticity, and it’s happening all the time in lots of different ways. Our brains are constantly evolving throughout our lives, forming new neural pathways as the result of our experiences and learning, and eliminating old connections that no longer serve us. The brain can even shift control of a bodily function from a damaged area to a new one — that’s how it’s possible to regain certain functions that were “lost” due to a stroke or encephalitis. Pretty remarkable, isn’t it?
In much the same way that physical exercise keeps our heart and muscles healthy, cognitive exercises do the same for our brains by establishing these new neural pathways. It’s incredibly important for everyone, but especially patients with CNS-GVHD.
You can do this by:
- Learning a new skill or hobby — take up an instrument, sport, knitting, dancing…just about anything that’s new to you!
- Learning a new language.
- Reading lots of different content and styles of writing to increase your vocabulary.
- Playing a variety of puzzles and games, especially things that challenge your memory and recollection.
- Meditating — there’s plenty of free apps like Headspace, Calm, or Insight Timer to help.
- Socializing — human connection and conversation is great for cognitive function, too!
This website has lots of suggestions for brain games and exercises to try: https://autoimmune-encephalitis.org/cognitive-exercises-for-ae-patients/. You might find this article helpful, too: https://www.medicalnewstoday.com/articles/brain-exercises.
It’s also very important to eat a nutritious diet that includes plenty of healthy fats, like extra virgin olive oil, avocados, or nuts, to “feed” your brain…after all, 60% of the human brain is comprised of fat! Staying physically fit and active is essential for a healthy brain, too — just be sure to talk to your doctor before beginning any kind of exercise program.
Treatments for PNS-GVHD
Just like CNS-GVHD, immunosuppressive agents like corticosteroids, IV immunoglobulin, plasmapheresis, or cyclophosphamide are often first line treatments for PNS-GVHD.
Additionally, doctors sometimes prescribe anti-seizure drugs like pregabalin and gabapentin, or the antidepressant amitriptyline to intercept and disrupt pain signals.
Other therapies might be used as well, including:
- Spinal cord stimulators, called neurostimulators, that send electrical impulses inside the body to interfere with pain signals.
- “Scrambler technology,” which trains the brain to recognize non-pain signals that can eventually replace pain signals.
- Physical therapy, which can help restore muscle strength and help with balance and mobility issues caused by the neuropathy.
Gels and creams that contain lidocaine may also lessen pain or discomfort, as can over the counter pain medications, like NSAIDS (if your doctor approves), and soaking your feet in cold water.
Many people find great relief through alternative treatments like acupuncture, biofeedback, yoga, and meditation as well, and certain supplements including alpha-lipoic acid and acetyl-L-carnitine have shown promise in improving neuropathy symptoms. Always talk to your doctor before taking a new supplement, medication, or therapy, however, to make sure it’s safe for you!
Living with Peripheral Neuropathy
Living with peripheral neuropathy can be annoying, to say the least.
Best case scenario, it’s uncomfortable…worst case scenario, it interferes with your ability to function day-to-day.
One of the greatest dangers of peripheral neuropathy is that it makes it difficult to realize when you’ve injured your skin, because you can’t feel it…which can leave the door wide open for infections to take hold.
If you have peripheral neuropathy, it’s important to:
- Get in the habit of checking your hands and feet daily for any signs of abrasions, like scrapes, cuts, cracks, bruises, burns, or punctures.
- Wash your feet daily with warm water and soap — same goes for hands, but most of us are already doing that!
- Never walk around barefoot, inside or outside. Always wear good shoes or slippers to protect your feet.
These tips may also help bring the neuropathy under control:
- Start an exercise program if your doctor has cleared you to do so; exercise will strengthen your muscles and combat the effects of motor (or muscular) neuropathy.
- If you smoke, stop; smoking makes peripheral neuropathy worse.
- Maintain a healthy weight and blood sugar balance. For tips on how to balance your blood sugar, check out the book “Glucose Revolution.”
- Wear shoes or slippers at all times — don’t go barefoot.
- Don’t apply heat directly to your legs or feet; it could burn you without you knowing it.
- If neuropathy is affecting your coordination, be extra careful to avoid falls both inside and outside your home. This may include using a cane or other supportive device, or outfitting your home with technology and devices that will make it safer. Memorial Sloan Kettering Cancer Center put together a great checklist: https://www.mskcc.org/cancer-care/patient-education/managing-peripheral-neuropathy
For an even deeper dive into neuropathy, check out this presentation by BMTinfonet.
Sources
- https://bmtinfonet.org/transplant-article/nervous-system-and-chronic-gvhd
- https://bmtinfonet.org/video/neuropathy-what-it-and-how-treat-it
- https://my.clevelandclinic.org/health/body/21202-nervous-system
- https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/symptoms-causes/syc-20352061
- https://www.mskcc.org/cancer-care/patient-education/managing-peripheral-neuropathy
- https://my.clevelandclinic.org/health/body/23123-peripheral-nervous-system-pns
- <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055885/
- https://www.mayoclinic.org/diseases-conditions/encephalitis/symptoms-causes/syc-20356136
- https://academic.oup.com/brain/article/133/10/2852/324822
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00668/full
- https://autoimmune-encephalitis.org/cognitive-exercises-for-ae-patients/
- https://www.astctjournal.org/article/S1083-8791(14)01226-9/pdf
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662398/
- https://www.encephalitis.info/rehabilitation-after-encephalitis/
- https://www.mayoclinic.org/diseases-conditions/encephalitis/symptoms-causes/syc-20356136
- https://www.verywellmind.com/what-is-brain-plasticity-2794886
- https://www.verywellmind.com/top-ways-to-improve-your-brain-fitness-2224137
- https://www.medicalnewstoday.com/articles/brain-exercises#engaging-hobbies