Managing dystonia in NBIA patients:
A treating doctor’s perspective
- By Dr. Tamara Zagustin
One of the most common and disabling symptoms of NBIA is dystonia, a movement disorder that causes problems with walking, motor function, posture, speech, swallowing, pain and breathing. Sometimes, spasticity and exaggerated reflexes occur in conjunction with dystonia. Because the course of NBIA is unpredictable, managing dystonia is daunting.
In individuals with NBIA, dystonia is considered secondary dystonia and has different features than a primary dystonia diagnosis. This is important because managing secondary dystonia is very different than primary dystonia.
Primary dystonia is usually associated with a genetic inherited disorder that is progressive yet without other neurological symptoms such as seizures, retinal degeneration or loss of intellectual function. Usually, primary dystonia is more responsive to treatments than secondary dystonia with systemic therapies such as carbidopa-levodopa, deep brain stimulation (and botulinum toxin intramuscular injections. For the purposes of this article, we will be referring to the management of secondary dystonia in the presence of NBIA.
So far, many of the interventions that seem to improve NBIA symptoms, including dystonia, become diminished over time. Consequently, clinicians continue to work closely with families and patients to adjust treatments, with the goal of maintaining as high a quality of life as possible for patients.
The search continues for treatments that would:
- Be successful in controlling dystonia and spasticity to improve motor function, care, comfort and quality of life.
- Target the specific brain regions where dystonia symptoms originate.
- Require the smallest effective dose with the least side effects.
- Provide flexibility in managing the drug or treatment, while maintaining safety and consistency over time.
- Allow individualization of the treatment.
- Be reversible with no permanent changes.
- Minimize invasiveness, side effects and complications.
- Be universally available and affordable.
- Be fit for use early in life so the disease could be treated aggressively from the start
Some of the medications for disabling dystonia with or without spasticity include baclofen, clonazepam, gabapentin, clonidine and trihexyphenidyl. Many times, more than one medication is needed to facilitate better management of dystonia’s involuntary movements, which can be very impairing and painful. Unfortunately, there is no perfect medication or intervention to address dystonia effectively. Moreover, side effects may crop up early on — before the drugs’ full potential can be seen.
Of note, medical cannabis has been reported to provide benefits to individuals with spasticity and dystonia by decreasing muscle spasms, neuropathic pain and/or alleviating gastrointestinal symptoms such as nausea and appetite loss.
To date, the FDA has not approved a marketing application for cannabis for the treatment of any disease or condition. There is one cannabis derived drug product cannabidiol (CBD) approved for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome and 2 synthetic type cannabis related drug products: dronabinol and nabilone which are indicated for nausea associated with cancer chemotherapy. None of these FDA products are indicated for hypertonia or neuropathic pain.
Any other cannabis product available is not FDA approved and therefore cannot have a medical prescription as the ingredients are unknown and uncertain. Medical insurance will not cover these other cannabis derived products as they are considered experimental, and state laws allowing medical cannabis vary. Potential side effects and interactions with other medications must be considered when using these products.
Any form of medical cannabis that has more than low amounts of THC, the psychoactive component of cannabis, can negatively affect a child’s neurodevelopment. However, optimal management of spasticity and neuropathic pain requires a higher ratio of THC to CBD than the typical low THC-high CBD therapy calls for. Those are important considerations when discussing medical cannabis as an intervention for dystonia in individuals younger than 21.
When dystonia symptoms are localized to specific muscles, it is reasonable to consider targeted intramuscular botulinum toxin injections. When more muscles are affected and/or the amount of botulinum toxin is limited by the child’s low body weight, a combination of botox and phenol (6%) or ethanol (60 to 70%) nerve injections could be considered — with or without systemic medications (oral medications or intrathecal therapy).
When oral baclofen is no longer effective, intrathecal baclofen therapy could be considered, probably earlier rather than later to obtain the most benefit. That involves the surgical implantation of a drug delivery device (a programmable pump with a catheter). The device delivers baclofen into the fluid-filled area surrounding the spinal cord and brain (cerebral spinal fluid), an area called the intrathecal space. Settings on the pump deliver baclofen continuously based on the doctor’s prescribed amount. The intrathecal baclofen therapy is not without risks, such as infection, baclofen withdrawal or overdosing.
On the plus side, intrathecal baclofen therapy is more effective than oral baclofen and at a much lower dosage (80 to 100 times less). The treatment is reversible at any time by removing the device, and there is flexibility in how the dosage is delivered by using a continuous or flexible mode or a combination of modes together. The intrathecal baclofen therapy is invasive and should be considered when conservative management of dystonia with oral medications, localized injections, orthotics, therapies and other interventions fail to address treatment goals.
To optimize intrathecal baclofen therapy for dystonia management, here are some tips for clinicians:
- Consider initially an intrathecal baclofen trial (via lumbar puncture or via an external intrathecal catheter) to see if there is any benefit before committing to surgery and ongoing management of the therapy.
- Consider the placement of the drug delivery device with the largest available reservoir for the intrathecal baclofen as the doses are usually elevated over time to manage dystonia. This would minimize the frequency of medical visits needed for the drug delivery device to be refilled within a timely fashion to prevent complications from withdrawal, which would happen if the device runs out of medication.
- The catheter tip should be placed as close as possible to the brain, the target for dystonia. The tip can either go up high in the cervical region or within the brain itself. Devices on the market are approved for intrathecal use, yet studies show that using them in the intraventricular region has the same rate of morbidity/mortality as using in the intrathecal space.
- Work with an experienced team of professionals, including neurosurgeons, neurologist, physiatrist and others on the rehabilitation team with expertise in movement disorders and experience with intrathecal baclofen therapy.
- Patients should make regular visits to the doctor after the drug delivery device is first implanted, at least once every week or two, to optimize baclofen therapy dose within the first three months. Dosage should be increased in a progressive but conservative way. Usually, the dose for dystonia management is much higher than the dose for spasticity. The upper limit is usually determined by the best response with minimal side effects. Many times, additional systemic medications already in place for dystonia, such as clonidine, gabapentin, clonazepam, trihexyphenidyl, must be continued.
- Consider implementing intrathecal baclofen with a flex mode in which boluses are programmed every three hours at relatively high dosages (which could be as high as 200 mcg per bolus) in addition to a basal rate (continuous mode).
- Treating physicians should maintain good communication with patients in case of complications. Withdrawal is probably more common than overdose given the possibility of an acute pump malfunction with an intrathecal baclofen dosage that is usually greater than 2,000 mcg/day).
- At each visit continue to re-evaluate the effectiveness of the treatment and the need for adjustments of the intrathecal baclofen therapy to optimize this intervention, especially given NBIA’s unpredictability, variability and progressive nature. This makes the therapy challenging for even the most experienced clinician.
- Be goal-oriented with all interventions. The goals can evolve throughout the different stages of the disease. Be realistic and recognize the limits of what can be achieved over time with the complexity of NBIA. Be objective, compassionate and thoughtful.
- Other therapies such as oral medications, botulinum toxin intramuscular injections, phenol/ethanol neural injections and deep brain stimulation can and should be used when appropriate in conjunction with intrathecal baclofen therapy to maximize outcomes and results.
More studies are needed on optimal management of secondary dystonia to improve our understanding of how to control it better and facilitate appropriate neurodevelopmental skills, maintain function with independence in activities of daily living, cost-effectiveness, care, comfort and quality of life for affected individuals with NBIA and their caregivers.
Feel free to contact me if there are any questions, comments or other at firstname.lastname@example.org
Tamara Zagustin, M.D. is board-certified in Physical Medicine and Rehabilitation, Brain Injury Medicine and Pediatric Rehabilitation Medicine. She earned her medical degree from the Universidad Central de Venezuela (1991) and completed her Physical Medicine and Rehabilitation residency both at the Universidad Central de Venezuela (1996) and at the University of Arkansas for Medical Sciences (2007). She completed a fellowship in Pediatric Rehabilitation Medicine at the Children’s Hospital in Denver, University of Colorado (December 2008) and later joined Rady Children’s Hospital San Diego in January 2009 - September 2010. Now she is practicing at Kapiolani Medical Center for Women and Children, Honolulu, Hawaii. She has great interest in the health of children and adults with chronic disabling neurological diseases such as cerebral palsy, neurodegenerative diseases, spinal cord injury, movement disorders, brain injury, palliative care in children with complex neurological disorders and chronic pain syndromes.
Dr. Zagustin has participated in NBIA clinical appointments family conferences since 2011, giving her valuable experience with NBIA individuals. She was the treating physician for NBIA Disorders Association President Patricia Wood's daughter Kimberly when she received her intrathecal baclofen pump in 2010.