The Collaborative Center for X-linked Dystonia-Parkinsonism (XDP) at Massachusetts General Hospital provides resources to physicians who are treating patients that exhibit signs of XDP.
What is X-linked Dystonia-Parkinsonism?
XDP is an adult-onset, genetic movement disorder occurring among the Illongo people of the Philippines, one of the largest ethnic groups in that country. It is a neurodegenerative disease that evolves over the course of many years, resulting in significant disability and a shortened life span.
Phases of XDP
XDP generally presents in three different clinical phases.
People with dystonia have involuntary, sustained muscle contractions. These involuntary muscle contractions can cause twisting, repetitive movements and abnormal postures. The twisting seen in XDP patients happens because the brain sends signals that tell muscles to tighten and contract involuntarily.
In XDP, dystonia can occur in any part of the body and may spread to other body parts during disease. It can manifest in many ways, including twisting/dragging a foot, repeated jaw opening and closing, abnormal turning or posture of the neck, tongue protrusion, mouth pursing or excessive eye blinking. Many patients begin showing symptoms in their forties, but the age of onset can vary greatly.
When one part of the body is affected, it is called focal dystonia.
Over time, more muscles become affected, leading to twisting and uncomfortable postures with muscle spasms. After five years, most patients have developed a generalized dystonia, where many different muscle groups and body parts are affected.
Dystonia and Parkinsonism
The next phase of XDP usually begins 7-15 years after onset of focal dystonia. During this phase, the patient has features of both generalized dystonia as well as parkinsonism.
Parkinsonism involves the development of symptoms that are classically associated with Parkinson's disease, but can also be seen in many other conditions. These involve slowing of movements, shuffling gait, development of a hand tremor and reduction of facial expression. Patients with XDP do not have Parkinson's disease, which is not a genetic condition and is caused by a different mechanism.
By 15 years after onset, XDP patients primarily show features of parkinsonism. In 6% of patients, XDP manifests primarily as parkinsonism, without evidence of dystonia.
As XDP progresses, patients become more disabled and are eventually unable to work. In the late stages of disease, patients become dependent on others, immobile and unable to care for themselves. Patients with XDP have a reduced life expectancy due to the complications of the disease.
Not all patients present with the same symptoms or progress at the same rate. CCXDP clinical researchers are currently conducting natural history studies in the Philippines and North America to define the full spectrum of disease to understand this variation. These studies are crucial for eventual clinical trials and may provide insights that allow earlier interventions to improve patient outcomes.
Patient Referrals to the Mass General Dystonia Clinic
Movement disorders can sometimes be very difficult to diagnose. Many patients come to the neurology department at Massachusetts General Hospital for additional diagnostic evaluations after seeing neurologists outside of the hospital.
Upon visiting the Dystonia Clinic, new patients undergo a comprehensive evaluation that can include a thorough clinical assessment, laboratory testing, cognitive evaluation and brain imaging. These capabilities—along with the experience and expertise of our on-staff neurologists—allow us to make quick and accurate diagnoses.
Once we have established the diagnosis, we are happy to provide ongoing care at our clinic or in collaboration with the patient's primary care physician or neurologist. In addition, we can make referrals to other specialists at Mass General for further testing or treatment when appropriate.
To refer a patient to the Dystonia Clinic at Mass General, please call 617-643-2083, or visit the Dystonia Clinic website.
Research Study Enrollment
The Center supports ongoing research studies in dystonia. Download the attached letter (PDF) if you have a patient with X-linked dystonia-parkinsonism (XDP) or another form of dystonia who might be interested in participating.
We do not give results as part of the research study. If a research participant has symptoms for which clinical genetic testing is recommended, the genetic counselor who works on our research study staff can help facilitate that. Please share our IRB-approved study brochure with your patients.
Download brochure (PDF)
If you have further questions about the study please contact our Study Coordinator, Trisha Multhaupt-Buell, by email at DystoniaResearch@partners.org
The Center for XDP supports training opportunities at Mass General or in the Philippines for clinicians interested in learning about the care and treatment of XDP and other forms of dystonia. For more information, please contact Amy Alessi, PhD at email@example.com.
Investigating Deep Brain Stimulation
Deep brain stimulation (DBS) is a surgical treatment in which an implanted device delivers electrical stimulation to the brain in order to alleviate neurologic symptoms.
Stimulation is applied through a surgically implanted wire (also called a lead or electrode) that is inserted into the brain. DBS is most commonly used to treat the symptoms of Parkinson’s disease, essential tremor and dystonia. In dystonia, the most common stimulation target is the globus pallidus internus (GPi). The electrical stimulation is generated by an implantable pulse generator (IPG) that is placed under the skin in the chest, similar to a cardiac pacemaker. The stimulation can be adjusted non-invasively by a neurologist in order to optimize symptom relief.
DBS is most effective for primary dystonias—that is, inherited dystonias like XDP and dystonias without a known cause—and less effective for secondary or acquired dystonias, such as those due to brain injury from cerebral palsy or stroke. With DBS, primary dystonia symptoms improve by 50-60% on average, although individuals may benefit substantially more or less than average. These benefits appear to last at least 10 years.
There is less known about the long-term benefit of DBS in XDP specifically, although ours' and others' experience has been that DBS can be a very effective treatment for the symptoms of XDP. In one study of eight individuals with XDP, all eight patients experienced an improvement in dystonia symptoms, with six of eight patients improving by more than 65% at three months (Neurology April 8, 2014 vol. 82 no. 10 Supplement P1.013).
With the DBS surgery, there is a 1-2% risk of brain bleeding or stroke that results in new symptoms such as weakness, numbness or problems with speech; in the majority of cases, these side effects fade with time. There is also a 3-4% risk of surgical infection, which may require removal of all or part of the stimulator.
Lastly, as the IPG battery depletes, it must be replaced in a minor surgery. The interval between replacement varies widely between individuals depending on the device and stimulation settings, but is typically 2-5 years for non-rechargeable batteries and up to 9 years for rechargeable batteries.Learn more about DBS for dystonia
Deep Brain Stimulation at Mass General
The neurosurgeons at the Functional Neurosurgery Center at Mass General use deep brain stimulation (DBS) to treat patients with a wide variety of movement disorders. The Neurosurgery Center uses the most advanced stereotactic technology—microelectrode recordings—for optimal lead positioning and the best patient outcome.
Mass General was one of the first hospitals to perform DBS, and today the Neurosurgery Center uses it to treat Parkinson’s disease as well as many different types of dystonia, including:
- Genetic dystonia, such as XDP
- Generalized dystonia
- Segmental dystonia
- Focal dystonia, such as spasmodic torticollis