More Than A Feeling: Program Focuses on “Other” Symptoms of PD

In an effort to promote awareness of the non-motor issues associated with Parkinson's, UCB, biopharmaceutical company, has started “More Than Motion.” The Facebook community, available at https://www.facebook.com/parkinsonsmorethanmotion, aims to educate about the “other” symptoms of PD including sleep disturbance, fatigue, trouble with memory, and more. Here, Practical Neurology talks with Zarya Rubin, MD, Medical Director, CNS, UCB about the project.

Why is there a need to focus on the non-motor problems associated with PD? What is the goal of the project?

Dr. Rubin: While the non-motor symptoms (NMS) of Parkinson's disease are very common, they often go unrecognized, both because patients may not identify these manifestations as part of their disease, and because physicians may not routinely screen for these symptoms. Studies have shown that the non-motor symptoms of PD can have a significant impact on patients. By creating an interactive, social network to bring education and a sense of community to PD patients and caregivers we are hoping to raise awareness and allow for increased dialogue about NMS between patients and their healthcare team.

Non-motor problems often go unreported. How can physicians do a better job of inquiring about and monitoring non-motor problems? Is testing with the UPDRS enough to uncover these problems?

Dr. Rubin: While the UPDRS has been the gold standard for the clinical evaluation of Parkinson's disease symptoms and progression over time, it has been weighted heavily towards motor symptoms. When the UPDRS was revised in 2007 (MDS-UPDRS), an entire section became devoted to the impact of NMS on activities of daily living. In addition, there are several validated tools specific to NMS, such as the NMSS (Non-Motor Symptom Severity Scale) and the NMSQuest (Non-Motor Symptom Questionnaire). Non-motor symptom checklists are often employed by Parkinson's centers to screen and track these symptoms at every patient visit. It's important for patients to voice concerns about new or worsening symptoms, and for physicians to ask about the full range of symptoms that may impact PD patients.

Even when identified, there is a common perception that many of these symptoms are untreatable (Chaudhuri KR, Schapira, 2009). How can physicians manage depression, anxiety, and sleep dysfunction, both pharmacologically or otherwise?

Dr. Rubin: Non-motor symptoms can present a challenge for patients and physicians as they may not respond as well as motor symptoms to treatments for Parkinson's disease. Furthermore, we still have a lot to learn as a scientific community in terms of the causes of NMS in order to find effective treatments. The management of a PD patient with significant NMS can be complex and often requires a multidisciplinary team that can include a psychiatrist and other sub-specialists to aid in developing a comprehensive treatment plan. Education and support for both the patient and their caregiver is key in the management of the NMS of PD.


FDA Grants Premarket Approval for NeuroPace RNS System to Treat Medically Refractory Epilepsy

The FDA has granted premarket approval for the NeuroPace RNS System, a treatment for adults with partial onset seizures that have not been controlled with two or more antiepileptic drugs. The RNS Stimulator consists of a small neurostimulator implanted within the skull under the scalp. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. The FDA notes the neurostimulator detects abnormal electrical activity in the brain and responds by delivering electrical stimulation intended to normalize brain activity before the patient experiences seizure symptoms.

The FDA's approval is supported by a three-month randomized control trial of 191 patients with drug-resistant epilepsy. The study showed that by three months after the implanted device was turned on (active use) patients experienced a nearly 38 percent reduction in the average number of seizures per month, compared to an approximately 17 percent reduction in the average number of seizures per month in patients who had the implanted device turned off. At the end of three months, the median reduction in seizures, which reflects a more typical patient experience, was 34 percent with active use and about 19 percent with the device turned off. During the trial, 29 percent of patients with an active device experienced at least a 50 percent reduction in the overall number of seizures, compared to 27 percent for those with the implanted device turned off.


FDA Approves Aptiom to Treat Partial Seizures in Adults

Additionally, FDA approved Aptiom (eslicarbazepine acetate, Sunovion) as an add-on medication to treat seizures associated with epilepsy. Three clinical studies in which participants with partial epilepsy were randomly assigned to receive Aptiom or placebo demonstrated that Aptiom is effective in reducing the frequency of seizures.

The most common side effects reported by patients receiving Aptiom in clinical trials included dizziness, drowsiness, nausea, headache, double-vision, vomiting, fatigue and loss of coordination. These and other side effects and recommendations for monitoring are described in the drug label.


Imaging Shows Long-term Impact of Blast-induced Brain Injuries

Using a special type of MRI, researchers at the RSNA meeting exhibited research showing that soldiers who suffered mild traumatic brain injury (MTBI) induced by blast exposure exhibit long-term brain differences. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with MTBI with those of 10 healthy controls. FA measures the uniformity of water diffusion throughout the brain, and low FA tends to indicate areas of axonal injury. The average time elapsed between the blastinduced injury and DTI among the patients was 51.3 months.

Using DTI, damage-associated changes in water movement along the axons are comparable in certain respects to what might happen with a garden hose, according to co-author Thomas M. Malone, BA, research associate. “As water passes through the hose from the faucet to the sprinkler, it goes in the same direction, but if you were to puncture the hose with a rake, the water would shoot out the sides,” Malone said.

Researchers said the time since injury is a novel component to the study. “Most blast-related MTBI studies examine patients in the acute phase of injury,” Dr. Roskos said.

Comparison of FA values showed significant differences between the two groups, and there were significant correlations between FA values and attention, delayed memory and psychomotor test scores. Te results suggest the presence of a long-term impact of blast injury on the brain.


New Therapeutic Target Identified for Huntington's Disease

A new study published in November in the open access journal PLOS Biology, identifies a new target in the search for therapeutic interventions for Huntington's disease.

Nuclear huntingtin aggregates have been found to interfere with the transcription of many genes, and previous work has shown beneficial effects for Huntington's disease of inhibiting a family of enzymes that are normally thought to regulate transcription— the histone deacetylases, or HDACs. Humans have 11 different HDAC enzymes, and it's been uncertain exactly which HDAC needs to be inhibited to see these benefits.

Researchers at King's College London say they have pinpointed just one of these enzymes as the target—HDAC4. The researchers noted that the HDAC4 protein naturally contains a region that, like mutant huntingtin, is rich in the amino acid glutamine. They show that HDAC4 can associate directly with huntingtin protein in a manner that depends on the length of the glutamine tracts, but that this association between HDAC4 and huntingtin occurs in the cytoplasm of nerve cells in the mouse brain, and— surprisingly—not in the nucleus, where HDAC4 is known to have its transcriptional role.

Bates and colleagues found that halving the levels of HDAC4 in the cells of Huntington's disease mice can delay the aggregation of huntingtin in the cytoplasm, thereby identifying a new route to modulating the toxicity of mutant huntingtin protein. Crucially, reducing HDAC4 levels can also rescue the overall function of nerve cells and their synapses, with corresponding improvements seen in coordination of movement, neurological performance and lifespan of the mice.


Survey Shows Effects of RLS/WED

Preliminary results from the “Patient Odyssey” survey, released by The Willis-Ekbom Disease (WED) Foundation and XenoPort, reveal challenges experienced by patients with Restless Legs Syndrome/Willis-Ekbom Disease (RLS/ WED). Results regarding treatment burden are available at www.Willis-Ekbom.org.

Survey participants included 1,709 RLS/WED patient members of the WED Foundation. Results showed that almost three in four patients experience symptoms daily, and only six percent believe that their RLS/WED symptoms are completely controlled by their current medication(s).

Sixty-eight percent of patients said they “strongly agreed” that there is a need for greater physician knowledge and understanding of RLS/WED, and 42 percent of patients “agreed” that their healthcare provider does not understand their disease. Ninety-three percent of patients “agreed” that they wished more effective medications were available.