New insights into movement disorders: highlights and expert commentary from MDS 2022

The Movement Disorder Society’s 2022 congress included some important new data that could help specialists and teams optimize patient care.

Here, Dr Thomas Tropea (University of Pennsylvania, Philadelphia, USA) provides commentary on selected highlights from the annual congress, held in Madrid, Spain, from 15-18 September. For more from the MDS congress, check out Neurodiem’s daily coverage of the event.

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At this year’s congress of the International Parkinsonism and Movement Disorder Society (MDS 2022), specialists learned of new findings in Parkinson’s disease (PD) and other disorders, with more than a thousand new studies presented. Many of the findings reported at the congress highlighted the growing importance of digital health technologies in guiding decisions on care.

One important study confirmed the feasibility of remote gait rehabilitation for people with PD. Specialists from centers in Italy and Israel presented the preliminary results of a 9-month training program, evaluating a novel tele-rehabilitation wearable device, which includes a smartphone and an inertial measurement unit (IMU) on each shoe and on the chest.

Patients performed gait training at home during their ON medication phase using the tele-rehabilitation system for 30 minutes, 3 times weekly. During training, a digital assistant provides audio feedback based on IMU data to correct or reinforce gait behavior (e.g. “Take longer steps”, “Walk faster”, or “Good job”).

The researchers reported that:

• Nine of 10 patients evaluated completed the remote rehabilitation program
• Average time spent walking, distance, and gait speed were 27.45 minutes, 1.77 km, and 1.1 m/s, respectively
• Approximately 70% of positive audio feedback reports (“Good job”) from the digital assistant accurately corresponded with patients following instructions correctly

Dr Tropea commented: “More and more studies are demonstrating the benefits of exercise, rehabilitation, and gait training for people with PD. The work demonstrated here highlights the potential value of a tele-rehab intervention that incorporates wearable sensors with a gait training program.

“These preliminary results show that a tele-rehab gait intervention is feasible and may improve gait training. The high proportion of positive feedback during the sessions is an indicator of correct and effective use by patients. Increasing access to effective gait training in PD patients via a tele-rehab intervention is a major need.”

“Increasing access to effective gait training is a major need”

Dr Thomas Tropea

Another study showed how telemedicine is helping to bridge gaps in neurological care in rural regions. Researchers in Kenya – where there are fewer than 20 neurologists, most based in the capital city – examined data from all patients diagnosed with movement disorders at the Meru Teaching and Referral Hospital and an affiliated clinic (Oregon Health Services) in 2020 and 2021. They examined how telehealth was used and how the final diagnosis was made.

The findings (see box) showed the positive impact of using telehealth platforms for the diagnosis, management, and follow-up of patients.

Dr Tropea commented: “The researchers report on a telehealth consultation approach for movement disorders in Kenya, where there is limited access to neurologists and movement disorders specialists.

“They demonstrate a successful model of telehealth consultation that is being employed to increase access to specialized movement disorders care when in-person evaluations are limited. Expanding this model to increase access would be valuable for people in Kenya suffering from movement disorders, and it can serve as a model for other areas with limited access to movement disorders specialists.” 

“This can serve as a model for other areas with limited access to movement disorder specialists”

Dr Thomas Tropea

Also at MDS 2022, specialists reported how combining digital technologies can provide comprehensive insights into patient behavior in the real world. The researchers from the University of Rochester Medical Center, New York, USA, revealed the results of a 2-year study of the use of wearable sensors, in-home monitoring, and other technologies.

People with PD, and control subjects were assessed by a video analytic tool to measure motor, speech, and facial expressions at baseline and at 6, 12, and 24 months. Patients could opt to use up to 3 additional technologies:

• A smartphone application (2-week sessions, quarterly)
• Wearable sensors (1-week sessions, worn in the daytime for 6 days and for 24 hours on the seventh day)
• An in-home monitoring system (continuous monitoring)

The researchers randomly selected one patient with PD (female, aged 63 years) and one control (female, aged 57 years) who used all four technologies to illustrate the difference between the cohorts. They identified the following characteristics for the PD patient, compared with the control:

• Less time walking (1.18 vs 1.39 hours)
• Fewer steps taken per day (4,257 vs 6,713 steps)
• Longer step duration (0.66 vs 0.57 seconds)
• More time spent lying down during the day (2.4 vs 1.5 hours)
• More frequent turns in bed (140 vs 35 turns)
• Less time spent in bed (6.7 vs 9.2 hours)
• Greater intensity raising the inner brow when smiling (0.18 vs 0.12)
• Less intensity raising the cheek when smiling (0.03 vs 0.92)
• Fewer finger taps on the smartphone (123 vs 243 taps)

Dr Tropea commented: “Wearable technologies have the potential to capture motor activity, lifestyle characteristics, and other motor and behavioral data. This study shows the extent and depth of data that can be collected using multiple devices intermittently or simultaneously.

“The differences in motor function and behaviors between PD and non-PD controls are convenient objective measures that could be used in clinical practice or potentially incorporated as outcome variables in research studies.”

“This study shows the extent and depth of data than can be collected using multiple devices”

Dr Thomas Tropea

With wearables offering much potential for personalized monitoring in PD, it is important to understand which aspects of PD should be evaluated – and a new study showed that the perspectives of patients and specialized healthcare providers differ on this.

Researchers used online questionnaires (completed by 434 PD patients and 166 providers specialized in PD care: 86 physiotherapists, 55 nurses and 25 neurologists) and smaller focus groups to investigate perspectives. They found that one-third of the patients had monitored their PD symptoms in the past year, most often by using a paper diary. The key barriers to monitoring were:

• Not wanting to focus too much on having PD
• Symptoms being relatively stable
• Lacking an easy-to-use tool

The prioritized symptoms of interest differed significantly between patients and providers – patients gave a higher priority to fatigue and problems with fine motor movements, while providers gave a higher priority to balance and freezing (see box).

Dr Tropea commented: “Wearable sensors hold promise as a passive, non-invasive symptom tracker or outcome measure for people with PD. Motivations and barriers to use are an important aspect of this line of research, which the authors investigate among key stakeholders.

“Key differences between providers and patients highlight the need for better informed targets of wearable technology that incorporate both patient and physician perspectives. Importantly, passive data collection through wearable sensors, as opposed to daily diary recording, may satisfy different aspects of patients’ and providers’ expectations.”

“Passive data collection through wearable sensors may satisfy different aspects of patients’ and providers’ expectations”

Dr Thomas Tropea

New insights into genetic factors associated with PD dementia were revealed at MDS 2022, where specialists reported three novel loci associated with faster progression to dementia.

Specialists at centers in the UK, Norway, and France, performed a genome-wide survival meta-analysis of data from 3,964 patients of European ancestry with clinically diagnosed PD. Overall, 6.7% of the patients developed dementia in the follow-up period (mean 6.7 years from disease onset or diagnosis).

The analysis showed that:

• The APOE-ε4 allele was confirmed as a major risk factor for conversion to PD dementia (hazard ratio [HR] 2.42; P<0.001)
• New loci were identified that were also associated with dementia, including the apoE and APP receptor LRP1B (HR 3.37; P<0.001)
• Other variants associated with faster progression to dementia included variants in SLC6A3 (HR 4.42; 95% CI 2.62-7.45; P<0.001) and near SSR1 (HR 2.31; P<0.001)
• Patients who developed dementia also had significantly lower levels of amyloid β42 in cerebrospinal fluid, compared with those who did not develop dementia

Dr Tropea commented: “Dementia is one of the most devastating long-term outcomes of PD, but the mechanism of dementia in PD remains elusive. This work replicates the well-described APOE-ε4 allele association and identifies novel candidate loci associated with dementia risk. The findings highlight novel pathways that could be explored in future mechanistic studies to understand their pathophysiological role.

“These approaches are essential to understanding why some people with PD develop dementia and to identify novel pathways for therapeutic development.”

“These [genetic] approaches are essential to understanding why some people with PD develop dementia”

Dr Thomas Tropea

How useful are the current risk scores for identifying older adults at risk of PD? Researchers in Austria presented new data supporting the use of the updated PREDICT-PD algorithm and MDS risk criteria.

They calculated risk scores for the 574 members of the longitudinal population-based Bruneck study cohort (aged 55-94 years), based on baseline data collected in 2005. The incidence of confirmed PD in the 10-year follow-up period was also determined.

The researchers found that:

• The updated PREDICT-PD algorithm score was associated with incident PD (odd ratio [OR] 4.61; P<0.001), yielding a higher odds ratio than the original PREDICT-PD algorithm (OR 2.38; P<0.001)
• Similarly, the risk score based on the updated MDS criteria was associated with incident PD (OR 7.13; P<0.001), which was numerically superior to both the original criteria and the updated PREDICT-PD algorithm, with overlapping confidence intervals

Dr Tropea commented: “Predicting risk of PD in the general population would allow for earlier identification of at-risk individuals. The researchers report on an improved prediction model called the enhanced PREDICT-PD to identify incident PD in a longitudinal observational study.

“Identifying individuals at risk of PD is highly useful for clinical research, clinical trial enrollment, and for clinical care. This work represents the iterative process of improved risk prediction modeling, and future studies may help to improve these prediction models.”

“This work represents the iterative process of improved risk prediction modeling”

Dr Thomas Tropea

In dystonia, specialists reported on a new algorithm that could help predict the optimal settings for pallidal deep brain stimulation (DBS) of the internal globus pallidus, and potentially lead to better symptom control.

The researchers at the University Hospital Würzburg, Germany, developed the C-SURF algorithm that tests different DBS contact settings in silico and then predicts the best possible stimulation settings for the individual patient.

In a feasibility study, patients receiving pallidal DBS were switched from standard, clinical programming to the stimulation parameters suggested by C-SURF. Motor symptom control, adverse events, and patient satisfaction were assessed in person 14 days later, and patients were interviewed by telephone 6 months later.

Ten patients were screened and 8 completed the study (mean age 43 years, 5 female, mean time since surgery 8 years):

• C-SURF resulted in significant improvements in motor symptom control compared with previous outcomes using clinical programming: the reduction in motor symptoms (compared with preoperative levels) was 75% with C-SURF and 66% with clinical programming (P=0.01)
• The improved performance observed with C-SURF was not associated with an increase in adverse events or energy consumption

A randomized controlled trial pf C-SURF (NCT05097001) is now underway.

Dr Tropea commented: “The iterative task of effectively programming DBS pallidal targets is an inefficient approach that is associated with prolonged suboptimal treatment time. A data-driven approach to optimal programming could improve treatment response and decrease suboptimal treatment time.  These preliminary results demonstrate that C-SURF was associated with better patient reported outcomes than clinical settings, and might be an ideal alternative to clinical programming. The additional potential to reduce physician time needed to program and decreased cost would be an added benefit.”

“C-SURF might be an ideal alternative to clinical programming [in DBS for dystonia]”

Dr Thomas Tropea

Finally for this MDS highlights round-up, specialists reported on challenges in the diagnosis of patients with hereditary ataxias (HA) and spastic paraplegias (HSP).

The researchers in Barcelona, Spain, performed a descriptive cross-sectional study of 59 patients of 56 families followed at one center (46 with HA, 9 with HSP, and 5 with a combination of HA and HSP):

• 39% of the patients had a positive family history, 37.2% pyramidal signs, 22% peripheral neuropathy, and 49.1% cerebellar atrophy
• Molecular diagnosis was achieved in 22% of patients: Friedreich’s ataxia was diagnosed in 5, SCA3 in 2, and the following in 1 patient: SCA7, SPG15, SPG26, SPG48, POLR3A-related spastic ataxia and episodic ataxia type 2
• The molecular diagnostic methods were single-gene tests including repeat primed PCR and Sanger sequencing (8 of 45 patients achieved diagnosis); gene panel (1 of 3 patients achieved diagnosis); and whole exome sequencing (4 of 8 patients achieved diagnosis)
• The mean cost per patient of all molecular diagnoses, excluding gene panels and exome sequencing, was 686.44 euros. In 13%, the cost was higher than the cost of exome sequencing

Dr Tropea commented: “There remain many challenges in the diagnosis of HSP and HA. Genetic testing has increased with better access to genetic testing. The authors highlight their experiences between 2009 and 2021, demonstrating their use of single gene tests, panels, and exome sequencing.

“A comparison of the estimated costs of the diagnostic workup compared to exome sequencing highlights the problem of a financial barrier to genetic testing for movement disorders. Exome sequencing had the highest yield among these tests in this small sample size. This work demonstrates that with decreased barriers, including cost, exome sequencing may become cost effective and have the highest yield for genetic testing in the work-up of ataxia and HSP.”

“Exome sequencing may have the highest yield for genetic testing in the work-up of ataxia and HSP”

Dr Thomas Tropea

For more information on new developments reported at MDS 2022, check out the daily coverage of the event on the Neurodiem website.