Parkinson’s treatment improves walking in small Dravet clinical trial

Gaits and distance, especially in younger patients, were better on levodopa

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by Steve Bryson, PhD |

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Levodopa, the standard treatment for motor symptoms associated with Parkinson’s disease, improved walking abilities in people with Dravet syndrome, according to a small clinical trial.

Most walking gains occurred in younger patients with better walking abilities before levodopa treatment.

“Our findings suggest that levodopa treatment may be beneficial in younger people with [Dravet syndrome] and progressive gait abnormality, although long-term efficacy has not been established,” the researchers wrote in the study, “Effect of levodopa on pathological gait in Dravet syndrome: A randomized crossover trial using three-dimensional gait analysis,” published in the journal Epilepsia.

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Dravet is primarily characterized by prolonged seizures, beginning in the first years of life, that are difficult to control with anti-epilepsy medications. Other symptoms may include intellectual disabilities, delays in speech, poor growth, and sleep disturbances.

People with Dravet syndrome can also experience a progressive loss in motor function, balance, and gait. Still, few established treatments for impaired gait in Dravet exist.

Levodopa, a precursor of the neurotransmitter called dopamine, is the standard treatment used to manage motor symptoms in people with Parkinson’s disease. While case reports have suggested its benefits for gait problems in Dravet patients, no clinical trials had been conducted.

Levodopa trial in Japan

Therefore, researchers in Japan launched a small clinical trial to evaluate the impact of levodopa on gait in nine patients (six male and three female) with Dravet, ages 6-20. All patients carried mutations in the SCN1A gene, which causes nearly all cases of the condition.

All patients had flat feet, four showed a lack of coordination (ataxia), three had scoliosis (a sideways curvature of the spine), and one had generalized rigidity. Severe intellectual disability was noted in seven patients while it was considered moderate in two.

After an initial gait assessment before treatment, participants were randomly assigned to one of two levodopa treatment regimens.

One group took oral levodopa three times daily (5 mg/kg/day) for four to six weeks and underwent a second gait assessment (on levodopa). The dose was then tapered over six days, after which it was terminated. Four to six weeks later, a third gait assessment was performed (off levodopa).

The second group underwent a second gait assessment at four to six weeks without taking levodopa (off levodopa). Four weeks later, these participants took levodopa for four to six weeks and underwent a third assessment (on levodopa).

Gait was assessed by three-dimensional gait analysis (3DGA), which used cameras to measure gait by detecting reflective markers attached to patients’ legs and pelvis. Measures included walking speed, step length, gait variability, six-minute walking test (6MWT), and the gait deviation index (GDI), an assessment based on the relative motion of the lower extremities.

Compared with off-levodopa periods, seven of the eight evaluable patients showed improvement in GDI values, a longer distance walked in six minutes, and better body sway (balance) while walking during the on-levodopa periods.

Gait and motion-related improvements were noted in four participants during on-levodopa periods, as indicated by the clinician-assessed Gillette Functional Assessment Questionnaire (FAQ).

Walking speed and GDI improved significantly in participants younger than 16, whereas no significant gains were seen in older participants. Still, the 6MWT distance improved significantly in both younger and older participants.

Younger participants with better gait before treatment, or a higher GDI and FAQ score in the first 3DGA, achieved a clinically meaningful increase in the GDI of more than 5 points after levodopa.

This study “provides evidence that levodopa is a generally well tolerated and potentially beneficial treatment for improving gait disturbance in people with [Dravet syndrome],” the team concluded. They noted that “the effect of levodopa was considered over only a short period, and its long-term effectiveness remains to be determined.”