Cerebello-spinal tDCS Reduced Symptoms of Neurodegenerative Ataxia

Alberto Benussi, MD, Department of Clinical and Experimental Sciences, University of Brescia

Alberto Benussi, MD

Treatment with cerebellar anodal and spinal cathodal transcranial direct current stimulation (tDCS), a non-invasive therapy, reduced symptoms in patients with neurodegenerative ataxias, according to findings from a recent study.

This 2-week first-in-humans investigational trial represents a promising therapeutic and rehabilitative approach for patients with neurodegenerative ataxia, an orphan disorder of any pharmacologic intervention.

“These results, if confirmed on a larger population, could potentially open a new avenue of rehabilitative approaches in this group of patients, also considering the very limited pharmacologic and nonpharmacologic treatment options for patients with ataxia,” Alberto Benussi, MD, Department of Clinical and Experimental Sciences, University of Brescia, told NeurologyLive. “Additionally, this treatment is potentially applicable to different types of cerebellar ataxias with different etiologies.”

Researchers performed a double-blind, randomized, sham-controlled, crossover trial with cerebello-spinal tDCS utilized 5 days a week for 2 weeks in 20 participants with neurodegenerative ataxia. Participants had the disease for an average of 13 years and were an average age of 55.

Study participants underwent a clinical evaluation before and after real tDCS or sham stimulation. Follow-up evaluation was performed at 1 and 3 months with a washout period of 3 months after the last visit. After the washout period, each participant received the opposite treatment, undergoing the same standardized assessment as in the first phase, at baseline, at 2 weeks after stimulation (T1), at 1 month (T2), and at 3 months (T3).

“For both clinical symptoms and quality of life, we observed a significant improvement for up to 3 months in the group of patients who underwent the real stimulation treatment compared to the sham (placebo) treatment,” Benussi stated. “These results were corroborated by the restoration of the physiological inhibition mediated by the cerebellum on the motor cortex, which is frequently impaired in patients with ataxia.”

The Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARDS) were used to evaluate cerebellar deficits. To evaluate finger dexterity and upper limb coordination, researchers conducted 4 timed trials of the 9-Hole Peg Test separately for each hand. The 8-m walking time was performed 4 times for each session to assess gait speed. The Italian version of the Short-Form Health Survey 36 was also used to assess changes in participant’s quality of life.

After 2-week treatment, researchers observed a significant improvement in clinical scores and in neurophysiologic measure of motor cortex excitability and cerebellar-cerebral connectivity. Participants that were less affected clinically and functionally demonstrated the greatest improvement in clinical scores, which lasted for at least 3 months.

Results showed that the milder the disease stage, the greater the observed clinical improvement, suggesting that tDCS should be delivered at an early stage for greatest efficacy.

There was no significant association between the percentage of improvement in SARA or ICARS and sex, age at evaluation, age at disease onset, duration of disease and disease subtype.

SARA scores revealed a significant time × treatment interaction (F_3,54 = 38.54, P <.001, partial η² = .68). The main effect of treatment showed a significant difference between real and sham stimulation at T1, T2 and T3 follow-up (all P <.001), but not baseline (P = .422). The main effect of time showed a significant difference in the main treatment group at T1, T2, and T3 compared to baseline (all P <.001) but not in the sham group (all P >.05).

There was a statistically significant time × treatment interaction (F3,54 = 32.11, P <.001, partial η² = .64) when researchers evaluated ICARS scores. The main effect of treatment showed a significant difference between tDCS and sham at T1, T2, and T3 (all P <.001) but not at baseline (P = .613), while the main effect of time showed a significant difference in the tDCS group at T1, T2, and T3 versus baseline (all P <.001) but not in the sham group (all P >.050).

Researchers observed a significant time × treatment interaction in both the dominant (F_3,48 = 7.36, P <.001, partial η² = .32) and nondominant (F_3,45 = 3.94, P = .014, partial η² = .208) hand in the 9HPT assessment. The main effect of treatment showed a significant difference between tDCS and sham at T1, T2, and T3 (all P <.010) in both the dominant and non- dominant hand but not at baseline (dominant P = .670, nondominant P = .926), while the main effect of time showed a significant difference in the tDCS group at T1, T2, and T3 when compared to baseline (all P <.050) but not in the sham group (all P >.050).

A significant time × treatment interaction was also found in the 8 MW (F_3,27 = 5.12, P = .006, partial η² = .34). The main effect of treatment showed a significant difference between tDCS and sham at T1, T2, and T3 (all P <.050) but not at baseline (P = .414), while the main effect of time showed a significant difference in the treatment arm at T1, T2, and T3 versus compared to baseline (all P <.050) but not in the sham arm (all P >.050).

“In patients with ataxia, the repeated concurrent electrical stimulation of the cerebellum and spinal cord may improve symptoms in patients with ataxia,” Benussi added. “This treatment has been shown to be easily applicable, without significant adverse effects and relatively low-cost compared to other pharmacologic treatments, which are still lacking in this group of diseases. Non-invasive brain stimulation techniques have become a rational alternative in diseases still orphan of pharmacologic interventions.”

Despite limited pharmacologic and nonpharmacologic treatment options for this patient population, the data demonstrate that 2-week treatment with cerebello-spinal tDCS may be considered a promising tool for future rehabilitative methods. tDCS proved to be effective, noninvasive and easily utilized with long-lasting effects, leading to the possibility of implementing multiple sessions over time in order to extend the duration of its effects.

“This study tries to answer some of the questions regarding the effects of electrical stimulation in patients with ataxia, however still further research is needed to completely understand what are the mechanisms involved in this improvement and how we could increase the intensity and duration of these effects,” Benussi concluded. “We learned that the electrical stimulation of both the cerebellum and spinal cord may improve symptoms in patients with ataxia. However, still much research is needed to identify the best stimulation parameters (in terms of intensity and duration), and electrode positioning. Another important question is whether we can increase the duration of the after-effects induced by the electrical stimulation, possibly by repeating the stimulation over time.”

REFERENCE

Benussi A, Dell’Era V, Cantoni V, et. al. Cerebello-spinal tDCS in ataxia. Neurology. 2018;91:1—12. doi:10.1212/WNL.0000000000006210.