Levodopa/Carbidopa Intestinal Gel May Help Treat Freezing of Gait After DBS

Levodopa/Carbidopa Intestinal Gel May Help Treat Freezing of Gait After DBS
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An infusion of levodopa/carbidopa to the intestines may be a therapeutic option for Parkinson’s disease patients who develop freezing of gait following deep brain stimulation, according to a recent study.

The study, “Intestinal Levodopa/Carbidopa Infusion as a Therapeutic Option for Unresponsive Freezing of Gait after Deep Brain Stimulation in Parkinson’s Disease,” was published in the journal Parkinson’s Disease.

Freezing of gait (FOG) is a relatively common gait problem in Parkinson’s. It is defined as short episodes where the patient is unable to start or continue walking forward. Although it is related to the duration and severity of Parkinson’s, its root cause remains unclear.

Treating freezing of gait presents a challenge. Although diverse therapeutic strategies have been met with varying success, there is currently no best treatment for this symptom. Treatments tried include modification of levodopa dosage, addition of apomorphine and various other medications, and non-pharmacological interventions such as electroconvulsive therapy and deep brain stimulation.

While deep brain stimulation (DBS) — a surgical procedure that involves implanting a device to stimulate targeted regions of the brain with electrical impulses — has demonstrated some success in treating freezing of gait in some Parkinson’s patients, it can aggravate or even cause it in others.

A limited number of studies and case reports have suggested that a levodopa/carbidopa intestinal gel (LCIG) infusion might prove useful in treating FOG resistant to conventional oral therapies.

This spurred researchers at the Bellvitge Biomedical Research Institute in Barcelona, Spain, to further evaluate LCIG in unresponsive freezing of gait following deep brain stimulation. FOG is considered “unresponsive” when it is present in both “off” and “on” states and does not respond to medication. Off periods in Parkinson’s are when the effects of a medication wear off before a new dose can be taken; in contrast, on periods are those in which the medication is exerting its effects.

In a retrospective study, the group found 48 patient records involving the treatment of Parkinson’s with deep brain stimulation, of which five cases involved unresponsive FOG and treatment with LCIG. These five patients were women, 57 to 69 years old, with no previous medical history of FOG. None of them had a history of cognitive impairment, and their episodes of FOG appeared unrelated to any surgical complications.

The five patients received LCIG — via surgical insertion of a soft plastic tube through the skin into the small intestine — as an alternative advanced therapy. In all cases, deep brain stimulation was switched off at least 24 hours prior to LCIG to better assess patients’ responses to the intestinal infusion.

Four patients showed clear improvement, as measured by an increase of two or more points on the “freezing” section (item 14) of the Unified Parkinson’s Disease Rating Scale (UPDRS) during an on state, measured at one month after treatment. This improvement remained stable for at least 12 months following treatment. For reference, the UPDRS measures both motor and non-motor symptoms associated with Parkinson’s.

The fifth patient did not experience a lessening of FOG symptoms. The LCIG treatment was stopped, and that patient was placed back on deep brain stimulation treatment.

These results add to a small but growing body of research on the benefits of LCIG in the treatment of freezing of gait. A 2015 study showed a benefit in LCIG treatment among five other patients. A longitudinal study found positive results in another 15 patients, and yet another study found evidence of the benefit of dual LCIG and deep brain stimulation treatment in a group of 19 patients.

Definitive conclusions remain difficult to draw from the current study, owing to its small size, retrospective nature, relatively short follow-up period, and the fact that only one item of the UPDRS was measured.

Nonetheless, the improvement seen in four of the five patients is still notable, according to the researchers. Combined with evidence from past studies, these results point toward the need for larger future studies on this treatment strategy, which might be “a valuable therapeutic option for unresponsive-FOG after [DBS],” they concluded.

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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