BACKGROUND: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. OBJECTIVE: To explore the long-term phenotypic progression of GBA-associated PD, in a DBS cohort. METHODS: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to 17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson's Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. RESULTS: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA-associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. CONCLUSIONS: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery.
BACKGROUND: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. OBJECTIVE: To explore the long-term phenotypic progression of GBA-associated PD, in a DBS cohort. METHODS: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to 17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson's Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. RESULTS: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA-associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. CONCLUSIONS: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery.
Entities:
Keywords:
Deep brain stimulation; Parkinson’s disease; glucosidase beta acid; phenotype
Authors: Gian Pal; Graziella Mangone; Emily J Hill; Bichun Ouyang; Yuanqing Liu; Vanessa Lythe; Debra Ehrlich; Rachel Saunders-Pullman; Vicki Shanker; Susan Bressman; Roy N Alcalay; Priscilla Garcia; Karen S Marder; Jan Aasly; M Maral Mouradian; Samantha Link; Marc Rosenbaum; Sharlet Anderson; Bryan Bernard; Robert Wilson; Glenn Stebbins; William C Nichols; Marie-Laure Welter; Sepehr Sani; Mitra Afshari; Leo Verhagen; Rob M A de Bie; Tom Foltynie; Deborah Hall; Jean-Christophe Corvol; Christopher G Goetz Journal: Ann Neurol Date: 2022-01-25 Impact factor: 11.274
Authors: Carlo Alberto Artusi; Alok K Dwivedi; Alberto Romagnolo; Gian Pal; Marcelo Kauffman; Ignacio Mata; Dhiren Patel; Joaquin A Vizcarra; Andrew Duker; Luca Marsili; Binith Cheeran; Daniel Woo; Maria Fiorella Contarino; Leonard Verhagen; Leonardo Lopiano; Alberto J Espay; Alfonso Fasano; Aristide Merola Journal: JAMA Netw Open Date: 2019-02-01