Objective: To report the impact of globus pallidus internus (GPi) Deep Brain Stimulation (DBS) on cognition and neuropsychiatric symptoms in a severe glucocerebrosidase (GBA1) mutation carrier.

Background: Multiple studies have shown GBA1-associated Parkinson’s disease (PD) patients have prominent early cognitive changes with higher risk of dementia and neuropsychiatric symptoms compared to idiopathic PD. Recent data also suggest that subthalamic nucleus (STN) DBS might have a negative impact on cognition in GBA1 carriers.

Method: We describe a 64-year-old female with a classic motor presentation of PD with OFF-anxiety and mild cognitive impairment who underwent bilateral GPi DBS to address severe motor fluctuations with dyskinesias and left foot dystonia.

Results: The post-op period was complicated by prolonged delirium for 2 weeks and new-onset of hallucinations, delusions, and panic attacks. CT Brain taken 2 weeks post-DBS showed no acute intracranial abnormalities or hemorrhage. She was treated with Sertraline, Alprazolam prn, and Temazepam. This helped her with panic attacks but she continued to have progressive psychosis and workup was negative (infectious workup, prolonged EEG, paraneoplastic and autoimmune encephalopathy panels negative). Over the next 9 months, she required titration of Rivastigmine, Quetiapine, Pimavanserin, Gabapentin, and Clozapine but symptoms worsened and she had progressive visual and auditory hallucinations, delusional jealousy, Capgras syndrome, and paranoia. Motorically, she responded well to stimulation and motor fluctuations, dyskinesias, dystonia have resolved with GPi stimulation. Pre-operative Montreal Cognitive Assessment (MoCA) scores fell from 25 to 18 five months post-operatively. There were severe impairments across constructional abilities, memory, attention, language, and executive function. CT Brain 1-year post-DBS showed progressive global brain atrophy. Genetic testing, 1.5 years following DBS implantation, was performed in the context of progressive psychosis and cognitive decline which found a heterozygous severe variant in GBA1 (p.Leu483pro, L444P).

Conclusion: This case report contributes to the growing body of evidence of impact of DBS in GBA1 mutation carriers and highlights the importance of genetic testing, counseling and comprehensive neuropsychological assessment in pre-surgical decision-making.

References: [1] Mangone G, Bekadar S, Cormier-Dequaire F, Tahiri K, Welaratne A, Czernecki V, Pineau F, Karachi C, Castrioto A, Durif F, Tranchant C, Devos D, Thobois S, Meissner WG, Navarro MS, Cornu P, Lesage S, Brice A, Welter ML, Corvol JC; contributors/investigators. Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson’s disease patients with GBA mutations. Parkinsonism Relat Disord. 2020 Jul;76:56-62.

[2] Pal, G., Mangone, G., Hill, E.J., Ouyang, B., Liu, Y., Lythe, V., Ehrlich, D., Saunders-Pullman, R., Shanker, V., Bressman, S., Alcalay, R.N., Garcia, P., Marder, K.S., Aasly, J., Mouradian, M.M., Link, S., Rosenbaum, M., Anderson, S., Bernard, B., Wilson, R., Stebbins, G., Nichols, W.C., Welter, M.-L., Sani, S., Afshari, M., Verhagen, L., de Bie, R.M.A., Foltynie, T., Hall, D., Corvol, J.-C. and Goetz, C.G. (2022), Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers. Ann Neurol, 91: 424-435

[3] Lythe, Vanessa et al. ‘GBA-Associated Parkinson’s Disease: Progression in a Deep Brain Stimulation Cohort’. 1 Jan. 2017 : 635 – 644.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rapid-cognitive-decline-and-new-onset-psychosis-after-gpi-dbs-in-a-severe-gba-mutation-carrier-a-case-demonstrating-the-importance-of-genetic-screening-pre-dbs/