What was first and what is next in selecting device-aided therapy in Parkinson’s disease? Balancing evidence and experience

Phokaewvarangkul, Onanong; Auffret, Manon; Groppa, Sergiu; Markovic, Vladana; Petrovic, Igor; Bhidayasiri, Roongroj

doi:10.1007/s00702-024-02782-2

Cited by 2 publications

(2 citation statements)

References 68 publications

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“…Studies have reported that DBS treatment for patients with PD with neuropsychiatric disorders, including depression, anxiety, and ICD, might further worsen their cognitive performance. Hence, patients with severe pre-existing neuropsychiatric disorders should be given DBS with caution [ 83 ]. However, despite all the diverse results, it would be interesting to explore the effect of DBS treatment on motor and cognitive symptoms simultaneously.…”

Section: Discussionmentioning

confidence: 99%

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A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

Nair,

Chakravarthy

2024

Brain Sciences

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Parkinson’s disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents.

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Section: Discussionmentioning

confidence: 99%

“…It was reported that post-DBS surgery, patients often face gait and balance issues [ 92 ]. DBS is not recommended for patients with balance problems since DBS exacerbates the gait and balance issues in patients with PD [ 83 ]. This gives an incentive to explore DBS options in combination with rehabilitation.…”

Section: Discussionmentioning

confidence: 99%

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

Nair,

Chakravarthy

2024

Brain Sciences

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Use of the MNCD Classification to Monitor Clinical Stage and Response to Levodopa-Entacapone-Carbidopa Intestinal Gel Infusion in Advanced Parkinson’s Disease

Santos-García,

López-Manzanares,

Muro

et al. 2024

Brain Sciences

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Background and objective: Staging Parkinson’s disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients’ quality of life and caregivers’ strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT). Patients and Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study). The MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) were collected by the neurologist at V0 (before starting LECIG) and V2 (follow-up visit). Wilcoxon’s signed rank and Marginal Homogeneity tests were applied to compare changes from V0 to V2. Results: Sixty-seven PD patients (58.2% males; 69.9 ± 9.3 years old) with a mean disease duration of 14.4 ± 6.5 years were included. The mean treatment duration (V2) was 172.9 ± 105.2 days. At V0, patients were classified as in stage 2 (35.8%), 3 (46.3%) or 4 (17.9%). The frequency of patients in stage 4 decreased to 9% at V2 (p = 0.001). The MNCD total score decreased from 6.27 ± 1.94 at V0 to 5.21 ± 2.23 (p < 0.0001). From V0 to V2, the motor (M; p < 0.0001) and non-motor symptom (N; p < 0.0001) burden decreased, and autonomy for the activities of daily living (D; p = 0.005) improved. Conclusions: The MNCD classification could be useful to classify advanced PD patients and to monitor the response to a DAT.

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What was first and what is next in selecting device-aided therapy in Parkinson’s disease? Balancing evidence and experience

Cited by 2 publications

References 68 publications

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor and Bradykinesia

Use of the MNCD Classification to Monitor Clinical Stage and Response to Levodopa-Entacapone-Carbidopa Intestinal Gel Infusion in Advanced Parkinson’s Disease

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