Subthalamic deep brain stimulation for Parkinson's disease outcome [Neurosurgery Wiki]

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====== Subthalamic deep brain stimulation for Parkinson's disease outcome ======

Numerous studies have investigated the outcomes of subthalamic deep brain stimulation patients, and overall, the results have been positive. Some of the key outcomes that have been observed include:

Improved motor function: Subthalamic DBS has been shown to improve motor symptoms such as tremors, rigidity, and bradykinesia (slowness of movement).

Reduced medication requirements: Many patients who undergo subthalamic DBS are able to reduce or eliminate their medication use, which can reduce the risk of medication-related side effects.

Improved quality of life: Patients who receive subthalamic DBS often report improvements in their quality of life, including better mood, greater independence, and improved ability to perform daily activities.

Long-term efficacy: Studies have demonstrated that the beneficial effects of subthalamic DBS can last for several years, with many patients experiencing sustained improvements in motor function and quality of life.

However, subthalamic DBS is not without risks, and potential complications include infection, bleeding, and device malfunction. Patients must also be carefully selected for the procedure based on a thorough evaluation of their medical history, PD symptoms, and other factors.

Overall, subthalamic DBS can be an effective treatment option for carefully selected PD patients who are experiencing significant motor symptoms and have not responded well to medication alone.
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Chen et al. found that the initial outcome of [[subthalamic deep brain stimulation]] was associated with functional/structural connectivities between the volume of tissue activated and multiple [[brain]] [[region]]s, including the [[supplementary motor area]], [[precentral]] and [[frontal]] areas, [[cingulum]], [[temporal cortex]], and [[striatum]]. These factors could be used to predict the initial [[outcome]], with an r-value of 0.4978 (P = 0.0255). The study demonstrates a correlation between a specific [[connectivity]] pattern and the initial outcome of STN-DBS, which could be used to predict the initial outcome of DBS
((Chen Y, Zhu G, Liu D, Liu Y, Zhang X, Du T, Zhang J. Seed-Based Connectivity Prediction of Initial Outcome of Subthalamic Nuclei Deep Brain Stimulation. Neurotherapeutics. 2022 Mar 23. doi: 10.1007/s13311-022-01208-9. Epub ahead of print. PMID: 35322352.)).
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The surgical and clinical outcomes of asleep [[DBS]] for [[Parkinson's disease]] are comparable to those of awake DBS
((Wang J, Ponce FA, Tao J, Yu HM, Liu JY, Wang YJ, Luan GM, Ou SW. Comparison of
Awake and Asleep Deep Brain Stimulation for Parkinson's Disease: A Detailed
Analysis Through Literature Review. Neuromodulation. 2019 Dec 12. doi:
10.1111/ner.13061. [Epub ahead of print] Review. PubMed PMID: 31830772.
)).
----
{{ ::subthalamic_deep_brain_stimulation_for_parkinson_s_disease.jpg?200|}}


Suboptimal [[target]]ing within the [[STN]] can give rise to intolerable sensorimotor side effects, such as [[dysarthria]], contractions and paresthesias
((Benabid AL, Chabardes S, Mitrofanis J, Pollak P: Deep brain
stimulation of the subthalamic nucleus for the treatment of
Parkinson’s disease. Lancet Neurol 8:67–81, 2009))
((Groiss SJ, Wojtecki L, Südmeyer M, Schnitzler A: Deep
brain stimulation in Parkinson’s disease. Ther Adv Neurol
Disorder 2:20–28, 2009))
((Zhang S, Zhou P, Jiang S, Wang W, Li P: Interleaving subthalamic
nucleus deep brain stimulation to avoid side effects
while achieving satisfactory motor benefits in Parkinson's disease:
a report of 12 cases. Medicine (Baltimore) 95:e5575,
2016)).
eye movement perturbations, and psychiatric symptoms
((Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Parés P: Mania following deep brain stimulation for Parkinson’s disease. Neurology 59:1421–1424, 2002))
((Mallet L, Schüpbach M, N’Diaye K, Remy P, Bardinet E,
Czernecki V, et al: Stimulation of subterritories of the subthalamic
nucleus reveals its role in the integration of the
emotional and motor aspects of behavior. Proc Natl Acad
Sci U S A 104:10661–10666, 2007))
((Raucher-Chéné D, Charrel CL, de Maindreville AD, Limosin
F: Manic episode with psychotic symptoms in a patient with
Parkinson’s disease treated by subthalamic nucleus stimulation:
improvement on switching the target. J Neurol Sci
273:116–117, 2008)),
limiting the management of motor symptoms.
The small size of the STN motor territory and the consequences of spreading current to immediately adjacent
structures obligate precise targeting. Neurosurgeons therefore rely on a combination of imaging, electrophysiology, kinesthetic responses, and stimulation testing to accurately place the DBS lead into the sensorimotor domain of STN
((Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting
D, Connolly PJ, et al: An international survey of deep brain
stimulation procedural steps. Stereotact Funct Neurosurg
91:1–11, 2013))
((Benabid AL, Chabardes S, Mitrofanis J, Pollak P: Deep brain
stimulation of the subthalamic nucleus for the treatment of
Parkinson’s disease. Lancet Neurol 8:67–81, 2009))
((Groiss SJ, Wojtecki L, Südmeyer M, Schnitzler A: Deep
brain stimulation in Parkinson’s disease. Ther Adv Neurol
Disorder 2:20–28, 2009)).

[[Deep Brain Stimulation]] has been associated with post-operative neuropsychology changes, especially in [[verbal memory]].

[[Deep brain stimulation]] (DBS) of [[subthalamic nucleus]] (STN) is widely accepted to treat advanced [[Parkinson's disease]] (PD). However, published studies were mainly conducted in Western centers
((Chiou SM, Lin YC, Huang HM. One-year Outcome of Bilateral Subthalamic Stimulation in Parkinson's disease: An Eastern Experience. World Neurosurg. 2015 Jun 10. pii: S1878-8750(15)00709-3. doi: 0.1016/j.wneu.2015.06.002. [Epub ahead of print] PubMed PMID: 26072454.)).


High frequency [[subthalamic nucleus]] (STN) [[deep brain stimulation]] (DBS) improves the cardinal motor signs of [[Parkinson's disease]] (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony.

Low-frequency stimulation of the subthalamic nucleus via the optimal contacts is effective in improving overall [[motor function]] of patients with [[Parkinson's disease]]
((Khoo HM, Kishima H, Hosomi K, Maruo T, Tani N, Oshino S, Shimokawa T, Yokoe M,
Mochizuki H, Saitoh Y, Yoshimine T. Low-frequency subthalamic nucleus stimulation
in Parkinson's disease: A randomized clinical trial. Mov Disord. 2014 Jan 21.
doi: 10.1002/mds.25810. [Epub ahead of print] PubMed PMID: 24449169.)).
In [[Parkinson's disease]] significantly improved important aspects of [[QoL]] as measured by [[PDQ-39]]. The improvements were maintained at 2 years follow-up except for social support and communication. 
Sobstyl et al., demonstrated a positive correlation between changes in the off condition of motor [[UPDRS]] scores and [[Unified Dyskinesia Rating Scale]] in several PDQ-39 dimensions, whereas fluctuation UPDRS scores were negatively correlated with PDQ-39 mobility scores
((Sobstyl M, Ząbek M, Górecki W, Mossakowski Z. Quality of life in advanced
Parkinson's disease after bilateral subthalamic stimulation: 2 years follow-up
study. Clin Neurol Neurosurg. 2014 Sep;124:161-5. doi:
10.1016/j.clineuro.2014.06.019. Epub 2014 Jun 23. PubMed PMID: 25051167.)).

The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. 

A study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes
((Cui Z, Pan L, Song H, Xu X, Xu B, Yu X, Ling Z. Intraoperative MRI for
optimizing electrode placement for deep brain stimulation of the subthalamic
nucleus in Parkinson's disease. J Neurosurg. 2016 Jan;124(1):62-9. doi:
10.3171/2015.1.JNS141534. Epub 2015 Aug 14. PubMed PMID: 26274983.)).

===== Non-motor symptoms =====

In 82 postural instability and gait difficulty (PIGD) and 33 tremor-dominant patients included in a study, baseline Non-Motor Symptom Scale (NMSS) total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores.

This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS
((Jost ST, Konitsioti A, Loehrer PA, Ashkan K, Rizos A, Sauerbier A, Dos Santos Ghilardi MG, Rosenkranz F, Strobel L, Gronostay A, Barbe MT, Evans J, Visser-Vandewalle V, Nimsky C, Fink GR, Silverdale M, Cury RG, Fonoff ET, Antonini A, Chaudhuri KR, Timmermann L, Martinez-Martin P, Dafsari HS; EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group. Non-motor effects of deep brain stimulation in Parkinson's disease motor subtypes. Parkinsonism Relat Disord. 2023 Feb 9:105318. doi: 10.1016/j.parkreldis.2023.105318. Epub ahead of print. PMID: 36842866.)).
----

The bilateral effects of [[deep brain stimulation]] (DBS) on [[motor]] and non-motor symptoms of [[Parkinson's disease]] (PD) have been extensively studied and reviewed. However, the unilateral effects-in particular, the potential lateralized effects of left- versus right-sided DBS-have not been adequately recognized or studied. 

Lin et al. summarized the current [[evidence]] and controversies in the [[literature]] regarding the lateralized effects of DBS on motor and non-motor outcomes in PD patients. [[Publication]]s in the English language before February 2021 were obtained from the [[PubMed]] database and included if they directly compared the effects of unilateral versus contralateral side DBS on the motor or non-motor outcomes in PD. The current literature is overall of low-quality and is biased by various confounders. Researchers have investigated mainly PD patients receiving [[subthalamic nucleus]] (STN) DBS while the potential lateralized effects of [[globus pallidus internus]] ([[GPi]]) DBS have not been adequately studied. Evidence suggests potential lateralized effects of STN DBS on axial motor symptoms and deleterious effects of left-sided DBS on language-related functions, in particular, the [[verbal fluency]], in PD. The lateralized DBS effects on appendicular motor symptoms as well as other neurocognitive and neuropsychiatric domains remain inconclusive. Future studies should control for varying methodological approaches as well as clinical and DBS management heterogeneities, including symptom laterality, stimulation parameters, location of active contacts, and lead trajectories. This would contribute to improved treatment strategies such as personalized target selection, [[surgical planning]], and postoperative management that ultimately benefit patients
((Lin Z, Zhang C, Li D, Sun B. Lateralized effects of deep brain stimulation in Parkinson's disease: evidence and controversies. NPJ Parkinsons Dis. 2021 Jul 22;7(1):64. doi: 10.1038/s41531-021-00209-3. PMID: 34294724.)).

===== Biomarkers =====

The ability of [[serum biomarker]]s to predict the [[prognosis]] and response to [[deep brain stimulation]] (DBS) therapy in [[Parkinson's disease]] (PD) patients is promising. 
Sanmartino et al. showed that [[NfL]] differed between healthy individuals and PD patients and that changes in NfL, [[GFAP]], and [[BDNF]] occurred only transiently after DBS surgery. Therefore, [[subthalamic deep brain stimulation]] does not promote [[neurodegeneration]], and these biomarkers do not serve as clinical improvement endpoints in PD DBS patients
((Sanmartino F, Cano-Cano F, Rashid-López R, Cruz-Gómez ÁJ, Lozano-Soto E, Macías-García P, Sánchez-Fernández FL, López-Sosa F, Gómez-Jaramillo L, Riqué-Dormido J, Escamilla-Sevilla F, Espinosa-Rosso R, González-Rosa JJ. Significance of neurodegeneration and neuroplasticity serum biomarkers in Parkinson's disease patients treated with subthalamic stimulation. NPJ Parkinsons Dis. 2024 Oct 24;10(1):197. doi: 10.1038/s41531-024-00808-w. PMID: 39448624.))

===== References =====