Asleep subthalamic deep brain stimulation for Parkinson’s disease

Asleep subthalamic deep brain stimulation for Parkinson’s disease

Deep brain stimulation (DBS) implantation under general anesthesia (GA) is of great importance for patients with disabling off-medication symptoms or medical comorbidities. However, the relative advantages/disadvantages of routine local anesthesia (LA) surgery versus GA regarding clinical outcomes are controversial, and the safety of DBS implantation under GA is debatable.

Meta-Analysis

Liu et al. systematically reviewed the literature to compare the efficacy and safety of awake and asleep deep brain stimulation surgery. They identified cohort studies from the Cochrane libraryMEDLINE, and EMBASE (January 1970 to August 2019) by using Review Manager 5.3 software to conduct a meta-analysis following the PRISMA guidelines. Fourteen cohort studies involving 1,523 patients were included. The meta-analysis results showed that there were no significant differences between the GA and LA groups in UPDRSIII score improvement (standard mean difference [SMD] 0.06; 95% CI -0.16 to 0.28; p = 0.60), postoperative LEDD requirement (SMD -0.17; 95% CI -0.44 to 0.12; p = 0.23), or operation time (SMD 0.18; 95% CI -0.31 to 0.67; p = 0.47). Additionally, there was no significant difference in the incidence of adverse events (OR 0.98; 95% CI 0.53-1.80; p = 0.94), including postoperative speech disturbance and intracranial hemorrhage. However, the volume of intracranial air was significantly lower in the GA group than that in the LA group. In a subgroup analysis, there was no significant difference in clinical efficacy between the microelectrode recording (MER) and non-MER groups. We demonstrated equivalent clinical outcomes of DBS surgery between GA and LA in terms of improvement of symptoms and the incidence of adverse events. Key Messages: MER might not be necessary for DBS implantation. For patients who cannot tolerate DBS surgery while being awake, GA should be an appropriate alternative 1).

Case series

The objective of a study of Senemmar et al. was to investigate whether asleep deep brain stimulation surgery of the subthalamic nucleus (STN) improves therapeutic window (TW) for both directional (dDBS) and omnidirectional (oDBS) stimulation in a large single-center population.

A total of 104 consecutive patients with Parkinson’s disease (PD) undergoing STN-DBS surgery (80 asleep and 24 awake) were compared regarding TW, therapeutic thresholdside effect threshold, improvement of Unified PD Rating Scale motor score (UPDRS-III) and degree of levodopa equivalent daily dose (LEDD) reduction.

Asleep DBS surgery led to significantly wider TW compared to awake surgery for both dDBS and oDBS. However, dDBS further increased TW compared to oDBS in the asleep group only and not in the awake group. Clinical efficacy in terms of UPDRS-III improvement and LEDD reduction did not differ between groups.

The study provides first evidence for improvement of therapeutic window by asleep surgery compared to awake surgery, which can be strengthened further by dDBS. These results support the notion of preferring asleep over awake surgery but needs to be confirmed by prospective trial2).


Clinical outcome studies have shown that “asleep” DBS lead placement, performed using intraoperative imaging with stereotactic accuracy as the surgical endpoint, has motor outcomes comparable to traditional “awake” DBS using microelectrode recording (MER), but with shorter case times and improved speech fluency 3).


Ninety-six patients were retrospectively matched pairwise (48 asleep and 48 awake) and compared regarding improvement of Unified PD Rating Scale Motor Score (UPDRS-III), cognitive function, Levodopa-equivalent-daily-dose (LEDD), stimulation amplitudes, side effects, surgery duration, and complication rates. Routine testing took place at three months and one year postoperatively.

Results: Chronic DBS effects (UPDRS-III without medication and with stimulation on [OFF/ON]) significantly improved UPDRS-III only after awake surgery at three months and in both groups one year postoperatively. Acute effects (percentage UPDRS-III reduction after activation of stimulation) were also significantly better after awake surgery at three months but not at one year compared to asleep surgery. UPDRS-III subitems “freezing” and “speech” were significantly worse after asleep surgery at three months and one year, respectively. LEDD was significantly lower after awake surgery only one week postoperatively. The other measures did not differ between groups.

Overall motor function improved faster in the awake surgery group, but the difference ceased after one year. However, axial subitems were worse in the asleep surgery group suggesting that worsening of axial symptoms was risked improving overall motor function. Awake surgery still seems advantageous for STN-DBS in PD, although asleep surgery may be considered with lower threshold in patients not suitable for awake surgery 4).

References

1)

Liu Z, He S, Li L. General Anesthesia versus Local Anesthesia for Deep Brain Stimulation in Parkinson’s Disease: A Meta-Analysis. Stereotact Funct Neurosurg. 2019;97(5-6):381-390. doi:10.1159/000505079
2)

Senemmar F, Hartmann CJ, Slotty PJ, Vesper J, Schnitzler A, Groiss SJ. Asleep Surgery May Improve the Therapeutic Window for Deep Brain Stimulation of the Subthalamic Nucleus [published online ahead of print, 2020 Jul 13]. Neuromodulation. 2020;10.1111/ner.13237. doi:10.1111/ner.13237
3)

Mirzadeh Z, Chen T, Chapple KM, Lambert M, Karis JP, Dhall R, Ponce FA. Procedural Variables Influencing Stereotactic Accuracy and Efficiency in Deep Brain Stimulation Surgery. Oper Neurosurg (Hagerstown). 2018 Oct 18. doi: 10.1093/ons/opy291. [Epub ahead of print] PubMed PMID: 30339204.
4)

Blasberg F, Wojtecki L, Elben S, Slotty PJ, Vesper J, Schnitzler A, Groiss SJ. Comparison of Awake vs. Asleep Surgery for Subthalamic Deep Brain Stimulation in Parkinson’s Disease. Neuromodulation. 2018 Aug;21(6):541-547. doi: 10.1111/ner.12766. Epub 2018 Mar 13. PubMed PMID: 29532

Transcranial direct current stimulation for progressive supranuclear palsy

Transcranial direct current stimulation for progressive supranuclear palsy

Case series

Alexoudi et al. conducted a pilot study in order to evaluate the effect of transcranial direct current stimulation over the motor cortex and premotor cortex in patients with progressive supranuclear palsy, with a particular emphasis on cognitive dysfunction. Eight patients affected by PSP were included (4 males and 4 females with mean age 67.4±7.4 years, range: 55-80 years and mean disease duration: 4.6±3.3 years, range: 1-11 years). The mean Unified Parkinson’s Disease Rating Scale Part III (UPDRS III) was 49±16.1 and the mean Hoehn & Yahr (H&Y) scale was 3.9±1 at baseline. All pharmacological treatments (L-dopa, pramipexole, rotigotine, rasagiline, amantadine) were maintained stable during the study. They aimed at evaluating along with the motor outcome (as it is reflected on a disease-specific rating scale), the post-tDCS cognitive status after the completion of the intervention. The clinical evaluation involved the PSP-Rating Scale, the UPDRS III, and the Timed Up and Go test. The neuropsychological assessment focused on auditory-verbal memory and learning, episodic memory, visuomotor coordination and speed of information processing, executive functions and verbal fluency (phonemic and semantic). Anodal tDCS was applied over primary motor and pre-motor cortices in 10 daily sessions. During the tDCS stimulation, a constant current of 2 mA was delivered for 30 minutes. Clinical evaluations were performed at baseline, day 11, day 30 and at day 90. The PSP-Rating score (total and sections I & III) improved significantly on day 11 compared to baseline and similarly on day 30. A positive effect was also seen in action tremor. In addition to the global mental status improvement, patients showed increases in neuropsychological performance in the domains of visuomotor coordination and processing speed, auditory-verbal learning, episodic memory, phonological and semantic fluency (access and retrieval from lexical memory, selective inhibition, and lexical access speed). The results suggest that tDCS has a beneficial effect on Progressive Supranuclear Palsy patients’ bulbar and motor symptoms, cognitive dysfunction, as well as daily activities, which lasts beyond the duration of the treatment 1).


sham-controlled double-blind crossover design to assess the efficiency of tDCS over the DLPFC in a cohort of 12 patients with PSP. In 3 separate sessions, we evaluated the ability to boost the left DLPFC via left-anodal (excitatory) and right-cathodal (inhibitory) tDCS, while comparing them to sham tDCS. Tasks assessing lexical access (letter fluency task) and semantic access (category judgment task) were applied immediately before and after the tDCS sessions to provide a marker of potential language modulation.

The comparison with healthy controls showed that patients with PSP were impaired on both tasks at baseline. Contrasting poststimulation vs prestimulation performance across tDCS conditions revealed language improvement in the category judgment task following right-cathodal tDCS, and in the letter fluency task following left-anodal tDCS. A computational finite element model of current distribution corroborated the intended effect of left-anodal and right-cathodal tDCS on the targeted DLPFC.

The results demonstrate tDCS-driven language improvement in PSP. They provide proof-of-concept for the use of tDCS in PSP and set the stage for future multiday stimulation regimens, which might lead to longer-lasting therapeutic effects promoted by neuroplasticity.

This study provides Class III evidence that for patients with PSP, tDCS over the DLPFC improves performance in some language tasks 2).

Case reports

Madden et al. report the case of KN, who presented with reduced verbal fluency and connected speech production in the context of PSP. KN completed a set of language tasks, followed by an alternate version of the tasks in conjunction with either sham or active tDCS over the left dorsolateral prefrontal cortex (DLPFC) across four sessions. Results showed improved performance with active stimulation compared to sham stimulation for phonemic fluency and action naming, as well as mixed results suggesting possible benefits for connected speech production. There were no benefits of active stimulation for control tasks, indicating that tDCS can produce specific benefits for phonemic fluency, action naming, and connected speech production in PSP. These promising, preliminary findings warrant further investigation into whether these benefits of tDCS can be a useful therapeutic tool for PSP patients to maintain language 3).

References

1)

Alexoudi A, Patrikelis P, Deftereos S, Fasilis T, Karakalos D, Verentzioti A, Korfias S, Sakas D, Gatzonis S. Effects of anodal transcranial direct current stimulation on cognitive dysfunction in patients with progressive supranuclear palsy. Psychiatriki. 2019 Oct-Dec;30(4):320-328. doi: 10.22365/jpsych.2019.304.320. PubMed PMID: 32283535.
2)

Valero-Cabré A, Sanches C, Godard J, Fracchia O, Dubois B, Levy R, Truong DQ, Bikson M, Teichmann M. Language boosting by transcranial stimulation in progressive supranuclear palsy. Neurology. 2019 Aug 6;93(6):e537-e547. doi: 10.1212/WNL.0000000000007893. Epub 2019 Jul 3. PubMed PMID: 31270217; PubMed Central PMCID: PMC6709997.
3)

Madden DL, Sale MV, O’Sullivan J, Robinson GA. Improved language production with transcranial direct current stimulation in progressive supranuclear palsy. Neuropsychologia. 2019 Apr;127:148-157. doi: 10.1016/j.neuropsychologia.2019.02.022. Epub 2019 Mar 2. PubMed PMID: 30836131.
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Zona incerta stimulation

Zona incerta stimulation

Surgical targets for Tourette’s syndrome have included the frontal lobes, the cingulate gyrus, the anterior limb of the internal capsule (ALIC), the limbic system, and the subthalamic zona incerta1) Current targets of interest for DBS include: GPiSTN, ALIC, and thalamus. Early results have been promising. 2).

Posterior subthalamic deep brain stimulation (DBS) targeting the zona incerta (ZI) is an emerging treatment for tremor syndromes, including Parkinson’s disease (PD) and essential tremor (ET).

Evidence from animal studies has indicated that the ZI may play a role in saccadic eye movements via pathways between the ZI and superior colliculus (incerto collicular pathways).


Optics can be used for guidance in deep brain stimulation (DBS) surgery. The aim of Zsigmond and Wårdell was to use laser Doppler flowmetry (LDF) to investigate the intraoperative optical trajectory along the ventral intermediate nucleus (VIM) and zona incerta (Zi) regions in patients with essential tremor during asleep DBS surgery, and whether the Zi region could be identified.

A forward-looking LDF guide was used for the creation of the trajectory for the DBS lead, and the microcirculation and tissue greyness, i.e., total light intensity (TLI) was measured along 13 trajectories. TLI trajectories and the number of high-perfusion spots were investigated at 0.5-mm resolution in the last 25 mm from the targets.

All implantations were done without complications and with significant improvement of tremor (p < 0.01). Out of 798 measurements, 12 tissue spots showed high blood flow. The blood flow was significantly higher in VIM than in Zi (p < 0.001). The normalized mean TLI curve showed a significant (p < 0.001) lower TLI in the VIM region than in the Zi region.

Zi DBS performed asleep appears to be safe and effective. LDF monitoring provides direct in vivo measurement of the microvascular blood flow in front of the probe, which can help reduce the risk of hemorrhage. LDF can differentiate between the grey matter in the thalamus and the transmission border entering the posterior subthalamic area where the tissue consists of more white matter tract3).


Sixteen patients (12 with PD and 4 with ET) underwent DBS using the MRI-directed implantable guide tube technique. Active electrode positions were confirmed at the caudal ZI. Eye movements were tested using direct current electrooculography (EOG) in the medicated state pre- and postoperatively on a horizontal predictive task subtending 30°. Postoperative assessments consisted of stimulation-off, constituting a microlesion (ML) condition, and high-frequency stimulation (HFS; frequency = 130 Hz) up to 3 V.

With PSA HFS, the first saccade amplitude was significantly reduced by 10.4% (95% CI 8.68%-12.2%) and 12.6% (95% CI 10.0%-15.9%) in the PD and ET groups, respectively. With HFS, peak velocity was reduced by 14.7% (95% CI 11.7%-17.6%) in the PD group and 27.7% (95% CI 23.7%-31.7%) in the ET group. HFS led to PD patients performing 21% (95% CI 16%-26%) and ET patients 31% (95% CI 19%-38%) more saccadic steps to reach the target.

PSA DBS in patients with PD and ET leads to hypometric, slowed saccades with an increase in the number of steps taken to reach the target. These effects contrast with the saccadometric findings observed with subthalamic nucleus DBS. Given the location of the active contacts, incerto-collicular pathways are likely responsible. Whether the acute finding of saccadic impairment persists with chronic PSA stimulation is unknown 4).

References

1)

Temel Y, Visser-Vandewalle V. Surgery in Tourette syndrome. Mov Disord. 2004; 19:3–14
2)

Martinez-Fernandez R, Zrinzo L, Aviles-Olmos I, et al. Deep brain stimulation for Gilles de la Tourette syndrome: a case series targeting subre- gions of the globus pallidus internus. Mov Disord. 2011; 26:1922–1930
3)

Zsigmond P, Wårdell K. Optical Measurements during Asleep Deep Brain Stimulation Surgery along Vim-Zi Trajectories. Stereotact Funct Neurosurg. 2020 Feb 20:1-7. doi: 10.1159/000505708. [Epub ahead of print] PubMed PMID: 32079023.
4)

Bangash OK, Dissanayake AS, Knight S, Murray J, Thorburn M, Thani N, Bala A, Stell R, Lind CRP. Modulation of saccades in humans by electrical stimulation of the posterior subthalamic area. J Neurosurg. 2019 Mar 15:1-9. doi: 10.3171/2018.12.JNS18502. [Epub ahead of print] PubMed PMID: 30875687.
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