Anterior Thalamic Stimulation

Anterior Thalamic Stimulation

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is a novel and promising treatment method for patients with drug-resistant epilepsy.

More than 70% of patients implanted with ANT-DBS benefit significantly from this method, i.e., they report seizure-reduction rates higher than 50%

The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001).

Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population.

Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years. 1).

When focusing on the adverse events reported in a study of stimulation of the anterior nuclei of thalamus (SANTE study), the patients reported paresthesia (18% patients), pain in the implant side (10.9% patients), and infection at the implant site (9.1% patients) 2)

Sobstyl et al. performed a literature search regarding the clinical efficacy of ANT DBS. They discussed the surgical technique of the implantation of DBS electrodes with special attention paid to the targeting methods of the ANT. Moreover, they present in detail the clinical efficacy of ANT DBS, with a special emphasis on the stimulation parameters, a stimulation mode, and polarity. They also report all adverse events and present the current limitations of ANT DBS.

In general, the safety profile of DBS in intractable epilepsy patients is good, with a low rate of surgery, hardware-related, and stimulation-induced adverse events. No significant cognitive declines or worsening of depressive symptoms was noted. At long-term follow-up, the quality-of-life scores have improved. The limitations of ANT DBS studies include a limited number of patients treated and mostly open-label designs with only one double-blind, randomized multicenter trial. Most studies do not report the etiology of intractable epilepsy or they include nonhomogeneous groups of patients affected by intractable epilepsy. There are no guidelines for setting initial stimulation parameters. All the variables mentioned may have a profound impact on the final outcome.

ANT DBS appears to be a safe and efficacious treatment, particularly in patients with refractory partial seizures (three-quarters of patients gained at least 50% seizure reduction after 5 years). ANT DBS reduces most effectively the seizures originating in the temporal and frontal lobes. The published results of ANT DBS highlight promise and hope for patients with intractable epilepsy 3).


A literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients. A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANT-DBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function. Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANT-DBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANT-DBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANT-DBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization. Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy 4).

Bilateral ANT electrodes were implanted into 18 patients suffering from focal, pharmacoresistant epilepsy. Antiepileptic treatment was kept unchanged from three months prior to operation. The Liverpool seizure severity scale (LSSS) was used to measure the burden of epilepsy.

Results: There was no significant difference between the 2 groups at the end of the blinded period at 6 months. However, when considering all patients and comparing 6 months of stimulation with baseline, there was a significant, 22% reduction in the frequency of all seizures (P = 0.009). Four patients had ≥50% reduction in total seizure frequency and 5 patients ≥50% reduction in focal seizures after 6 months of stimulation. No increased effect over time was shown. LSSS at 6 months compared to baseline showed no significant difference between the 2 groups, but a small, significant reduction in LSSS was found when all patients had received stimulation for 6 months.

Conclusions: Our study supports results from earlier studies concerning DBS as a safe treatment option, with effects even in patients with severe, refractory epilepsy. However, our results are not as encouraging as those reported from many other, mainly unblinded, and open studies 5).

A case of relapsing herpes simplex encephalitis (HSE) as a newly reported and potentially fatal stimulation-related adverse effect following stimulation of the anterior thalamic nucleus (ANT-DBS) accompanied by fever, confusion, and cognitive impairment in a 32-year-old epileptic patient with a history of herpes meningoencephalitis 31 years earlier. The T2-weighted/FLAIR high-signal intensity in the temporal lobe developed at a “distance” from the stimulation target. The positive polymerase chain reaction of herpes virus deoxyribonucleic acid in the cerebrospinal fluid confirmed the diagnosis. The condition improved partially on acyclovir and stimulation stopped. Seizures disappeared and then returned after few months. The unique case report presents a rationale for considering history of herpes encephalitis as a relative contraindication for ANT-DBS, and HSE relapse should be suspected in patients with post-stimulation fever and/or altered consciousness 6).


1)

Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Tröster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25. doi: 10.1212/WNL.0000000000001334. Epub 2015 Feb 6. PMID: 25663221; PMCID: PMC4352097.
2)

Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N; SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010 May;51(5):899-908. doi: 10.1111/j.1528-1167.2010.02536.x. Epub 2010 Mar 17. PMID: 20331461.
3)

Sobstyl M, Stapińska-Syniec A, Iwański S, Rylski M. Clinical Efficacy and Safety Profile of Anterior Thalamic Stimulation for Intractable Epilepsy. J Neurol Surg A Cent Eur Neurosurg. 2021 Jun 14. doi: 10.1055/s-0041-1725954. Epub ahead of print. PMID: 34126641.
4)

Bouwens van der Vlis TAM, Schijns OEMG, Schaper FLWVJ, Hoogland G, Kubben P, Wagner L, Rouhl R, Temel Y, Ackermans L. Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy. Neurosurg Rev. 2019 Jun;42(2):287-296. doi: 10.1007/s10143-017-0941-x. Epub 2018 Jan 6. PMID: 29306976; PMCID: PMC6502776.
5)

Herrman H, Egge A, Konglund AE, Ramm-Pettersen J, Dietrichs E, Taubøll E. Anterior thalamic deep brain stimulation in refractory epilepsy: A randomized, double-blinded study. Acta Neurol Scand. 2019 Mar;139(3):294-304. doi: 10.1111/ane.13047. Epub 2018 Dec 11. PMID: 30427061.
6)

Hamdi H, Robin E, Stahl JP, Doche E, Azulay JP, Chabardes S, Bartolomei F, Regis J. Anterior Thalamic Stimulation Induced Relapsing Encephalitis. Stereotact Funct Neurosurg. 2019;97(2):132-136. doi: 10.1159/000499072. Epub 2019 May 3. PMID: 31055582.

Gelatin Sponge

Gelatin Sponge

see Spongostan.

see also Hemostat.


Expanding the range of medical sponges and researching new excipients for their manufacture are a promising area of modern medicine and pharmacy 1).


Gelatin sponge is a non-antigenic protein that can absorb 45 times its weight in blood, and, when wet, is plastered to the irregularities of the bleeding surface. It enables the repair of torn veins, such as the superior sagittal sinus, without compromising the patency of the vessel 2).


Many ablative procedures are effective for hemifacial spasm (HFS) (including sectioning of divisions of the facial nerve), however, this leaves the patient with some degree of facial paresis. The current procedure of choice for HFS is microvascular decompression (MVD) wherein the offending vessel is physically moved off of the nerve, and a sponge (e.g. Ivalon®, polyvinyl formyl alcohol foam) is interposed as a cushion.


For Chang et al. from the Department of Neurosurgery Xinhua Hospital in hemifacial spasm (HFS) patients undergoing microvascular decompression (MVD) , using Teflon plus gelatin sponge can remarkably reduce the incidence of recurrence, facial palsy, and hearing loss compared with those using Teflon alone 3).


A study proves that, during the dural closure, placing a thin layer of gelatin sponge in the subdural space is a safe and effective method for preventing meningocerebral adhesions 4)


1)

Pavliuk B, Chubka M, Hroshovyi T, Stechyshyn I. Characteristics of structured medical hemostatic sponges as a medical devices for stop bleeding and for close the wound. Pol Merkur Lekarski. 2020 Dec 22;48(288):422-426. PMID: 33387430.
2)

Signorelli F, Montano N. Use and Efficacy of Hemostats in Neurosurgery. Surg Technol Int. 2020 Nov 28;37:414-419. PMID: 32944921.
3)

Chang B, Tang Y, Wei X, Li S. A New Application of Gelatin Sponge in the Treatment of Hemifacial Spasm by Microvascular Decompression: A Technical Note. J Neurol Surg A Cent Eur Neurosurg. 2021 May 19. doi: 10.1055/s-0040-1720994. Epub ahead of print. PMID: 34010981.
4)

Gonzalez-Lopez P, Harput MV, Türe H, Atalay B, Türe U. Efficacy of placing a thin layer of gelatin sponge over the subdural space during dural closure in preventing meningo-cerebral adhesion. World Neurosurg. 2015 Jan;83(1):93-101. doi: 10.1016/j.wneu.2014.02.032. Epub 2014 Feb 19. PubMed PMID: 24560706.

Magnetic resonance guided focused ultrasound thalamotomy for essential tremor

Magnetic resonance guided focused ultrasound thalamotomy for essential tremor

Magnetic resonance guided focused ultrasound is a minimally invasive surgical procedure for symptomatic treatment of Parkinson Disease. With this technology, the ventral intermediate nucleusSTN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures.

In a pilot study published in 2013, essential tremor improved in 15 patients treated with magnetic resonance guided focused ultrasound thalamotomy1).

Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown.

It might change the way that patients with essential tremor and potentially other disorders are treated 2).

The post-treatment effectiveness was evaluated using the clinical rating scale for tremors. Thalamic MRgHIFU had substantial therapeutic effects on patients, based on MRgHIFU-mediated improvements in movement control and significant changes in brain mu rhythms. Ultrasonic thalamotomy may reduce hyper-excitable activity in the motor cortex, resulting in normalized behavioral activity after sonication treatment. Thus, non-invasive and spatially accurate MRgHIFU technology can serve as a potent therapeutic tool with broad clinical applications 3).

Magnetic resonance guided focused ultrasound (MRgFUS) for thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory essential tremor (ET). However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment 4).

Jung et al. found different MRI pattern evolution after MRgFUS for white matter and gray matter. Their results suggest that skull characteristics, such as low skull density, should be evaluated prior to MRgFUS to successfully achieve thermal rise 5).

In a large academic medical center in the mid-Atlantic region, the Department of Neurosurgery conducted a continued access study, recently approved by the Food and Drug Administration, to evaluate the effectiveness of transcranial FUS thalamotomy for the treatment of medication-refractory ET.

One patient’s experience will be introduced, including discussion of evidence-based treatment options for ET and information on the nursing management of the patient undergoing FUS thalamotomy 6).

A PubMed search was performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if hand tremor scores (HTS), total Clinical Rating Scale for Tremor (CRST) scores, or Quality of Life in Essential Tremor Questionnaire (QUEST) scores at regular intervals following MRgFUS treatment for essential tremor were documented. Data analyses included a random effects model of meta-analysis and mixed-effects model of meta-regression. Twenty-one articles reporting HTS for 395 patients were included. Mean pre-operative HTS was 19.2 ± 5.0. Mean HTS at 3 months post-treatment was 7.4 ± 5.0 (61.5% improvement, p < 0.001). Treatment effect was mildly decreased at 36 months at 9.1 ± 5.4 (8.8% reduction). Meta-regression of time since treatment as a modifier of HTS revealed a downward trend in effect size, though this was not statistically significant (p = 0.208). Only 4 studies included follow-up ≥ 24 months. Thirteen included articles reported total CRST scores with standardized follow-up for 250 patients. Mean pre-operative total CRST score decreased by 46.2% at 3 months post-treatment (p < 0.001). Additionally, mean QUEST scores at 3 months post-treatment significantly improved compared to baseline (p < 0.001). HTS is significantly improved from baseline ≥ 24 months post-treatment and possibly ≥ 48 months post-treatment. There is a current paucity of long-term CRST and QUEST score reporting in the literature 7).

In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions 8).

see Magnetic resonance guided focused ultrasound thalamotomy for essential tremor case series.

De Vloo et al. reported on an ET patient who underwent an Magnetic resonance guided focused ultrasound thalamotomy but experienced tremor recurrence. They expanded the MRgFUS-induced thalamic cavity using radiofrequency (RF), with good effect on the tremor but transient sensorimotor deficits and permanent ataxia. This is the first report of a patient undergoing RF thalamotomy after an unsuccessful MRgFUS thalamotomy. As they used microelectrode recording to guide the RF thalamotomy, they could also study for the first time the electrophysiological properties of previously sonicated thalamic neurons bordering the MRgFUS-induced cavity. These neurons displayed electrophysiological characteristics identical to those recorded from nonsonicated thalamic cells in ET patients. Hence, this findings support the widespread assumption that sonication below the necrotic threshold does not permanently alter neuronal function 9).



1)

Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013 Aug 15;369(7):640-8. doi: 10.1056/NEJMoa1300962. PubMed PMID: 23944301.
2)

Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, Hynynen K, Lozano AM. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 2013 May;12(5):462-8. doi: 10.1016/S1474-4422(13)70048-6. Epub 2013 Mar 21. PubMed PMID: 23523144.
3)

Chang JW, Min BK, Kim BS, Chang WS, Lee YH. Neurophysiologic correlates of sonication treatment in patients with essential tremor. Ultrasound Med Biol. 2015 Jan;41(1):124-31. doi: 10.1016/j.ultrasmedbio.2014.08.008. Epub 2014 Oct 22. PubMed PMID: 25438838.
4)

Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW. Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):257-64. doi: 10.1136/jnnp-2014-307642. Epub 2014 May 29. PubMed PMID: 24876191.
5)

Jung HH, Chang WS, Rachmilevitch I, Tlusty T, Zadicario E, Chang JW. Different magnetic resonance imaging patterns after transcranial magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus of the thalamus and anterior limb of the internal capsule in patients with essential tremor or obsessive-compulsive disorder. J Neurosurg. 2015 Jan;122(1):162-8. doi: 10.3171/2014.8.JNS132603. PubMed PMID: 25343176.
6)

Shaw KD, Johnston AS, Rush-Evans S, Prather S, Maynard K. Nursing Management of the Patient Undergoing Focused Ultrasound: A New Treatment Option for Essential Tremor. J Neurosci Nurs. 2017 Aug 16. doi: 10.1097/JNN.0000000000000301. [Epub ahead of print] PubMed PMID: 28817495.
7)

Miller WK, Becker KN, Caras AJ, Mansour TR, Mays MT, Rashid M, Schwalb J. Magnetic resonance-guided focused ultrasound treatment for essential tremor shows sustained efficacy: a meta-analysis. Neurosurg Rev. 2021 May 12. doi: 10.1007/s10143-021-01562-w. Epub ahead of print. PMID: 33978922.
8)

Moosa S, Martínez-Fernández R, Elias WJ, Del Alamo M, Eisenberg HM, Fishman PS. The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson’s disease. Mov Disord. 2019 Jul 10. doi: 10.1002/mds.27779. [Epub ahead of print] Review. PubMed PMID: 31291491.
9)

De Vloo P, Milosevic L, Gramer RM, et al. Microelectrode Recording and Radiofrequency Thalamotomy following Focused Ultrasound Thalamotomy [published online ahead of print, 2020 Sep 16]. Stereotact Funct Neurosurg. 2020;1-4. doi:10.1159/000510109
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