5-aminolevulinic acid fluorescence guided resection of low-grade glioma

5-aminolevulinic acid fluorescence guided resection of low-grade glioma

Radiologically suspected low-grade gliomas (LGG) represent a special challenge for the neurosurgeon during surgery due to their histopathological heterogeneity and indefinite tumor margin. Therefore, new techniques are required to overcome these current surgical drawbacks. Intraoperative visualization of brain tumors with the assistance of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence is one of the major advancements in the neurosurgical field in the last decades. Initially, this technique was exclusively applied for fluorescence-guided surgery of high-grade glioma (HGG). In the last years, the use of 5-ALA was also extended to other indications such as radiologically suspected LGG. Kiesel et al. discussed the current role of 5-ALA for intraoperative visualization of focal malignant transformation within suspected LGG. Furthermore, they discussed the current limitations of the 5-ALA technology in pure LGG which usually cannot be visualized by visible fluorescence. Finally, they introduced new approaches based on fluorescence technology for improved detection of pure LGG tissue such as spectroscopic PpIX quantification fluorescence lifetime imaging of PpIX and confocal microscopy to optimize surgery 1).


A growing body of evidence has revealed the potential utility of 5-aminolevulinic acid (5-ALA) as a surgical adjunct in selected lower-grade gliomas. However, a reliable means of identifying which lower-grade gliomas will fluoresce has not been established.

Widhalm found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift 2).

A systematic review of PubMedGoogle Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. The quality index of the selected papers was provided. No patient information was used, so Institutional Review Board approval and patient consent were not required.

A total of 12 articles met the selection criteria with 244 histologically confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n = 60/244; 24.5%) demonstrated visual intraoperative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies; however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10-17), which correlated with an overall good quality.

There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection 3).

Müther et al. investigated a cohort of patients with WHO Grade 2 glioma and WHO Grade 3 gliomas who received 5-ALA before resection at a single institution. Using a logistic regression-based model, they evaluated 14 clinical and molecular variables considered plausible determinants of fluorescence. They then distilled the most predictive features to develop a model for predicting both fluorescence and tumor grade. They also explored the relationship between intraoperative fluorescence and diagnostic molecular markers.

One hundred seventy-nine subjects were eligible for inclusion. Our logistic regression classifier accurately predicted intraoperative fluorescence in our cohort with 91.9% accuracy and revealed enhancement as the singular variable in determining intraoperative fluorescence. There was a direct relationship between enhancement on MRI and the likelihood of observed fluorescence. Observed fluorescence correlated with MIB-1 index but not with isocitrate dehydrogenase (IDH) status, 1p19q codeletion, or methylguanine DNA methyltransferase promoter methylation.

They demonstrated a strong correlation between enhancement on preoperative MRI and the likelihood of visible fluorescence during surgery in patients with intermediate-grade glioma. The analysis provides a robust method for predicting 5-ALA-induced fluorescence in patients with grade II and grade III gliomas 4).


Valdés et al. describe their initial experience with 5-aminolevulinic acid (ALA)-induced PpIX fluorescence in twelve patients with presumed LGGs after receiving 20 mg/kg of ALA approximately 3 hours prior to surgery under an institutional review board-approved protocol.

Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology.

Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively.

The authors’ initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors’ initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs 5).


1)

Kiesel B, Freund J, Reichert D, Wadiura L, Erkkilae MT, Woehrer A, Hervey-Jumper S, Berger MS, Widhalm G. 5-ALA in Suspected Low-Grade Gliomas: Current RoleLimitations, and New Approaches. Front Oncol. 2021 Jul 30;11:699301. doi: 10.3389/fonc.2021.699301. PMID: 34395266; PMCID: PMC8362830.
2)

Widhalm G. Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence. Clin Neuropathol. 2014 Jul-Aug;33(4):260-78. PubMed PMID: 24986206.
3)

Almekkawi AK, El Ahmadieh TY, Wu EM, Abunimer AM, Abi-Aad KR, Aoun SG, Plitt AR, El Tecle NE, Patel T, Stummer W, Bendok BR. The Use of 5-Aminolevulinic Acid in Low-Grade Glioma Resection: A Systematic Review. Oper Neurosurg (Hagerstown). 2020 Jul 1;19(1):1-8. doi: 10.1093/ons/opz336. Erratum in: Oper Neurosurg (Hagerstown). 2020 Jul 1;19(1):107. PMID: 31828346.
4)

Müther M, Jaber M, Johnson TD, Orringer DA, Stummer W. A Data-Driven Approach to Predicting 5-Aminolevulinic Acid-Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas. Neurosurgery. 2022 Mar 16. doi: 10.1227/NEU.0000000000001914. Epub ahead of print. PMID: 35285461.
5)

Valdés PA, Jacobs V, Harris BT, Wilson BC, Leblond F, Paulsen KD, Roberts DW. Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. J Neurosurg. 2015 Jul 3:1-10. [Epub ahead of print] PubMed PMID: 26140489.

Fluorescein sodium guided resection of high-grade glioma

Fluorescein sodium guided resection of high-grade glioma

Naik et al. compared 5 aminolevulinic acid fluorescence guided resection of high-grade gliomaFluorescein sodium guided resection of high-grade glioma. (FS), and Intraoperative magnetic resonance imaging-guided resection of high-grade glioma (IMRI) with no image guidance to determine the best intraoperative navigation method to maximize rates of gross total resection (GTR) and outcomes. A frequentist network meta-analysis was performed following standard PRISMA guidelines (PROSPERO registration CRD42021268659). Surface-under-the-cumulative ranking (SUCRA) analysis was executed to hierarchically rank modalities by the outcome of interestHeterogeneity was measured by the I2 statisticPublication bias was assessed by funnel plots and the use of Egger’s test. Statistical significance was determined by p < 0.05. Twenty-three studies were included for analysis with a total of 2,643 patients. Network meta-analysis comparing 5-ALA, IMRI, and FS was performed. The primary outcome assessed was the rate of GTR. Analysis revealed the superiority of all intraoperative navigation to control (no navigation). SUCRA analysis revealed the superiority of IMRI + 5-ALA, IMRI alone, followed by FS, and 5-ALA. Overall survival (OS) and progression-free survival (PFS) were also examined. FS (vs. control) was associated with improved OS, while IMRI was associated with improved PFS (vs. control, FS, and 5-ALA). Intraoperative navigation using IMRI, FS, and 5-ALA lead to greater rates of GTR in HGGs. FS and 5-ALA also yielded improvement in OS and PFS. Further studies are needed to evaluate differences in survival benefit, operative duration, and cost 1).


Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed 2).

5-ALA fluorescence-guided surgery has shortcomings such as drug’s phototoxicity, extortionate price, and not being approved by Food and Drug Administration, which limited its widespread application.

Due to the above limitations, sodium fluorescein guided surgery had been paid more attention by neurosurgeons than 5-ALA. FL is an easily available and biosafe fluorescein dye with a peak excitation at 465 to 490 nm and emission between 500 and 550 nm and has been used extensively and safely for many years especially in ophthalmology 3) 4).

5 aminolevulinic acid is still the preferred and more established fluorescent dye used during high-grade gliomas resection, with Fluorescein sodium gaining-attention, really cheaper and more ductile alternative 5).

The use of fluorescein fluorescence-guided stereotactic needle biopsy has been shown to improve diagnostic accuracy and to expedite operative procedure in the stereotactic needle biopsy of high-grade gliomas.

see Fluoropen.

The first use of fluorescence for brain tumour surgery was in 1948 by G.E. Moore 6) using fluorescein sodium, a strongly fluorescing and non-toxic (apart from rare anaphylaxis 7) compound). In malignant brain tumours with their inherent blood-brain barrier breakdown, fluorescein is extravasated and might serve to mark tumours.

Today, fluorescein sodium is again under scrutiny 8) 9). using a novel filter system by Zeiss (YELLOW 560) for the microscope. This filter visualises fluorescein and allows good background discrimination. Furthermore, fluorescein can be injected any time and is low in cost. Nevertheless, its use in brain tumour surgery is off-label and thus restricted to clinical studies. Little is known about the best timing of i.v. fluorescein application before resection. Injecting fluorescein too early might result in unspecific propagation with oedema, whereas acute injections might be useful for detecting abnormally perfused tumour tissue. Levels in the blood will be high, especially with acute injections, leading to fluorescence of all perfused brain tissue. Such time-resolved in- formation on the specificity of fluorescein are not available.

Overall, Schwake et al observed no clear value of fluorescein in a small study, which they closed prematurely. Clearly, further work elucidating optimal timing and dosing of fluorescein is warranted. 10)


Sodium fluorescein (SF) was first used for the identification of different types of brain tumors in 1948 11).

Since then, the use of SF and others fluorescent tracers have been described in literature particularly that dealing with glioblastoma multiforme resection 12) 13) 14)

Metastatic lesion were also enhanced by SF 15)16).

Also in skull base tumors 17).

“Fluorescein sodium”, the sodium salt of fluorescein, is used extensively as a diagnostic tool in the field of ophthalmology and optometry, where topical fluorescein is used in the diagnosis of corneal abrasions, corneal ulcers and herpetic corneal infections. It is also used in rigid gas permeable contact lens fitting to evaluate the tear layer under the lens. It is available as sterile single-use sachets containing lint-free paper applicators soaked in fluorescein sodium.

Intravenous or oral fluorescein is used in fluorescein angiography in research and to diagnose and categorize vascular disorders including retinal disease macular degeneration, diabetic retinopathy, inflammatory intraocular conditions, and intraocular tumors. It is also being used increasingly during surgery for brain tumors.

Diluted fluorescein dye has been used to localise multiple muscular ventricular septal defects during open heart surgery and confirm the presence of any residual defects.


Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross total resection (GTR) using high doses of fluorescein sodium under white light. The introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore.

Fluorescein sodium does not appear to selectively accumulate in astrocytoma cells but in extracellular tumor cell rich locations, suggesting that fluorescein is a marker for areas of compromised blood brain barrier within high grade astrocytoma. Fluorescein fluorescence appears to correlate intraoperatively with the areas of MR enhancement, thus representing a practical tool to help the surgeon achieve GTR of the enhancing tumor regions 18).


Magnetic resonance diffusion tensor imaging (MR-DTI) and fluorescein sodium dyeing guiding for surgery of glioma located in brain motor functional areas can increase the gross total resection rate, decrease the paralysis rate caused by surgery, and improve patient quality of life compared with traditional glioma surgery 19).


Intrathecal fluorescein (ITF) is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair 20).


1)

Naik A, Smith EJ, Barreau A, Nyaeme M, Cramer SW, Najafali D, Krist DT, Arnold PM, Hassaneen W. Comparison of fluorescein sodium, 5-ALA, and intraoperative MRI for resection of high-grade gliomas: A systematic review and network meta-analysis. J Clin Neurosci. 2022 Feb 22;98:240-247. doi: 10.1016/j.jocn.2022.02.028. Epub ahead of print. PMID: 35219089.
2)

Hansen RW, Pedersen CB, Halle B, Korshoej AR, Schulz MK, Kristensen BW, Poulsen FR. Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study. J Neurosurg. 2019 Oct 4:1-8. doi: 10.3171/2019.6.JNS191531. [Epub ahead of print] PubMed PMID: 31585425.
3)

Novotny H. R., Alvis D. L. A method of photographing fluorescence in circulating blood in the human retina. Circulation. 1961;24:82–86. doi: 10.1161/01.cir.24.1.82.
4)

Kwan A. S. L., Barry C., McAllister I. L., Constable I. Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience. Clinical and Experimental Ophthalmology. 2006;34(1):33–38. doi: 10.1111/j.1442-9071.2006.01136.x.
5)

Acerbi F, Restelli F, De Laurentis C, Falco J, Cavallo C, Broggi M, Höhne J, Schebesch KM, Schiariti M, Ferroli P. Fluorescent tracers in neurosurgical procedures: an European survey. J Neurosurg Sci. 2018 Jul 17. doi: 10.23736/S0390-5616.18.04494-6. [Epub ahead of print] PubMed PMID: 30014688.
6)

Moore GE, Peyton WT, French LA, Walker WW (1948) The clinical use of fluorescein in neurosurgery; the localization of brain tumors. J Neurosurg 5:392–398
7)

Dilek O, Ihsan A, Tulay H (2011) Anaphylactic reaction after fluo- rescein sodium administration during intracranial surgery. J Clin Neurosci 18:430–431
8)

Acerbi F, Broggi M, Eoli M, Anghileri E, Cuppini L, Pollo B, Schiariti M, Visintini S, Ori C, Franzini A, Broggi G, Ferroli P (2013) Fluorescein-guided surgery for grade IV gli- omas with a dedicated filter on the surgical microscope: pre- liminary results in 12 cases. Acta Neurochir (Wien) 155: 1277–1286
9)

Schebesch KM, Proescholdt M, Höhne J, Hohenberger C, Hansen E, Reimenschneider MJ, Ullrich W, Doenitz C, Schlair J, Lange M, Brawanski A (2013) Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:693–699
10)

Schwake M, Stummer W, Suero Molina EJ, Wölfer J. Simultaneous fluorescein sodium and 5-ALA in fluorescence-guided glioma surgery. Acta Neurochir (Wien). 2015 May;157(5):877-9. doi: 10.1007/s00701-015-2401-0. Epub 2015 Mar 28. PubMed PMID: 25820632.
11) , 15)

Moore GE, Peyton WT, French LA, Walker WW. The clinical use of fluorescein in neurosurgery. J Neurosurg. 1948;5:392–8.
12)

Chae MP, Song SW, Park SH, Park CK. Experience with 5- aminolevulinic Acid in fluorescence-guided resection of a deep sylvian meningioma. J Korean Neurosurg Soc. 2012;52:558–60.
13)

Kuroiwa T, Kajimoto Y, Ohta T. Development of a fluorescein operative microscope for use during malignant glioma surgery: A technical note and preliminary report. Surg Neurol. 1998;50:41–9.
14)

Kuroiwa T, Kajimoto Y, Ohta T. Comparison between operative findings on malignant glioma by a fluorescein surgical microscopy and histological findings. Neurol Res. 1999;21:130–4.
16)

Okuda T, Kataoka K, Taneda M. Metastatic brain tumor surgery using fluorescein sodium: Technical note. Minim Invasive Neurosurg. 2007;50:382–4.
17)

da Silva CE, da Silva JL, da Silva VD. Use of sodium fluorescein in skull base tumors. Surg Neurol Int. 2010;1:70.
18)

Diaz RJ, Dios RR, Hattab EM, Burrell K, Rakopoulos P, Sabha N, Hawkins C, Zadeh G, Rutka JT, Cohen-Gadol AA. Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance. J Neurosurg. 2015 Jun;122(6):1360-9. doi: 10.3171/2015.2.JNS132507. Epub 2015 Apr 3. PubMed PMID: 25839919.
19)

Liu JG, Yang SF, Liu YH, Wang X, Mao Q. Magnetic resonance diffusion tensor imaging with fluorescein sodium dyeing for surgery of gliomas in brain motor functional areas. Chin Med J (Engl). 2013 Jul;126(13):2418-23. PubMed PMID: 23823811.
20)

Raza SM, Banu MA, Donaldson A, Patel KS, Anand VK, Schwartz TH. Sensitivity and specificity of intrathecal fluorescein and white light excitation for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base surgery: a prospective study. J Neurosurg. 2016 Mar;124(3):621-6. doi: 10.3171/2014.12.JNS14995. Epub 2015 Aug 21. PubMed PMID: 26295912.

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.

A 55-yr-old man with a history of right frontal craniotomy for resection of a colloid cyst underwent a left ventrointermedius nucleus thalamotomy through MRgFUS. The prior craniotomy flap was not excluded in the treatment plan; however, all bony defects and hardware were marked as “no-pass” regions. Clinical outcomes were collected at the 6-mo follow-up.

Transducer elements whose acoustic paths would have been altered by the craniotomy defect were turned off. Sonications reaching lesional temperatures of up to 56°C were successfully delivered. The procedure was well-tolerated, without any persistent intra-ablation or post-ablation adverse effects. The presence of a lesion was confirmed on MRI, which was associated with a significant reduction in the patient’s tremor that was sustained at the 6-mo follow-up.

This case demonstrates the safety and efficacy of MRgFUS thalamotomy in a patient with prior craniotomies and highlights our strategy for acoustic lesioning in this setting 9).


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 10).



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)

Wathen C, Yang AI, Hitti FL, Henry L, Chaibainou H, Baltuch GH. Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy. Oper Neurosurg (Hagerstown). 2022 Feb 1;22(2):61-65. doi: 10.1227/ONS.0000000000000012. PMID: 35007218.
10)

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
WhatsApp WhatsApp us
%d bloggers like this: