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).

Effectiveness

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).

Safety

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).

Nursing management

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).

Prospective randomized clinical trials

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 7).

Case series

References

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)

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.

Fluorescence-Guided Neurosurgery

Fluorescence-Guided Neurosurgery

see 5 aminolevulinic acid fluorescence guided resection.

see Fluorescein sodium guided resection.

see Fluorescence guided surgery of glioma.

The first use of fluorescence for brain tumour surgery was in 1948 by G.E. Moore 1) using fluorescein sodium.

Achieving a maximal safe extent of resection during brain tumor surgery is the goal for improved patient prognosisFluorescence-guided neurosurgery using 5-aminolevulinic acid (5-ALA) induced Protoporphyrin IX has thereby become a valuable tool enabling a high frequency of complete resections and a prolonged progression free survival in glioblastoma patients.

Erkkilä et al., from the Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Advanced Development Microsurgery, Carl Zeiss Meditec AG, Christian Doppler Laboratory for Innovative Optical Imaging and Its Translation to Medicine, Medical University of Vienna, Institute of Neurology, Department of Neurosurgery, General Hospital and Medical University of Vienna, presented a widefield fluorescence lifetime imaging device with 250 mm working distance working under similar conditions like surgical microscopes based on a time-of-flight based dual tap CMOS camera. In contrast to intensity-based fluorescence imaging this method is invariant to light scattering and absorption while being sensitive to the molecular composition of the tissue. They evaluated the feasibility of lifetime imaging of Protoporphyrin IX using the system to analyze brain tumor phantoms and fresh 5-ALA labeled human tissue samples. The results demonstrate the potential of this lifetime sensing device to go beyond the limitation of current intensity-based fluorescence-guided neurosurgery 2).

Books

Fluorescence-Guided Neurosurgery: Neuro-oncology and Cerebrovascular Applications September 10, 2018 The definitive textbook on state-of-the-art fluorescence-guided neurosurgery

Advances in fluorescence-guided surgery (FGS) have resulted in a paradigm shift in neurosurgical approaches to neuro-oncological and cerebrovascular pathologies. Edited by two of the foremost authorities on the topic, Fluorescence-Guided Neurosurgery: Neuro-oncology and Cerebrovascular Applications encompasses the depth and breadth of this groundbreaking, still nascent technology. The book reflects significant contributions made by world renowned neurosurgeons Constantinos Hadjipanayis, Walter Stummer, and esteemed contributors on the growing uses of 5-aminolevulinic acid (5-ALA) and other FGS agents.

The European Medicine Agency approved 5-ALA in 2007, heralding the birth of FGS globally. In 2017, the U.S. Food and Drug Administration approved 5-ALA (Gleolan) as an imaging agent to facilitate realtime detection and visualization of malignant tissue during glioma surgery. In the two decades since Dr. Stummer’s initial description of 5-ALA FGS in a human patient, major strides have been made in its practical applications, leading to improved resection outcomes. As FGS is increasingly incorporated into neurosurgical practice, it holds promise for future innovations. Generously-illustrated and enhanced with online videos, this textbook is the definitive resource on the subject.

Key Features

The improved efficacy of 5-ALA for resecting high- and low-grade gliomas, recurrences, meningiomas, brain metastases, spinal cord tumors, pediatric brain tumors, and other adult tumors The future of fluorescence, including potentially powerful new fluorophores molecularly targeted specifically to tumors The use of the fluorescent agent indocyanine green (ICG) for brain tumors, cerebral aneurysms, AVMs, and cerebral vascularization Special topics such as fluorescein, illuminating tumor paint, confocal microscopy, Raman spectroscopy, and integrating FGS with intraoperative imaging and brain mapping This single accessible reference presents the current state-of-the-art on this emerging, exciting surgical technology. As such, it is a must-have for neurosurgical residents, fellows, and practicing neurosurgeons.

1)

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
2)

Erkkilä MT, Bauer B, Hecker-Denschlag N, Madera Medina MJ, Leitgeb RA, Unterhuber A, Gesperger J, Roetzer T, Hauger C, Drexler W, Widhalm G, Andreana M. Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence-guided neurosurgery: an ex vivo feasibility study. J Biophotonics. 2019 Jan 12. doi: 10.1002/jbio.201800378. [Epub ahead of print] PubMed PMID: 30636030.

5 aminolevulinic acid fluorescence guided resection of spinal tumor

Multiple studies have attempted to evaluate the utility of 5-ALA-aided resection of spinal neoplasms.

Wainwright et al., from the Westchester Medical CenterTohoku University Hospital, reviewed the existing literature on the use of 5-ALA and PpIXfluorescence as an aid to resection of primary and secondary spinal neoplasms by searching the PUBMED and EMBASE database for records up to March 2018. Data was abstracted from all studies describing spinal neurosurgical uses in the English language.

In the reviewed studies, the most useful fluorescence was observed in meningiomas, ependymomas, drop metastases from cerebral gliomas, and spinal hemangiopericytoma, which is consistent with applications in cerebral neoplasms.

The available literature is significantly limited by a lack of standardized methods for measurement and quantification of 5-ALA fluorescence. The results of the reviewed studies should guide future development of rational trial protocols for the use of 5-ALA guided resection in spinal neoplasms1).


Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of Protoporphyrin IX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification.

Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy.

In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci 2).


A study included 10 patients who underwent surgical resection of an intramedullary ependymoma. Nine patients were orally administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA fluorescence was visualized with an operating microscope. Tumors were removed in a standardized manner with electrophysiological monitoring. The extent of resection was evaluated on the basis of intraoperative findings and postoperative magnetic resonance imaging. Histopathological diagnosis was established according to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki-67 labeling index.

5-ALA fluorescence was positive in 7 patients (6 grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative findings were dichotomized: Tumors covered by the cyst were easily separated from the normal parenchyma, whereas tumors without the cyst appeared to be continuous to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in delineating the ventral and cranial and caudal margins. Ki-67 labeling index was significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases. All patients improved neurologically or stabilized after surgery.

5-ALA fluorescence was useful for detecting tumor margins during surgery for intramedullary ependymoma. When combined with electrophysiological monitoring, fluorescence-guided resection could help to achieve maximum tumor resection safely 3).

References

1)

Wainwright JV, Endo T, Cooper JB, Tominaga T, Schmidt MH. The role of 5-aminolevulinic acid in spinal tumor surgery: a review. J Neurooncol. 2018 Dec 29. doi: 10.1007/s11060-018-03080-0. [Epub ahead of print] Review. PubMed PMID: 30594965.
2)

Millesi M, Kiesel B, Woehrer A, Hainfellner JA, Novak K, Martínez-Moreno M, Wolfsberger S, Knosp E, Widhalm G. Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus. 2014 Feb;36(2):E11. doi: 10.3171/2013.12.FOCUS13485. PubMed PMID: 24484249.
3)

Inoue T, Endo T, Nagamatsu K, Watanabe M, Tominaga T. 5-aminolevulinic acid fluorescence-guided resection of intramedullary ependymoma: report of 9 cases. Neurosurgery. 2013 Jun;72(2 Suppl Operative):ons159-68; discussion ons168. doi: 10.1227/NEU.0b013e31827bc7a3. PubMed PMID: 23149963.
× How can I help you?
WhatsApp WhatsApp us
%d bloggers like this: