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Article: Focused Ultrasound Thalamotomy for Tremor Relief in Atypical Parkisnsonism.

Sinai, Alon / Nassar, Maria / Shornikov, Lev / Constantinescu, Marius / Zaaroor, Menashe / Schlesinger, Ilana

2024 Volume 2024, Page(s) 6643510

Abstract: Background: Magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) VIM-thalamotomy has established efficacy and safety in tremor relief in patients with essential tremor and Parkinson's disease. The efficacy and safety in patients with ... ...

Abstract	Background: Magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) VIM-thalamotomy has established efficacy and safety in tremor relief in patients with essential tremor and Parkinson's disease. The efficacy and safety in patients with atypical parkinsonism have not been reported. Objective: To report on the efficacy and safety of FUS VIM-thalamotomy in 8 patients with parkinsonism, multiple system atrophy-Parkinsonian type (MSA-P) ( Methods: Tremor was assessed in the treated hemibody using the Clinical Rating Scale for Tremor (CRST). The motor Unified MSA Rating Scale (UMSAR) was used in the MSA-P and motor sections of the Unified Parkinson's Disease Rating Scale (UPDRS-III) in DLB patients. Cognition was measured using the Montreal Cognitive Assessment (MoCA). Results: In MSA-P and DLB patients, there was immediate tremor relief. CRST scores measured on the treated side improved compared to baseline. During the follow-up of up to 1 year tremor reduction persisted. The change in CRST scores at different time points did not reach statistical significance, probably due to the small sample size. Adverse events were transient and resolved within a year. Conclusions: In our experience, FUS VIM-thalamotomy was effective in patients with MSA-P and DLB. Larger, controlled studies are needed to verify our preliminary observations.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573854-9
ISSN	2042-0080 ; 2090-8083
ISSN (online)	2042-0080
ISSN	2090-8083
DOI	10.1155/2024/6643510
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Article: New US device versus imaging US to assess tumor-in-brain.

Halevy-Politch, Jacob / Zaaroor, Menashe / Sinai, Alon / Constantinescu, Marius

Chinese neurosurgical journal

2020 Volume 6, Page(s) 28

Abstract: Background: Applying ultrasonic imaging system during surgery requires the poring of saline, performing the measurement, and acquiring data from its display-which requires time and is highly "performer dependent," i.e., the measure is of a subjective ... ...

Abstract	Background: Applying ultrasonic imaging system during surgery requires the poring of saline, performing the measurement, and acquiring data from its display-which requires time and is highly "performer dependent," i.e., the measure is of a subjective nature. A new ultrasonic device was recently developed that overcomes most of these drawbacks and was successfully applied during tumor-in-brain neurosurgeries. The purpose of this study was to compare the two types of US devices and demonstrate their properties. Methods: The study was performed in the following stages: (i) an ex vivo experiment, where slices of the muscle and brain of a young porcine were laid one on top the other. Thicknesses and border depths were measured and compared, using the two types of US instruments. (ii) During human clinical neurosurgeries, tumor depth was compared by measuring it with both devices. (iii) Following the success of stages (i) and (ii), using solely the new US device, the tumor thickness was monitored while its resection.Correlation, Pearson's coefficient, average, mean, and standard deviation were applied for statistical tests. Results: A high correlation was obtained for the distances of tissue borders and for their respective thicknesses. Applying these ultrasonic devices during neurosurgeries, tumor depths were monitored with high similarity (87%), which was also obtained by Pearson's correlation coefficient (0.44). The new US device, thanks to its small footprint, its remote measurement, and the capability of monitoring intraoperatively and in real-time, provides the approach to tumor's border before its complete resection. Conclusions: The new US device provides better accuracy than an ultrasonic imaging system; its data is objective; it enables to
Language	English
Publishing date	2020-08-05
Publishing country	England
Document type	Journal Article
ISSN	2095-9370
ISSN	2095-9370
DOI	10.1186/s41016-020-00205-1
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Article: Immunological Aspects of Malignant Gliomas.

Cohen-Inbar, Or / Zaaroor, Menashe

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques

2016 Volume 43, Issue 4, Page(s) 494–502

Abstract: Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor ...

Abstract	Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM.
MeSH term(s)	Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Glioblastoma/immunology ; Glioblastoma/therapy ; Humans ; Immunotherapy/methods
Language	English
Publishing date	2016-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	197622-9
ISSN	0317-1671
ISSN	0317-1671
DOI	10.1017/cjn.2016.34
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Article ; Online: A Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

Schlesinger, Ilana / Zaaroor, Menashe

The New England journal of medicine

2016 Volume 375, Issue 22, Page(s) 2201–2202

Language	English
Publishing date	2016--01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1612210
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Article ; Online: Glioblastoma multiforme targeted therapy: The Chlorotoxin story.

Cohen-Inbar, Or / Zaaroor, Menashe

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2016 Volume 33, Page(s) 52–58

Abstract: Glioblastoma multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival of <24months. Scorpion toxins are considered promising cancer drug candidates, primarily due to the discovery of hlorotoxin, derived from the venom ... ...

Abstract	Glioblastoma multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival of <24months. Scorpion toxins are considered promising cancer drug candidates, primarily due to the discovery of hlorotoxin, derived from the venom of the Israeli yellow scorpion. This intriguing short peptide of only 36 amino-acids length and tight configuration, possess the ability to bind to GBM cells in a grade-related manner with ∼100% of GBM cells staining positive and no cross reactivity to normal brain. Chlorotoxin has an anti-angiogenic effect as well. Molecular targets for Chlorotoxin include voltage gated chloride channels (GCC), calcium-dependent phospholipid-binding protein Annexin-2, and the inducible extracellular enzyme Matrix Metalloproteinase-2 (MMP-2). Of all its targets, MMP-2 seems to bear the most anti-neoplastic potential. Chlorotoxin is a promising tumortargeting peptide. Its small size and compact shape are convenient for intracranial delivery. We present a short discussion on Chlorotoxin. The structure, biological activity, molecular targets and possible clinical role of Chlorotoxin are discussed. Chlorotoxin can be utilized as a targeting domain as well, attaching different effector functions to it. Clinical applications in GBM therapy, intraoperative imaging, nano-probes and nano-vectors based technology; targeted chemotherapy and immunotherapy are discussed as well. Chlorotoxin is likely to play a significant role in effective GBM immunotherapy in the future.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Brain Neoplasms/drug therapy ; Glioblastoma/drug therapy ; Humans ; Neurotoxins/pharmacology ; Scorpion Venoms/pharmacology
Chemical Substances	Antineoplastic Agents ; Neurotoxins ; Scorpion Venoms ; Chlorotoxin (06UV5RFW57)
Language	English
Publishing date	2016-11
Publishing country	Scotland
Document type	Journal Article ; Review
ZDB-ID	1193674-5
ISSN	1532-2653 ; 0967-5868
ISSN (online)	1532-2653
ISSN	0967-5868
DOI	10.1016/j.jocn.2016.04.012
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Article ; Online: Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson's Disease: Long-Term Results.

Sinai, Alon / Nassar, Maria / Sprecher, Elliot / Constantinescu, Marius / Zaaroor, Menashe / Schlesinger, Ilana

Journal of Parkinson's disease

2021 Volume 12, Issue 1, Page(s) 199–206

Abstract: Background: MRI-guided focused ultrasound (FUS) has established short-term efficacy in tremor relief.: Objective: We report our long-term experience of treating tremor with unilateral FUS unilateral VIM-thalamotomy in tremor dominant Parkinson's ... ...

Abstract	Background: MRI-guided focused ultrasound (FUS) has established short-term efficacy in tremor relief. Objective: We report our long-term experience of treating tremor with unilateral FUS unilateral VIM-thalamotomy in tremor dominant Parkinson's disease (TDPD) patients. Methods: We report outcome of FUS thalamotomy in TDPD patients with 1-5 years of follow-up. Outcomes: tremor reduction assessed with Clinical Rating Scale for Tremor (CRST) and Unified Parkinson's Disease Rating Scale (UPDRS part III) overall and in the treated hemibody and safety. Results: Twenty-six TDPD patients completed 1-5 years of follow-up (median follow-up 36 months, range 12-60 months). Median age was 60 years (range 46-79), with median disease duration of 6 years (range 2-16). Immediately, treatment resulted in 100%improvement in tremor in the treated arm in 23 patients and 90%improvement in 3 patients. In 15 patients with leg tremor, 2 patients with chin tremor and 1 patient with head tremor, tremor was significantly improved. Up to 5 years, median CRST score, median UPDRS score, overall and in treated hemibody, decreased significantly as compared with baseline (p < 0.0001). In 2 patients tremor returned completely and in 8 patients there was partial return of tremor. Adverse events were mild and resolved within 3 months. At baseline 4 patients were not receiving any medication vs. 3 at last follow-up and 15 were not taking levodopa vs.9 at last follow-up. Conclusion: Unilateral FUS VIM-thalamotomy in TDPD patients was effective and safe and provided long-term tremor relief in most patients. FUS thalamotomy for tremor may delay initiation of levodopa treatment.
MeSH term(s)	Aged ; Essential Tremor ; Humans ; Levodopa ; Middle Aged ; Parkinson Disease/complications ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/surgery ; Thalamus/diagnostic imaging ; Thalamus/surgery ; Treatment Outcome ; Tremor/diagnostic imaging ; Tremor/etiology ; Tremor/surgery
Chemical Substances	Levodopa (46627O600J)
Language	English
Publishing date	2021-10-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-212810
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Article ; Online: Assessing Tremor and Adverse Events in Patients With Tremor-Dominant Parkinson Disease Undergoing Focused Ultrasound Thalamotomy.

Schlesinger, Ilana / Sinai, Alon / Zaaroor, Menashe

JAMA neurology

2018 Volume 75, Issue 5, Page(s) 632–633

MeSH term(s)	Humans ; Parkinson Disease ; Thalamus ; Tremor ; Ultrasonic Therapy
Language	English
Publishing date	2018-03-23
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2018.0263
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Article: [EFFECT OF GENDER ON OUTCOME OF TREATMENT FOR TREMOR WITH MRI GUIDED FOCUSED ULTRASOUND].

Schlesinger, Ilana / Sinai, Alon / Nassar, Maria / Eran, Ayelet / Zaaroor, Menashe

Harefuah

2019 Volume 158, Issue 6, Page(s) 343–346

Abstract: Introduction: Thalamotomy is an effective treatment for medication-resistant tremor. MRI-guided focused ultrasound (MRgFUS) has been shown to be an effective and safe treatment for alleviating tremor.: Objectives: We examined whether there is a ... ...

Abstract	Introduction: Thalamotomy is an effective treatment for medication-resistant tremor. MRI-guided focused ultrasound (MRgFUS) has been shown to be an effective and safe treatment for alleviating tremor. Objectives: We examined whether there is a gender difference in the efficacy and safety of thalamotomy using MRgFUS. Methods: Seventy patients with moderate to severe medication-resistant tremor were treated with MRgFUS at Rambam Medical Center. Thermal ablation with ultrasound waves was carried out in the MRI suite while real-time monitoring of treatment efficacy and adverse events were recorded. A comparison was made between outcomes in men and women. Results: Seventy patients, 47 men and 23 women with essential tremor, Parkinson's disease, paraneoplastic syndrome, and multiple system atrophy were treated. Both men and women reported the disappearance of tremor after MRgFUS with the exception of one patient with a paraneoplastic syndrome. In all patients, there was a significant decrease in the tremor scores (p <0.001), with no gender difference, and all patients reported a significant improvement in quality of life (p<0.001) regardless of gender. In ten patients, 8 men and 2 women, the tremor returned, but was bothersome in only 4, all men. This gender difference was not statistically significant. Transient adverse events were observed in the same frequency in men and women. The most common adverse event was transient gait instability and ataxia. Conclusions: In this series of patients, MRgFUS was an effective and safe treatment for both sexes with no significant difference in efficacy or adverse events.
MeSH term(s)	Essential Tremor ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Quality of Life ; Sex Factors ; Treatment Outcome ; Tremor/therapy ; Ultrasonic Therapy
Language	Hebrew
Publishing date	2019-06-19
Publishing country	Israel
Document type	Journal Article
ZDB-ID	953872-0
ISSN	0017-7768
ISSN	0017-7768
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Article ; Online: Major-histocompatibility complex harnessing and lymphocytic recruitment: a new tool for glioblastoma multiforme immunotherapy.

Cohen-Inbar, Or / Reiter, Yoram / Zaaroor, Menashe

Journal of neurosurgical sciences

2017 Volume 61, Issue 4, Page(s) 422–428

Abstract: Glioblastoma multiforme (GBM) is the most common malignant primary brain neoplasm, notorious for being able to evade and suppress the immune-system. We present a new immunotherapeutic approach that can potentially overcome or circumvent many of the GBM ... ...

Abstract	Glioblastoma multiforme (GBM) is the most common malignant primary brain neoplasm, notorious for being able to evade and suppress the immune-system. We present a new immunotherapeutic approach that can potentially overcome or circumvent many of the GBM laden obstacles for an efficient antitumor immune response. In this molecular construct, a soluble major-histocompatibility complex (MHC), presenting an immunogenic peptide is directed towards GBM cells. This soluble complex is known to be able to activate relevant cytotoxic T-lymphocyte (CTL's) populations, mounting an effective local immune response. The chimeric protein consists of a targeting domain, a function that can be fulfilled by an antibody or other small molecule that binds tumor associated antigens, and an effector domain. A single chain MHC directly linked to an immunogenic Cytomegalovirus derived peptide (phosphoprotein 65) can be used as such an effector domain. Targeting MHC complexes to the tumor enables to recruit different lymphocyte populations using MHC-molecules bearing a single, highly antigenic peptide derived from immunogenic T cell epitopes. Moreover, the recruited potent memory CTL's at the tumor's milieu may prove resistant to the previously described local immunosuppressive environment, and may enable the shift to TH1 cytokine profile resulting in specific massive tumor destruction.
Language	English
Publishing date	2017-08
Publishing country	Italy
Document type	Journal Article
ZDB-ID	193139-8
ISSN	1827-1855 ; 0390-5616 ; 0026-4881
ISSN (online)	1827-1855
ISSN	0390-5616 ; 0026-4881
DOI	10.23736/S0390-5616.16.03755-3
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Article: MRI-Guided Focused Ultrasound in Parkinson's Disease: A Review.

Schlesinger, Ilana / Sinai, Alon / Zaaroor, Menashe

Parkinson's disease

2017 Volume 2017, Page(s) 8124624

Abstract: MRI-guided focused ultrasound is a new technology that enables intracranial ablation. Since lesioning ameliorates some of the symptoms of PD, this technology is being explored as a possible treatment for medication resistant symptoms in PD patients. The ... ...

Abstract	MRI-guided focused ultrasound is a new technology that enables intracranial ablation. Since lesioning ameliorates some of the symptoms of PD, this technology is being explored as a possible treatment for medication resistant symptoms in PD patients. The purpose of this paper is to review the clinical use and treatment outcomes of PD patients treated to date with this technology.
Language	English
Publishing date	2017-03-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573854-9
ISSN	2042-0080 ; 2090-8083
ISSN (online)	2042-0080
ISSN	2090-8083
DOI	10.1155/2017/8124624
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