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Article ; Online: Long-term safety of medical cannabis in Parkinson's disease: A retrospective case-control study.

Goldberg, Tomer / Redlich, Yonatan / Yogev, David / Fay-Karmon, Tsvia / Hassin-Baer, Sharon / Anis, Saar

2023 Volume 112, Page(s) 105406

Abstract: Background: Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson's disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or ... ...

Abstract	Background: Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson's disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or its safety profile. This study examined the effects of MC on PD in a real-life setting. Methods: A retrospective case-control study of 152 idiopathic PD patients (mean age 69.1 ± 9.0 years), followed at the Sheba Medical Center Movement Disorders Institute (SMDI) from 2008 to 2022 was conducted. Seventy-six patients who used licensed whole-plant medical cannabis (MC) for at least a year were compared to a matched group who did not receive MC in terms of their Levodopa Equivalent Daily Dose (LEDD), Hoehn and Yahr (H&Y) stage, and cognitive, depressive, and psychotic symptoms. Results: The median monthly dose of MC was 20 g (IQR: 20-30), with a median Tetrahydrocannabinol (THC) percentage of 10 (IQR: 9.5-14.15) and a median Cannabidiol (CBD) percentage of 4 (IQR: 2-10). There were no significant differences between the MC and the control groups for LEDD or H&Y stage progression (p = 0.90, 0.77, respectively). A Kaplan-Meier analysis showed no evidence of relative worsening of psychotic, depressive, or cognitive symptoms reported by patients to their treating physicians over time in the MC group (p = 0.16-0.50). Conclusion: Over the 1-3 years of follow-ups, the MC treatment regimens appeared to be safe. MC did not exacerbate neuropsychiatric symptoms and had no detrimental effects on disease progression.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Parkinson Disease/complications ; Parkinson Disease/drug therapy ; Medical Marijuana/adverse effects ; Retrospective Studies ; Case-Control Studies ; Levodopa/therapeutic use
Chemical Substances	Medical Marijuana ; Levodopa (46627O600J)
Language	English
Publishing date	2023-05-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2023.105406
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Article ; Online: Are LRRK2 p.G2019S or GBA1 variants associated with long-term outcomes of deep brain stimulation for Parkinson's disease?

Anis, Saar / Goldberg, Tomer / Shvueli, Ethan / Kozlov, Yuval / Redlich, Yonatan / Lavi, Naama / Lavie, Inbar / Sosero, Yuri Ludwig / Gan-Or, Ziv / Ungar, Lior / Zibly, Zion / Greenbaum, Lior / Fay-Karmon, Tsvia / Hassin-Baer, Sharon

Parkinsonism & related disorders

2024 , Page(s) 106008

Abstract: Background: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be ... ...

Abstract	Background: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized. Methods: We conducted a retrospective single-center case-control study involving PD patients who were carriers of a GBA1 variant (GBA1-PD), the LRRK2 p.G2019S variant (LRRK2-PD), and non-carriers (Nc-PD). All participants underwent DBS and were followed up for at least a year. Assessments before surgery and at 1, 2, 3, 5, and 10 years post-DBS included the following: the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part III, Hoehn and Yahr scale, Levodopa Equivalent Daily Dose (LEDD) and non-motor symptoms (psychotic episodes, depressive symptoms, and cognitive decline). Results: The sample was composed of 103 patients (72 males, mean age at DBS surgery 61.5 ± 8.7 years, mean postoperative follow-up 7.0 ± 4.1 years). Of these, 19 were LRRK2-PD, 20 GBA1-PD, and 64 were Nc-PD. No significant differences in motor outcomes were observed between the groups. Compared to the Nc-PD patients, the GBA1-PD patients were at increased risk of both psychotic episodes [hazard ratio (HR) 2.76 (95 % CI: 1.12-6.80), p = 0.027], and cognitive decline [HR 2.28 (95 % CI: 1.04-5.00), p = 0.04]. Conclusion: LRRK2 and GBA1 variant status did not affect the motor outcomes of DBS in PD patients. However, GBA1-PD patients were at increased risk for psychosis and cognitive decline. Further studies are required to determine the role of genetic stratification in referral to DBS.
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2024.106008
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Article ; Online: Adult-onset Alexander disease among patients of Jewish Syrian descent.

Anis, Saar / Fay-Karmon, Tsvia / Lassman, Simon / Shbat, Fadi / Lesman-Segev, Orit / Mor, Nofar / Barel, Ortal / Dominissini, Dan / Chorin, Odelia / Pras, Elon / Greenbaum, Lior / Hassin-Baer, Sharon

Neurogenetics

2023 Volume 24, Issue 4, Page(s) 303–310

Abstract: Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological ... ...

Abstract	Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological manifestations. Adult-onset AxD manifests as a chronic and progressive condition, characterized by bulbar, motor, cerebellar, and other clinical signs and symptoms. Neuroradiological findings typically involve the brainstem and cervical spinal cord. Adult-onset AxD has been described in diverse populations but is rare in Israel. We present a series of patients diagnosed with adult-onset AxD from three families, all of Jewish Syrian descent. Five patients (4 females) were diagnosed with adult-onset AxD due to the heterozygous mutation c.219G > A, p.Met73Ile in GFAP. Age at symptoms onset ranged from 48 to 61 years. Clinical characteristics were typical and involved progressive bulbar and gait disturbance, followed by pyramidal and cerebellar impairment, dysautonomia, and cognitive decline. Imaging findings included medullary and cervical spinal atrophy and mostly infratentorial white matter hyperintensities. A newly recognized cluster of adult-onset AxD in Jews of Syrian origin is presented. This disorder should be considered in differential diagnosis in appropriate circumstances. Genetic counselling for family members is required in order to discuss options for future family planning.
MeSH term(s)	Female ; Humans ; Adult ; Middle Aged ; Alexander Disease/diagnostic imaging ; Alexander Disease/genetics ; Jews/genetics ; Syria ; Glial Fibrillary Acidic Protein/genetics ; Mutation ; Atrophy
Chemical Substances	Glial Fibrillary Acidic Protein
Language	English
Publishing date	2023-09-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1339887-8
ISSN	1364-6753 ; 1364-6745
ISSN (online)	1364-6753
ISSN	1364-6745
DOI	10.1007/s10048-023-00732-w
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Article ; Online: Botulinum Injections for Idiopathic Cervical Dystonia: a Longitudinal Study.

Yahalom, Gilad / Fay-Karmon, Tsvia / Livneh, Vered / Israeli-Korn, Simon / Ephraty, Lilach / Hassin-Baer, Sharon

Neurotoxicity research

2021 Volume 39, Issue 4, Page(s) 1352–1359

Abstract: Botulinum toxin (BT) injections into the cervical muscles are an effective and commonly practiced treatment approach for cervical dystonia. In this retrospective longitudinal study, we collected data from the Sheba electronic medical records on ... ...

Abstract	Botulinum toxin (BT) injections into the cervical muscles are an effective and commonly practiced treatment approach for cervical dystonia. In this retrospective longitudinal study, we collected data from the Sheba electronic medical records on consecutive patients with idiopathic cervical dystonia (ICD), treated regularly with periodic BT injections between the years 2008-2020. All treatment visits were analyzed regarding type of toxin, dose injected, and clinical outcomes. The vast majority of patients were treated with abobotulinum toxin A. Sixty-four ICD patients (51 (79.7%) females, onset at age 45.8 ± 13.7 years) were treated over 17.1 ± 13.9 (range 3 to 49) visits per patient; BT treatment efficacy increased gradually from initial treatment sessions to visit 13, when it achieved a steady state. While the subjective report of percentage improvement and its duration were around 78.9 ± 17.1% for 2.8 ± 1.0 months, respectively, the dose of BT increased significantly over the years (p = 0.006). Side effects (SE) were not rare, and commonly recurred after subsequent sessions and were usually mild and short-lasting, with dysphagia being the most common (~17.5%), followed by neck/arm weakness (11.9%) and cervical pain (8.9%). Repeated injections of BT for ICD remain beneficial for patients over several years of therapy, and despite mild SE, patients tend to adhere to a 3-4 months interval schedule.
MeSH term(s)	Acetylcholine Release Inhibitors/administration & dosage ; Adult ; Botulinum Toxins/administration & dosage ; Cohort Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Retrospective Studies ; Torticollis/diagnosis ; Torticollis/drug therapy ; Torticollis/physiopathology
Chemical Substances	Acetylcholine Release Inhibitors ; Botulinum Toxins (EC 3.4.24.69)
Language	English
Publishing date	2021-05-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2036826-4
ISSN	1476-3524 ; 1029-8428
ISSN (online)	1476-3524
ISSN	1029-8428
DOI	10.1007/s12640-021-00378-2
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Article ; Online: Psychiatric Patients on Neuroleptics: Evaluation of Parkinsonism and Quantified Assessment of Gait.

Yahalom, Hila / Israeli-Korn, Simon / Linder, Muli / Yekutieli, Ziv / Karlinsky, Keren Tchelet / Rubel, Yarin / Livneh, Vered / Fay-Karmon, Tsvia / Hassin-Baer, Sharon / Yahalom, Gilad

Clinical neuropharmacology

2019 Volume 43, Issue 1, Page(s) 1–6

Abstract: Objectives: We aimed to characterize parkinsonian features and gait performance of psychiatric patients on neuroleptics (PPN) and to compare them to Parkinson's disease (PD) and healthy controls (HC).: Methods: Hospitalized PPN (n = 27) were ... ...

Abstract	Objectives: We aimed to characterize parkinsonian features and gait performance of psychiatric patients on neuroleptics (PPN) and to compare them to Parkinson's disease (PD) and healthy controls (HC). Methods: Hospitalized PPN (n = 27) were recruited, examined, and rated for parkinsonian signs according to the motor part of the Movement Disorders Society Unified Parkinson's Disease Rating Scale and performed a 10-m "timed-up-and-go" (TUG) test with a smartphone-based motion capture system attached to their sternum. Gait parameters and mUPDRS scores were compared to those of consecutive age-matched PD patients (n = 18) and HC (n = 27). Results: Psychiatric patients on neuroleptics exhibited parkinsonism (mUPDRS score range: 8-44) but less than that of PD patients (18.2 ± 9.2 vs 29.8 ± 10.3, P = 0.001). TUG times were slower for PPN and PD versus HC (total: 30.6 ± 7.6 seconds vs 30.0 ± 7.3 seconds vs 20.0 ± 3.2 seconds, straight walking: 10.6 ± 2.7 seconds vs 10.6 ± 2.4 seconds vs 6.8 ± 1.2 seconds) (P < 0.001), and cadence and step length were similar among PPN and PD and different from HC as well. Although their gait speed was slower than HC but similar to PD, PPN had lower mediolateral sway (4.3 ± 1.1 cm vs 6.7 ± 2.9 cm vs 6.9 ± 2.9 cm, respectively, P < 0.001) than both. Conclusions: Parkinsonism is very common in hospitalized PPN, but usually milder than that of PD. It seems that wearable sensor-based technology for assessing gait and balance may present a more sensitive and quantitative tool to detect clinical aspects of neuroleptic-induced parkinsonism than standard clinical ratings.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antipsychotic Agents/adverse effects ; Antipsychotic Agents/therapeutic use ; Case-Control Studies ; Female ; Gait Analysis/methods ; Gait Analysis/statistics & numerical data ; Humans ; Inpatients ; Male ; Mental Disorders/complications ; Mental Disorders/drug therapy ; Mental Disorders/physiopathology ; Middle Aged ; Monitoring, Ambulatory/methods ; Parkinson Disease/physiopathology ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/complications ; Parkinson Disease, Secondary/physiopathology ; Young Adult
Chemical Substances	Antipsychotic Agents
Language	English
Publishing date	2019-12-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	199293-4
ISSN	1537-162X ; 0362-5664
ISSN (online)	1537-162X
ISSN	0362-5664
DOI	10.1097/WNF.0000000000000371
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Article ; Online: Carriers of both GBA and LRRK2 mutations, compared to carriers of either, in Parkinson's disease: Risk estimates and genotype-phenotype correlations.

Yahalom, Gilad / Greenbaum, Lior / Israeli-Korn, Simon / Fay-Karmon, Tsvia / Livneh, Vered / Ruskey, Jennifer A / Roncière, Léanne / Alam, Armaghan / Gan-Or, Ziv / Hassin-Baer, Sharon

Parkinsonism & related disorders

2018 Volume 62, Page(s) 179–184

Abstract: Introduction: The clinical characteristics of Parkinson's disease (PD) associated with both the LRRK2 p.G2019S mutation and a GBA variant (LRRK2-GBA-PD) have not yet been determined.: Methods: In this retrospective observational study of Ashkenazi- ... ...

Abstract	Introduction: The clinical characteristics of Parkinson's disease (PD) associated with both the LRRK2 p.G2019S mutation and a GBA variant (LRRK2-GBA-PD) have not yet been determined. Methods: In this retrospective observational study of Ashkenazi-Jewish (AJ) PD patients, we describe the clinical course and characteristics of LRRK2-GBA-PD and estimate the risk to develop PD for the double mutation carriers. Odds ratios (OR) were estimated using published data on frequencies of GBA and LRRK2 mutations. Demographic and clinical data was retrieved from medical records and from rating at last visit. Results: Our analysis included 236 PD patients, divided into four groups: LRRK2-PD (n = 66), GBA-PD (n = 78), GBA-LRRK2-PD (n = 12) and mutation-negative PD (MNPD, n = 80 randomly selected). The estimated ORs in different models for GBA-LRRK2 PD were 15-28 (95% CI 6.7-72.0, p < 0.0001), compared to AJ controls. Using logistic regression (while controlling for sex, age at onset and PD duration), we found that probable REM-sleep behavior disorder (RBD) was significantly more common for GBA-PD than for LRRK2-PD, while none of the GBA-LRRK2-PD patients reported RBD. Dementia was significantly more common for GBA-PD than for the LRRK2-PD and MNPD. Psychosis was the most common for GBA-PD and least common for LRRK2-GBA-PD. Conclusions: While GBA-PD is characterized by higher rates of dementia, probable RBD and psychosis, it seems that compared to the other groups, these features are less common for LRRK2-GBA-PD. This may imply to a possible protective effect of LRRK2 p.G2019S mutation among GBA variant carriers.
MeSH term(s)	Adult ; Aged ; Cohort Studies ; Female ; Genetic Association Studies/methods ; Genetic Predisposition to Disease/genetics ; Glucosylceramidase/genetics ; Heterozygote ; Humans ; Jews/genetics ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Male ; Middle Aged ; Mutation/genetics ; Parkinson Disease/diagnosis ; Parkinson Disease/genetics ; Retrospective Studies
Chemical Substances	LRRK2 protein, human (EC 2.7.11.1) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1) ; GBA protein, human (EC 3.2.1.45) ; Glucosylceramidase (EC 3.2.1.45)
Language	English
Publishing date	2018-12-13
Publishing country	England
Document type	Comparative Study ; Journal Article ; Observational Study
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2018.12.014
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Article ; Online: Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.

Ruskey, Jennifer A / Greenbaum, Lior / Roncière, Léanne / Alam, Armaghan / Spiegelman, Dan / Liong, Christopher / Levy, Oren A / Waters, Cheryl / Fahn, Stanley / Marder, Karen S / Chung, Wendy / Yahalom, Gilad / Israeli-Korn, Simon / Livneh, Vered / Fay-Karmon, Tsvia / Alcalay, Roy N / Hassin-Baer, Sharon / Gan-Or, Ziv

European journal of medical genetics

2018 Volume 62, Issue 1, Page(s) 65–69

Abstract: Background: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated ... ...

Abstract	Background: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered. Methods: GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD patients and 662 AJ controls, from Israel and New York. Additional AJ control data (n = 3044) from the Inflammatory Bowel Disease Exome Portal was used. Results: Full GBA sequencing increased the number of variants discovered by 17.4%, compared to targeted genotyping. An additional 17 PD patients were identified with GBA-associated PD. The p.E326K variant was found in 1.6% of AJ PD patients, making it the second most common PD-associated GBA variant in AJ. GBA variants were found in 18% of PD patients and 7.5% of controls (OR = 2.7, 95%CI = 1.9-3.8, p < 0.0001). Conclusion: Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials.
MeSH term(s)	Adult ; Aged ; Female ; Genetic Carrier Screening/methods ; Genetic Carrier Screening/standards ; Genome-Wide Association Study/standards ; Glucosylceramidase/genetics ; Heterozygote ; Humans ; Jews/genetics ; Male ; Middle Aged ; Parkinson Disease/genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/standards
Chemical Substances	Glucosylceramidase (EC 3.2.1.45)
Language	English
Publishing date	2018-05-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2184135-4
ISSN	1878-0849 ; 1769-7212
ISSN (online)	1878-0849
ISSN	1769-7212
DOI	10.1016/j.ejmg.2018.05.005
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