Journal of Movement Disorders

Youssef Abida

2 Articles

The Impact of LRRK2 G2019S on Parkinson’s Disease: Clinical Phenotype and Treatment in Tunisian Patients: Guedi Ali Barreh, Ikram Sghaier, Youssef Abida, Alya Gharbi, Amina Nasri, Saloua Mrabet, Amira Souissi, Mouna Ben Djebara, Sameh Trabelsi, Imen Kacem, Amina Gargouri-Berrechid, Riadh Gouider; J Mov Disord. 2024;17(3):294-303. Published online April 23, 2024; DOI: https://doi.org/10.14802/jmd.23276

1,800 View
109 Download
1 Web of Science
1 Crossref

Objective
LRRK2-G2019S is the most frequent mutation in North African Parkinson’s disease (PD) patients. Data on its impact on disease progression and treatment response remain elusive. Therefore, we investigated the clinical features, treatments, and complications of PD in Tunisian patients according to their LRRK2-G2019S profile.
Methods
This longitudinal retrospective study was performed in the Department of Neurology, Razi University Hospital. We included clinically diagnosed PD patients according to the Movement Disorders Society criteria and reviewed their medical records for clinical, treatment, and neuropsychological assessments. All patients were screened for the LRRK2-G2019S mutation using Sanger sequencing. The correlation between LRRK2-G2019S and clinical PD features was evaluated.
Results
We included 393 PD patients, 41.5% of whom had LRRK2-G2019S mutations. Patients with mutations were younger (p = 0.017), and female PD patients had a greater mutation frequency (p = 0.008). Mutation carriers exhibited distinct clinical features, with a greater frequency of postural instability gait difficulty forms (adjusted-p < 0.001). During disease progression, carriers showed a faster annual progression in the Unified Parkinson’s Disease Rating Scale Section III scores (adjusted-p = 0.009), and significantly higher levodopa equivalent dose values in later stages (1060.81 vs. 877.83 for 6-8 years). Motor complications, such as dyskinesia (adjusted-p < 0.001) and motor fluctuations (31.9% vs. 25.7%, adjusted-p < 0.001), were more prevalent in carriers, particularly in the later stages. LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms, including episodic memory (adjusted-p < 0.001), attention (adjusted-p < 0.001), and dysexecutive disorders (adjusted-p = 0.038), as well as neuropsychiatric symptoms and dysautonomic signs.
Conclusion
The present study demonstrated that the variability of the clinical profile among Tunisian PD patients was explained by the incomplete penetrance of LRRK2-G2019S, which increased with age. Further studies using biomarker and disease progression data are necessary to improve PD management.

Citations

Citations to this article as recorded by

Glutathione S-transferase polymorphisms (GSTM1/GSTT1) outcomes in clinical profile and treatment responsiveness among Tunisian cohort of Parkinson’s disease
Ali Barreh Guedi, Sghaier Ikram, Abida Youssef, Gharbi Alya, Souissi Amira, Mrabet Saloua, Nasri Amina, Ben Djebara Mouna, Kacem Imen, Gargouri-Berrechid Amina, Gouider Riadh
Journal of Neural Transmission.2024;[Epub] CrossRef

Phenotypic Spectrum of Progressive Supranuclear Palsy: Clinical Study and Apolipoprotein E Effect: Amina Nasri, Ikram Sghaier, Anis Neji, Alya Gharbi, Youssef Abida, Saloua Mrabet, Amina Gargouri, Mouna Ben Djebara, Imen Kacem, Riadh Gouider; J Mov Disord. 2024;17(2):158-170. Published online January 30, 2024; DOI: https://doi.org/10.14802/jmd.23178

1,899 View
91 Download
1 Web of Science
1 Crossref

Abstract PDF

Objective
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder encompassing several phenotypes with various motor and cognitive deficits. We aimed to study motor and cognitive characteristics across PSP phenotypes and to assess the influence of apolipoprotein E (APOE) gene variants on PSP phenotypic expression.
Methods
In this 20-year cross-sectional study, we retrospectively reviewed the charts of all patients classified as PSP patients and recategorized them according to phenotype using the Movement Disorder Society criteria (2017). Phenotypes were divided into three subgroups, Richardson’s syndrome (PSP-RS), PSP-cortical (PSP with predominant frontal presentation [PSP-F] + PSP with predominant speech/language disorder [PSP-SL] + PSP with predominant corticobasal syndrome [PSP-CBS]) and PSP-subcortical (PSP with predominant parkinsonism [PSP-P] + PSP with progressive gait freezing [PSP-PGF] + PSP with predominant postural instability [PSP-PI] + PSP with predominant ocular motor dysfunction [PSP-OM] + PSP with cerebellar ataxia [PSP-C] + PSP with primary lateral sclerosis [PSP-PLS]), based on clinical presentation during the first 3 years after symptom onset, which defines the early disease stage. Clinical and neuropsychological assessment data were collected. Genotyping of APOE was performed using restriction fragment length polymorphism polymerase chain reaction and verified by Sanger sequencing.
Results
We included 112 PSP patients comprising 10 phenotypes classified into 48 PSP-RS, 34 PSP-cortical (PSP-CBS, 17.6%; PSP-F, 9.4%; PSP-SL, 8.2%) and 30 PSP-subcortical (PSP-P, 11.6%; PSP-PI, 8%; PSP-OM, 2.7%; PSP-PGF, 1.8%; PSP-C, 1.8%; PSP-PLS, 0.9%) subgroups. PSP-RS patients were older at disease onset (p = 0.009) and had more akinetic-rigid and levodopa-resistant parkinsonism (p = 0.006), while PSP-cortical patients had more tremors and asymmetric and/or levodopa-responsive parkinsonism (p = 0.025). Cognitive domains were significantly less altered in the PSP-subcortical subgroup. Overall, PSP-APOEε4 carriers developed parkinsonism earlier (p = 0.038), had earlier oculomotor dysfunction (p = 0.052) and had more altered cognitive profiles. The APOEε4 allele was also associated with a younger age of parkinsonism onset in the PSP-RS phenotype group (p = 0.026).
Conclusion
This study demonstrated the wide phenotypic spectrum of PSP among Tunisians. Disease onset and akinetic-rigid and levodopa-resistant parkinsonism were the hallmarks of the PSP-RS phenotype, while milder cognitive impairment was characteristic of the PSP-subcortical subgroup. The APOEε4 allele was associated with earlier parkinsonism and oculomotor dysfunction and seemed to play a role in defining a more altered cognitive profile in PSP patients.

Citations

Citations to this article as recorded by

Clinical and molecular predictors of survival among atypical parkinsonian syndromes in a North African tertiary referral center
Ikram Sghaier, Amina Nasri, Amal Atrous, Youssef Abida, Alya Gharbi, Amira Souissi, Saloua Mrabet, Mouna Ben Djebara, Imen Kacem, Amina Gargouri-Berrechid, Riadh Gouider
Journal of the Neurological Sciences.2024; 464: 123155. CrossRef

Author index