الفهرس 
Review of literatureOnly 14 pages are availabe for public view
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Abstract
Parkinson’s disease (PD) is a neurodegenerative disease of the central nervous system caused due to the loss of dopaminergic neurons. It is classified under movement disorder as patients with PD present with tremor, rigidity, postural changes, and a decrease in spontaneous movements. Co-morbidities including anxiety, depression, fatigue, and sleep disorders are observed before the diagnosis of PD. Gene mutations, exposure to toxic substances and aging are considered as the causative factors of PD even though its genesis is unknown (Bhat et al., 2018).
Repetitive Transcranial magnetic stimulation (rTMS) is a noninvasive technique for brain stimulation, which is used to treat a variety of neuropsychiatric disorders including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines (Lefaucheur et al., 2014).
The pathophysiological mechanisms underlying the effects of TMS remain unclear. the effects of rTMS on neurotransmitters, synaptic plasticity, the genetic apparatus of neurons, glial cells, the prevention of neuronal death, dendritic growth and neurotrophic factors are described, Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols (Chervyakov et al., 2015).
Patients with PD may need additional nonpharmacological therapeutic interventions to preserve independent mobility and function (Kakkar and Dahiya, 2015). Repetitive TMS therapy has been tried for many aspects of PD. Motor symptoms are a cardinal feature of PD, for which evidence suggested moderate efficacy of rTMS. High-frequency (HF) rTMS over the M1 including less focal stimulation (e.g., leg and bilateral hand M1 rTMS) or over the DLPFC, and low-frequency (LF) rTMS over the SMA were most favorable. Also rTMS has been tried for non-pharmacological treatment of non-motor symptoms of PD including depression. A “weak recommendation” in favor of HF rTMS of the left DLPFC can be given for the treatment of depressive symptoms associated with PD. As such, rTMS has a potential to become an important adjunctive treatment for PD (Shirota et al., 2014).
In this study (double-blind placebo-controlled, randomized trial), sixty patients recruited with idiopathic Parkinson’s disease (IPD) and were randomized equally in case (received active rTMS stimulation) and control (received sham rTMS stimulation) groups. We aimed to assess the short term and long term effects of HF rTMS applied on left DLPFC (F3) on motor and non-motor manifestations of PD patients while patients in ON_state.
The current study data showed improvement of the motor function represented by an improvement of UPDRS III total motor score, rigidity, bradykinesia, axial and PIGD subscores in the active group not in the sham group only at T2. Bradykinesia subscore showed the highest improvement at T2 among all motor subscores. On the contrary, tremor subscore showed no statistically significant changes either in the active or sham groups.
Regarding cognitive functions which showed improvement in attention visual scanning, speed of eye-hand coordination which assessed by improving DS and TMTA scores in the active group only, executive functions also improved especially cognitive flexibility (lexical fluency and shifting set), inhibitory control, programming, sensitivity to interference which assessed by improving FAB score in T2 and T3, WCST PE score in T3 and TMTB score all favoring active group. Also, visuo-spatial functions assessed by CDT showed improvement in T2 favoring active group.
The results of this study confirming the antidepressant effect of rTMS in PD patients. The mean score of BDI decreased with significant improvement in the active group not in the sham group at T2 not T3. The current study showed also improvement of fatigue score which assessed by FSS with post hoc favoring T2. Also, day time sleepiness improved which assessed by ESS but with negative post hoc results.
Conclusion & Recommendations
The current study showed that HF-rTMS to the DLPFC resulted in highly significant improvement of motor functions (bradykinesia, rigidity, axial, postural instability and gait disturbance), depressive symptoms, visuo-spatial functions, and fatigue in patients with idiopathic PD. It also resulted in moderate significant improvement of cognitive functions (attention, working memory, inhibitory control and cognitive flexibility) and sleep disturbance (day time sleepiness). this improvement limited to the immediately after rTMS phase not maintained in the follow up except for FAB and WCST preservative errors which continued improvement in four weeks follow up. There was a moderate degree of correlation between most of baseline cognitive state and motor manifestations also between baseline depression and motor manifestations (daily activities and severity of disease).
from this conclusion, the following recommendations could be proposed:
rTMS could be an adjunctive treatment for PD patients to improve motor manifestations, cognitive dysfunction, depressive symptoms and fatigue when applied over DLPFC.
Replicating this study in a head to head comparison with the primary motor area (M1), stimulation to identify the optimum site of rTMS application.
Increase public awareness of therapeutic benefits and safety of rTMS among general practitioners, patients and caregivers.
Further studies are needed to investigate the long term effects of stimulation of this site (DLPFC) to confirm the null results in our study.