The goal of this observational study is to learn about impulse control disorders in Parkinson's disease patients.

The main question: it aims to answer:

• Detect Relative frequency of impulse control disorder among Parkinson's disease patients
• Detect Relation between impulse control disorders, and other non motor and motor symptoms in Parkinson's disease patients, using clinical, neurophysiological and radiological assessment

Parkinson disease (PD), is a multisystem disease with motor and non-motor (NM) deficits. Dementia and mild forms of cognitive impairment as well as neuropsychiatric symptoms (i.e., impulse control disorders) are frequent and disabling non-motor symptoms of Parkinson's disease (PD). According to the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-5), impulse control disorders are defined as "disruptive, impulse-control, while conduct disorders include conditions involving problems in the self-control of emotions and behaviors".

Many studies have highlighted potential risk factors for these behaviors, including the fact that that ICDs are associated with younger age, male sex and younger age at disease onset. Also these behaviors have been consistently linked to the use of dopaminergic medications used to treat Parkinson's disease motor symptoms (dopamine agonists, levodopa, and other agents) and less consistently to neuro-modulation techniques such as deep brain stimulation (DBS).

Up to 14-17% of patients with Parkinson's disease display a set of impulsive-compulsive spectrum disorders during the course of illness. Once uncontrolled behaviors develop, either patients fail understand or recognize the severity of their actions or hide them in shame with devastating social and financial results for themselves and their families.

Previous neuropsychological studies have also demonstrated that impulse control disorders in Parkinson's disease are associated with an altered cognitive profile, characterized by impaired cognitive flexibility and planning capability as well as by more inappropriate behavior and poor feedback processes. Also, Cognitive impairment and dementia in particular are associated with adverse outcomes, including gait impairment and falls, greater disability and caregiver burden, higher economic costs, and increased mortality.

Motor deficits have been repeatedly associated with changes in the activity of the motor cortex, in patients with Parkinson's disease. A key regulator of cortical motor output is the balance between excitation and inhibition, which can be assessed in humans with transcranial magnetic stimulation (TMS) techniques.

A common measure to explore inhibitory mechanisms is the short-interval intracortical inhibition (SICI) induced by paired-pulse TMS stimuli. Several studies have described reduced SICI (i.e. less inhibition) in the motor cortex of patients with Parkinson's disease.

The development of neuroimaging techniques, including Voxel-based morphometry (VBM), which is an automated quantitative magnetic resonance imaging (MRI) technique extensively used to assess the grey matter (GM) morphology changes in the brain and has been widely used in Parkinson's disease. The majority of the studies focused on grey matter (GM) changes in Parkinson's disease associated with motor and non-motor symptoms.

Reduced cortical thickness of fronto-striatal regions has been reported as the key feature to differentiate Parkinson's disease with impulse control disorders from Parkinson's disease without impulse control disorders patients, but a concomitant increased amygdala volume and a positive relationship between impulse control disorders severity and middle frontal and parietal cortical volumes have been also shown. In addition, two studies showed an increased cortical thickness in meso-limbic regions and another one reported a relatively preserved grey matter in Parkinson's disease with impulse control disorders patients compared with Parkinson's disease without impulse control disorders cases. Also studies showed that changes in grey matter volume are associated with lack of inhibition related to impulse control disorders behaviors in Parkinson's disease.

Therefore; impulse control disorder is becoming an increasingly recognized psychiatric complication in Parkinson's disease; and whether or not it's associated with cortical dysfunction, and further cognitive and gait and balance affection, need further clinical, neurophysiological and radiological analysis, to further understand the underlying mechanism.

1. Inclusion criteria:

   • The study will include patients with Parkinson's disease, diagnosed according to the UK Parkinson's Disease Society Brain Bank criteria. (16)
   • Bradykinesia (slowness of initiation of voluntary movements with progressive reduction in speed and amplitude of repetitive actions).
   • And at least one of the following: Muscular rigidity, 4-6 Hz rest tremor Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction

2. Exclusion criteria:

   • History of strokes with stepwise progression of Parkinsonian features.
   • History of head injury.
   • History of definite encephalitis.
   • Oculogyric crises.
   • Neuroleptic treatment at onset of symptoms.
   • Strictly unilateral features after three years.
   • Supranuclear gaze palsy.
   • Cerebellar signs.
   • Early severe autonomic involvement.
   • Early severe dementia with disturbances of memory, language and praxis.
   • Babinski sign.
   • Presence of a cerebral tumor or communicating hydrocephalus on CT scan.
   • Negative response to large doses of levodopa (if malabsorption excluded).

Patients with Parkinson's disease attending Assiut University neurology outpatient clinic and internal department

The confidentiality of patient's information will be maintained throughout the study, only clinical data will be shared