Zonisamide (ZNS) (1,2-Benzisoxazole-3-methanesulfonamide) is an anti-epileptic drug. In three double blinded placebo controlled studies, ZNS- as an adjunctive treatment- showed beneficial effects on motor symptoms of PD with a low incidence of adverse events. As a result 25 mg daily of ZNS was approved in 2009 in Japan as an adjunctive treatment in PD patients whose condition responded insufficiently to Levodopa treatment.

Most observations of a beneficial effect of ZNS have been in Japanese people, and the antiparkinsonian mechanism of action is unclear. So, ZNS is a promising but still investigational drug to treat PD and more studies are warranted.

this study will investigate the efficacy and tolerability of Zonisamide as an adjunctive treatment in Egyptian patients with advanced PD, including motor fluctuations, levodopa induced dyskinesia and existing nonmotor symptoms. Additionally it investigates its effects on quality of life of PD patients.

Type of Study: Randomized double blinded Placebo controlled study.

• Study Setting: Movement disorders clinic of neurology department, Ain Shams University Hospitals.
• Study Period : 2 years.
• Study Population: Patients with advanced PD and insufficient response to dopaminergic drugs .

Inclusion Criteria:

• Age older than 18 years of both male and female genders.
• Individuals diagnosed with PD based on the presence of 2 of 3 cardinal features & United Kingdom bank criteria for idiopathic Parkinson's disease.
• Patients with manifestations of advanced PD defined according to the consensus on the definition of advanced PD.
• Inadequate response to dopaminergic medications due to limitations related to side effects, or levodopa related long-term problems as wearing-off phenomena, "on"-"off" fluctuation, levodopa induced dyskinesia and freezing phenomena, no-"on" and delayed-"on,".

Exclusion Criteria:

1. Patients with atypical or secondary parkinsonian syndromes excluding PD.
2. Patients who could not perform the tests.
3. Women who were or might be pregnant, who did not practice effective contraception and were of childbearing potential, or who were breastfeeding.

Ethical Considerations:

All of the patients will be informed of the objectives, procedures and possible benefits and risks of the study and will provide written voluntary consent.

The study will conform to the standards of the Ethical Review Committee, Ain Shams University.

Study Procedures:

- Patients diagnosed with PD will be evaluated for inclusion and exclusion criteria. Eligible patients will be randomly assigned to one of three groups: placebo group , ZNS group 25 mg and ZNS group 50 mg (30 patients each).In ZNS 50 mg group, ZNS will be started with a dose of 25 mg daily for one week then increased to 50 mg once daily to minimize side effects. The dosage and regimen of ongoing antiparkinsonian drugs and other drugs that may affect PD symptoms will remain unchanged one month before and through the treatment period.

Inclusion Criteria:

1 -Age older than 18 years of both male and female genders. 2-Individuals diagnosed with PD based on the presence of 2 of 3 cardinal features & UK bank criteria for idiopathic Parkinson's disease. 3-Patients with motor complications of PD (Hoehn and Yahr stage 2-3)(on therapy) and at least 2 hours off time.

Exclusion Criteria:

1 -Patients with atypical or secondary Parkinsonism syndromes excluding PD. 2-Patients who could not perform the tests. 3-Women who were or might be pregnant, who did not practice effective contraception and were of childbearing potential, or who were breastfeeding.

the PD will be randomized to 3 arms. Randomization was done by a research randomization, The copy of the randomization table of patients to the 3 groups was kept with 2 different personnel not working on the study.