The main determinants of treatment strategies for Parkinson’s disease (PD) include the type, character, and extent of the main symptoms. In turn, the major symptoms depend on the course of the disease and vary widely among individuals. Some pathologic studies have reported that patients with PD enter the progressive stage with almost total loss of nigrostriatal dopamine 4 years after the onset of the disease. Thus progressive PD faces several therapeutic challenges. Treatment of motor and non-motor symptom exacerbations that occur with disease progression and treatment of associated motor and non-motor complications. As the disease progresses, the motor deficits further worsen with the development of increased postural gait disturbances and the occurrence of falls. Refractory tremor develops. As well as the development of non-motor symptoms such as dementia, psychiatric symptoms, postural hypotension, and dysuria. Disease progression is also a major contributor to motor complications. Dose-related dose fluctuations (end-of-dose phenomenon) can occur in the middle stages of the disease, and unpredictable symptomatic fluctuations and anisotropy that are not dose-related can occur in the late stages of the disease. Therefore, we need to develop treatment strategies for progressive PD based on evidence-based guidelines. I. Treatment of motor complications End-of-dose phenomenon refers to the shortening of the effective duration of action of each dose and the regular fluctuation of symptoms with blood concentration. The incidence of end-dose phenomenon has been reported differently in different studies, but it can be seen that the incidence of end-dose phenomenon increases with the course of the disease.Risk factors for end-dose phenomenon identified in the STRIDE-PD study include low age of onset (more affected by impulse-like stimulation); high UPDRS ability to perform activities of daily living scores as well as dyskinesia scores (the extent of the disease is an endogenous cause of end-dose phenomenon); female (probably low body weight); and low body weight. (possibly related to low body weight and high LD dose per unit of body weight); and high LD dose (LD dose is an independent risk factor for end-of-agent phenomenon, and a daily dose of up to 400 mg is relatively safe). Therefore, the pathogenesis and etiology of end-of-dose phenomenon may depend on the disease progression, including disease extent and duration, on the one hand, and on the treatment-related aspects, including the cumulative LD dose, in particular the LD dose per unit of body weight, as well as the duration of LD dosing, on the other hand. and the timing of LD initiation. non-LD dopaminergic drugs such as DA. Whether the latter two are related remains to be further explored. Some reports have found no clear correlation between motor complications and the timing of LD application and correlation with disease duration and LD dose per unit body weight. EFNS-2013 recommendations for the treatment of end-of-dose phenomena: 1. Adjust the number of levodopa administrations (this may be effective in the early stages of exercise fluctuations, increasing the daily dose of LD, which may further exacerbate LD-associated exercise complications in the long term); 2. Add a COMT inhibitor or a B-type MAO inhibitor (both types of drugs reduce the off period by 1-1.5 h per day.) The only direct comparative study showed that No significant difference between entacapone and resagiline in improving end-of-dose phenomena. Tolcapone, although more efficacious than entacapone, should only be used when other methods are ineffective due to potential hepatotoxicity. Resagiline should not be added to selegiline; serious cardiovascular adverse effects can occur); 3. Addition of dopamine agonists (non-ergot dopamine agonists are first-line drugs. Ergot is a second-line drug. There is no evidence to date that one type of dopamine agonist is superior to other types of dopamine agonists. Switching from one dopamine agonist to another may be effective in some patients. (Note the dose-efficacy relationship for dopamine agonists); 4. Addition of amantadine or anticholinergic medication (if the patient has severe end-of-dose phenomenon and improvement is not clear with the above adjustments, anticholinergic medication (for younger patients) or amantadine may be added and may be effective for some patients). Most patients with PD will eventually require a combination of multiple medications. For severe motor fluctuations: first try the efficacy of the oral medication approaches described above, and if these approaches have been tried and remain ineffective for severe predictable motor fluctuations, then continuous dopaminergic stimulation is recommended to treat severe motor fluctuations. The following methods are recommended: STN-DBS; subcutaneous apomorphine injection syringe pump; transjejunal levodopa/carbidopa gel infusion. II. Treatment of Unpredictable On-Off Phenomena Unpredictable on-off phenomena are fluctuations between sudden remission (on period) and exacerbation (off period). There is a lack of evidence as to whether oral medication regimens that are effective for end-of-dose phenomena are also effective for unpredictable on-off phenomena.The 2011 edition of the EFNS guidelines suggests that oral levodopa dispersible tablets may improve delayed on periods; SYN-DBS is effective. Third, the treatment of anisocoria Anisocoria is often characterized by involuntary dance-like, dystonia-like movements that can involve the head, face, limbs, and trunk. There are three main forms: dystonic anisotropy, dystonia, and biphasic anisotropy. Risk factors for anisokinesis include: low age of onset (more affected by impulse-like stimuli); high LD dose (linear correlation between incidence of anisokinesis and positive correlation with LD dose); low body weight, females (LD dose per unit of body weight); and high UPDRS daily living skills scores. Recommended treatment for dose-peak anisotropy: reduce levodopa dose, reduce or discontinue MAO-B inhibitors or COMT inhibitors, add amantadine, STN-DBS, add atypical antipsychotics, continuous subcutaneous infusion of apomorphine, transdermal jejunal infusion of levodopa. Recommended treatment for bipolar disorder: bipolar disorder is difficult to treat and research evidence is lacking.STN-DBS is efficacious for bipolar disorder, the dose and frequency of administration of levodopa can be increased, a further option would be to produce a predictable response to levodopa in larger doses and fewer doses, and a final option would be to try apomorphine and transjejunal infusion of levodopa. IV Neuromodulation of Severe Tremor The targets of DBS for PD tremor: the STN (STC pathway) and the VIM (CTC pathway).