I. Treatment principles
(A) Comprehensive treatment including drug therapy, surgery, rehabilitation, psychotherapy and nursing care.
(B) Medication principles Dose titration; to achieve satisfactory results with the smallest dose; individualized treatment.
Second, drug treatment
(A) Protective therapy
1. Monoglutinin oxidase type B (MAOB) inhibitors such as selagiline, resagiline, etc.
2. Coenzyme Q10 1200mg/d. Peng Liebiao, Department of Neurology, Foshan Hospital of Traditional Chinese Medicine
3. Vitamin E 2000U/d.
(II) Symptomatic treatment
1. Early treatment (Hoehn-Yahr grade I-II)
(1) Patients are <65 years old and not associated with cognitive impairment
(1) Non-ergot DR agonist
Piribedil (Tamsulosin, 50mg x 15 tablets/box): start with 50mg/d and increase by 50mg/d weekly, maintenance dose is 50-250mg/d;
Pramipexole (Senfuro, 0.25mg x 30 tablets/box, 1mg x 30 tablets/box): 0.125mg tid to start, increasing by 0.375mg/d every 5-7 days, increasing by 0.75mg/d per week at 1.5mg/d, maintenance dose 1.5-4.5mg/d;
Methanesulfonic acid-alpha-dioxyergotryptine (Crepa, 5mg x 30 tablets/box, 20mg x 20 tablets/box): 2.5mg or 5mg bid to start, increasing 2.5mg/d every 5 days, maintenance dose 30-60mg/d.
②MAO-B inhibitor or add vitamin E
Silegiline (Midodrine, 5mg x 100 tablets/bottle):2.5-5mg bid (morning, noon).
Vitamin E 2000U/d.
③ Amantadine (0.1×100 tablets/bottle): 0.1 bid-tid, last dose before 4 pm;
If tremor is significant and other anti-PD drugs are ineffective then anticholinergics may be used.
Benzhexol (Antan, 2mg/tablet x 100 tablets/bottle): 1-2mg/d to start and increase by 1-2mg every 2-5 days for a total of 6-12mg/d in 3-4 doses;
Biperiden (Ankle spasm, 2mg/tablet): 2mg bid-qid;
Procyclidine (Kaimajun, 2mg/tablet, 5mg/tablet): 2-2.5mg tid to start, may be increased to 5mg tid.
④Add compound levodopa if the above regimen is not effective.
Dobutamine (Medopa, 0.25×30 tablets/box, levodopa/benserazide 200/50mg): 0.625 bid-tid to start, increasing by 0.625/d every 3-7 days, effective amount 0.375-0.75, maximum amount 1.0g;
Levodopa controlled-release tablets (Benadryl, 0.25/tablet, levodopa/carbidopa 200/50mg): 0.5-1 tablet bid-qid, gradually increase the dosage as needed, usually not more than 75mg of carbidopa and 750mg of levodopa daily.
(4) Compound levodopa + catechol-oxygenation-methyltransferase (COMT) inhibitor (entacapone, kotan, 0.2 x 30 tablets/bottle, 0.1-0.2 tid-qid).
(2) Patients aged >65 years with cognitive impairment
Prefer compounded levodopa, with DR agonists, MAO-B or COMT inhibitors if necessary. Benzedrine has more side effects and should not be used if possible, especially in elderly male patients, unless there is severe tremor and significantly affects the patient’s ability to perform daily activities.
2. Intermediate treatment ( Hoehn-Yahr grade III)
(1) Patients treated with DR agonists, MAO-B inhibitors or amantadine/anticholinergic drugs in the early stage should be treated with the addition of levodopa in the middle stage, when the improvement of symptoms is no longer obvious.
(2) Patients who are treated with low-dose combination levodopa in the early stage, and whose symptoms do not improve significantly in the middle stage, should be treated with an appropriate dose increase or addition of DR agonists, MAO-B inhibitors, amantadine or COMT inhibitors.
(3) Motor complications and/or non-motor symptoms are treated as detailed in the late stage treatment.
3. Late treatment (Hoehn-Yahr grade IV-V)
(1) Treatment of motor complications
①Treatment of symptom fluctuation
For end-dose deterioration: adjust protein diet; increase the number of compound levodopa; switch to compound levodopa controlled-release tablets; add DR agonist or conversion DR agonist; add COMT inhibitor or MAO-B inhibitor; surgical treatment (DBS).
Heterodynia: A. Treatment of dose peak heterodynia: reduce the dose of compound levodopa each time; if the patient is on compound levodopa alone, reduce the dose appropriately and add a DR agonist or add a COMT inhibitor; add amantadine; switch to compound levodopa aqueous solvent. B. Treatment of biphasic heterodynia: change controlled-release tablets to standard tablets or aqueous solvent; add a DR agonist or COMT inhibitor.
Continuous dopaminergic stimulation.
Surgical treatment.
② Treatment of postural gait disorders: active adjustment of body weight, stepping, striding, listening to commands, listening to music, walking with clapping or crossing objects (real or imaginary) may be beneficial. Use a walker or even a wheelchair if necessary and be well protected.
③ Treatment of non-motor symptoms.
A. Psychiatric disorders: reduce or stop the following drugs in sequence: anticholinergics, amantadine, MAO-B inhibitors, DR agonists; levodopa reduction; symptomatic treatment: cholinesterase inhibitors for cognitive impairment, clozapine and quetiapine for hallucinations and delusions, SSRI or additional DR agonists for depression.
B. Autonomic dysfunction: constipation – increase water intake and foods with high fiber content, discontinue cholinesterase inhibitors, use fructose, Long Yun Pills, rhubarb tablets, senna, etc.; urinary dysfunction – urinary frequency, urgency and urge incontinence available peripheral anti Cholinergic drugs, cholinergic preparations for those without reflexes in the forceps urinary muscle, intermittent clean catheterization for urinary retention, if caused by prostatic hyperplasia, surgery is feasible if necessary in severe cases; postural hypotension – increase salt and water intake, elevate the head position during sleep instead of lying down, wear elastic pants, do not get up quickly from the prone position, apply alpha-adrenergic agonist Midodrine.
C. Sleep disorders: if associated with nocturnal PD symptoms, add levodopa controlled-release tablets, DR agonist or COMT inhibitor; if caused by allodynia, anti-PD drugs taken at bedtime need to be reduced; choose short-acting sedative sleeping drugs; with restless legs syndrome and periodic limb movement disorder, use DR agonist or compound levodopa within 2h before going to sleep.
Third, surgical treatment
Surgery can be considered for those who have early drug treatment with markedly reduced efficacy of long-term treatment, and those who also have anisokinesis. Surgery has good effect on limb tremor and/or muscle ankylosis, but it has obvious effect on somatic mid-axis symptoms such as postural gait abnormalities and balance disorders.
Surgical approaches: 1. neurodesis – eliminated; 2. DBS. surgical targets include the pallidum medialis ( GPi), ventral intermediate nucleus of the thalamus (VIM), and STN.