Parkinson’s, a chronic multisystem degenerative disease of the central nervous system accompanied by tremors. Today, let’s unravel the mystery of tremors! The culprit: reduced dopamine levels in the brain The pathological changes in primary Parkinson’s disease are mainly in the substantia nigra, striatum, brainstem and cerebral cortex, and the lack of dopamine production due to degeneration of nigrostriatal dopamine nerve cells is the key to the disease. The nigrostriatal cells act like a processing plant to produce dopamine, and if the processing plant is destroyed, then dopamine production in the brain is reduced, which is the main cause of Parkinson’s disease. Four major motor symptoms indicate Parkinson’s disease Resting tremor Involuntary trembling of the limbs while watching TV or talking to others, and the trembling can be reduced or stopped transiently when changing position or moving. This is the most important characteristic of tremor in Parkinson’s disease. The tremor increases when the patient is emotionally or mentally stressed and can disappear completely after sleep. Muscle rigidity The patient’s limbs and trunk usually lose their flexibility and become rigid. Initially, they feel inflexible, stiff and awkward in the movement of their arms and legs, and it gradually worsens. They are slow in movement, reluctant to move actively, and have difficulty even doing some movements of daily life. Fewer facial expressions, patients seldom blink their eyes, their eyes turn less, and their expressions are dull, as if they are wearing a mask. Once walking, the body leans forward, the center of gravity shifts forward, the pace is small and faster, and the patient cannot stop in time and rush forward, sometimes falling, i.e. “panic gait”. Sometimes patients write smaller and smaller, also known as “small writing disorder”. Postural balance disorder At rest, flexor muscle tone is higher than that of the extensor muscles. Patients have special postures such as head tilting forward, trunk slightly flexed, upper arm inward, elbow bending, wrist slightly extended, finger metacarpal joint bending and interphalangeal joint straightening, thumb to palm, hip and knee joints mildly bent. Tremor is not necessarily Parkinson’s In fact, almost everyone may have had tremor in different situations. Tremor can be divided into many types, usually into physiological tremor and pathological tremor, and postural tremor and resting tremor. Parkinson’s disease: often manifests as resting tremor. The main characteristics of tremor in Parkinson’s disease are resting, involuntary and continuous, and not controlled by voluntary consciousness. In the early stage, the tremor is small in amplitude or intermittent, with a slightly slower frequency. The hand tremor can be manifested as a pill-rubbing action, which can be reduced or disappear transiently when the limb changes position or does the action, and can be aggravated when emotionally excited, often gradually developing from one limb to other limbs on the same or opposite side. Idiopathic tremor: It is often manifested as postural tremor. Idiopathic tremor often occurs when doing fine movements (e.g., when clamping dishes, pouring tea, standing for too long, etc.) and is easily affected by tension and exertion. In severe cases, tremor occurs whenever something is held and becomes more severe the closer one gets to the target. Calming emotions and active conscious control can improve symptoms to a certain extent. Parkinson’s disease and idiopathic tremor are two different diseases. In addition to the differences in the manifestation of tremor, the main point of discrimination is that patients with Parkinson’s disease have other manifestations such as slow movements and high muscle tone at the same time, and all symptoms develop more rapidly, while idiopathic tremor does not. Drug treatment should take into account age and the extent of the disease Currently, symptomatic and partially neuroprotective treatments for Parkinson’s disease are often used clinically. To date, we do not have a cure for Parkinson’s disease, nor do we have a more ideal drug. Usually doctors implement Parkinson’s disease treatment based on our Parkinson’s disease clinical treatment guidelines. In recent years the philosophy of early drug selection and treatment for Parkinson’s disease has faded on the age cut-off values, and only the younger or older groups are recommended. Younger, less symptomatic: Patients with early Parkinson’s disease with mild functional impairment and no cognitive decline should prefer monoamine oxidase B inhibitors, such as selagiline and resagiline or the neuroprotective agent coenzyme Q10, and also concurrent dopamine agonists, such as tamsulosin, pramipexole or ropinirole. Older, more symptomatic patients: In patients with early Parkinson’s disease or with moderate-to-severe functional impairment and cognitive decline, levodopa preparations should be preferred for treatment, such as dobutamine and carzodopa controlled-release or levodopa + carbidopa + cortexan (triple) preparations. Principles of Parkinson’s drug therapy All drugs are dosed by dose titration to avoid the occurrence of recent adverse drug reactions. The minimum dose is used to maintain a fair functional status or a satisfactory quality of life. In order to maintain a long, satisfactory outcome, a long flow of drugs should be used, without seeking full effectiveness. Early treatment is recommended to use a combination of multiple drugs in small doses; try to avoid the occurrence of motor complications due to excessive doses of levodopa in the long term. Scientific and reasonable medication can enable most patients to control symptoms and survive for 20-25 years, or even longer. Once Parkinson’s disease is diagnosed, it should be treated with medication immediately. Studies have concluded that early treatment has a disease-modifying effect on degenerative lesions like Parkinson’s disease that require long-term treatment. Although there is no definite drug cure for Parkinson’s disease, taking disease-modifying medications can contain, delay or reverse the course of the disease, and early medication can certainly alter the disease process, improve symptoms and enhance quality of life. Patients should be encouraged to work, participate in social activities and medical physical therapy, walk, swim and play tai chi in the early stage of the disease without psychological or physical effects on the patient. Response to adverse reactions to medication Medication has always been the most basic method in the treatment of Parkinson’s disease, but medication is a double-edged sword, and the adverse reactions it brings are just like a shadow, and these adverse reactions are the most difficult problems in the late stage of treatment. End-of-Dose Phenomenon: A sign of diminished efficacy in the early stages of drug therapy. The end-of-dose phenomenon is a phenomenon of decreasing efficacy after early application of levodopa for Parkinson’s disease, mainly manifested as the duration of levodopa’s efficacy is getting shorter and shorter, for example, the efficacy of compound levodopa can be maintained for about 4 h at the beginning of the medication, but after 2~3 years of administration, the efficacy of compound levodopa can only be maintained for 2~3 h or even shorter, and if the number of doses is not increased, the symptoms of Parkinson’s disease will appear in the medication interval. If the number of doses is not increased, the symptoms of Parkinson’s disease may worsen or worsen in the early morning. Countermeasures Increase the number of doses of levodopa, shorten the dosing interval, or use controlled-release tablets. The half-life of levodopa is only 1-2 h, which is relatively short. Increasing the number of levodopa doses or using controlled-release tablets can maintain steady-state plasma drug concentrations in an effective therapeutic concentration range. If this method does not improve the end-of-dose phenomenon, the dose of levodopa can be increased appropriately, or dopamine receptor agonists and monoamine oxidase inhibitors can be used in combination to improve symptoms. The current new concept of Parkinson’s disease treatment is to try to control the daily dose to 400 mg when applying levodopa therapy in the early stage, otherwise take other drugs in combination. Switching phenomenon: the kink in the late stage of drug therapy. The switching phenomenon occurs late in the course of medication (about 3 to 5 years of medication). Throughout the day, the patient’s symptoms fluctuate between sudden remission (on phase) and exacerbation (off phase), which can alternate several times over and over again. This change is very rapid and unpredictable (known), like a power switch. The clinical image of this physiological phenomenon is called the switch phenomenon. Countermeasures ① While continuing medications such as methadopa, it is preferred to add COMT inhibitors (e.g. Kodan, Tolcapone, etc.), which can optimize the efficacy of levodopa and also reduce the dosage of levodopa, followed by the addition of dopamine receptor agonists with long half-lives (e.g. bromoxynil, pramipexole, piribedil, etc.), or monoamine oxidase B inhibitors (sellegrin). ② Reduce the dose of each dose and increase the number of doses while maintaining the total dose of medication such as methyldopa. (3) Subcutaneous injection of apomorphine can be used in patients with severe “off phase”. If all of the above methods are ineffective, surgical treatment can be considered. Hyperkinesia: a sign of high dose of medication. “Heterokinesia is a choreographic, tachycardia or simple repetitive involuntary movements that commonly occur in the facial muscles, neck, back and limbs. In severe cases, it can affect daily life, activities and longevity, as the involuntary movements can be large in magnitude and can continue throughout the levodopa onset period. When xerostomia occurs, it is often a sign of an overdose of the drug. Countermeasures If the involuntary movements are only mild and are made worse by reducing the medication, the original treatment can be maintained. If the anisocoria is obvious, the dose of dopamine can be reduced and the COMT inhibitor can be increased, or a dopamine agonist can be applied, and if necessary, levodopa and dopamine agonist can be taken separately with an interval of 1~1.5 h. If the anisocoria seriously affects the patient’s ability to take care of himself and cannot be solved by the adjustment of medication, minimally invasive surgical treatment can be considered.