Parkinson’s disease management

The occurrence of motor fluctuations and dyskinesias in response to anti-Parkinson medications, and the unpredictable deterioration of motor functions in the off medication state and dyskinesias in the on medication state may render patients disabled for many hours each day.

There is no evidence that delaying levodopa or dopaminergic therapy has any benefit or that levodopa is toxic.

The initiation of medications occur when patients experience functional impairment or social embarrassment from their disease symptomatology.

Oral formulations of levodopa are the main treatment for motor symptoms, although tremor may be less responsive than bradykinesia and rigidity in some patients.

The  duration of effect after a levodopa dose typically several hours, starts to shorten on average after four years.

Reduced efficacy results in periods of reduce symptomatic relief.

Motor fluctuations are probably due to the short half-life of levodopa, inconsistent G.I. absorption, progressive degeneration of dopaminergic neurons.

Common dose related side effects include dyskinesia, worsening of hallucinations, or behavioral problems, orthostatic hypotension and nausea.

If the disease and motor symptoms are mild but require therapy, an initial monoamine oxidase type B inhibitor such a selegiline or rasagiline may be tried before moving to more potent treatments such as a dopamine agonist or levodopa.

In early Parkinson’s disease a small symptomatic benefit is demonstrated by monoamine oxidase type B inhibitors.

Anti-cholinergic medications a more effective than placebo in improving motor functions in PD, but their benefits for tremor are inconclusive.

Dopamine agonist so currently less commonly used than in the past because unfavorable side effect profiles, including dose, dependent dyskinesia when used as injunctive therapy.

Anticholinergic drugs, targeting tremor are less commonly used now than in the past because they may cause worsening cognition in older patients.

On demand therapies for dopaminergic therapies for severe frequent off episodes include subcutaneous injection with sublingual apomorphine and inhaled levodopa.

Continuous enteral delivery of levodopa through aan intrajejunal pump, subcutaneous delivery of apomorphine, or delivery of levodopa means of subcutaneous pump has been used in advanced cases.

Beta blockers such as propranolol may improve parkinsonian tremor and motor function.

Clozapine improves Parkinson’s disease tremor.

Amantadine results for efficacy is not clear

For more seriously impaired PD patients levodopa or a dopamine agonist is administered.

Trials demonstrate levodopa provides the greatest symptomatic benefit.

Levodopa associated with fewer side effects such as edema, somnolence, impulse control disorders, freezing and hallucinations than dopamine agonists.

Dopamine agonists are have fewer dopaminergic motor complications of dyskinesia than levodopa.

Dopamine agonists usually initiated in individuals younger than 60 years since dyskinesia more common in younger patients.

The early advantage of dopamine agonists over levodopa decreases over time.

The effect of levodopa can be enhanced by adding catecholamine inhibitors or MAO inhibitors which block synaptic dopamine metabolism.

Patient with Parkinson’s disease presenting with non-motor symptoms including worsening of symptoms with disease progression, response to dopamine or acetylcholine therapy, and potential decrease in Parkinson’s disease-related dementia.

Patients also experience depression, anxiety, hallucinations, delusions, autonomic symptoms like orthostatic hypotension, pain, and constipation.

Treatment options for nonmotor symptoms are anticholinesterase inhibitors, memantine, selective serotonin reuptake inhibitors, dopamine agonists, anti-psychotic medications, cognitive behavioral therapy counseling, increased fluid intake, dietary changes, medications like fludrcortisone, midodrine, droxydopa, doperminergic therapy, atropine drops, dietary fiber, stool softeners, and laxatives.

Patients with complex presentation of Parkinson’s disease with various non-motor symptoms and psychiatric manifestations.

Pain management and constipation are multifactorial.

Autonomic symptoms and cognitive symptoms also need attention.

Exercise is the most common rehabilitative therapy with stretching, strength training, and aerobic exercises.

 

Deep brain stimulation of the subthalamic nucleus or the Globus pallidus internus  is an established treatment for Parkinson’s disease.

 

Deep brain stimulation (DBS) requires intracranial placement of thin leads on one side, or both, sides of the brain, typically into the subthalamic nucleus or globus pallidus, connected to a neurostimulator subcutaneously in the subclavicular  region.

 

 Most patients undergoing deep brain stimulation have motor fluctuations that are poorly controlled by medication, which justifies the procedure.

DBS improves the quality life and alleviates motive, fluctuations, and symptoms that occur in the absence of medication.

 

DBS increases the period of time that symptoms occur in the absence of medication and allows for reduction in medication dose of approximately 50%, especially when the subthalamic nucleus is targeted.

 

The motor benefit from DBS may persist for up to 15 years.

 

Most non-motor symptoms of PD, such as cognitive impairment, mood changes, apathy, and autonomic symptoms, and some motor symptoms, such as impaired balance, and freezing of gait, typically do not improve with the use of DBS.

 

DBS complications include dyskinesia and worsening of speech, gait, and balance, and in rare cases, alteration in mood, cognition or behavior may occur.

 

Focused ultrasound ablation, a noninvasive, externally employed sonication energy, allows for ablative surgery without the need of craniotomy, and can focus on brain lesions and is potentially safer than  radiofrequency surgery.