Question

a 72 year old Male patient comes to the clinic with his wife. John says that his balance is off and he is having difficulty walking. He feels lightheaded if he stands up too quickly and is incontinent of urine at times. On physical examination, the client has a noticeable right hand tremor. He shuffles his feet while walking, his facial expression is flat, and his speech is slow and monotone. Identify each abnormality and explain how its mechanism can be explained by Parkinson's disease. What treatment options would you discuss with the patient and his wife? Explain the pathophysiology reason that the treatment works.

Answer 1

The symptoms John is experiencing due to Parkinsons are:

• Tremor. A tremor, or shaking, usually begins in a limb, often hand or fingers. The patient may rub his thumb and forefinger back and forth, known as a pill-rolling tremor. The hand may tremble when it's at rest.
• Slowed movement (bradykinesia). Over time, Parkinson's disease may slow the movement, making simple tasks difficult and time-consuming. The steps may become shorter when he walks.
• Impaired posture and balance. The posture may become stooped, or may have balance problems as a result of Parkinson's disease.
• Speech changes. He may speak softly, quickly, slur or hesitate before talking. Speech may be more of a monotone rather than have the usual inflections.
• Bladder problems. Parkinson's disease cause bladder problems, including being unable to control urine or having difficulty urinating.
• People with Parkinsonian gait usually take small, shuffling steps. They might have difficulty picking up their feet.

Pathophysiology of Parkinsons disease;

Degeneration of dopamine neurons is particularly evident in a part of the substantia nigra called the pars compacta. Significantly, the loss of dopamine in the pars compacta increases the overall excitatory drive in the basal ganglia, disrupting voluntary motor control and causing the characteristic symptoms of Parkinsons disease.

As the severity of Parkinsons disease increases, the depletion of dopamine leads to further changes in the basal ganglia pathways, including altered function of other basal ganglia neurotransmitters such as glutamate, GABA, and serotonin. Although there is relative vulnerability of dopamine-producing neurons in the substantia nigra, not all dopamine cells are affected in Parkinson’s disease; in some parts of the brain the dopamine-producing neurons are relatively spared.

Lewy bodies are abnormal aggregates and inclusions of protein that develop inside nerve cells in people with Parkinson’s disease. The aggregations usually consist of insoluble fibrillary aggregates containing misfolded proteins. A large number of molecules have been identified in Lewy bodies but a protein called alpha-synuclein is the main component.

Treatment Options:

Parkinson's disease can't be cured, but medications can help control symptoms, often dramatically. In some more advanced cases, surgery may be advised.

People with Parkinson's disease have low brain dopamine concentrations. However, dopamine can't be given directly, as it can't enter the brain.

Carbidopa-levodopa. Levodopa, the most effective Parkinson's disease medication, is a natural chemical that passes into the brain and is converted to dopamine

Carbidopa-levodopa infusion. Duopa is a brand-name medication made up of carbidopa and levodopa. However, it's administered through a feeding tube that delivers the medication in a gel form directly to the small intestine.

Dopamine agonists. Unlike levodopa, dopamine agonists don't change into dopamine. Instead, they mimic dopamine effects in the brain. However, they last longer and may be used with levodopa to smooth the sometimes off-and-on effect of levodopa. Dopamine agonists include pramipexole (Mirapex), ropinirole (Requip) and rotigotine (Neupro, given as a patch). Apomorphine (Apokyn) is a short-acting injectable dopamine agonist used for quick relief.

MAO B inhibitors. These medications include selegiline (Zelapar), rasagiline (Azilect) and safinamide (Xadago). They help prevent the breakdown of brain dopamine by inhibiting the brain enzyme monoamine oxidase B (MAO B). This enzyme metabolizes brain dopamine. Selegiline given with levodopa may help prevent wearing-off.

Catechol O-methyltransferase (COMT) inhibitors. Entacapone (Comtan) is the primary medication from this class. This medication mildly prolongs the effect of levodopa therapy by blocking an enzyme that breaks down dopamine.

Anticholinergics. These medications were used for many years to help control the tremor associated with Parkinson's disease. Several anticholinergic medications are available, including benztropine (Cogentin) or trihexyphenidyl.

Amantadine. Doctors may prescribe amantadine alone to provide short-term relief of symptoms of mild, early-stage Parkinson's disease. It may also be given with carbidopa-levodopa therapy during the later stages of Parkinson's disease to control involuntary movements (dyskinesia) induced by carbidopa-levodopa.

Surgical Procedures include:

Deep brain stimulation. In deep brain stimulation (DBS), surgeons implant electrodes into a specific part of the brain. The electrodes are connected to a generator implanted in the chest near the collarbone that sends electrical pulses to the brain and may reduce Parkinson's disease symptoms.