A 65-year-old man has recently retired from working at a savings & loan institution. He is looking forward to having more time to do the things he has always wanted to do, such as building his own sailboat, and spending more time traveling with his 68-year-old wife. He returns home one evening after spending a day at the local home center. He sits down to eat dinner. Bleaahhh. Something is wrong. The food tastes terrible. "What did you do, honey?" he asks his wife. She replies, "It is your favorite." She doesn't appear to notice. He goes into the kitchen and looks around. He quickly determines that, instead of cooking oil, dishwashing liquid has been used on the food. This incident becomes a focal point for the realization that things have not been going that well at home...for some time. He now remembers that his wife used to pay all the bills, but she began to miss payments, and he started performing this function 3 years ago. She has become more housebound and sleeps more in the past year. Friends have remarked that she seems less sociable. He recalls several episodes in the past year in which she remarked, "Did you see that?" and he didn't see what she claimed was there. She has had minor falls, without injuries other than superficial contusions of arms and legs.

Questions:

2.1 What problems should you consider?

The possibilities include depression, dementia, and a metabolic disorder such as hypothyroidism.

2.2 What can you do next?

On physical examination she has a temperature of 37 C, heart rate of 73/min, and blood pressure 140/90 mm Hg. Her lungs are clear to auscultation with a respiratory rate of 15/min. The abdominal exam shows a low transverse scar 5 cm above the pubis. She has prominent venous varicosities of the lower extremities.

The neurologic examination reveals 5/5 motor strength in all extremities. There is an increase in resistance to passive movement. With rhythmic pronation-supination of her forearms, a 6 to 7 Hz tremor occurs involving both her forearms and hands. The "get up and go" test reveals that she has difficulty arising from a sitting position in a chair. She has to lean forward to start walking, and then she walks with short, shuffling steps. She exhibits blepharospasm and drooling.

The mental status exam shows that she is apathetic and her thinking is slowed. She is oriented to time, place, and person. She can remember 2 of 3 objects after 3 minutes. She has difficulty with serial 7's. She exhibits perseveration.

Laboratory studies show Hgb 13.3 g/dL, Hct 39.6%, MCV 79 fL, platelet count 255,600/microliter, WBC count 5730/microliter, glucose 75 mg/dL, creatinine 0.9 mg/dL, and TSH 2 mU/mL.

2.3 What do these findings suggest?

She has a dementia along with psychiatric manifestations, as well as a movement problem. The problems are not explained by Alzheimer disease or Pick disease. Frontotemporal dementia may account for some psychiatric problems (mainly behavioral) but not movement problems. The movement problems suggest Parkinson disease. Her problems may be explained by diffuse Lewy body disease, which can have a component of Parkinson disease.

2.4 What pharmacologic therapy may be useful?

Parkinson disease can be treated with L-DOPA plus carbidopa (a peripheral dopa-decarboxylase inhibitor).

Other treatments may include dopamine agonists such as pergolide, ropinirole, and pramipexole.

Amantadine, selegiline, a "capone", or a muscarinic antagonist such as trihexiphenydyl or benztropine) can be used.

2.5 Explain the neurophysiology of the drug therapy.

L-DOPA plus carbidopa leads to increased levels of dopamine. Dopamine agonists directly stimulate the receptors (particularly D2 receptors) to mimic the effect of dopamine.

Amantidine enhances the releaseof dopamine.

Selegiline inhibits monoamine oxidase type B activity.

Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that decreases metabolic breakdown of dopamine.

Muscarinic blockers restore the acetylcholine/dopamine balance by reducing cholinergic activity.