CNS Patient B


The following is a patient described in JAMA, June 6, 2012, vol. 307 p.21.

Patient's and Doctor's Comments

Mr L is a 64-year-old man with a past history of stroke who has advanced Parkinson disease. He has Medicare insurance.

Mr L was diagnosed with Parkinson disease in 1999. He initially presented with left-sided clumsiness, loss of dexterity, and depression. He was treated with dopaminergic medications with good response. However, over the years his symptoms progressed, and he has had increasing difficulty with fluctuating on/off symptoms. His current medication regimen is carbidopa-levodopa-entacapone, 31.25-125-200 mg every 4 hours at 6 AM, 10 AM, 2 PM, and 6 PM; along with carbidopa-levodopa, 25-100 mg at 10 PM and 2 AM; and pramipexole, 1 mg with each dose of carbidopa-levodopa-entacapone. On this regimen, he has experienced increasing difficulty with fine motor activities, such as buttoning or tying his shoelaces, and with gross motor activities such as turning a screwdriver. Walking has slowed considerably and, when his carbidopa-levodopa-entacapone dose wears off, he frequently experiences episodes of gait freezing. His tremor is minor and intermittent. His voice has become softer, making it harder for him to be understood. His mood has been depressed since he was diagnosed. More recently he has developed significant anxiety due to embarrassment over his appearance in public. These concerns have forced him into early retirement.

Levodopa (L-dopa) is the precursor of the neurotransmitter dopamine. Carbidopa and entacapone inhibit enzymes that break down levodopa, thereby increasing its availability.

Pramipexole is a dopamine agonist, and this class of drugs is also used to treat Parkinson's.

Mr L's past medical history is significant for a left thalamic infarct in 1991 without residual symptoms and benign prostatic hypertrophy.

Mr L is a retired electrician who is married and lives with his wife. He has 2 adult children who live nearby. There is no family history of Parkinson disease. He continues to work in his woodshop and recently began exercising on a stationary bicycle. He is a nonsmoker and denies alcohol consumption.

On physical examination Mr L had no resting or action tremor. Four hours after his last carbidopa-levodopa-entacapone dose, he had mild rigidity in the right upper extremity and moderate rigidity in the left upper extremity with normal tone in the lower extremities. He had moderate bradykinesia for repetitive movements in the right hand and moderate to severe bradykinesia in the left hand. He walked with mildly stooped posture with decreased stride length and foot elevation. Forty-five minutes after taking his carbidopa-levodopa-entacapone dose, he developed dyskinesia of the head and upper extremities....

I was diagnosed with Parkinson's in 1999. They told me there was no test for Parkinson’s, but they were pretty sure that's what it was. They put me on medication and it helped immediately, but over time the symptoms have gotten worse. My main symptom is my walking. I get episodes of freezing where I can't move. I feel like my feet are glued to the floor, which makes me self-conscious. They increased the medication to compensate for this, which has caused a lot of involuntary movements, mainly with my head. It gets worse if I get anxious in a social situation, and in the past year it has become really bothersome for me....

Recently, I’ve been talking to my neurologist about deep brain stimulation. It seemed like it would be the best decision because my medications were wearing off and I had so much dyskinesia. I’m in a preliminary stage now where I’m considering it, but I’ve also seen that the recent change in medication has helped quite a bit. Therefore, I don't feel an urgency to do deep brain stimulation right now. I think we will definitely do it within the next 6 months. I’m hoping deep brain stimulation will improve my quality of my life and enable me to do more around the house. The advantages of doing the surgery now, as opposed to later, don't seem to be a whole lot. My basic health is good right now and lord knows what's in the future. I think I would like to wait 6 months, see how the medication change works out, and see if they make any improvements in the equipment.

Mr L presented at age 53 years with unilateral clumsiness, impaired dexterity, and depression. The diagnosis of Parkinson disease was made. He was treated with a dopamine agonist followed by the addition of levodopa, with a good response that lasted for several years. Later, he began experiencing shorter duration responses to levodopa, which at first were managed by taking levodopa every 4 hours, followed by the addition of entacapone to extend levodopa effect by slowing its metabolism. As the disease progressed, his walking slowed. He experienced gait freezing when the effects of levodopa wore off. Dyskinesias of his neck and extremities appeared during peak levodopa effects. He was referred for consideration of deep brain stimulation (DBS) to manage these motor complications.

Parkinson disease is second to Alzheimer disease as the most common neurodegenerative disorder.1 Men are affected more often than women, and peak age of onset is between 55 and 65 years. It occurs in 0.3% of the general population and about 1% to 2% of individuals older than 60 years. Estimated prevalence is 1 million individuals in the United States and 5 million individuals worldwide.1Idiopathic Parkinson disease is the most common cause of parkinsonism and has 4 cardinal manifestations: resting tremor, bradykinesia, rigidity, and gait disturbance. Parkinson disease also causes important nonmotor symptoms such as sleep disturbance, mood disorder, cognitive impairment, and autonomic dysfunction....

Parkinson disease typically presents with unilateral or asymmetric motor signs as it did for Mr L. Natural history varies considerably with slow and more rapid rates of progression. Older patients with predominant akinesia, rigidity, and postural instability appear to have a more rapid clinical course than younger patients. By contrast, based on some studies, tremor-dominant Parkinson disease is thought to be associated with a relatively slower and more benign clinical course... Resting tremor is one of the first symptoms to appear but, as in Mr L's case, is mild or not always present. ... As the disease progresses, increasing signs of bradykinesia occur. Motor slowing may initially be limited to muscles of one extremity, but with time, both sides of the body and trunk may become affected often causing a slow, shuffling gait, and stooped posture. Nonmotor manifestations such as dementia, depression, anxiety, sleep disturbance, and autonomic disorders may occur early or late in the course. In more advanced stages, other midline motor manifestations may occur such as gait freezing, postural instability, falls, and speech and swallowing disturbances.



QUESTION: What is bradykinesia?

Answer

QUESTION: But it says his resting tremor is minor and intermittent? Shouldn't we see that if this is Parkinson"s?

Answer

QUESTION: Suppose you have a friend whose hand develops a tremor as she reaches for something. Is she developing Parkinson's?

Answer



Tests and Diagnosis

The details of the test and diagnosis are not given. The clinical symptoms observed over time are very important. But may not rule other, much more rare disorders. Response of the patient to drugs, such as levodopa, can be helpful. An MRI will appear normal in Parkinson's. Diagnosis after death can be confirmed by histological examination of the midbrain removed at autopsy.

Treatment

Given that this patient for the most part responds well to levodopa, deep brain stimulation was not advised. His existing medications were adjusted, with an additional drug added to control the dyskinesias caused by the levodopa. But at some point in the future, he may need to consider deep brain stimulation, in which a stimulating electrode is implanted in a region of the basal ganglia (or subthalamus).