April 9, 2011

A Primer on Parkinson's and Its Treatment

 Last month I went to the annual symposium sponsored by the local (National Capital Area) chapter of the Parkinson' Foundation.  The opening presentation was an excellent overview of current treatment options available to those diagnosed with Parkinson's. It was presented by Dr. Linda Sigmund, the medical director of the local chapter, and a doctor at the Neurology Center of Fairfax, VA. 

Luckily for me, Dr. Sigmund has posted the slides that accompanied her presentation on the chapter's website, so the summary of her talk that follows isn't just dependent on my note-taking abilities.

(To see the slides, go to: http://www.parkinsonfoundation.org/2011_Symposiumslides.html.)

Early symptoms that predate motor symptoms

Typically with Parkinson's, the following symptoms develop years before the motor symptoms:

  • loss of sense of smell -- occurs in up to 90% of PD patients and may predate clinical PD by at least  four years.
  • constipation -- occurs in 60-80% and may predate motor symptoms by 10 years
  • sleep disorders -- RBD (acting out vivid dreams as you sleep) may precede motor symptoms by years; 15-38% of RBD patients are subsequently diagnosed with PD.
  • depression -- may occur in up to 28% of early stage PD patients

The  stages of PD after onset of motor symptoms

  • Stage 1 -- Unilateral (one side) motor symptoms
  • Stage 2 -- Onset of bilateral motor symptoms
  • Stage 3 -- Postural instability and restriction of activities
  • Stage 4-5  -- Severely disabled with possible cognitive decline
The duration of each stage is highly variable among individual PD patients, Usually there is a robust response to therapy at the outset that lasts for several years.

Azilect -- Several studies show that the early use of Azilect is effective in slowing the progress of PD. Studies also show that a 1 mg dose is better than 2 mg.

Treatment strategies for younger (under age 70) patients

Younger patients:

  • Are at greater risk of developing motor fluctuation and dyskinesia.
  • Have a longer treatment time horizon
Since long-term use of  levodopa can lead to motor fluctuations and dyskinesia, the treatment strategy for younger patients most often involves delaying the start of levodopa and instead using at the outset an MAO-B inhibitor and then supplement with a dopamine agonist.

[Note: Motor fluctuations are caused by the wearing off of the levodopa's effectiveness between doses, resulting in unpredictable "on-off" periods. Dyskinesia is the uncontrollable movement of, most commonly, the upper body but can also be seen in the lower extremities. A related symptom is dystonias in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.]

Treatment strategies for older (age 70 and beyond) patients

These older patients:

  • Are at a lower risk of developing motor fluctuations and dyskinesia
  • But are more prone to acute side effects, particularly confusion and hallucinations 
The treatment strategy here may involve starting with levodopa immediately or starting with an MAO-B inhibitor and instituting levodopa later.

Levodopa Treatment

All PD patients sooner of later are put on levodopa which provides relatively rapid symptomatic release and  is well tolerated, with few side effect initially. But prolonged use of levodopa is associated with the development of motor fluctuations and dyskinesias.

This happens with about 80% of patients on levodopa and close to 100% of young-onset patients. It is a major source of disability and  is the commonest problem leading to surgical intervention.

When a patient is started on levodopa, it's usually carbidopa/levodopa IR (Sinemet or its generic). The controlled release version (Sinemet CR or its generic) may be used at bedtime since it has a longer duration of benefit. Later on, when patients are experiencing end-of-dose wearing off, they may be put on carbidopa/levodopa/entacapone (Stalevo) which provides more sustained levodopa levels.

(Since this blog is focused on issues relating to aging, I'll skip the part of the presentation that covered drugs prescribed for young-onset PD to treat the symptoms so as to delay as long as possible resort to levodopa/carbidopa  because of the problems noted above that result from prolonged use of levodopa/carbidopa.)

When patients on levodopa/carbidopa begin to experience significant off episodes, the drug apokyn may be introduced with the intention of reducing the dosage of levodopa which, at this stage, is causing a great deal of dyskinesia and off periods. Apokyn is administered by injection and begins to work within five to 10 minutes and is effective for 30 to 90 minutes. Administered several times a day, it can reduce the "off" periods by an average of two hours a day.  Adverse effects are yawning, drowsiness, hypotension (abnormally low blood pressure), nausea and vomiting. It also can result is some dyskinesias.

Symptoms  that Levodopa Doesn't Address

While levodopa is the gold" standard" med for treating Parkinson's, it doesn't provide relief from all of the symptoms associated with PD. Here are symptoms that aren't affected:
  • Motor symptoms of postural instability, the freezing phenomenon (patient freezes in one spot while walking and finds it difficult to take next step), and speech abnormalities (most frequently a lowering of the voice level).
  • Mental changes of dementia and depression
  • Autonomic nervous system dysfunctions, including constipation, sexual dysfunction, urinary problems and sweating.
  • Sensory phenomenon such as hallucinations
  • Sleep problems
Non-Pharmacological Treatment 

 Throughout the symposium, speaker after speaker emphasized the importance of exercise in treating PD. One speaker said exercise was even more important that pharmacological treatment. Other recommended non-med treatments include:
  • Support groups
  • Education
  • Nutrition
  • Psychosocial needs
  • Therapies -- occupational, physical, speech.

Deep Brain Stimulation

Deep brain stimulation is being used increasingly to alleviate the motor complications that accompany long-term use of levodopa. 

The Food and Drug Administration (FDA) approved deep brain stimulation as a treatment for essential tremor  in 1997, for Parkinson's Disease in 2002, and for dystonia in 2004.  It involves surgical implantation of a brain pacemaker that sends electrical impulses to specific portions of the brain.

The expected improvements with DBS include decreases in dyskinesias, dystonia, the wearing-off symptoms, and tremor. It may not have any impact on speech and gait problems. Also with DBS, the best that the patient can expect is to get back to the best he/she was while on levodopa.  Patients won't get better than that.

Usually patients over age 70 will not be accepted for DBS intervention.  Evidence of dementia also is a disqualifier as is significant untreated depression or anxiety.

Future Treatment Needs and What's in the Pipeline

The single most important unmet medical need in Parkinson's disease today is effective neuroprotection therapy.  Neuroprotection is a treatment that slows, stops, or reverses the disease progression by protecting, rescuing , or restricting nerve cells that degenerate in PD (primarily dopamine).

Things in the pipeline include:

  • Meds with more continuous action -- dopamine agonist patches, levodopa patch, subcutaneous infusions of the meds lisuride and apomorphine, intraintestinal administation of duodopa
  • Antidyskinetic meds 
  • Surgical interventions -- transplanting fetal or retinal epithelial cells, stem cell transplantation, gene therapy.

1 comment:

Hillary said...

How are you coping with PD currently and what solutions have you tried that reduce the symptoms?