Featured articles - Parkinson Disease

Described in 1817 by Dr James Parkinson, this motor system disease characterized by dopamine deficiency is one of the most common causes of neurological disability in the elderly. People who have this disease are recognizable at airports, shopping malls, and in public parks (where Parkinson himself made his observations). The most obvious feature of the disease is a slow, shuffling stopping gait with a paradoxic tendency to festinate or "hurry-up" to chase the center of gravity of the body to prevent falling forward. Another obvious sign of the disease is a resting tremor of 3-5 Hz ("pill rolling") of one or both hands. Movement almost always abolishes the tremor, but sadly, Parkinson patents are characterized by a disinclination to move, which gives rise to their characteristic mask-like facial expression, often correctly interpreted as a sign of depression or sadness common in this disease. There are a number of medical treatments, but none wholly satisfactory and certainly none curative. A promising newer treatment in the last decade has been the refinement of deep brain stimulation, which, through brain surgery, can minimize the plight of the patient who is disabled by tremor or motor fluctuations.

Although the traditional focus of the disease has been on substantial nigra of the midbrain, the pathologic hallmark of Parkinson disease, the Lewy body, has been found in the cerebral cortex, diencephalon, other midbrain nuclei, the pons, medulla, spinal cord, sympathetic ganglia and the gastrointestinal tract. As one might predict from this widespread distribution of Lewy bodies, markers of neuronal loss, dementia, visual symptoms, instability, postural hypotension, hypophonia and constipation are very common. There is even a school of thought regarding the pre-Parkinson, hypodopamine state in which "future Parkinson patients" stand out from the crowd by virtue of their neatness, orderliness, punctuality, perfectionism and general persnicketiness, all of which, can, at times, alienate them from their less fastidious compatriots. Certainly no one would seriously advocate preemptive treatment with dopamine agonists or selegeline, but it is fascinating to consider these treatment avenues if the person with these characteristics actually sought treatment for "depression" resulting from such alienation. The zeitgeist of the early 21st century would result in almost certain treatment with one of the ubiquitous SSRIs to "enhance serotonin".

The dementia of Parkinson disease is quite troublesome because the treatment for the underling disease state, levodopa or dopamine agonists, can produce hallucinations which are very disturbing and upsetting to any domestic equilibrium. The ensuing response (often panic) may cause the patient to fall, with all the implications of that unfortunate occurrence, usually hip fracture. In theory, the treatments for dementia (central cholinesterase inhibition) can worsen Parkinsonism motor symptoms, but in clinical reality, this seldom seems to the the case.

In summary, the management of Parkinson disease is painstakingly time-consuming for physicians and frustratingly incremental for patients and their families.

 

Huntington Disease

This autosomal dominant (chromosome 4) neurodegenerative disease is fortunately rather uncommon (5-10 patients prevail in every 100,000 of population, except Lake Maracaibo, VZ where the prevalence rate is greater than 100 per 100,000), but is particularly tragic because the disease may become symptomatic only after the patient has already had his/her family (and often large families, for reasons which are poorly understood unless one may consider some chronic limbic disinhibition due to ongoing caudate nucleus pathology).

The disease is characterized by choreiform (dancing) movements of the upper body, dementia, disinhibition and ultimately general debility, aspiration and terminal pneumonia.

There are no proven therapies, other than symptomatic treatments. In the early 21st century, a medicine called Miraxion was being studied to improve motor scores in Huntington patients. Central cholinergic inhibition can be attempted to ameliorate deficits in attention and memory.

Genetic testing, for patients and consenting family members, is currently advised. Later in the course of the disease, the striking caudate nuclei atrophy gives rise to the characteristic "bat wing" appearance of the frontal horns of the lateral ventricles. The neuropathological changes are prominent, resulting in reduction of brain weight b 20-25%. The loss of dopamine and glutamate receptors and the loss of GABA innervation in the lateral globus pallidus appear to be responsible for the development of choreiform movements, the clinical hallmark of the disorder.