This past week and a half, we covered basal ganglia in several DES Neuroscience discussions outside of the classroom.  One of the diseases discussed in detail was Parkinson’s disease – relating to the degeneration of the substantia nigra pars compacta, leading to a pathological state involved in the direct pathway communication from the putamen-caudate to the thalamus and the Brodmann’s #6 pre-motor cortex.  Parkinsonism actually refers to a clinical syndrome which consists of: Tremor at rest (pill-rolling), Rigidity (“lead-pipe”), Akinesia/hypokinesia, Posturing (stooped posture) – hence the acronym TRAP.  Other signs and symptoms include diminished facial expression, and a shortened accelerated steps gait.  If the lesion is UNILATERAL, the patient only shows CONTRALATERAL Parkinsonism.

That’s great, but what types of things actually cause this Parkinsonism? 

1) Striatonigral Degeneration -  In this form of Parkinsonism, the substantia nigra is only mildly affected, while other areas of the brain show more severe damage than occurs in patients with primary Parkinson's disease.  Patients with this type of Parkinsonism usually demonstrate a greater degree of rigidity.  The signs and symptoms also
appear sooner than in classical Parkinson’s disease.
 

2) Toxin-Induced Parkinsonism -  Toxins such as manganese dust, carbon disulfide, carbon monoxide, and a chemical known as MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) cause Parkinsonisms.   In the case of MPTP the Parkinsonism implicated is permanent after one single ingestion, and closely resembles Parkinson’s disease.  Researchers discovered this reaction in the 1980s when heroin addicts in California who had taken an illicit street drug contaminated with MPTP began to develop severe Parkinsonism. Structurally MPTP is a meperidine derivative.  This discovery, which demonstrated that a toxic substance could damage the brain and produce Parkinsonian symptoms, caused a dramatic breakthrough in Parkinson's research.  MPTP allows scientists to simulate Parkinson's disease in animals and conduct studies to increase understanding of the disease. A reversible form of Parkinsonism sometimes results from use of certain drugs (chlorpromazine, haloperidol) prescribed for patients with psychiatric disorders.  Some GI meds (metoclopramide) and high blood pressure meds (reserpine) may also produce Parkinsonian symptoms.  Stopping the medication or lowering the dosage eliminates the unwanted presence of these symptoms.
 

3) Postencephalitic Parkinsonism –  Shortly after WWI, the viral disease encephalitis lethargica struck almost 5 million people throughout the world.  The disease then suddenly disappeared in the 1920s.  Known as sleeping sickness in the United States, this disease killed one third of its victims and in many others led to post-encephalitic Parkinsonism - a particularly severe form of movement disorder in which some patients developed, often years after the acute phase of the illness, disabling neurological disorders, including various forms of catatonia.  For those who have already had Dr. Pensick for Microbiology, does the name "Von Economo's" disease ring a bell?  If it did not then, it should now - the Powerpoint slide with the guy looking into the microscope, but no good description as to why he was doing that.  A neurologist named Oliver Sacks published Awakenings in 1973.  This was an account of his work in the late 1960's with surviving post-encephalitic patients in a New York hospital. Using the then-experimental drug levodopa, Dr. Sacks was able to temporarily "awaken" these patients from their statue-like state.  In rare cases, other viral infections, including western equine encephalomyelitis, eastern equine encephalomyelitis, and Japanese B encephalitis, can leave patients with Parkinsonian symptoms.
 

4)  Arteriosclerotic Parkinsonism –  Referred to as pseudoparkinsonism, arteriosclerotic Parkinsonism involves damage to brain vessels due to multiple small strokes. Tremor is rare in this type of Parkinsonism, while dementia is common.  Antiparkinsonian drugs have little efficacy on this form of Parkinsonism.
 

5) The Bizarre Dementia In Guam -  This form of Parkinsonism occurs among the Chamorro populations of Guam and the Mariana Islands and may be accompanied by a disease resembling amyotrophic lateral sclerosis (Lou Gehrig's disease). The disease has a rapid onset, with death typically occurring within five years.  Some researchers suspect an environmental cause, perhaps the use of flour from the highly toxic seed of the cycad plant. This flour was a dietary staple for many years when rice and other food supplies were unavailable in this region, particularly during WWII (as Archie Bunker would say – “The Big One”).
 

6) The Others -  (Always my favorite section of any discussion -- the freak cases).  Parkinsonian symptoms may also appear in patients with other, clearly distinct neurological disorders such as Shy-Drager syndrome (sometimes called multiple system atrophy – Parkinsonism along with ANS failure – loss of sympathetic neurons in the intermediolateral column of the spinal cord), progressive supranuclear palsy (striatal syndrome in people >50yrs old, with widespread neuronal loss and neurofibrillary tangles in many areas of the brain), Wilson's disease (AR disorder of copper metabolism), Huntington's disease (AD disorder with degeneration of the caudate nucleus), Hallervorden-Spatz syndrome (very rare disorder with increasing dysarthria and progressive dementia, and at autopsy brown discoloration of the globus pallidus and substantia nigra), Alzheimer's disease (cerebral cortex degeneration), Creutzfeldt-Jakob disease (prion spongiform encephalopathy), olivopontocerebellar atrophy (AD disorder with shrinkage in basis pontis from loss of pontine nuclei + widespread loss of Purkinje cells), and post-traumatic encephalopathy.
 

(References: Robbins, S. Pathological Basis of Disease; DeMyer, W. NMS Neuroanatomy; many web sites.)