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From Medicineworld.org: Parkinsonism (Parkinson's disease)

Neurology main Migraine headaches Trigeminal neuralgia  

Parkinsonism (Parkinson's disease)

    By Kottapurath Kunjumoideen MD


Introduction
Parkinson disease is degenerative disease of the nervous system often characterized by rigidity of the muscles, involuntary movements and general sluggishness of movement and speech difficulty (Ref 1). Normally the basal ganglia part of the brain exerts a stimulatory effect on the brain cortex. In patients with Parkinson disease this stimulatory effect is lost resulting in the above mentioned defects. The basal ganglia produce dopamine which acts as a neurotransmitter and this is responsible for the stimulating effects on the brain cortex. Lack of production of dopamine is the basic defect of Parkinson disease. Cognitive defects may be associated with the disorder from initial phase of the disease (Ref 2).

Parkinson disease is generally considered to be a non-genetic disease but, a small percentage (5-10%) of patients is now known to get this disease through genetic mechanisms (Ref 3, 4).

Classical Parkinson disease is also called as shaking palsy or Paralysis Agitans. It was first described by James Parkinson in 1817 and hence the name. Parkinsonism may be primary or secondary to various other causes. All cases are caused by the loss of dopamine (a neurotransmitter in the brain) production in the brain.

Parkinsonism affects approximately 1% of the Americans aged more than 50 years. Most of the cases occur in male population (Male to female ratio is 3:2). There is no clear correlation between the disease and environmental and genetic factors.

What is the cause of Parkinson disease?
It is now accepted that a loss of pigmented cells in the substantia nigra ( a region in the brain) and other pigmented nuclei is the most constant finding in the brain of Parkinson patient. This leads to reduced amount of dopamine (it is a neurotransmitter in the brain which sends signals to various parts of the brain) in the neostriatum (its also a region in the brain).

Symptoms of Parkinson disease
The following are some of the commonest symptoms of Parkinson's disease:

  • Resting tremor (fine movement of the hand while in rest)
  • Sometimes patient suffer from dementia (impaired memory) or depression (Ref 5).
  • Rigidity (stiffness of the muscles)
  • Bradykinesia (slowness in initiation and execution of any movements of the body)
  • Patient frequently loses balance while walking.
  • Micrographia (while writing the letters become very small)
  • Mask like facies(expressionless face)
  • Festinating gait or small shuffling steps (marche a' petits pas). Patient walks with small steps and spine and limbs become less pliable and elastic.
  • Infrequent blinking is another feature. Usually normal person blinks 12-20 times per minute and the Parkinson's patient only 5-10.
  • While speaking the patient voice become monotonous without any melody and finally he only whispers.
  • Sometimes patient suffer from dementia (impaired memory).

Secondary Parkinsonism or Parkinson's like disease
There are several other conditions that have the features of Parkinson's disease and are called secondary Parkinsonism or Parkinson's like disease. These are:
  • Olivopontocerebellar degeneration
  • Drug induced like antipsychotics, prochlorperazine, metoclopromide
  • Poisoning with carbon monoxide
  • Following head trauma.
  • Huntington's disease

What are the treatment options available?
Although there is no known treatment that will halt or reverse the neuronal degeneration that causes Parkinson's disease, methods are available that will cause considerable relief from symptoms. Treatment can be medical (by drugs) or by surgery.

At present, L-dihydroxyphenylalanine (L-dopa) is unquestionably the most effective agent for the treatment of Parkinson disease, and the results, even in those patients with advanced disease, are much better than have been obtained with other drugs, even newer ones.

Drugs like bromocriptine, pergolide and lisuride are also useful. Newer drugs like ropinirole and pramipexole seems to have fewer side effects and are being increasingly used as the initial drug.

Does surgery cures Parkinson's disease?
Since there are many side effects for the drugs and also patient in long course of treatment may show resistance to the drugs, newer surgical therapies have evolved.
Tissue transplantation from fetal (obtained from the aborted babies or dead born babies) brain cells or patient's own adrenal medulla into Parkinson patient brain is still in the research stage.

Patients refractory to medical therapy and having serious side effects to L-dopa and patients with rigidity or bradykinesia are suitable candidates for surgery. Patients who have serious bleeding tendency, age more than 85 years, memory disturbances, and with secondary Parkinsonism are not suitable for surgery.

Surgery like pallidotomy and deep brain stimulation of certain areas of brain using implanted electrodes in the brain are helpful. If properly done, surgical effects may last more than five years, with failures possibly due to improper case selection. Permanent cure is not possible with surgery and to a greater extent the symptoms can be reduced (Ref 6).

Gene therapy
Gene therapy is currently under investigation for Parkinson disease (Ref 7). Gene therapy is usually done using a vector virus that is not harmful for human being. The necessary genetic material is transferred to the patient using the vector virus. The gene is to be transferred to subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA ( Ref 8) GABA acts as a direct inhibitor on the overactive cells in the STN.

Maintaining good general health
Finally, in managing the patients with Parkinson disease, proper general health of the patient must be looked into. Exercise, proper nutrition and yoga may be helpful in achieving these goals.



References
  1. Jankovic J (April 2008). "Parkinson's disease: clinical features and diagnosis". J. Neurol. Neurosurg. Psychiatr. 79 (4): 368–76.
  2. Davie CA (2008). "A review of Parkinson's disease". Br. Med. Bull. 86: 109–27.
  3. Lesage S, Brice A (April 2009). "Parkinson's disease: from monogenic forms to genetic susceptibility factors". Hum. Mol. Genet. 18 (R1): R48–59.
  4. Chade AR, Kasten M, Tanner CM (2006). "Nongenetic causes of Parkinson's disease". J. Neural Transm. Suppl. (70): 147–51.
  5. Cummings, J. (1992). Depression and Parkinson’s disease: A review. American Journal of Psychiatry, 149, 443-54.
  6. Fukuda M, Kameyama S, Yoshino M, Tanaka R, Narabayashi H (2000). "Neuropsychological outcome following pallidotomy and thalamotomy for Parkinson's disease". Stereotactic and Functional Neurosurgery 74 (1): 11–20.
  7. Feng, LR, Maguire-Zeiss KA. "Gene Therapy in Parkinson's Disease: Rationale and Current Status
  8. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ (2007). "Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial". Lancet 369 (9579): 2097–105.



Did you know?
Parkinsonism affects approximately 1% of the Americans aged more than 50 years. Most of the cases occur in male population (Male to female ratio is 3:2). There is no clear correlation between the disease and environmental and genetic factors.

Medicineworld.org: Parkinsonism (Parkinson's disease)

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