Parkinsonism and Parkinson’s Disease

Parkinson disease the long-term progressive neurodegenerative disorder primarily affecting the motor area of the brain which is called the substantia nigra. This area of the brain is rich in dopamine producing neurons. Dopamine is a chemical neurotransmitter that is responsible for the transmission of signals from one part of the brain to another and is responsible for the control of movement and coordination. The symptoms of Parkinson’s disease continue and worsen over time affecting millions of people all over the world. Currently there is no definite medical or surgical treatment options to completely manage its symptoms.

However, the typical motor symptoms of Parkinson’s disease such as tremor, rigidity, slowness of movement, and postural instability may also occur in certain other conditions not related to Parkinson’s disease. These symptoms are grouped together under the term “Parkinsonism” and the conditions may be called “secondary Parkinsonism”. It can also be said that parkinsonism is a clinical syndrome or  symptom Complex. The characteristic feature of Parkinsonism is bradykinesia or slowness of movements.  There is a myriad of underlying causes of parkinsonism and the diagnosis is usually complex.

Causes

PD is a relentlessly progressive neurodegenerative disorder of the brain. Lack of dopamine produces the symptoms of Parkinson’s disease.

Parkinsonism may be caused by a number of conditions, such as :

  • Dementia with Lewy bodies:
  • Progressive supranuclear palsy
  • Multiple system atrophy
  • Corticobasal degeneration
  • Shy-Drager syndrome
  • Wilson’s disease
  • Benign essential tremor
  • Dystonic tremor
  • Huntington’s disease.
  • Creutzfeldt-Jakob disease (CJD or “Mad Cow Disease”)
  • Pick’s disease
  • Alzheimer’s disease
  • Encephalitis
  • Meningitis
  • Brain tumors
  • Stroke
  • Head injury, particularly repeated head trauma, as in boxing
  • Drugs- pharmaceutical and narcotic
  • Other toxins – manganese, carbon monoxide, methanol

Drug-Induced Parkinsonism

Some of the people with Parkinsonism are known to develop their symptoms after the treatment with certain medications. These drugs and toxins interfere or block the action of dopamine and other neurotransmitters which help the nerve cells to communicate with each other and help in the muscle movement control and coordination and are commonly referred to as dopamine antagonists. This is called as Drug-Induced Parkinsonism.

The onset of drug induced Parkinsonism is more rapid than that of PD. On withdrawal of the offending drug the symptoms often improve but some percentage of patients develop persistent and progressive Parkinsonism. In these cases it is believed that the drug did not cause the Parkinsonism but rather unmasked a latent condition. Most of the people recover within 2 months after the consumption of offending drug is stopped. However, this time duration is variable and the symptoms can vanish away as early as within hours or days of stoppage or it might take as long as after 2 years.

Many medicines have been implicated in producing parkinsonism, including :

    • Antiemetics – metoclopramide. Thus, in a patient of parkinsonism, who complains of nausea and vomiting, metoclopramide is best avoided and other anti-sickness drugs such as domperidone and ondansetron are the drugs of choice.
    • Antidepressants – selective serotonin-reuptake inhibitors (SSRI)
    • Antipsychotics (used to treat severe paranoia and schizophrenia) – chlorpromazine, haloperidol. Antipsychotics used to treat psychotic disorders such as behaviour disturbances especially in the patients of dementia are known to be the major cause of drug induced parkinsonism worldwide. However atypical antipsychotics like Clozapine, Quetiapine, Olanzapine and risperidone have lower incidence of this so called extrapyramidal side effects and thus they have a lesser tendency to induce secondary parkinsonism.
    • Anti-seizure medication – valproic acid.
    • Antihypertensives – methyldopa, reserpine
    • Brain damage caused by anesthetic drugs

MPTP seems to be selectively toxic to the cells in the substantia nigra, producing not only sudden irreversible Parkinsonism but all other associated features of PD too. Inadvertent synthesis and use of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) while trying to manufacture MPPP (1-methyl-4-phenyl-4-propionpiperidine), an illicit narcotic compound, led to symptoms of PD.Use of MPPP contaminated with MPTP, which was sold in the street as synthetic heroin, led to similar symptoms with toxicity and death.

Drug induced parkinsonism is symmetrical that is, it  occurs on both sides of the body and is less likely to be linked with tremors. However, tremors can sometimes be present asymmetrically.  Akinesia along with the loss of arm swing is usually the earliest symptom of drug drug induced parkinsonism.

Atypical Parkinsonism

Parkinson’s disease contributes to about 80% cases of Parkinsonism and is the most common neurodegenerative cause of Parkinsonism. Other neurodegenerative causes include multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration, fronto-temporal dementia and are together grouped under “Atypical Parkinsonism” or “Parkinson-Plus Syndromes”.

Similar to the Parkinson’s disease, a typical parkinsonism is also diagnosed clinically by a neurological examination. Some of the features of the atypical parkinsonism that differentiate it from Parkinson’s disease include symmetrical presentation of the symptoms along with early cognitive and postural balance problems.. The disease usually has a faster progression rate, and  shows limited improvement with medicines.

Symptoms

PD and Parkinsonism may have similar symptoms. Tremor, rigidity, slowness of movements, postural instability, slow shuffling gait, unilateral involvement (symptoms only on one side of the body) or other associated symptoms of PD such as dementia, difficulty with speech, swallowing difficulties and other features may also be present with secondary Parkinsonism.

Diagnosis

Differentiation between Parkinsonism due to some other cause and that due to PD may become difficult in patients presenting with early symptoms, especially in the elderly.

  • A thorough history, noting other signs and symptoms, and a neurological examination may help to arrive at a diagnosis.
  • There are no definite tests to confirm the diagnosis of PD, which is often diagnosed by eliminating other causes of Parkinsonism.
  • Investigations, including a CT scan and MRI, may be done as indicated.
  • A dramatic improvement of symptoms with levodopa can sometimes support the diagnosis of Parkinson’s disease.

Treatment

Treatment of PD is usually with a combination of anti-Parkinson drugs, including levodopa, and auxilliary therapies like physical therapy.

In Parkinsonism, treatment will be directed the cause, once it is identified. Parkinsonism caused by drugs or toxins often improve on stopping the drugs or eliminating the toxins. Specific treatment may be undertaken for other diagnosed conditions.

In most cases, Parkinsonism due to other causes does not respond, or responds only moderately, to anti-Parkinson drugs.

 

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