PARKINSON’S DISEASE:

PARKINSON’S DISEASE:

·         It is also known as paralysis agitans, resulting from widespread destruction of that portion of the substantia Niagra that sends dopamine secreting nerve fibers to tha caudate nucleus and putamen. Characterized by : (a) rigidity of much of the musculature of body

·          (b) involuntary tremor (even when a person is resting)

·         (c) serious difficulty in initiating movement, called akinesia.

·         Normally, the dopamine secreted in the caudate nucleus and putamen is an inhibitory transmitter. Therefore destruction of dopaminergic neurons in the subtantia nigra of the patient would allow the caudate nucleus and putamen to become overly active and possibly cause continuous output of excitatory signals to the corticospinal motor control system. These signals could overly excite many or all of the muscles of the body, thus leading to rigidity.

·         It is a progressive neurological disorder with problems of smooth and coordinated muscles movement. Dopamine is produced in substantia nigra. In Parkinson's disease, cells of substantia nigra start to die hence resulting in reduced dopamine levels. When it is dropped to 60-80% , symptoms start to appear. It usually affect the individual of 60 years or more age. It is chronic and worsen overtime. It is named after the doctor James Parkinson, who first described the disorder as “shaking palsy”.

Symptoms :

Often affect one side of body, later both. Primary symptoms related to voluntary and involuntary motor function. These include :

A.              Tremors : often occur when person is resting but not while involved in task. Trembling of fingers, hands, feets, eyes, jaws or head.

B.               Rigidity : stiffness of limbs and trunk

C.               Bradykinesia: slowness of voluntary movement. Overtime, it becomes difficult to initiate and complete the movement.

D.              Postural instability : impaired or lost reflexes make it difficult to adjust posture and to maintain balance.

E.               Parkinsonian gait : usually take small, shuffling steps and might have difficulty picking up feets.

F.               Continued damage to the brain lead to secondary symptoms. Anxiety, confusion, dementia, depression, increased sweating.

Causes:

It may have both genetic and environmental component. Dopamine acts as a messenger between two brain areas- the substantia niagra and the corpus striatum to produce smooth, controlled movements, this communication becomes ineffective and movements becomes impaired.

In most people, it is idiopathic means that it arises sporadically with no known cause. There are several genes associated with it:

·         SNCA (synuclein, alpha non A4 component of amyloid precursor)

·         PARK 2 (Parkinson's autosomal recessive, juvenile 2)

·         PARK7 (early onset7)

·         PINK1 ( PTEN- induced kinase 1)

·         LRRK2 ( leucine rich repeat kinase

 Several other chromosome regions and the genes GBA (glucosidase beta acid), SNCAIP ( synuclein, alpha interacting protein) may also be linked to PD.

Diagnosis and treatment:

Health history and neurological examination

Diagnosis is more likely if :

(a) symptoms are not due to secondary causes

(b) at least 2-3 major symptoms

 (c) symptoms are significantly improved with L-DOPA.

Therapies are available.

Levodopa which convert to dopamine in brain . Dopamine aganoists are used which initiate the action of dopamine. Less effective than levo-dopa.

Amantadine can be used along with carbidopa-levodopa. It offers short term relief for the involuntary movements.

Anticholinergic are used to block the PNS and help with rigidity.

L-DOPA : it is converted in the brain into dopamine which is then restored. The normal balance between inhibition and excitation in the caudate nucleus and putamen.

Administration of dopamine itself does not have the same effect because dopamine has a chemical structure that will not allow it to pass through the blood-brain barrier.

L-deprenyl: this drug inhibits monoamine oxidase, which is responsible for destruction of dopamine after it has been secreted. This treatment helps to slow destruction of the dopamine-secreting neurons in the substantia niagra. Therefore appropriate combinations of L-dopa therapy along with l-deprenyl therapy usually provide better treatment.

Treatment with transplanted fetal dopamine cells and by destroying part of the feedback circuitry in the basal ganglia.