Parkinson Disease And Other Neurodegenerative Disorders
Parkinsonism has four cardinal features:
- Bradykinesia (slowness and poverty of movement),
- Muscular rigidity,
- Resting tremor (which usually abates during voluntary movement),
- Impairment of postural balance leading to disturbances of Gait and falling.
*The pathological hallmark of PD is a loss of the pigmented, dopaminergic neurons of the substantia nigra pars compacta (SNpc) that provide dopaminergic innervation to the striatum (caudate and putamen).
Management of the Nonmotor and Nondopaminergic Features of Parkinsons Disease
- Majority of the cases are idiopathic, stroke, some are arteriosclerotic whIle postencephalitic are now rare. Wilson's Disease (hepatolenticular degeneration) due to chronic copper poisoning, is a rare cause. Drugs in common clinical use that may cause Parkinsonism include antipsychotics such as haloperidol and thiorid azine and antiemetics such as prochloperazine and metoclopramide.
Dopamine is broken down into inactive metabolites by a set of enzymes, monoamine oxidase (MAO), aldehyde dehydrogenase (ALDH), and catechol-O-methyl transferase (COMT), acting in sequence.
Drugs affecting brain Dopaminergic system
Drugs affecting brain Cholinergic system
(a) Dopamine precursor: Levodopa (L-dopa)
(b) Peripheral decarboxylase inhibitors: Carbidopa, Benserazide.
(c) Dopaminergic agonists: Bromocriptine, Ropinirole, Pramipexole etc (see below)
(d) MAO-B inhibitor: Selegiline, Rasagiline
(e) COMT inhibitors: Entacapone, Tolcapone
(f) Dopamine facilitator: Amantadine.
(a) Central anticholinegics: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden, Benzatropine
(b) Antihistaminics : Orphenadrine, Promethazine.
- Dopamine agonists (DA)
Symptoms of Parkinsonâ€™s disease
b. Tremors (MC)
d. Festinating Gait
Surgical Procedures For PD
High-frequency deep brain stimulation
Thalamotomy (for conspicuous tremor) or posteroventral pallidotomy.
Gene Therapy In Pd (In Phase 1 Trial):
Infusion into the striatum of Adeno-associated virus type 2 as the vector for the gene:
- The genes were for glutamic acid decarboxylase (GAD) to facilitate synthesis of GABA, an inhibitory neurotransmitter), infused into the subthalamic nucleus to cause inhibition;
- For aromatic acid decarboxylase (AADC), infused into the putamen to increase metabolism of levodopa to dopamine; and
- For neurturin (a growth factor that may enhance the survival of dopaminergic neurons), infused into the putamen.