Parkinsonism

ETIOPATHOGENESIS:

• The degeneration of neurons in-
  • Substantia nigra pars compacta
  • Nigrostriatal tract 
• This results in deficiency of dopamine in striatum which controls muscle tone and coordinates movements. 
• Tyrosine Hydroxylase enzymes is believed to be deficient in Parkinsonism
• Nerve fibers from cerebral cortex and thalamus secrete acetylcholine in the neostriatum causing excitatory effects that initiate and regulate gross intentional movements of the body. 
• Can be seen in CO poisioning
• Carbidopa and Benserazide:irreversibly bind to and permanently deactivate pyridoxal 5′-phosphate (PLP), the active form of vitamin B6
• In Parkinson’s disease, due to deficiency of dopamine in striatum, an imbalance between dopaminergic (inhibitory) and cholinergic (excitatory) system occurs, leading to excessive excitatory actions of cholinergic neurons on striatal GABA ergic neurons.
• Mangnese (Mn)  is associated with secondary Parkinsonisms

CHARACTERISTICS:

Parkinsonism is a progressive degenerative, extrapyramidal disorder of muscle movement, due to dysfunction in basal ganglia, comprising four cardinal features

Bradykinesia or hypokinesia:

• It is slowness in initiating and carrying out voluntary movements. 
• It is called poverty and suppression of voluntary movements. 
• It is caused partly by muscle rigidity and partly by inertia of the motor system, which means that motor activity is difficult to stop as well as to initiate. 
• It is hard to start walking, and once in progress, the patient can not stop quickly.

Muscle rigidity:

• Rigidity is due to increased muscle tone. 
• The rigidity affects the opposing muscles equally, flexors and extensors. 
• Rigidity is detectable as an increased resistance in passive limb movement.

Resting tremor:

• Tremors are defined as rhythmic oscillatory movements caused by the opposing muscles around a joint. 
• Tremors of Parkinsonism are slow. 
• Hand tremors involve all the fingers and thumb (pill rolling tremor) which tend to diminish during voluntary activity. 
• The “resting tremors” are present at rest and disappear (abate) during voluntary movements.
•  Impairment of postural balance leading to disturbances of gait, and falling. 
• The secondary manifestations are mask-like face, siallorrhoea, difficulty in speech, slowing of mental process and dementia.
• Dyskinesia: Abnormal involuntary movements 
• Chorea: It consists of irregular, unpredictable, involuntary muscle jerks that occur in different parts of the body and impaired voluntary activity. 
• Athetosis: Abnormal movements are slow and writhing in character 
• Dystonia: The abnormal movements are slow in character and are sustained so that they are regarded as abnormal postures
• Tics: They are coordinated abnormal movements that tend to occur repetitively particularly about the face and head, especially in children 

TREATMENT:

Medical treatment:

Drugs influencing brain dopaminergic system

• Levodopa
• Bromocriptine, Pramipexole, Ropinirole 
• Amantadine 
•  Selegiline 
• Tolcapone, Entacapone 
• Carbidopa, Benserazide 

Drugs affecting brain cholinergic system

• Centrally acting anticholinergics : benztropine, benzhexol, procyclidine 
• Antihistaminics (H1 blockers) with anticholinergic activity : promethazine, diphenhydramine Large amount of levodopa is converted to dopamine in the peripheral tissues by peripheral dopa decarboxylase enzyme 
• Low bioavailability in the CNS 

Surgical procedures

Deep brain stimulation: 

• In deep brain stimulation (DBS), surgeons implant electrodes into a specific part of your brain.
• The electrodes are connected to a generator implanted in your chest near your collarbone that sends electrical pulses to your brain and may reduce your Parkinson’s disease symptoms.
• Subthalamic Nucleus is the most commonly used site for Transcranial Magnetic Stimulation

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