Parkinsonism

ETIOPATHOGENESIS:
  • The degeneration of neurons in-
  1. Substantia nigra pars compacta
  2. 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. 
  1. It is called poverty and suppression of voluntary movements. 
  2. 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. 
  3. It is hard to start walking, and once in progress, the patient can not stop quickly.
  • Muscle rigidity:
  1. Rigidity is due to increased muscle tone. 
  2. The rigidity affects the opposing muscles equally, flexors and extensors.
  3. Rigidity is detectable as an increased resistance in passive limb movement.
  • Resting tremor:
  1. Tremors are defined as rhythmic oscillatory movements caused by the opposing muscles around a joint.
  2. Tremors of Parkinsonism are slow. 
  3. Hand tremors involve all the fingers and thumb (pill rolling tremor) which tend to diminish during voluntary activity. 
  4. 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.
  1. Dyskinesia: Abnormal involuntary movements 
  2. Chorea: It consists of irregular, unpredictable, involuntary muscle jerks that occur in different parts of the body and impaired voluntary activity. 
  3. Athetosis: Abnormal movements are slow and writhing in character 
  4. Dystonia: The abnormal movements are slow in character and are sustained so that they are regarded as abnormal postures
  5. 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
  1. Levodopa
  2. Bromocriptine, Pramipexole, Ropinirole 
  3. Amantadine 
  4. Selegiline 
  5. Tolcapone, Entacapone 
  6. Carbidopa, Benserazide 
  • Drugs affecting brain cholinergic system
  1. Centrally acting anticholinergics : benztropine, benzhexol, procyclidine 
  2. 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
  • Risks:
  1. Infections
  2. Stroke 
  3. Brain hemorrhage.
  • Indication:
  1. Advanced Parkinson's disease with unstable medication (levodopa) responses.
  2. DBS can stabilize medication fluctuations
  3. Reduce or halt involuntary movements (dyskinesias), tremor, rigidity, and improve slowing of movement.
  4. DBS is effective in controlling erratic and fluctuating responses to levodopa or for controlling dyskinesias that don't improve with medication adjustments.
  • Although DBS may provide sustained benefit for Parkinson's symptoms, it doesn't keep Parkinson's disease from progressing.
Exam Question
  • Patient presenting with pellagra, parkinsonism, convulsions, anemia and kidney stones has deficiency of Pyridoxal phosphate
  • Tyrosine Hydroxylase enzymes is believed to be deficient in Parkinsonism
  • Mangnese (Mn) is associated with secondary Parkinsonisms
  • Hypokinesia, Rigidity & Static tremors are seen in Parkinsonism
  • Dinesh, a 56 yr aged man presents with complaints of slowness of movements, postural instability, tremors, rigidity and memory loss. Most likely diagnosis is Parkinsonism
  • Subthalamic Nucleus is the most commonly used site for Transcranial Magnetic Stimulation to reduce frequency of Parkinsonism symptoms
  • Parkinsonism like features are evident in surviving patients of CO poisoning
  • Deep brain stimulation used in treatment of Parkinsonism
Don't Forget to Solve all the previous Year Question asked on Parkinsonism