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12/24/2012
Function
Function
Part of extra-pyramidal motor system Facilitate behaviour & movement required and appropriate Inhibit unwanted & inappropriate
Involuntary Motor Movements Bradykinesia (slow) or Hypokinesia (slow or diminished) Altered Posture Changes in Muscle Tone
Parkinsons Disease
Degenerative (progressive) disorder of CNS Hypokinetic movement disorder due to decreased motor cortex stimulation by BG (decreased DA release)
Nigrostriatal Pathway (DA-secreting
cells activity)
Parkinsons Disease
Disease of mesostriatal dopaminergic system
PD
normal
PARKINSONISM
Parkinson's
disease is a degenerative disease of the brain that often impairs motor skills, speech, and other functions.
Parkinson's
disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia).
Parkinsons Disease
Substantia Nigra, Pars Compacta (SNc) DOPAminergic Neuron
Clinical Feature (1) Slowness of Movement - Difficulty in Initiation and Cessation of Movement
Parkinsons Disease
The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, Normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain.
PD is also called "primary parkinsonism" or "idiopathic PD" (classically meaning having no known cause although many genetic mutations associated with PD have been discovered). While many forms of parkinsonism are "idiopathic", "secondary" cases may result from toxicity most notably of drugs, head trauma, or other medical disorders. The disease is named after English physician James Parkinson, who made a detailed description of the disease in his essay: "An Essay on the Shaking Palsy" (1817).
Postencephalitic Severe carbon monoxide poisoining. Toxic agents in well water, agricultural pesticides oxidative metabolities released affect dopamine neurons.
receptor blocker}.
Antihypertensive: Reserpine [pre synaptic dopamine
receptor blocker].
Symptoms of parkinsonism accompany- cerebrovascular
Motor symptomsThe cardinal symptoms are (mnemonic "TRAP"): Tremor: normally 46 cps tremor, maximal when the limb is at rest, and decreased with voluntary movement. It is typically unilateral at onset. This is the most apparent and well-known symptom, though an estimated 30% of patients have little perceptible tremor; if patient has stroke/ hemeplegia- tremor disappear on that side. Rigidity: stiffness; increased muscle tone. In combination with a resting tremor, this produces a leadpipe, "cogwheel" rigidity when the limb is passively moved. Akinesia/ bradykinesia absence of movement and slowness in initiating movements, respectively. Postural instability: failure of postural reflexes, which leads to impaired balance and falls.
Postural instability Shuffling gait Dec arm swing Turning en bloc Mask face Micrographia
Other motor symptoms include: Gait and posture disturbances: Shuffling: gait is characterized by short steps, with feet barely leaving the ground, producing an audible shuffling noise. Small obstacles tend to cause the patient to trip. Decreased arm-swing, mask face, voice low, monotonus, micrographia. Turning "en bloc": rather than the usual twisting of the neck and trunk and pivoting on the toes, PD patients keep their neck and trunk rigid, requiring multiple small steps to accomplish a turn.
Pathophysiology
The symptoms of Parkinson's disease result from the loss of pigmented dopamine-secreting (dopaminergic) cells in the pars compacta region of the substantia nigra These neurons project to the striatum and their loss leads to alterations in the activity of the neural circuits within the basal ganglia that regulate movement, an inhibition of the direct pathway and excitation of the indirect pathway. The direct pathway facilitates movement and the indirect pathway inhibits movement, thus the loss of these cells leads to a hypokinetic movement disorder. The lack of dopamine results in increased inhibition of the VAN of the thalamus, which sends excitatory projections to the motor cortex, thus leading to hypokinesia.
Hypokinetic disorders result from overactivity in the indirect pathway. example: Decreased level of dopamine supply in nigrostriatal pathway results in akinesia, bradykinesia, and rigidity in Parkinsons disease (PD).
somatosensory cortices
motor cortices
excitation Putamen
D1
inhibition
D1 & D2
GPe
D2
Dopamine receptors
GPi
Thalamus
GPe/i: Globus pallidus internal/external STN: Subthalamus Nucleus SNc: Pars Compacta
(part of substantia nigra)
STN SNc
Huntingtons Disease
Parkinsons Disease
(-) (-)
(-)
(+)
(-)
(-)
Treatment
Parkinson's disease is a chronic disorder that requires broad-based management including patient and family education, physiotherapy, exercise, and nutrition. At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms.
The most widely used form of treatment is L-dopa in various forms. L-dopa is transformed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase),
Carbidopa and benserazide are dopa decarboxylase inhibitors. They help to prevent the metabolism of Ldopa before it reaches the dopaminergic neurons
Huntingtons disease hereditary disease of unwanted movements. It results from degeneration of the caudate and putamen, and produces continuous dance-like movements of the face and limbs -choreoathetosis
- Predominantly autosomal dominantly inherited chronic fatal disease (Gene: chromosome 4) - Insidious onset: Usually 40-50 - Choreic movements in onset - Frequently associated with emotional disturbances - Ultimately sever dysarthria, progressive dementia ensues.
Principal Pathologic Lesion:
SYDENHAMS CHOREA
Clinical Feature - Fine, disorganized , and random movements of extremities, face and tongue - Accompanied by Muscular Hypotonia - Typical exaggeration of associated movements during voluntary activity - Usually recovers spontaneously in 1 to 4 months Principal Pathologic Lesion: Corpus Striatum
HEMIBALLISM
Clinical Feature - Usually results from CVA (Cerebrovascular Accident) involving subthalamic nucleus - sudden onset - Violent, writhing, involuntary movements of wide excursion confined to one half of the body - The movements are continuous and often exhausting but cease during sleep - Sometimes fatal due to exhaustion - Could be controlled by phenothiazines and stereotaxic surgery
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