PARKINSON’S DISEASE

I.ANATOMY
• Parkinson’s Disease is considered predominantly a disorder of the basal ganglia
• BASAL GANGLIA also known as basal nuclei is a group of subcortical gray structures
found deep within the white matter of the brain. .
• It consist of five pairs of nuclei:
o Caudate nucleus
• an elongated C-shaped nuclei
• integrates sensory information about the spatial position of the body and
according to that, it sends the information about the necessary fine tunes of the
motor response to that stimuli to the thalamus.
• contributes to body and limb posture and the speed and accuracy of directed
movement
• caudate nucleus also involves many tasks, such as memory, goal-pursuit,
learning, language processing, emotions, etc
o Putamen
• regulate motor functions and influence various types of learning and it employs
dopamine to perform its functions.
o Globus Pallidus
• composed of inhibitory GABAergic projection neurons, which fire spontaneously
and irregularly at high frequency
• divided by a vertically placed sheet of white matter, the medial (internal)
medullary lamina, into external (GPe) and internal (GPi) segments.Both the GPe
and GPi play an essential role in the modulation of the motor program:
1. Direct pathway
2. Indirect pathway
o Subthalamic nucleus
• Also known as Luys’ bodies.
• Not an anatomical part of the basal ganglia. However, given their functional
connection, the subthalamus is listed as a functional part of the basal ganglia
• subthalamic nuclei are composed of excitatory glutamatergic projection neurons.
It receives excitatory inputs from the frontal cortex in a somatotopically organized
manner
• subthalamic nucleus is considered the “pace-maker” of the basal ganglia
o Substantia nigra
• A small motor nucleus, within the anterior part of the midbrain
• consists of two parts with very different connections and functions:
 1. Pars Compacta (SNc) - serve mainly as an output to the basal ganglia
circuit, supplying the striatum with dopamine, through specific D1 and D2
neurons within the nigrostriatal pathways. The loss of dopamine neurons
in SNc is believed to be the reason for the development of Parkinson's
disease and some other parkinsonic syndromes
2. Pars Reticulata (SNr) - serves mainly as an input, conveying signals from
the basal ganglia to the thalamus.
• The basal ganglia are one of the components in the neural chain that controls voluntary
motor activity. The supreme component of this chain is the CEREBRAL CORTEX which
generates the commands that define the motor activity of all skeletal muscles in the
body. Basically, Basal Ganglia is a part of a basic feedback circuit, receiving information
from several sources including the cerebral cortex. The basal ganglia feed this
information back to the cortex, via the thalamus. and work in tandem with the pyramidal
and limbic systems.

PRIMARY FUNCTION OF BASAL GANGLIA

• Control conscious and proprioceptive movements. It receives signals from the cortex,
weighs those signals, and determines what actions to “disinhibit”
• Serves to fine-tune the voluntary movements.
• Basal ganglia mediate some and other higher cortical functions well: planning and
modulation of movement, memory, eye movements, reward processing, and motivation.

Direct Pathway
• Composed of inhibitory projections from the caudate or putamen (STRIATUM).
• Activity in the “Direct pathway” releases or “disinhibits” motor movement by inhibiting the
GPI/SNpr.
• DOPAMINE, via the nigrostriatal pathway, synapses on striatal neurons that express the
D1-family of receptors.
• The excite D1R neurons send inhibitory projections to inhibit the GPi/SNpr.
• The GPi/SNpr has GABAergic inhibitory neurons that project to the VA and VL of the
thalamus both of which send excitatory projections to the motor cortex.
• In this way, the “Direct pathway” inhibits the GPi which in turn is no longer inhibiting the
VA and VL of the thalamus.
• As a result, the VA/VL are said to be “disinhibited” and can excite the motor cortex to
promote movement through its corticospinal projections.
• END RESULT: Movement
Indirect Pathway

• Inhibits motor activity.

• The dorsal striatal neurons expressing the D2-family of dopamine receptors are inhibited
by dopamine from the SN.
• These D2R neurons send inhibitory GABAergic connections to the GPe.
• The GPe inhibits the subthalamic nucleus, which excites the GPi/SNpr, completing the
“Indirect pathway.”
• The GPi sends inhibitory GABAergic signals to the VA and VL of the thalamus.
• Activation of the “Indirect pathway” results in stimulation of the GPi which then inhibits
the VA/VL of the thalamus, ultimately inhibiting movement.
• NET RESULT: reduction of movement - hyperactive in hypokinetic disorders.

II. DEFINITION
• Parkinson’s Disease is an age-related degenerative brain disorder.
• PD causes unintended or uncontrollable movement such as shaking, stiffness,
imbalance and difficulty with coordination
• Most cases happen for unknown causes, others are inherited
• A nerve cell damage in the brain
• PD is not curable but can be effectively managed through medications.
STAGES:
Stage I lesions are found in the medulla oblongata (dorsal IX/X nucleus or intermediate reticular
zone)

Stage II pathology is expanded to involve lesions of the caudal raphe nuclei, the
gigantocellular reticular nucleus, and coeruleus-subcoeruleus complex

Stage III involvement of nigrostriatal system is apparent (pars compacta of the substantia nigra)

Stage lesions are also found in the cortex (temporal mesocortex and allocortex)
IV

Stage V involves the sensory association areas of the neocortex and prefrontal neocortex

Stage involves the sensory association areas of the neocortex and premotor areas.
VI
III. ETIOLOGY
• Idiopathic
• Head Trauma
• Drug Induced (antipsychotic)
• Genetic (Park1,Park3,Park12)
• Abnormal Proteasome System
• Old age

IV. EPIDEMIOLOGY
• M>W (2:1)
• Mean age of onset is 50 years

V. CLINICAL MANIFESTATION
Motor Skill Symptoms: Non-Motor Skill Symptoms:

• Bradykinesia • Mental/Behavioral issues (depression, visual

• Rigidity hallucination, difficulty in sleeping and
• Postural thinking)
instability • Sense of smell
• Tremors • Sweating and melanoma
• Gait difficulties • GI issues
• Dystonia • Pain
• Difficulty in
speaking

VI. PATHOPHYSIOLOGY

• The direct pathway model involves glutamate neurons that project from the
thalamus to motor regions of the cerebral cortex. These excitatory projections are
thought to be involved with stimulating movement. Neurons from the globus
pallidus internal and substantia nigra pars reticulata, however, project to the
thalamus and maintain a steady release of the neurotransmitter GABA which
acts to inhibit the thalamic neurons and suppress movement. This mechanism is
thought to be important in keeping unwanted movements from occurring. When
we want to make a movement, however, information about the movement is sent
from the cortex to the striatum via the corticostriatal pathway. Glutamate neurons
in this pathway excite neurons in the striatum, and the activated striatal neurons
release GABA in the globus pallidus internal and substantia nigra pars reticulata,
inhibiting the activity of these regions and stopping the inhibition of neurons in the
thalamus that are involved with movement. This effectively opens a gate for
movement to occur. Activity along this pathway tends to occur just prior to a
movement, and thus has been linked to the facilitation of movement.
• The indirect pathway model involves GABA neurons that project from the
external segment of the globus pallidus to a region called the subthalamic
nucleus. These globus pallidus neurons typically exert an inhibitory effect on
glutamate neurons in the subthalamic nucleus, but when the indirect pathway is
 activated by signals from the cerebral cortex, this causes the activation of GABA
neurons in the striatum, which project to the globus pallidus external and inhibit
the activity of neurons there. This keeps the globus pallidus external neurons
from being able to inhibit neurons in the subthalamic nucleus. The subthalamic
nucleus neurons are activated by projections from the cortex, and they stimulate
GABA neurons in the globus pallidus internal segment and substantia nigra pars
reticulata. These GABA neurons in turn project to the thalamus, inhibiting
thalamic neurons that travel to motor regions of the cerebral cortex to stimulate
movement. The inhibition of these thalamic neurons thus inhibits movement. This
activity in the indirect pathway is thought to antagonize the activity of the direct
pathway and act to keep unwanted movements from occurring. Neurons from the
substantia nigra pars compacta travel to the striatum via the nigrostriatal
pathway, and they can modulate the activity of the indirect pathway through
dopamine release in the striatum. One effect of this seems to be the inhibition of
activity in the indirect pathway, which leads to the facilitation of movement. This
is thought to be one reason why dopamine depletion in disorders like Parkinson’s
disease may lead to difficulties initiating movement.

VII. DIAGNOSIS
• Physical Examination
• PET Scan (Positron Emission Tomography) - used to assess activity and function of
brain regions involved in movement and scans for loss of dopamine, which is the major
chemical responsible for some symptoms of PD.
• MRI - can spot damaged brain neurons that can indicate Parkinson's and help predict
the severity of future symptoms
• CT Scan - may be used to rule out structural and other causes of parkinsonian
symptoms

VIII. PROGNOSIS
• a neurodegenerative condition for which there is neither treatment nor medication to
slow the progression of the condition. The course is hence progressive. Eventually,
unilateral symptoms develop into bilateral ones.
• The American Academy of Neurology notes that the following clinical features may help
predict the rate of progression of Parkinson’s:
• Older age at onset and initial rigidity/hypokinesia can be used to predict (1) a
more rapid rate of motor progression in those with newly diagnosed Parkinson
disease and (2) earlier development of cognitive decline and dementia; however,
initially presenting with tremor may predict a more benign disease course and
longer therapeutic benefit from levodopa
• A faster rate of motor progression may also be predicted if the patient is male,
has associated comorbidities, and has postural instability/gait difficulty (PIGD)
• Older age at onset, dementia, and decreased responsiveness to dopaminergic
therapy may predict earlier nursing home placement and decreased survival

Hoehn and Yahr Scale

• This scale is used in Parkinson’s Disease to measure for charting the progression of the
disease
stage Character of disability

I Minimal or absent, unilateral if present

II Minimal bilateral or midline involvement; balance not impaired

III Impaired righting reflexes, unsteadiness when turning or rising from a chair. Some activities are
restricted, but patient can live independently and continue some forms of employment

IV All symptoms are present and severe. Standing and walking possible only with assistance

V Confined to bed or wheelcahir

IX. DIFFERENTIAL DIAGNOSIS

Alzheimer’s • Slow progression
• Symptoms don’t go away
• Hallucinations in late stage

Huntington • Progressive breakdown (degenerative) of nerve cells

Disease • Rare and inherited (defective gene)
• Loss of thinking ability

Dementia • Progressive cognitive impairment (loss of memory)

• Visual hallucination

Multiple System • Rare and progressive

Atrophy • Affects movement and autonomic nervous system which controls several
basic functions, such as breathing, digestion and bladder control

SIMILARITIES • They are neurological conditions caused by neurodegeneration (gradual

damage to brain cells)

X. MEDICAL MANAGEMENT
• Carbidopa-Levodopa - primarily used to manage the symptoms of Parkinson's disease,
but it does not slow down the disease or stop it from getting worse. It is taken by mouth.
This drug combination is considered standard treatment for Parkinson's disease
symptoms such as tremor, muscle stiffness, and slowness of movement
• Apomorphine - a strong type of dopamine agonist. Dopamine agonist drugs act like
dopamine to stimulate nerve cells. These nerve cells then control movement and other
body functions, to help reduce the symptoms of Parkinson's
• Amantadine - a medication that is useful in treating some symptoms of Parkinson's
disease. It may cause greater amounts of dopamine to be released in the brain.
Amantadine can be used by itself to treat people in the early stages of Parkinson's
disease.
XI. SURGICAL MANAGEMENT
• Deep Brain Stimulation - the most common surgical treatment for Parkinson's disease
and aims to help treat movement disorders. The procedure involves using implanted
electrodes to interrupt disorganized electrical signals in the brain that cause movement
symptoms such as tremors.

XII. PT MANAGEMENT
• Aerobic exercise - For people with Parkinson disease, physical therapists should
recommend moderate- to high-intensity aerobic exercise to increase VO2, lessen the
severity of motor illness, and enhance functional outcomes.
• Resistance training - Physical therapists should implement resistance training to reduce
motor disease severity and improve strength, power, nonmotor symptoms, functional
outcomes, and quality of life in individuals with Parkinson disease
• Pulmonary Rehabilitation
1. diaphragmatic breathing exercises
2. air-shifting techniques
3. exercises that recruit neck, shoulder, and trunk muscles
4. manual techniques such as vibration and shaking can be used to ensure
complete exhalation, distal alveoli opening, and to assist with secretion
clearance.
• Balance training - To lessen postural control deficiencies and enhance mobility, balance
confidence, and quality of life in Parkinson's disease patients.
• Flexibility exercises - to improve ROM in individuals with PD. Flexibility exercises should
be performed a minimum 2 to 3 days per week and ideally 5 to 7 days per week.
• Gait training - to reduce motor disease severity and improve stride length, gait speed,
mobility, and balance in individuals with Parkinson disease
• Bed mobility skills - essential skills that are often very difficult owing to truncal rigidity
and bradykinesia. (example are
1. Side-lying rolling activities - emphasize segmental rotation patterns (i.e., isolated
upper and lower trunk rotations) should be practiced rather than a log-rolling
pattern. Patients with very stiff trunks may benefit from compensatory rolling
strategies using the UE or LE to reach over and initiate the movement (e.g., D1F
patterns of the UE or LE).
2. Rolling - should be practiced on different surfaces progressing from firm to soft
and finally simulating the patient’s bed surface at home.
3. Bridging - is an important activity that improves scooting in bed as well as sit-to-
stand transfers
4. Sitting - can be enhanced through exercises designed to improve pelvic mobility
as the patient with PD typically sits with a stiff and posteriorly tilted pelvis (i.e.,
sacral sitting position) along with a flexed upper trunk. Anterior and posterior tilts,
side-to-side tilts, and pelvic clock exercises can be practiced while sitting on a
therapy ball, which enhances ease of movement
5. Sit to stand - sitting on an inflated disc can also assist in the forward weight shift
and seat-off. Standing-up is enhanced by improved LE muscle strength.
Strengthening of the hip and knee extensors can be achieved using modified wall
squats. Practice standing up from a firm raised seat decreases the total
 excursion and work of extensor muscles and promotes ease of rise. Once control
is achieved, progression is then to lower, standard height seats.
• Group/Home Exercises
• Spinal Orthotics - spinal bracing may be an appropriate adjunct to therapy for patients
with postural deformities common to PD (e.g., increased thoracic kyphosis, decreased
costal expansion, and forward head posture).
• TENS - an efficient intervention for tremor suppression
• Patient, family, and caregiver education

References:
https://academic.oup.com/ptj/article/102/4/pzab302/6485202
https://www.physio-pedia.com/Parkinson%27s_-
_Physiotherapy_Management_and_Interventions
https://www.medicalnewstoday.com/articles/parkinsons-
surgery#:~:text=Deep%20brain%20stimulation%20(DBS)%20is,movement%20symptom
s%20such%20as%20tremors.
https://www.mayoclinic.org › side-effects › drg-20061695
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776563/
https://parkinsonsdisease.net/diagnosis/diagnosis-imaging
Neuroanatomy 2ndyear, Basal Ganglia Topic by Doc.Tayo
Medcounter.com/.instagram
O’Sullivan, S., Physical Rehabilitation, 6th Edition