Physiology Lecture

1. Basal Ganglia Disorders
Dr Raghuveer Choudhary
Dept. of Physiology
Dr S.N.Medical College
Jodhpur
8/30/2021

3. BG dysfxn
Slow, inefficient actions, rigidity,
bradykinesia, unwanted movement

4. Function
 Cerebral cortex, basal ganglia, cerebellum and
thalamus
– motor activity
– muscle tone
– organisation of movement
 What type ? -cerebral cortex
 How to perform? -basal ganglia+cerebellum
 Assist in regulation-thalamus

5. Function
 Part of extra-pyramidal motor system
 Facilitate behaviour & movement – required and
appropriate
 Inhibit unwanted & inappropriate

6. Results of Basal Ganglia
Impairment
 Involuntary Motor Movements
 Bradykinesia (slow) or Hypokinesia (slow or
diminished)
 Altered Posture
 Changes in Muscle Tone
6

8. Disease of basal ganglia
– Huntington’s 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
– Hemiballism -
 Spontaneous,wild & voilent involuntary movements
of one arm and leg (one-sided), which is caused by
damage (i.e., stroke) of the subthalamic nucleus.

9. Parkinson’s 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)
 (-) Direct Pathway
 (+) Indirect Pathway
 (-) Thalamus

10. Muhammad Ali in Alanta Olympic
Parkinson’s
Disease
Disease of mesostriatal
dopaminergic system
PD
normal

11. 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).

12. Triad of Signs in Parkinson’s
 Bradykinesia (esp. movement
initiation)
 Resting Tremor (Rolling pill)
 Rigidity
What did you see?

13. Substantia Nigra,
Pars Compacta (SNc)
DOPAminergic Neuron
Slowness of Movement
- Difficulty in Initiation and Cessation
of Movement
Clinical Feature (1)
Parkinson’s Disease

14. Clinical Feature (2)
Resting Tremor
Parkinsonian Posture
Rigidity-Cogwheel Rigidity
Parkinson’s Disease

15.  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.

16.  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).

17. Other causes of parkinsonism-
 Postencephalitic
 Severe carbon monoxide poisoining.
 Toxic agents in well water, agricultural pesticides-
– oxidative metabolities released affect dopamine neurons.
 Drug induced-
– Antipsychotic: phenothiazines {post synaptic dopamine
receptor blocker}.
– Antihypertensive: Reserpine [pre synaptic dopamine
receptor blocker].
– Symptoms of parkinsonism accompany- cerebrovascular
diseases, Brain tumors, repeated headtrauma.

19.  Motor symptoms-
 The cardinal symptoms are (mnemonic "TRAP"):
 Tremor: normally 4–6 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.

20. Other signs of Parkinson’s
 Postural instability
 Shuffling gait
 Dec arm swing
 Turning “en bloc”
 Mask face
 Micrographia

21.  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.

22. – Festination: a combination of stooped
posture, imbalance, and short steps. It leads
to a Stooped, forward-flexed posture.
– It leads to Gait that gets progressively faster
and faster, often ending in a fall.
– In severe forms, the head and upper shoulders
may be bent at a right angle relative to the trunk
(camptocormia).

26. 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.

31. • 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 Parkinson’s disease (PD).
excitation
inhibition
D1
D2
D1 & D2
Dopamine
receptors
somatosensory
cortices
Thalamus
Putamen
GPe
GPi
STN
SNc
motor cortices
GPe/i: Globus
pallidus
internal/external
STN: Subthalamus
Nucleus
SNc: Pars Compacta
(part of substantia
nigra)

35. (-)
(-)
(-)
(+)
Parkinson’s
Disease
Huntington’s
Disease
(-)
(-)

36. 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.

38.  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),

39.  Carbidopa and benserazide are dopa
decarboxylase inhibitors.
 They help to prevent the metabolism of L-
dopa before it reaches the dopaminergic
neurons
 generally given as combination preparations
of carbidopa/levodopa

40. Huntington’s 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

44. Clinical Feature
Principal Pathologic Lesion:
Corpus Striatum (esp. caudate nucleus)
and Cerebral Cortex
- 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.
HUNTINGTON’S CHOREA

45. SYDENHAM’S CHOREA
- 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
Clinical Feature
Principal Pathologic Lesion: Corpus Striatum

48. HEMIBALLISM
- 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
Clinical Feature
Lesion: Subthalamic Nucleus

49. Thank you

50. Thank you for
not listening