1. Case Discussion: Joint Session
Presenters: By Dr. Zeleke W/Y (NR-II)
Dr. Yizengaw IMR-II
Moderators: Dr. Nebiyu B.(Consultant Neurologist)
Dr. Tesfaye Y.(Consultant Internist)
Date:Feb 20, 2023
5/10/2023 1
3. History
• This is a right handed 42 yrs old patient from Metemma who was last
relatively healthy 02 years ago during which he started to have aching
pain and discomfort over his right side upper and lower limbs that
improves with exercise.
• Since 08 months, he has been experiencing progressive slowness on
his right side limbs, speech slowness and tendency to fall forward
while walking but no swaying to either side.
• He has also history of pronation suppination types of shaking of his
right hand and forearm and leg at resting position which become
prominent during activities like holding holding coffee cup and water
glass same duration.
5/10/2023 3
4. History....
• There is also involvement of left hand which is very subtle notice
since 02 months.
• He has been complaining urge incontinence since 08 months.
• Following above symptoms patient can’t use his right hand for
feeding and using support during walking.
5/10/2023 4
5. History....
• He didn’t learn formal education but he can write and read Amharic language.
• He was serving on national defense force before current problem.
• He used known alcoholic patient for the past 20 years he drinks 3-4 days per
week and it was 4-5 beers per days but he claims that no history of
intoxication. He discontinued it for the past 09 months.
• He is married and has 03 kids.
5/10/2023 5
6. History....
Otherwise;
• No history of headache vomiting or neck pain
• No history of change in mentation or behavioral change
• No history of forgetfullnesss
• No history of abnormal body movement
• No history of TB symptoms complex
• Difficulty of controlling feaces or constipation
• No history of chronic illnesses like DM, HTN or cardiac illness
5/10/2023 6
7. History....
• No difficulty of swallowing or choking episodes during swallowing
• No history of sexual dysfunction
• No history of loss of smell
• No history of sleep disturbance
• No history of hallucinatory experience or other psychiatric symptoms.
• No history of head trauma
• No self or family history of similar compliant
5/10/2023 7
8. Physical Examination
• General Medical Examination
• General Appearance: well looking
• Vital signs
• Bp= 130/75 (both at supine and sitting position) RR=22
• PR= 80 regular full in volume Temp.= 36.4 SpO2=95%
room air
• HEENT=pink conjuctive non-icteric sclera
• Lymphoglandular system=no lymph node enlargement over the
accessible site
5/10/2023 8
9. General Medical Examination....
Respiratory system:
• Chest is clear and resonsnt bilaterally with good air entry symmetrically
Cardiovascular system:
• all accessible arteries are palpable symmetrically with good volume regualr rate and soft
consistency
• Precordium is quite and PMI is not shifted
• S1 and S2 are heard well no murmur no gallop
5/10/2023 9
10. General Medical Examination....
Abdomeninal examination
• flat and moves with respiration no scars
• No signs of fluids collection. no organomegally
Integumentary system
• no rashes, no palmar pallor
5/10/2023 10
12. Neurologic Examination
• Mental state exam
• Concsious
• Orientation
• Spatial orientation:he can identiy his village being at hospital
• Non-spatial: oriented to time place and person
5/10/2023 12
13. Mental state exam.....
• Attention
• He can draw clock and put
numbers on respective site and
cancel line
• He can count months of Ethiopian
backward and forward
5/10/2023 13
14. Mental state exam.....
• Language:
• fluent,comprehend spoken langauge,can name familiar objects
• Speech pattern: hypophonic monotony
• Memory:
• immediate: he can register cow,car and pen
• Short term: he recalled above three items
• Remote:he can narrate about his past,remember president of Amhara region
5/10/2023 14
15. Mental state exam.....
• Abstract thinking:
• He can interprate Amharic proverb like “dir biyabir anbessa yasir’’
• He can tell me clearly the similarity and difference between farmer and teacher
• Judgement: good
• Insight: patient understand problem he is having and seek medical by himself
5/10/2023 15
16. Mental state exam.....
• Executive function:He can copy pentagon
• Caculation: He can serially substruct 7 from 100 till 55
• Praxis:He can show how to brush teeth and comb hair ideally
5/10/2023 16
18. Neurologic Examination....
• Cranial nerves
• Both nostrils are patent and can smell orange peel bilaterally
• Pupils are round midpositioned and midsized with reactivity for direct
and consencual light reflex
• Visual field:
• he can count fingers on all quadrants both on the right and left
• Visual acuity:
• he can count finger with both eyes alternatively at the distance of 20 feet
5/10/2023 18
20. Neurologic Examination....
• Corneal reflex is present
• Facial sensation is intact symmetrically
• Mastication is strong bilaterally
• Can move his eyes to 06 cardinal directions
5/10/2023 20
21. Neurologic Examination....
• Symmetric facial profile at rest and during smiling
• Has difficulty of articulating labialis consonants
• Can hear rubbing finger bilaterally
• Swallowing passed for all forms of diet
5/10/2023 21
22. Neurologic Examination....
• Can shrug up shoulder and moves head against resistance bilaterally
• Can protrudes rolls and moves side to side his tongue no tremor no
fasciculation but there is tremor
5/10/2023 22
23. Neurologic Examination....
• Motor exam
• No spontaneous or induced fasciculation,symmetrically placed
extremities
• There is high frequency and high amplitude postural,kinetic and
tagret pronation-suppination types of right upper limb has also subtle
resting tremor,yes-yes type of head tremor.
• There is also resting subtle tremor on the left hand.
5/10/2023 23
24. Neurologic Examination....
• There is dragging of right lower limb
• Tone=Cogwheel rigidity on the right limbs
• Power=right side 5/5 left side left side =5/5
5/10/2023 24
25. Neurologic Examination....
• Deep tendon reflexes
• Plantar=Right extensor where as left side flexor
response
5/10/2023 25
Biceps Triceps Brachioradialis Knee Ankle
Right
+2 +2
+2 +3 +2
Left +2 +2 +2 +3 +2
26. Neurologic Examination....
• Sensory exam
• Touch sensation is decreased on the right upper and lower limbs
• Position and vibration is intact bilaterally
5/10/2023 26
27. Neurologic Examination....
• Cortical sensation
Stereognosis: she can identify coin by touching unaided by vision
Graphesthesia: she can also identify number 3 written on her palm
Two-point discrimination=distinguish two simultaneous, closely placed
pinpricks on the fingertips
Double simultaneous stimulation=can identify when simultaneously touched
5/10/2023 27
29. Neurologic Examination....
• Cerebellar function and gait
• Finger to nose and RAM on left side can perform without difficulty but on the
right side tremor worsen and very bradykinetic
• Finger tapping and toe tapping,fist open and close: significant reduction in
speed and amplitude on the right side
• Heel-knee-shin: can perform but slowly
5/10/2023 29
30. Neurologic Examination....
• Cerebellar function and gait....
Can stand from sitting position without
support
Impaired tandem walk
Decreased arm swing more on the right
side
Takes three steps to turn (Turn en block)
Stooped posture
Romberg’s test negative
Pull test negative
Check and rebound intact
Wide-based gait
5/10/2023 30
36. Summary
• Subjective summary
• 42 yr old male from Metemma
• Right uppper and lower extremities aching type of pain and
discomfort/2yrs which improve with exercise.
• Progressive slowness of right upper and lower limbs and speech. of
08 months.
• Pronation suppination types of shaking of his right hand and forearm
and leg at resting position which become prominent during activities
like holding holding coffee cup and water glass.
• There is also involvement of left hand which is very subtle notice
since 02 months.
5/10/2023 36
37. Subjective summary....
• He has been complaining urge incontinence since 08 months.
• He used to drink 4-5 beers for 20 years,he drinks 3-4 days per week
which he discontinued it for the past 08 months.
5/10/2023 37
38. Summary....
• Objective: G/A: less interactive masked face
• Vital sign at normal range
• General medical exam..no abnormalities detected
Neurologic exam:
• Mental state exam:
Hypophonic speech
• Cranial nerves
Has difficulty of articulating labials consonants
5/10/2023 38
39. Objective summary....
• There is high frequency and high amplitude postural,kinetic and
target types of tremor over right hand and forearm and at rest
• And there is also subtle resting tremor on the left side
• yes-yes type of head tremor.
• There is dragging of right lower limb
• Cogwheel rigidity on the right extremities
• Brisk DTR on the patella bilaterally
• Plantar=Right extensor where as left side flexor response
5/10/2023 39
40. Objective summary....
• Touch sensation is decreased on the right upper and lower limbs.
Cerebellar function and gait
• Finger to nose and RAM: on left side can perform without difficulty but on the
right side tremor worsen and very slow
• Finger tapping and toe tapping,fist open and close: significant reduction in
speed and amplitude on the right side
• Heel-knee-shin: can perform but slowly on the right side
5/10/2023 40
41. • Impaired tandem walk
• Decreased arm swing more on the right side
• Takes three steps to turn (Turn en block)
• Stooped posture
5/10/2023 41
43. Basal Ganglia anatomy
• Refers to masses of gray matter deep within the cerebral hemispheres.
• It includes the CAUDATE NUCLEUS, PUTAMEN & GLOBUS PALLIDUS
• The Caudate Nucleus + Putamen = STRIATUM
• The Putamen + Globus Pallidus = LENTICULAR NUCLEI
• Functionally, the Basal Ganglia & their interconnections form the extrapyramidal
system, which includes midbrain nuclei such as the Substantia Nigra, and the
Subthalamic Nuclei.
• Blood supply is via MCA.
5/10/2023 43
44. Anatomy of BG....
• INPUT ZONES
• Corpus Striatum
• Caudate
• Putamen
• OUTPUT ZONES
• Globus Pallidus Interna (GPi)
• Substantia Nigra Pars Reticulata
• INTERMEDIATE ZONE /NUCLEI/
• Globus Pallidus Externa
(GPe)
• Subthalamic Nucleus
(STN)
• Substantia Nigra Pars
Compacta (SNc)
THE THALAMUS, ACT AS A
MOTOR “GATE KEEPER”
5/10/2023 44
46. MOTOR (BG) LOOP & NON MOTOR LOOPS
• BG regarded as motor structure, it regulates initiation of motor movements.
• It is also a center for anatomical circuits involved in modulating non motor
loops w/h terminates out side primary & premotor cortices (in frontal lobe)
• so, deterioration in cognitive and emotional function in both HD and PD
could be the result of disruption of these non motor loops
46
LOOPS Functions
MOTOR LOOP Control initiation of movements
NON MOTOR LOOPS
Prefrontal loop Initiation and termination of cognitive
processes: planning, working memory and
attention
Limbic loop Regulates emotional behavior and motivation
Oculomotor loop Controls eye movements
47. Dopamine receptors
• D1 / D2 RECEPTORS located in striatum.
• From the striatum, GABAergic projections to the substantia nigra contain
mainly D1 receptors
• While those project to the globus pallidus contain mainly D2 receptors
• D1 facilitates excitatory in the direct pathway
• D2 facilitates inhibitory in the indirect pathway
• Dopamine inhibits indirect pathways through D2 receptors, and stimulates direct
pathways through D1 receptors.
5/10/2023 47
48. Pathways of motor loop
• Direct pathways
• DISINHIBITION OF THALAMIC NUCLEUS
• Keeps the thalamus exciting cortex
• Facilitate the ongoing cortically initiated movements in the spinal cord
and brain stem
5/10/2023 48
50. DIRECT PATHWAY
Brain stem/
Spinal cord
VA/VL
Striatum
DIRECT PATHWAY:
facilitates
movement
* * tonically active
~100 Hz
GPe
STN
*
Disinhibition
Cortex
GPi/SNr
Excitation (glutamate)
Inhibition (GABA)
50
51. Indirect pathways
• STIMULATION OF CORTICOSTRIATAL inhibitory SYSTEM
• Inhibition of GPe Causing disinhibition /stimulation/ of STN and
increased stimulation of Gpi/SNr
• Resulting in an increased inhibition of Thalamic Nucleus to the
cortex
• REDUCED THALAMO-CORTICAL OUTPUT
• Inhibition of unwanted movements
5/10/2023 51
53. • Motor systems disorders are the imbalance between the direct/indirect outputs.
Manifestations include:
• HYPOKINETIC DISORDERS are associated with abnormal slowness of movements
• insufficient direct pathway
• excess indirect pathway
• HYPERKINETIC DISORDERS associated with abnormal, involuntary movements
• excess direct pathway
• insufficient indirect pathway
5/10/2023 53
55. Parkinsonism
• It is a clinical syndrome presenting with any combination of the
following cardinal features:
Tremor- at- rest
Bradykinesia/hypokinesia/akinesia
Rigidity
Flexed posture of neck, trunk and limbs
5/10/2023 55
56. Parkinson disease
5/10/2023 56
• The most common form of parkinsonism
• It is a chronic, progressive disorder caused by degenerative loss of dopaminergic neurons
in the brain.
• The second most prevalent neurodegenerative condition next to AD.
• Clinically characterized
• asymmetric parkinsonism and
• a clear, dramatic, and sustained benefit from dopaminergic therapy
57. EPIDEMIOLOGY
• PD affects millions of people worldwide, and the number of affected patients
may double by 2030.
• Estimated to affects about 1% of people older than 60 years of age in the United
States.
• The mean age of onset of PD is about 60 years, and the lifetime risk is ~2% for
men and 1.3% for women
• Men carry a greater chance than women.
5/10/2023 57
58. Contd....
• Juvenile parkinsonism onset at younger than 20 years.
• Many cases are due to mutations in the PRKN gene
• Heredodegenerative diseases such as HD and Wilson disease.
• Young-onset PD: onset between 20 and 40 yrs
5/10/2023 58
59. ETIOLOGY
• Most PD cases occur sporadically (~85–90%) and are of unknown cause.
• genetic (10-15%)
• PARK2, LRRK2 mutation
• Environmental factors
• MPTP, heavy metals (manganese, lead, and copper)
• Exposure to pesticides: paraquat, rotenone.
• Rural living
• Drinking well water
• Exposure to toxins, including carbon monoxide, trace metals, organic solvents,
and cyanide
• Reduced risk with cigarette smoking & caffeine
5/10/2023 59
60. 60
Schematic diagram of the basal ganglia thalamocortical circuitry under normal conditions
(A) and in Parkinson’s disease (PD) (B). Inhibitory connections are shown as black arrows
and excitatory connections as red arrows.
61. PATHOGENESIS
• Two major pathogenic hypotheses
• Mitochondrial dysfunction and oxidative stress critical in the pathogenesis
• Misfolding and aggregation of proteins are instrumental in the PD neurodegenerative
process.
• These two hypotheses are not mutually exclusive, and interactions among
these pathogenic factors are likely to be important in understanding the
mechanisms of neurodegeneration in PD.
5/10/2023 61
62. CLINICAL SYMPTOMS
• Gradual
• The most common presentation
• Rest tremor in one hand, often associated with decreased arm
swing and shoulder pain
• Asymmetric especially early
5/10/2023 62
64. Motor Symptoms: Tremor
• It present in the distal parts of the extremities and the lips while the
involved body part is “at rest.”
• “Pill-rolling” tremor of the fingers and flexion–extension or
pronation–supination tremor of the hands are the most typical.
• The tremor ceases on active movement of the limb but can reemerge
when the limb remains in a posture against gravity.
5/10/2023 64
65. • Rest tremor at a frequency of 4 to 5 Hz is present in the extremities,
almost always distally.
• Rest tremor is also common in the lips, chin, and tongue
5/10/2023 65
66. Motor Symptoms:Rigidity
• Marked hypertonia, which principally affects the axial muscles and
the proximal and flexor groups of the extremities.
• Cogwheel rigidity-superimposition of the tremor.
5/10/2023 66
67. Motor Symptoms: Bradykinesia
• It is a slowness of movement
• It is usually the most disabling component
• Because of the rigidity and bradykinesia: Strength may seem to be
decreased, there is no true loss of power such as is seen in CST lesions.
• Generalized bradykinesia may cause difficulty arising from a chair or
turning in bed.
5/10/2023 67
68. Bradykinesia in the arms
Loss of spontaneous movement such as gesturing
Smallness and slowness of handwriting (micrographia)
Slowness and decrementing amplitude of repetitively opening and
closing the hands, tapping a finger, and twisting the hand back and
forth
5/10/2023 68
69. Contd....
Difficulty with hand dexterity for shaving, brushing teeth, and putting
on makeup; and
Decreased arm swing when walking
• In the trunk
• It is manifested by difficulty arising from a chair, getting out of
automobiles, and turning in bed.
5/10/2023 69
70. Bradykinesia in the legs
• Slowness and decrementing amplitude in repetitively tapping toes.
• Slowness in making the number 8 with the foot
• A slow, short- stride, shuffling gait with reduced heel strike when
stepping forward.
• Typically in PD, there is a narrow base, that is, the feet are close
together when the patient walks.
5/10/2023 70
71. Contd....
• The face loses spontaneous expression (masked facies, hypomimia )
with decreased frequency of blinking
• Poverty of spontaneous movement is characterized by loss of
gesturing and by the patient's tendency to sit motionless.
• Speech becomes soft ( hypophonia ), and the voice has a monotonous
tone with a lack of inflection (aprosody).
5/10/2023 71
72. ABNORMALITIES OF BALANCE AND POSTURE
• Tend to increase as the disease progresses.
• Flexion of the head, stooping and tilting of the upper trunk, and a
tendency to hold the arm in a flexed posture while walking.
• Postural instability falls and injuries
• It can be tested in the office with the "pull test"
5/10/2023 72
73. Flexed posture
• Commonly begins in the arms and spreads to involve the entire body.
• The head is bowed; the trunk is bent forward; the back is kyphotic; the arms are
held in front of the body; and the elbows, hips, and knees are flexed.
• Deformities of the hands include ulnar deviation of the hands, flexion of the
metacarpophalangeal joints, and extension of the interphalangeal joints (striatal
hand).
• Inversion of the feet is apparent, and the big toes may be dorsiflexed (striatal toe)
and the other toes curled downward.
5/10/2023 73
75. Motor sysmptom: Postural instability
• Loss of postural reflexes occurs later in the disease.
• Postural instability falls and injuries
• It can be tested in the office with the "pull test"
• The patient has difficulty righting himself or herself after being pulled or
tilted off balance.
• Typically, after a practice pull, a normal person can recover within two steps.
5/10/2023 75
76. Loss of postural reflexes.....
• Mild can be detected if the patient requires several steps to recover
balance.
• A moderate loss is manifested by a greater degree of retropulsion.
• More severe loss the patient would fall if not caught by the examiner.
5/10/2023 76
77. GAIT DISTURBANCE
• Shuffling gait :- short steps and a tendency to turn en bloc.
• Festinating gait :- accelerate in an effort to “catch up” with the body's center
of gravity
• Freezing of gait (advanced PD)
• At the onset of locomotion (start hesitation)
• When attempting to change direction or turn around
• Upon entering a narrow space such as a doorway
5/10/2023 77
78. 5/10/2023 78
The gait is slow, stiff, and shuffling;
the patient walks with small,
mincing steps.
Involuntary acceleration
(festination),
decreased arm swing
en bloc turning
start hesitation, and
freezing (obstacles)
79. AUTONOMIC DYSFUNCTION
• Orthostatic hypotension, constipation, urinary urgency & frequency,
excessive sweating, and seborrhea.
• Orthostatic Hypotension - present in many pts resulting from
sympathetic denervation of the heart or as a side effect of
dopaminomimetic therapy.
• Paroxysms of Drenching Sweats may occur in advanced PD, often
related to the wearing off of antiparkinsonian medications.
5/10/2023 79
80. Secondary motor symptoms
diminished arm swing,
decreased blink rate
masked facies (hypomimia)
decreased voice volume (hypophonia), and
difficulty turning over in bed
5/10/2023 80
81. Pathologic hallmark
• Degeneration of dopaminergic neurons in the SNc
• Reduced striatal dopamine, and
• Intraneuronal proteinaceous inclusions known as Lewy bodies and
Lewy neurites that primarily contain the protein α-synuclei.
5/10/2023 81
82. “Nondopaminergic” pathology
• Responsible for the development of the nondopaminergic clinical feature
• Neuronal degeneration with inclusion body formation can also affect
cholinergic neurons of the nucleus basalis of Meynert (NBM),
norepinephrine neurons of the locus coeruleus (LC),
serotonin neurons in the raphe nuclei of the brainstem, and
neurons of the olfactory system, cerebral hemispheres, spinal cord, and
peripheral autonomic nervous system.
5/10/2023 82
85. PHARMACOLOGIC AGENTS
• Levodopa is gold standard
Particularly benefits the classic motor features
(akinesia and rigidity)
prolongs independence and employability
improves quality of life, and increases life span
Almost all PD patients experience improvement
5/10/2023 85
• Different formulations:
immediate-release
extended-release,
orally disintegrating tablets
intestinal gel
86. Levodopa-induced motor complications
• Consist of fluctuations in motor
response
• “On” episodes
drug is working and involuntary
movements appeared such as
dyskinesias
• ‘’Off’’ episodes
when parkinsonian features
return
5/10/2023 86
87. Dopamine agonists
• Stimulate dopamine receptors directly
• bypassing degenerating dopaminergic
neurons in the brain
• Ergot derivative: bromocriptine, pergolide,
cabergoline
• Second generation nonergot: pramipexole,
ropinirole, rotigotine
5/10/2023 87
• Side effecs
• Acute: nausea,vomiting, and orthostatic
hypotension
• Chronic (use dose related):
hallucinations and cognitive impairment
Sedation with sudden unintended
episodes of falling asleep
impulse-control disorders, including
pathologic gambling, hypersexuality, and
compulsive eating and shopping.
88. COMT inhibitors
• Reduce the breakdown of levodopa to 3-O-methyldopa and increase the
plasma half-life of levodopa.
• Combining levodopa with a COMT inhibitor reduces “off” time and
prolongs “on” time in fluctuating patients while enhancing motor scores
• Currently available COMT inhibitors include entacapone and tolcapone
• Tolcapone is most effective despite its hepatotocixity
5/10/2023 88
89. MAO-B inhibitors
• Block central dopamine metabolism and increase synaptic concentrations of the
neurotransmitter.
• Prevent levodopa degradation in the brain and limit its reuptake.
• Provide antioxidative properties in patients with Parkinson disease.
• They have disease-modifying effects.
• Selegiline is a selective and irreversible MAO-B inhibitor approved as adjunctive medication to
levodopa in patients with motor fluctuations.
• Rasagiline, a second-generation MAO-B inhibitor
• Safinamide recently approved as adjunct therapy in patients with PD with motor fluctuations.
5/10/2023 89
90. Anticholinergic medications
• They are used to treat tremor in younger patients
• Due to elderly individuals’ propensity to induce a
variety of side effects
• confusion,dry mouth, urinary retention, and constipation,
glaucoma, and particularly cognitive impairment.
• Trixeyphenidyl and benztropine
5/10/2023 90
91. Amantadine: An antiviral agent
• Antiparkinsonian effects that are thought to be due to N-methyl-d-aspartate
receptor antagonism.
• It is most widely used as an antidyskinesia agent in patients with advanced PD.
• Major side effect: cognitive impairment.
• Amantadine should always be discontinued gradually because patients can
experience withdrawal-like symptoms.
5/10/2023 91
92. MANAGEMENT OF THE NONMOTOR AND NONDOPAMINERGIC
FEATURES OF PD
• Dementia in PD (PDD) is common, ultimately affecting as many as
80% of patients.
• DLB
• Dopaminergic drugs can worsen cognitive function in demented
patients
• Use the lowest dose of standard levodopa.
• Anticholinesterase agents
5/10/2023 92
93. • Autonomic disturbances
• Orthostatic hypotension
Initial treatment should include
adding salt to the diet and
elevate the head of the bed to
prevent overnight sodium natriuresis.
Low doses of fludrocortisone or
midodrine provide control for most
cases.
• Sexual dysfunction
• Urinary compliants
• Constipation
• Sleep disturbances
RLS, sleep apnea, RBD
Low doses of clonazepam (0.5–1
mg at bedtime)
5/10/2023 93
94. Nonpharmacologic Therapy
• Gait dysfunction with falling
• Canes and walkers
• Freezing may occur during “on” or
“off” periods.
• “Off” periods may respond to
dopaminergic therapies
• No specific treatments for “on” period
freezing.
• Speech impairment: speech therapy
• Exercise
Recommended for all PD patients.
reduce the risk of arthritis and frozen
joints
Neuroprotective effects....
Exercise modalities include core strength
training exercises, tai chi, yoga, boxing,
and dance and music therapy
• Overall care plan:education, assistance
with financial planning, social services,
and attention to home safety.
5/10/2023 94
95. Advanced Parkinson Disease
• The reduced storage and release capacity of endogenous dopamine
can lead to the shortened duration of levodopa benefit.
• ‘’Predictable wearing off’’
• Patients will experience a decline in medication efficacy in which
symptoms return prior to the next dose.
• Motor fluctuations and levodopa-induced dyskinesia set in.
• Gastric emptying issues with advanced disease may further
contribute to uneven medication absorption.
• Nonmotor fluctuations: depression, fatigue, and anxiety.
5/10/2023 95
96. Contd....
• So, optimize on time and reduce off time while minimizing troublesome
levodopa-induced dyskinesia.
• Off time may be treated by
More frequently taking PD medications
Using an extended-release form of levodopa
Adding a COMT inhibitor or MAO-B inhibitor, or
Addition of dopamine agonist
5/10/2023 96
98. Deep brain stimulation
• Apart from tremor, DBS will provide no additional symptom relief over levodopa.
• Reducing the variability of response (motor fluctuations) is the main target of this
treatment.
• Structures targeted:
Subthalamotomy and subthalamic nucleus stimulation
Pallidotomy and pallidal stimulation
Thalamotomy and thalamic stimulation
5/10/2023 98
101. Atypical parkinsonism
• A group of neurodegenerative conditions that usually are associated with more
widespread pathology than found in PD.
• There is degeneration of striatum, globus pallidus, cerebellum and brainstem as
well as the SNc.
5/10/2023 101
102. Contd....
• Pathologically, neurodegeneration involves the SNc (typically without Lewy bodies)
and has more extensive neurodegeneration than occurs in PD.
• Neuroimaging of the dopamine system can’t differentiate PD from atypical
parkinsonism (striatal dopamine depletion in both).
• Metabolic imaging of the basal ganglia/thalamus network (using 2-F-deoxyglucose)
show a pattern of decreased activity in the GPi with increased activity in the
thalamus.
• The reverse works PD.
5/10/2023 102
103. When should one suspect an Atypical Parkinsonian Disorder?
5/10/2023 103
The incidence prior to age 50 is low but increases with advanced age.
Motor symptoms become evident when 60% to 80% of dopaminergic neurons are lost in the SNPc.
Lateral tilting of the trunk commonly develops (Pisa syndrome), and extreme flexion of the trunk (camptocormia) is sometimes seen.
freezing when encountering obstacles such as doorways
Indeed, epidemiologic studies suggest
that clinical symptoms reflecting early involvement of nondopaminer-
gic neurons such as constipation, anosmia, rapid eye movement (REM)
behavior sleep disorder, and cardiac denervation can precede the onset
of the classic motor features of PD by several years if not decades.
Based on these findings, efforts are underway to accurately define a
premotor stage of PD.
Particularly effective in treating akinesia and rigidity, with more variable effects on tremor.
The precise cause of these prob-
lems, and why they appear to occur more frequently with dopamine
agonists than levodopa, remains to be resolved, but reward systems
associated with dopamine and alterations in the ventral striatum
and orbitofrontal regions have been implicated
Acute side eff ects of dopamine agonists include nausea, vom_x0002_iting, and orthostatic hypotension. As with levodopa, these can
usually be avoided by slow titration.
Drugs are usually
discontinued in the following sequence: anticholinergics, amantadine, dopamine agonists, COMT inhibitors, and MAO-B inhibitors
An effective therapy for gait impairment is an important unmet need in PD.
In the early stages, they may show a modest benefit from levodopa and can be difficult to distinguish from PD,
On the later course the diagnosis becomes clearer.
