For practitioners, physicians and DM Neurology residents.

1. DR GANESHGOUDA MAJIGOUDRA
CONSULTANT NEUROLOGIST
NANJAPPA HOSPITALS DAVANAGERE
9380906082
ganeshgoudam4@gmail.com
APPROACH TO PARKINSONISM

2. INTRODUCTION
• Parkinson disease (PD) is the most common neurodegenerative movement disorder.
• Progressive degeneration of dopamine-producing neurons in the substantia nigra of the midbrain
accounts for the manifestation of this disease
• Classical clinical triad includes- tremor, rigidity, and bradykinesia.
• Other symptoms includes non-motor and neuropsychiatric manifestations that affect function and
quality of life.

3. CLINICAL FEATURES OF PD
• Resting Tremor (70%) “TRAP”
• Bradykinesia
• Rigidity
• Postural Instability
• Signs start in one limb, usually an arm, and spread to the other
limb on that side

4. PARKINSON’S DISEASE SYMPTOMS
• Secondary features of the disease:
• Depression
• Dementia
• Dysphagia
• Anxiety
• Orthostatic hypotension
• Constipation

5. PARKINSON’S DISEASE COURSE

6. PROGNOSIS
• First 5 years are the “honeymoon period”, and patients generally do well
• Between 5 and 10 years, most patients experience medication-related difficulty
• By 10 years, many develop poor balance

7. DIAGNOSING PARKINSON'S DISEASE
UNITED KINGDOM PD SOCIETY BRAIN BANK
CRITERIA
• Step 1
• Bradykinesia
• At least 1…
• Rigidity
• 4-6 Hz rest tremor
• Postural instability
• Not visual
• Not vestibular
• Not cerebellar
• Not sensory
Hughes et al. JNNP;55:181-184

8. DIAGNOSING PARKINSON'S DISEASE
UNITED KINGDOM PD SOCIETY BRAIN BANK
CRITERIA
• Step 2—exclusions
• Stepwise progression
• Head injuries
• Encephalitis
• Oculogyric crises
• Neuroleptics
• Familial
• Remission
• Strictly unilateral
• Supranuclear gaze palsy
• Cerebellar signs
• Early, severe ANS
• Early, severe dementia
• Babinski sign
• Tumor/hydrocephalus
• Dopa unresponsive
• MPTP
Hughes et al. JNNP;55:181-184

9. DIAGNOSING PARKINSON'S DISEASE
UNITED KINGDOM PD SOCIETY BRAIN BANK
CRITERIA
• Step 3—supportive features
• Unilateral onset
• Rest tremor
• Progressive disorder
• Persistent asymmetry, worse on onset side
• 70-100% response to levodopa
• Severe levodopa-induced dyskinesias
• > 5 year history levodopa-responsiveness
• Disease course > 10 years
Hughes et al. JNNP;55:181-184

10. RISK FACTORS FOR PD
• Increased risk
• Age
• Family history
• Exposure
• Well water
• Pesticides
• Head injury
• REM behavior disorder
• Constipation
• Depression
• Decreased risk
• Caffeine
• Cigarettes
these are more likely
early disease symptoms

11. PARKINSON-PLUS SYNDROME
(PPS)
• Also called atypical parkinsonism,
refers to a group of
neurodegenerative movement
disorders that resemble idiopathic
Parkinson's disease (PD) with
certain distinguishing clinical and
patho physiological features.
• Ex; MSA,PSP,LBD &CBD

12. PARKINSON-PLUS SYNDROME
(PPS)

14. PARKINSON-PLUS SYNDROME
(PPS)

15. Ubiquitin-dependent
proteasomal proteolysis
System failure
Susceptibility
 Expression of UPS components
Age-related  UPS activity
Oxidative dopamine metabolism
Toxic processes
Oxidative stress
Mitochondrial dysfunction
Toxins
Gene mutations
-synuclein
Parkin
UCH L1
LRRK2
Protein accumulation Cell dysfunction Lewy body formation
Cell death
modified from McNaught & Olanow. Ann Neurol 2003;53:S73-86.
ETIOPATHOGENESIS OF
PARKINSON

16. POTENTIAL MECHANISMS IN PD
• Oxidative stress
• Mitochondrial failure
• Excitotoxicity
• Protein aggregation
• Transport problems
• Interference with DNA
transcription
• Nitric oxide
• Inflammation
• Apoptosis
• Trophin deficiency
• Infection
Mandel et al. CNS Drugs 2003;17(10):729-762.

21. HOEHN AND YAHR STAGES OF PD

22. DIAGNOSTIC TESTING

24. D
I
A
G
N
O
S
T
I
C
T
E
S
T
I
N
G

25. NIGROSOME AND DOPAMINE TRANSPORTER
IMAGING

26. DIAGNOSTIC TESTING

27. DIAGNOSTIC TESTING

28. DIAGNOSTIC TESTING

29. DIAGNOSTIC TESTING
NBIA SPECTRUM WILSONS DISEASE

30. INITIATION OF PHARMACOLOGICAL THERAPY IN
PARKINSON’S DISEASE: WHEN, WHY, AND HOW

31. MANAGEMENT
• Management of PD requires careful consideration of the patient's symptoms
and signs, age, stage of disease, degree of functional disability, and level of
physical activity and productivity.
• A wide range of symptomatic pharmacologic, nonpharmacologic, and surgical
therapies are available to maximize motor and nonmotor function and quality
of life throughout the disease course.

32. MANAGEMENT OF PD
1. Non-pharmacological management
2. Medical management
3. Management of motor fluctuations and dyskinesia
4. Device assisted and lesioning procedures
5. Management of non-motor symptoms

33. IS THERE A THERAPY THAT SHOWS DISEASE-MODIFYING
EFFECTS?
• Beginning with the first large neuro protective trial, deprenyl and tocopherol
antioxidative therapy of parkinsonism (DATATOP) multiple studies of putative disease-
modifying therapies, using various designs and outcome measures, have not shown a
difference between the therapy and placebo
• In an attempt to resolve this issue, the Levodopa in Early Parkinson’s Disease
(LEAP) study used a delayed-start design to evaluate if levodopa had a disease-
modifying effect.

34. • However, concern persists about the potential for dopamine (and thus levodopa) to
acceler ate disease progression by mediating mitochondrial and lysosomal dysfunction
and increasing concentrations of potentially toxic α-synuclein oligomers
• Concerns about levodopa potentially causing a toxic effect by inducing oxida tive stress
provided the incentive for the Earlier versus Later Levodopa Therapy in Parkinson
Disease (ELLDOPA) study,31 in which 361 patients with early Parkinson’s disease
were randomly allocated to placebo or 150 mg, 300 mg, or 600 mg of levodopa per day.
• After 40 weeks, a 2–4 week levodopa washout did not lead to a deterioration of motor
function, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS), to the
same level as in the placebo group, suggesting a disease-modifying effect.
IS THERE A THERAPY THAT SHOWS DISEASE-MODIFYING
EFFECTS?

35. NON-PHARMACOLOGICAL MANAGEMENT
• Exercise and physical therapy
• Nutrition

36. EXERCISE AND PHYSICAL THERAPY
• May help to slow motor progression, improve non-motor symptoms, and
alleviate some secondary orthopaedic effects of rigidity and flexed posture
such as shoulder, hip, and back pain
• Regular aerobic exercise has a small positive impact on PD
• Both yoga and stretching/resistance training demonstrated improvements in
mobility and motor dysfunction, and yoga yielded additional benefits in anxiety,
depression, and health-related quality of life.

37. EXERCISE AND PHYSICAL
THERAPY
• Exercise to improve balance, flexibility, and strength should be
emphasized.
• Brisk walks, swimming, and water aerobic exercises are particularly
useful.

38. EXERCISE AND PHYSICAL
THERAPY
Modalities that may improve functional outcome for patients with PD include the following
Multidisciplinary rehabilitation with standard physical and occupational therapy components
Use of compensation strategies to facilitate gait (eg, external auditory, proprioceptive, or visual
cuing)
Treadmill training
Balance training and high-intensity resistance training

39. EXERCISE AND PHYSICAL
THERAPY
High-intensity agility training
Cued exercises with visual (mirror), auditory (metronome), and
tactile feedback
Active music therapy
Dance therapy

40. NUTRITION
No consensus guidelines on a specific PD diet, certain recommendations can be
made
A high-fiber diet, adequate hydration, and regular exercise help manage the
constipation of PD.
Large, high-fat meals that slow gastric emptying and interfere with medication
absorption should be avoided.

41. NUTRITION
The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative
Delay)may delay the onset and reduce the incidence and progression of
parkinsonism.
Dietary protein restriction is not necessary except in some patients with advanced
disease and motor fluctuations in whom competition with other amino acids
interferes with L-dopa absorption.

42. MEDICAL MANAGEMENT
• Complex neurodegenerative disorder with a broad spectrum of motor and non-motor
features that require individualized therapeutic approach.
• UPDRS is used most frequently as the clinical assessment of response to treatment
offered
• Conventional therapy includes symptomatic treatment of motor symptoms and neuro-
protective or disease-modifying therapies.

43. MEDICAL MANAGEMENT
• Treatments to manage motor symptoms work by increasing dopaminergic activity.
• This is broadly achieved by three mechanisms:
1. Administration of dopamine precursor (e.g. levodopa preparations such as co-careldopa);
2. Activation of dopamine receptors using dopamine agonists (e.g. ropinirole);
3. Enzyme inhibition to prevent the breakdown of dopamine (e.g. monoamine oxidase B inhibitors
[MAO-B] and catechol-O-methyl transferase [COMT] inhibitors).

44. MEDICAL MANAGEMENT
• The choice of first-line treatment has been long debated and there are no absolute
rules on which medication should be initiated first.
• NICE recommends that people with PD who have symptoms affecting their daily life
are offered a levodopa preparation as first-line treatment.
• The PD MED Study supports this, showing that levodopa has advantages in the
management of motor symptoms when compared with dopamine agonists and
monoamine oxidase inhibitors.

45. WHEN TO START ?
The effect of disease on the dominant hand
• ●The degree to which the disease interferes with work, activities of daily living, or
social and leisure function
• ●The presence of significant bradykinesia or gait disturbance
• ●Patient values and preferences regarding the use of medications

46. • Mild symptoms, preference for once-daily medication – In patients of any age preferring
once-daily medication and only requiring modest benefit, monoamine oxidase type B (MAO
B) inhibitors are a reasonable alternative to levodopa.
• Younger patients at high risk for dyskinesia – In patients under 50 years of age who are at
high risk of dyskinesia, initial monotherapy with a dopamine agonist (DA) can be considered.
Risk factors for dyskinesia include younger age at disease onset, lower body weight, and
female sex
• Amantadine monotherapy can also be considered, particularly when tremor is prominent.
WHEN TO START ?

47. TREMOR-PREDOMINANT PD,
• Which can require high doses of levodopa to control tremor
• The addition of amantadine and/or anticholinergic medications may be helpful in
this setting, but at the risk of adverse effects, especially in older adults.
• If satisfactory control of tremor cannot be reached with these medications, such
patients should be considered for surgical therapies, specifically, deep brain
stimulation or focused ultrasound.
• Anticholinergic drugs are sometimes useful as monotherapy in patients with
bothersome tremor but are less well tolerated in older patients because of the risk
of cognitive impairment, constipation, and prostatism

48. DOPA RECEPTOR AGONIST
• In patients under 50 years of age who are at high risk of dyskinesia (eg, younger age at
disease onset, lower body weight, female sex), initial monotherapy with a DA is an
alternative to early levodopa
• DAs have intermediate potency for improving motor symptoms and have a lower risk of
motor complications than levodopa.
• When given alone, DAs rarely cause dyskinesia, and they have the advantage of being
available in once-daily formulations.
• DAs are ineffective in patients who have shown no therapeutic response to levodopa, but
they do have a role in patients with advanced PD as a treatment for motor complications
of levodopa.

49. IF ORAL DRUGS NOT POSSIBLE?
• When treatment is still desired for patients who are restricted to take nothing by
mouth (NPO), options include transdermal rotigotine and apomorphine by injection
or continuous infusion.
• The use of apomorphine requires a test dose prior to ongoing treatment. Initiation
of transdermal rotigotine or apomorphine in the inpatient setting

50. COST OF THERAPY
DRUG COST PR 10 TAB
ENTACAPONE 100MG 125RS
LEVODOPA 110MG 20RS
PRAMIPIXOLE O.125MG 65RS
RESALLAGINE 0.5 106RS
SAFINAMIDE 50 142RS
SELEGELLINE 5MG 75RS
APOMORPHINE INJ 100MG/20ML 13000RS
DBS 15-20 LAKHS

51. MEDICAL MANAGEMENT
• All people with PD should be offered a levodopa preparation, dopamine agonist or
MAO-B inhibitor.
• There is no significant difference in benefits of dopamine agonists over monoamine
oxidase inhibitors when chosen as initial therapy
• Anticholinergics, such as benztropine and trihexyphenidyl, are not routinely
prescribed in idiopathic PD but may be introduced for the management of tremor
when dopaminergic medications are not effective.

52. MEDICAL MANAGEMENT
• Dopaminergic therapy is the mainstay of pharmacologic treatment for PD.
• Dopaminergic agents or classes of agents, listed in descending order of dopaminergic potency:
• Levodopa, most commonly in the form of carbidopa-levodopa
• Non-ergot dopamine agonists (DAs; pramipexole, ropinirole, and rotigotine)
• Monoamine oxidase type B (MAO B) inhibitors (rasagiline, safinamide, and selegiline)
• Amantadine, a dopamine promoter with anticholinergic effects

53. MEDICAL MANAGEMENT
• Selection is based on patient characteristics (age, comorbidities), disease severity,
and drug efficacy and side effects.
• In addition to the dopaminergic therapies, anticholinergic drugs are also used for
tremor management in select patients with early PD.

54. MEDICAL MANAGEMENT
When should drug therapy be started? —
• Decision to initiate symptomatic medical therapy in patients with PD is determined by the
degree to which symptoms interfere with functioning or impair quality of life.

55. MEDICAL MANAGEMENT
The timing of this decision varies greatly among patients but is influenced by a number of
factors, including
I. The effect of disease on the dominant hand
II. The degree to which the disease interferes with work, activities of daily living, or social
and leisure function
III. The presence of significant bradykinesia or gait disturbance
IV. Patient values and preferences regarding the use of medications

56. TREATMENT
OF MOTOR
SYMPTOMS

58. LEVODOPA
• Guiding principles with regard to initiating levodopa therapy include the following:
• Delay to onset of therapeutic benefit can be hastened by taking the medication on an
empty stomach (if tolerated without nausea),
• Avoiding or reducing protein intake,
• By crushing the LD tablet and mixing it with a carbonated beverage.

59. LEVODOPA
• Levodopa is more likely to cause dyskinesia than other options within the first five
years, and thus the minimum effective dose should be used and patients should be
counselled regarding this risk.
• Patients should be monitored for development of dyskinesia, for which the dose can
be reduced.

60. LEVODOPA
• Levodopa is the most effective agent for control of motor symptoms of PD but also requires
the most frequent dosing and is associated with the highest risk of dopaminergic motor
complications, such as "wearing off" and dyskinesia.
• Dopaminergic motor complications should be discussed with patients who are fearful of
initiating levodopa early.
• Immediate-release (IR) carbidopa-levodopa is the preferred initial formulation.

61. LEVODOPA
• Initial dosing and titration —
• Levodopa should be initiated using an IR formulation.
• For carbidopa-levodopa, use the 25 mg/100 mg IR tablet for initial titration, starting
at one-half tablet two to three times daily.
• Should always aim for the lowest levodopa dose that produces a useful clinical
response.

62. LEVODOPA
• The majority of patients with idiopathic PD will enjoy a significant initial therapeutic
response to total daily doses of levodopa in the range of 300 to 1000 mg.
• Levodopa should not be stopped abruptly in patients with PD,
• Sudden withdrawal has been associated (rarely) with a syndrome resembling neuroleptic
malignant syndrome or akinetic crisis.

63. AGENTS ALTERING METABOLISM OF
LEVODOPA
• This includes- monoamine oxidase (MAO) inhibitors and catechol-o-methyltransferase
(COMT) inhibitors.
• Both MAO and COMT inhibitors increase CNS dopamine levels by blocking enzymes in
the degradative pathway for levodopa or dopamine, thus producing higher CNS
dopamine levels.
• MAO inhibitors may be useful as monotherapy for mild symptoms.
• Both MAO and COMT inhibitors are often used as adjunctive therapy for motor
fluctuations later in the course of PD.

64. MAO INHIBITORS
• Rasagiline and selegiline – selective MAO-B inhibitors
• Safinamide- a MAO inhibitor with novel glutamate-blocking activity.
• Selegiline has amphetamine metabolites, which may be helpful in patients with
excessive daytime sleepiness.

65. MAO INHIBITORS
Rasagiline:
• Used alone or as adjunct to levodopa with dopa-decarboxylase inhibitor.
• Dose-1mg daily.
Selegiline:
• Used alone or as adjunct to levodopa with dopa-decarboxylase inhibitor.
• Dose-5 mg
• To avoid initial confusion and agitation, it may be appropriate to start treatment with a dose of 2.5
mg daily, particularly in the elderly.

66. MAO INHIBITORS
Safinamide
• As add-on therapy to a stable dose of levodopa alone or in combination with other
medicines in mid to late-stage fluctuating patients.
• Dose-Treatment should be started at one 50mg tablet per day.
• The dose may be increased to 100mg/day on the basis of individual clinical need.
• No change in dose is required for elderly patients.

67. COMT INHIBITORS
• Entacapone blocks peripheral metabolism of dopamine
• Tolcapone blocks COMT both centrally and peripherally
• Tolcapone has been associated with some cases of fatal hepatotoxicity
• Entacapone has been associated with secretory diarrhea
• COMT inhibitors enhance levodopa side effects

68. COMT INHIBITORS
• Use as an adjunct to LEVODOPA for patients with Parkinson’s disease who
experience ‘end-of-dose’ deterioration
Entacapone
• As adjunct to levodopa with dopa-decarboxylase inhibitor in Parkinson’s disease and
‘end-of-dose’ motor fluctuations.
• Dose-200 mg with each dose of levodopa with dopa-decarboxylase inhibitor max. 1.6
g daily.

69. COMT INHIBITORS
Opicapone
• As adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors in adult
patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilized
on those combinations.
• Dose-50mg daily, taken at bedtime, at least one hour before or after levodopa combinations.
• Opicapone enhances the effects of levodopa, requiring adjust levodopa dosage within the first
days to first weeks after initiating treatment with opicapone.

70. DIRECT-ACTING DOPAMINE AGONISTS
• Pramipexole, ropinirole, rotigotine, and apomorphine stimulate striatal dopamine receptors
• Less effective and more poorly tolerated than levodopa and require very slow titration.
• Most helpful as adjunctive agents in patients with difficult motor fluctuations
• Injectable apomorphine has a rapid onset of action, a short half life, and is used for sudden
off periods or early morning akinesia as a bridge between oral levodopa doses.

71. DIRECT ACTING DOPAMINE
AGONIST
Ropinirole
• Initially 750 micrograms daily in 3 divided doses
• Increased by increments of 750 micrograms at weekly intervals to 3 mg daily
• Further increased by increments of up to 3 mg at weekly intervals according to response;
• Usual range 9–16 mg daily (but higher doses may be required if used with levodopa);
• Max. daily dose -24 mg

72. DIRECT ACTING DOPAMINE
AGONIST
Pramipexole
Initially 125 ug salt three times daily
Dose doubled every 5–7 days if tolerated to 500 ug 3 times daily;
further increased if necessary, by 250 ug 3 times daily at weekly
intervals
Max. dose 4.5 mg daily in 3 divided doses

73. APOMORPHINE
• A non-ergoline DA,
• Water soluble and lipophilic and is therefore suitable for intravenous,
subcutaneous, sublingual, intranasal, or transdermal administration.
• An acute intermittent subcutaneous injection, as a rapid rescue from
hypomobility off episodes (end-of dose wearing off and unpredictable on/off
episodes) associated with advanced PD.

74. APOMORPHINE
• Dose-By subcutaneous injection, usual range 3–30 mg daily in divided doses
• Subcutaneous infusion may be preferable in those requiring division of injections
into more than 10 doses daily
• Max. single dose 10 mg
• Child and adolescent under 18 years not recommended.

75. AMANTADINE
• Antagonism of the NMDA glutamate receptor.
• Most often used to treat patients with PD who have mild motor disability or to reduce the
severity of levodopa-induced dyskinesia for patients with more advanced PD
• Dose- 100 mg daily increased after one week to 100 mg twice daily,
• Max. 300 mg daily;
• Elderly 65 years and over, 100 mg daily adjusted according to response.

76. ANTICHOLINERGICS
• Includes trihexyphenidyl, benztropine
• Can be helpful for tremor that persists despite dopaminergic therapy,
• Modestly reduce rigidity and dystonia
• More elderly or cognitively impaired patients are particularly sensitive to
anticholinergic side effects and should be monitored for cognitive and
neuropsychiatric changes.

81. MEDICAL MANAGEMENT OF MOTOR
FLUCTUATION AND DYSKINESIAS
• Motor complications of levodopa, in the form of motor fluctuations and dyskinesia, occur in
30 to 40 percent of patients during the first five years of use and nearly 60 percent or more
by 10 years
• Alterations between periods marked by a positive response to levodopa ("on"), and
periods marked by reemergence of parkinsonian symptoms ("off") as the response to
levodopa wears off.
Types of motor fluctuations include the following:
I. Wearing off
II. Unpredictable on-off
III. Freezing of gait
IV. Delayed ON response
V. Early morning akinesia

82. MOTOR FLUCTUATIONS
• Wearing off - most common type of motor fluctuation. is return of parkinsonian
symptoms following the previous dose in advance of the next scheduled
antiparkinsonian dose.
• On/off is unpredictable reappearance of parkinsonism at a time when central levels
of antiparkinsonian drugs are expected to be within the target therapeutic range.
• Delayed on is a prolongation of the time required for the central antiparkinsonian
drug effect to appear.
• Dose failure is a complete failure to develop a favorable response to an incremental
dopaminergic dose.

83. MOTOR FLUCTUATIONS
Motor Fluctuations Treatment
Delayed ON response Take additional doses of short acting levodopa, liquid levodopa,
apomorphine injection
Early morning akinesia Controlled release levodopa at bedtime, dispersible levodopa in the early
morning, apomorphine injection
End of dose weaning off Increase dosage frequency, add long-acting levodopa, add COMT
inhibitors, MAO-B inhibitors or dopamine agonist, DBS
Unpredictable on-off Liquid levodopa, apomorphine injection
Episodes of freezing Physical therapy or occupational therapy

84. DYSKINESIAS
Levodopa-related dyskinesia refers to abnormal, involuntary movements brought on by
use of levodopa.
• Peak-dose dyskinesia appears when the patient is "on" and is often choreiform in
nature. Peak-dose dyskinesia usually starts 30 to 90 minutes after a dose of
levodopa.

85. DYSKINESIAS
• Diphasic dyskinesia- two separate periods of involuntary movement after a levodopa
dose, the first occurring when patients turn "on" and the second when they begin to
wear "off." Characterized by large-amplitude leg movements.
• "Wearing off" dystonia manifests as dystonia, usually involving the limbs but
sometimes involving the face, neck, or trunk, which emerges during "off" periods.
These are particularly common first thing in the morning, before a dose of levodopa

86. DYSKINESIAS
Dyskinesia Treatment
Peak dose dyskinesia Reduce previous dose of levodopa, Discontinue COMT inhibitors
and MAO-B inhibitors, add amantadine, avoid controlled release
levodopa, add or increase dopamine agonist, DBS
Off dystonia Increase levodopa dose, Botulinum toxin, Baclofen
Diphasic dyskinesia Increase levodopa dose, DBS

87. TREATMENT OF MOTOR COMPLICATIONS

88. DEVISE ASSISTED LESIONING PROCEDURES
Includes
• Procedures for motor complications
• Procedures for refractory tremor

89. ELIGIBILITY FOR LESIONING PROCEDURES
• Patients with PD who maintain a clear response to levodopa are candidates for
device-assisted therapies when motor fluctuations and/or dyskinesia cause
disability or reduced quality of life despite optimal oral levodopa or adjunctive
therapies.
• Levodopa-resistant tremor, can be improved with deep brain stimulation (DBS).

90. EXCLUSIONS AND PRECAUTIONS
I. Patients with secondary causes of parkinsonism (eg, drug-induced, vascular) or atypical
parkinsonian disorders (eg, multiple system atrophy)
II. Patients with PD who have dementia or significant cognitive impairment
III. For patients with active psychiatric issues, such as anxiety, depression, hallucinations, and
delusions, device-assisted therapies should be delayed until psychiatric symptoms are
stabilized.
IV. DBS, particularly of the sub-thalamic nucleus (STN), may increase the risk for suicide.

91. PROCEDURES FOR MOTOR COMPLICATIONS
For patients with Parkinson disease (PD) who experience motor complications interfering with quality
of life, device-assisted treatment options include:
i. Deep brain stimulation (DBS)
ii. Continuous levodopa-carbidopa intestinal gel (LCIG) infusion delivered through a percutaneous
gastrojejunostomy tube by battery-powered pump
iii. Continuous subcutaneous apomorphine infusion (CSAI) administered by a battery-powered
pump
iv. Unilateral MRI-guided focused ultrasound (FUS) pallidotomy
v. Traditional unilateral lesioning procedures such as pallidotomy and sub-thalamotomy

92. PROCEDURES FOR MOTOR COMPLICATIONS
• These treatments are useful for reducing "off" time and increasing "on" time
without troublesome dyskinesia.
• Patients with PD who may be appropriate candidates for these treatments
should be referred for evaluation by a movement disorder specialist

93. PROCEDURES FOR REFRACTORY TREMOR
For patients with PD who experience levodopa-resistant tremor,
the surgical or device-assisted treatment options include:
I. DBS
II. Unilateral MRI-guided focused ultrasound (FUS) thalamotomy
III. Conventional lesioning procedures (unilateral thalamotomy)

94. DEEP BRAIN STIMULATION

95. MANAGEMENT OF NON-MOTOR
SYMPTOMS
Constipation
• Osmotic laxative, is a first-line therapy for treating constipation
• In addition, ensuring a high-fiber diet, exercise (if possible) and adequate fluid intake to prevent
constipation should be encouraged
• Probiotics, including fermented milk
Sialorrhea-
• For mild symptoms, use of chewing gum or hard candy to encourage swallowing
• Severe symptoms, botulinum toxin injection in salivary gland
• Glycopyrrolate, 1 mg three times daily

96. MANAGEMENT OF NON-MOTOR
SYMPTOMS
Rhinorrhea
• No proven treatment for gustatory rhinorrhea
• Ipratropium nasal spray can be given
Sexual Dysfunction
• Hypersexuality tends to occur more often in younger men, can be treated with dopamine agonist
therapy or DBS
• Men with erectile dysfunction may benefit with sildenafil

97. MANAGEMENT OF NON-MOTOR SYMPTOMS
Excessive daytime sleeping
• PD medications, particularly dopamine agonists, can cause excessive daytime sleepiness or
sudden onset of sleep.
• good sleep hygiene measures
• modafinil can be considered
Patients who experience daytime sleepiness or sudden onset of sleep should not drive and should
inform their workplace in case of occupational hazards
Rapid eye movement sleep behavior disorder
• Clonazepam or melatonin can be given
• Benzodiazepines are cautioned in the elderly population

98. Nocturnal akinesia
• Can be helped with slow-release levodopa at night or oral, long-acting dopamine agonists.
• A rotigotine patch may also be considered
Orthostatic hypotension
• Medication review should be undertaken to address pharmacological causes, such as
antihypertensives or anticholinergics.
• Midodrine can be used to treat orthostatic hypotension
• If midodrine is contraindicated, fludrocortisone can be used
MANAGEMENT OF NON-MOTOR
SYMPTOMS

99. Depression-
• Antidepressant medication, cognitive behaviour therapy (CBT) or both can be offered on individual
basis
• SSRIs and SNRIs are generally safe in PD patients.
Anxiety-
• May be a symptoms of wearing off of dopaminergic medication
• SSRIs, SNRIs can be given
Psychosis-
• Visual hallucination and paranoid delusion are frequent, particularly with dopa agonists
• Pimavanserin, quetiapine and clozapine are preferred
MANAGEMENT OF NON-MOTOR
SYMPTOMS

100. Fatigue-
Amantadine, methylphenidate can be given
Parkinson’s disease dementia
Can be treated with cholinesterase inhibitors (e.g. rivastigmine, donepezil) or a glutamate receptor
antagonist (e.g. memantine).
Swallowing dysfunction-
• Swallowing exercises
• Postural modification- Chin tuck posture, head rotation towards weak side with asymmetric
swallowing function.
• Alteration in food and liquid texture and consistency
• Individualized calorie dense foods or high calorie supplements
MANAGEMENT OF NON-MOTOR
SYMPTOMS

101. SAMPLE
DIARY FOR
PARKINSON
ISM
PATIENT

102. MANAGEMENT OF MSA
Mainly Symptomatic.
Parkinsonism -
• First Line - Levodopa - Only 1/3 rd responsive.
• Trial - up to 2 g total daily dose of levodopa (titrated from 100 to 300 mg 3-4 times
daily) for at least 3 months
• may worsen orthostatic hypotension
Alternatives - Dopamine agonists
 Amantadine, up to 300 mg in 3 divided doses
• DBS -Not recommended

103. • RBD - First line - clonazepam 0.5 to 2
mg at night with lower doses often quite
effective.
• In case of apnea - second-line agent -
melatonin at a starting dose of 3 mg
• OSA - 37 to 65% of MSA patients -
CPAP

104. TREATMENT OF PSP
• Levodopa provide temporary improvement in bradykinesia in approximately 40% of
patients
• Usually does not improve dysarthria, gait, or balance problems.
• Amitriptyline - helpful in improving pseudobulbar affect and emotional incontinence
• Botulinum toxin injections - treat blepharospasm or retrocolic neck posture in
PSP.
• Poor Prognosis - Median duration of survival of approximately 8 years.

105. TREATMENT OF CBD
• Parkinsonism - levodopa, - poor and only transient response
• Dystonia - botulinum toxin,
• Clonazepam - first choice treatment for myoclonus
• prognosis - poor, with a reported median survival after onset of about 7
years.

106. TREATMENT OF COGNITIVE SYMPTOMS IN
DLB
• Cholinesterase inhibitors - both donepezil and rivastigmine
• Benefit on cognitive function in DLB > AD
• Efficacy of memantine in DLB is less clear, though increasingly memantine is
used in addition to a cholinesterase inhibitor in clinical practice

107. NEUROPSYCHIATRIC SYMPTOMS IN
DLB
• Non-pharmacologic interventions - caregiver training,
• physical activities,
• social stimulation
• environmental modification
• Antipsychotic medications - should be avoided in DLB
• Profound changes in conscious state which can be fatal and occur in around 50% of
people with DLB
• Despite limited efficacy, quetiapine, is the generally preferred option by
• Severe neuropsychiatric disturbances due to the perceived less risk of parkinsonism

108. MOTOR SYMPTOMS IN DLB
• Physical therapy, Fall prevention strategies.
• Levodopa - shown to benefit around 30% of DLB patients with motor symptoms but the
response is typically less pronounced compared to PD.
• Increased risk of psychosis, including hallucinations.
• Dopamine agonists - can substantially worsen psychotic symptoms and exacerbate
confusion, and should be avoided.
• RBD - melatonin is an effective and generally well-tolerated option
• Clonazepam and pramipexole are second-line treatment options for RBD, but the
potential side effects of drowsiness and confusion limit their use in DLB

109. 2K23 UPDATES ON PARKINSONS DISEASE

110. BIOMARKERS FOR PARKINSON’S DISEASE - Α-SYNUCLEIN
 The identification of
α- synuclein
aggregates in samples
from skin or CSF can
provide high
diagnostic accuracy,
but requires relatively
invasive procedures.
 A breakthrough was
achieved this year by
Okuzumi and
colleagues, who
successfully detected
misfolded α-
synuclein in serum
through a modified
seed amplification
assay.

111. WEARABLE DEVICES CAN IDENTIFY PARKINSON’S
DISEASE UP TO 7 YEARS
BEFORE CLINICAL DIAGNOSIS
 More than 100 000 individuals were monitored using a triaxial accelerometer on
their dominant hand over a 7-day period.
 Both prodromal participants (n=196; defined as those who were diagnosed with
Parkinson’s disease 2 years or more after the data collection) and participants
diagnosed with Parkinson’s disease (n=273) exhibited a significantly reduced
acceleration profile during the daytime, compared with age-matched and sex-
matched controls.
 A machine-learning model using the accelerometry data surpassed other models,
including genetics, lifestyle, blood biomarkers, or prodromal presentations, in
predicting a diagnosis of Parkinson’s disease.
 Crucially, this predictive capability suggests the feasibility of screening the
general population using this method
Lancet Neurol. 2024 Jan;23(1):20-22.

112. IPX203 – NEW EXTENDED-RELEASE FORMULATION
OF CARBIDOPA– LEVODOPA (CD-LD)
• In this trial, 506 participants with Parkinson’s disease
were randomly assigned to receive either IPX203 or
immediate-release CD-LD.
• The trial showed a significant increase of 0·53 h per
day in good on-time compared with the immediate-
release formulation.
• The IPX203 group also showed marked reduction in
off-time compared with immediate-release CD-LD.
• A substantially higher proportion of patients treated
with IPX203 reported improvements, according to the
Patient Global Impression of Change scale, compared
with those receiving immediate-release CD-LD.
Lancet Neurol. 2024 Jan;23(1):20-22.

113. THANK YOU
DR GANESHGOUDA MAJIGOUDRA
CONSULTANT NEUROLOGIST
NANJAPPA HOSPITALS DAVANAGERE
9380906082
ganeshgoudam4@gmail.com