DR.NANNIKA PRADHAN

1. EXTRA PYRAMIDAL
DISEASE

2. Presenter
Dr. Nannika Pradhan
P.GT,Dept.Of General Medicine,NBMC&H
Dt.of Presentation-15.11.23
EXTRA PYRAMIDAL DISEASES

3. Approach to a case of Extrapyramidal Disorder
Definition
Classification
 Etiology
Pathophysiology
Distinguishing Features
•Brief discussion on
Parkinsonism
Huntington Disease

4. DEFINATION
Coined by British
neurologist Kinnier
Wilson
The neural network
which is a part of the
motor system that is
outside the pyramidal
tracts in the medulla.
Refers to basal ganglia
and an array of brain
stem nuclei to which
they are connected

5. Hypokinetic Disorders
Idiopathic Parkinson’s disease
Drug Induced Parkinsonism
MPTP induced Parkinsonism
Postencephalitic Parkinsonism
ParkinsonsPlus Syndrome
Childhood akinetic-rigid
syndrome
Hyperkinetic Disorders
Essential Tremors
Chorea
Hemiballismus
Myoclonus
Tic or “Habit Spasm”
Torsion Dystonia
Paroxysmal Dyskinesias
CLASSIFICATION

6. Hyperkinetic Movement Hypokinetic Movement

7. HOW TO APPROACH
Age
Past History
Drug History
Family History
Associated neuropsychiatry features
Autonomic features
Alcohol responsiveness

8. HOW TO ANALYZE
Specific distribution
Chorea/Athetosis-mainly in the distal groups
Hemiballismus-mainly proximal
Parkinson's disease-mainly unilateral and asymmetric
Blepharospasm
Specific action and relationship to voluntary movement
Task specific tremor (intention tremor) during pick up a glass of water
Task specific dystonia eg. Writers cramp, musician cramp

9. How to analyze…contd…
• Speed of Movement
• Rhythm
• Continuous-Tremor
• Intermittent-Asterixis
• Relationship to sleep:
• Palatal Myoclonus,Segmental myoclonus,fasciculation and myokymia-persist on
sleep
Dystonia-Diminished on sleep
Slow Intermediate Fast
Parkinsonism Chorea Myoclonus
Dystonia Tremor Tics
Athetosis

10. How to analyze : contd….
Suppressibility-tics may be voluntarily suppressed
Aggravating of precipitating factors: stress and anxiety worsen all
movement disorder
Associated Sensory symptoms
Ameliorating factor

11. PARKINSON’S DISEASE
Alpha synuclein deposition, Lewy bodies
Depletion of the pigmented dopaminergic neurons in the substantia
nigra
Loss of brain cells in Substantia Nigra and basal ganglia starts many
years before the symptoms appear
Progressive loss of dopamine causes most of the disease sign
Can be considered as a TH-deficiency syndrome of the stratium

12. Neurotransmitters in Parkinson’s Disease

13. Clinical Picture
Increases sharply with age ,particularly over 70 years, M>F
Static Tremors
Rhythmic occurring at the rate of 4-8/second
May start in one hand and spread to other parts of the body
Characterized pill-rolling movements between the thumb and the
forefinger are seen
Tremors increase with emotional, anxiety and fatigue and disappear
during sleep and during active voluntary movements
More proximal than distal

14. Parkinson’s Disease:Pin rolling

15. Clinical Picture contd…..
Flexors are affected more than extensors: lead pipe rigidity/cog wheel
rigidity
Stiffness of the limbs develops causing difficulty in starting
movements and walking(slow, shuffling gait)
Akinesia-Loss of emotional and associative movements resulting in:
Monotonous speech
Loss of swinging of arms during walking

16. Parkinson’s Gait

17. Pathology and Pathogenesis
Degeneration of the dopaminergic
neuron in the substantia niagra pars
compacta, reduced stratal dopamine
and intracytoplasmic proteinaceous
inclusions known as Lewy bodies.
Can also affect NBM,LC and neurons
of the olfactory system ,cerebral
hemispheres, spinal cord and
peripheral autonomic nervous
system.
Dopamine neurons are affected in
midstage disease.

18. Differential Diagnosis
Essential Tremors
Side effects of antipsychotics-dopamine blockers
Progressive Supranuclear Palsy
Normal Pressure Hydrocephalus
Dementia with Lewy bodies
Multiple system Atrophy
Cortico-basal degeneration
Multiple Strokes

19. PARKINSON PLUS SYNDROME
Grouped into 2 types: Synucleopathies and Tauopathies
Clinically 5 separate Parkinsonism Plus disease has been identified:
• Multiple system atrophy
• Progressive Supranuclear Palsy
• Parkinsonism-dementia-Amlytropic lateral sclerosis complex
• Corticobasal ganglionic degeneration
• Diffuse Lewy body disease

20. Diagnosis of PD
Clinical Examination
No disease specific biological
marker available
PET/SPECT with dopaminergic
radioligands
Exclusion of several causes of
secondary Parkinsonism

21. Strategy of Treatment
(A)Acetylcholine
Anticholinergic-
Trihexyphenidyl 6-20mg
Benzhexol 1-2mg TID more commonly used
antipsychotic driug induced parkinsonism
Orphenadrine 50-100mg TID
They reduce tremors and rigidity than bradykinesia
Amantaidine-100mg BD mainly used to improve dyskinesia and
bradykinesia in advanced disease.
(B)Dopamine
Carbidopa/L-dopa-Carbidopa/Levodopa
(10/100),(25/100),(25/250)2-3 times dialy with meals
Benserazide –levodopa is available in 25/100 and
50/200mg
(c)Dopaminergic agonist
Ropinorole- 0.25 mg TID,increase to 6-16,g/day
Pramipexole-0.125mgTID ,increase to 0.375-
3.0mg/d
Rotigotine 2-4mg/24 hours patch once dialy
Apomorphine 2mg,maximum dose 6mg can be
administered parentally for “rescue therapy”‘ in patients
experiencing sudden akinetic episodes
Lisuride 2.5-5mg
(D)COMT Inhibitors
Tolcapone 100mg TID with each dose of
Levodopa,upto maximum of 8doses/day
Entacapone-200mg with each dose of Levodopa
(E)MAO Inhibitors
Selegline-5-10 mg BD
Rasagiline-1mg/day and 0.5 mg/day when
used with levodopa
Safinamide-should be given with
levodopa,strting with 50mg OD and can be increased to 100mg
od after 14 days based upon toolerability
Inhibitors of dopamine re-uptake-Amantadine-100mg BD

22. Motor Fluctuations

23. Other lines of Therapy
Stereotactic neurosurgery:Palliatomy:thalamotomy:subthalamotomy
Indications:
Idiopathic Parkinson's
Levodopa unhelpful
Intractable PD
Drug dyskinesia
Deep brain stimulation: Dyskinesia
Tissue Transplantation
Neuropsychiatric aspects

24. Deep Brain Stimulation

25. Focused Ultrasound

26. Surgery for PD

27. CHOREA
Sudden,brief,rapid,jerky,purposeless,non-repetitive,involuntarily
movement.
Most characteristically in the distal parts of upper extremity but may
also involved proximal part, lower extremity,trunk,face and tongue.
Pathology
Damage to Caudate Nucleus

28. Disease characterized by Chorea
Inherited Disorder: Huntington disease, Wilson's Disease, Benign
hereditary chorea neuroacanthocytosis
Infectious Causes: Rheumatic Chorea, HIV disease
Structural lesion of the basal ganglia:Infract ,Neoplasm,Trauma
Chorea of Systematic Disease :SLE, Thyrotoxicosis, Polycythemia
Vera,HyperOsmolar Non-ketotic hyperglycemia
Pregnancy
Drugs

29. Cardinal features of Chorea
Hypotonia
Pronator Sign
Milkmaid’s Grip
Spooning Sign
Pendular knee jerk
Lizard tongue
Sydenham Chorea-more common in females and childhood
Huntington Disease-autosomal dominant disorder

30. Etiology of Chorea
Increase in number of Polyglutamine repeats(CAG)>40 in the coding sequence of
the Huntingtin gene located on the short arm of chromosome4.
The larger the number of repeats ,the earlier the disease manifest.
Treatment: Multidisclipinary Approach
Dopamine blocking agents:Tetrabenaxine
Antidepressants and Anxiety drugs
Psychosis can be treated with atypical neuroleptics such as Clozapine,Quetiapine
and risperidone
There is no adequate treatment for the cognitive or motor decline.

31. Huntington Chorea
Loss of Caudate
and Putamen

32. Huntintgon’s
Chorea

33. Sydenham
Chorea

34. ATHETOSIS
Slow, distal purposeless writhing involuntary movement.
More sustained and larger in amplitude than those in Chorea
Mainly involve the extremities ,face neck and trunk
Movements-combination of flexion, extension,abduction,pronation
and supination often alternating and in varying degree.
Predominant pathologic changes are in the Putamen.

35. Athetosis Contd….
Causes:Cerebral palsy,perinatal injury to basal ganglia,wilsons disease
Choreoathetosis:the movement liove between chorea and sthetosis
in rate and rythymicity e.g Cerebral Palsy(Neonatal Jaundice)
Psedoathetosis:Sensory Athetosis-loss of position change as a result
of parietal lobe lesion e.g tabes dorslis,peripheral nerve disease.

36. HEMIBALLISMUS
A wild flinging,large amplitude movements on one side ofvthe body.
Proximal upper limb muscles predomibately affected
Ballistic movement-rapid and forceful
Movement ceaseless during the walkinh stat and disappear only
with the dee[p sleep.
Usually self limiting and leads to resolve spontaneously after weeks
to months.
Treatment-Dopa blocking agents
Pallidotomy can be done

37. Drug used in Chorea
Tetrabenazine 12.5 mg/day inm 1st week,12.5mg BD in second week
Neuroleptics-Quetiapine (50-600mg/day),Resperidone(2-8 mg/day)
 Olanzipine (2.5-10mg/day),Haloperidol (0.5 to 1mg/day
and increased upto 8mg/day
Dopamine blocking agents
Propanolol(20-80 mg/day) or Primidone (25-1000mg/day)
Clonazepan
Baclofen

38. DYSTONIA
Sustained or repetitive involuntarily muscle contraction leading to
twisting movemnts and abnormal posture.
Can involve individual /multiple muscle groups
Often involve the extremities,neck,trunk,eyelids,face and vocal cords
Duration less-less than one seconds :Dystoinic Spasm
Duration more-minutes to hours:Dystonic Movement
Pathophysiology of Dystonia:
Not known

39. Classification of Dystonia
Generalized Dystonia-inbvolves larger portion of body often
producing distorted podture of limbs and trunk(torsion Dystonia)
Idiopathic-Predominately childhood onset,autosomal dominant ,may
start distally in the foot,peculiar axial involvement of spine.
Dopa responsive Dystonia(Segawa Variant)-dystonia in early
childhood (1-12yrs),typically foot dystonia.Excellent response to
small doses of dopa.Diurnal variation
Focal dystonia-4th-6th decade,mlore common in fe,male:
Blepherospasm
Oromandibular dydtonia
Spasmodic dysphonia
Cervical dystonia
Limb Dystonia(writer’s cramp)

40. Classification contd…
Secondary Dystonia:Due to drugs,discterte lesion in the
stratium,pallidium,thalamus,cortex and brain stem.
Dystonia plus Syndromes:May occur in neurodegenerative
condition(Huntington Disease,Cortico basal degeneration,Wilson
disease,progressive supranuclear palsy)

41. Treatment of Dystonia
Levodopa
High dose anticholinergic –trihexyphenidyl 20-120mg/d
Oral baclofen -20-120mg
Tetrabenazine 25-75mg/d
Botulunim Toxin
Surgical Therapy-Rhizotomy and Myotomy

42. MYOCLONUS
Sudden,brief(100ms) shock like jerky involuntary movement
consisting of single or repetitive muscle discharges.
Seen in muscles of extremities and trunk but the involvement is often
multifocal diffuse or wide spread.
Differ from tics in that they interfere with normal movement and not
suppressive.

43. Symptomatic cause of Myclonous
Metabolic endogenous-Hypoxia,uremia,hepatic failure
Degenerative-Alzhemier’s disease.Huntington disease
Infectious-EVB
Autoimmune-Multiple Sclerosis
Neoplastic-Neuroblastoma,Paraneoplastic disorders
Drugs-Lithium,Metaclopromide,cocaine,levodopa

44. Myoclonus:contd…..
• Opsoclonus:Myoclonus (Kinsbourne Syndrome)-Dancing eye and
dancing feet.
• Palatal Myoclonus:Involuntary rythymic movement of soft palate and
pharynx
• Astrexis:hepatic encephalopathy
Negative myoclonus inability gto sustain noirmal muscle tone
presenting with slow and irregular flapping motion.

45. Drug Induced Movements Disorders
(Neuroleptics)
• Acute-Dystonia is thwe most commonacute drug reaction ,cn develop within minutes of
exposure
• Treatment-parental administration of antocholinergic
• Subacute-Akasthisia is commonest reaction,consists of motor restlessness within in need to
move and that to elevated by movement
• Treatment-benzodiazepenes or dopamine agonist for sympotomatic improvement
• Chronic- Tardive Syndrome after months to years after initiation of treatment
• Typically comprises choreiform movement involving the mouth,lips,tongue and in severe cases
trunk ,limbs and respiratory muscles can be affected
• Treatment:
• Stopping the offending agent
• Replacement with atypical antipsychotic
• Refractory cases-Baclofen,Clonazepam or valproic acid

46. Side effects of Antipsychotics(Haloperidol)

47. Tardive Dyskinesia

48. TICS
Brief,repeated sterotyped muscle contraction that often suppressible.
Quick,irregular,seemingl;e purposeful act but relatively involuntarily
Exaggerated by emotional strain and tension and stop during sleep
May involve any part of the body
e.g-Tourette Syndrome

49. PARKINSONS PLUS SYNDROME
Respond poorly to the standard treatments for Parkinsons Disease
Clinical clues suggestive of Parkinsons Plus Syndrome
Early onset of dementia,postural instability,hallucinations,psychosis
Ocular Signs-Impaired vertical gaze,blinking on
saccade,nystagmus,blepharospasm,apraxia of eyelid
Pyramidal tract signs not explained by previous stoke or spinal cord lesion
Autonomic Symptoms-postural hypotension ,incontinence
Alien limb phenomenon
Marked symmetry of signs in early stages of the disease
Absence of structural abnormality-normal pressure hydrocephalus

50. TREMORS
Is rhytmic,involuntary,purposeless oscillatory movement of body part
due to intermittent muscle contraction.
Types:
Rest Tremors-maximum at rest and becomes less prominent with
activity e.g Parkinson’s Disease
Postural Tremors-is maximum while limb posture is actively
maintained against gravity(arms outstretched)e.g essential tremors
Intention Tremor-Most prominent during voluntary movement
toward a target e.g Cerebral Disease

51. Etiology
Parkinsonism
Essential Tremors
Physiological
Alcohol
Anxiety
Thyrotoxicosis
Wilson’s
Drugs
Red Nuclear Tremor
Poison-Mercury

52. Fasciculation
Fine rapid, flickering or vermicular twitching movements due to
contraction of a bundle or fasciculus of muscle fibres,
More gross,continue in sleep
Exagerrated by fatigue,cold,cholinergic drugs,caffeine
Characteristic feature of Motor Neuron disease,anterior horn disease

53. MYOKYMIA
Involuntary, spontaneous ,localized ,transient or persistent quivering
movement that affect a few muscle bundles within a single muscle.
Coarse,slower,worm like usually more prolonged and involved in wide
local area than fasciculation
Most common in Orbicularis Oculi
Generalized Myokymia(ISSAC’S Syndrome)

54. Myokymia