Extrapyramidal System and Disorders of Extrapyramidal System

1. EXTRAPYRAMIDAL SYSTEM
AND
DISORDERS OF
EXTRAPYRAMIDAL SYSTEM
Dr Chandrashekar K
Asst Professor
Dept of Medicine
KIMS, Hubballi

2.  The term extrapyramidal system, coined by British
neurologist Kinnier Wilson, refers to the BASAL
GANGLIA AND AN ARRAY OF BRAIN STEM
NUCLEI (red nucleus, reticular formation etc.) to which
they are connected.
Components of the extrapyramidal system include
 Basal Ganglia,
 The red nuclei
 Vestibular nuclei,
 Superior colliculus and
 Reticular formation in the brain stem,

3. Basal ganglia and
Subcortical nuclei –
NAMES USED ARE AS
FOLLOWS
Caudate,putamen &
globus pallidus : corpus
straitum
Caudate & putamen
:straitum
Globus pallidus &
putamen : lentiform
nuclei
Globus pallidus :
pallidum

4. Extrapyramidal Tracts
They are consisted of a series of tracts:
•Rubrospinal Tract.
•Reticulospinal Tract,
Dividid into 2 types:
1. Pontine reticulospinal tract. (Medial)
2. Medullary reticulospinal tract. (Lateral)
•Tectospinal Tract.
•Vestibulospinal Tract.

5. Rubrospinal Tract
Originated from the red nucleus located in
the mesencephalon
Terminate in the lateral column
of spinal cord.
Function:Motor functions of skeletalmuscles
of the limbs, hands, and feet.

6. Reticulospinal Tract
A- pontine reticulospinal tract. (Medial & Excitatory)
Originated from pontine reticular nuclei in pons which terminate
in the medial anterior column.
anterior
B- Medullary reticulospinal tract. (Lateral & Inhibatory)
Originated from medulla and terminate in lateral
column.
Function: It Facilitates extensor reflexes & Inhibits Flexor
reflexes.

7. Tectospinal Tract
Origin: Superior colliculus of midbrain.
Terminate in the Anterior Column.
Function: Motor function of the Skeletal
muscles of the head and eyes in response to
visual stimuli.

8. Vestibulospinal Tract
Origin: vestibular nucleus in medulla.
Terminate in the Anterior Motor Neuron.
Function: Motor function of muscle for
maintaining balance in response to head
movements

12.  Phylogenetically, corpus striatum is primarily
responsible for stereotyped motor activities to
maintain tone, posture, locomotion and automatic
associated movement.
 Regulation of voluntary motor activity
 Control of the muscle tone
 Maintenance of emotional and associative
movements

13. Disturbance in the control of voluntary motor activity resulting
in involuntary movements which may be of two main types:
 Rhythmic and regular as in parkinsonism
 Dysrhythmic and irregular as in chorea, athetosis and dystonia
 Hypokinetic movements or Hyperkinetic movements are found

14. Extrapyramidal disorders are classified
broadly on clinical grounds into:
1. The akinetic-rigid syndromes in which
poverty of movements predominates
2. The dyskinesisas in which there are a
variety of excessive involuntary
movements

15. Akinetic-rigid syndromes
Idiopathic Parkinson's disease
Drug-induced parkinsonism (e.g. phenothiazines)
MPTP-induced parkinsonism [methylphenyltetrahydropyridine]
Postencephalitic parkinsonism
Parkinsonism-plus
Childhood akinetic-rigid syndrome
Dyskinesias
Essential tremor
Chorea
Hemiballismus
Myoclonus
Tic or 'habit spasms'
Torsion dystonias
Paroxysmal dyskinesias

16. Rhythmical
Tremor
Irregular
Slow or sustained
(Athetosis / dystonia)
Rapid
Controllable
(Tics)
Uncontrollable
Distal
(Chorea)
Proximal
(Ballismus)
Multifocal
(Myoclonus)

17. pyramidal system extrapyramidal system
function Skilful volitional
movements
Modulate volitional motor
movements
Finalizes an act Initiate an act
connection Direct linkage to
spinal cord
Multi neuronal and multi
synaptic via descending tracts
Cortico bulbar and
cortical spinal tract
reticulo-spinal, rubro-spinal,
olivo-spinal and vestibulo-spinal
tract.
Clinical features spasticity Rigidity( lead pipe/ cog wheel)
Reflexes brisk normal
Power diminished Usually not affected
Planters extensor flexor
Involuntary movements absent present

18.  Age- age of disease onset is very important tourette
syndrome, typically begins in the first decade,
parkinsons disease usually occurs in late age
 Past history –About infection (rheumatic fever),
jaundice(wilsons disease)
• Medical history & Toxin exposure
 Drug history- of current, previous & recreational use
should be taken details : parkinsonism & dystonia
may be produced by dopamine receptor blocking
agent
 Family history – should be taken and make a
pedigree chart if necessary (huntington disease)

19. Associated neuropsychiatric features –
Wilson disease, Huntington disease
Autonomic symptoms- dizziness,
bladder complaints, impotence etc may be
prominent & early in MSA,
neurodegenerative disease
, Alcohol responsiveness - essential
tremor is characteristically response to
alcohol

20.  Specific distribution-
• Chorea/ athetosis - mainly in the distal groups
• Hemiballismus- mainly proximally
• Parkinsons disease- mainly unilateral & asymmetric
• Blepherospasm- affect both eye
 Specific action & relationship to voluntary
movement-
• task specific tremor (intention tremor) during pick up a
glass of water
• Task specific dystonia eg: Writers cramp, musician
cramp

21.  Speed of movement-
 Rhythm-
Continuous – tremor
Intermittent – astrexis
 Relationship to sleep- Palatal myoclonus,
segmental myoclonus, fasciculation &
myokymia, persist during sleep , Dystonia
diminished on sleep
 Supresibility- tics may be voluntary suppressed
Slow Intermediate Fast
Parkinsonism Chorea Myoclonus
Dystonia Tremor Tics
Athetosis

22.  Aggravating or precipitating factor- stress and anxiety
worsen all movement disorder
• Myoclonus may be triggered by specific stimuli-
sudden loud noise or touch
• Carbohydrate heavy meal, fatigue may precipitate
paroxysmal dystonia
 Associated sensory symptom- RLS
associated with pain or discomfort, tics may be
associated with vague discomfort or abnormal
sensation
 Ameliorating factor- alcohol dramatically
improved essential tremor and myoclonic
dystonia

23. • Parkinson's disease (PD) is the second
commonest neurodegenerative disease.
• It is estimated 1 million persons in the US
• 5 million persons in the world.
• English doctor James Parkinson, who
published the first detailed description in An
Essay on the Shaking Palsy in 1817
PARKINSON’S DISEASE

24. Clinical Features of Parkinson's Disease
Cardinal Features
Bradykinesia
Rest tremor
Rigidity
Other Motor Features
Micrographia Masked
facies
(hypomimia)equalize
Gait disturbance/postural Reduced eyeblink
Dysphagia
Freezing
Nonmotor Features
Anosmia
Sensory disturbances
(e.g., pain)
Mood disorders (e.g.,
instability Soft voice (hypophonia) depression)
Sleep disturbances
Autonomic disturbances
Orthostatic hypotension
Gastrointestinal
disturbances
Genitourinal disturbances
Sexual dysfunction
Cognitive
impairment/Dementia

25. • AGE -The most important risk factor
• Positive family history
• Male gender
• Environmental exposure: Herbicide and pesticide
exposure, metals (manganese, iron), well water, farming,
rural residence, wood pulp mills; and steel alloy industries
• Life experiences (trauma, emotional stress, personality
traits such as shyness and depressiveness)
Risk factors of PD

26. CLASSIFICATION

27. 1- Static tremors
 Rhythmic occuring at a rate of 4-8 / second
 May start in one hand and spread to other
parts of the body
 Characteristically 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

28. 2- Rigidity of the muscles
 More proximal than distal
 Flexors are affected more than extensor
 On clinical examination the resistance may be
continuous throughout the act to the same
degree (lead pipe rigidity) or interrupted by
the tremors (cog wheel rigidity)
 Stiffness of the limbs develops causing
difficulty in starting movements and walking
(slow, shuffling gait)

29. 3- Akinesia: Loss of emotional and
associative movements resulting in:
Immobile face with infrequent blinking
(mask face)
Monotonous speech
Loss of swinging of the arms during
walking

30.  Pathologically, the HALLMARK FEATURES OF PD ARE
DEGENERATION OF DOPAMINERGIC NEURONS IN THE
SUBSTANTIA NIGRA PARS COMPACTA (SNC), reduced
striatal dopamine, and intracytoplasmic proteinaceous
inclusions known as Lewy bodies.
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.

31.  It has been proposed that most cases of PD are due to a
"DOUBLE HIT" involving an interaction between a gene
mutation that induces susceptibility coupled with exposure to
a toxic environmental factor.
 The most significant of these mechanisms appear to be
protein misfolding and accumulation and mitochondrial
dysfunction.
 Lewy bodies and Lewy neurites, which are composed of
misfolded and aggregated proteins.
PD – Etiology and Pathogenesis

32. PD – Etiology and
Pathogenesis.

37. Three cardinal symptoms:
1. Resting tremor
2. Bradykinesia (generalized slowness of
movements)
3. Muscle rigidity
Symptoms worsen as disease progresses.
Clinical features of PD

38.  Resting tremor: Most common first
symptom, most evident in one hand
with the arm at rest.
♦ usually unilateral
♦ becomes bilateral
♦ worsens with stress

39. Tremors
Usually –
♦ first symptom
♦ occurs in the hands or arms can occur in head,
face, jaw, & leg
♦ disappears with purposeful movement

40. Postural manifestations –
■ postural instability ■ rigidity
■ stooped
Postural changes cause balance instability

41. Patients also suffer from non- motor symptoms such as:
♦ cognitive impairments
♦ olfactory impairments
♦ dysphagia
♦ GI dysfunction
♦ sleep disturbances
♦ depression

42. Modern immunocytochemical techniques and genetic findings
suggest that Parkinson-plus syndromes can be broadly grouped
into 2 types: SYNUCLEINOPATHIES AND TAUOPATHIES.
Clinically, however, 5 separate Parkinson-plus syndromes have
been identified, as follows:
1. Multiple system atrophy
2. Progressive supranuclear palsy
3. Parkinsonism-dementia-amyotrophic lateral sclerosis complex
4. Corticobasal ganglionic degeneration
5. Diffuse Lewy body disease
Parkinson-plus syndromes respond poorly to the standard
treatments for Parkinson disease (PD).

44. DIAGNOSIS
Parkinsonism is predominantly DIAGNOSED
CLINICALLY.
However, the other investigations helpful are :
1. MRI
2. SPECT Imagining
3. Biopsy useful in case of Parkinsonism Plus
Syndromes
4. Autopsy specimen to confirm the diagnosis

45. SPECT IMAGING

46. (A)  Dopamine
 Carbidopa/l-dopa
 Dopamine agonists: Apomorphine(offphenomenon),
 s/c, i.v.
Cabergoline
Ropinirole,
Pramipexole
 COMT inhibitors: Entacapone, Tolcapone
 MAO Inhibitors: e.g. Selegiline, Rasageline(B-type)
 Inhibitors of dopamine re-uptake: Amantadine
(2)  Acetylcholine
 Anticholinergic
 Antihistaminics

47. Drugs commonly used in
the treatment of
Parkinson disease
MEDICATION
Carbidopa-L-dopa
(Sinemet)
MAIN BENEFIT
Reduction of tremor and
bradykinesia; less effecton
postural difficulties
SIDE EFFECTS
Nausea, dyskinesias, orthostatic
hypotension, hallucinations,
confusion, arrhythmia
Controlled release
carbidopa-L-dopa
Dopamine agonists
Ropinirole(D3)
Moderate effects on all
aspects; reduced motor
fluctuations of L-dopa,
neuroprotective, neurotrophic
Orthostatic hypotension,
excessive and abrupt
sleepiness, confusion,
hallucinations, impulse control
disorders
Pramipexole(D2)

48. Tremor reduction, less effect
on other features, drug
Atropinic effects: dry mouth,
urinary outlet obstruction,
confusion and psychosisInduced parkinsonism
Neuroprotection, adjuntive
therapy
Insomnia
Anticholinergics
Benztropine
(Cogentin)
Trihexyphenidyl
(Artane)
MAO-B inhibitor
selegiline,
Rasagiline
COMT inhibitors
Entacapone
Urine discoloration, diarrhea,
increased dyskinesias
Glutamate agonist
Amantadine
(Symmetrel)
Smoothing of motor
fluctuations
Leg swelling, congestive heart
failure, prostatic outlet
obstruction, confusion,
hallucinations, insomnia

49.  Contrary to dopamine, it can pass into the brain
where it is decarboxylated into dopamine
 Levodopa is combined with a peripheral L-AA
decarboxylase inhibitor e.g. carbidopa or
benserazid to
  delivery of l-dopa into the brain
  peripheral adverse effects of dopamine
  Carbidopa if peripheral adverse effects are
prominent
 It has dramatic initial response, decreases with
time (wear off) due to the progressive loss of
neurons

51. Combined with carbidopa is the most
potent oral therapy for Parkinson’s disease
Symptoms of Parkinson’s disease but
does not stop the progression
(deterioration) of the disease i.e.
Symptomatic treatment
From the third year its efficacy declines

52.  Peripheral:
• GIT: Nausea & Vomiting
• CVS: Orthostatic hypotension, Dysrhythmias
• Blood dyscrasias & Positive reaction to Coombs
test
• Mydriasis and Brownish discoloration of urine &
saliva
 CNS Effects:
• Visual & Auditory hallucinations & vivid dreams
• Dyskinesias: opposite of Parkinsonian symptoms
• Mood changes, depression & Anxiety
 Long-term levodopa Complications:
• Wearing off (fluctuations), Dyskinesias

53.  Ergot alkaloid derivatives:
Bromocriptine & Pergolide
 Non-ergot alkaloid derivatives:
Pramipexole & Ropinirole

54. Have longer duration less fluctuation
Have less tendency to induce dyskinesia
Ineffective in patients not responding to
levodopa
Can be used in early cases to delay use
of levodopa (in levodopa-naïve patients) & in
advanced cases to augment
levodopa and to decrease fluctuations to
its response

55.  Pergolide is more potent than Bromocriptine
 Their side effects limit their use and slow rapid
build up of doses (over 2-3 Months)
 Side effects include levodopa side effects in
addition to spasmogenicity & fibrosis (of serous
membranes)
ERGOT DERIVATIVES

56. Pramipexole & Ropinirole
Pramipexole: is cleared by renal
excretion
Ropinirole: is cleared by liver metabolism
Side effects as levodopa with less
dyskinesia and fluctuation and
No spasmogenicity and fibrosis

57. Antiviral (influenza) drug
The mode of action is unknown
• NMDA glutamate receptors (the primary action)
• Muscarinic receptors
• Increases release of dopamine
It has little effect on tremors &
Tolerance develops rapidly

58.  Augment the effect of dopamine
 Weak and play an adjuvant role
 They are the same in efficacy but with some inter-
individual variation in response
Side effects:
 Mood changes
 Xerostomia, blurred vision, constipation, urinary
retention
 Hallucination, confusion
C/I: in glaucoma, SPH, Pyloric stenosis

59. PARKINSON PLUS SYNDROME
THE RESPONSETO DRUGS ARE POOR WHENTHE PATIENT HAS PARKINSONS PLUS
SYNDROME.
Clinical clues suggestive of Parkinson-plus syndromes include the
following:
 Early onset of dementia
 Early onset of postural instability
 Early onset of hallucinations or psychosis with low doses of
levodopa/carbidopa or dopamine agonists
 Ocular signs, such as impaired vertical gaze, blinking on saccade,
square-wave jerks, nystagmus, blepharospasm, and apraxia of eyelid
opening or closure
 Pyramidal tract signs not explained by previous stroke or spinal cord
lesions
 Autonomic symptoms such as postural hypotension and incontinence
early in the course of the disease
 Prominent motor apraxia
 Alien-limb phenomenon
 Marked symmetry of signs in early stages of the disease
 Truncal symptoms more prominent than appendicular symptoms
 Absence of structural etiology such as a normal-pressure hydrocephalus
(NPH)

61.  Stereotactic neurosurgery: pallidotomy, thalamotomy ,sub
thalamotomy
Indications
1.idiopathic parkinsons
2.levodopa unhelpful
3.intractable PD
4.drug dyskinesias
 Deep brain stimulation: dyskinesia
 Tissue transplantation: Experimental transplantation of fetal
or autologous dopamine-containing adrenal medulla or stem
cell research has produced no promising results in PD to date.
 Physiotherapy and physical aids
 Neuropsychiatric aspects: Cognitive impairment and
depression are common as PD progresses. SSRIs are the
drugs of choice for depression.

62. • Associated with drugs, stroke, tumour, infection, or
exposure to toxins such as carbon monoxide or
manganese.
SECONDARY PARKINSONISM

63. •Side effects of some drugs, especially those that affect
dopamine levels in the brain, can actually cause symptoms of
Parkinsonism.
•Although tremor and postural instability may be less severe,
this condition may be difficult to distinguish from Parkinson’s
disease.
• Medications that can cause the development of Parkinsonism
include:
– Antipsychotics
– Metaclopramide
– Reserpine
– Tetrabenazine
– Some calcium channel blockers
– Stimulants such as amphetamines and cocaine
– Usually after stopping those medications Parkinsonismgradually
disappears
Drug-induced Parkinsonism

64. • Multiple small strokes can cause Parkinsonism.
• Patients with this disorder are more likely to present
with gait difficulty than tremor, and are more likely to
have symptoms that are worse in the lower part of the
body.
• Some will also report the abrupt onset of symptoms or
give a history of step-wise deterioration (symptoms get
worse, then plateau for a period).
• Dopamine is tried to improve patients’mobility
although the results are often not as successful.
• Vascular Parkinsonism is static (or very slowly
progressive) when compared to other
Vascular Parkinsonism

65. •Atypical parkinsonism refers to a group of neurodegenerative
conditions that usually are associated with MORE WIDESPREAD
NEURODEGENERATION THAN IS FOUND IN PD (often
involvement of SNc and striatum and/or pallidum).
•As a group, they PRESENT WITH(RIGIDITY AND
BRADYKINESIA) but typically have a slightly different clinical
picture than PD, reflecting differences in underlying pathology.
•In the EARLY STAGES, THEY MAY SHOW SOME
MODEST BENEFIT FROM LEVODOPA and be difficult
to distinguish from PD.
PARKINSON PLUS SYNDROME

66. •NEUROIMAGING of the dopamine system
is USUALLY NOT HELPFUL, as several
•Atypical parkinsonisms also have degeneration
of dopamine neurons. Pathologically,
neurodegeneration occurs without Lewy bodies

67. Metabolic imaging of the basal ganglia/thalamus network may be
helpful, reflecting a pattern of decreased activity in the GPi with
increased activity in the thalamus, the reverse of what is seen in
PD.
TYPES ATYPICAL PD.
•Progressive Supranuclear Palsy (PSP)
•Corticobasal Degeneration (CBD)
•Multiple System Atrophy (MSA)
Shy-Drager syndrome (DSD), Striatonigral degeneration (SND) and
OlivoPontoCerebellar Atrophy (OPCA).
PARKINSON PLUS SYNDROME