Extrapyramidal disorders

 WHAT IS EXTRAPYRMIDAL SYSTEM?
 DEFINITION
 ANATOMY
 FUNCTIONS
 APPROACH TO A CASE OF EXTRAPYRMIDAL
DISORDER
• CLASSIFICATION OF EXTRAPYRMIDAL DISORDER
• DEFINATION
• ETIOLOGY
• PATHOPHYSIOLOGY
• DISTINGUISHING FEATURES
 BRIEF DISCUSSION ON
• PARKINSONISM
• HUNTINGTON’ DISEASE

 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 the
red nuclei, vestibular nuclei, superior colliculus and
reticular formation in the brain stem, all of which
project via discrete pathways to influence spinal cord
motor neurons. Cerebellar projections are also
included since they influence not only these brainstem
motor pathways, but also the motor cortex itself via the
dentatothalamic projection.

Basal ganglia
Subcortical nuclei
Caudate,
putamen &
globus pallidus
: corpus
straitum
Caudate &
putamen :
straitum
Globus pallidus &
putamen :
lentiform nuclei
Globus pallidus :
pallidum

Perhaps the most important structures to retain an
extrapyramidal definition are the basal ganglia,
Sub cortical cell stations for the extra pyramidal
motor pathway
The neostriatum (caudate and putamen) receives
widespread cortical afferents, including those from
high order sensory association and motor areas,
and projects mainly to the globus pallidus. The
latter nucleus is the major outflow for the basal
ganglia and, via the ventral anterior thalamus,
exerts its major influence on premotor and hence
the motor cortices.
This pattern of connections suggests that the basal
ganglia are involved in complex aspects of motor
control, including motor planning and the initiation
of movement.

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

 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

It is now clear that in many extrapyramidal disorders there are
specific changes in neurotransmitter profile rather than
discrete anatomical lesions
1. 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
2. Disturbance in the normal muscle tone resulting in hypertonia
(rigidity)
3. Disturbance in the maintenance of emotional and associated
movements resulting in bradykinesia (mask face, infrequent
blinking and loss of swinging during walking)

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

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

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

Only Cogwheel
rigidity or rest
tremor
(Parkinsonism)
Cognitive, language,
upper motor neuron
or sensory sign
(Degenerative
disease with
parkinsonism)

 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)

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

 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

 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

 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

 2nd commonest neurodegenerative
disease of neurons in the nigrostrial
dopamine system
Clinical Features of Parkinson's Disease
Cardinal Features Other Motor Features Nonmotor Features
Bradykinesia
Rest tremor
Rigidity
Gait disturbance/postural
instability
Micrographia
Masked facies
(hypomimia)equalize
Reduced eye blink
Soft voice (hypophonia)
Dysphagia
Freezing
Anosmia
Sensory disturbances
(e.g., pain)
Mood disorders (e.g.,
depression)
Sleep disturbances
Autonomic disturbances
Orthostatic hypotension
Gastrointestinal
disturbances
Genitourinal disturbances
Sexual dysfunction
Cognitive
impairment/Dementia

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

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)

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

 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.
 Indeed, there is evidence that pathology begins in the peripheral autonomic
nervous system, olfactory system, and dorsal motor nucleus of the vagus nerve in
the lower brainstem, and then spreads in a sequential manner to affect the upper
brainstem and cerebral hemispheres. These studies suggest that dopamine
neurons are affected in midstage disease.
 Several studies suggest that symptoms reflecting nondopaminergic degeneration
such as constipation, anosmia, rapid eye movement (REM) behavior sleep
disorder, and cardiac denervation precede the onset of the classic motor features
of the illness.

Differential Diagnosis of Parkinsonism
Parkinson's Disease
Genetic
Sporadic
Dementia with Lewy
bodies
Atypical
Parkinsonisms
Multiple-system
atrophy
Cerebellar type
(MSA-c)
Parkinson type
(MSA-p)
Progressive
supranuclear palsy
Corticobasal
ganglionic
degeneration
Frontotemporal
dementia
Secondary
Parkinsonism
Drug-induced
Tumor
Infection
Vascular
Normal-pressure
hydrocephalus
Trauma
Liver failure
Toxins (e.g.,
carbon monoxide,
manganese,
MPTP, cyanide,
hexane, methanol,
carbon disulfide)
Other Neurodegenerative
Disorders
Wilson's disease
Huntington's disease
Neurodegeneration with
brain iron accumulation
SCA 3 (spinocerebellar
ataxia)
Fragile X–associated
ataxia-tremor-
parkinsonism
Prion disease
Dystonia-parkinsonism
(DYT3)
Alzheimer's disease with
parkinsonism

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).

In addition to lack of response to levodopa/carbidopa
(Sinemet) or dopamine agonists in the early stages of
the disease, other clinical clues suggestive of
Parkinson-plus syndromes include the following:
History and Examination Features Suggesting Diagnoses Other Than Parkinson's
Disease
Symptoms/Signs Alternative Diagnosis to Consider
History
Falls as the first symptom PSP
Exposure to neuroleptics Drug-induced parkinsonism
Onset prior to age 40 If PD, think genetic causes
Associated unexplained liver disease Wilson's disease
Early hallucinations Lewy body dementia
Sudden onset of parkinsonian symptoms Vascular parkinsonism
Physical Exam
Dementia as first symptom Dementia with Lewy bodies
Prominent orthostasis MSA-p
Early dysarthria MSA-c
Lack of tremor Various Parkinson's-plus syndromes
High frequency (8–10 Hz) symmetric tremor Essential tremor

Diagnosis of PD
 clinical examination
 No disease-specific biological marker
available
 Positron Emission Tomography (PET)
or Single-photon Emission Computed
Tomography (SPECT) with
dopaminergic radioligands
 Exclusion of several causes of
secondary Parkinsonism

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

Drugs commonly used in the treatment of Parkinson disease
MEDICATION
STARTING
DOSE
TARGET
DOSE MAIN BENEFIT SIDE EFFECTS
Carbidopa-L-dopa
(Sinemet)
25/100 tid
empty
stomach
Up to 50/250
q 3 h
Reduction of tremor and
bradykinesia; less effect on
postural difficulties
Nausea, dyskinesias, orthostatic
hypotension, hallucinations,
confusion, arrhythmia
Controlled release
carbidopa-L-dopa
25/100 tid Up to 50/200
q 4 h
Dopamine agonists
Ropinirole(D3) 0.125 mg
tid
0.5 to 1.5
mg/day
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) 0.25 mg tid 8 to 24
mg/day
Glutamate agonist
Amantadine
(Symmetrel)
100
mg/day
100 mg bid-tidSmoothing of motor
fluctuations
Leg swelling, congestive heart
failure, prostatic outlet
obstruction, confusion,
hallucinations, insomnia
Anticholinergics
Benztropine
(Cogentin)
0.5 mg per
day
Up to 4 mg
per day
Tremor reduction, less effect
on other features, drug
induced parkinsonism
Atropinic effects: dry mouth,
urinary outlet obstruction,
confusion and psychosisTrihexyphenidyl
(Artane)
0.5 mg bid Up to 2 mg tid
MAO-B inhibitor
selegiline, 5mg/day bd Neuroprotection, adjuntive
therapy
Insomnia
Rasagiline 1mg/day
COMT inhibitors
Entacapone 200 mg with L-dopa Urine discoloration, diarrhea,
increased dyskinesias

 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.

 Sudden, brief, rapid, jerky, purposeless, non-
repetitive, involuntary movement
 Most characteristically in distal parts of upper
extremity but may also involved proximal part,
lower extremity, trunk, face & tongue
PATHOLOGY
 Damage to caudate nucleus

 Disease characterized by chorea:
 Inherited disorder: Huntington disease, wilson
disease, benign hereditry chorea,
neuroacanthocytosis
 Infectious causes: Rheumatic chorea
(sydenham chorea), HIV disease
 Structural lesion of the basal ganglia- infarct,
neoplasm, trauma
 Chorea of systemic disease: SLE,
thyrotoxicosis, polycythemia vera,
hyperosmolar non-ketotic hyperglycemia
 Pregnancy (chorea gravidarum)
 Drugs: Neuroleptics, OCP, excessive dose of
levodopa or dopamine agonist, phenytoin
cocaine

 Hypotonia
 Pronator sign
 Milkmaid’s grip
 Spooning sign
 Pendular knee jerk “hung up reflex”
 Lizard tongue
Increased by excitement, diminished by sleep
Sydenham chorea (Saint vitus dance) more common in
female and childhood (5-15yrs), associated with prior
exposer to group a streptococcal infection, late
manifestation
Huntington's disease progressive fatal autosomal
dominant disorder characterized by motor, behavioral
& cognitive dysfunction, in early stages chorea is focal
or segmental but it progress over time to involve
multiple body region

Etiology
 HD is caused by an increase in the
number of polyglutamine (CAG)
repeats (>40) in the coding sequence
of the huntingtin gene located on the
short arm of chromosome 4. The larger
the number of repeats, the earlier the
disease is manifest.
Treatment
 multidisciplinary approach
 Dopamine-blocking agents may control
the chorea. Tetrabenazine
 depression and anxiety can be greater
problems, and patients should be
treated with appropriate antidepressant
and antianxiety drugs and monitored for
mania and suicidal ideations.
 Psychosis can be treated with atypical
neuroleptics such as clozapine,
quetiapine, and risperidone
 There is no adequate treatment for the
cognitive or motor decline

 Slow, distal, purposeless, writhing involuntary
movement
 They are more sustained and larger in amplitude
than those in chorea
 The mainly involved the extremities (distal
portion, fingers & hands) face, neck & trunk
 Movement are characterized by any combination
flexion, extension, abduction, pronation, &
supination often alternating and in varying
degree
 Predominant pathologic changes are in the
putamen

Causes: cerebral palsy, perinatal injury to
basal ganglia, wilson disease
Choreoathetosis: the movement live
between chorea & athetosis in rate and
rhythmicity eg: cerebral palsy ( Neonatal
jaundice)
Pseudoathetosis: (sensory athetosis)
undulating & writhing movement of
extremities due to loss of position sense as
a result of parietal lobe lesion, tabes
dorsalis, peripheral nerve disease

A wild, flinging, large amplitude
movements on one side of the body
Proximal upper limb muscles
predominantly affected
Ballastic movement of hemiballismus
resemble that of chorea but are more
pronounced, rapid & forceful
Movement ceaseless during the walking
state and disappear only with the deep
sleep

 Usually self limiting and tends to resolve
spontaneously after weeks to months
 Due to infarction or hemorrhage in the
regions of contralateral subthalamic nucleus,
results in disinhibition of the motor thalamus
and cortex resulting in contralateral
hyperkinetic movement.
 Treatment:
 Dopa blocking agent
 Pallidotomy can be done.

 Sustained or repetitive involuntary muscle contraction leading to twisting
movements and abnormal posture
 Can involve individual muscle or multiple muscle groups.
 Often affect the extremities neck, trunk, eyelids, face & vocal cords
 Dystonic movements are patterned tending to recur in same location
 When duration is very brief less than one second- dystonic spasm, when
for several seconds, dystonic movement & when prolonged minutes to
hours- dystonic posture
Pathophysiology of Dystonia
 not known.
 co-contracting synchronous bursts of agonist and antagonist muscle groups
due to loss of inhibition at multiple levels of the nervous system as well as
increased cortical excitability and reorganization.
 Attention has focused on the basal ganglia as the site of origin of at least
some types of dystonia as there are alterations in blood flow and metabolism
in basal ganglia structures. Further, ablation or stimulation of the globus
pallidus can both induce and ameliorate dystonia.

 Dystonia can be generalized or focal: primary or
secondary
 Generalized dystonia is mainly primary
dystonia involving larger portion of body often
producing distorted posture of limbs & trunk
(Torsion dystonia)
 Idiopathic torsion dystonia (dystonia musculorm
deformance) is predominantly childhood onset
form of dystonia with autosomal dominant
pattern of inheritance
 May starts distally usually in the foot in the
planter flexation & inversion & speed to opposite
side, upper extremity trunk & face
 There is peculiar axial involvement of spine
(twisting)

 Dopa responsive dystonia ( Segawa variant)
dominantly inherited form of dystonia in early
childhood 1-12yrs typically present with foot
dystonia resulting in gait disturbance and there is
excellent response to small doses of levodopa.
 Diurnal variation, worsen with day progresses
Focal dystonia is a most common, 4th to 6th
decade and more common in female:
• Blephero spasm
• Oromandibular dystonia
• Spasmodic dysphonia
• Cervical dystonia
• Limb dystonia (writer’s cramp)

Secondary dystonia:
Due to drugs: Neuroleptics,
(Phenothiazine, Butyrophenone), chronic
levodopa treatment in parkinsons disease
 Discrete lesion in the stratum, palladum,
thalamus, cortex & brain stem
Dystonia plus syndrome:
May occur in the neurodegenerative
condition (Huntington disease, Wilson
disease, parkinson disease, corticobasal
degeneration & progressive supranuclear
palsy)

symptomatic
 Levodopa should be tried in all cases of childhood-onset dystonia to
rule out DRD.
 High-dose anticholinergics (e.g., trihexyphenidyl 20–120 mg/d) may
be beneficial in children, but adults can rarely tolerate high doses
because of cognitive impairment with hallucinations.
 Oral baclofen (20–120 mg), Tetrabenazine (the usual starting dose is
12.5 mg/d and the average treating dose is 25–75 mg/d) may be
helpful in some patients, but use may be limited by sedation and the
development of parkinsonism.
 Botulinum toxin has become the preferred treatment for patients with
focal dystonia, particularly where involvement is limited to small
muscle groups such as in blepharospasm, torticollis, and spasmodic
dysphonia.
 Surgical therapy is an alternative for patients with severe dystonia
who are not responsive to other treatments. Peripheral procedures
such as rhizotomy and myotomy were used in the past to treat
cervical dystonia, but are now rarely employed. DBS of the pallidum
can provide dramatic benefits for patients with primary DYT1
dystonia
 Supportive treatments such as physical therapy and education are
important and should be a part of the treatment regimen.

 Sudden, brief (<100ms) shock like, jerky
involuntary movement consisting of single or
repetitive muscle discharges
 Myoclonus is seen principally in the muscles of
extremities and trunk but the involvement is often
multifocal, diffuse or wide spread
 Can often spontaneously, association with
voluntary movement (action myoclonus) or in
response to external stimulus (reflex or startle
myoclonus)
 Myoclonic jerks defer from tics in that they
interfere with normal movement and not
suppressible

Symptomatic causes of myoclonus:
 Metabolic endogenous- Hypoxia, uraemia,
hepatic failure, hypoglycemia, hyponatraemia,
non-ketotic hyperglycemia
 Degenerative: Alzheimer’s disease, Huntington
disease, multisystem atrophy, corticobasal
degeneration
 Infectious: Creutzfeldt –Jakob disease, EBV etc
 Autoimmune: Multiple sclerosis
 Neoplastic: Neuroblastoma, paraneoplastic
disorders (ovarian, lung & breast)
 Frequently associated with epilepsy, electric
shock, heat stroke
 Drugs: Amantadine, lithium, metoclopramide,
levodopa & dopamine agonist, cocaine,
strychnine

 Opsoclonus- Myoclonus (Kinsbourne
syndrome)- Dancing eye & dancing feet
 Due to the post infectious encephalopathy or as a
paraneoplastic syndrome due to neuroblastoma
 Palatal myoclonus- involuntary rhythmic movement
of soft palate and pharynx the movements are
generally not influenced by drugs or sleep palatal
myoclonus occur with lesions involving the
connections between the inferior olivary, dentate &
red nuclei
 Astrexis: particularly in hepatic encephalopathy,
negative myoclonus inability to sustained normal
muscle tone presenting with slow & irregular
flapping motion

 Acute- Dystonia is most common acute drug
reaction can develop within minutes of exposure
typically generalized in children and focal in adults
 Treatment: parenteral administration of
anticholinergics (benztropine or diphenhydramine)
or benzodiazepines (lorazepam or diazepam).
 Subacute- Akathisia is commonest reaction it
consist of motor restlessness within in need to move
and that to elevated by movement.
 Treatment: Removing the offending agent.If not
possible, give benzodiazepines, anticholinergics,
blockers, or dopamine agonists for symptomatic
improvement.

Chronic- Tardive syndrome after months to years after initiation
of treatment
A typically comprises choreiform movement involving the mouth
lip, tongue, and in severe cases trunk, limbs and respiratory
muscles can be affected
Is more common in elderly women & with underlying organic
cerebral dysfunction (Schrizophrenia)

 Brief, repeated, sterotyped muscle contraction
that often suppressible
 Quick, irregular, seemingly purposeful act but
relatively involuntary
 Patient have some degree of awareness of
movement and in response to urge of some
compelling inner forces
 Exaggerated by emotional strain and tension and
stop during sleep
 May involved any portion of body

 Eg: Repetitive blinking, facial contortions,
shoulder shrugging, also involved vocal tract
producing throat clearing
 Gilles de la Tourette Syndrome characterized
by multiple motor tics and vocalizations
 Motor tics can be simple/ complex & vocal
tics can be simple (grunting) or complex
(echolalia)
 Tourette syndrome is a disease of early
childhood in the first decade and mainly in
Boys an associated with some regressive
behaviour

 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

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

 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

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

Have longer duration less fluctuation
Have less tendency to induce dyskinesia
Ineffective in patients not responding to
leveodopa
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

 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)

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

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

 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

Parkinson-plus syndromes respond poorly to the standard treatments
for Parkinson disease (PD).
In addition to lack of response to levodopa/carbidopa (Sinemet) or
dopamine agonists in the early stages of the disease, other 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)

 Tremor is rhythmic, involuntary, purposeless
oscillatory movement of body part due to
intermittent muscle contraction
 Types: i. Rest ii. Postural iii. Intention
 Rest Tremor: is maximum at rest & becomes less
prominent with activity eg: parkinson disease,
 Postural Tremor: is maximum while limb posture
is actively maintained against gravity (arm
outstretched) eg: Essential tremor, enhanced
physiologic tremor,
 Intention Tremor: Most prominent during
voluntary movement toward a target eg: cerebellar
disease

 Etiology:
Parkinsonism
Essential tremor
Physiologic tremor
Alcohol
Anxiety
Thyrotoxicosis
Cerebellar disease
Wilson disease
Red nuclear tremor
Drugs (-2agonist, sympathomimetics,
methylxanthine, amphetamine, anticonvulsant,
Poison (Mercury, MPTP)

Essential tremor: Most common involuntary
movement disorder
 High frequency, coarse mainly distal upper
extremity & later become bilateral symmetrical
 Maximum when trying to maintain a posture
 Autosomal dominant pattern of inheritance
 Characteristically improve with alcohol & -
blocker
 Parkinsonism is a slow (4-6 Hz) coarse, rest
tremor typically appears unilaterally, pill rolling
tremor

Physiologic Tremor: In normal individual
8-12Hz, mainly young adults
Cerebellar tremor: intention tremor,
coarse & irregular
Thyrotoxic tremor: fine & rapid but may
be complicated by choreiform involuntary
movement
Red nuclear tremor: the severe, large
amplitude, slow 2-5 Hz, involve both
proximal & distal muscle present at rest
but made worse with action

 Fine rapid, flickering or vermicular twitching
movements due to contraction of a bundle or
fasciculus of muscle fibers
 Fasciculations are much more gross than
fibrillation and can be seen through intact skin
and this continue during sleep
 Exaggerated by fatigue, cold, cholinergic drugs,
caffine
 Characteristic feature of motor neuron disease,
anterior horns cell disease

 Involuntary, spontaneous, localized, transient or
persistent quivering movement that affect a few
muscle bundles with in a single muscle
 Coarse, slower, worm like, usually more
prolonged and involved in wide local area than
fasciculation
 Not affected by motion or position and persist
during sleep
 Most commonly present in orbicularis oculi
 Generalized myokymia (Isaac’s syndrome)
generalized muscle stiffness and persistent
contraction due to underlying continuous
muscle fiber activity

 Slow 2-3Hz rhythmic alternating movement
resemble tremor
 Wide spread involvement, may involved multiple
body parts
 Absent during sleep
 May be intermittent or continuous, synchronous
or asynchronous
 Eg: CNS whipple’ disease

Extrapyramidal disorders

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