RANDA AL-HARIZY
DEFINITION: The extrapyramidal system is a general
term for the basal ganglia
 Centers: the corpus striatum, the substantia nigra,
  thalamic and subthalamic nuclei
 Inter connections: the above centers are
  interconnected with: The cerebral cortex, the
  cerebellum, the reticular formation, the cranial nerve
  nuclei (particularly the vestibular nerve) and the
  spinal cord
  Functions of the extrapyramidal

 Regulation of voluntary motor activity

 Control of the muscle tone

 Maintenance of emotional and associative movements
    Disturbance of extrapyramidal
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
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
              Movement disorders
Akinetic-rigid syndromes
Idiopathic Parkinson's disease
Drug-induced parkinsonism (e.g. phenothiazines)
MPTP-induced parkinsonism [methylphenyltetrahydropyridine]
Postencephalitic parkinsonism
Childhood akinetic-rigid syndrome
Essential tremor
Tic or 'habit spasms'
Torsion dystonias
Paroxysmal dyskinesias
 Parkinsonism (shaking palsy) is a condition in which
 there are static regular tremors, hypertonia of the
 muscles of the body with bradykinesia
Changes in neuromuscular profile occur as follows:
1. Putamen:
 Dopamine 90%
 Noradrenaline 60%
 5- hydroxytryptamine 60%
2. Substantia nigra:
 Dopamine 90%
 Glutamic acid decarboxylate (GDA)+γ-amino butyric acid
3. Cerebral cortex
 Glutamic acid decarboxylate (GDA)+γ-amino butyric acid
  1- Idiopathic Parkinson’s disease
 the cause is unknown. There is degeneration of the
  pigmented cells of the substantia nigra, and basal
  ganglia neurones
 It affects both sexes and occurs usually above the age of
  fifty years
 The onset is usually gradual with slowly progressive
 Static tremors are more manifest than rigidity
 Occurs with acute onset, regressive or stationary
  course at any age
 May be associated with other clinical manifestations:
Oculogyric crisis: spasm of conjugate eye movements
  mainly upwards
Greasy face
Diabetes insipidus
Pyramidal signs
 Static tremors and rigidity are equally manifest
 The age of onset is usually above the age of sixty years
 The onset is gradual with remissions and
 Rigidity is more manifest than static tremors
 May be associated with hypertension, diabetes
  mellitus and coronary heart disease
           4- DRUG-INDUCED
 Reserpine
 Phenothiazines

               5- NEOPLASTIC
 tumours of the basal ganglia

               6- TRAUMATIC
 Repeated trauma to the head as in boxers
1- Static tremors
 Rhythmic occuring at a rate of 4-8 / second
 May start in one hand and spread to other parts of the
 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
Strategy of Treatment
           (A)  Dopamine
 Carbidopa/l-dopa
 Dopamine agonists:        Apomorphine,
 COMT inhibitors: Entacapone
 MAO Inhibitors: e.g. Selegiline (B-type)
 Inhibitors of dopamine re-uptake: Amantadine
Strategy of Treatment
              (2)  Acetylcholine
   Anticholinergic
   Antihistaminics

(3) Other Neurotransmitters
(4) Surgery: Thalamotomy - Pallidotomy
            Transplantation of dopamine-containing adrenal medulla
            (fetal or autologus)
1- L-Dopa
 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
    delivery of l-dopa into the brain
    peripheral adverse effects of dopamine
  Carbidopa if peripheral adverse effects are
 It has dramatic initial response, decreases with time
  (wear off) due to the progressive loss of neurons
L-Dopa: Action & Use
 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
 L-Dopa: Adverse effects
 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
Dopamine Receptor Agonists
 Ergot alkaloid derivatives:
      Bromocriptine & Pergolide

 Non-ergot alkaloid derivatives:
        Pramipexole & Ropinirole
DA Receptor Agonists
   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
DA Agonists: Ergot derivatives
 Pergolde 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
DA Agonists: Non Ergot derivatives
  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
 Anti-Muscarinic drugs:
 (Beztropine, Trihexyphenidyl, Biperiden)
 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
 Hallucination, confusion
C/I: in glaucoma, SPH, Pyloric stenosis
 Stereotactic neurosurgery
 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.
 Involuntary static dysrhythmic jerky pseudo purposive
  movements of the face, trunk and/or limbs

 Rheumatic chorea (Sydenhan’s Chorea)
 Huntington’s chorea
             Rheumatic chorea
            (Sydenhan’s Chorea)
 This is a post infective chorea occuring largely in
  children and young adults
 Although rheumatic heart disease is sometimes found,
  the patient usually does not have a fever or other
  features of rheumatic fever. The antistreptolysin-O
  titer and ESR are sometimes normal.
 It may recur, or appear in adult life during pregnancy
  as chorea gravidarum or in those taking hormonal
   Rheumatic chorea (Sydenhan’s
Clinical picture:
 Choreic movements: the movements increase with
  emotional stress and disappear during sleep
 Hypotonia
 Emotional instability
 Patients may require sedation but recovery occurs
  spontaneously within weeks or months
 Acetyl salicylic acid
 Haloperidol 3mg 2-3 times daily
 Corticosteroids in cases of rheumatic activity
         Huntington’s Chorea
 A heridofamilial type of chorea inherited as autosomal
  dominant . The children of an affected parent have a
  50% chance of inheriting the disease
 The onset is gradual with a progressive course occuring
  in middle age
 The choreic movements are usually gross interfering
  with feeding and walking
 Associated with marked mentality changes
  progressing to dementia
           Huntington’s Chorea

1.   Relatives of patients should perform genetic
     counseling to detect any carrier state

2. Phenothiazines or haloperidol to control the
     involuntary movements
 Acute onset of severe violent swinging movements of
 one side of the body

 Due to a lesion mostly vascular (infarction or
 hemorrhage) in the subthalamus

 Treated by phenothiazines or haloperidol to control
 the movements
 Involuntary, irregular static, snake like movements
 affecting the extremities

 They are associated with hypertonia

 May occur due to hypoxic neonatal brain damage or
 post encephalitic

 Anticholinergic drugs may be helpful
 Involuntary, irregular static, very slow, torsion or
  twisting movements involving the neck, trunk or
  proximal muscles of the extremities

 Associated with hypertonia during the movement
1. Generalized: a familial disorder starting in childhood

2. Focal:
 Spasmodic torticollis
 Oromandibular dystonia
 Writer’s cramp: there is dystonia of the muscles of
    the hand on attempting to write
   Hepatolenticular degeneration
        (Wilson’s disease)
 Autosomal recessive disorder of copper metabolism
 leading to deposition of copper in the basal ganglia
 causing extrapyramidal manifestations in the form of
 choreo-athetosis, dystonia, tremors and bradykinesia

 Deposition of copper in the cornea produces Kayser-
 Fleicher ring

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