MOVEMENT DISORDERS

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					                                   MOVEMENT DISORDERS
     THE EXTRAPYRAMIDAL SYSTEM

     DEFINITION: The extrapyramidal system is a general
     term for the basal ganglia
     STRUCTURE:
         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 system
   Regulation of voluntary motor activity
   Control of the muscle tone
   Maintenance of emotional and associative movements

Disturbance of extrapyramidal functions
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
                                           Movement disorders

                      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

PARKINSONISM
  Parkinsonism (shaking palsy) is a condition in which there are static regular tremors, hypertonia of the
   muscles of the body with bradykinesia

PATHOGENESIS
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 (GABA)
3. Cerebral cortex
    Glutamic acid decarboxylate (GDA)+γ-amino butyric acid (GABA)

CAUSES
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 course
Static tremors are more manifest than rigidity
2- POST ENCEPHALITIC
    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
    Sialorrhoea
    Diabetes insipidus
    Pyramidal signs
    Static tremors and rigidity are equally manifest



3- CEREBRO-VASCULAR ATHEROSCLEROSIS
    The age of onset is usually above the age of sixty years
    The onset is gradual with remissions and exacerbations
    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

CLINICAL PICTURE
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
     Strategy of Treatment

                                                      (A)  Dopamine
       Carbidopa/l-dopa
       Dopamine agonists:         Apomorphine,
                                   Cabergoline
                                   Ropinirole,
                                   Pramipexole
       COMT inhibitors: Entacapone
       MAO Inhibitors: e.g. Selegiline (B-type)
       Inhibitors of dopamine re-uptake: Amantadine

                                             (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 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

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
     membranes)

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

Amantadine
  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 retention
     Hallucination, confusion
C/I: in glaucoma, SPH, Pyloric stenosis
OTHER LINES OF THERAPY
  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.

CHOREA
DEFINITION:
   Involuntary static dysrhythmic jerky pseudo purposive movements of the face, trunk and/or limbs

TYPES
   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 contraceptives

Clinical picture:
    Choreic movements: the movements increase with emotional stress and disappear during sleep
    Hypotonia
    Emotional instability

Treatment:
    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



Treatment:

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

2.       Phenothiazines or haloperidol to control the involuntary movements
HEMIBALLISMUS
  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



ATHETOSIS
  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



DYSTONIA
  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

TYPES
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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