This document provides an overview of orofacial dyskinesia, also known as tardive dyskinesia. It begins with an introduction defining orofacial dyskinesia as involuntary, repetitive stereotyped movements involving the head, face, and oral structures. It then discusses the etiology, typically being drug-induced by antipsychotics, and risk factors like older age, female sex, and long-term antipsychotic use. The document outlines the clinical features, diagnosis using scales like AIMS, management beginning with discontinuing the offending drug, and differential diagnosis from other movement disorders.

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OROFACIAL DYSKINESIA

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INTRODUCTION
 “ Orofacial or tardive dyskinesias are involuntary,
repetitive and stereotyped movements, involving the
head, face and oral structures.”
 In most cases, they occur in older psychotic patients
who are in institutions and in whom long-term
treatment with antipsychotic drugs of the
phenothiazine and butyrophenone groups is being
carried out.
 These dyskinesias are frequent in occurrence and
characteristically are irreversible.

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o Tardive Dyskinesia,
o Orobuccolingual Dyskinesia,
o Facial Dyskinesia,
o Extrapyramidal Insufficiency Syndrome,
o Drug-induced Dyskinesia,
o Cephalic Dyskinesia
o Dyskinetic Syndrome.
 Tardive dyskinesia , was applied at first to abnormal orofacial movements that
appear only following a long course of treatment or even after the
discontinuation of therapy with the implicated drug, and hence the designation
that the dyskinesia is "tardive.“
 However, because in some cases the dyskinesia occurs even in the early
phases of the administration of the offending drug or the history of drug

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ETIOLOGY
 Drug-induced [most common]
( anti-psychotics like phenothiazines & butyrophenones ; anti-
Parkinsonian like L-dopa )
Other proposed etiological factors :
 Brain damage
( leukotomies , ECT in chronic Schizophrenia)
 Spontaneous (rare , 1-2 % )
 Dental malocclusion / Edentulous state

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CLINICAL FEATURES
 AGE : incidence higher in older patients
 SEX : females >males (2:1 or 5:1)
 When drug-induced, these manifestations may appear :
o while the drug is being given,
o after termination of treatment or
o upon reinstitution of treatment.
 In many cases, the dyskinesias persist for months or years
 Irreversible.

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o tongue protrusion with licking of the
lips,
o sucking and smacking movements
with the lips,
o chewing movements,
o grunting and similar sounds,
o puffing of the cheeks,
o forehead furrowing and
o eye opening and closing.
 Many cases accompanied by:
o Cervical or Truncal dyskinesias
(including involvement of respiratory
function)
o Limb dyskinesias, including

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 These movements appear to be a common expression of a diverse
group of disorders and occur in patients in whom dyskinesia is part of a
more generalized disorder or in whom it is the major if not solitary
manifestation.
 Thus it may be most appropriate to view orofacial dyskinesia as part of a
symptom complex rather than as a specific expression of particular
diseases.

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NORMAL PHYSIOLOGY

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PATHOPHYSIOLOGY
NEURO-
TOXICITY
GABA
INSUFFICIENC
Y
DOPAMIN
E
SENSITIVI
TY
OTHERS

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DIAGNOSIS

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PHYSICAL EXAMINATION:
 Abnormal Involuntary
Movement Scale (AIMS)
 A rating of 2 or higher on the
AIMS scale is evidence of
tardive dyskinesia.
 If the patient has mild TD in
two areas or moderate
movements in one area, then
he or she should be given a
diagnosis of TD.
 Extremely reliable

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LABORATORY INVESTIGATIONS
 Complete blood count- to rule out polycythemia vera and other disorders
 Serum electrolytes- to omit abnormalities of sodium and calcium metabolism
that may cause movement disorders.
 Liver function test- know the other causes of liver dysfunction.
 Thyroid function test- to check possible hyperthyroidism.
 Serum copper and ceruloplasmin and urinary copper and amino acid in
case of suspected wilson’s disease.

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MANAGEMENT
 First Approach : discontinuation or reduction in dose
 Benzodiazepines ( Chlordiazepoxide HCl)
 Dopamine Antagonist (Tetrabenazine )
 Dopamine Agonists ( Apomorphine , Dopamine)
 Marijuana
 Vitamin B6 & E
 Adrenergic Antagonists ( Clonidine , Propandol)

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DIFFERENTIAL DIAGNOSIS
 Local conditions causing oral dyskinesia (eg. ill-fitting dentures)
 Neurological disorders (Huntington’s chorea)
 Psychogenic movement disoders (eg. Schizophrenic mannerisms)
 Due to other drugs (eg. L-dopa for Parkinsonism)
 Acute Akasthisia
 Acute Dystonia

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“ AN OVERVIEW OF
TARDIVE DYSKINESIA “
Narsi Reddy K , David Banji , Otilia Banji ,
Jyothi Reddy P , Swetha M
International Journal of Pharmaceutical Sciences
Review & Research
Sept-Oct 2010 , Vol 4 , Issue 3

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INTRODUCTION
 One of the muscular side effects of anti-psychotic drugs
especially the older generation anti-psychotic drugs
 Occurs after many months or years of antipsychotic therapy.
 Characterized by random movements of tongue, lips or jaw as
well as facial grimacing, movements of arms, legs, fingers and
toes, or even swaying movements of the trunk or hips and
which disappear during sleep.

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DIFFERENCE BETWEEN TYPICAL &
ATYPICAL ANTIPSYCHOTIC DRUGS
TYPICAL
ANTIPSYCHOTICS
 More affinity towards
nigrostriatal D2
receptors.
 Alleviate positive
symptoms
(of Schizophrenia)
ATYPICAL
ANTIPSYCHOTICS
 More affinity to
mesolimbic D2
receptors
 Alleviate negative
symptoms

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SIDE EFFECTS OF ANTI
PSYCHOTIC DRUGS
 + elevation of prolactin levels

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CLASSIFICATION OF
TARDIVE DYSKINESIA

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• Involuntary lip smacking and
pursing, movement of the tongue
sideto- side (bon-bon sign),
tongue protrusion (Fly-catcher’s
tongue), chewing movements,
respiratory dyskinesia (diaphragm
and intercostal involvement),
pelvic thrusting, choreiform limb
movements, tapping and side-to-
side foot movements, and
marching in place.
• Affect the lower face more than
the upper face.
• Central and Peripheral syndromes.
CLASSICAL
TARDIVE
DYSKINESIA
•Idiopathic torsion dystonia & other drug
induced movement disorders, including
classical orolingual buccal TD, tardive
akathisia, or myoclonus.
•Younger patients show a more
generalized involvement, while adults
demonstrate a focal or segmental
involvement.
TARDIVE
DYSTONIA

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INCIDENCE
 Prolonged exposure to antipsychotic treatment is the major reason .
 The risk factors that increase the chances of developing TD are::
a) Duration of exposure to antipsychotics (especially the older generation),
b) Older age,
c) Postmenopausal females,
d) Alcoholism and substance abuse,
e) Mental retardation
f) Experiencing a lot of EPS in the acute stage of antipsychotic therapy.

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SYMPTOMS

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DIAGNOSIS

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PHYSICAL EXAMINATION:
 Abnormal Involuntary
Movement Scale (AIMS)
 A rating of 2 or higher on the
AIMS scale is evidence of
tardive dyskinesia.
 If the patient has mild TD in
two areas or moderate
movements in one area, then
he or she should be given a
diagnosis of TD.
 Extremely reliable

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LABORATORY INVESTIGATIONS
 Complete blood count- to rule out polycythemia vera and other disorders
 Serum electrolytes- to omit abnormalities of sodium and calcium metabolism
that may cause movement disorders.
 Liver function test- know the other causes of liver dysfunction.
 Thyroid function test- to check possible hyperthyroidism.
 Serum copper and ceruloplasmin and urinary copper and amino acid in
case of suspected wilson’s disease.

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MECHANISMS OF ANTIPSYCHOTICS
INDUCTION OF TD
Postsynaptic
dopamine receptor
hypersensitivity
Damage to striatal
GABA-containing
neurons
Damage or
degeneration of
striatal cholinergic
interneurons
Prolonged
blockade of
postsynaptic
dopamine
receptors.

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PATHOPHYSIOLOGY
• The nigrostriatal dopamine system develops
increased sensitivity to dopamine as a
consequence of chronic dopamine receptor
blockade induced by neuroleptic drugs.
Dopamine
Hypersensitivity
• Due to neurotoxic effects of free radical by products
from catecholamine metabolism.
• The basal ganglia, by virtue of their high oxidative
metabolism, would be particularly vulnerable to
membrane lipid peroxidation as a result of the
increased catecholamine turnover induced by
neuroleptic drugs.
Neurotoxicity
• Gammaaminobutyric acid (GABA)
insufficiency in the neuroanatomical loop
controlling movement.
GABA Insufficiency
• A noradrenergic dysfunction theory
• Serotonin may modulate dopamine activity and
thus be involved with TD.
Other Neurochemical
Hypotheses

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GENETIC SUSCEPTIBILITY TO
TARDIVE DYSKINESIA
 Genetic factors may cause some people to be more
susceptible to developing tardive dyskinesia than others.
 Genetic polymorphisms coding for dopamine receptors may
explain differences in susceptibility to tardive dyskinesia.
 Genetic polymorphisms for dopamine receptors may impact
dopamine binding affinity, which would potentially make some
patients on neuroleptic medications more susceptible to
tardive dyskinesia than others.

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ANIMAL MODELS FOR
TARDIVE DYSKINESIA
RAT MODELS
• From chronic administration of
chlorpromazine,trifluoperazine,
or thoridazine for 12 months in
drinking water
• Reduced GAD activity and GABA
levels in substantia nigra, Globus
pallidus, and hypothalamic
nucleus
MONKEY MODELS
• A valid model which in many ways can serve as a
replication of this syndrome in humans.
• Prolonged administration of haloperidol or
chlorpromazine to cebus paella monkey result in
abnormal oral behavior.
• After three and six months of treatment, two of
these monkeys developed buccolingual
movements, grimacing and tongue protrusion that
were pronounced before each dose of activity
• GABA levels in substantia nigra, medial Globus
pallidus, and subthalamic mucleus relative to
control monkeys.

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PREVENTION OF TD
 By :
o early recognition and discontinuation of the
antipsychotic medication or
o reduction in dosage (first approach)
 Treatment with antipsychotic drugs plus high doses
of vitamins found less chances of getting TD.
(vitamin C, niacin, vitamin B6, and vitamin E)

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TREATMENT OF TD
 Discontinuation of medication or
reduction in dosage is the first
approach.
 BZDs (eg. chlordiazepoxide
hydrochloride)
 Dopamine Antagonists (eg.
Tetrabenazine)
 Marijuana (cannabis)
 Vitamin B6 & E
 Adrenergic antagonists (eg. Clonidine)

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CONCLUSION
Tardive Dyskinesia/ Orofacial Dyskinesia is the
extra pyramidal side effect of antipsychotic drugs
can be effectively diagnosed by AIMS scale and
managed by reducing dose of antipsychotic drugs.
For the screening of Tardive Dyskinesia animal
models are available and different drugs to treat
Tardive Dyskinesia like cholinergic agents,
benzodiazepines, calcium channel blockers,
catecholamines etc.


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COMMENTS
POSITIVE :
 Well-written with all details of the condition.
 Referred a good no. of articles.
 Easy language.
 Good tabular representation.
NEGATIVE :
 Grammatical errors at certain places.
 No diagrams.
 The pathophysiological hypothses haven’t been elaborated

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REVIEW OF LITERATURE
“A Review on Tardive Dyskinesia”, A
Saravana Kumar, T Sunil Kumar Reddy,
International Journal of Preclinical &
Pharmaceutical Research, 2012, Vol 3 ,
Issue 1:
 The clinical course of TD varies by
psychiatric diagnosis, age, sex, and
concomitant medical or neurologic illness.
Data from a prospective study of 971
young adult psychiatric patients followed
for up to 20years indicated a increasing
cumulative incidence rate of TD over the
20-year interval. The cumulative incidence
of persistent TD was lower but increased
proportionally . These data are consistent
with a declining rate of TD over time,
illustrated by the declining hazard rate .
Hazard Rate is the rate of tardive
dyskinesia occurrence per year among
those remaining at risk. The number
represents the average yearly hazard rate
over the 5-year block of time.

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 Classic Orobuccolinguomasticatory syndrome :
• First type of TD described.
• Stereotyped oral and facial movements, including twisting and protrusion of the tongue, lip
smacking and puckering, and chewing.
• One of the early signs of OBLD is slow, writhing movements of the tongue in the floor of the
mouth.
• Movements sometimes spread to involve the extremities.
• Occasionally, diaphragmatic dyskinesia can result in dyspepsia and hypoxia.
• OBLD is frequently associated with tardive akathesia, tardive dystonia, and Parkinsonism.
Differential diagnosis of orobuccolingualdyskinesias
Spontaneous dyskinesia of elderly(usually dystonic) Edentulous dyskinesia

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 OXYGEN FREE RADICALS AND TD
• Neuroleptic treatment activates oxidative processes in the brain. These, in turn increase free radical generation and
may cause oxidative membrane and subcellular damage.
• The basal ganglia are particularly vulnerable to this effect, leading to the development of dyskinetic movement.
• Treatment with antioxidants might then prevent or reverse both the pathophysiology and symptomatology.
• The brain is particularly susceptible to free radical damage because of its high oxygen use, its high concentration of
transition metals such as iron, manganese and copper (which acts as a catalyst for free radical formation), its low
concentrations of antioxidants (e.g.: vitamin C and E) and low levels of the enzymes of the antioxidant defence system
and because of its high concentrations of polyunsaturated fatty acids which are targets for free radical attack

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• There are several mechanisms by which chronic treatments with
neuroleptics may increase free radical formation and cause tissue
damage.
• Catecholamine metabolism via monoamine oxidase produces hydrogen
peroxide, and catecholamine themselves can be oxidized to quinines
and semiquinones, which can generate free radicals.
• Further, in animals chronic neuroleptic treatment increases the
accumulation of iron and manganese in brain, particularly the basal
ganglia structures associated with movement disorders. Patients’
treated with neuroleptics have elevated CSF indices of lipid
peroxidation and copper compared to untreated control patients.

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 Glutamate induced Excitotoxicity :
• Preserving the balance of dopamine and glutamate release seems to be a
major factor in maintaining normal striatal motor functions. Imbalance of
dopaminergic-glutamergic functions could alter normal striatal activity,
possibly resulting in motor abnormalities as in Parkinsonism.
• Moreover, neuroleptic treatment, which is known to block striatal dopamine
receptors, has been shown to alter striatal glutamergic activity at both
structural and functional levels.
• Thus, it is intriguing to speculate that neuroleptic-induced alterations in
glutamatergic neurotransmission may play a role in TD pathophysiology .

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Diagram shows glutamatergic nerve endings
forming synapses with a postsynaptic neuron
containing N-methyl-D-aspartic acid (NMDA)
receptor/channel complex. Neuroleptics can
cause disinhibition of glutamatergic input
through the presynaptic D2 receptor. The
NMDA receptor has been shown to be
regulated by glycine (Gly), which acts on an
allosteric site of the receptor.Increased
glutamate (Glu), N-acetylaspartate (NAA), N-
acetylaspartylglutamate (NAAG), and aspartate
(Asp) concentrations in tardive dyskinesia may
enhance postsynaptic NMDA conductance. In
addition, superoxide dismutase (SOD) activity is
reduced and protein carbonyl content is
increased in TD.

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 “Orofacial Dyskinesia” , Ronald M Kobayashi, Western Journal
of Medicine , 1976, vol.125:
Spontaneous Orofacial Dyskinesias-
• Dyskinesias occurring in the absence of drug exposure and diseases known to be associated with dyskinesias-
• Considered to be rare, with a reported incidence of 1 to 2 percent.
• Most spontaneous dyskinesia cases occurred in patients residing in nursing homes or mental hospitals, and most of the
patients were of advanced age.
• As in the druginduced variety, the spontaneous cases occur more often in women and in those with organic brain disease.
• Spontaneous orofacial dyskinesia presents -a clinical picture indistinguishable from the drug-induced form.
• The natural history, including spontaneous remissions, is largely unknown and no extensive series has been reported
concerning this aspect.

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“Etiological characteristics and
treatm ent of tardive dyskinesia”
Zhe Li，Xueli Sun，Che Zhou ,
Journal Of Neuronal Regeneration
Research , 2006:

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REFERENCES
 “ AN OVERVIEW OF TARDIVE DYSKINESIA” Narsi Reddy K , David Banji , Otilia Banji
,Jyothi Reddy P , Swetha M, International Journal of Pharmaceutical Sciences Review &
Research , Sept-Oct 2010 , Vol 4 , Issue 3
 “A Review on Tardive Dyskinesia”, A Saravana Kumar, T Sunil Kumar Reddy, International
Journal of Preclinical & Pharmaceutical Research, 2012, Vol 3 , Issue 1
 “Orofacial Dyskinesia” , Ronald M Kobayashi , Western Journal of Medicine , 1976, vol.125
 “Etiological characteristics and treatm ent of tardive dyskinesia” Zhe Li，Xueli Sun，
Che Zhou , Journal Of Neuronal Regeneration Research , 2006
 Internet sources (Pubmed , Medline , ScienceDirect , Wikipedia)

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