chorea is the ceaseless occurrence of rapid , jerky , dyskinetic , involuntary flicking movement of hands , face , and other parts of body .
huntington 's disease ( hd ) and drugs account for more than 50% of such patients .
basic pathology involved in chorea and other hyperkinetic movements is damage to various parts of basal ganglia that ultimately leads to disturbances in neurotransmission . in chorea
, there is degeneration of gamma aminobutyric acid ( gaba ) secreting neurons in the caudate nucleus and putamen of basal ganglia .
the normal inhibition by gaba neurons is lost in globus pallidus , and substantia nigra resulting in over activity of excitatory transmitters causing the distortional movements .
phenytoin sodium is an anti - seizure drug widely used for generalized tonic clonic seizures .
few cases have been reported to cause hyperkinetic movements by various anti - seizure drugs . here
, we report a case of phenytoin induced chorea in a child possibly due to interaction between anti - seizure drugs .
a 3-year - old female patient weighing 10.5 kg was admitted in pediatric ward of sir takhtsinhji general hospital , bhavnagar , gujarat , with complaint of low grade fever for three days and convulsions with frothing , involuntary micturition , and altered sensorium for one hour .
patient was treated with injection lorazepam ( 0.04 mg / kg ) followed by injection phenytoin ( 5 mg / kg ) intravenously to control the seizures . all investigations like total leukocyte count , differential leukocyte count , liver function tests , renal function tests , random blood sugar , and cerebrospinal fluid ( csf ) examination were normal except hemoglobin ( 9.0 g / dl ; reference value : 12.0 to 18.0 g / dl ) , positive c - reactive protein ( crp ) , and ionized calcium ( 1.01 mmol / l ; reference value : 1.16 to 1.32
injection phenytoin ( 5 mg / kg / day ) and injection phenobarbital ( 5 mg / kg / day ) intravenously were given for five days and tablet clobazam ( 0.75 mg / kg / day ) was given for three days to control seizures .
injection acyclovir ( 40 mg / kg / day ) and injection methyl prednisolone ( 2 mg / kg / day ) were started as empirical therapy on 5 day . from 6 day ,
syrup phenytoin ( 30 mg/5 ml ) , 4 ml , 12 hourly , and syrup phenobarbital ( 20 mg/5 ml ) , 6 ml , 12 hourly , were started after stopping injectable anti - seizure drugs .
on the 8 day , patient developed involuntary , continuous , uncontrolled , jerky movements of head and upper limbs , which was diagnosed as chorea .
there was no family history of hd and diagnosis of viral encephalitis was not confirmed so it was suspected as drug induced chorea with phenytoin being an offending agent .
patient was having an attack of convulsions two days after stopping phenytoin ; hence , sodium valproate ( 15 mg / kg / day ) was added to treatment .
naranjo 's scale showed that the relationship between phenytoin and chorea was probable . according to modified schumock and thornton 's criteria ,
this reaction was probably preventable and modified hartwig and siegel 's scale showed that the reaction was moderately severe ( level 3 ) .
chorea and hyperkinetic movements are the rare side effects of phenytoin . in this case ,
recovery on de - challenging the phenytoin therapy and normal laboratory investigations are in favor of diagnosis of the phenytoin induced chorea .
normal ct - scan report after emergence of reaction has ruled out any structural damage to basal ganglia .
involuntary movements caused by phenytoin are mainly related to its high plasma concentration ( 40 - 50
prolonged phenytoin therapy or its high plasma concentration is related with increased dopaminergic and serotonergic activity in basal ganglia that may be considered as a cause of chorea .
phenytoin toxicity depends on the route of administration , duration , exposure , drug interaction , and dosage .
drugs that alter the functions of these enzymes can place the patient at risk of toxicity .
addition of clobazam to the patients who had been taking maximum tolerable dose of phenytoin is reported to result in its intoxication .
though , both are enzyme inducers , they may increase plasma concentration of each other by competitive inhibition of their metabolism .
acyclovir decreases plasma concentration of phenytoin due to interference in absorption . in our case ,
acyclovir was started parentrally on 5 day and is less likely to affect the plasma level of phenytoin .
use of phenytoin along with clobazam and phenobarbital may have resulted in increased plasma concentration of phenytoin due to an interaction between them which may have caused the reaction .
combined use of phenytoin and lamotrigine has been reported to cause the hyperkinetic movement disorder .
a possible interaction between phenytoin , phenobarbital and clobazam may have resulted in chorea in this case .
it is important that therapeutic drug monitoring should be done and drug interactions should be kept in mind especially when two or more anti - seizure drugs are prescribed .
early detection and withdrawal of suspected drug in such cases can help to prevent further harm to the patient .
 a 3-year - old female patient developed chorea possibly due to an interaction between phenytoin , phenobarbital and clobazam used for generalized tonic clonic seizures . 
 phenytoin withdrawal resulted in recovery within 24 hours . 
 post reaction computerized tomography ( ct)-scan of brain was normal . 
 combined use of anti - seizure drugs and interactions between them may be responsible for the reaction . 
 therapeutic drug monitoring is important while prescribing two or more anti - seizure drugs . 
Introduction
Case Report
Discussion