EFFICACY OF COMBINED THERAPY VAL
EFFICACY OF COMBINED THERAPY
VALPROATE AND LACOSAMIDE IN RESISTANT EPILEPTIC CHILD WITH CEREBRAL PALSY-ACASE
Jai Singh Yadav* Samiksha Kaur**
Asst. Prof. IMS BHU,*Psychologist
An 11 year female child has history of cerebral palsy. She was not able
to care herself. She had history of seizure, when she was 3 years old that was
subsided with taken treatment. Three year back she again developed seizure, the
frequency of seizure and motor functioning were worsen, despite of taken
treatment, some times she felt into status epilepticus, therefore, she received
higher doses of antiepileptic in farm of single, as well as combination AEDs,
but in both condition she not improved. The symptoms of spasticity in whole
body was increased so much that often she felt on ground. When she brought to
OPD she was receiving 1500 mg diproex, 200mg lamotrgine, 200mg topiramate. She
was delirious, seizure frequently used to occur at half hours of interval.
Patient was admitted and hematological as well as biochemical examination find
normal, MRI of brain shown callosal agenesis and cerebral dysplasia. She was
rated on Barry-Albright Dystonia Scale (BADS). Result-The severity of
dystonia on BADS scale scores was 27, all AEDs were stopped and after
mamagement of GC the doses of valproate and lacosamide gradually increases up
1000mg/day and 200mg/day simultaneously. After 6 months of management her
seizures reduction was 95%and BADS score improved.
combination of valproate and Lacosamide were more effective than other AEDs in
children with seizure of callosal agenesis.
Key Words:- cerebral palsy, callosal agenesis
and cerebral dysplasia, Resistant epilepsy
Children with functionally compromised brain are special group of
children those needs special medical support along with seizure management.
These group also more venerable to tolerate the drug side effects and easily
develops serious problem. In compromised brain where cerebral perfusion is decreased
causes hypoxia and hypoglycemia those leads to critical shortage of energy in
respective area of nerve cells. The patients those taking treatment for
seizures prevention, neurons use up glucose and oxygen faster than they are
supplied, and discharge glutamate. Glutamate is the most common excitatory
neurotransmitter. In small amounts, it is indispensable for neuronal function.
In excessive amounts, it is a neuronal poison, a toxin, and has been called
excitotoxin. Some glutamate receptors are non-selective cation-permeable ion
channels. Initially, over-activation of these channels causes a passive influx
of Cl- (and Na+) into cells causing osmotic (cytotoxic) edema and rapid death.Therefore choice of any AED needs more precaution, especially in
children those having co morbid problem of resistant seizure. These children
mainly show poor academic, social development and failure of thrive. In attempt
to control resistant seizures of many cases, we are bound to increase dose or
prescribe add-on therapy, but there are certain stages where these practice of
increasing doses of AEDs became less effective and child developed serious side
effects. Therefore there are hopes on new AEDs in these among the AED drugs lacosamide is effective in seizure
reduction as adjunctive therapy in patients with uncontrolled partial-onset
seizures.1,2 Lacosamide may also prevent the formation of
inappropriate neuronal connections by binding to the collapsin response
mediator protein-2, a modulator of axon development. In randomized,
double-blind, placebo-controlled clinical trials of adult patients with
uncontrolled partial-onset seizures with or without secondary generalization,
the addition of lacosamide to other AEDs produced significantly greater
reduction in seizure frequency than placebo.3-5 Lacosamide (LCM) is
approved as adjunctive therapy in 17 years and older for partial onset
seizures. Little is known about the use of LCM in children. Case studies
suggest that LCM may benefit children who have failed to respond to previous
antiepileptic drugs (AEDs). Lacosamide
should be used with extreme caution in children younger than 17 years old;
safety and effectiveness in these children have not been confirmed.
An 11 year female child
brought to OPD, she has history of seizure four to five times/day since three
years. She was receiving combination of AEDs (1500 mg diproex, 200mg lamotrgine, 200mg
topiramate).Last three days the general conditions of patient got worsened she
has repeated seizures of half hour interval, she was delirious and not able to
support herself. She borned difficult delivery life support was given after
birth. The mild stone were delayed she started supporting herself after three
years and speech developed monosyllabic in six year. She not sends to school
because she needs assistance for her routine activities. She developed seizure
when she was three year old but recovered fully after taken treatment. She
again developed seizure at age of eight year, for this episode she received
mono as well as combinations of AEDs, but despite of effort general conditions
deteriorated and body tone increases along increase in seizure frequency. When
she became delirious she brought to OPD and got admitted.
Management and Procedure
After admission her systemic
examination serological and hematological examination were done and found
within normal limit, MRI finding shown callosal agenesis with cerebral
dysplasia. All AEDs
stopped, her general conditions were managed and in between if she had any
seizure that was managed with giving parentrel valproate.The dose of valproate
again maintained upto 1000mg/day. She was applied Albright Dystonia Scale (BADS) for measurement of dystonia.
The attaindents of patient were given a check diary for seizues. The severity of dystonia on BADS
scale scores was 27, the doses of lamotrigine and topiramate were gradually
tapered and simultaneously the dose of lacosamide gradually increases up 200mg
within 2 weeks, during the period her general condition were managed
conservatively. Evaluation of patient done at one, three, and
six months intervals CGI scores were 45%, 60%,65%respectively,
BADS rating scores on decreases 60%. The seizure frequency decreases up to 95%
at end of six month.
Seizures are commonly associated
with poor development of brain, because in many times physiologically and
anatomically compromised area of brain have poor blood and nutritional supply.
Repeated seizure leads to excessive glutamate and lactic acid in those areas,
these substances further enhance the seizure frequency. Children are less
tolerated to side effects of many AEDs, in such condition if a higher dose of
one drug combines with other AEDs, the chance of side effect increases more
than beneficial. In our case the probability of previously given all AEDs acts
through similar receptor in prevention of seizure and their interaction causes
more side effects. In our case region of less side effects can be action of LCM
and its non interaction with other combined AED valproate. The response rate of
antiepileptic was 95% and due to reductions in spasticity beneficial effect
find in improvements of general condition. Similar action with LCM was also
noticed by Maschio.etal1 in 14 patients with BTRE(brain
tumor-related epilepsy) The mean duration of follow up was 5.4 months (min <
1 max 10 months). Mean seizure number in the last month prior to the
introduction of LCM had been 15.4. At last follow-up, the mean seizure number
was reduced to 1.9/month. Lacosamide mean dosage was of 332.1 mg/day (min 100
max 400 mg/day), responder rate was 78.6%. But ours study differ as patient has
compromised brain functions as well as spastic symptoms which worsened due to
repeated seizure there fore we bound to add new AED lacosamide.
The combination of valproate and
Lacosamide were more effective than other
AEDs in children with seizure of callosal
M.Maschio et al; Lacosamide as add-on
in brain tumor-related epilepsy: preliminary report on efficacy and
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Newton HB,ComnellyJ, et al.
Lacosamide in brain tumour patients with refractory seizure: efficacy and
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Ben Menachem E, Biston V, jatuzis D, abou khalil B,
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P. Lacosamide for the prevention of partial onset seizures in epileptic adults.
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Chung S, Sperling
MR, Biton V, et al; SP754 Study Group. Lacosamide as
adjunctive therapy for partial-onset seizures: a randomized controlled
trial. Epilepsia 2010; 51(6):958-67.
Kelemen A, Halasz
P. Lacosamide for the prevention of partial onset
seizures in epileptic adults. Neuropsychiatric Dis Treat 2010; 6:465-71.