Choice of Anti epileptic drugs:
Type Clinical features Effective drug half life therpeutic
(h) blood level
(mcg/ml)
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Partial(focal):
Focal motor or sen- Valproic acid 12 50 to 100
Simple partial sory disturbances Carbamazepine 12 4 to 10
conciousness not Phenytoin 24 10 to 20
impaired.
Complex parti- Bizarre behaviour As mentioned
al. and impaired con- above.
ciousness;auras
prominent.
Generalized:
Absence Brief loss of con- Valproic acid
ciousness,staring Ethosuximide 55 50 to 100
little or no motor
activity.
Myoclonic Isolated clonic jerks Valproic acid
often evoked by a
sensory stimulus.
Continual :
Status epilep Continual seizure Diazepam
ticus. activity Phenytoin
Carbamazepine
Valproic acid.
Treatment of chronic epilepsy is ideally with a single drug determined principally by the classification of the seizure disorders. Valproic acid(VPA) may be the preferable drug in the initial treatment of most forms of epilepsy.Only after failure of single drug therapy is combination therapy likely to be considered.
The need to treat a patient after a single seizure is controversial. The likelihood of a recurrent seizure is about 50% during the first three years with the greatest incidence during the first six months.
For this reason there may be some logic in treating for six months after an initial seizure. Conversely most agree that gradual withdrawal of anticonvulsant therapy is a considera
tion,when seizure activity has been controlled for sustained
period often two years.
There is an increased risk of congenital malformation in the infant of a mother who conceives during anti convulsant drugs therapy, A surgical procedure such as cortical resection and transection of the anterior of the corpus callosum may be considered in the patient who is resistant to control with anticonvulsant therapy.
The use of positron emission tomography to measure brain glucose metabolism may be helpful in preoperative localization of the epileptogenic foci.
Pharmacologic of Anti Epileptic Drugs(AEDs):(2,3)
At the time in hospital preoperative assessment,anti epileptic medication may be accutely changed either to increase and optimize drug treatment, to evaluate the response of the seizure activity to new drugs or to facilitate
observation of vital and interictal activity consecutive to drug withdrawal.
Most AEDs are metabolized by oxidative enzymes in the hepatocytes.
Elevation of liver enzymes has been reporting in 5% to 10%, but these changes are rarely of clinical significance.
Carbamazepine(CBZ),phenytoin,valproic acid (VPA) and phenobarbital are all effective in reducing,the frequency of partial seizures. Phenobarbital however is used a second line drug in most cases, since it tends to cause sedation and depression in adults and hyperactivity and aggression in
children.
CBZ is effective for the treatment of partial and generali
zed tonic clonic seizures and the drug can cause a range of idiosyncratic reactions,the most common being a morbili
form rash,which develop in about 10% of patients.
Mild lekopenea is common but blood dyscrasia and toxic hepatitis are rare.
At high plasma conentration,CBZ has an antidiuretic like action and the resulting hyponatremia is usually mild and asymptomatic.
CBZ can accelerate the hepatic oxidation and conjugation of other lipid soluble drugs.The metabolism of VPA,cortico
steroid,anticoagulant and antipsychotic drugs,non depoli
zing muscle relaxant and opioids is increased.
Drugs that inhibit the metabolism of CBZ sufficiently to cause toxic effects :
include,cimetidine,propoxyphen,erythromycine,isoniazid,diltiazem and verapamil.
Phenytoin :(PHT)
It is effective for the treatment of partial and tonic clonic seizures and can cause a range of dose related and idiosyn
cratic adverse effects. Reversible cosmetic changes (gum hypertrophy,acne,hirsutism,facial coarsening) although often mild,can be trouble some.
Neurotoxic symptom(drowsiness,dysarthria,tremor,ataxia,
cognitive difficulties) become increasingly likely when the plasma drugs concentration exceeds 20 mcg/ml.PHT can induce the oxidative metabolism of many lipid soluble drugs including VPA,anticoagulant agents,corticosteroids,opioids and cyclosporine. PHT induces the metabolism of CBZ,CBZ inhibits the metabolism of PHT. Thus adding PHT decreases plasma CBZ concentration by about one third, whereas plasma adding CBZ increases plasma PHT concentration by a similar amount.
A similar effect on VPA has been reported.
Theophylline half life is reduced in the presence of PHT and patients may require an upward adjusment of their doses.
Drugs that inhibit the metabolism of PHT include amioda
rone,cimetidine,some sulfonamides (sulfadiazine,sulfa methiazole,sulfa phenazole).
PHT affects pituitary and adrenal function by induction of P450 hepatic enzyme which resultant accentuation of endo
genous hormon metabolism.
Accelerated metabolism of exogenously administered steroid hormones may occur as well.
Hypothalamic function can be affected with altered release of anti diuretic hormone(ADH).
Valproic acid(VPA):
VPA is effective in patients with all type of seizures especially in those with idiopathic generalized epilepsy.
Common side effects of VPA are dose related tremor,weight gain due to appetite stimulation,thinning or loss of hair and menstrual irregularities.
The incidence of hepatotoxic effects is less than 1 in 20.000
Approximately 20% of all patients receiving the drug have hyperammonemia without hepatic damage.
VPA is potent inhibitor of hepatic metabolic process,inclu
ding oxydation,conjugation and epoxidation and this may affect PHT,CBZ, and phenobarbital(PB).
Aspirin displace VPA from its binding,sites on plasma protein and inhibits its metabolism. It has been suggested that VPA might increase surgical bleeding due to quantitative throm
bocytopressive and functional defects in platelet aggrega
tion. VPA may also decrease plasma coagulation factors. Consequently many epilepsy centers discontinue VPA preoperatively.
Phenobarbital (PB):
PB abolishes partial and generalized tonic clonic seizures.
PB can cause fatigue,isomnia,hyperactivity and aggressively in children.
PB is among the best examples of enzyme inducer and it will accelerate the metabolism of many lipid soluble drugs including PHT.
IMAGING STUDIES :(3)
As part of the initial evaluation of the patient with seizures ,an imaging study is often waranted. If clear etiology for a seizure is present such as with hypoglycaemia or an electrolyte disturbance, no futher evaluation may be
necessary. However, in the patient with no obvious cause for a seizure or with accompanying neurologic findings further investigation of intracranial causes of seizure is often informative.
In acute evaluation of seizures of undetermined etiology,a CT scan may be used with great efficacy to examine evolving or ongoing process such as neoplasms, hemorrhage, or stroke or for the detection of intracranial calcifications such as those seen in neurocutaneous syndromes.
However,for more substle manifestations of metabolic abnormalities,trauma or cerebrovascular accident,the Magnetic Resonance Imaging(MRI) is superior.In the case of less emergent evaluations of seizures,the MRI is the study
of choice to detect pathologic process affecting the hippo
campal formation or other brain regions.
Hippocampal sclerosis is easily demonstrable with high quality MRI, as are developmental anomalies of brain including holoprosencephaly,schizencephaly or lissen cephaly.MRI has proven to be a more flexible tool than CT because the ability to perform magnetic resonance spectroscopy(MRS) and functional MRI(fMRI).
MRS provide information on the distribution of Nacetylas
partate,creatinine and phosphocreatinine,indicating regions of possible neuronal loss or gliosis. FMRI involves the dyna
mic properties of blood flow in the brain during cognitive tasks,which can be evaluated in real time,allowing for re
gional mapping of brain function and the detection of regions demonstrating pathologic brain activation. Finally,single photon emission computed tomography (SPECT) and positron emission tomography(PET) hold great promise in the detailed evaluation of seizure localization. SPECT is essentially a measure of cerebral blood flow(CBF) and analysis during a seizure yields valuable data that,when considered concurrently with MRI,provide information on the site of seizure focus possible resection. PET scanning is helpful because its ability to measure various markers of interictal metabolism and is useful in the evaluation of
temporal lobe epilepsy.
Laboratory test :(3)
Unless indicated for medical problems unrelated to the epileptic condition only the very basic laboratory test will be required. These include a complete hematology count,
liver function test and plasma drug level for the AEDs.
Coagulation studies are routinely performed prior to any major neurosurgical procedure as in an EEG.
to be continued:
to be continued
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