Anesthesia For Epilepsi Surgery (PART 5)

ANESTHETIC MANAGEMENT (CONCIOUS ANALGESIA):(1,2,3)
One must be assessed the ability of an individual patient to tolerate the procedure awake.There is significant associated discomfort and possibly pain which must be explained very clearly to the patient.
In ability to comprehend this (e.g.in mentally retarded  patients or children ) is a relative contra indication to awake craniotomy.
The upper airway should be assessed;a patient in whom 
difficulty with tracheal intubation is predicted may not be
suitable candidate for awake craniotomy because intuba-
tion sometimes is needed emergently even with the patient
in the akward position required for surgery.


Another factor is the anesthesiologist experience;local anesthesia with concious sedation should not be used without proper training.
The patient must be concious and alert while electrical stimulation is being carried out. On the day of surgery only steroid are given prior to admission to the operating suite Anxiety should be dealt with without use of pharmalogic means. Unneccessary verbal comments and noise should be kept to a minimum.The temperature in the room should be comfortable for the patient. Anesthesia equipment and medication for control of a seizure episode should be at hand. After transfer to the table patient's position them selves on the operating table so that they are as comfortable as possible.
Although they are need to be restrained, a small amount of movement should be allowed to maintain comfort throughout  this long procedure. 


The lateral position is preferred because freedom of the airway is easier to maintain.
Careful attention is paid to the protection of pressure points which should be padded.
At this time an iv lines is secured at once,an a saline infusion started at a low flowrate which will be maintained through the procedure.
To limit the discomfort of a full bladder the drip rate is a adjusted to 1 ml/kg per hour. An indwelling urinary catheter is inserted although some prefer to limit the amount of iv fluids and withhold the catheter.
Oxygen is delivered through nasal prongs while capnography can be performed via an 18-20 g Teflon catheter in one nasal prong.


Before surgical incision local anesthesia is injected subcutaneously into the scalp.Some patients dont require futher sedation at incision.
However,the painful parts of the procedure should be anticipated. They mostly occur early during surgical exposure.Using a neurolept analgesia technique has demonstrated that adequate ventilation could be maintain in such conditions.
An infusion of propofol (8mg/ml)mix with alfentanil
(50 mcg/ml) and lidocaine (2 t0 4mg/ml)is begun at 
100 to 200mcg/kg/min,reading the propofol dosage 
(alfentanil is simultaneously administered at a ratio
of 1:160 (i.e.when propofol is 80 mcg/kg,alfentanil
is 0,5 mcg/kg/min).
This dose is occasionally supplemented with bolus doses through the infusion pump to achieve sedation.
The patient has little or no response to these manouvers yet ventilated and oxygenated well.
The infusion is typically decreased to 50 to 80 mcg per kg per min propofol while the patient is unstimulated.


Trap has described in detail about concious sedation analgesia. Before the surgeon starts skin preparation and aplication of the drapes fentanyl 0,5-0,75 mcg/kg and dropridol 0,15 mg/kg are given intravenously.Immediately before the episodes the patients need reassurance and
possibly,supplementation of sedation analgesia with fentanyl 25 to 100 mcg/kg per min,titrated to maintain a comfortable level of analgesia and respiratory rate of 12 breaths/min.


More recently Rosa et all and Silbelger et all have reported similar view using propofol. A bolus of propofol (0,3 to 1 mg/kg) is used followed by a continuous infusion at 75 to 100 mcg/kg per min.


In case of insufficient sedation,supplementary boluses at 0,5 mg/kg are added and the infusion rate is gradually increased to 125 mcg/kg/min.
Small increments of fentanyl (1 mcg/kg) are injected at 3 min intervals. A minute amount of dropridol (0,015 mcg/kg) is given for prevention of nausea and vomiting. 
An appropriate level of sedation is achieved on the average within 10 minutes.


Most patients tolerate the procedure especially when the anesthesiologist has been able to established good communication and is able to predict and control painful stimulation. 
Possible complication of awake craniotomy include rest-
lessness and agitation, with a good rapport with the patient in the preoperative period and at times a change in the level of sedation will resolve this complications.


A three pin Mayfield head holder is applied after infiltration of the sites of pin placement with local anesthesia.
Not only are patients able to tolerate the head holder well, but the head remains secure even during seizure.
Craniectomy and dural stimulation sometimes require additional bolus dosing of iv anesthesia.
A fairly large craniotomy incision is usually needed, extending down to the zygoma for maximum visualization of the tip of the temporal lobe and the inferior temporal circumvolution.
Local anesthesia is achieved with a mixture of bupivacaine 0,25% and lidocaine 1,0% both with 1:200.000 epinephrine.
Optimal points of injection for scalp anesthesia include the origin of the greater and lesser occipital nerves below superior nuchal line,the auriculo temporal nerve just in front of the ear and the supraorbital nerve above the eye brow. Finally an injection made into the subctaneous tissue of the anterior temporal region will join the zygomatic are with the lateral part of the superior orbital ridge.
To optimize the homeostasis the injections must be made into the subcutaneous tissue of the scalp and not exclusively into the subgaleal region.
At least 10 to 15 ml of solution must be injected into the deep part of the temporalis muscle extending from the supraorbital ridge through to the posterior part of the zygoma.
Intracranial structures that are painful to touch and traction include the dura and meningeal vessels.
Once the dura is exposed pain sensation is blocked by intradural injection of small amounts of local anesthetic on each side of the middle meningeal artery and its mayor branches.
The patients are usually awakened before opening the dura.
The propol infusion was titrated down from its original rate so as  to maintain a grade 3 to 4 sedation score is now set to zero.


Sedation scores according Wilson et al :
Grades                              Degree of sedation
    1.                             Fully awake and oriented
    2.                             Drowsy
    3.                             Eyes closeed but rousable to   
                                    command
    4.                             Eyes closed but rousable to mild     
                                    physical stimulation.
    5.                             Eyes closed and unrousable to mild 
                                    physical stimulation.


Patients wake up and within 5 to 10 minutes, are able to speak and answer commands.
At least 30 minutes before ECoG the propofol is stopped although some anesthesiologist will wait until tha last
few minutes.
The patients usually awaken abruptly and demonstrated no lingering confusion.


Spontaneous seizures sometimes have occured in severe epileptic asleep with propofol,methohexital may be 
needed to control the seizure.
With the patient awake and the brain exposed direct cortical readings are performed.The goal of ECoG recording is to delineate the full extent of interictal epileptiform activity, Draps must be placed in a way that allows access to the face and also allows the anesthesiologist to converse with the patient.
Face and arm must be clearly visible and permit monitoring the peripheral response to cortical stimulation.


Following recording of spontaneous electrical activity the exposed cortex is stimulated to map out important neurologic areas.
Depending on the degree of surgical confidence and on the location of the planned resection only topographyc landmarks are used for identification of the central sulcus and the central area.
Stimulation of motor cortex results involuntary movements of the face and extrimities.The area representing the face and the mouth is at the inferior portion of the precentral gyrus (motor cortex) just above temporal lobe.
Although the patient is usually aware of the involuntary movements direct observation is important.


Stimulation of the post central gyrus (sensory cortex) may result in paresthesia. Tingling or prickly sensation in tongue,gums,face and extrimities. It is important to instruct the patient prior to the procedure to report any unusual feeling.
The patient may also be asked to perform certain task during stimulation.Usually the effect of stimulation on speech is evaluated during counting or reciting such familiar concepts as days of the week or months of the year.


Stimulation of speech area is signaled by an abrupt interuption in speech, which will resume immediately upon cessation of the stimulation. If localization of the seizure focus is still in doubt after cortical recording depth electrodes are positioned toward deeper structures in the vicinity of the amygdala and the hypocampus.Spontaneous activity is again recorded followed by stimulation.


Activation of epileptic activity is attempted by adminis-
tration of a 0,5mg/kg of methohexital and its effect on the ECoG is observed.
Resection is initiated after the epileptogenic focus is identified and functional areas of the exposed brain have been mapped out.


To relief anxiety and pain with unwanted side effects for instance tachycardia and hypertension,movements,the profol infusion is reinitiated and additional amounts of fentanyl administered especially when there is traction or coagulation blood vessels.
The continuous infusion of propofol during resection of an epileptogenic focus under local anesthesia has considerably facilitated the anesthetic management of procedure. If the propofol is not available,neurolept analgesia has proved to be a safe technique. Intra operative nausea and vomiting is rare with the use of propofol.
However the potential pharmacologic interference with the intraoperative ECoG tracings recently has been demonstra-
ted such as beta activity triggered by propofol.
Seizure control is occasionally necessary;methohexital (1 mg/kg) or benzodiazepine (midazolam) is effective.
At the completion of the surgery all patients are taken to the recovery room awake and responsive.


MONITORING:(3)
Non invasive monitoring is used as a rule for concious sedation analgesia. The oxygenation status of the patient is monitored with a pulse oximeter. Et CO2 is continuously sampled at the nose and the information is utilized essentially as a means to monitor respiration rate.
Non invasive blood pressure measurements are displayed every 5 minutes.
ECG tracing displayed continuously on the video screen to monitor hemodynamic parameter.
Blood loss is estimated and corrected when it approaches 20% of circulating blood volume.


COMPLICATION OF EPILEPSY SURGERY:(1,3)
General complication include acute post operative hemor-
rhage,infection and hydrocephalus.
Spesific complication may be subdivided in transient and permanent deficits which relate directly to the nature the original lesion,the location of the epileptogenic focus and the extent of the surgical removal.
During concious sedative  analgesia the intraoperative problems included convulsions,nausea and vomiting,exces-
sive sedation,tight brain and local anesrthetic toxicity.   
However as stated by Girvin,the most frequent and promi-
nent risk of epilepsy surgery is the failure to achieve the goal of the investigation and treatment.


SUMMARY :
Epilepsy is a common disease that has major effect both on individuals carrying the diagnosis and society as a whole.
Approximately 10% of  the epilepsy patient have medically intractable seizure resulting in progressive neurologic impairment.
These patients may benefit from surgical therapy which should be carried out in a medical center with well organized program consisting neurologist,neurosurgeon and anesthesiologist and experienced electro encephlographer necessary to perform prolonged electroencephaloraphy
studies and resultant neurologic procedures.
One of the most important toll for the investigation of seizures and epilepsy is the EEG.
One of the more important of these concerns is the most appropriate anesthetic approach for surgery that's wether to use general anesthesia or concious analgesia with local anesthesia.
Other disputed area include the optimal anesthetic technique, wether anesthetic induced seizure activity can cause brain damage and the appropriateness of inducing a seizure with an anesthetic drug during ECoG.
Concious sedation analgesia remains a useful technique when approaching an epiloptogenic lesion in crucial zones such as the motor and speech areas.When preoperative anatomic and electrophysiologic studies have clearly demarcated the epileptogenic zone in the non crucial area,general anesthesia can be used quite satisfactorily.


REFERENCES :
1.Johnson O Joel: Anesthesia for epilepsy surgery;Stone 
   JD,Sperry JR:The Neuroanesthesia Handbook,Mosby Year 
   Book Company,Newyork inc,1989,pp 201-9.


2.Kofke Andrew W,Tempelhoff Rene,Dasheeff Richard:
   Anesthesia for epileptic patients and for epilepsy 
   surgery;Cottrel E James,Smith S David: Anesthesia and 
   Neurosurgery ;4th edition,Mosby Company,St Louis
   London,Philadelphia, Sydney,Toronto.2001 pp.474-90


3.Dure S Lean :Seizures and epilepsy;Albin S Maurice,
   Textbook of Neuroanesthesia with Neurosurgical  and 
   Neuroscience perspectives; McGraw Hill,USA,1997.
   pp.613-17


4.Stoelting K Robert,Dierdarf F Stephes: Epilepsy Aneshesia
   and coexisting disease,3rd edit,Churchill Livingstone
   Newyork,Melbourne,1993,pp.232-4.


5.Mc Namara Brian,& Boniface J Simon:Electrophysiological 
   Monitoring of The Central Nervous System; Matta F Basil,
   Menon K David,Turner M John:Textbook of Neuroanesthe
   sia and Critical Care,Greenwich Medical Media,1st edition
   London,2000.pp.69-83


Ltd.,London,2000.pp.69-76.

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Anesthesia For Epilepsi Surgery (PART 4)

ANESTHETIC MANAGEMENT :
Based  on location and the structure of the epileptogenic 
abnormalities a variety of surgical interventions are perfor-
med under local or general anesthesia.The main disadvan-
tages using local anesthetics are the limitation in head fi-
xation the extra time involved and the availability of an
experienced neuroanesthesiologist.
But local anesthesia remains a useful technique when ap-
proaching an epileptogenic lesion in crucial zones such as 
the motor and speech areas.When preoperative anatomic 
and electrophysiologic studies have clearly demarcated 
the epileptogenic zone in the non crucial area,general 
anesthesia can be used quite satisfactorily .
Most resection are performed nowadays under general anesthesia.


General anesthesia for resection of epileptogenic structures Preanesthetic preparation :
As a rule patients arrive in the operating room unpremedi
cated.
If neither ECoG or cortical mapping is planned the patients
usual antiepileptic medication is administered early in the
morning prior to surgery and anxiety is controlled with a
short acting benzodiazepine.
The intraoperative use of eletrophysiological diagnostic 
techniques including activation precludes the using of any
sedative with anticonvulsant properties with the exception 
of patients presenting with hyperactive epileptic features
who would be at risk otherwise,the AEDs are withdrawn 
for at least 48 hr.Forty eight hours to surgery all patients 
are started on a coticosteroid regiment of hydrocortisone 
prednisone or dexamethesone to minimize brain swelling.


Epilepsy patients are likely to convulse at anytime particularly when they are off medication,a potent anti epileptic agent that can be used at immediately to abort a tonic clonic phenomenon in the short period preceding the
induction. Methohexital are prefered but sodium thiopental,
propofol or midazolam are acceptable alternatives.


Monitoring during the procedure is kept simple as the ma-
jority of patients coming for surgery are healthy except
for their neurologic dysfunction.In recent years,elevation
of the head to improve acess to deep mesial structures has
resulted in the utilization of precordial Doppler monitor
for observation of potential air embolism.But the use of 
a central venous catheter for management of air embolism
is controversial because patients usually supine or have mi-
nimal head elevation during surgery and venous air emboli
(VAE) has not been reported as a significant problem.
A CVC may be inserted but only after careful consideration 
of its risk in a given patient.
ECG automatic sphygmanometer,oxygen saturation and end tidal CO2 are standard and apnoe monitor is useful.


Positioning requires breaking the table at various angles to
improve comfort and padding exposed bodypart and atten-
tion to details(eg.eye protection ) are important.
Straps and retainers to limit movements of freeparts should
the patient awaken or develop a seizure during the procedu
re but a small amount of movement should be allowed to maintain comfort throughout this long procedure.
An unobstructed view of the patient is essential if cortical
stimulation of the motor area is planned.


A heating-cooling blanket is wrapped around the patient.
Placement of a large bore (gauge 16) iv catheter is perfor-
med in the unpremedicated awake patient while introduc-
tion of an intra arterial catheter is usually postphoned un-
til after induction.A bladder catheter is always inserted.


INDUCTION OF ANETHESIA :
Ultra short acting thio barbiturate are usually recomended
for induction.If ECoG is planned either ethomidate or metho
hexital is suitable  alternative.If ECoG is not planned an an-
ticonvulsant anethetic maintenance regiment such isoflu-
rane with or without N20 or moderate dose of opioid should
be used.Consideration in  anethetic management should be
given to the effect of long term anticonvulsant therapy that
increases the dosage requirement for opioid and muscle re-
laxant.Intubation is facilitated by the administration of neuromuscular blocking drugs. Fluctuation of heart rate and BP in response to intubation are prevented by the additional injection of iv lidocaine and opioid and/or esmolol.


After endotracheal intubation controlled ventilation with 
normocapnia because hypocapnia can produce or potentiate 
seizure activity by the decrease in mesencephalic reticular
function activity unless needed for surgical exposure,then 
initiated in a conventional way with a N20:O2 mixture and
isoflurane with concentration below 0,5 MAC are known to 
interfere minimally with electrical brain activity.
When the time comes for recording of interictal electrical 
activity and brain mapping the concentration can be rapidly reduced.At the some centers if ECoG is planned the pa-
tients should be maintain with N20-based or enflurane base
technique with added methohexital as indicated and both
isoflurane and halothane should be avoided.
When used judiciuosly,enflurane may effectively synchroni-
ze and activate an epileptogenic focus making easier to 
identify. Methohexital and alfentanil have also been used as 
activating agents.Methohexital has been used preoperative-
ly and intraoperatively and was observed in 87% cases to
cause selective activation of epileptogenic focus during acute ECoG. As little as 25 mg of methohexital was needed to induce activation.In a study comparing alfentanil and methohexital use in patients with epilepsy,alfentanil more riably provoked epileptiform discharge.
From the outset analgesia is provided using any
one of the potent narcotic agent such fentanyl. Alfentanil 
sufentanil appears are effectively during anesthesia.
Continuous infusion has the potential for maintaining analgesia at constant level throughout the procedure and is
taught to optimize any total iv anesthesia technique.
Intermittent administration of drugs on the contrary will result in variable plasma drug levels overtime with larger to total doses utilized ultimately. 
Indeed,however as observed during procedures under local 
anesthesia the largest part of the surgical procedure is painless with painful episodes restricted to the incision of the extracranial tissue,the exposure of brain and the final sutures at the end of the procedure.


For the first 30 minutes the total sufentanil dose average 5.0 to 7,5 mcg/kg,if moderate hypotension and bradycardia observed may be compensated by the rapid administration of iv fluids,vagolytic drugs (atropine or glycopyrolate) 
and vasopressors (ephedrine or phenylephrine).


An alternative technique for maintaining an adequate level of anesthesia is continuous propofol administration with
or without N20.Whatever the methode that elected consideration should be given to the effect of all agents on the ECoG and the spontaneous or activated epileptogenic patterns. If cortical stimulation and mapping are planned only intermediate or short acting of muscle relaxants are used during the first part of the procedure and are deliberately held to allow for observation of the peripheral muscle responses.A return of better than 90% of the strenght of the musculus adductor policis as estimated with
a TOF technique is usually needed.


Intraoperatively the prerolandic motor area is identified by
direct stimulation of the non paralyzed patients. 
The absence of muscular paralyses deemed necessary to optimize the motor response to cortical stimulation of motor strip combined with a very light level of anesthesia to avoid interference with the ECoG represent of a state of inadequate anesthesia. As a result patients then wake up and at times attempt to move. In sometimes verbal reassurance may succeed in controlling the patients but it is often necessary to resort at once to pharmaclogic means of control.
A few patients may,as a response to stimulation procced 
with focal seizures that may progress to full tonic clonic 
convulsions. The early administration of an appropriate do-
se of barbiturate (methohexital or penthotal) or propofol 
will help abort a full fledged seizure.
As reported that non depolarizing muscle relaxant and steroids which frequently used at the time of neurosurgical procedures will also shorten the duration of action of muscle relaxant. 


Craniotomy for epilepsy surgery are long procedure and re-
quire a large exposure of the brain and these factors should 
result in higher than average incidence of bleeding.
A cautious and unhurried approach throughout the procedure will minimize blood loss.As an additional benefit the vasoconstricting resulting from infiltration with 1:200.000 epinephrine solution limits the volume blood loss at opening.


More commonly patients experience nausea or vomiting 
may be exacerbated by surgical stimulation, such as stripping of dura or temporal lobe or meningeal vessel manipulation or by unsufficient analgesia combined with hypovolemia.
Dropridol is used for its antiemetic properties.
In the small amount the drug has no effect on ECoG.While
the control of vomiting and nausea extends over many hours
Other anti emetic agents are not used although ondansetron  
appears to be a valid alternative.Metoclopramide is contra indicated in epilepsies.


After the complete removal of the epileptogenic tissue,the
AEDs level is restored.Phenytoin 15mg/kg is administered 
intraoperatively.
Emergence after craniotomy for seizure surgery involves 
prevention of post operative hypertension ,facilitation of
rapid emergences and prevention of excessive coughing.
In planning for the completion of the procedure the some
times dramatic antiepileptic induce decrease in the duration of neuromuscular blocking agents and opioid drugs should be anticipated.


POST ANESTHETIC MANAGEMENT :
In the PARU vital signs and neulogic responses are closely 
monitored for the next 12 h.Hypotension is corrected with
fluid administration and if indicated (Ht below 25%) with
blood replacement.Ephedrine and phenylephrine are rarely
indicated,Severe hypertension and tachycardia are treated 
witha beta blocker(esmolol) or combined alpha and beta
blocker(labetalol). Moderate hypertension is frequently related to agitation and sometimes to pain and appropriate 
measures should be considered for correction.
Bradycardia is managed with vagolytic agents.
At times abnormal movements of dystonic or myoclonic nature,uni or bilateral,as well as other abnormal neurologic
symptoms (hypo or hyperreflexia,disconjugated eye movement,tremor) or shivering may be confused with post surgical seizure activity.Small amount of propofol,large enough to give sedation without interference with spontaneous respiration.With doses 25 mcg/kg per min,patient remain alert and answer questions,they become sedated.


Corticosteroid treatment initiated prior to surgery is pursued for a few days.Histamine H2 antagonist are commenly given along with the steroid.
As the occurence of early post operative seizures may be re-
lated to variations in the AEDs level,it look wise to follow 
plasma levels closely during the first week.

to be continued:






to be continued

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Anesthesi For Epilepsi Surgery (PART 3)

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Choice of Anti epileptic drugs:
Type             Clinical features             Effective drug       half life    therpeutic
                                                                                       (h)        blood level
                                                                                                     (mcg/ml)
==================================================
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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