Frontal lobe epilepsy (FLE) can be defined as a condition
that is characterized by recurrent seizures arising from the frontal lobes of
brain. Generally, frontal lobe seizure could be simple partial or complex
partial, often with secondary generalization. In frontal lobe epilepsy,the
origin of seizures may be from any of the frontal lobe areas, including
frontopolar, orbitofrontal, opercular, dorsolateral, supplementary motor area,
cingulate gyrus or motor cortex.
Major causes that can lead to frontal lobe seizures could be
encephalitis, tumors, frontal lobe lesions, certain birth defects, head trauma,
birth defects and certain genetic diseases like an autosomal dominant disease
i.e Autosomal Dominant Nocturnal Frontal Lobe
Age of onset was variable from 10 months to 16 years (mean 7.5
years).The seizures are brief (often < 30 seconds to 2 minutes),
stereotypic, nocturnal, and frequent . Frontal lobe seizures
are also termed as "complex partial seizures frontal lobe type," "frontal lobe seizures with hypermotor
automatisms," "frontal lobe seizures with frenetic automatisms,"
"frontal lobe seizures with agitated behavior," or "seizures
with hyperactive automatisms". They were also termed “hyperkinetic
seizures” or “focal motor seizures with hyperkinetic automatisms” in certain
According to the latest
report of the ILAE Commission on Classification and
Terminology, frontal lobe seizures are classified as “focal seizures” with further
descriptors such as “with or without impairment of consciousness” or “with or
without observable motor components”.
In the US in most centers frontal lobe epilepsy accounts for 20-30% of
operative procedures involving intractable epilepsy. 
Approximately 456,000 people in the UK have epilepsy
(based on 2003 census and a total UK population of 59,554,000) In the UK the annual incidence is approximately 46
per 100,000 or 0.46 cases per 1,000 of population. Epilepsy affects around 50
million people worldwide, 80 per cent of them are in developing countries. In
these countries, although most cases can be treated, around 90 per cent of
people with epilepsy are not receiving appropriate treatment. 
Epilepsy is a relatively common disorder in Pakistan. Based
on current data, it is estimated that 1.38 million people suffer from epilepsy
in the country.  In general population, prevalence of epilepsy is estimated
to be 9.99 per thousand. Highest prevalence is
seen in people younger than 30 years of age. A slight decrease in prevalence is
noted between the ages of 40 and 59. Higher prevalence is observed in
rural population. Etiology of epilepsy is more commonly identified in
pediatric population. Epilepsy was considered idiopathic in 21 to 76% cases. Only
27.5% epileptic persons in urban areas and 1.9% in the rural areas were treated
with AEDs (anti epileptic drugs). 
A 2 year old child (boy), Nazeer-ud-din was
presented in the pediatric ward of private hospital, Islamabad, Pakistan on 7th
October 2011 with the chief complaint of fever and seizures. He had a history
of left sided focal fits for past 2 months. According to his family history
nobody in his family had epilepsy or diabetes mellitus, though his grandmother
was a patient of hypertension. He had no allergy. His thorough physical examination
depicted HR 136/min, RR 36/min, weight
of 12 Kg, 101 °F temperature, pulse
110/min, pallor skin, pallor eye that
were reactive to light but decrease response and focal seizure on left side of
body that lasted for not more than 30 seconds.
Patient was keenly observed and monitored to see
whether seizures are epileptic or non epileptic. Patient EEG (Electroencephalography) was conducted. It was diagnosed that child was suffering from
frontal lobe epilepsy, and the seizure were simple partial seizures or febrile
focal seizures. Major cause of seizures was reported to be encephalitis. On basis of present illness and primary
diagnosis physician prescribed him ceftriaxone 100mg/Kg/day;
acyclovir 100mg/Kg/day; Panadol suspension (
Paracetamol) 120mg/5ml/4hrs; phenytoin 180 mg diluted in 100cc Normal Saline
over 1 hr as a loading dose; phenobarbitone
200mg diluted in 100cc Normal Saline over 1/2 hrs.
Therapy was initiated with ceftriaxone 100mg/Kg/day;
acyclovir 100mg/Kg/day; Panadol suspension ( Paracetamol) 120mg/5ml/4hrs and
phenytoin 180 mg diluted in 100cc Normal Saline over 1 hr as a loading dose.
Encephalography was done; the result was consistent with left sided focal
seizures. CT scan showed a subtle region of increased density in left parietal
On the 2nd day of therapy, vital signs
showed fever of HR 138/min, RR 37/min,
pulse 110/min, and 100 °F temperature. From 2nd
day of therapy, maintenance doses (24h after load): 6 mg/kg IV in
divided doses q8 to 12h of phenytoin was given to patient.
On the 3rd day child did not had fever and
vital signs showed HR 121/min, RR
36/min, pulse 108/min, and 98 °F temperature, thus
panadol suspension ( Paracetamol) was discontinued.
day of therapy ceftriaxone was discontinued, after bacterial culture tests
showed negative result. Therapy was continued with acyclovir 100mg/Kg/day; and
phenytoin 180 mg diluted in 100cc Normal Saline over 1 hr as a loading dose
until the 12th day of therapy when phenytoin was discontinued and
replaced by phenobarbitone 200mg diluted in 100cc Normal Saline over 1/2 hrs
loading dose, 18-24 hrs after the loading dose patient was given oral
maintainence doses of 3mg/kg/day in divided doses of Phenobarbital elixer (20mg
per 5ml). The therapy continued till 14th day, and acyclovir was
discontinued after the EEG and CT scan were normal and patient was discharged
from the hospital. Child parents were told to continue Phenobarbital syrup for
up to 2 weeks.
Aciclovir was prescribed to treat encephalitis;
the primary cause of seizure, ceftriaxone was given for presumed bacterial
meningitis. Paracetamol was prescribed to treat high grade fever of child, as
it is antipyretic. Phenytoin and Phenobarbital were prescribed to deal with seizures.
doses of ceftioxone for children is 50mg/kg daily by IV infusion, but the
prescribed dose is 100 mg/kg/day i.e double the dose recommended. According to
BNF IV infusion dose of acyclovir dose in children is 5mg/kg after every 8 hrs,
so in 24 hrs the recommended dose is 15mg/kg, but the prescribed dose of
acyclovir is 10mg/kg/day. Phenytoin and paracetamol doses prescribed are
according to the recommended doses. Phenobarbital loading dose prescribed was
200mg diluted in 100cc Normal Saline, it is higher
than the recommended loading dose i.e 180mg diluted in 100cc Normal Saline.
The prescribed drug
regimen showed number of drug interactions. Drug- drug interactions in the
regimen and their appropriate management are given as follows:
Amltava et al.,  reported an in vitro
and in vivo displacement of phenytoin by ceftriaxone has been observed. Increased
displacement of phenytoin will result in increased free phenytoin plasma
levels. Thus; during therapy monitoring of free phenytoin levels in patients is
required. While; Acetaminophen is metabolized in
part by cytochrome P450 (CYP) 2E1, and inducers of CYP2E1 are known to
predispose patients to acetaminophen-related hepatotoxicity.
Brackett & Phenytoin induces CYP2C and CYP3A4 isoforms,
but not CYP2E1. They suggest, however, that CYP3A4 may participate in
acetaminophen metabolism to a greater extent than previously realized, and
induction of this isoform may predispose patients to acetaminophen-induced
hepatotoxicity. Thus; interaction may be avoided by close monitoring of liver
function is recommended.
et al.,  reported that acyclovir
has potential to decrease the level of phenytoin and seizure activity may increase. Aciclovir can reduce phenytoin plasma concentrations to
subtherapeutic values. Therefore;
the dose of phenytoin should be adjusted to
Gemma et al. , reported aciclovir and ceftriaxone when given concomitantly
has potential to cause nephrotoxicity. That need close monitoring of serum
The regimen designing
(particularly in frontal lobe epilepsy) is a quite critical job and need
special attention of health care experts. Though; some time regimen seems to be
rational but in real sense that is irrational and need to be optimized by drug
experts. Thus; the pharmacists are needed to perform their actual clinical role;
patient counseling, prescription review, therapeutical drug monitoring,
documentation etc. to optimize and rationalize the therapy planes.
Sinclair DB, Wheatley M, Snyder T 2004 Mar;30(3):169-76, Frontal lobe epilepsy in childhood, http://www.ncbi.nlm.nih.gov/pubmed/15033198
2. Barbara C Jobst MD, author. Dr. Jobst of
Dartmouth Medical School and Dartmouth Hitchcock Medical Center has received
research support from Neuropace, Inc. and travel reimbursement as a lecturer
from Eisai Inc, June 17, 2003, Frontal
lobe seizures http://www.medlink.com/medlinkcontent.asp
Program Director, Assistant Professor, Departments of Clinical Neurology
and Neurophysiology, Montefiore Medical Center, Albert Einstein College of
eMedicine Journal, March 1 2002, Volume 3, Number 3,
Frontal lobe epilepsy.
Prevalence, Incidence and other statistics, Joint Epilepsy Council August
Mughis Sheerani (Section of
Neurology, Department of Medicine, Aga Khan University Hospital, Karachi) ,Development of a Comprehensive Epilepsy Surgery Programme
in Pakistan, http://www.jpma.org.pk/full_article_text.php?article_id=552
A. Khatri,S. T. Iannaccone ( Departments
ofNeurology, Texas Scottish Rite Hospital for Children, Dallas, TX, USA) ,M. S.
Ilyas ( and Dow Medical College and Civil Hospital ) ,M.
Abdullah ( Dow Medical College and Civil Hospital ) ,S.
Saleem ( Department of Community Health Sciences, Aga Khan
University, Karachi. ) ,
Epidemiology of Epilepsy in Pakistan: review of literature. http://www.jpma.org.pk/full_article_text.php?article_id=1321
Dasgupta, David A. Dennen,Roger Dean, and Ronald W. McLawhon, CLIN. CHEM.37/1,
98-100 (1991)Displacement of phenytoin from serum protein carriers by
antibiotics: studies with ceftriaxone, nafcillin, and sulfamethoxazole, http://www.clinchem.org/cgi/reprint/37/1/98.pdf
Brackett CC, Bloch JD. Division of Pharmacy Practice and Administration, College of Pharmacy,
The Ohio State University, Columbus 43210, USA. Pharmacotherapy. 2000 Feb;20(2):229-33.Phenytoin as a possible cause of acetaminophen
hepatotoxicity: case report and review of the literature.
Parmeggiani A, Riva R, Posar A, Rossi PG. Department of Child Neurology and Psychiatry, University of Bologna,
Bologna, Italy. Ther
Drug Monit. 1995 Jun;17(3):312 Possible interaction between acyclovir and antiepileptic treatment.
Robb and Guido
Filler, Volume 17, Number 8, , DOI: 10.1007/s00467-002-0867-5 Combination of ceftriaxone and acyclovir - an
underestimated nephrotoxic potential?) http://www.springerlink.com/content/m2t2ghmtla0fj7u7/