Romanian Journal of Oral Rehabilitation

Vol. 6, No. 2, April - June 2014

PERIODONTAL MANIFESTATIONS IN THE DRUG THERAPY OF

EPILEPTIC SYNDROMES
Liliana Păsărin1, Sorina Solomon1, Cătălina Dănilă1, Silvia Teslaru1, Irina Ursărescu1*,
Nicoleta Ioanid2, Silvia Mârţu1
1
“Grigore T. Popa" University of Medicine and Pharmacy - Iași, Romania, Faculty of Dentistry,
Department of Periodontology
2
“Grigore T. Popa" University of Medicine and Pharmacy - Iași, Romania, Faculty of Dentistry,
Department of Prosthetics

*Corresponding author: Irina Ursărescu, PhD Student

“Grigore T. Popa" University of Medicine and Pharmacy
Iași, Romania
e-mail: irina_ursarescu@yahoo.com

ABSTRACT
The anti-convulsivant drug therapy represents a risk factor for the periodontal impairments in patients with
epileptic syndromes. Aim of the study We proposed an evaluation of the periodontal changes in epileptic
patients, correlated to the systemic alterations induced by the disease and to the drug intake. Material and
methods We examined the periodontal status on a number of 58 patients with epilepsy; the data regarding the
seizure type, drug therapy and periodontal changes were registered and statistically analyzed. Results A high
percentage of patients followed mono-therapy; from these patients, 69.04% presented periodontal changes.
Phenytoin determined the most frequent and severe forms of gingival overgrowth. Discussions We observed a
high percentage of periodontal lesions, determined by a complex mixture of risk factors (local risk factors,
associated to the anti-epileptic systemic medication). The periodontal impairment was directly proportional to
the disease and drug history (as period of time). Conclusions The anti-epileptic drug regime determines
significant changes in the periodontal tissues. The anti-epileptic drugs are an important systemic risk factor
but, still, the bacterial plaque quantity and quality remains the main determinant factor for the various forms
of periodontal disease.

Keywords: epilepsy, anti-epileptic therapy, gingival overgrowth, risk factors

INTRODUCTION dramatic convulsive activity, with or without

Epilepsy is the most common chronic
neurological disorder in humans [1]. The
prevalence of epilepsy in developed countries
reaches approximately 1%, rising to 2% in
less developed nations [2]. Epilepsy is a
condition in which a person has recurrent
seizures due to a chronic underlying process.
A seizure is a paroxysmal event, due to
abnormal central nervous system activity, that
can have various manifestations ranging from
loss of consciousness, to phenomena not
discernible by an observer [3]. Currently
available anti-epileptic drugs act by
depressing the neuronal activity in the focus
of origin or by blocking the spreading
mechanisms.
According to their mechanism of action
this wide group of drugs is classified as:
1 Drugs that block the maintenance of
high frequency repetitive discharges

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Vol. 6, No. 2, April - June 2014
(phenytoin, carbamazepine, sodium valproate,
lamotrigine);
2 Drugs that increase the inhibitory
activity induced by GABA (sodium valproate,
vigabatrin, progabide, benzodiazepines,
phenobarbital);
3 Drugs that alter the calcium channels
(phenytoin, phenobarbital, benzodiazepines)
[4].
Gingival enlargement or overgrowth has
been associated with multiple factors
including inflammation, adverse drug effects,
and neoplastic conditions [5]. Chronic
inflammation due to accumulation of dental
plaque frequently causes gingival overgrowth
[6]. Gingival enlargement is one of the most
frequent and troublesome adverse effects
associated with the administration of
phenytoin. Since 1939, when gingival
enlargement was first described by Kimball
[7], other authors have reported the
overgrowth associated with Phenobarbital
(phenobarbitone) [8, 9], valproic acid
(sodium valproate) [10] and vigabatrin [11].
Phenytoin remains as one of the most
commonly prescribed medications to treat
epilepsy and it may also be used in cases of
neuralgias and cardiac arrhythmias [12]. It is
estimated that about 30 to 50% of patients
taking phenytoin develop significant gingival
alterations [13].
To date several studies have tried to
determine the pathogenesis of drug-induced
GO but the mechanisms that trigger such
condition are not fully elucidated.
Clinically, gingival enlargement begins in
the interdental papillae, which increase and
coalesce [14]. Tissue appearance may range
from a normal aspect to a hyperemic state.
Growth is slow but in more severe cases it
may go so far as to cover the whole tooth
crown. Few cases of gingival overgrowth
have also been reported in edentulous patients
[15] and around deciduous teeth [16].
Likewise, there were some reports of GO in
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areas of dental implants in patients taking
phenytoin [17].
Microscopic analysis of gingival biopsies
reveals a redundant tissue of apparently
regular composition or with an increased
amount of collagen and number of
fibroblasts. Frequently, the overlying surface
epithelium presents rete pegs elongating into
the underlying lamina propria [14]. The level
of inflammatory cell infiltrate varies
significantly.
Many studies correlate the dose of
phenytoin with the severity of the gingival
overgrowth. Some works suggest a possible
positive relationship once the reduction in the
prescribed phenytoin dose results in
improvement of PGO severity [12]. Other
evidence is that patients who present more
extensive gingival lesions exhibit higher
serum levels of phenytoin when compared to
those without overgrowths [18].
Pathogenesis of gingival overgrowths
involves a decrease in collagen degradation
which is related to alterations in calcium
metabolism, levels of MMPs and TIMPs,
integrins expression and fibroblast apoptosis.
Not all patients taking phenytoin develop
PGO. Evidence suggests that genetic factors
also might have a significant role in the
pathogenesis of PGO and in the patient’s
susceptibility to this unwanted effect. A
genetic predisposition could influence a
variety of factors in the drugplaque-induced
inflammation. These include gingival
fibroblast functional heterogeneity,
collagenolytic activity, drug metabolism and
collagen synthesis [19].
AIM OF THE STUDY
We proposed an evaluation of the
periodontal changes in epileptic patients with
various types of seizures, correlated to the
systemic alterations induced by the disease
and to the drug intake.
 Romanian Journal of Oral Rehabilitation
Vol. 6, No. 2, April - June 2014

MATERIAL AND METHODS bleeding, hypertrophy/hyperplasia, gingival

The study was conducted on 58 patients,
examined and treated in the Neurology Clinic
of the Neurosurgery Hospital Iasi, presenting
various forms of epilepsy, for a period of time
ranging between a few months to a few years.
The methodology of the present study
followed the international standard and the
principles of the Helsinki Declaration. Every
patient was informed regarding the nature of
the study, a signed informed consent being
obtained from every subject.
The data regarding the demographic
conditions, the neurological assessment and
the dug protocol were obtained from the
clinical charts of the patients. On every
patient a rigorous clinical examination was
conducted, including the periodontal probing
in six sites per tooth and the evaluation of
periodontal indices (Gingival Overgrowth,
bleeding on probing, clinical attachment
loss). Following the clinical examination,
associated with radiographic images, the
periodontal diagnosis was established.
The periodontal examination assessed the
changes of the gingival colour, texture,
recessions, false/true pockets.
The obtained data were recorded and
statistically analysed. For this purpose we
used Microsoft Excel and PASW Statistics 18
software.
RESULTS
We examined a total number of 58 patients
with epileptic syndromes. The gender
distribution inside the study group was a
homogenous one: 30 females (51.72%) and
28 males (48.28%). Regarding the
environment, 39 patients (67,24%) were from
urban environment and 19 (32.76%) from
rural environment. The age distribution is
presented in Table 1.
Regarding the seizure type, 26 patients
presented generalized paroxysm seizures
(44.82%) and 32 patients (55.18%) – partial
paroxysm seizures.
The mono-therapy was administrated to 42
patients (72.41%) (Table 2) and the multi-
drug therapy – to 16 patients (27.59%) (Table
3).

Table 1. The age distribution inside the study group

Age group Number of Percentage
patients
<20 years old 7 12.06%
21-30 years old 24 41.37%
31-40 years old 12 20.68%
41-50 years old 7 12.06%
>50 years old 8 13.83%

Table 2. The drugs in patients with mono-therapy

Drug type Number Percentage in
of patients the mono-
therapy group
Carbamazepine 14 33.33%
Valproic acid 8 16.04%
Phenytoin 14 33.33%
Primidone 4 9.52%
Phenobarbital 2 4.76%

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Vol. 6, No. 2, April - June 2014

Table 3. The drugs in patients with multi-drug therapy

Drug association
Primidone+Nytrazepam
Phenobarbital+Phenytoin
Carbamazepine+Diazepam
Valproic acid + Phenobarbital
Valproic acid + Diazepam
Number of Percentage in the
patients multi-drug group
4 25.00%
4 25.00%
3 18.75%
3 18.75%
2 12.5%

In the mono-therapy group, 29 patients
from 42 (69.04%) presented periodontal
changes. Inside the multi-drug therapy group,
14 patients from 16 (87.50%) presented signs
of inflammation and gingival overgrowth.
The periodontal signs included spontaneous
bleeding, gingival hyperplasia, dental
mobility and periodontal pockets.
Furthermore, the analysis of the local risk
factors revealed a high significance for the
bacterial plaque and calculus, as signs of
improper oral hygiene; 27 patients (46.55%)
presented plaque deposits, 50 patients
(86.20%) – calculus and 42 patients (72.41%)
exhibited signs pf occlusal trauma.
The patients receiving phenytoin therapy
presented the most severe forms of gingival
overgrowth (Table 4).

Table 4. The distribution of the gingival overgrowth degree on drug types inside the study
group
Drug type Gingival overgrowth (number of patients)
I-st Degree II-nd Degree III-rd Degree IV-th Degree
Phenytoin 1 3 2 9
Carbamazepine 3 4 5 2
Sodium valproate 4 2 0 0

The diagnosis chart revealed 8 patients
with gingivitis and 50 patients with different
forms of chronic periodontitis (superficial –
10 patients, moderate – 11 patients and severe
– 18 patients). We could not observe any case
of aggressive periodontitis.
DISCUSSIONS
The present study was conducted on a
group of 58 patients, with different forms of
epileptic seizures, ranging from a few months
to a few years. The majority of the studied
subjects came from urban environment; this
aspect could be explained by a low
addressability of the rural patients to the
medical services.
We observed a high percentage of
periodontal lesions, determined by a complex
mixture of risk factors (local risk factors,
associated to the anti-epileptic systemic
medication). The highest percentages of
gingival changes were observed in patients
receiving phenytoin and carbamazepine. The
most severe changes occurred on incisor and
molar levels. The periodontal impairment was
directly proportional to the disease and drug
history (as period of time).
The periodontal examination revealed
various degrees of gingival overgrowth, a
congestive mucosa, edema, hypertrophic
papillae, with changes in consistency and
surface aspect and with a high degree of
gingival bleeding on probing.
First degree of gingival overgrowth was
encountered in one patient with phenytoin, 3
patients with carbamazepine and 4 patients

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Vol. 6, No. 2, April - June 2014

with sodium valproate; these patients exerted
a slight tumefaction, with a change in
gingival consistency, with granular aspect,
rounded papillae and probing depth lower
than 3mm.
In 3 cases of phenytoin, 4 with
carbamazepine and 2 cases with sodium
valproate we observed a moderate
overgrowth, with more important volume
changes, a higher V-O diameter, probing
depths lower than 6mm and a slightly
detachable papilla.
An important overgrowth (IIIrd Degree)
was observed in 2 cases with phenytoin and 5
with carbamazepine, manifested by a coronal
migration of the gingival margin, a gingival
diameter higher than 3mm, probing depths
higher than 6mm and a definitely detachable
papilla.
A severe overgrowth (IVth Degree) was
observed in 7 cases with phenytoin and 2
cases with carbamazepine, characterized by
an extreme gingival thickness, a very small
clinical coronal component and a clearly
detachable papilla.
The data analysis revealed no severe
gingival overgrowths in patients with valproic
acid. The most severe changes occurred in
cases of phenytoin intake. Our findings are
similar to the ones presented in the literature
[20, 21].
Due to the similarity of the therapeutical
efficiency of a certain type of seizure, the
general adverse effects of the drugs become
the most important criterion in choosing the
anti-epileptic drug [22]. Oral pathological
alterations represent an important adverse
reaction of the AED, such as gingival
enlargements, xerostomia, glositis, stomatitis,
ulcerations, slow tissue regeneration,
postsurgical gingival bleeding etc. The
epilepsy patients are affected not only by the
medical aspects of the disease but also by
adjacent aspects of psychosocial and
economic nature, with important implications
on the quality of life on epilepsy subjects
[23].
Without a doubt, the anti-epileptic drugs
have an important impact on the tissues of the
oral cavity and also on the quality of life in
patients with epileptic syndromes.
CONCLUSIONS
The anti-epileptic drug regime determines
significant changes in the periodontal tissues.
The most common impairment is related to
the gingival overgrowth. The therapy with
phenytoin as an anti-convulsive drug
determined the most severe and frequent
cases of gingival hyperplasia. A main risk
factor for the onset and progression of
gingival inflammation is represented by the
oral hygiene. The anti-epileptic drugs are an
important systemic risk factor but, still, the
bacterial plaque quantity and quality remains
the main determinant factor for the various
forms of periodontal disease.

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