**4.2 Dental status and oral health**

#### **4.2.1 Trauma**

Dentofacial trauma occurring during seizures has been reported to include injuries to the tongue, buccal mucosa, facial fractures, avulsion, luxation or fractures of teeth, and subluxation of the temporomandibular joint (Ogunbodede et al., 1998).

Generalized tonic–clonic seizures often cause minor oral injuries, such as tongue biting, (Pick & Bauer, 2001) but also frequently lead to tooth injuries (Buck et al., 1997), and in some cases to maxillofacial trauma (Aragon et al., 2001).

Epilepsy and Oral Health 163

newer medications that are equally effective and have fewer side effects, phenytoin remains one of the most commonly used drugs. Evidence regarding best treatment for gingival hyperplasia is lacking. Some clinicians advocate the use of chlorhexidine, folic acid rinses or both, but excellent oral hygiene will probably prevent or significantly decrease the severity

The newer antiepileptic drugs produce oral manifestations only infrequently. Xerostomia and stomatitis have been reported rarely as side effects of carbamazepine, (Ogunbodede, et al., 1998) and rash that may involve the oral cavity has been associated with lamotrigine and

Although phenytoin-induced gingival enlargement has been better studied, its pathogenesis is still unclear. Several mechanisms related to an interaction between phenytoin and the gingival fibroblasts have been hypothesized. Phenytoin decreases cellular folate uptake possibly by inhibiting cation currents, leading to local folate deficiency. This results in insufficient synthesis of collagenase activator proteins, which play a role in connective tissue catabolism. As connective tissue catabolism is limited, gingival enlargement develops (Brown et al., 1991). The sensitivity of gingival fibroblasts to phenytoin is different in each individual and is genetically determined. This might, in some degree, explain why not all phenytoin-treated individuals develop gingival enlargement. Recently, several reports revealed that the pathogenesis of phenytoin-induced gingival enlargement might be related to certain cytokines, including interleukin-1, -6, and -8; platelet-derived growth factor BB; and basic fibroblast growth factor (Hong & Trackman, 2002; Modeer et al., 2000; Sasaki & Maita, 1998). Whether similar mechanisms play a role in valproate-induced gingival

Valproic acid can cause direct bone marrow suppression, which can impair wound healing and increase post-operative bleeding and infections. Decreased platelet count is the most common and best-recognized hematologic effect of valproic acid; the incidence varies from 5% to 40%. Clinically significant bleeding is uncommon because the thrombocytopenia is usually not severe. For elective surgery, laboratory evaluation — including bleeding time, fibrinogen level, prothrombin time, partial thromboplastin time and von Willebrand factor level — is needed to assess the risk of peri- and postoperative bleeding. Bleeding as a potential side effect should be discussed with patients and their families in preparation for

According to Tan et al., VPA can be associated with side-effects in gingival tissue in children by a mechanism attributable to the drug rather than oral hygiene or inflammation (Tan et

Those findings are consistent with the present results. Seymour reported that the most important determinant of phenytoin-induced gingival enlargement was poor oral hygiene

The pathogenesis of phenytoin-induced gingival enlargement is still not well known but several mechanisms, all related to an interaction between phenytoin and the gingival fibroblast, have been hypothesized. Valproic acid can cause direct bone marrow suppression, which can impair wound healing and increase postoperative bleeding and infections (Aragon & Burneo, 2007). The reaction begins as a diffuse swelling of the interdental papillae, which enlarge and coalesce. Clinically significant overgrowth occurs in approximately 50% of patients (Cameron & Widmer, 2008). The incidence and severity of overgrowth are the greatest

on the labial surfaces on maxillary and mandibular anterior teeth (Fig. 1).

of the condition. In severe cases, surgical reduction is needed (Stoopler et al., 2003).

can be exacerbated by the concomitant use of valproic acid (Li et al., 1996).

enlargement is unclear.

surgery (Acharya & Bussel, 2000).

al., 2004).

(R.A. Seymour, 1992).

Gurbuz et al. (Gurbuz & Tan, 2010) found a traumatic anterior dental injury rate of 68.8% in children with epilepsy in Erzurum, Turkey. This probably resulted from insufficient seizure control or from placing hard objects between the teeth of patients during seizures. According to O'Sullivan, the prevalence of traumatic anterior dental injury was 11–30% in children without epilepsy (Curzon, 2001). Generalized tonic–clonic seizures often cause minor oral injuries, such as tongue biting, but also frequently lead to tooth injuries (Buck, et al., 1997) and in some cases to maxillofacial trauma (Aragon, et al., 2001).

Patients with epilepsy can be at increased risk of fracture because enzyme-inducing antiepileptic drugs (e.g., phenytoin, phenobarbital, carbamazepine) alter the metabolism and clearance of vitamin D and have been associated with osteopenia and osteomalacia. Of interest, increased fracture risk has also been associated with the use of benzodiazepines, antidepressants and antipsychotics, suggesting that underlying brain disease or adverse effects of the medication are responsible for falls and injuries (Mattson & Gidal, 2004).

Fractures can have catastrophic effects on the lives of patients with epilepsy, and measures are available to minimize the risk of fractures, such as ensuring adequate calcium and vitamin D supplementation (a minimum of 1,000 mg and 400 IU daily, respectively) especially in patients taking phenobarbital, phenytoin or primidone (Sato et al., 2001).

#### **4.2.2 Periodontal problems**

Children younger than 15 years constitute a large group among epileptic individuals, and a considerable proportion of them also have mental and motor deficits (Bourgeois, 1995; Brodie & Dichter, 1996). These patients are at risk for oral health due to their poor self-care and the side-effects of anticonvulsant treatment: in particular, the use of phenytoin and phenobarbital can be associated with gingival enlargement (Delasnerie-Laupretre & Turpin, 1991; Thomason et al., 1992)**.** Patients with epilepsy can be at increased risk of fracture because enzyme-inducing anti-epileptic drugs (AED; e.g., phenytoin, phenobarbital, carbamazepine) alter the metabolism and clearance of vitamin D and have been associated with osteopenia and osteomalacia (Mattson & Gidal, 2004). The association of phenytoin with gingival enlargement was first described by Kimball in 1939 (Kimball, 1939); subsequently, many articles have reported on its incidence or severity in different populations. The literature reveals a wide variation in its incidence, ranging from 3 to 93%. The variability is primarily due to differences in criteria for assessing the severity of the hyperplasia, the different sizes and ages of studied groups, and variations in the duration and dosage of phenytoin treatment. However, it is now widely accepted that clinically significant hyperplasia is seen in about 50% of patients taking phenytoin (Majola et al., 2000; Ogunbodede, et al., 1998; Perlik et al., 1995; Thomason, et al., 1992).

The logical approach in drug-induced gingival enlargement is a reduction of the dose or replacement with another drug (Dahllof et al., 1991; Lundstrom et al., 1982; R. A. Seymour et al., 1985).

Because gingival enlargement has not been reported with carbamazepine so far and appears to be extremely rare with valproate, these drugs have been proposed as alternatives in the treatment of patients who develop or are at risk of phenytoin-induced gingival enlargement (R. A. Seymour, et al., 1985).

Gingival enlargement as a complication of phenytoin use has been well studied (Angelopoulos, 1975a, 1975b). About 50% of patients taking this medication will develop gingival hyperplasia within 12–24 months of initiation of treatment. Despite the existence of

Gurbuz et al. (Gurbuz & Tan, 2010) found a traumatic anterior dental injury rate of 68.8% in children with epilepsy in Erzurum, Turkey. This probably resulted from insufficient seizure control or from placing hard objects between the teeth of patients during seizures. According to O'Sullivan, the prevalence of traumatic anterior dental injury was 11–30% in children without epilepsy (Curzon, 2001). Generalized tonic–clonic seizures often cause minor oral injuries, such as tongue biting, but also frequently lead to tooth injuries (Buck, et

Patients with epilepsy can be at increased risk of fracture because enzyme-inducing antiepileptic drugs (e.g., phenytoin, phenobarbital, carbamazepine) alter the metabolism and clearance of vitamin D and have been associated with osteopenia and osteomalacia. Of interest, increased fracture risk has also been associated with the use of benzodiazepines, antidepressants and antipsychotics, suggesting that underlying brain disease or adverse effects of the medication are responsible for falls and injuries (Mattson & Gidal, 2004). Fractures can have catastrophic effects on the lives of patients with epilepsy, and measures are available to minimize the risk of fractures, such as ensuring adequate calcium and vitamin D supplementation (a minimum of 1,000 mg and 400 IU daily, respectively) especially in patients taking phenobarbital, phenytoin or primidone (Sato et al., 2001).

Children younger than 15 years constitute a large group among epileptic individuals, and a considerable proportion of them also have mental and motor deficits (Bourgeois, 1995; Brodie & Dichter, 1996). These patients are at risk for oral health due to their poor self-care and the side-effects of anticonvulsant treatment: in particular, the use of phenytoin and phenobarbital can be associated with gingival enlargement (Delasnerie-Laupretre & Turpin, 1991; Thomason et al., 1992)**.** Patients with epilepsy can be at increased risk of fracture because enzyme-inducing anti-epileptic drugs (AED; e.g., phenytoin, phenobarbital, carbamazepine) alter the metabolism and clearance of vitamin D and have been associated with osteopenia and osteomalacia (Mattson & Gidal, 2004). The association of phenytoin with gingival enlargement was first described by Kimball in 1939 (Kimball, 1939); subsequently, many articles have reported on its incidence or severity in different populations. The literature reveals a wide variation in its incidence, ranging from 3 to 93%. The variability is primarily due to differences in criteria for assessing the severity of the hyperplasia, the different sizes and ages of studied groups, and variations in the duration and dosage of phenytoin treatment. However, it is now widely accepted that clinically significant hyperplasia is seen in about 50% of patients taking phenytoin (Majola et al., 2000;

The logical approach in drug-induced gingival enlargement is a reduction of the dose or replacement with another drug (Dahllof et al., 1991; Lundstrom et al., 1982; R. A. Seymour et

Because gingival enlargement has not been reported with carbamazepine so far and appears to be extremely rare with valproate, these drugs have been proposed as alternatives in the treatment of patients who develop or are at risk of phenytoin-induced gingival enlargement

Gingival enlargement as a complication of phenytoin use has been well studied (Angelopoulos, 1975a, 1975b). About 50% of patients taking this medication will develop gingival hyperplasia within 12–24 months of initiation of treatment. Despite the existence of

al., 1997) and in some cases to maxillofacial trauma (Aragon, et al., 2001).

Ogunbodede, et al., 1998; Perlik et al., 1995; Thomason, et al., 1992).

**4.2.2 Periodontal problems** 

al., 1985).

(R. A. Seymour, et al., 1985).

newer medications that are equally effective and have fewer side effects, phenytoin remains one of the most commonly used drugs. Evidence regarding best treatment for gingival hyperplasia is lacking. Some clinicians advocate the use of chlorhexidine, folic acid rinses or both, but excellent oral hygiene will probably prevent or significantly decrease the severity of the condition. In severe cases, surgical reduction is needed (Stoopler et al., 2003).

The newer antiepileptic drugs produce oral manifestations only infrequently. Xerostomia and stomatitis have been reported rarely as side effects of carbamazepine, (Ogunbodede, et al., 1998) and rash that may involve the oral cavity has been associated with lamotrigine and can be exacerbated by the concomitant use of valproic acid (Li et al., 1996).

Although phenytoin-induced gingival enlargement has been better studied, its pathogenesis is still unclear. Several mechanisms related to an interaction between phenytoin and the gingival fibroblasts have been hypothesized. Phenytoin decreases cellular folate uptake possibly by inhibiting cation currents, leading to local folate deficiency. This results in insufficient synthesis of collagenase activator proteins, which play a role in connective tissue catabolism. As connective tissue catabolism is limited, gingival enlargement develops (Brown et al., 1991). The sensitivity of gingival fibroblasts to phenytoin is different in each individual and is genetically determined. This might, in some degree, explain why not all phenytoin-treated individuals develop gingival enlargement. Recently, several reports revealed that the pathogenesis of phenytoin-induced gingival enlargement might be related to certain cytokines, including interleukin-1, -6, and -8; platelet-derived growth factor BB; and basic fibroblast growth factor (Hong & Trackman, 2002; Modeer et al., 2000; Sasaki & Maita, 1998). Whether similar mechanisms play a role in valproate-induced gingival enlargement is unclear.

Valproic acid can cause direct bone marrow suppression, which can impair wound healing and increase post-operative bleeding and infections. Decreased platelet count is the most common and best-recognized hematologic effect of valproic acid; the incidence varies from 5% to 40%. Clinically significant bleeding is uncommon because the thrombocytopenia is usually not severe. For elective surgery, laboratory evaluation — including bleeding time, fibrinogen level, prothrombin time, partial thromboplastin time and von Willebrand factor level — is needed to assess the risk of peri- and postoperative bleeding. Bleeding as a potential side effect should be discussed with patients and their families in preparation for surgery (Acharya & Bussel, 2000).

According to Tan et al., VPA can be associated with side-effects in gingival tissue in children by a mechanism attributable to the drug rather than oral hygiene or inflammation (Tan et al., 2004).

Those findings are consistent with the present results. Seymour reported that the most important determinant of phenytoin-induced gingival enlargement was poor oral hygiene (R.A. Seymour, 1992).

The pathogenesis of phenytoin-induced gingival enlargement is still not well known but several mechanisms, all related to an interaction between phenytoin and the gingival fibroblast, have been hypothesized. Valproic acid can cause direct bone marrow suppression, which can impair wound healing and increase postoperative bleeding and infections (Aragon & Burneo, 2007). The reaction begins as a diffuse swelling of the interdental papillae, which enlarge and coalesce. Clinically significant overgrowth occurs in approximately 50% of patients (Cameron & Widmer, 2008). The incidence and severity of overgrowth are the greatest on the labial surfaces on maxillary and mandibular anterior teeth (Fig. 1).

Epilepsy and Oral Health 165

than the general population. This situation can be especially true in patients who have development disabilities, who may have trouble accessing dental care anyway. The seizures themselves can cause injuries to the teeth and dental prostheses. Some of the drugs can cause periodontal disease. Specific considerationsfor epileptic patients include the treatment of oral soft tissue side effects of medications and damage to the hard and soft tissue of the orofacial region secondary to seizure trauma, especially in patients who suffer from poorly

Dentists with a thorough knowledge of seizure disorders and the medications used to treat them can provide necessary dental and oral health care for those patients. Patients with seizure disorders may report a history of fainting or dizzy spells, seizures, or epilepsy, as well as medications to treat the seizures. A thorough evaluation of a patient's seizure disorder is necessary before initiation of any dental treatment. Important aspects to evaluate include the type of seizures, any known cause, frequency, duration, known triggers such as stress or bright lights, presence of aura before seizure activity, and history of injuries related to effects or drug interactions noted. The drug history can give some indication as to the degree of seizure seizures. Drug history should be carefully reviewed and updated at each visit, and any potential drug side severity or control (Robbins, 2009). The general goal of dental management is the avoidance of a seizure. It is important to know the type of epilepsy and any precipitating factors, medications and dosage, compliance and degree of seizure control before commencing treatment. In addition, drug interactions with anticonvulsants are common and their half-life and blood levels can be increased substantially. Consultation with the child's neurologist is essential before commencement of treatment (Cameron & Widmer, 2008). Unfortunately, even if the patient has been compliant with the

Fig. 2. Tooth eruption problem in a child with epilepsy.

controlled generalized tonic-clonic seizures (Robbins, 2009).
