**3. Patient information and prevention**

There is no consensus regarding the information if risk of SUDEP should be delivered to all patients with epilepsy, but it seems reasonable to individualize this information according to patient particularities (Ryvlin et al, 2009). Some authors recommend universal discussion of SUDEP considering that patients and their families have the right to know about the risks of epilepsy and the reasons for treatment, while others consider that SUDEP should be discussed

Sudden Unexpected Death in Epilepsy: An Overview 125

Confirming this statement studies involving epilepsy surgery programs clearly suggested that successful epilepsy surgery reduces the impending risks of SUDEP. In cohorts in whom the estimated risk of SUDEP is almost 1% per year without surgery, SUDEP incidence was significantly lower following epilepsy surgery (Schuele et al, 2007; Jehi & Najm, 2008). Although, not all refractory epilepsy patient is eligible for surgery and in this way, clarification of risk factors and establishment of the mechanisms of SUDEP are important so that as many people as possible can be saved from SUDEP (Bells & Sander, 2006). Further large-scale, multicenter, case-control or cohort prospective studies are needed to assess the role of AEDs and other potential risk factors in order to form a basis for treatment strategies aiming seizure control and prevention of SUDEP (Tomson et al, 2005). Postmortem examinations of all potential SUDEP patients are also essential, with a dedicated forensic

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Bell GS, Sander JW. Sudden unexpected death in epilepsy. (2006) Risk factors, possible mechanisms and prevention: a reappraisal. *Acta Neurol Taiwan*.; 15(2):72-83. Beran RG, Weber S, Sungaran R, Venn N, Hung A. (2004) Review of the legal obligations of

Epileptic patients who survived sudden cardiac death have increased risk of recurrent arrhythmias and death. *J Cardiovasc Med* (Hagerstown); 11(11):810-814. Bateman LM, Li CS, Seyal M. (2008) Ictal hypoxemia in localization-related epilepsy: analysis of incidence, severity and risk factors. *Brain*; 131(Pt 12):3239-3245. Bateman LM, Spitz M, Seyal M. (2010) Ictal hypoventilation contributes to cardiac

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the doctor to discuss Sudden Unexplained Death in Epilepsy (SUDEP)--a cohort

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38(11 Suppl):S9-12.

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**4. References** 

only with patients at high risk (Brodie & Holmes, 2008). This controversial issue has greater weight due the reports of patients with idiopathic epilepsies, with rare seizures that suffered SUDEP and considering these patients are more susceptible to poor drug compliance and then tonic-clonic seizures, it should be advisable to discuss this matter with them.

A study conducted in Ingland found that people with epilepsy wanted to know more information about the causes of epilepsy and other matters, such as SUDEP (Prinjha et al, 2005). However, a study conducted in Australia demonstrated that risk factors for SUDEP are not amenable to modification and in this way, discussion of SUDEP with patients could not alter outcome. Authors consider that information of SUDEP may adversely affect patients and families quality of life and suggested that an open and frank discussion of SUDEP risk should be reserved to those patients that seek the information (Beran et al, 2004).

The mechanisms underlying SUDEP are unclear, and there are no effective preventative therapies (Brodie & Holmes, 2008). However, even without precise knowledge of the underlying pathogenic mechanism(s), SUDEP prevention could start with the identification of the most prominent risk factors. SUDEP seems to occur more commonly during sleep and it preferentially affects young adults with medically intractable epilepsy (especially tonicclonic seizures), individuals who also have neurologic comorbidity, and patients receiving antiepileptic drug polytherapy (Asadi-Pooya & Sperling, 2009). Considering SUDEP is probable a multifactorial event and not all risk factors are determined, now prevention should be centered on that most potential suspected risk factors, with effective seizure control, an optimal antiepileptic drug compliance, night supervision (since almost all deaths occur at night), control of tonic-clonic seizures, prevention of airway obstruction and postictally respiratory stimulation (Tao et al, 2010; Ryvlin et al, 2009; Langan et al, 2005; Langan et al, 2000). Also patients should routinely be investigated for the presence of ictal arrhythmias and whenever necessary the insertion of a pacemaker may be indicated, preventing life-threatening cardiac arrest, syncope and trauma (Strzelczyk et al, 2008). Ideally, caregivers should be able to deliver appropriate first aid after epileptic seizures with the guarantee of properly airway flow, stimulation to decreases the duration of postictal apnea and encourage epilepsy patients to sleep in the supine position. It is not clear whether these practices will prevent SUDEP, but they may be reasonable measures to suggest when discussing this issue with patients (Walczak et al, 2001). This prophylaxis orientation should be a routine during epilepsy patient attendance (Jehi & Najm, 2008).

Early identification of patients at risk of SUDEP would offer a unique opportunity for intervention to prevent this devastating condition (Jehi & Najm, 2008). Compliance with treatment clearly influences the frequency of tonic-clonic seizures, being of paramount importance in SUDEP prevention. Also compliance should be encouraged since it may prevent SUDEP in an epilepsy population with rare seizures, which is less closely followed. Physicians should make an effort to control tonic-clonic seizures with the fewest antiepileptic drugs as possible since politherapy has been also implicated as a risk factor for SUDEP (Walczak et al, 2001).

There are few studies that examined thoroughly brain of patients that suffered SUDEP especially that areas considered to have a main function on respiratory and cardiovascular regulation and these issues represent a specific line of research in the SUDEP field that should be investigated. Early and successful epilepsy surgery for drug-resistant epilepsy may significantly reduce the risk of SUDEP, thus patients with definite pharmacologic refractory epilepsies should be referred to an epilepsy surgery center (Shuele et al, 2007). Confirming this statement studies involving epilepsy surgery programs clearly suggested that successful epilepsy surgery reduces the impending risks of SUDEP. In cohorts in whom the estimated risk of SUDEP is almost 1% per year without surgery, SUDEP incidence was significantly lower following epilepsy surgery (Schuele et al, 2007; Jehi & Najm, 2008).

Although, not all refractory epilepsy patient is eligible for surgery and in this way, clarification of risk factors and establishment of the mechanisms of SUDEP are important so that as many people as possible can be saved from SUDEP (Bells & Sander, 2006). Further large-scale, multicenter, case-control or cohort prospective studies are needed to assess the role of AEDs and other potential risk factors in order to form a basis for treatment strategies aiming seizure control and prevention of SUDEP (Tomson et al, 2005). Postmortem examinations of all potential SUDEP patients are also essential, with a dedicated forensic protocol that will permit the correct differential diagnosis (So, 2006).

#### **4. References**

124 Novel Aspects on Epilepsy

only with patients at high risk (Brodie & Holmes, 2008). This controversial issue has greater weight due the reports of patients with idiopathic epilepsies, with rare seizures that suffered SUDEP and considering these patients are more susceptible to poor drug compliance and then

A study conducted in Ingland found that people with epilepsy wanted to know more information about the causes of epilepsy and other matters, such as SUDEP (Prinjha et al, 2005). However, a study conducted in Australia demonstrated that risk factors for SUDEP are not amenable to modification and in this way, discussion of SUDEP with patients could not alter outcome. Authors consider that information of SUDEP may adversely affect patients and families quality of life and suggested that an open and frank discussion of SUDEP risk should

The mechanisms underlying SUDEP are unclear, and there are no effective preventative therapies (Brodie & Holmes, 2008). However, even without precise knowledge of the underlying pathogenic mechanism(s), SUDEP prevention could start with the identification of the most prominent risk factors. SUDEP seems to occur more commonly during sleep and it preferentially affects young adults with medically intractable epilepsy (especially tonicclonic seizures), individuals who also have neurologic comorbidity, and patients receiving antiepileptic drug polytherapy (Asadi-Pooya & Sperling, 2009). Considering SUDEP is probable a multifactorial event and not all risk factors are determined, now prevention should be centered on that most potential suspected risk factors, with effective seizure control, an optimal antiepileptic drug compliance, night supervision (since almost all deaths occur at night), control of tonic-clonic seizures, prevention of airway obstruction and postictally respiratory stimulation (Tao et al, 2010; Ryvlin et al, 2009; Langan et al, 2005; Langan et al, 2000). Also patients should routinely be investigated for the presence of ictal arrhythmias and whenever necessary the insertion of a pacemaker may be indicated, preventing life-threatening cardiac arrest, syncope and trauma (Strzelczyk et al, 2008). Ideally, caregivers should be able to deliver appropriate first aid after epileptic seizures with the guarantee of properly airway flow, stimulation to decreases the duration of postictal apnea and encourage epilepsy patients to sleep in the supine position. It is not clear whether these practices will prevent SUDEP, but they may be reasonable measures to suggest when discussing this issue with patients (Walczak et al, 2001). This prophylaxis orientation should

Early identification of patients at risk of SUDEP would offer a unique opportunity for intervention to prevent this devastating condition (Jehi & Najm, 2008). Compliance with treatment clearly influences the frequency of tonic-clonic seizures, being of paramount importance in SUDEP prevention. Also compliance should be encouraged since it may prevent SUDEP in an epilepsy population with rare seizures, which is less closely followed. Physicians should make an effort to control tonic-clonic seizures with the fewest antiepileptic drugs as possible since politherapy has been also implicated as a risk factor for

There are few studies that examined thoroughly brain of patients that suffered SUDEP especially that areas considered to have a main function on respiratory and cardiovascular regulation and these issues represent a specific line of research in the SUDEP field that should be investigated. Early and successful epilepsy surgery for drug-resistant epilepsy may significantly reduce the risk of SUDEP, thus patients with definite pharmacologic refractory epilepsies should be referred to an epilepsy surgery center (Shuele et al, 2007).

tonic-clonic seizures, it should be advisable to discuss this matter with them.

be reserved to those patients that seek the information (Beran et al, 2004).

be a routine during epilepsy patient attendance (Jehi & Najm, 2008).

SUDEP (Walczak et al, 2001).


Sudden Unexpected Death in Epilepsy: An Overview 127

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**8** 

 *Greece* 

**Hallmarks in the History of Epilepsy:** 

Emmanouil Magiorkinis, Kalliopi Sidiropoulou

*Office for the Study of History of Hellenic Naval Medicine,* 

and Aristidis Diamantis

 *Naval Hospital of Athens,* 

**From Antiquity Till the Twentieth Century** 

The history of epilepsy is intervened with the history of humanity. One of the first descriptions of epileptic seizures can be traced back to 2,000 B.C. in ancient Akkadian texts, a language widely used in the region of Mesopotamia. The author described a patient with

*his neck turns left, his hands and feet are tense and his eyes wide open, and from his mouth froth is flowing without having any conciousness.*  The exorciser diagnosed the condition as *'antasubbû'* (the hand of Sin) brought about by the

Later reports on epilepsy can also be found in Ancient Egyptian medical texts. The Edwin Smith surgical papyrus (1700 B.C.) refers to epileptic convulsions in at least five cases (cases 4, 7, 29, 40, 42). Descriptions of epilepsy can also be found in ancient babylonian texts; epileptics are thought to be afflicted by evil spirits. (Longrigg, 2000). The *Sakikku,* one of the oldest Babylonian medical texts (1067-1046 B.C.), refers to epilepsy with the terms *'antasubba'* and *'miqtu'1*. The translated babylonian text describes unilateral and bilateral epileptic fits, the epileptic cry, the incontinence of feces, the description of simple and complex epileptic seizures, the epileptic aura and narcolepsy (Eadie & Bladin, 2001). The Hamurabbi code (1790 B.C.) also refers to epilepsy. The code states that a slave could be returned and the money refunded, if *bennu*, another word for epilepsy (Stol, 1993), appeared within the month after the purchase. In Indian medicine, Atreya attributed epilepsy to a brain dysfunction and not to divine intervention. In the *Caraka Saṃhitā Sutra* 

*"paroxysmal loss of consciousness due to disturbance of memory and [of] understanding of mind attented with convulsive seizures"* (Pirkner, 1929). In the Indian text, four different kinds of epilepsy are descibed along with a description of premonitory symptoms and a type of epilepsy called '*Abasmara*', in which the patients lose

1 One can easily note the similarity between the Akkadian word *antasubbû* and the Babylonian *antasubba*

**1. Introduction** 

**1.1 First reports on epilepsy** 

symptoms resembling epilepsy:

god of the moon (Labat, 1951).

(6th century B.C.), he defines epilepsy as:

their memories.

