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Seizures and Epilepsy Chronic traumatic encephalopathy is being recognized patients treated with warfarin has significant morbidity and a with increasing frequency in athletes who play contact sports. mortality as high as 50%; immediate correction of the INR The result of multiple concussions and head trauma, chronic limits hematoma expansion. Reversal of direct-acting antico- traumatic encephalopathy may manifest as progressive neu- agulant agents also should be performed (see MKSAP 19 ropsychiatric symptoms, including depression and dementia, Hematology for more detailed information). The reinitiation of years after the inciting events. See Cognitive Impairment for anticoagulation after intracranial hemorrhage is clinically more information. challenging and is supported by scant empirical evidence. Hemorrhagic complications in this population appear to be greatest within the first 24 hours of injury, and the risk of e Any athlete suspected of sustaining a mild traumatic thromboembolism is highest between days 3 through 5 after brain injury should be immediately removed from play injury. For patients with lower risk of hematoma expansion and assessed by a healthcare provider trained in the (such as younger patients or those whose hemorrhage is small) evaluation and management of concussion. and higher risk of thromboembolism (such as those with a mechanical heart valve), the optimal time to resume antico- Military Personnel agulation may be 72 hours after trauma. TBI is acommon consequence of service in the armed forces, par- ticularly among those deployed to a combat theater. Mild TBI, which often lacks abnormalities on neurologic examination or imaging, is highly prevalent and accounts for 80% of TBI diagnoses. Seizures and Epilepsy Guidelines recommend that military personnel undergo screening Clinical Presentation of Seizures for TBI when exposed to trauma involving a direct blow to the head, a vehicular accident, or an explosive blast and when they are Epilepsy is defined as at least two unprovoked seizures more

Chronic traumatic encephalopathy is being recognized patients treated with warfarin has significant morbidity and a with increasing frequency in athletes who play contact sports. mortality as high as 50%; immediate correction of the INR The result of multiple concussions and head trauma, chronic limits hematoma expansion. Reversal of direct-acting antico- traumatic encephalopathy may manifest as progressive neu- agulant agents also should be performed (see MKSAP 19 ropsychiatric symptoms, including depression and dementia, Hematology for more detailed information). The reinitiation of years after the inciting events. See Cognitive Impairment for anticoagulation after intracranial hemorrhage is clinically more information. challenging and is supported by scant empirical evidence. Hemorrhagic complications in this population appear to be greatest within the first 24 hours of injury, and the risk of e Any athlete suspected of sustaining a mild traumatic thromboembolism is highest between days 3 through 5 after brain injury should be immediately removed from play injury. For patients with lower risk of hematoma expansion and assessed by a healthcare provider trained in the (such as younger patients or those whose hemorrhage is small) evaluation and management of concussion. and higher risk of thromboembolism (such as those with a mechanical heart valve), the optimal time to resume antico- Military Personnel agulation may be 72 hours after trauma. TBI is acommon consequence of service in the armed forces, par- ticularly among those deployed to a combat theater. Mild TBI, which often lacks abnormalities on neurologic examination or imaging, is highly prevalent and accounts for 80% of TBI diagnoses. Seizures and Epilepsy Guidelines recommend that military personnel undergo screening Clinical Presentation of Seizures for TBI when exposed to trauma involving a direct blow to the head, a vehicular accident, or an explosive blast and when they are Epilepsy is defined as at least two unprovoked seizures more instructed to by a superior officer. The Military Acute Concussion than 24 hours apart, or one unprovoked seizure with a risk of

Chronic traumatic encephalopathy is being recognized patients treated with warfarin has significant morbidity and a with increasing frequency in athletes who play contact sports. mortality as high as 50%; immediate correction of the INR The result of multiple concussions and head trauma, chronic limits hematoma expansion. Reversal of direct-acting antico- traumatic encephalopathy may manifest as progressive neu- agulant agents also should be performed (see MKSAP 19 ropsychiatric symptoms, including depression and dementia, Hematology for more detailed information). The reinitiation of years after the inciting events. See Cognitive Impairment for anticoagulation after intracranial hemorrhage is clinically more information. challenging and is supported by scant empirical evidence. Hemorrhagic complications in this population appear to be greatest within the first 24 hours of injury, and the risk of e Any athlete suspected of sustaining a mild traumatic thromboembolism is highest between days 3 through 5 after brain injury should be immediately removed from play injury. For patients with lower risk of hematoma expansion and assessed by a healthcare provider trained in the (such as younger patients or those whose hemorrhage is small) evaluation and management of concussion. and higher risk of thromboembolism (such as those with a mechanical heart valve), the optimal time to resume antico- Military Personnel agulation may be 72 hours after trauma. TBI is acommon consequence of service in the armed forces, par- ticularly among those deployed to a combat theater. Mild TBI, which often lacks abnormalities on neurologic examination or imaging, is highly prevalent and accounts for 80% of TBI diagnoses. Seizures and Epilepsy Guidelines recommend that military personnel undergo screening Clinical Presentation of Seizures for TBI when exposed to trauma involving a direct blow to the head, a vehicular accident, or an explosive blast and when they are Epilepsy is defined as at least two unprovoked seizures more instructed to by a superior officer. The Military Acute Concussion than 24 hours apart, or one unprovoked seizure with a risk of Evaluation and a requisite 24-hour rest period are mandated, with further seizures that is similar to the risk after two unprovoked

Chronic traumatic encephalopathy is being recognized patients treated with warfarin has significant morbidity and a with increasing frequency in athletes who play contact sports. mortality as high as 50%; immediate correction of the INR The result of multiple concussions and head trauma, chronic limits hematoma expansion. Reversal of direct-acting antico- traumatic encephalopathy may manifest as progressive neu- agulant agents also should be performed (see MKSAP 19 ropsychiatric symptoms, including depression and dementia, Hematology for more detailed information). The reinitiation of years after the inciting events. See Cognitive Impairment for anticoagulation after intracranial hemorrhage is clinically more information. challenging and is supported by scant empirical evidence. Hemorrhagic complications in this population appear to be greatest within the first 24 hours of injury, and the risk of e Any athlete suspected of sustaining a mild traumatic thromboembolism is highest between days 3 through 5 after brain injury should be immediately removed from play injury. For patients with lower risk of hematoma expansion and assessed by a healthcare provider trained in the (such as younger patients or those whose hemorrhage is small) evaluation and management of concussion. and higher risk of thromboembolism (such as those with a mechanical heart valve), the optimal time to resume antico- Military Personnel agulation may be 72 hours after trauma. TBI is acommon consequence of service in the armed forces, par- ticularly among those deployed to a combat theater. Mild TBI, which often lacks abnormalities on neurologic examination or imaging, is highly prevalent and accounts for 80% of TBI diagnoses. Seizures and Epilepsy Guidelines recommend that military personnel undergo screening Clinical Presentation of Seizures for TBI when exposed to trauma involving a direct blow to the head, a vehicular accident, or an explosive blast and when they are Epilepsy is defined as at least two unprovoked seizures more instructed to by a superior officer. The Military Acute Concussion than 24 hours apart, or one unprovoked seizure with a risk of Evaluation and a requisite 24-hour rest period are mandated, with further seizures that is similar to the risk after two unprovoked return to duty requiring complete recovery. Headache is the most seizures (at least 60%). The term “epileptic seizure” does not

Evaluation and a requisite 24-hour rest period are mandated, with further seizures that is similar to the risk after two unprovoked return to duty requiring complete recovery. Headache is the most seizures (at least 60%). The term “epileptic seizure” does not common symptom after TBI and the best prognostic indicator in imply that the seizure is related to epilepsy; rather, it means returning service members. A posttraumatic headache present at 1 that the seizure is secondary to abnormal electrical activity in year postinjury is likely to be permanent. Other sequelae of mild the brain and not to some other cause (such as syncope or TBI in this population include posttraumatic stress disorder psychiatric disease). The diagnosis of epilepsy relies on a (PTSD), depression, anxiety, insomnia, and disorders of cognition detailed patient history. Seizures are characteristically stereo- and balance. Specific screening for PTSD and depression is manda- typed; symptom variability from event to event suggests an tory (see MKSAP 19 General Internal Medicine 1). The prevalence of alternative diagnosis. Epilepsy usually requires antiepileptic PTSD is higher in military personnel with mild TBI compared with drug (AED) therapy, but isolated seizures may not, especially if civilian populations, and both groups are at increased risk for sui- provoked by reversible or preventable causes. The terminology cide. Returning service members with any TBI are best treated of seizure classification is evolving but is usually divided into through a multidisciplinary approach, with referral to mental focal and generalized categories (Figure 5).

PTSD is higher in military personnel with mild TBI compared with drug (AED) therapy, but isolated seizures may not, especially if civilian populations, and both groups are at increased risk for sui- provoked by reversible or preventable causes. The terminology cide. Returning service members with any TBI are best treated of seizure classification is evolving but is usually divided into through a multidisciplinary approach, with referral to mental focal and generalized categories (Figure 5). health specialists frequently indicated. Treatments are largely symptomatic and supportive. Focal Seizures Focal seizures may be classified as “aware” or “impaired aware- ness” (formerly, simple partial and complex partial, respec- e The prevalence of posttraumatic stress disorder is tively). The first type includes auras, which are very localized higher in military personnel with mild traumatic brain focal seizures with varying manifestations depending on the injury (TBI) than in civilians with mild TBI. site of origin within the brain (Table 14). Seizures involving impaired awareness may affect memory, responsiveness, lan- Older Patients guage, or cognition. Both focal seizures and generalized Adults older than 75 years are at particular risk for hospitali- absence seizures can present as “staring episodes” and must be

health specialists frequently indicated. Treatments are largely symptomatic and supportive. Focal Seizures Focal seizures may be classified as “aware” or “impaired aware- ness” (formerly, simple partial and complex partial, respec- e The prevalence of posttraumatic stress disorder is tively). The first type includes auras, which are very localized higher in military personnel with mild traumatic brain focal seizures with varying manifestations depending on the injury (TBI) than in civilians with mild TBI. site of origin within the brain (Table 14). Seizures involving impaired awareness may affect memory, responsiveness, lan- Older Patients guage, or cognition. Both focal seizures and generalized Adults older than 75 years are at particular risk for hospitali- absence seizures can present as “staring episodes” and must be zation and death from TBI. Falls, motor vehicle accidents, carefully differentiated (Table 15). and accidental blows to the head are the leading mecha- nisms of injury in this population. Prevention of these events Generalized Seizures is an essential aspect of geriatric medicine. See MKSAP 19 Generalized tonic-clonic seizures (GTCS) have a characteristic General Internal Medicine 1 for more information. tonic phase of whole-body stiffening with eyes wide open and a single loud groan (or “ictal cry”), followed by a clonic phase Patients Receiving Anticoagulation of rhythmic synchronous limb jerking that is initially fast and Anticoagulation is associated with an increased risk of intrac- gradually slows and ceases. The seizure typically lasts 1 to ranial hemorrhage after trauma. Intracranial hemorrhage in 3 minutes and is often followed by stertor (deep, slow snoring). 14

Seizures and Epilepsy Focal (Partial) Generalized = 1 one Impair: : Aware? f- - ---- > B . awareness’ !IF = Sa <—_ FIGURE 5. Common seizure types based on iol 1 ot International League Against Epilepsy classification. I ! 1 ot The dashed arrows represent the possibility of one 1 1 ol Tonic — , Tae seeroracet ; 1 iol seizure type transitioning directly into another when i iol 1 ot ; a patient is seizing. Note that generalized tonic clonic ! tot Kea . seizures may start out focal or generalized. Vv vVvv *Also known as simple partial seizures. Generalized Tonic Clonic Atonic <— Also known as complex partial or focal dyscognitive seizures.

1 ot ; a patient is seizing. Note that generalized tonic clonic ! tot Kea . seizures may start out focal or generalized. Vv vVvv *Also known as simple partial seizures. Generalized Tonic Clonic Atonic <— Also known as complex partial or focal dyscognitive seizures. A postictal state with confusion, hypersomnolence, and Absence seizures are characterized by brief episodes of fatigue is common and can persist for hours or even days. staring (see Table 15). They may occur as the only seizure type GTCS may be preceded by other seizure types, either in school-age children and are often confused with attention- generalized or focal. Aura or automatisms before GTCS and deficit/hyperactivity disorder. postevent unilateral weakness (Todd paralysis) suggest focal Myoclonus is a single quick jerk of a limb or the entire body onset. lasting less than a second and is not always associated with a seizure (see Movement Disorders). A diagnosis of myoclonic sei- zures can be confirmed by electroencephalography (EEG), with TABLE 14. Examples of Focal Aware Seizures® each jerk associated with a generalized spike-and-wave discharge Lobe Clinical Presentation |

A postictal state with confusion, hypersomnolence, and Absence seizures are characterized by brief episodes of fatigue is common and can persist for hours or even days. staring (see Table 15). They may occur as the only seizure type GTCS may be preceded by other seizure types, either in school-age children and are often confused with attention- generalized or focal. Aura or automatisms before GTCS and deficit/hyperactivity disorder. postevent unilateral weakness (Todd paralysis) suggest focal Myoclonus is a single quick jerk of a limb or the entire body onset. lasting less than a second and is not always associated with a seizure (see Movement Disorders). A diagnosis of myoclonic sei- zures can be confirmed by electroencephalography (EEG), with TABLE 14. Examples of Focal Aware Seizures® each jerk associated with a generalized spike-and-wave discharge Lobe Clinical Presentation | (Figure 6). Myoclonic seizures also can occur repetitively and | Frontal Focal contralateral motor activity (clonic jerking) | result in falls. Awareness is maintained and duration is very short | Temporal — Epigastric rising sensation (nausea, butterflies); (<1 second), which differentiates myoclonic seizures from GTCS. aphasia; déja vu; fear; elation; auditory, Tonic seizures present as episodes of increased muscle olfactory,’ and gustatory® sensations tone, ranging from mild extension of the arms and head to a Parietal Focal contralateral pain, numbness, or paresthesias | more severe stiffening of the entire body. Atonic seizures pre- i}

(Figure 6). Myoclonic seizures also can occur repetitively and | Frontal Focal contralateral motor activity (clonic jerking) | result in falls. Awareness is maintained and duration is very short | Temporal — Epigastric rising sensation (nausea, butterflies); (<1 second), which differentiates myoclonic seizures from GTCS. aphasia; déja vu; fear; elation; auditory, Tonic seizures present as episodes of increased muscle olfactory,’ and gustatory® sensations tone, ranging from mild extension of the arms and head to a Parietal Focal contralateral pain, numbness, or paresthesias | more severe stiffening of the entire body. Atonic seizures pre- i} Occipital Contralateral homonymous visual loss or nonformed sent with sudden loss of muscle tone. Both tonic and atonic hallucinations (dots, lines, flashes of light) seizures occur with no warning, last a few seconds, and cause | Also known as simple partial seizures (which include auras). altered awareness, which often leads to falls and physical inju- | Altered smell and taste also can be seen in psychogenic nonepileptic events. ries; they lack postevent confusion. Prolonged episodes of wy

Occipital Contralateral homonymous visual loss or nonformed sent with sudden loss of muscle tone. Both tonic and atonic hallucinations (dots, lines, flashes of light) seizures occur with no warning, last a few seconds, and cause | Also known as simple partial seizures (which include auras). altered awareness, which often leads to falls and physical inju- | Altered smell and taste also can be seen in psychogenic nonepileptic events. ries; they lack postevent confusion. Prolonged episodes of wy increased or decreased tone with long duration of loss of con- sciousness are unlikely to represent seizures. TABLE 15. Clinical Differentiation of Seizure Types Presenting As Staring Episodes e Epilepsy is defined as at least two unprovoked seizures | Seizure Feature Absence Focal Impaired | Seizure Awareness Seizure? | more than 24 hours apart or one unprovoked seizure with a risk of further seizures that is similar to the risk | Aura No Possible | after two unprovoked seizures (at least 60%). | Onset Abrupt Gradual or abrupt | e Although both may present as staring spells, focal seizures Duration <15s >30s with impaired awareness can be distinguished from | Termination Abrupt Usually gradual | absence seizures by longer duration, lower frequency, and Postictal state Normal Lethargy, confusion | the presence of aura and postictal confusion. Frequency Multiple daily Once weekly or | monthly Precipitated by Usually Unlikely | Epilepsy Syndromes hyperventilation | Focal Epilepsies | Associated Generalized Focal onset seizures Identifiable causes of focal epilepsies include structural lesions | seizure types onset seizures (simple partial or (myoclonic, secondarily | that may be seen on MRI, such as mesial temporal sclerosis with primarily generalized tonic- | hippocampal atrophy (Figure 7), cavernous malformations, cor- generalized clonic) tical dysplasia (Figure 8), traumatic brain injury, stroke, and tonic-clonic, tonic, atonic) tumors. EEG may show focal spikes or sharp waves in the appro- priate brain region (Figure 9). In most adults with focal epilepsy, Also known as a complex partial or focal dyscognitive seizure. however, brain MRI is normal and the cause is unknown.

increased or decreased tone with long duration of loss of con- sciousness are unlikely to represent seizures. TABLE 15. Clinical Differentiation of Seizure Types Presenting As Staring Episodes e Epilepsy is defined as at least two unprovoked seizures | Seizure Feature Absence Focal Impaired | Seizure Awareness Seizure? | more than 24 hours apart or one unprovoked seizure with a risk of further seizures that is similar to the risk | Aura No Possible | after two unprovoked seizures (at least 60%). | Onset Abrupt Gradual or abrupt | e Although both may present as staring spells, focal seizures Duration <15s >30s with impaired awareness can be distinguished from | Termination Abrupt Usually gradual | absence seizures by longer duration, lower frequency, and Postictal state Normal Lethargy, confusion | the presence of aura and postictal confusion. Frequency Multiple daily Once weekly or | monthly Precipitated by Usually Unlikely | Epilepsy Syndromes hyperventilation | Focal Epilepsies | Associated Generalized Focal onset seizures Identifiable causes of focal epilepsies include structural lesions | seizure types onset seizures (simple partial or (myoclonic, secondarily | that may be seen on MRI, such as mesial temporal sclerosis with primarily generalized tonic- | hippocampal atrophy (Figure 7), cavernous malformations, cor- generalized clonic) tical dysplasia (Figure 8), traumatic brain injury, stroke, and tonic-clonic, tonic, atonic) tumors. EEG may show focal spikes or sharp waves in the appro- priate brain region (Figure 9). In most adults with focal epilepsy, Also known as a complex partial or focal dyscognitive seizure. however, brain MRI is normal and the cause is unknown. 15

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TEBEMY emerSa epemaiome amma ae ht y \ SON eenssahainaniad hemiachiieanes i kane 2 Fo2-M2 en Vee ee F VASWypri rn re nN A 3 F3M1 pncreascemiatad vainmeaadewend f,Vv =Jf“.Nien ch Detain ry nei 4 FAM? ‘eenidedtie tink bites daenaan enIN WWWV i) phyAWNPOI Frenne en 6 cAM2 mena anemone hyYaycg epbeseSaichane aineaee eetetahs Gemma ieamenctaaae 5 CoMI ity nt cere ae |‘yl my yy powNa Mone foeaeee CeeAA 7 P3MI AA Antnmnoninnanbee ti ynrnntinnraehf “AMVy oesow nwacmaaaeee MeenasPann 8 PAMZ PN Anrentnrtinmmrer rerncnenreenrnacel feMA FY,Mu fPr—rpJNW S\evePte oral ft ANG teAone 9 01-M1 aVA Anand,cahcanaiemndiet tania dani ten dan |“yd py Net nara enedee CO ae 10 02-2 UN Rennteam nersmadtarmnanenpacenf hyonTMAP er nanenLeena trim 11 F7-M4 beret reane aaawom Ay nL nahin rama ponent rataymay Ne 12 Fe-M2 schaananeneiaamnaaes eaaaemaeade te Ww VnPiatt Nea tarebetndt tame aehinn ants 13 TMI ennacacti Goetitenl a ateetibationtat o n on ~*~{a Ee OR SS BES ge RseULeN 4oreenenectmenentyaanmntneinlN NN | vaa: a eaeieed acetal pnanmentiee aada 15 P7MI PN eaten nnn enti ati sneer areal MyTino¥|‘aePN pSSan aes ee 16 Pe-M2 aa ne enn ee va eaecameacs uadeneamae aiemecenit att VW? Feet fan,ee ere eae AAG ya evVeeA vineeee tame acteme aces 18 C21 ie LAA, ednaeaaamanae Sammaen A‘/ v

7 P3MI AA Antnmnoninnanbee ti ynrnntinnraehf “AMVy oesow nwacmaaaeee MeenasPann 8 PAMZ PN Anrentnrtinmmrer rerncnenreenrnacel feMA FY,Mu fPr—rpJNW S\evePte oral ft ANG teAone 9 01-M1 aVA Anand,cahcanaiemndiet tania dani ten dan |“yd py Net nara enedee CO ae 10 02-2 UN Rennteam nersmadtarmnanenpacenf hyonTMAP er nanenLeena trim 11 F7-M4 beret reane aaawom Ay nL nahin rama ponent rataymay Ne 12 Fe-M2 schaananeneiaamnaaes eaaaemaeade te Ww VnPiatt Nea tarebetndt tame aehinn ants 13 TMI ennacacti Goetitenl a ateetibationtat o n on ~*~{a Ee OR SS BES ge RseULeN 4oreenenectmenentyaanmntneinlN NN | vaa: a eaeieed acetal pnanmentiee aada 15 P7MI PN eaten nnn enti ati sneer areal MyTino¥|‘aePN pSSan aes ee 16 Pe-M2 aa ne enn ee va eaecameacs uadeneamae aiemecenit att VW? Feet fan,ee ere eae AAG ya evVeeA vineeee tame acteme aces 18 C21 ie LAA, ednaeaaamanae Sammaen A‘/ v MU rennernyo 19 PM aheteee s eaaneaemai shaman aMfnN i[arnt Armeventctenetannnn nmr Ne TM ' it"i 1 100uv FIGURE 6. Electroencephalogram showing generalized spike-and-wave discharges. In an appropriate clinical setting, this strongly supports a diagnosis of generalized epilepsy.

MU rennernyo 19 PM aheteee s eaaneaemai shaman aMfnN i[arnt Armeventctenetannnn nmr Ne TM ' it"i 1 100uv FIGURE 6. Electroencephalogram showing generalized spike-and-wave discharges. In an appropriate clinical setting, this strongly supports a diagnosis of generalized epilepsy. FIGURE 8. Focal cortical dysplasia with periventricular nodular heterotopia. FIGURE 7. Mesial temporal sclerosis. The coronal fluid-attenuated inversion Coronal MRI showing a focal area of thickened cortex in the right temporal region recovery MRI shows increased signal intensity and atrophy of the left mesial temporal (thick arrow) and nodules of abnormal neuronal tissue along the ventricular surface lobe (arrow). (thin arrow). 16

Seizures and Epilepsy per rrerer pet vavrenrange ERD GLC SI LER Tye pe CHIP Ve ear se Ry 8 Bae See ee ee ee ee 2 dese 2 Fo2-AV 4 FAV 4 AAV 5 caAy 6 CAV 7 P3AV 8 PLAV 9 O1-AV 10 02AV 11 F7AY 12 Feav 13 TLAV 14 TZAV 18 174V 16 TRAV 17 P7AV 18 PRAY 19 FraV 20 CzAv 21 P2av ¢ FIGURE 9. Electroencephalogram showing focal (left temporal) sharp waves. In an appropriate clinical setting, this strongly supports a diagnosis of temporal lobe epilepsy. Temporal lobe epilepsy is the most common adult-onset The presence of myoclonic seizures is required for the diag- focal epilepsy. Typical symptoms of a temporal lobe focal sei- nosis of JME; patients may report dropping items from their zure include aura of déja vu, fear, or a rising sensation in the hands, often a coffee cup or hairbrush, because myoclonic sei- stomach; loss of awareness; staring; behavior arrest; and amne- zures in JME generally occur in the morning. Most affected sia. Semipurposeful repetitive mouth or ipsilateral hand move- patients have GTCS, and approximately 30% of patients have ments, called automatisms, may be observed. Speech arrest absence seizures. Patients are usually otherwise neurologically may be seen with involvement of the dominant hemisphere. healthy and can live relatively normal lives because seizures are often controlled with one or two AEDs. Brain MRI is typically normal, and EEG may show generalized spike-and-wave dis- ¢ Mesial temporal sclerosis with hippocampal atrophy is charges (see Figure 6). Lifelong AED therapy is typically required. commonly associated with temporal lobe epilepsy. ¢ Temporal lobe epilepsy is the most common adult-onset focal epilepsy; typical symptoms include aura, loss of e The presence of myoclonic seizures is required for the

Temporal lobe epilepsy is the most common adult-onset The presence of myoclonic seizures is required for the diag- focal epilepsy. Typical symptoms of a temporal lobe focal sei- nosis of JME; patients may report dropping items from their zure include aura of déja vu, fear, or a rising sensation in the hands, often a coffee cup or hairbrush, because myoclonic sei- stomach; loss of awareness; staring; behavior arrest; and amne- zures in JME generally occur in the morning. Most affected sia. Semipurposeful repetitive mouth or ipsilateral hand move- patients have GTCS, and approximately 30% of patients have ments, called automatisms, may be observed. Speech arrest absence seizures. Patients are usually otherwise neurologically may be seen with involvement of the dominant hemisphere. healthy and can live relatively normal lives because seizures are often controlled with one or two AEDs. Brain MRI is typically normal, and EEG may show generalized spike-and-wave dis- ¢ Mesial temporal sclerosis with hippocampal atrophy is charges (see Figure 6). Lifelong AED therapy is typically required. commonly associated with temporal lobe epilepsy. ¢ Temporal lobe epilepsy is the most common adult-onset focal epilepsy; typical symptoms include aura, loss of e The presence of myoclonic seizures is required for the awareness, staring, behavior arrest, and amnesia. diagnosis of juvenile myoclonic epilepsy (JME); JME often is not diagnosed, however, until the first general- ized tonic-clonic seizure occurs because myoclonic Idiopathic (Genetic) Generalized Epilepsies seizures often remain unrecognized. Idiopathic epilepsies are “pure” without an underlying neurologic disorder, often having complex, polygenic inheritance (thus, often e Lifelong antiepileptic drug therapy is typically required

awareness, staring, behavior arrest, and amnesia. diagnosis of juvenile myoclonic epilepsy (JME); JME often is not diagnosed, however, until the first general- ized tonic-clonic seizure occurs because myoclonic Idiopathic (Genetic) Generalized Epilepsies seizures often remain unrecognized. Idiopathic epilepsies are “pure” without an underlying neurologic disorder, often having complex, polygenic inheritance (thus, often e Lifelong antiepileptic drug therapy is typically required no family history or identifiable single genetic mutation). In for patients with juvenile myoclonic epilepsy. adults, juvenile myoclonic epilepsy (JME) is the most common form of idiopathic/genetic generalized epilepsy. Seizures in JME Diagnostic Evaluation of Seizures are often called “college seizures” because of the age of onset (teens or twenties) and associated triggers (sleep deprivation, alco- and Epilepsy hol use, and stress). Epilepsy may not be diagnosed until the first Initial Approach to the Patient with a First Seizure GTCS occurs because myoclonic seizures often remain unrecog- For any patient with a first seizure, obtaining a detailed history nized until a physician takes a careful and complete history. is crucial to distinguish seizures from other causes of 17

Seizures and Epilepsy symptoms. The distinction between seizures and nonepileptic volunteers had nonepileptic myoclonus (generalized or multi- events and clarification of first-time versus recurrent episodes focal) when syncope was induced; only a minority had classic, are key. A history of previous staring events or myoclonus may motionless syncope. For distinguishing seizures from syncope help identify patients with epilepsy and should be specifically and psychogenic loss of consciousness, video EEG can be very sought through careful questioning. useful, in combination with tilt-table testing, because it can specifically differentiate these events. ¢ A history of previous staring events or myoclonus may Psychogenic Nonepileptic Spells/Events help identify patients with epilepsy. Psychogenic nonepileptic spells/events (PNES) were formerly called pseudoseizures or psychogenic nonepileptic seizures.

¢ A history of previous staring events or myoclonus may Psychogenic Nonepileptic Spells/Events help identify patients with epilepsy. Psychogenic nonepileptic spells/events (PNES) were formerly called pseudoseizures or psychogenic nonepileptic seizures. Differential Diagnosis of Seizures These latter terms should be avoided because “pseudo” implies falseness and “seizure” is a misnomer. PNES are most often Many episodic disorders mimic seizures but are nonepileptic related to posttraumatic stress disorder or conversion disorder. events. These include syncope, migraine, movement disorders Factitious disorder and malingering are rare and far less likely. (tremor, tics), sleep disorders, stroke, and psychogenic events. Patients with PNES often have a history of military combat, Seizures usually have positive symptoms, such as jerking, tingling, sexual or physical abuse, chronic medical illness, or promi- and visual flashes, whereas strokes have negative symptoms, such as weakness, numbness, and loss of vision. Normal mentation nent life stressors. PNES often mimic GTCS, but certain fea-

Differential Diagnosis of Seizures These latter terms should be avoided because “pseudo” implies falseness and “seizure” is a misnomer. PNES are most often Many episodic disorders mimic seizures but are nonepileptic related to posttraumatic stress disorder or conversion disorder. events. These include syncope, migraine, movement disorders Factitious disorder and malingering are rare and far less likely. (tremor, tics), sleep disorders, stroke, and psychogenic events. Patients with PNES often have a history of military combat, Seizures usually have positive symptoms, such as jerking, tingling, sexual or physical abuse, chronic medical illness, or promi- and visual flashes, whereas strokes have negative symptoms, such as weakness, numbness, and loss of vision. Normal mentation nent life stressors. PNES often mimic GTCS, but certain fea- with a headache after the episode suggests migraine. Occurrence tures help distinguish the diagnoses (Table 17). Event capture during video EEG monitoring usually is required to confirm only in public suggests panic disorder with agoraphobia. Associated lightheadedness or chest pain may suggest the diagnosis. PNES are commonly associated with treatment failure; management should emphasize early video EEG moni- syncope or cardiac disease. Syncope often presents with shak- toring over polypharmacy. ing (“convulsive syncope”) and must be differentiated from GTCS (Table 16). In one study, more than 90% of healthy Returning combat veterans who develop seizures require careful evaluation, often including video EEG monitoring. Many have had head trauma and are at increased risk for epi- TABLE 16. Clinical Differentiation of Generalized lepsy, but many also have posttraumatic stress disorder and Tonic-Clonic Seizures and Syncope may have PNES. Assuming a diagnosis of epilepsy and empiri- | Seizure Generalized Tonic- Syncope cally treating the patient can be detrimental, especially | Feature Clonic Seizures | because veterans tend to have a delay in the diagnosis of PNES | Warning Possible epileptic Prodrome of | compared with the general population. | symptoms aura immediately lightheadedness, | | before onset nausea, warmth, | diaphoresis, blurred | or tunnel vision, e Syncope often presents with shaking (“convulsive syn- | generalized cope”); video electroencephalography with tilt table | weakness, | testing can be useful to differentiate syncope from sei- | palpitations, anda | | “faint” feeling zures and nonepileptic events.

with a headache after the episode suggests migraine. Occurrence tures help distinguish the diagnoses (Table 17). Event capture during video EEG monitoring usually is required to confirm only in public suggests panic disorder with agoraphobia. Associated lightheadedness or chest pain may suggest the diagnosis. PNES are commonly associated with treatment failure; management should emphasize early video EEG moni- syncope or cardiac disease. Syncope often presents with shak- toring over polypharmacy. ing (“convulsive syncope”) and must be differentiated from GTCS (Table 16). In one study, more than 90% of healthy Returning combat veterans who develop seizures require careful evaluation, often including video EEG monitoring. Many have had head trauma and are at increased risk for epi- TABLE 16. Clinical Differentiation of Generalized lepsy, but many also have posttraumatic stress disorder and Tonic-Clonic Seizures and Syncope may have PNES. Assuming a diagnosis of epilepsy and empiri- | Seizure Generalized Tonic- Syncope cally treating the patient can be detrimental, especially | Feature Clonic Seizures | because veterans tend to have a delay in the diagnosis of PNES | Warning Possible epileptic Prodrome of | compared with the general population. | symptoms aura immediately lightheadedness, | | before onset nausea, warmth, | diaphoresis, blurred | or tunnel vision, e Syncope often presents with shaking (“convulsive syn- | generalized cope”); video electroencephalography with tilt table | weakness, | testing can be useful to differentiate syncope from sei- | palpitations, anda | | “faint” feeling zures and nonepileptic events. | Self- Auramay ormaynot Lying orsittingdown | e Psychogenic nonepileptic spells/events are most often be long enough to may prevent | | ensure patient progression to LOC protection related to posttraumatic stress disorder or conversion

| Self- Auramay ormaynot Lying orsittingdown | e Psychogenic nonepileptic spells/events are most often be long enough to may prevent | | ensure patient progression to LOC protection related to posttraumatic stress disorder or conversion safety, but seizure is | disorder, and factitious disorder and malingering are | not preventable rare; management should emphasize early video EEG | Muscle tone Generalized Generalized loss of | monitoring over polypharmacy. | stiffening tone | Motor activity | Generalized clonic Generalized | Diagnostic Evaluation shaking (rhythmic, myoclonic shaking | Neuroimaging is recommended for all patients with a first | synchronous whole- (whole-body body jerks) shaking or isolated seizure. CT of the head is adequate initially to rapidly exclude

| Muscle tone Generalized Generalized loss of | monitoring over polypharmacy. | stiffening tone | Motor activity | Generalized clonic Generalized | Diagnostic Evaluation shaking (rhythmic, myoclonic shaking | Neuroimaging is recommended for all patients with a first | synchronous whole- (whole-body body jerks) shaking or isolated seizure. CT of the head is adequate initially to rapidly exclude | subtle twitching of | emergent pathology, including hemorrhage, but MRI is rec- limbs) ommended in most patients. The use of contrast may be _ Color May have cyanosis May have pallor | deferred unless infection, tumor, or vascular lesions are | Duration of Usually >1 minute Usually <1 minute suspected. Because temporal lobe epilepsy is common, MRI | LOC sequences focusing on the hippocampus and temporal lobes | Postictal state Confusion, lethargy, Normal, otherthana | are useful (coronal T2-weighted imaging, fluid-attenuated combativeness, situationally | inversion recovery imaging, and thin-slice Tl-weighted | somnolence appropriate memory | loss of event imaging). | Outpatient EEG also is recommended in patients with a LOC = loss of consciousness. i first seizure. Because capture of an actual seizure is unlikely,

| subtle twitching of | emergent pathology, including hemorrhage, but MRI is rec- limbs) ommended in most patients. The use of contrast may be _ Color May have cyanosis May have pallor | deferred unless infection, tumor, or vascular lesions are | Duration of Usually >1 minute Usually <1 minute suspected. Because temporal lobe epilepsy is common, MRI | LOC sequences focusing on the hippocampus and temporal lobes | Postictal state Confusion, lethargy, Normal, otherthana | are useful (coronal T2-weighted imaging, fluid-attenuated combativeness, situationally | inversion recovery imaging, and thin-slice Tl-weighted | somnolence appropriate memory | loss of event imaging). | Outpatient EEG also is recommended in patients with a LOC = loss of consciousness. i first seizure. Because capture of an actual seizure is unlikely, 18

Seizures and Epilepsy TABLE 17. Clinical Differentiation of GTCS and PNES Seizure Feature GTCS PNES | | Stereotyped Yes No (varies from event to event) | | Eyelids Open Closed (may resist opening) | | Color May have cyanosis May turn red | Vocalization Ictal cry (sharp, loud, deep single inspiration against Intermittent breath holding alternating with gasping/ | | contracted epiglottis) rapid breaths, or crying/sobbing | | Muscle tone Starts with stiffening of all limbs (tonic) Patients usually limp or limber; may resist movement or | | make atypical postures (fists, claws) | Motor activity Synchronous shakingofall limbs (clonic) Asynchronous flailing of variable limbs, side-to-side | | head shaking, pelvic thrusting? | Motor pattern Shaking starts at high frequency and gradually slows Shaking may speed up or vary in frequency | | down |

| Stereotyped Yes No (varies from event to event) | | Eyelids Open Closed (may resist opening) | | Color May have cyanosis May turn red | Vocalization Ictal cry (sharp, loud, deep single inspiration against Intermittent breath holding alternating with gasping/ | | contracted epiglottis) rapid breaths, or crying/sobbing | | Muscle tone Starts with stiffening of all limbs (tonic) Patients usually limp or limber; may resist movement or | | make atypical postures (fists, claws) | Motor activity Synchronous shakingofall limbs (clonic) Asynchronous flailing of variable limbs, side-to-side | | head shaking, pelvic thrusting? | Motor pattern Shaking starts at high frequency and gradually slows Shaking may speed up or vary in frequency | | down | | Duration Usually ends within <5 min Prolonged, or waxes and wanes over >5 min or even | | hours | | Consciousness/ Impaired/lost May be retained (may hear or remember but not memory respond) | Postictal state Confused, lethargic May have relatively normal mental status despite high | frequency of “seizures”

| Duration Usually ends within <5 min Prolonged, or waxes and wanes over >5 min or even | | hours | | Consciousness/ Impaired/lost May be retained (may hear or remember but not memory respond) | Postictal state Confused, lethargic May have relatively normal mental status despite high | frequency of “seizures” | Postictal Slow, deep, loud, snoring-like stertor Normal or rapid panting | breathing | GTCS = generalized tonic-clonic seizure; PNES = psychogenic nonepileptic spell/event. | ®These typically psychogenic symptoms may be seen in true epileptic frontal lobe seizures. |

| Postictal Slow, deep, loud, snoring-like stertor Normal or rapid panting | breathing | GTCS = generalized tonic-clonic seizure; PNES = psychogenic nonepileptic spell/event. | ®These typically psychogenic symptoms may be seen in true epileptic frontal lobe seizures. | the physician must rely on “epileptiform” abnormalities, such WEY DOUNTS i 105 > Ge Se) a as focal sharp waves (see Figure 9) or generalized spike-and- ¢ MRI and electroencephalography are recommended for HVC wave discharges (see Figure 6). These findings are not diagnos- all patients with a first seizure; lumbar puncture is rec- tically confirmatory; rather, they may help support the ommended only if an infectious cause is suspected. diagnosis in an appropriate clinical context. A single routine EEG is only 40% to 50% sensitive for such findings, so clinical ° A single routine electroencephalographic study is only judgment based on history remains critical. Emergent lumbar 40% to 50% sensitive in diagnosing epilepsy. : puncture is recommended in adults only if an infectious cause, (Continued) such as meningitis or encephalitis, is suspected. TABLE 18. Indications for Immediate Continuous Video Electroencephalographic Monitoring in the Critical Care Setting Epilepsy Monitoring Units AMS following CSE? or clinical seizures A normal EEG does not rule out epilepsy. Capturing events during continuous video EEG monitoring is the gold standard AMS with acute brain injury (such as hemorrhage, trauma, | infection, stroke, hypoxia, cardiac arrest) | in diagnosis, typically performed in a multiple-day epilepsy | unit hospitalization in parallel with AED withdrawal under Unexplained AMS with subacute or chronic brain injury (tumor, | close supervision. Patients who have not responded to two | history of epilepsy) Unexplained AMS (or mental fluctuation) without acute brain adequately dosed AEDs are considered to have refractory dis- injury (as in sepsis) ease (see Drug-Resistant Epilepsy and Epilepsy Surgery); they | Unexplained AMS following a CNS procedure or CNS should be referred to an epilepsy center, where such an evalu- instrumentation ation can both confirm the diagnosis of epilepsy and deter- | Deep sedation and paralysis that limit the ability to perform a mine candidacy for epilepsy surgery. neurologic examination (as is used with therapeutic hypothermia, ECMO)

the physician must rely on “epileptiform” abnormalities, such WEY DOUNTS i 105 > Ge Se) a as focal sharp waves (see Figure 9) or generalized spike-and- ¢ MRI and electroencephalography are recommended for HVC wave discharges (see Figure 6). These findings are not diagnos- all patients with a first seizure; lumbar puncture is rec- tically confirmatory; rather, they may help support the ommended only if an infectious cause is suspected. diagnosis in an appropriate clinical context. A single routine EEG is only 40% to 50% sensitive for such findings, so clinical ° A single routine electroencephalographic study is only judgment based on history remains critical. Emergent lumbar 40% to 50% sensitive in diagnosing epilepsy. : puncture is recommended in adults only if an infectious cause, (Continued) such as meningitis or encephalitis, is suspected. TABLE 18. Indications for Immediate Continuous Video Electroencephalographic Monitoring in the Critical Care Setting Epilepsy Monitoring Units AMS following CSE? or clinical seizures A normal EEG does not rule out epilepsy. Capturing events during continuous video EEG monitoring is the gold standard AMS with acute brain injury (such as hemorrhage, trauma, | infection, stroke, hypoxia, cardiac arrest) | in diagnosis, typically performed in a multiple-day epilepsy | unit hospitalization in parallel with AED withdrawal under Unexplained AMS with subacute or chronic brain injury (tumor, | close supervision. Patients who have not responded to two | history of epilepsy) Unexplained AMS (or mental fluctuation) without acute brain adequately dosed AEDs are considered to have refractory dis- injury (as in sepsis) ease (see Drug-Resistant Epilepsy and Epilepsy Surgery); they | Unexplained AMS following a CNS procedure or CNS should be referred to an epilepsy center, where such an evalu- instrumentation ation can both confirm the diagnosis of epilepsy and deter- | Deep sedation and paralysis that limit the ability to perform a mine candidacy for epilepsy surgery. neurologic examination (as is used with therapeutic hypothermia, ECMO) Other Continuous Electroencephalographic Monitoring Clinical episodes concerning for seizures (such as unexplained Continuous video EEG monitoring also is useful in the ICU muscle or eye movements)?

the physician must rely on “epileptiform” abnormalities, such WEY DOUNTS i 105 > Ge Se) a as focal sharp waves (see Figure 9) or generalized spike-and- ¢ MRI and electroencephalography are recommended for HVC wave discharges (see Figure 6). These findings are not diagnos- all patients with a first seizure; lumbar puncture is rec- tically confirmatory; rather, they may help support the ommended only if an infectious cause is suspected. diagnosis in an appropriate clinical context. A single routine EEG is only 40% to 50% sensitive for such findings, so clinical ° A single routine electroencephalographic study is only judgment based on history remains critical. Emergent lumbar 40% to 50% sensitive in diagnosing epilepsy. : puncture is recommended in adults only if an infectious cause, (Continued) such as meningitis or encephalitis, is suspected. TABLE 18. Indications for Immediate Continuous Video Electroencephalographic Monitoring in the Critical Care Setting Epilepsy Monitoring Units AMS following CSE? or clinical seizures A normal EEG does not rule out epilepsy. Capturing events during continuous video EEG monitoring is the gold standard AMS with acute brain injury (such as hemorrhage, trauma, | infection, stroke, hypoxia, cardiac arrest) | in diagnosis, typically performed in a multiple-day epilepsy | unit hospitalization in parallel with AED withdrawal under Unexplained AMS with subacute or chronic brain injury (tumor, | close supervision. Patients who have not responded to two | history of epilepsy) Unexplained AMS (or mental fluctuation) without acute brain adequately dosed AEDs are considered to have refractory dis- injury (as in sepsis) ease (see Drug-Resistant Epilepsy and Epilepsy Surgery); they | Unexplained AMS following a CNS procedure or CNS should be referred to an epilepsy center, where such an evalu- instrumentation ation can both confirm the diagnosis of epilepsy and deter- | Deep sedation and paralysis that limit the ability to perform a mine candidacy for epilepsy surgery. neurologic examination (as is used with therapeutic hypothermia, ECMO) Other Continuous Electroencephalographic Monitoring Clinical episodes concerning for seizures (such as unexplained Continuous video EEG monitoring also is useful in the ICU muscle or eye movements)? (Table 18) . It can determine if episodic events are truly sei- AMS = altered mental status; CNS = central nervous system; CSE = convulsive F r . status epilepticus; ECMO = extracorporeal membrane oxygenation; EEG = zures, particularly in sedated or confused patients who cannot | electroencephalography. provide a history. This type of EEG is often the only method @lf CSE is suspected, treatment should begin before EEG is performed or results ' of diagnosing nonconvulsive status epilepticus (see later | are available; if nonconvulsive status epilepticus is suspected, treatment most | rm “ often should await EEG results. discussion).

(Table 18) . It can determine if episodic events are truly sei- AMS = altered mental status; CNS = central nervous system; CSE = convulsive F r . status epilepticus; ECMO = extracorporeal membrane oxygenation; EEG = zures, particularly in sedated or confused patients who cannot | electroencephalography. provide a history. This type of EEG is often the only method @lf CSE is suspected, treatment should begin before EEG is performed or results ' of diagnosing nonconvulsive status epilepticus (see later | are available; if nonconvulsive status epilepticus is suspected, treatment most | rm “ often should await EEG results. discussion). 19

Seizures and Epilepsy TABLE 19. Potential Causes of Seizures or Epilepsy Ss eizure-Provoking Factors Epilepsy Risk Factors Seizure Triggers | Hypo- or hypernatremia Febrile seizures Sleep deprivation | | , Hypo- or hypercalcemia Family history (especially first-degree Fever | | | : relatives) | Hypomagnesemia Emotional stress | Past meningitis/encephalitis | Hypoglycemia Acute infection (nonneurologic) | History of structural brain lesion (such as Hyperammonemia or hepatic failure woke, fumer) Hyperventilation | } | Uremia or kidney failure Past significant head trauma (loss of Photic stimulation | |

| Uremia or kidney failure Past significant head trauma (loss of Photic stimulation | | | Acute head trauma, meningitis, consciousness or amnesia >30 min, Music, reading, eating (only in specific reflex | | encephalitis, stroke, or hypoxia/ischemia penetrating skull injury) epilepsies) | } | Alcohol intoxication or withdrawal | Preterm birth | | Recreational drug use Birth injury, asphyxia, or stroke | | Benzodiazepine withdrawal Neurologic developmental delay | Baclofen withdrawal Intellectual disability | Fluoroquinolones History of brain surgery | Carbapenems Cefepime | Metronidazole | Tramadol | Meperidine | Morphine | Bupropion | Clozapine? | Lithium? | Tricyclic antidepressants? Typical antipsychotic agents® \ | is Can be used in patients with epilepsy, if needed. | Typically does not trigger seizures in patients without epilepsy and is not considered a provoking factor. L

| Tramadol | Meperidine | Morphine | Bupropion | Clozapine? | Lithium? | Tricyclic antidepressants? Typical antipsychotic agents® \ | is Can be used in patients with epilepsy, if needed. | Typically does not trigger seizures in patients without epilepsy and is not considered a provoking factor. L in patients with pre-existing epilepsy but do not cause epilepsy. e Continuous video electroencephalography is the only Determining the risk of recurrence guides the decision to method of diagnosing nonconvulsive status epilepticus, treat. The 2-year recurrence risk after a single unprovoked but diagnosis often requires clinical correlation as con- seizure is approximately 40%. Risk is lower (20%-30%) if there firmation. are no epilepsy risk factors and the MRI and EEG are normal. A first unprovoked seizure is often not treated; although treat- Provoked, Unprovoked, and Triggered Seizures ment may reduce the risk of seizure over the next 2 years, it Provoking factors, risk factors, and triggers all can lead to does not change a patient’s long-term prognosis for develop- seizures (Table 19), and differentiating among them is essen- ing epilepsy. Treatment is recommended in the setting of two tial. Provoking factors can cause seizures in patients with or unprovoked seizures (or one unprovoked seizure with signifi- without epilepsy; avoidance of these provocations should cant EEG or MRI abnormalities, such as trauma or stroke) prevent further seizures. Attention should be paid to the because recurrence risk is at least 60%. patient’s medications, and drugs that can cause a seizure or lower seizure threshold (such as tramadol, meperidine, bupropion, fluoroquinolones, carbapenems, and cefepime) e After a single unprovoked seizure with no abnormali- HvC should be avoided. Risk factors increasing the chance of ties on MRI or electroencephalography and with no developing epilepsy include a history of brain trauma, men- risk factors for epilepsy, the 2-year recurrence risk is ingitis, or stroke, but an acute symptomatic seizure (occur- approximately 20% to 30%, and treatment is typically ring within the first week afterward) may not necessarily withheld. (Continued) lead to the development of epilepsy. Triggers lead to seizures

in patients with pre-existing epilepsy but do not cause epilepsy. e Continuous video electroencephalography is the only Determining the risk of recurrence guides the decision to method of diagnosing nonconvulsive status epilepticus, treat. The 2-year recurrence risk after a single unprovoked but diagnosis often requires clinical correlation as con- seizure is approximately 40%. Risk is lower (20%-30%) if there firmation. are no epilepsy risk factors and the MRI and EEG are normal. A first unprovoked seizure is often not treated; although treat- Provoked, Unprovoked, and Triggered Seizures ment may reduce the risk of seizure over the next 2 years, it Provoking factors, risk factors, and triggers all can lead to does not change a patient’s long-term prognosis for develop- seizures (Table 19), and differentiating among them is essen- ing epilepsy. Treatment is recommended in the setting of two tial. Provoking factors can cause seizures in patients with or unprovoked seizures (or one unprovoked seizure with signifi- without epilepsy; avoidance of these provocations should cant EEG or MRI abnormalities, such as trauma or stroke) prevent further seizures. Attention should be paid to the because recurrence risk is at least 60%. patient’s medications, and drugs that can cause a seizure or lower seizure threshold (such as tramadol, meperidine, bupropion, fluoroquinolones, carbapenems, and cefepime) e After a single unprovoked seizure with no abnormali- HvC should be avoided. Risk factors increasing the chance of ties on MRI or electroencephalography and with no developing epilepsy include a history of brain trauma, men- risk factors for epilepsy, the 2-year recurrence risk is ingitis, or stroke, but an acute symptomatic seizure (occur- approximately 20% to 30%, and treatment is typically ring within the first week afterward) may not necessarily withheld. (Continued) lead to the development of epilepsy. Triggers lead to seizures 20

Seizures and Epilepsy in older patients, especially in those with concomitant diuretic use. e In the setting of two unprovoked seizures or one unpro- Enzyme-inducing AEDs (Table 22) increase statin clear- voked seizure with significant electroencephalographic ance and necessitate higher doses or alternative options; they or MRI abnormalities, the recurrence risk is at least 60%, also can increase bone catabolism. Therefore, bone density and treatment is recommended. testing and supplementation of calcium and vitamin D are recommended with chronic use of valproic acid or enzyme- inducing AEDs. This precautionary step is recommended even Treatment of Epilepsy in patients without traditional osteoporosis risk factors. Antiepileptic Drug Therapy Phenytoin, carbamazepine, phenobarbital, and lamotrig- Empiric pharmacologic treatment generally is not recom- ine are AEDs that commonly cause rash, which usually mended unless the patient’s history is strongly suggestive of resolves with discontinuation of the drug but sometimes may seizures or epilepsy. The exception is convulsive status epilep- be severe and life-threatening. For example, rapid titration of ticus, which must be treated emergently if clinically suspected. lamotrigine has been associated with the development of Similarly, prophylactic treatment is avoided except in specific Stevens-Johnson syndrome, toxic epidermal necrolysis, drug- situations, such as during the week after severe head induced hypersensitivity syndrome, and hemophagocytic trauma or brain tumor resection. Alcohol- or benzodiazepine- lymphohistiocytosis. Gabapentin has a low incidence of rash withdrawal seizures typically are not treated with AEDs. and also has good evidence of efficacy in epilepsy in older adults. Selection and Adverse Effects of Antiepileptic Drugs Nevertheless, expert consensus considers lamotrigine to Many AEDs are available for patients with epilepsy (Table 20). be a first-line, broad spectrum AED with an overall excellent Older AEDs, such as phenobarbital, phenytoin, carbamaze- safety and efficacy profile, when titrated slowly. pine, and valproate, are typically not preferred; although All AEDs carry a warning about worsening depression newer AEDs are not more effective in controlling seizures, they and suicidality, and all patients must be screened and moni- typically have fewer adverse effects, fewer drug interactions, tored for these symptoms. Levetiracetam may cause depres- and a reduced need for laboratory monitoring, although cost sion, anxiety, anger, or agitation. Perampanel may cause may be higher. Most often, treatment is guided by the seizure homicidal ideation. Topiramate may cause psychosis. type rather than AED mechanism or epilepsy cause. Lamotrigine and valproic acid, on the other hand, are mood Common adverse effects and monitoring recommenda- stabilizers. tions are listed in Table 21. Key dose-dependent adverse effects include oxcarbazepine-related hyponatremia and valproate- Monitoring and Discontinuing Antiepileptic Drugs related thrombocytopenia. Hyponatremia is a major concern Measuring serum levels of certain AEDs (phenytoin, carba- with use of oxcarbazepine, carbamazepine, or eslicarbazepine mazepine, valproic acid, phenobarbital, oxcarbazepine,

in older patients, especially in those with concomitant diuretic use. e In the setting of two unprovoked seizures or one unpro- Enzyme-inducing AEDs (Table 22) increase statin clear- voked seizure with significant electroencephalographic ance and necessitate higher doses or alternative options; they or MRI abnormalities, the recurrence risk is at least 60%, also can increase bone catabolism. Therefore, bone density and treatment is recommended. testing and supplementation of calcium and vitamin D are recommended with chronic use of valproic acid or enzyme- inducing AEDs. This precautionary step is recommended even Treatment of Epilepsy in patients without traditional osteoporosis risk factors. Antiepileptic Drug Therapy Phenytoin, carbamazepine, phenobarbital, and lamotrig- Empiric pharmacologic treatment generally is not recom- ine are AEDs that commonly cause rash, which usually mended unless the patient’s history is strongly suggestive of resolves with discontinuation of the drug but sometimes may seizures or epilepsy. The exception is convulsive status epilep- be severe and life-threatening. For example, rapid titration of ticus, which must be treated emergently if clinically suspected. lamotrigine has been associated with the development of Similarly, prophylactic treatment is avoided except in specific Stevens-Johnson syndrome, toxic epidermal necrolysis, drug- situations, such as during the week after severe head induced hypersensitivity syndrome, and hemophagocytic trauma or brain tumor resection. Alcohol- or benzodiazepine- lymphohistiocytosis. Gabapentin has a low incidence of rash withdrawal seizures typically are not treated with AEDs. and also has good evidence of efficacy in epilepsy in older adults. Selection and Adverse Effects of Antiepileptic Drugs Nevertheless, expert consensus considers lamotrigine to Many AEDs are available for patients with epilepsy (Table 20). be a first-line, broad spectrum AED with an overall excellent Older AEDs, such as phenobarbital, phenytoin, carbamaze- safety and efficacy profile, when titrated slowly. pine, and valproate, are typically not preferred; although All AEDs carry a warning about worsening depression newer AEDs are not more effective in controlling seizures, they and suicidality, and all patients must be screened and moni- typically have fewer adverse effects, fewer drug interactions, tored for these symptoms. Levetiracetam may cause depres- and a reduced need for laboratory monitoring, although cost sion, anxiety, anger, or agitation. Perampanel may cause may be higher. Most often, treatment is guided by the seizure homicidal ideation. Topiramate may cause psychosis. type rather than AED mechanism or epilepsy cause. Lamotrigine and valproic acid, on the other hand, are mood Common adverse effects and monitoring recommenda- stabilizers. tions are listed in Table 21. Key dose-dependent adverse effects include oxcarbazepine-related hyponatremia and valproate- Monitoring and Discontinuing Antiepileptic Drugs related thrombocytopenia. Hyponatremia is a major concern Measuring serum levels of certain AEDs (phenytoin, carba- with use of oxcarbazepine, carbamazepine, or eslicarbazepine mazepine, valproic acid, phenobarbital, oxcarbazepine, TABLE 20. Spectrum of Use of Antiepileptic Drugs

in older patients, especially in those with concomitant diuretic use. e In the setting of two unprovoked seizures or one unpro- Enzyme-inducing AEDs (Table 22) increase statin clear- voked seizure with significant electroencephalographic ance and necessitate higher doses or alternative options; they or MRI abnormalities, the recurrence risk is at least 60%, also can increase bone catabolism. Therefore, bone density and treatment is recommended. testing and supplementation of calcium and vitamin D are recommended with chronic use of valproic acid or enzyme- inducing AEDs. This precautionary step is recommended even Treatment of Epilepsy in patients without traditional osteoporosis risk factors. Antiepileptic Drug Therapy Phenytoin, carbamazepine, phenobarbital, and lamotrig- Empiric pharmacologic treatment generally is not recom- ine are AEDs that commonly cause rash, which usually mended unless the patient’s history is strongly suggestive of resolves with discontinuation of the drug but sometimes may seizures or epilepsy. The exception is convulsive status epilep- be severe and life-threatening. For example, rapid titration of ticus, which must be treated emergently if clinically suspected. lamotrigine has been associated with the development of Similarly, prophylactic treatment is avoided except in specific Stevens-Johnson syndrome, toxic epidermal necrolysis, drug- situations, such as during the week after severe head induced hypersensitivity syndrome, and hemophagocytic trauma or brain tumor resection. Alcohol- or benzodiazepine- lymphohistiocytosis. Gabapentin has a low incidence of rash withdrawal seizures typically are not treated with AEDs. and also has good evidence of efficacy in epilepsy in older adults. Selection and Adverse Effects of Antiepileptic Drugs Nevertheless, expert consensus considers lamotrigine to Many AEDs are available for patients with epilepsy (Table 20). be a first-line, broad spectrum AED with an overall excellent Older AEDs, such as phenobarbital, phenytoin, carbamaze- safety and efficacy profile, when titrated slowly. pine, and valproate, are typically not preferred; although All AEDs carry a warning about worsening depression newer AEDs are not more effective in controlling seizures, they and suicidality, and all patients must be screened and moni- typically have fewer adverse effects, fewer drug interactions, tored for these symptoms. Levetiracetam may cause depres- and a reduced need for laboratory monitoring, although cost sion, anxiety, anger, or agitation. Perampanel may cause may be higher. Most often, treatment is guided by the seizure homicidal ideation. Topiramate may cause psychosis. type rather than AED mechanism or epilepsy cause. Lamotrigine and valproic acid, on the other hand, are mood Common adverse effects and monitoring recommenda- stabilizers. tions are listed in Table 21. Key dose-dependent adverse effects include oxcarbazepine-related hyponatremia and valproate- Monitoring and Discontinuing Antiepileptic Drugs related thrombocytopenia. Hyponatremia is a major concern Measuring serum levels of certain AEDs (phenytoin, carba- with use of oxcarbazepine, carbamazepine, or eslicarbazepine mazepine, valproic acid, phenobarbital, oxcarbazepine, TABLE 20. Spectrum of Use of Antiepileptic Drugs Population First-Line Agent Second-Line Agent Considerations

in older patients, especially in those with concomitant diuretic use. e In the setting of two unprovoked seizures or one unpro- Enzyme-inducing AEDs (Table 22) increase statin clear- voked seizure with significant electroencephalographic ance and necessitate higher doses or alternative options; they or MRI abnormalities, the recurrence risk is at least 60%, also can increase bone catabolism. Therefore, bone density and treatment is recommended. testing and supplementation of calcium and vitamin D are recommended with chronic use of valproic acid or enzyme- inducing AEDs. This precautionary step is recommended even Treatment of Epilepsy in patients without traditional osteoporosis risk factors. Antiepileptic Drug Therapy Phenytoin, carbamazepine, phenobarbital, and lamotrig- Empiric pharmacologic treatment generally is not recom- ine are AEDs that commonly cause rash, which usually mended unless the patient’s history is strongly suggestive of resolves with discontinuation of the drug but sometimes may seizures or epilepsy. The exception is convulsive status epilep- be severe and life-threatening. For example, rapid titration of ticus, which must be treated emergently if clinically suspected. lamotrigine has been associated with the development of Similarly, prophylactic treatment is avoided except in specific Stevens-Johnson syndrome, toxic epidermal necrolysis, drug- situations, such as during the week after severe head induced hypersensitivity syndrome, and hemophagocytic trauma or brain tumor resection. Alcohol- or benzodiazepine- lymphohistiocytosis. Gabapentin has a low incidence of rash withdrawal seizures typically are not treated with AEDs. and also has good evidence of efficacy in epilepsy in older adults. Selection and Adverse Effects of Antiepileptic Drugs Nevertheless, expert consensus considers lamotrigine to Many AEDs are available for patients with epilepsy (Table 20). be a first-line, broad spectrum AED with an overall excellent Older AEDs, such as phenobarbital, phenytoin, carbamaze- safety and efficacy profile, when titrated slowly. pine, and valproate, are typically not preferred; although All AEDs carry a warning about worsening depression newer AEDs are not more effective in controlling seizures, they and suicidality, and all patients must be screened and moni- typically have fewer adverse effects, fewer drug interactions, tored for these symptoms. Levetiracetam may cause depres- and a reduced need for laboratory monitoring, although cost sion, anxiety, anger, or agitation. Perampanel may cause may be higher. Most often, treatment is guided by the seizure homicidal ideation. Topiramate may cause psychosis. type rather than AED mechanism or epilepsy cause. Lamotrigine and valproic acid, on the other hand, are mood Common adverse effects and monitoring recommenda- stabilizers. tions are listed in Table 21. Key dose-dependent adverse effects include oxcarbazepine-related hyponatremia and valproate- Monitoring and Discontinuing Antiepileptic Drugs related thrombocytopenia. Hyponatremia is a major concern Measuring serum levels of certain AEDs (phenytoin, carba- with use of oxcarbazepine, carbamazepine, or eslicarbazepine mazepine, valproic acid, phenobarbital, oxcarbazepine, TABLE 20. Spectrum of Use of Antiepileptic Drugs Population First-Line Agent Second-Line Agent Considerations Patients with focal seizures Lamotrigine Carbamazepine Includes treatment of secondarily generalized tonic-clonic seizures (i.e., Levetiracetam Gabapentin focal evolving to bilateral tonic-clonic) Oxcarbazepine Pregabalin | Topiramate | Zonisamide

Patients with focal seizures Lamotrigine Carbamazepine Includes treatment of secondarily generalized tonic-clonic seizures (i.e., Levetiracetam Gabapentin focal evolving to bilateral tonic-clonic) Oxcarbazepine Pregabalin | Topiramate | Zonisamide Patients with generalized Ethosuximide (absence only) Topiramate May be worsened by gabapentin, seizures pregabalin, carbamazepine, and Lamotrigine (may worsen Zonisamide ; oxcarbazepine | myoclonic seizures) Levetiracetam Valproate | Women of childbearing Lamotrigine Oxcarbazepine Avoid carbamazepine, phenobarbital, | potential phenytoin, topiramate, and valproate | Levetiracetam

Valproate | Women of childbearing Lamotrigine Oxcarbazepine Avoid carbamazepine, phenobarbital, | potential phenytoin, topiramate, and valproate | Levetiracetam Older patients Gabapentin Higher risk for hyponatremia with carbamazepine, oxcarbazepine, and Lamotrigine eslicarbazepine, especially with Levetiracetam concomitant diuretics 21

Seizures and Epilepsy TABLE 21. Adverse Effects of Selected Antiepileptic Drugs and Recommended Laboratory Monitoring Drug Common Adverse Effects Serious Adverse Effects Recommended Laboratory | Monitoring I f | Carbamazepine, Sedation, nausea, ataxia, tremor, diplopia, Hyponatremia, rash, CBC, liver chemistry studies, | oxcarbazepine, imbalance, headache, and dose-dependent pancytopenia, osteoporosis, bone density, serum drug and eslicarbaze- dizziness hepatotoxicity level pine Felbamate Insomnia, weight loss, nausea, vomiting, and Aplastic anemia and CBC, liver chemistry studies diarrhea hepatotoxicity? Gabapentin and Sedation, weight gain, edema, and dose- pregabalin dependent dizziness Lacosamide Sedation, nausea, ataxia, tremor, diplopia, Atrioventricular block, atrial ECG imbalance, headache, dose-dependent dizziness, fibrillation and PR-interval prolongation Lamotrigine Sedation, nausea, ataxia, tremor, diplopia, Rash Serum drug level imbalance, headache, insomnia, and dose- dependent dizziness Levetiracetam Sedation, irritability, psychosis, and depression Suicidal ideation® and | and brivara- thrombocytopenia (rare) cetam Perampanel Dizziness, headache, and sedation Homicidal ideation

Levetiracetam Sedation, irritability, psychosis, and depression Suicidal ideation® and | and brivara- thrombocytopenia (rare) cetam Perampanel Dizziness, headache, and sedation Homicidal ideation Phenobarbital Sedation (but paradoxical hyperactivity in Rash, pancytopenia, CBC, liver chemistry studies, children) osteoporosis, hepatotoxicity bone density, serum drug level Phenytoin Sedation, nausea, ataxia, tremor, diplopia, imbalance, Rash, gingival hyperplasia, CBC, liver chemistry studies, headache, and dose-dependent dizziness; if given cerebellar atrophy, peripheral bone density, serum drug \V, tissue necrosis (with extravasation), bradycardia, neuropathy, pancytopenia, level hypotension, and asystole osteoporosis, hepatotoxicity | Tiagabine Sedation, nausea, ataxia, tremor, diplopia, imbalance, Acute confusion and Tiagabine headache, and dose-dependent dizziness encephalopathy | Topiramate and Sedation, nausea, ataxia, tremor, diplopia, Nephrolithiasis, acute angle BMP in select cases | zonisamide imbalance, headache, word finding difficulty, glaucoma, psychosis poor concentration, paresthesias, weight loss, anhidrosis, and dose-dependent dizziness

| Topiramate and Sedation, nausea, ataxia, tremor, diplopia, Nephrolithiasis, acute angle BMP in select cases | zonisamide imbalance, headache, word finding difficulty, glaucoma, psychosis poor concentration, paresthesias, weight loss, anhidrosis, and dose-dependent dizziness | Valproic acid Sedation, nausea, ataxia, tremor, diplopia, Pancytopenia, osteoporosis, CBC, liver chemistry studies, imbalance, headache, and dose-dependent hepatotoxicity, pancreatitis, bone density, serum drug dizziness; weight gain, hair loss, PCOS, and hyperammonemia level, serum ammonia level reversible parkinsonism with dementia in select cases BMP= basic metabolic profile; CBC = complete blood count; IV, intravenously; PCOS = polycystic ovary syndrome. °A serious and potentially fatal adverse effect that limits this drug’s use (and requires close monitoring). ®A concern with all antiepileptic drugs, but especially levetiracetam.

| Valproic acid Sedation, nausea, ataxia, tremor, diplopia, Pancytopenia, osteoporosis, CBC, liver chemistry studies, imbalance, headache, and dose-dependent hepatotoxicity, pancreatitis, bone density, serum drug dizziness; weight gain, hair loss, PCOS, and hyperammonemia level, serum ammonia level reversible parkinsonism with dementia in select cases BMP= basic metabolic profile; CBC = complete blood count; IV, intravenously; PCOS = polycystic ovary syndrome. °A serious and potentially fatal adverse effect that limits this drug’s use (and requires close monitoring). ®A concern with all antiepileptic drugs, but especially levetiracetam. TABLE 22. Key Pharmacologic Issues with Selected Antiepileptic Drugs Inducers of Inhibitors of Requires Dose Avoid in Hepatic Highly Albumin No Significant Hepatic Hepatic Enzymes? Adjustment in Dysfunction Bound‘ Drug-Drug | | Enzymes?» Kidney Dysfunction Interactions Carbamazepine Valproic acid? Gabapentin Carbamazepine Phenytoin Gabapentin | Oxcarbazepine Levetiracetam Phenobarbital Valproate Lacosamide | Phenobarbital Pregabalin Phenytoin Levetiracetam | Phenytoin Valproic acid Pregabalin | Topiramate Zonisamide

TABLE 22. Key Pharmacologic Issues with Selected Antiepileptic Drugs Inducers of Inhibitors of Requires Dose Avoid in Hepatic Highly Albumin No Significant Hepatic Hepatic Enzymes? Adjustment in Dysfunction Bound‘ Drug-Drug | | Enzymes?» Kidney Dysfunction Interactions Carbamazepine Valproic acid? Gabapentin Carbamazepine Phenytoin Gabapentin | Oxcarbazepine Levetiracetam Phenobarbital Valproate Lacosamide | Phenobarbital Pregabalin Phenytoin Levetiracetam | Phenytoin Valproic acid Pregabalin | Topiramate Zonisamide May cause osteoporosis and interact with lamotrigine. | | May decrease statin and oral contraceptive efficacy. | i] | ‘Warrants checking unbound (free) blood level, especially in kidney failure and hypoalbuminemia.

May cause osteoporosis and interact with lamotrigine. | | May decrease statin and oral contraceptive efficacy. | i] | ‘Warrants checking unbound (free) blood level, especially in kidney failure and hypoalbuminemia. May accelerate bone catabolism and lead to osteoporosis. { i 22

Seizures and Epilepsy lamotrigine) is useful, given their known therapeutic windows they are not completely seizure free. Patients should avoid and predictable dose-related adverse effects. However, in a operating heavy machinery, using firearms, lifting more than patient whose epilepsy is well-controlled without clinical 9 kg (20 lb), taking tub baths, swimming in unsupervised adverse effects, dose reduction because of high levels usually locations, and being near open flames or heights (such as is not warranted. rooftops). Generic AEDs are appropriate for most patients, given recent guidelines. Well-designed studies have not shown dif- ferences in AED bioequivalence (according to FDA standards) Comorbidities and Complications when switching between generic drugs or switching from a of Epilepsy brand to a generic drug. Monitoring for AED toxicity and sei- Sudden Unexpected Death in Epilepsy Patients zures is advised if any change is made. Besides the risk of trauma, asphyxia, and death froma sei- Tapering of AEDs can be considered in patients remain- zure or status epilepticus, epilepsy patients are at risk for ing seizure free for at least 2 to 5 years. The best predictor of unexpected death. This risk is approximately 1 in 1000 and seizure freedom is time; a prolonged period of seizure free- increases to approximately 1 in 100 in patients with drug- dom predicts further seizure freedom. Factors prohibiting resistant seizures, especially those with uncontrolled GTCS AED weaning include the presence of JME, a history of dif- and those taking multiple AEDs. Mechanisms are unknown ficulties in early seizure control, and the presence of signifi- and may involve cardiac, respiratory, and autonomic dys- cant epilepsy risk factors (see Table 19). Relevant MRI regulation. Studies show that patients prefer to discuss sud- abnormalities, significant EEG abnormalities (especially den unexpected death in epilepsy openly; doing so can when not taking AEDs), risk of physical injury, and risk of encourage medication adherence and home safety planning activity restriction (e.g., work or driving) are additional (such as using webcams and bed monitors and sharing of considerations. There are no standardized AED tapering bedrooms). schedules.

lamotrigine) is useful, given their known therapeutic windows they are not completely seizure free. Patients should avoid and predictable dose-related adverse effects. However, in a operating heavy machinery, using firearms, lifting more than patient whose epilepsy is well-controlled without clinical 9 kg (20 lb), taking tub baths, swimming in unsupervised adverse effects, dose reduction because of high levels usually locations, and being near open flames or heights (such as is not warranted. rooftops). Generic AEDs are appropriate for most patients, given recent guidelines. Well-designed studies have not shown dif- ferences in AED bioequivalence (according to FDA standards) Comorbidities and Complications when switching between generic drugs or switching from a of Epilepsy brand to a generic drug. Monitoring for AED toxicity and sei- Sudden Unexpected Death in Epilepsy Patients zures is advised if any change is made. Besides the risk of trauma, asphyxia, and death froma sei- Tapering of AEDs can be considered in patients remain- zure or status epilepticus, epilepsy patients are at risk for ing seizure free for at least 2 to 5 years. The best predictor of unexpected death. This risk is approximately 1 in 1000 and seizure freedom is time; a prolonged period of seizure free- increases to approximately 1 in 100 in patients with drug- dom predicts further seizure freedom. Factors prohibiting resistant seizures, especially those with uncontrolled GTCS AED weaning include the presence of JME, a history of dif- and those taking multiple AEDs. Mechanisms are unknown ficulties in early seizure control, and the presence of signifi- and may involve cardiac, respiratory, and autonomic dys- cant epilepsy risk factors (see Table 19). Relevant MRI regulation. Studies show that patients prefer to discuss sud- abnormalities, significant EEG abnormalities (especially den unexpected death in epilepsy openly; doing so can when not taking AEDs), risk of physical injury, and risk of encourage medication adherence and home safety planning activity restriction (e.g., work or driving) are additional (such as using webcams and bed monitors and sharing of considerations. There are no standardized AED tapering bedrooms). schedules. e The risk of sudden unexpected death in epilepsy is e Newer antiepileptic drugs (AEDs), although not more approximately 1 in 1000 and increases to approximately effective in controlling seizures than older AEDs, are 1 in 100 in patients with drug-resistant seizures, espe- often preferred because they have fewer adverse effects, cially those with uncontrolled generalized tonic-clonic fewer drug interactions, and a reduced need for labora- seizures and those taking multiple antiepileptic drugs. tory monitoring.

e The risk of sudden unexpected death in epilepsy is e Newer antiepileptic drugs (AEDs), although not more approximately 1 in 1000 and increases to approximately effective in controlling seizures than older AEDs, are 1 in 100 in patients with drug-resistant seizures, espe- often preferred because they have fewer adverse effects, cially those with uncontrolled generalized tonic-clonic fewer drug interactions, and a reduced need for labora- seizures and those taking multiple antiepileptic drugs. tory monitoring. e Epilepsy treatment usually is guided by the seizure type Drug-Resistant Epilepsy and Epilepsy Surgery rather than drug mechanism or epilepsy cause. Any patient who does not achieve seizure freedom after e Enzyme-inducing antiepileptic drugs (AEDs) increase treatment with two adequately dosed, appropriately chosen statin clearance and necessitate higher doses or alterna- AEDs is considered to have drug-resistant epilepsy. Referral tive options; because these AEDs and valproic acid also to an epilepsy center is indicated both to confirm the diag- can increase bone catabolism, bone density testing and nosis and to evaluate the patient for surgical candidacy, supplemental calcium and vitamin D are recommended starting with video EEG monitoring. Because the chance of with chronic use. achieving seizure control from additional medications (a e Tapering of antiepileptic drugs can be considered in regimen of three or more AEDs) is less than 10%, other treat- most patients who remain seizure free for 2 to 5 years; ment options must be considered. In appropriately chosen factors prohibiting weaning include the presence of surgical candidates, especially those with temporal lobe juvenile myoclonic epilepsy, a history of difficulties in epilepsy due to mesial temporal sclerosis, resection can lead early seizure control, and the presence of significant to seizure freedom in 60% to 70% of patients. Implantable epilepsy risk factors. vagus nerve stimulators and the ketogenic diet are available

e Epilepsy treatment usually is guided by the seizure type Drug-Resistant Epilepsy and Epilepsy Surgery rather than drug mechanism or epilepsy cause. Any patient who does not achieve seizure freedom after e Enzyme-inducing antiepileptic drugs (AEDs) increase treatment with two adequately dosed, appropriately chosen statin clearance and necessitate higher doses or alterna- AEDs is considered to have drug-resistant epilepsy. Referral tive options; because these AEDs and valproic acid also to an epilepsy center is indicated both to confirm the diag- can increase bone catabolism, bone density testing and nosis and to evaluate the patient for surgical candidacy, supplemental calcium and vitamin D are recommended starting with video EEG monitoring. Because the chance of with chronic use. achieving seizure control from additional medications (a e Tapering of antiepileptic drugs can be considered in regimen of three or more AEDs) is less than 10%, other treat- most patients who remain seizure free for 2 to 5 years; ment options must be considered. In appropriately chosen factors prohibiting weaning include the presence of surgical candidates, especially those with temporal lobe juvenile myoclonic epilepsy, a history of difficulties in epilepsy due to mesial temporal sclerosis, resection can lead early seizure control, and the presence of significant to seizure freedom in 60% to 70% of patients. Implantable epilepsy risk factors. vagus nerve stimulators and the ketogenic diet are available palliative therapies but do not result in complete seizure Counseling and Lifestyle Adjustments control.

e Epilepsy treatment usually is guided by the seizure type Drug-Resistant Epilepsy and Epilepsy Surgery rather than drug mechanism or epilepsy cause. Any patient who does not achieve seizure freedom after e Enzyme-inducing antiepileptic drugs (AEDs) increase treatment with two adequately dosed, appropriately chosen statin clearance and necessitate higher doses or alterna- AEDs is considered to have drug-resistant epilepsy. Referral tive options; because these AEDs and valproic acid also to an epilepsy center is indicated both to confirm the diag- can increase bone catabolism, bone density testing and nosis and to evaluate the patient for surgical candidacy, supplemental calcium and vitamin D are recommended starting with video EEG monitoring. Because the chance of with chronic use. achieving seizure control from additional medications (a e Tapering of antiepileptic drugs can be considered in regimen of three or more AEDs) is less than 10%, other treat- most patients who remain seizure free for 2 to 5 years; ment options must be considered. In appropriately chosen factors prohibiting weaning include the presence of surgical candidates, especially those with temporal lobe juvenile myoclonic epilepsy, a history of difficulties in epilepsy due to mesial temporal sclerosis, resection can lead early seizure control, and the presence of significant to seizure freedom in 60% to 70% of patients. Implantable epilepsy risk factors. vagus nerve stimulators and the ketogenic diet are available palliative therapies but do not result in complete seizure Counseling and Lifestyle Adjustments control. All patients experiencing a seizure, even a single provoked seizure, must be instructed about seizure precautions, e Any patient who does not achieve seizure freedom after including driving restrictions. Most states restrict driving in treatment with two adequately dosed, appropriately patients with any episode of altered awareness or motor chosen antiepileptic drugs is considered to have drug- control, with the restriction varying by state from 3 to resistant epilepsy and should be referred to an epilepsy 12 months (see www.epilepsy.com/driving-laws). Additionally, center to both confirm the diagnosis and evaluate the patients should avoid common triggers and provoking factors patient for surgical candidacy. (see Table 19). Most patients with epilepsy can work, even if

All patients experiencing a seizure, even a single provoked seizure, must be instructed about seizure precautions, e Any patient who does not achieve seizure freedom after including driving restrictions. Most states restrict driving in treatment with two adequately dosed, appropriately patients with any episode of altered awareness or motor chosen antiepileptic drugs is considered to have drug- control, with the restriction varying by state from 3 to resistant epilepsy and should be referred to an epilepsy 12 months (see www.epilepsy.com/driving-laws). Additionally, center to both confirm the diagnosis and evaluate the patients should avoid common triggers and provoking factors patient for surgical candidacy. (see Table 19). Most patients with epilepsy can work, even if 23