EPILEPSY. Jassin M. Jouria, MD

Transcription

1 EPILEPSY Jassin M. Jouria, MD ABSTRACT Epilepsy is a seizure disorder of varied etiology and symptomology and its treatment depends on multiple factors, including age of onset and type of seizure. Sometimes the seizure is absent or mild enough to go untreated by medication and resolves over time. Most often, epilepsy is a life long condition that requires close medical management. Anti-epileptic drug therapy often requires serum monitoring for dose adjustment and drug interaction surveillance. Screening for comorbid medical and psychiatric conditions, especially depression, anxiety, and feelings of social stigma and isolation is needed. Educating patients and families to increase awareness of epilepsy and treatment options in their unique circumstance will assist them to overcome stereotypes and help them obtain a higher quality of life. Introduction Epilepsy is a complex brain disorder that is characterized by seizures, which are caused by disturbances in the brain s electrical functions. The term epilepsy encompasses a variety of different neurological syndromes, each ranging in its symptoms, severity, and duration. The characteristic seizures are present in all types of epilepsy, but they differ in clinical presentation and symptom severity depending on the type of epilepsy. Epilepsy is most common in young children and the elderly, but it can affect individuals of all ages. In many cases, the cause of epilepsy is unknown. In those instances when a cause is identified, we find that the cause varies ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 1

2 between environmental or genetic factors, or as part of traumatic injury. Some epileptic syndromes will only last a short time, especially those caused by trauma; however, some other epileptic syndromes will be lifelong conditions that cannot be cured. While many individuals will experience a single, unprovoked seizure at some point in their lives, epilepsy is not considered as a diagnosis until the patient has had two or more unprovoked seizures. Once this occurs, the patient will begin the process for assessing and diagnosing the type of epilepsy. Overview Of Epilepsy Epilepsy affects the central nervous system, thereby causing disruptions in the nerve cell activity in the brain. When this activity is disrupted, seizures occur (1). These seizures will cause the patient to experience abnormal behavior, symptoms, and sensations. In some instances, patients will lose consciousness. The presentation of seizures will vary. Some patients will stare blankly for a brief period of time, typically a few seconds. Other patients may experience twitching and jerking of their bodies (2). The type of seizure experienced by the patient depends upon the etiology and the severity of the condition. Regardless of the severity of the seizures, most patients will require treatment, as seizures can pose a significant risk to the patient. Seizures can occur when the patient is engaging in activities such as driving, operating machinery, or swimming, When this occurs, the patient is at an increased risk of experiencing significant injuries (3). Specific symptoms and features typically define epileptic syndromes. The categories include: (4) ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 2

3 Seizure types Age when seizures begin Electroencephalogram (EEG) findings Brain structure (usually assessed with a brain MRI scan) Family history of epilepsy or genetic disorder Prognosis (future outlook) Approximately fifty percent of epilepsy cases are caused by unknown factors. In the remaining cases, the causes are typically genetic, environmental, or trauma related (5). The following table provides an explanation of the potential cause in cases where the cause of epilepsy may be identified (6): Genetic Influence Some types of epilepsy, which are categorized by the type of seizure the individual experiences, run in families. In these cases, it's likely that there's a genetic influence. Researchers have linked some types of epilepsy to specific genes; though it's estimated that up to 500 genes could be tied to the condition. For most people, genes are only part of the cause of epilepsy. Certain genes may make a person more sensitive to environmental conditions that trigger seizures. Generalized epilepsy seizure types appear to be more related to genetic influences than partial seizure epilepsies. Head Trauma Head trauma that occurs due to a car accident or other traumatic injury can cause epilepsy. Head injuries can cause epilepsy in both adults and children, with the risk highest in severe head trauma. A ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 3

4 first seizure related to the injury can occur years later, but only very rarely. People with mild head injuries that involve loss of consciousness for fewer than 30 minutes have only a slight risk that lasts up to 5 years after the injury. Brain conditions - Brain conditions that result in damage to the brain, such as brain tumors or strokes, also can cause epilepsy. Stroke is a leading cause of epilepsy in adults older than age 35. Infectious Diseases Infectious diseases, such as meningitis, AIDS and viral encephalitis, can cause epilepsy. Prenatal injury Before birth, babies are sensitive to brain damage that could be caused by several factors, such as an infection in the mother, poor nutrition or oxygen deficiencies. This brain damage can result in epilepsy or cerebral palsy. Developmental Disorders Epilepsy can sometimes be associated with developmental disorders, such as autism and neurofibromatosis. Brain Chemistry Factors Ion Channels - sodium, potassium, and calcium - act as ions in the brain. They produce electric charges that must fire regularly in order for a steady current to pass from one nerve cell in the brain to another. If the ion channels that carry them are genetically damaged, a chemical imbalance occurs. This can cause nerve signals to misfire, leading to seizures. Abnormalities in the ion channels are believed to be responsible for absence and many other generalized seizures. Neurotransmitters - Abnormalities may occur in neurotransmitters, the chemicals that act as messengers between nerve cells. Three neurotransmitters are of particular interest: Gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. Serotonin's role in epilepsy is also being studied. Serotonin is a brain chemical that is important for well-being and associated ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 4

5 behaviors (such as eating, relaxation, and sleep). Imbalances in serotonin are also associated with depression. Acetylcholine is a neurotransmitter that is important for learning and memory. Risk Factors Epilepsy and seizure disorders affect nearly 3 million Americans and more than 45 million people worldwide. While anyone can develop epilepsy, there are a number of factors (outlined below) that will increase an individual s risk of developing epilepsy and seizure disorders (7). Age factor: Epilepsy affects all age groups. The risk is highest in children under the age of 2 and older adults over age 65. In infants and toddlers, prenatal factors and birth delivery problems are associated with epilepsy risk. In children age 10 and younger, generalized seizures are more common. In older children, partial seizures are more common. Gender factors: Men have a slightly higher risk than women of developing epilepsy. Family History: People who have a family history of epilepsy are at increased risk of developing the condition. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 5

6 While there are numerous factors that may cause epilepsy, as well as a variety of epileptic syndromes, all types share one common feature: all forms of epilepsy are characterized by recurrent seizures (1). These seizures are caused by uncontrolled electrical discharges in the nerve cells in the cerebral cortex. Many individuals will experience a single seizure at some point in their lifetime. This is not considered epilepsy (3). Very few initial seizures will recur. In fact, only approximately twenty five percent of initial seizures will recur (8). Once a patient experiences two or more recurring seizures, he or she has a 70 % chance of experiencing recurring seizures. This will result in a diagnosis of epilepsy. Epilepsy is generally classified into (Photo Courtesy of: two main categories based on seizure type, and these are described in the table below (9): PARTIAL SEIZURES These seizures are more common than generalized seizures and occur in one or more specific locations in the brain. In some cases, partial seizures can spread to wide regions of the brain. They are likely to develop from specific injuries, but in most cases the exact origins are unknown (idiopathic). Simple Partial A person with a simple partial seizure (sometimes known as Seizures Jacksonian epilepsy) does not lose consciousness, but may experience confusion, jerking movements, tingling, or odd mental and emotional events. Such events may include déjà vu, mild hallucinations, or extreme responses to smell and taste. After the seizure, the patient usually has temporary weakness in certain muscles. These seizures typically last about 90 seconds. Complex Partial Slightly over half of seizures in adults are complex partial Seizures type. About 80% of these seizures originate in the temporal ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 6

7 lobe, the part of the brain located close to the ear. Disturbances there can result in loss of judgment, involuntary or uncontrolled behavior, or even loss of consciousness. Patients may lose consciousness briefly and appear to others as motionless with a vacant stare. Emotions can be exaggerated; some patients even appear to be drunk. After a few seconds, a patient may begin to perform repetitive movements, such as chewing or smacking of lips. Episodes usually last no more than 2 minutes. They may occur infrequently, or as often as every day. A throbbing headache may follow a complex partial seizure. In some cases, simple or complex partial seizures evolve into what are known as secondarily generalized seizures. The progression may be so rapid that the initial partial seizure is not even noticed. GENERALIZED SEIZURES Generalized seizures are caused by nerve cell disturbances that occur in more widespread areas of the brain than partial seizures. Therefore, they have a more serious effect on the patient. They are further subcategorized as tonic-clonic (or grand mal), absence (petit mal), myoclonic, or atonic seizures. Tonic-Clonic (Grand Mal) Seizures. The first stage of a grand mal seizure is called the tonic phase, in which the muscles suddenly contract, causing the patient to fall and lie stiffly for about seconds. Some people experience a premonition or aura before a grand mal seizure; most, however, lose consciousness without warning. If the throat or larynx is affected, there may be a high-pitched musical sound (stridor) when the patient inhales. Spasms occur for about 30 seconds to 1 minute. Then the seizure enters the second phase, called the clonic phase. The muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control. The seizure usually lasts a total of 2-3 minutes, after which the patient remains unconscious for a while and then awakens to ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 7

8 Absence (Petit Mal) Seizures. confusion and extreme fatigue. A severe throbbing headache similar to migraine may also follow the tonic-clonic phases. Absence (petit mal) seizures are brief losses of consciousness that occur for 3-30 seconds. Physical activity and loss of attention last for only a moment. Such seizures may pass unnoticed by others. Young children may simply appear to be staring or walking distractedly. Petit mal may be confused with simple or complex partial seizures, or even with attention deficit disorder. In petit mal seizures, a person may experience attacks as often as times a day. Atonic (Akinetic) Seizures. Simply Tonic or Clonic Seizures Myoclonic seizures are a series of brief jerky contractions of specific muscle groups, such as the face or trunk. A person who has an atonic (akinetic) seizure loses muscle tone. Sometimes it may affect only one part of the body so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person can suddenly fall. A brief atonic episode is known as a drop attack. Seizures can also be simply tonic or clonic. In tonic seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic or jerking phase. Clonic seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not tonic rigidity. Types of Epilepsy While there are a number of different epilepsy syndromes, there are two primary types of epilepsy that affect a number of individuals. Each type has specific features that distinguish it (10). ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 8

9 Idiopathic Epilepsy In idiopathic generalized epilepsy, there is often, but not always, a family history of epilepsy. Idiopathic generalized epilepsy tends to appear during childhood or adolescence, although it may not be diagnosed until adulthood. In this type of epilepsy, no nervous system (brain or spinal cord) abnormalities, other than the seizures, can be identified on either an EEG or magnetic resonance imaging (MRI) studies. The brain is structurally normal on a brain (MRI) scan, although special studies may show a scar or subtle change in the brain that may have been present since birth. People with idiopathic generalized epilepsy have normal intelligence and the results of the neurological exam and MRI are usually normal. The results of the EEG may show epileptic discharges affecting a single area or multiple areas in the brain (so called generalized discharges). The types of seizures affecting patients with idiopathic generalized epilepsy may include: Myoclonic seizures (sudden and very short duration jerking of the extremities) Absence seizures (staring spells) Generalized tonic-clonic seizures (grand mal seizures) Idiopathic generalized epilepsy is usually treated with medications. Some people outgrow this condition and stop having seizures, as is the case with childhood absence epilepsy and a large number of patients with juvenile myoclonic epilepsy. Symptomatic Idiopathic partial epilepsy begins in childhood (between ages 5 and 8) and may be part of a family history. Also known as benign focal epilepsy of childhood (BFEC), this is considered one of the mildest types of epilepsy. It is almost always outgrown by puberty and is never diagnosed in adults. Seizures tend to occur during sleep and are most often simple partial motor seizures that involve the face and secondarily generalized (grand mal) seizures. This type of epilepsy is usually diagnosed with an EEG. Symptomatic generalized epilepsy (SGE) encompasses a group of ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 9

10 Generalized Epilepsy challenging epilepsy syndromes. As a group, SGE has 3 main features: (1) multiple seizure types, especially generalized tonic and atonic seizures; (2) brain dysfunction other than the seizures, in the intellectual domain (mental retardation or developmental delay) and in the motor domain (cerebral palsy); and (3) EEG evidence of diffuse brain abnormality. The following are examples of epilepsy syndromes that are included in the category of SGE: Early myoclonic encephalopathy Early infantine epileptic encephalopathy with suppression bursts or Ohtahara syndrome West syndrome Epilepsy with myoclonic atonic seizures Epilepsy with myoclonic absence Lennox-Gastaut syndrome Progressive myoclonic epilepsies Epilepsy Syndromes There are a number of different syndromes that fall under the umbrella of epilepsy. These syndromes are defined based upon the type and severity of seizures, as well as the area of the brain that is affected. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 10

11 (Photo Courtesy of: To further distinguish these syndromes, factors such as age, cause, and outcome are also included in the defining characteristics. The following section provides a thorough overview of the various epilepsy syndromes (9,11 16). Temporal Lobe Epilepsy Temporal Lobe Epilepsy (TLE) means that the seizures arise in the temporal lobe of the brain. Experiences during temporal lobe seizures vary in intensity and quality. Sometimes the seizures are so mild that the person barely notices. In other cases, the person may be consumed with feelings of fear, pleasure, or unreality. A patient may also report an odd smell, an abdominal sensation that rises up through the chest into the throat, an old memory or familiar feeling, or a feeling that is impossible to describe. Types of seizures in TLE The most common seizure type in TLE is a complex partial seizure. During complex partial seizures, people with TLE tend to perform repetitive, automatic movements (called automatisms), such as lip smacking and rubbing their hands together. Three-quarters of people with TLE also have simple partial seizures, and about half have tonic-clonic seizures at some time. Some people with TLE experience only simple partial seizures. Temporal lobe seizures usually begin in the deeper portions of the temporal lobe. This area is part of the limbic system, which controls emotions and memory. This is why the seizures can include a feeling of déjà vu, fear, or anxiety, and why some people with TLE may have problems with memory and depression. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 11

12 In most cases, the seizures associated with TLE can be fully controlled with medications used for partial seizures. If drugs are ineffective, brain surgery is often an option for patients with TLE. Temporal lobectomy is the most common and successful form of epilepsy surgery. Vagus nerve stimulation can also be beneficial in cases where temporal lobectomy is not recommended or has failed. Frontal lobe epilepsy is the next most common form of epilepsy after temporal lobe epilepsy (TLE), and involves the frontal lobes of the brain. As in temporal lobe epilepsy, seizures in frontal lobe epilepsy are partial, though seizure symptoms differ depending on the frontal lobe area involved. Frontal Lobe Epilepsy Since the frontal lobes are responsible for a wide array of functions including motor function, language, impulse control, memory, judgment, problem solving, and social behavior, seizure symptoms in the frontal lobes vary widely. Also, the frontal lobes are large and include many areas that do not have a precisely known function. Therefore, when a seizure begins in these areas, there may be no symptoms until it spreads to other or most areas of the brain, causing a tonic-clonic seizure. When motor areas controlling motor movement are affected, abnormal movements occur on the opposite side of the body. Seizures beginning in frontal lobe motor areas can result in weakness or the inability to use certain muscles, such as the muscles that allow someone to speak. Complex partial seizures of frontal lobe origin are usually quite different from temporal lobe seizures. Frontal lobe seizures tend to be short (less than 1 minute), and occur in clusters and during sleep. They include strange automatisms such as bicycling movements, screaming, or even sexual ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 12

13 activity, followed by confusion or tiredness. Sometimes a person will remain fully aware during a frontal lobe seizure, while at the same time having wild movements of the arms and legs. In fact, a seizure from the frontal lobe may even involve laughing or crying as the only symptom, though both laughing (gelastic) and crying (dacrystic) seizures could come from the temporal lobe as well. The EEG might be the only way to determine which lobe is involved in these cases. In many cases, frontal lobe seizures can be well controlled with medications for partial seizures. If antiepileptic drugs are not effective, surgery to remove the seizure focus may be an option in selected cases. Those patients with abnormalities on the brain MRI or CT scans limited to one frontal lobe are the best candidates, but even those with normal imaging studies may be successfully treated with surgery. Vagus nerve stimulation can also be beneficial in cases where brain surgery is not recommended or fails. Parietal Lobe Epilepsy Parietal lobe epilepsy is a relatively rare form of epilepsy, comprising about 5% of all epilepsy, in which seizures arise from the parietal lobe of the brain. Parietal lobe epilepsy can start at any age and occurs in both males and females equally. It may be a result of head trauma, birth difficulties, stroke, or tumor, though the cause is unknown in 20% of patients. The parietal lobe is located just behind the frontal lobe and it plays important roles in touch perception, the integration of sensory information and in visual perception of spatial relationships among objects (visuospatial processing). In the language dominant side of the brain (the left side for most right-handed individuals), the parietal lobe is also involved with ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 13

14 language, planned movements such as writing, as well as mathematical skills. Since the parietal lobe involves the processing and integration of sensory and visual perception, seizures originating from the parietal lobe can involve both sensory and visual sensations. Seizure duration varies, from a few seconds in some patients to a few minutes in others. The following are the different types of symptoms associated with parietal lobe seizures. Somatosensory seizures These are the most common type of seizures in parietal epilepsies. Patients with these types of seizures describe feeling physical sensations of numbness and tingling, heat, pressure, electricity and/or pain. Pain, though a rare symptom in seizures overall, is quite common in parietal seizures, occurring in up to one quarter of patients. Some patients describe a typical Jacksonian march, in which the sensation marches in a predictable pattern from the face to the hand up the arm and down the leg. Rarely, a patient will describe a sensation in the genitalia, occasionally leading to orgasm. Somatic illusions During a somatic illusion, another common symptom of parietal seizures, patients may experience a feeling like their posture is distorted, that their arms or legs are in a weird position or are in motion when they are not, or that a part of their body is missing or feels like it does not belong. Patients with parietal seizures may also experience vertigo, a sensation of movement or spinning of the environment, or of their body within the environment. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 14

15 Visual illusions and hallucinations Patients with visual illusions report a distortion of visual perception. Objects seem too close, too far, too large, too small, slanted, moving or otherwise not right. A patient with hallucinations describes seeing objects that seem very real, though in fact they do not exist. Rarely, a patient with a parietal seizure will report difficulty understanding spoken words or language, difficulty reading or performing simple math. Treatment with antiepileptic medication is usually effective in controlling seizures in parietal lobe epilepsy. In severe cases, surgery may be an option. Occipital Lobe Epilepsy In occipital lobe epilepsy, seizures arise from the occipital lobe of the brain, which sits at the back of the brain, just below the parietal lobe and just behind the temporal lobe. The occipital lobe is the main center of the visual system. Occipital lobe epilepsy accounts for about 5-10% of all epilepsy syndromes. This kind of epilepsy can be either idiopathic (of unknown, presumed genetic, cause) or symptomatic (associated with a known or suspected underlying lesion). Benign occipital epilepsies usually begin in childhood and are discussed elsewhere. Occipital seizures usually begin with visual hallucinations like flickering or colored lights, rapid blinking, or other symptoms related to the eyes and vision. They may occur spontaneously but can often be triggered by particular visual stimuli, such as seeing flashing lights or a repeating pattern. Occipital seizures are often mistaken for migraine headache because they ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 15

16 share similar symptoms including visual disturbances, partial blindness, nausea and vomiting, and headache. The following are the different types of seizure symptoms associated with occipital lobe seizures: Visual hallucinations and/or illusions Blindness or decreased vision Pallinopsia or image repetition (image replayed again and again) can occur: Sensation of eye movements Eye pain Involuntary eye movement to one or other side Nystagmus or eye jerking to one or other side (rapid involuntary rhythmic eye movement, with the eyes moving quickly in one direction (quick phase), and then slowly in the other (slow phase), Eyelid fluttering As with any epilepsy syndrome, detailed patient history, neurological examination, and EEG are very important. In occipital lobe epilepsy, the EEG may provide information that is very helpful in making the correct diagnosis. An abnormal response in the EEG to intermittent photic stimulation (rapidly flashing strobe light) often occurs in occipital lobe epilepsy; however, this response can occur in other epilepsy syndromes as well. Treatment with a drug used for partial epilepsy, often carbamazepine, is usually effective. In intractable cases (those that do not respond to medication), surgical options may be considered. Primary Generalized Epilepsy Primary Generalized Epilepsy (PGE), also called Idiopathic Generalized Epilepsy (IGE), refers to an epilepsy syndrome of idiopathic or unknown cause. An idiopathic disease is a primary or intrinsic disorder that cannot be ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 16

17 attributed to a known underlying condition. So, while other types of epilepsy may be caused by a brain tumor, stroke, or other neurological disorder, idiopathic epilepsy is a primary brain disorder of unknown cause. In fact, most idiopathic epilepsy syndromes are presumed to be due to a genetic cause, but in most cases the specific genetic defect is not known and a family history of epilepsy may not be present. There are a number of different PGE syndromes. Each syndrome has its own characteristic seizure type(s), typical age of onset, and specific EEG patterns. Some of these syndromes are: Childhood absence epilepsy Juvenile myoclonic epilepsy Juvenile absence epilepsy Epilepsy with generalized tonic-clonic seizures on awakening Generalized epilepsies with febrile seizures PGE is a generalized type of epilepsy, which means there is no single part of the brain where seizures originate. In fact, EEG results may show epileptic discharges affecting the entire brain. The types of seizures patients with PGE exhibit may include myoclonic seizures and absence seizures. Generalized tonic-clonic seizures The seizures in PGE usually respond well to medication. Some of the more commonly prescribed medications for these syndromes include: valproate, lamotrigine, topiramate, levetiracetam; and, in Childhood Absence Epilepsy, ethosuximide. Nearly all patients with PGE begin having seizures in childhood or adolescence. Most patients with childhood absence epilepsy (CAE) start having seizures before age 10, and outgrow their seizures within a few years, meaning that they no longer need medication to control their ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 17

18 seizures. On the other hand, juvenile myoclonic epilepsy (JME) is generally considered a life-long disease. Once seizures start, usually in adolescence, most patients need medication treatment for life to prevent seizure recurrence. Individuals with PGE syndromes usually have normal development and intelligence. Idiopathic Partial Epilepsy Just as there are generalized epilepsies of unidentifiable, presumably genetic, cause, there are also partial epilepsy syndromes of unknown or idiopathic cause, or Idiopathic Partial Epilepsies. An idiopathic disease is a disorder that cannot be attributed to a known underlying condition. So, while other types of epilepsy may be caused by a brain tumor, stroke, or other neurological disorder, idiopathic epilepsy is a primary brain disorder of unknown cause. In fact, most idiopathic epilepsy syndromes are presumed to be due to a genetic cause, but in most cases the specific genetic defect is not known and a family history of epilepsy may not be present. Benign rolandic epilepsy There are a few idiopathic partial epilepsy syndromes. Each individual syndrome generally has its own characteristic seizure type(s), typical age of onset, and specific EEG patterns. Some of these syndromes are known as: benign rolandic epilepsy, is also known as benign epilepsy of childhood with centrotemporal spikes, early onset benign childhood occipital epilepsy, and, late onset benign childhood occipital epilepsy. The seizures in idiopathic partial epilepsy typically respond well to medications used for other partial epilepsy syndromes. However, depending on the seizure type, time of day, and frequency, some providers and parents choose not to treat the individual with medication at all. For example, a ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 18

19 patient with benign rolandic epilepsy who experiences rare nocturnal seizures consisting of only brief face and arm twitching may do well without any medication treatment. Though the prognosis of these syndromes varies by syndrome type, it is usually quite good. Younger patients with these syndromes most often outgrow their seizures by teenage years or young adulthood, and also have normal intelligence and motor skills. Symptomatic Generalized Epilepsy Symptomatic Generalized Epilepsy (SGE) refers to epilepsy syndromes in which the majority of seizures are generalized, but partial onset seizures can also occur. The types of generalized seizures that occur in SGE include myoclonic, tonic, atonic, atypical absence, and generalized tonic-clonic. Virtually any type of partial onset seizure can also occur, depending on the underlying brain pathology. Usually (but not always) there is a known underlying brain disorder or injury, which is often severe. These syndromes may occur in the setting of certain neurological diseases, such as Tuberous Sclerosis (a rare genetic mutation that affects several organ systems), or may be due to lack of oxygen at birth, trauma, infection, developmental malformations, chromosomal abnormalities or other causes. SGE syndromes typically begin in early life. The following is a list of some symptomatic generalized epilepsy syndromes: West Syndrome Lennox-Gastaut Syndrome Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences Early myoclonic encephalopathy ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 19

20 Early infantile epileptic encephalopathy with suppression burst Progressive myoclonic epilepsies Antiepileptic medications are the mainstay of treatment in SGE, though certain syndromes may require additional treatments including adrenocorticotropic hormone (ACTH) or Immunoglobulin. The ketogenic diet may be helpful in some patients. The vagus nerve stimulator has been studied extensively in patients with SGE. In some patients it has been very helpful, while others have experienced no benefit. In patients with atonic, or drop seizures, a surgical procedure called corpus callosotomy may help reduce the falls that may result from seizures. There are, however, some SGE syndromes in which other surgical options may be considered. In Tuberous Sclerosis, for example, where the epilepsy is often considered a SGE syndrome, certain tubers may be more epileptogenic than others. If such a tuber is found to be the cause of the most disabling seizures, removal of it could reduce the frequency of seizures. The prognosis of SGE depends largely on the underlying cause of the seizures. For example, up to 15-30% of patients with West Syndrome, affecting infants, without known cause become seizure free and have normal or near normal intelligence. However, patients with Lennox-Gastaut Syndrome or progressive myoclonic epilepsy tend to have seizures throughout life, and some level of cognitive impairment. Progressive Myoclonic Epilepsy Progressive myoclonic epilepsies are rare and frequently result from hereditary metabolic disorders. They feature a combination of myoclonic and ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 20

21 tonic-clonic seizures. Unsteadiness, muscle rigidity, and mental deterioration are often also present. Progressive myoclonic epilepsies are treated with medication, which usually proves to be successful for a short period of time (months to years). However, as the disorder progresses, drugs become less effective and adverse effects may be more severe as more drugs are used at higher doses. Valproate and zonisamide are most commonly used. Other commonly prescribed drugs include clonazepam, lamotrigine, topiramate, phenobarbital and carbamazepine. Types of Progressive Myoclonic Epilepsies include: Mitchondrial Disorders, involving mutation of genes, and; Unverricht-Lundborg Syndrome, a myoclonic disorder. Reflex Epilepsy In reflex epilepsies, seizures are triggered by specific stimuli in the environment. In the most common type of reflex epilepsy, flashing lights trigger absence, myoclonic or tonic-clonic seizures. This is called photosensitive epilepsy, which usually begins in childhood and is often outgrown by adulthood. Other environmental triggers in reflex epilepsy include sounds such as church bells, a certain type of music or song, or a person s voice. For some people, activities such as arithmetic, reading, writing, and even thinking about specific topics can provoke seizures. These non-visual stimuli may trigger generalized or partial-onset seizures. Some patients with reflex epilepsy can have spontaneous seizures that occur without exposure to their specific trigger. A two-pronged approach is usually best in treating reflex epilepsy: avoiding the triggering stimulus as much as possible, and treatment with antiepileptic ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 21

22 drugs. Valproate, carbamazepine and clonazepam have been most commonly prescribed to control reflex seizures, though lamotrigine, levetiracetam and other newer antiepileptic medication are promising. Epilepsy Syndromes In Children Febrile Seizures Children aged 6 months to 5-6 years may have tonic-clonic seizures when they have a high fever. These are called febrile seizures and occur in 2% to 5% of children. There is a slight familial (hereditary) tendency toward febrile seizures. In other words, the chances are slightly increased that a child will have febrile seizures if their parents, brothers or sisters, or other close relatives have had them. The peak age of febrile seizures is about 18 months. The usual situation is a healthy child with normal development, who has a viral illness with high fever. As the child's temperature rapidly rises, he or she has a tonic-clonic seizure. The seizure usually involves muscles on both sides of the body. Febrile seizures can be as short as a minute or two, or as long as 30 minutes or more. They also can be repetitive. In most instances, hospitalization is not necessary, although a prompt medical consultation is essential after the first seizure. Most children with recurrent febrile seizures do not require daily antiepileptic drug therapy. Children who have had more than three febrile seizures or prolonged febrile seizures, or who have seizures when they have no fever, are usually treated with antiepileptic drugs including phenobarbital and/or valproate. Diazepam (Valium), if given by mouth or rectum at the time of fever, has been used effectively to both treat and prevent recurrent febrile ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 22

23 seizures. However, the dose that is effective when given by mouth can cause irritability, insomnia, or other troublesome side effects that last for days. The prognosis for febrile seizures is excellent. There is no reason for a child who has had a single febrile seizure to receive antiepileptic drugs unless the seizure was unusually long or other medical conditions warrant it. Recurrence rates (the chances of having another seizure) vary from 50% if the seizure occurred before age one year to 25% if the seizure occurred after that age. In addition, 25% to 50% of recurrent febrile seizures are not preceded by a fever. In some cases, the seizure is the first sign of an illness (usually viral) and the fever comes later. The vast majority of children with febrile seizures do not have seizures without fever after age five. Risk factors for later epilepsy include: Abnormal development before the febrile seizure Complex febrile seizures (seizures lasting longer than 15 minutes, more than one seizure in 24 hours, or body movements during the seizure restricted to one side) A history of seizures without fever in a parent or a brother or sister. If none of these risk factors is present, the chances of later epilepsy are the same or nearly the same as in the general population; if one risk factor is present, the chances of later epilepsy are 2.5%; if two or more risk factors are present, the chances of later epilepsy range from 5% to over 10%. Rarely, febrile seizures that last more than 30 minutes may cause scar tissue in the temporal lobe and chronic epilepsy that can be effectively treated with medication or a temporal lobectomy. Benign Rolandic Epilepsy ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 23

24 Benign rolandic (sylvian) epilepsy (BRE, also called BECTS (benign epilepsy of childhood with centrotemporal spikes), is a common childhood seizure syndrome, with seizures beginning between 2 and 13 years of age. A hereditary factor is often present. The seizures most commonly observed in BRE are partial motor seizures (twitching) or a sensory seizure (numbness or tingling sensation) involving the face or tongue and which may cause garbled speech. In addition, tonic-clonic seizures may occur, especially during sleep. Although the seizures are often infrequent, or may occur in infrequent clusters, some patients need medication. These include children, in addition to the typical seizure disorder, that have daytime seizures, a learning disorder, a mild mental handicap, or multiple seizures at night, which leave the child lethargic in the morning. The EEG shows a characteristic pattern of abnormal spikes over the central and temporal regions of the brain, especially during sleep. Despite the abundant abnormal spike activity, the child may have only one or a few seizures. This illustrates that the amount or frequency of abnormal spike activity in the EEG is not necessarily related to the severity of the epileptic disorder. Siblings or close relatives may have the same EEG pattern during childhood without ever having seizures. The seizures are usually easily controlled with low to moderate doses of carbamazepine, oxcarbazepine, or gabapentin (or, outside the United States, clobazam). Medication is usually continued until age 15, when the seizures spontaneously stop in almost all patients. Juvenile Myoclonic Epilepsy Juvenile myoclonic epilepsy (JME) accounts for about 7% of the cases of epilepsy, making it one of the most common epilepsy syndromes. The ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 24

25 syndrome is defined by myoclonic seizures (jerks) with or without tonicclonic or absence seizures. The EEG usually shows a pattern of intermittent spike-and-wave or polyspike-and-wave, even in between seizures. CT and MRI scans of the brain are normal and typically are not needed. Seizures usually begin shortly before or after puberty, or sometimes in early adulthood. They usually occur in the early morning, within a couple hours of awakening. Persons with JME often have photosensitive myoclonic seizures in addition to spontaneous seizures. The intellectual functions of persons with JME are the same as those in the general population. Juvenile myoclonic epilepsy often has a genetic basis. In some families, genes associated with an increased risk of JME are located on chromosomes 6, 8, or 15. The chance that a child born to a parent with JME will also have JME is about 15%. In most cases, the seizures are well controlled with medication, but the disorder is lifelong. Valproate is the treatment of choice. Other options include lamotrigine, levetiracetam, or topiramate. Carbamazepine may actually worsen the myoclonic jerks. Infantile Spasms Infantile spasms (West's syndrome), a very uncommon form of epilepsy, begins between 3 and 12 months of age. The seizures, or spasms, consist of a sudden jerk followed by stiffening. With some spells, the arms are flung out as the body bends forward (also called jackknife seizures). Other spells have more subtle movements limited to the neck or other body parts. A brain disorder or brain injury, such as birth trauma with oxygen deprivation, precedes the seizures in 60% of these infants, but in the other 40% no cause can be determined, and development is normal prior to the onset of seizures. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 25

26 Several antiepileptic drugs and hormonal therapy can be used to treat infantile spasms. Some experts recommend a trial of an antiepileptic drug (e.g., vigabatrin, valproate, topiramate) before hormonal therapy, but others use hormonal therapy as the first treatment. In countries where it is available, vigabatrin (Sabril) is often used as the initial therapy because it is relatively safe (especially for short-term use) and effective. Vigabatrin is especially effective in children with infantile spasms due to tuberous sclerosis (a disorder associated with abnormalities involving the brain, skin, heart, and other parts of the body). If vigabatrin does not control the seizures in 3 or 4 days, adrenocorticotropic hormone (ACTH) is usually used next. ACTH is a hormone made by the pituitary gland. It stimulates the adrenal glands to make and release additional cortisol, which acts much like prednisone. ACTH has been proven to be slightly more effective than prednisone, but it must be given as an injection, once a day for the first several weeks, then every other day. Steroid hormones such as prednisone, on the other hand, can be given by mouth. ACTH stops seizures in more than half of children with infantile spasms. In the United States, ACTH is often used as the first therapy and is typically given for 1 month. The dosage is highest during the first 2 weeks and then usually lowered gradually. The adverse effects of ACTH depend on the dose used, the duration of therapy, and the baby s sensitivity to the drug. Although rare allergic reactions may occur, all other adverse effects occur because ACTH stimulates the infant s body to produce cortisol, a steroid hormone. Excessive cortisol can cause the following: Irritability ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 26

27 Increased appetite High blood pressure Kidney problems Redistribution of body fat to make the face and trunk fatter and the arms and legs thinner Increased risk of infection or gastrointestinal bleeding Metabolic changes that alter the concentrations of glucose (sugar), sodium, and potassium in the blood. For most babies with infantile spasms, the adverse effects of ACTH can be safely managed. Often the baby will be given another anti-epileptic drug after the spasms have stopped and the ACTH therapy has been completed. The future course of the disorder and of the child's development is related to the cause of the seizures, the child's intellectual and neurological development before the seizures began (the better the condition at that time, the better the outlook), and whether they are controlled quickly. The sooner therapy is begun, the better the results. When the spasms stop, some children will later develop other types of seizure. Untreated children often have frequent spasms for many years, and later develop partial and generalized seizures. Approximately one-fifth of the cases of West s syndrome will evolve into Lennox-Gastaut syndrome. Lennox-Gastaut Syndrome Lennox-Gastaut syndrome is serious but uncommon. Three things define it: Difficult-to-control generalized seizures Mental handicap Slow spike-and-wave pattern on the EEG ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 27

28 The seizures usually begin between 1 and 6 years of age, but can begin later. The syndrome involves some combination of tonic, atonic, atypical absence, myoclonic, and tonic-clonic seizures that are usually resistant to medications. Useful medications for controlling the seizures of patients with Lennox-Gastaut syndrome include valproate, carbamazepine, clobazam (not available in the US), lamotrigine, and topiramate. Felbamate is also an effective drug and can often improve behavior and quality of life, but it carries a risk of life-threatening blood or liver disorders and must be used carefully. In children or adults with frequent, poorly controlled seizures, it is often wise to avoid high doses of antiepileptic drugs because they may intensify the behavioral, social, and intellectual problems, especially when two or more drugs are used together. It may be better to tolerate slightly more frequent seizures in order to have a more alert and attentive family member. In those patients whose seizures are not controlled with medication, there are other options. These include the vagus nerve stimulator, the ketogenic diet or corpus callosotomy (a palliative surgical procedure). Vagus nerve stimulation or corpus callosotomy can be helpful treatments for some patients. However, experts typically recommend vagus nerve stimulation before consideration of corpus callosotomy because of lower risks. Most children with Lennox-Gastaut syndrome have intellectual impairment ranging from mild to severe. Behavioral problems are also common and probably relate to a combination of the brain dysfunction, seizures, and antiepileptic drugs. The course of the seizures varies greatly. Some children ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 28

29 will later have fairly good seizure control. Others will continue to have multiple types of poorly controlled seizures throughout life. The intellectual and behavioral development of children whose seizures come under fair to good control may be almost normal, but the development of those who have frequent seizures and are given high doses of more than one drug may be severely delayed. This syndrome usually persists into adulthood and affected persons often need to live in a residential (adult foster care) group home when their parents are no longer able to care for them. Childhood Absence Epilepsy Absence seizures are generalized seizures that occur in school-aged children usually between the ages of 5 and 9. Sometimes childhood absence epilepsy (CAE) can be inherited, but it can also occur as a sporadic event. Typical absence seizures consist of sudden cessation of movement, staring, and sometimes blinking. Sometimes, there may be a mild loss of body tone, causing the child to lean forwards or backwards slightly. Unlike other types of seizures, absence seizures occur without an aura or warning. When diagnosing CAE, typical absence seizures need to be differentiated from atypical absence seizures, which can occur at an earlier age. An EEG of a child with CAE will show a typical pattern known as 3-Hz generalized spike and wave complexes. Many children with CAE have normal neurological examinations and intellectual abilities. However, some children may have developmental and intellectual impairments and may have other types of seizures including, but not limited to, tonic clonic seizures. The medications that are usually used to treat CAE include ethosuximide and valproic acid, but other medications can ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 29

30 also be used successfully. Usually children are treated for a minimum of 2 years. The prognosis for CAE is excellent. Remission can be achieved in approximately 80% of patients. Close attention must be paid to seizure control to avoid academic or social difficulties. Benign Occipital Epilepsy In this epilepsy syndrome, seizures usually begin between the ages of 5 and 7, and originate in the occipital lobe. Seizure symptoms often include the following: visual hallucinations loss of vision, or forced deviation of the eyes vomiting The hallucinations can take any form, but tend to be of brightly colored shapes of all sizes. Children may then complain of intense headache and may have extended periods of nausea and/or vomiting. Benign occipital epilepsy (BOE) can sometimes be mistaken for migraines due to the visual changes and headaches associated with this type of epilepsy. In addition to hallucinations and visual disturbances children may also experience jerking movements on one side of their body. The EEG of a child with BOE shows spikes in the occipital region of the head during sleep, or when the eyes are closed during wakefulness. An MRI scan of the brain will be normal. By definition, BOE is not caused by a structural lesion or abnormality. Since the seizures are of partial origin, medications such as carbamazepine and oxcarbazepine are good treatment options. Children with BOE are usually neurologically normal and complete seizure control can be attained in 60% of patients. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 30

31 Mitochondrial Disorders Mitochondria are the energy factories of the cell. Abnormalities in mitochondrial DNA or genes produce metabolic disorders that affect different parts of the body, including muscle and brain. Mitochondrial disorders can be inherited or sporadic. When inherited, the abnormal genes always come from the mother, since all mitochondria are of maternal origin. Two mitochondrial disorders can be associated with epileptic seizures: one is MELAS (which stands for mitochondrial encephalopathy), lactic acidosis (too much lactic acid in the blood), and stroke-like episodes. MELAS can lead to stroke-like episodes at a young age (usually before 40), seizures, dementia, headaches, vomiting, unsteadiness, and ill effects from exercise. Persons with MELAS can have both generalized (including myoclonic and tonic-clonic) and partial seizures. The other mitochondrial disorder with epileptic seizures is MERRF, which stands for myoclonic epilepsy with ragged red muscle fibers. MERRF is one of the progressive myoclonic epilepsies. It can also be associated with hearing loss, unsteadiness, dementia, and ill effects from exercise. In addition to myoclonic seizures, patients with MERRF often have generalized tonic-clonic seizures. There are other mitochondrial disorders that do not fit clearly into the MELAS or MERRF syndromes but which can cause epilepsy and additional neurological problems. There is no specific cure yet for mitochondrial disorders. Treatment is geared towards controlling symptoms and slowing the progression of the disease. A medical provider may prescribe a combination of supplements such as Coenzyme Q 10 or L-Carnitine in addition to other supplements. For patients who have isolated deafness, evaluation for a cochlear implant may be possible. For patients with seizures, standard antiepileptic medications are ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 31

32 used, such as those mentioned below in the section on Anti-Epileptic Medications. Landau-Kleffner Syndrome The Landau-Kleffner syndrome (acquired epileptic aphasia) is another rare disorder. Acquired aphasia means the loss of language abilities that had been present. In the typical case, a child between 3 and 7 years of age experiences progressive language problems, with or without seizures. The language disorder may start suddenly or slowly. It usually affects auditory comprehension (understanding spoken language) the most, but it may affect both understanding speech and speaking ability, or it may affect speaking only. Seizures are usually rare and often occur during sleep. Simple partial motor seizures are most common, but tonic-clonic seizures can also occur. Seizure control is rarely a problem. The EEG is often the key to the diagnosis. A normal EEG, especially one done when the child is awake, does not rule out this disorder. Sleep activates the abnormal spike activity, and therefore sleep recordings are extremely important. The boundaries of the Landau-Kleffner syndrome are imprecise. Some children may first have a delay in language development followed by a loss of speech abilities. Landau-Kleffner syndrome (or a variant of it) may also occur in some children in whom language function never develops, or in others whose language skills move backward but who very seldom have spike-wave discharges on the EEG. The exact relationship between the EEG findings and the language disorder is imprecise, although in some cases the epilepsy activity may contribute to the language problems. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 32

33 Standard antiepileptic drugs may help the seizures but are ineffective in treating the language disorder. Steroids are effective in some children, improving both the EEG abnormalities and the language problems. A form of epilepsy surgery, multiple subpial transections, may improve both the EEG abnormalities and the language disorder in a small number of children, but results to confirm this finding are still coming in from various epilepsy centers. In some cases, intravenous immunoglobulin (IVIG) has proven to be helpful. Rasmussen Syndrome Rasmussen syndrome usually begins between 14 months and 14 years of age and is associated with slowly progressive neurologic deterioration and seizures. Seizures are often the first problem to appear. Simple partial motor seizures are the most common type, but in one-fifth of these children, the first seizure is an episode of partial or tonic-clonic status epilepticus. Although Rasmussen syndrome is rarely fatal, its effects are devastating. Progressive weakness on one side (hemiparesis) and mental handicap are common, and language disorder (aphasia) often occurs if the disorder affects the side of the brain that controls most language functions, which is usually the left side. Mild weakness of an arm or leg is the most common initial symptom besides seizures. The weakness and other neurologic problems often begin 1 to 3 years after the seizures start. CT and MRI scans of the brain show evidence of a slow loss (atrophy) of brain substance. Recent studies suggest that the cause of Rasmussen s syndrome is an autoimmune disorder (antibodies are produced against the body s own tissues) directed against receptors on the brain cells. The process may be triggered by a viral infection. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 33

34 Treatment of this disease with antiepileptic drugs has been disappointing. Steroids may be effective, but additional studies are needed. Immunologic therapies (gamma globulin, plasmapheresis, prednisone) may be helpful in some cases. In children with severe weakness and loss of touch sensation and vision on the side of the body opposite to the involved hemisphere of the brain, a surgical procedure called a functional hemispherectomy may be successful. Hypothalamic Hamartoma & Epilepsy Small tumors in the base of the brain that affect the hypothalamus can cause a syndrome consisting of abnormally early puberty, partial seizures with laughing as a frequent feature, and increased irritability and aggression between the seizures. The partial seizures may be simple or complex and there may be secondary generalized tonic-clonic seizures. Affected individuals are often short and have mild abnormalities in their physical features (dysmorphisms). A high-quality MRI brain scan is necessary for diagnosis. If the tumor extends beyond the hypothalamus and below the brain, treatment with surgery may be an option. Antiepileptic drugs can also be beneficial, as well as drugs aimed at hormonal and behavioral problems, if needed. Treatment Treatment is typically required to control the seizures associated with epilepsy. However, some patients may not require treatment. The initiation and continuation of treatment will depend on a number of factors, including the severity of the condition, the extent and duration of seizures, the presence of other physical conditions, and the patient s individual needs. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 34

35 Therefore, it is important for providers to work with each patient to determine what type of treatment will best meet the needs of the patient. In addition, regular monitoring is crucial once treatment is initiated, as the patient may require adjustments depending on how he or she responds to the therapy. This is especially crucial when treating the patient pharmacologically (17). Some patients will require lifelong treatment to manage their seizures, while others will only require short term, intermittent treatment to manage their symptoms. In many instances, patients will only experience seizures during specific periods in their lifetime. In fact, a number of cases of epilepsy will include seizures that present in childhood and diminish over time (18). In these instances, treatment will only be required during the time that the patient is experiencing seizures. The following guidelines are typically used when determining if treatment is required: (15) Usually, Anti-Epileptic Drug (AED) treatment will not begin until after an individual has had a second seizure. This is because a single seizure is not a reliable indicator that an individual has epilepsy. In some cases, treatment will begin after a first seizure if: An electroencephalogram (EEG) test shows brain activity associated with epilepsy. A magnetic resonance imaging (MRI) scan shows damage to the brain. The patient has a condition that has damaged the brain, such as a stroke. For some people, surgery may be an option. However, this is only the case if removing the area of the brain where epileptic activity starts would not cause damage or disability. If successful, there is a chance the epilepsy will be cured. If surgery is not an option, an alternative may be to implant a small device under the skin of the chest. The device sends electrical messages to the brain. This is called vagus nerve stimulation. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 35

36 A variety of treatment options are available to patients experiencing epileptic seizures. Most patients will attempt to manage their symptoms through non-pharmacologic therapies. If these treatments are not successful, the patient will begin pharmacologic treatment (19). Diet Some patients will attempt to manage the symptoms of epilepsy through a change in diet. The ketogenic diet is a high fat, low carbohydrate diet that has been shown to reduce symptoms of epilepsy, especially in children (20). While the diet is effective, it is also very difficult to manage and can be quite limiting for the patient. The success of the ketogenic diet relies on strict adherence to carbohydrate restriction. Therefore, patients cannot allow any flexibility in their daily eating patterns (21). When excess amounts of carbohydrates are consumed, the patient will reset ketone metabolism for up to two weeks, which will minimize the efficacy of the diet in managing seizure activity (22). Many patients find the diet too restrictive and are unable to fully adhere to it. In fact, less than ten percent of patients are able to commit to the diet for more than a year (23). Ketogenic, and in some instances, modified Atkins diets have been shown to reduce epileptic seizures by approximately fifty percent (24). The most significant results occur in patients who reduce daily carbohydrate levels to ten grams or ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 36 (Photo courtesy of:

37 less per day. However, some patients will still experience a reduction in seizures while allowing for a higher number of carbohydrates each day. In these patients, twenty to thirty grams of carbohydrates appears to be an appropriate number (25). The diet is especially successful in children, but does appear to be helpful in adults experiencing epileptic seizures (26). In most cases, patients will require a period of adjustment to determine if the diet will reduce symptoms. Often, physicians will require patients to adhere to the diet for three months before making a determination regarding its effectiveness (23). In the early stages of the diet, the patient will continue medication. However, once the patient has had time to adjust to the diet, medication will be tapered. The eventual goal is complete discontinuation, but, in some instances, the patient will still require low doses of medication (27). While the ketogenic diet is quite effective, there are some potential side effects (28). Reported side effects include dehydration, constipation, and, sometimes, complications from kidney stones or gall stones. Adult women on the diet may have menstrual irregularities. Pancreatitis (inflammation of the pancreas), decreased bone density and certain eye problems have also been reported. Again, this is why the medical team closely follows children or adults who are on the diet. The diet lacks several important vitamins, which have to be added through supplements. Sometimes high levels of fat build up in the blood, especially if a child has an inborn defect in his ability to process fat. This possibility can lead to serious effects, which is another reason for careful monitoring. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 37

38 The ketogenic diet is very effective, but it is not the right treatment for all patients. If a patient will be unable to adhere to the strict guidelines required of the diet, it is not considered an appropriate method of treatment. Therefore, the treating provider must work with the patient to determine of if he or she is a viable candidate for diet therapy. If it is determined that the patient is not suited for this type of treatment, other methods must be considered. Electroencephalography Biofeedback Electroencephalography (EEG) biofeedback has been used to treat many forms of epilepsy since the early 1970 s. It is especially helpful in treating petit mal, grand mal, and complex partial seizures (29). In earlier years, the technique was used infrequently, as it was quite expensive. In addition, training for the procedure required a long term commitment and was not easily accessible (30). However, recent advances in technology and methodology have made the procedure more affordable, while also reducing the cost and length of training. Therefore, biofeedback is utilized more frequently as a treatment for epilepsy (31). Although access to the procedure has increased the number of individuals who revive biofeedback treatment, there are still discrepancies in the outcomes experienced. Some patients will respond to treatment quickly, requiring only a few sessions to experience a reduction in seizures. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 38 (Photo courtesy of:

39 Other patients may require a more extensive treatment period, often requiring treatment sessions before experiencing any reduction in seizures (32). Therefore, the procedure is still not a viable option for some patients. In addition, many patients will require complementary treatment with other therapies in conjunction with biofeedback (33). In most instances, biofeedback is used as part of a comprehensive treatment program that includes other therapies such as dietary management, lifestyle changes, and pharmacologic intervention. This multi-faceted approach to treatment typically produces the greatest results in patients who have more severe cases of epilepsy. In patients with less severe cases, a single treatment such as biofeedback is often adequate for reducing seizures (30). Biofeedback can help regulate behavioral disturbances in patients with epilepsy, even when it does not eliminate seizures. In addition, it can help reduce the dose of medication the patient requires to achieve seizure elimination (34). The neurons in the brain are divided into bands, some slow, some moderate and some fast, measured by cycles per second (30). Delta (.05-3 hertz) Produced in deep, dreamless sleep Theta (4-7 hertz) Drowsiness, inattention, deep meditation. A person with epilepsy will often ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 39

40 produce bursts of theta. Alpha (8-12 hertz) General relaxation and meditation SMR (sensorimotor rhythm) (12-15 hertz) Relaxed concentration. Often used for seizure control. Beta (15-18 hertz) Focused attention ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 40

41 Gamma (24 hertz and above) Intense concentration or anxiety EEGs of people with epilepsy appear as follows: Spike-and-slow-wave 3-second spike-and-wave (Absence or Petit Mal) During Tonic Clonic seizure ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 41

42 An EEG of a person without epilepsy appears as: Melatonin Melatonin is a hormone secreted by the pineal gland in the brain. It helps regulate other hormones and maintains the body's circadian rhythm. It also plays an important role in epilepsy treatment and management. Many individuals with epilepsy have lower than normal melatonin levels. In fact, seizure activity may be linked to the body s need to increase melatonin levels, as the individual experiences a significant increase of melatonin when a seizure occurs (35). Therefore, some recent clinical studies have attempted to link melatonin supplementation with reduced seizure activity. In some studies, there was a direct link between melatonin supplementation and a decrease in seizure activity, especially in children (36). However, other trials have been inconclusive (37). Since melatonin supplementation is relatively new, there is no standard dosage amount that is recommended. Some individuals may only require low doses, while others will benefit from a larger dose. The physician will need to experiment with dosage amounts to identify the appropriate amount for each patient (38). Melatonin can cause side effects in individuals. Therefore, the patient should be closely monitored to ensure the side effects do not become problematic. The most common side effects include: (39) ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 42

43 Some people may have vivid dreams or nightmares when they take melatonin. Taking too much melatonin may disrupt circadian rhythms ( body clock ). Melatonin can cause drowsiness if taken during the day. If an individual is drowsy the morning after taking melatonin, a lower dose may be necessary. Additional side effects include stomach cramps, dizziness, headache, irritability, decreased libido, breast enlargement in men (called gynecomastia), and decreased sperm count. Pregnant or nursing women should not take melatonin because it could interfere with fertility. Some studies show that melatonin supplements worsened symptoms of depression. For this reason, people with depression should consult their doctor before using melatonin supplements. Melatonin may interact with various medications. The following table provides an overview of the drugs that have the highest risk of interacting with melatonin: (40) Antidepressant medications In an animal study, melatonin supplements reduced the antidepressant effects of desipramine and fluoxetine (Prozac). More research is needed to know if the same thing would happen in people. In addition, fluoxetine (a member of a class of drugs called selective serotonin reuptake inhibitors, or SSRIs) can cause low levels of melatonin in people. Antipsychotic medications A common side effect of antipsychotic medications used to treat schizophrenia is a condition called tardive dyskinesia, which causes involuntary movements. In a study of 22 people with schizophrenia and tardive dyskinesia caused by antipsychotic medications, those who took melatonin supplements had fewer ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 43

44 symptoms compared to those who did not take the supplements. Benzodiazepines The combination of melatonin and triazolam (Halcion) improved sleep quality in one study. In addition, a few reports have suggested that melatonin supplements may help people stop using long-term benzodiazepine therapy, which is habit-forming. Blood pressure medications Melatonin may make blood pressure medications like methoxamine (Vasoxyl) and clonidine (Catapress) less effective. In addition, medications in a class called calcium channel blockers may lower melatonin levels. Calcium channel blockers include: Nifedipine (Procardia) Amlodipine (Norvasc) Verapamil (Calan, Isoptin) Diltiazem (Cardizem) Felodipine (Plendil) Nisoldipine (Sular) Bepridil (Vascor) Beta-blockers Use of beta-blockers may lower melatonin levels in the body. Beta-blockers include: Acebutolol (Sectral) Atenolol (Tenormin) Bisoprolol (Zebeta) Carteolol (Cartrol) Metoprolol (Lopressor, Toprol XL) Nadolol (Corgard) Propranolol (Inderal) Anticoagulant medications Melatonin may increase the risk of bleeding from anticoagulant medications such as warfarin (Coumadin). ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 44

45 Interleukin-2 In one study of 80 cancer patients, use of melatonin along with interleukin-2 led to more tumor regression and better survival rates than treatment with interleukin-2 alone. Nonsteroidal antiinflammatory drugs (NSAIDs) Steroids and immunosuppressant medications NSAIDs such as ibuprofen (Advil, Motrin) may lower levels of melatonin in the blood. Melatonin may cause these medications to lose their effectiveness. Do not take melatonin with corticosteroids or other medications used to suppress the immune system. Tamoxifen Preliminary research suggests that the combination of tamoxifen (a chemotherapy drug) and melatonin may benefit some people with breast and other cancers. More research is needed to confirm these results. Other Caffeine, tobacco, and alcohol can all lower levels of melatonin in the body. Vitamins Many epileptic patients will benefit from supplementation with vitamins. In many instances, epileptic seizures and other symptoms increase if the patient is deficient in a specific vitamin (41). In other instances, patients may benefit from an increase in nutritional supplementation as it will improve basic body composition and increase the patient s ability to withstand the negative effects of epilepsy (42). The following section provides a thorough overview of the vitamins most beneficial in epilepsy treatment: (41,43 51) Folic acid ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 45

46 Supplementation with folic acid on a daily basis is important for both women as well as men. The vitamin named folic acid (also known as folate) is an important part of the production of blood cells, of the function of some nerves and to help prevent heart disease. Low levels (deficiency) of folic acid can be the cause of intrauterine growth delay, inherited malformations, miscarriages and neural tube defects in women, and heart disease in both men and women. For patients who have epilepsy, this is especially important since some seizure medicines can cause low levels of folic acid by changing the way it is absorbed in the body. Patients who take more than one seizure medicine may be advised to take higher doses of folic acid. Babies born to women who did not get enough folic acid early in their pregnancies are more likely to have birth defects, especially a type called neural tube defects, which affect the brain and spinal cord. The most well-known of these is spina bifida, in which the spinal column is not completely closed. By the time a woman knows for sure that she is pregnant, it may be too late to prevent these defects. Folic acid should be added to a person s daily diet, either as food or as a supplement, starting in the teenage years for women, and young adulthood for men with epilepsy. Some providers recommend up to 4 mg per day for patients who have been taking daily anti-seizure medications for many years. Epileptologists are now concerned that folic acid may be too low in persons with epilepsy taking some antiepileptic drugs. Low serum and red blood cell levels of folic acid in women of childbearing potential increase the risk of fetal birth defects. For men and women, low levels of folic acid are ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 46

47 associated with elevated homocysteine and an increased risk for cardiovascular disease. A convincing argument now develops that routine folic acid supplementation is important for women and men receiving antiepileptic drugs. Folic acid (vitamin B9) is a water-soluble B vitamin that is essential for DNA repair, cell division, and normal cellular growth. Low folic acid levels during pregnancy in women with epilepsy have been associated with fetal malformation, and older enzyme-inducing antiepileptic drugs are known to reduce serum folate levels. As mentioned earlier, profound deficiency of folic acid during pregnancy has been associated with neural tube defects such as spina bifida. Deficiency in adults has been associated with megaloblastic anemia and peripheral neuropathy. In both men and women, low serum levels of folate can increase homocysteine levels, which are correlated with elevated cardiovascular risk. Certain antiepileptic drugs, but not all agents, can potentially decrease folate levels, either via hepatic enzyme induction and/or decreased absorption. Addressing the question of which patients on AEDs need folic acid supplementation is challenging because it depends on whether the patient is pregnant or has a history of epilepsy. For example, the risk of having a pregnancy complicated by a major congenital malformation (e.g., neural tube defect) is doubled in epileptic women taking AEDs compared with those women with a history of epilepsy not taking these agents. In fact, that risk is tripled with AED polypharmacy, especially when valproic acid is included. Additionally, many AEDs are used for conditions other than epilepsy, such as chronic pain and mood disorders, but the effect of AEDs on folate has not been adequately assessed in this population. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 47

48 There are some general guidelines about folic acid supplementation. Consensus statements recommend mg of folic acid per day in all women planning a pregnancy. Ideally, this should be started at least 1 month prior to pregnancy if possible. These guidelines recommend higher daily folic acid doses (4 mg/day) in women with a history of neural tube defects. In addition, enzyme-inducing anticonvulsants, such as phenytoin, carbamazepine, primidone, and phenobarbital, are known to decrease folate levels, and valproic acid may interfere with folate metabolism. Other AEDs, such as oxcarbazepine, lamotrigine, and zonisamide, do not appear to alter folate levels. Unfortunately, the effectiveness of folic acid supplementation for the prevention of AED-induced teratogenicity and the appropriate dose of folic acid for specific AEDs has not been determined. Not all studies designed to determine effects of fetal AED exposure consistently demonstrate a protective effect against congenital malformations with folic acid supplementation. However, this may be due in part to inadequate dosage. Because many pregnancies are unplanned, most authorities recommend that folic acid supplementation be given routinely to all women of childbearing potential at 0.4 mg/day. Women who have already had a child with a neural tube defect are encouraged to consult with their clinician regarding appropriate dosage, and those on AEDs should receive mg/day. Current data are inconclusive to support high-dose folic acid use in women without epilepsy on AEDs for other indications, though supplemental folic acid should not be regarded as harmful. For men and women on AEDs that reduce folate levels, such as phenytoin, carbamazepine, primidone, and phenobarbital, it seems prudent to monitor homocysteine and folate levels and monitor for the development of megaloblastic anemia. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 48

49 The Comprehensive Epilepsy Center has developed guidelines for folate supplementation for women of childbearing years. These guidelines were established to enhance patient education and awareness of the potential vitamin deficiencies that can occur when taking antiepilepsy medications (AED's). They help to promote the general health of women, and minimize potential birth defects associated with folate deficiency. Folate (or folic acid) deficiency and medications used to treat epilepsy are associated with an increased risk of birth defects. Specifically, they are associated with spina bifida and anencephaly, two of the most common and severe neurologic birth defects. Clinical studies have shown that supplementing a woman's diet with folate can reduce this risk by 50-75%. In order to reduce the risk of neural tube defects, the Center for Disease Control and Prevention (CDC) recommends that all women who are capable of becoming pregnant should take 0.4 mg of folate each day. Neural tube defects occur early in the pregnancy, often before a woman is aware that she is pregnant. In additional, about one-half of pregnancies in the United States are unplanned. Therefore, supplementation with folate should continue throughout a woman's reproductive years. A woman who has a family history of neural tube defects or has a previous child born with neural tube defects should receive folate supplementation of 4.0 mg per day. The Comprehensive Epilepsy Center Guidelines for Folate supplementation are as follows: All women should supplement their diet by taking 1 prenatal multivitamin each day. Prenatal multivitamins are available over-thecounter (OTC) or by prescription. OTC prenatal multivitamins contain ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 49

50 0.8 mg of folate while prescription prenatal multivitamins contain 1.0 mg of folate. Generic multivitamins are generally the least expensive, followed in order of expense by brand name over-the-counter vitamins, and finally prescription tablets. A woman who is planning on becoming pregnant or who is pregnant, and has a family history of neural tube defects, or has had a previous child born with neural tube defects, or is on either Tegretol or Depakote, should receive 3.0 mg of folate in addition to a prenatal multivitamin. All other women who are planning to become pregnant or are pregnant and taking an antiepilepsy medication other than Tegretol or Depakote should receive 1.0 mg of folate in addition to a prenatal multivitamin. Calcium Calcium is an important element in the body, and so important that an individual has more calcium in his or her body than any other mineral. Calcium is a necessary part of bone formation, development and repair. The majority of calcium in the body is stored within bones, while the rest is in the blood and the body s other fluids. Abnormal calcium levels may result in major health problems. Both hypocalcemia (low calcium levels), and hypercalcemia (high calcium levels) can cause seizures. The main sources of calcium are dairy products, such as milk, yogurt and ice cream. Green leafy vegetables, such as broccoli and kale, canned sardines and shellfish are also good sources of calcium. Initially, low calcium levels may not give any warning signs. However, as the level decreases, a person may feel confused and have hallucinations, memory loss and depression. Because of calcium s importance in muscle ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 50

51 movement and the function of the nervous system, hypocalcemia can cause muscle aches, spasms, stiffening of the muscles, and tingling sensations in the face, mouth, lips, fingers and toes. Low calcium levels can also cause several types of seizures, including the following: tonic-clonic seizures, categorized by whole body shaking and loss of consciousness; focal muscle seizures, during which a set of muscles contract against a person s will; and absence seizures, during which a person appears to be staring off into space. Certain anti-seizure medications can contribute to lowering calcium levels, especially when taken daily for a long time period. This happens when the medication makes the liver work harder than usual, and it causes the elimination of the calcium deposits from the bone, leading to what is known as brittle bones, bone loss or osteoporosis. From a physiological perspective, it is logical that calcium supplementation may be indicated when myoclonic seizures are encountered. For when the calcium ion concentration falls below about one half of normal, a person is likely to experience tetanic contraction of muscles throughout the body because of spontaneous nerve impulses in the peripheral nerves (42). Since calcitonin and the parathyroid hormone affect serum calcium concentrations, it is possible that problems in the production of either can lead to limited tetanic contractions. Significant changes in important body chemicals such as calcium and magnesium can cause seizures; so can a lack of certain vitamins. These chemical changes may provoke a disturbance in the brain, or a single seizure, by influencing the thresholds for firing. Calcium is a very important mineral for the normal functioning of brain cells, and low levels of calcium ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 51

52 (hypocalcemia) can cause seizures. Hypocalcemia can be a consequence of severe kidney disease when too much calcium escapes from the kidney into the urine. It may also, but rarely, be caused by a hormonal problem that has the same effects. A deficiency of magnesium, a mineral that interacts with calcium, may cause low blood calcium and, thus, seizures. With a ketogenic diet, a calcium supplement must be taken every day to be nutritionally complete. There is growing evidence that elevated extra-cellular calcium levels and homeostatic calcium control mechanisms may be factors in developing acquired epilepsy (epilepsy that occurred after an injury). It is important to evaluate the possible functional consequences of altered CA 2+ dynamics in epileptogenesis. The ability of the neuron to restore CA 2+ loads to resting [CA 2+] is regulated by CA 2+ homeostatic mechanisms. Increased or prolonged entry of extracellular CA 2+ could contribute to the altered CA 2+ homeostatic mechanisms in epilepsy. It is important to note that cellular calcium levels tend to be inversely correlated with extra-cellular calcium levels. Thus, it does not seem unreasonable to conclude that those without injury could have seizures caused by calcium problems. Those that were on long-term anticonvulsant medications had higher levels of calcium than non-medicated controls. This might suggest that one of the reasons that some of these medications are continued long-term is that for some people, they somehow increase the retention of calcium, which may account for some of their anticonvulsant effects. Some forms of juvenile myoclonic epilepsy can result from mutations of a Ca 2+ channel. This line of evidence suggests the involvement of channels expressed in the brain in the pathogenesis of certain types of epilepsy. Ca ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 52

53 2+ influx into excitable cells is a prerequisite for neurotransmitter release and regulated exocytosis. Within the group of ten-cloned voltage-gated Ca 2+ channels, the Ca(v) 2.3-containing E-type Ca 2+ channels are involved in various physiological processes, such as neurotransmitter release and exocytosis together with other voltage-gated Ca 2+ channels of the Ca(v)1, Ca(v)2 and Ca(v)3 subfamily. The interaction of Ca(v) 2.3 with the EF-hand motif containing protein EFHC1 is involved in the etiology and pathogenesis of juvenile myoclonic epilepsy. However, E-type Ca 2+ channels also exhibit several subunit-specific features, most of which still remain poorly understood. While they are not fully understood, it seems apparent that calcium control mechanisms play some role in myoclonic seizures. Mutations in the calcium-sensing receptor gene (CaSR) may result in disorders of calcium homeostasis manifesting as familial benign hypocalciuric hypercalcemia (FBHH), neonatal severe hyperparathyroidism (NSHPT) or autosomal dominant hypocalcemia with hypercalciuria (ADHH). The ADHH condition may result in asymptomatic hypocalcemia and a minority experience seizures in infancy, which can recur into adulthood. Even in generalized seizures, epileptics are generally mildly hypocalcemic, especially in the period before the seizure. Stress, which releases epinephrine and corticotropin, results in high serum citrate concentration, which probably contributes to decreased serum [Ca2+] just before a seizure. Long-term treatment of epileptic children with various anticonvulsant medications was found to raise the TSH and diminished T3 and T4. Calcitonin levels were lowered as well. Long-term use of certain anticonvulsant medications tended to impair at least a portion of thyroid function. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 53

54 Myoclonic seizures tend to be resistant to drug therapies. Since many antiepileptic medications impair thyroid function and/or somehow result in increased calcium levels, perhaps a partial reason for their occasional success with myoclonic seizures is the partial suppression of the thyroid hormone calcitonin, which results in an increase of serum calcium levels. There are scattered reports that the anticonvulsant medications phenobarbital, carbamazepine, valproate, lamotrigine, gabapentin, and vigabatrin can cause or induce myoclonic seizures in epileptics who had not been experiencing those types of seizures. It is possible this occurs because some anticonvulsant medications can reduce vitamin D levels. Other researchers have thus suggested supplemental vitamin D when taking certain anticonvulsant medications. Myoclonic seizures can have an appearance of a limited tetanic contraction associated with insufficient calcium levels. It is important to note that others, while not specifically discussing myoclonic seizures, have also suggested that somehow increasing calcium levels should be looked at for the treatment of epileptics. Hence, it may be wise to consider nutritional interventions that affect calcium levels as a first-line treatment Currently, this is rarely the case. Even though some antiepileptic drugs could also worsen some types of seizures, it is known that other therapies can be efficient in refractory epilepsies; steroids, vague nerve stimulation, ketogenic diet and surgery, nutritional therapies (especially outside the ketogenic diet) seem to be often overlooked. It should be noted that it is theoretically possible that, for some types of seizures, calcium could be contraindicated. ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 54

55 Yet it is not unheard of that nutrition, including calcium supplementation, should be considered as a first-line treatment for intractable forms of epilepsy, as others have sometimes advocated it (though this investigator appears to be the first advocating supplemental calcium, vitamin D, etc., as first-line nutrients, as well as first to advise nutrients specifically for myoclonic seizures). One of the reasons that nutrition should be considered as a front-line therapy is that it is low risk. Consumption of calcium-containing foods and/or calcium-containing supplements is so safe that, although calcium can react with some medications, over dosage has not been reported with calcium supplements. Forms other than calcium carbonate are preferred, as calcium carbonate may cause gastrointestinal side reactions such as constipation, bloating, gas and flatulence. Prolonged use of large doses of calcium carbonate greater than 12 grams daily (about 5 grams of elemental calcium) may lead to milk-alkali syndrome, nephrocalcinosis and renal insufficiency. There is no specific quantitative recommendation for each possible substance that could affect calcium levels, as the amount needed appears to vary by individual (as well as size in the case of children). But irrespective of the quantities, it does appear reasonable to conclude that calcium control mechanisms can play a causal role in myoclonic seizures and that calcium and other nutrients should be considered as possible front-line therapies for these hard to treat myoclonic seizures. Vitamin D Vitamin D is a necessary part in the process of proper breakdown and use of calcium. Because of this, vitamin D deficiency caused or worsened by daily use of anti-seizure medications for a long time can make the bones very soft ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 55

56 and brittle, causing them to break more easily. Adding vitamin D to the daily diet can prevent this. In addition, patients taking anti-seizure medications should increase their calcium intake every day. Exposure to sunlight is a natural way to speed up the body s ability to produce vitamin D. Nearly half of people with epilepsy are also vitamin D deficient, but despite this well-known association, only a single study has been published on the effect of vitamin D for seizure control in the last 40 years. That study revealed that treating epileptic patients with vitamin D2 the far inferior type of synthetic vitamin D reduced the number of seizures, and in 1974 researchers concluded the results may support the concept that epileptics should be treated prophylactically with vitamin D (46). Now, nearly four decades later researchers have again revealed that the normalization of serum vitamin 25(OH)D [vitamin D] level has an anticonvulsant [anti-seizure] effect (50). The findings are even more important given that people with epilepsy face an even greater risk of vitamin D deficiency than the general population (and even the general population is vastly vitamin D deficient). The reasons are two-fold, with the first being that having frequent seizures may interfere with a person s ability to get outdoors and stay active. If an individual spends most of his or her time inside, they will miss out on regular sun exposure, which is key for the natural production of vitamin D. Even exposing the skin to sunlight through a windowpane will prevent the entry of the UVB rays, which are the specific wavelength that produces vitamin D in the skin. It is crucial for epilepsy patients to get outside and experience direct skin contact with the sunlight instead of sunning in a sunroom, for instance. Second, anti-epileptic drugs that are often given to epilepsy patients can interfere with vitamin D metabolism, leading to ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 56

57 deficiency. If these drugs are taken, it is especially crucial that vitamin D levels are actively monitored to avoid this side effect. Vitamin D has a significant impact on epileptic seizures because epilepsy is a disorder of the central nervous system, particularly of the brain. Vitamin D is a vitamin that is also a neuroregulatory steroidal hormone that influences nearly 3,000 different genes in the body. Vitamin D receptors can be found in the brain, spinal cord, and central nervous system, and may enhance the amount of important chemicals in the brain needed to protect brain cells. Surgical Options A number of individuals with epilepsy may benefit from surgical intervention. There are a variety of surgical procedures that can help with various aspects of the disorder. While medication is effective at controlling most seizure activity, approximately thirty percent of individuals will not respond to pharmacologic treatment and will require more advanced therapy (52). These individuals often benefit from surgery. There are three primary forms of surgery that are used to treat individuals with epilepsy: (53) Surgery to remove the area of the brain producing seizures Surgery to interrupt the nerve pathways through which seizure impulses spread within the brain Surgery to implant a device used to treat epilepsy Surgery is an invasive procedure and should only be considered if the section of the brain where the seizures originate can be clearly identified (54). In addition, the physician must ensure that surgery will not negatively affect ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 57

58 any areas that are responsible for critical functions (55). A thorough assessment is required before determining if surgery is a viable option. There are a number of different surgical procedures that can be used to treat epilepsy. The specific type of surgery performed on a patient will be determined based upon the type of seizures the patient is experiencing and the area of the brain where seizure activity originates (52). The following section provides an overview of the risks and benefits of various surgical procedures (14,56 83). (Photo courtesy of: ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com ce4less.com 58