Cyclical Ketogenic Diets Review

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Ketogenic Diet for Child Epilepsy and Seizure Control

Purpose - Excerpt Twenty to thirty percent of children with epilepsy continue to suffer from seizures, even when treated with currently available anticonvulsant medications. Children with Lennox-Gastaut Syndrome (LGS) are particularly handicapped by atonic-myoclonic seizures. Preliminary data suggest that even when other medications have failed, these seizures may respond rapidly and dramatically to a high-fat-low-carbohydrate ketogenic diet. The purpose of the study is to assess if the classic ketogenic diet is efficacious in reducing seizure frequency, medication toxicity, and improves quality of life.

Ketogenic Diet A Treatment for Epilepsy Third Edition

Summary The Ketogenic Diet A Treatment for Epilepsy introduces the ketogenic diet as a means of seizure control in epilepsy. It is intended for physicians, dieticians, and parents of children with epilepsy who might benefit from the treatment. The book is based on the experience acquired in using the ketogenic diet at the Johns Hopkins Pediatric Epilepsy Center. The book is divided into six sections. The 12 chapters (1) provide an introduction to the ketogenic diet, (2) provide answers to common questions about the diet, (3) present a historical overview of the ketogenic diet, (4) provide information on starting the diet, (5) describe how to fine tune the diet, (6) describe how to make the diet work at home and on the road, (7) discuss going off the diet, (8) describe how to make the necessary calculations for the diet, (9) discuss adapting the diet to liquid formulas and tube feedings, (10) provide sample meal plans, (11) discuss the results of new research studies of the diet, and...

What is the ketogenic diet

The ketogenic diet (KD) is a high-fat, adequate protein, very low carbohydrate diet that is both calorie and fluid restricted and carefully calculated by a ketogenic diet-trained dietitian to create and maintain ketosis 2 Typical foods eaten include butter, eggs, cheese, heavy whipping cream, canola and olive oils, mayonnaise, green vegetables, chicken, hot dogs, and ground beef Sugar-free and carbohydrate-free snacks can be incorporated to help make the KD more palatable The KD is started gradually in a child as an inpatient, typically following a 24- to 48-hour fasting period designed to rapidly induce ketosis .2 It is provided in a typically 4 1 or 3 1 ratio (of fat to protein and carbohydrate combined) and is slightly calorie and fluid restricted The fasting has been demonstrated in several retrospective and prospective studies to be unnecessary for long-term control however, it

MoDifiED Atkins Diet

Since first reported in 2003, the modified Atkins diet has emerged as a viable dietary treatment for seizures 7 This diet is less restrictive than, but perhaps equally effective as, the traditional KD and figures in seven papers published to date . The term modified describes the lower carbohydrate limit compared to published Atkins diet recommendations for the induction phase (10 versus 20 g per day) and the emphasis on high fat intake The modified Atkins diet is able to induce ketosis without any protein, fluid, or calorie restriction . In addition, this diet does not require an admission or a fast In reviewing food records of children on this diet, it approximates a 1 1 ratio of fat carbohydrate and protein, compared to a typical 3 1 or 4 1 ketogenic diet . 14 Children do not appear to reduce their calorie intake while on this diet . Low carbohydrate foods and meals can also be eaten in restaurants

Ketogenic Diet

The increase in ketone bodies associated with a diet rich in lipids and low in carbohydrates decreases seizure frequency in a significant percentage of patients with pharma-coresistant epilepsy. The mechanisms through which the ketogenic diet exerts its antiepileptic effect are not fully understood. Open studies report that some patients may become seizure free and that more than 50 achieve a significant reduction in seizure fre- quency. The need for absolute compliance with the diet and gastrointestinal side effects are the main deterrents to its use. Although a multidisciplinary support team of diet specialists, clinicians, and psychologists is usually considered necessary for effective implementation of the ketogenic diet in the industrialized world, this alternative therapy has been successfully and cost-effectively used in developing countries without such support.

The Ketogenic Diet

The ketogenic diet has been used in the treatment of epilepsy for almost 100 years. This is a high-fat diet, designed to mimic the effects on starvation in the production of ketones. Several studies have shown benefit in older children with drug-resistant epilepsy, in the use of both the classical diet (where the diet is based on the ratio of long-chain fat to carbohydrate including protein) 106 and the medium-chain triglyceride diet 107 . Criticism has been directed at the high dietetic resource required, and the unpalatability of the diet, but neither should be consideration to non-use. The availability of liquid preparation in the use of either diet (medium-chain triglyceride emulsion or liquigen with which a formula can be made up, or Ketocal , a complete formula of 4 1 ratio SHS International Ltd - Nutricia Clinical Care ) allows availability to a younger population, as well as those with gastrostomy feeding. Limited data are available with regard to its use in infants. Many of...

Are There IndicatioNs FoR The Diet

It is also important to recognize that there are metabolic disorders that are contraindications to the KD . Such disorders involve difficulties with the metabolism of a high-fat diet and include pyruvate carboxylase deficiency, carnitine deficiencies, and fatty-acid oxidation defects Mitochondrial disorders are also a relative contraindication to the diet, although recent literature has suggested that the diet can be successfully maintained in even these patients 6 Although it is not a true contraindication, children with Lafora body disease do not appear to respond well to the ketogenic diet, and in our anecdotal experience, the same is true of other progressive myoclonic epilepsies Lastly, children who are candidates for surgery (e g , a focal dysplasia or stroke) do not appear likely to be seizure free with the KD when compared to resective surgery 20

Medications and the diet

Considering the intractable nature of the epilepsy of most children starting the KD, it is not surprising that they remain on medications during their time on the KD For the majority of children, they are not mutually exclusive therapies . Medications are often changed from solution to tablet formulations to ensure an absence of carbohydrates, although some antiepileptic liquid preparations such as levetiracetam, felbamate, and gabapentin do have lower amounts of carbohydrates when provided as liquids 2 It is important for the physician to realize, however, that the second most common reason for starting the ketogenic diet following seizure reduction is medication reduction . Although our center (John M . Freeman Pediatric Epilepsy Center at the Johns Hopkins Hospital) generally discourages making two changes at once by immediately reducing medications, evidence would suggest it is safe to do so if parents request and physicians believe it is prudent Phenobarbital and clonazepam have...

Epilepsy You and Your Treatment

Summary Epilepsy You and Your Treatment is a booklet from the Epilepsy Foundation of America that provides basic information about tests, diagnosis, and management. Topics include (1) what seizures are and how physicians will work with individuals who have seizures (2) blood tests (3) electroencephalograph tests (4) brain imaging techniques (5) tests during treatment (6) drugs prescribed to prevent seizures (7) things to do to help treatment work (8) side effects of drugs (9) pregnancy (10) the effect of taking more than one anticonvulsant drug (11) the benefits of brain surgery for certain types of epilepsy and (12) other treatments, such as the ketogenic diet, biofeedback, ACTH injection, vitamin therapy, and experimental medicines.

Low Glycemic Index Treatment

There is also recent evidence that a low-glycemic index treatment, similar in many ways to the South Beach diet, can be helpful for seizure control as well. 17 This diet is perhaps even less restrictive than the modified Atkins diet and does not induce similar levels of ketosis, possibly acting by stabilizing serum glucose Foods are still relatively high in fat and protein, but allow 40-60 g of low-glycemic (glycemic index 90 reduction in seizures, and 25 had a 50-90 improvement . 17 Further studies of this diet are also under way.

Doubleblind placebocontrolled trial of vitamin E as addon therapy for children with epilepsy

Not have adequate seizure control with established antiepileptic drugs (AEDs). Other options for patients with uncontrolled epilepsy are newer antiepileptic medications, ketogenic diet and surgery. However, a small percentage of patients are candidates for these options. Therefore, additional treatments are needed to improve seizure control in patients with uncontrolled epilepsy. Animal studies have shown an association between vitamin E supplementation and seizure reduction. A study in children also showed that vitamin E helped reduce seizures. However, a similar study in adults did not show a reduction in seizures with vitamin E supplementation. Therefore, this research study is being done to help define vitamin E's usefulness and safety as a treatment for epilepsy. Fifty patients will be recruited from the Children's Epilepsy Program at The Children's Hospital in Denver, Colorado. Qualifying patients will have a confirmed diagnosis of epilepsy that is currently uncontrolled with...

Treatment Of Symptomatic Generalized Epilepsy Lennox Gastaut Syndrome LGS

Other AEDs often used in treatment of LGS, without data from controlled trials, include VPA, vigabatrin (VGB), ZNS, PB, benzodiazepines and adrenocorticotropic hormone (ACTH) or prednisolone. Additional options include the ketogenic diet, vagus nerve stimulator or corpus callosotomy.

Differential diagnosis

Localization-related, epilepsy syndromes . Vagus nerve stimulation or the ketogenic diet may be helpful in selected medically refractory cases Resective epilepsy surgery is generally not indicated in patients, but rare individuals with hippocampal sclerosis have been reported in GEFS+ families .

Treating Based On Aetiology

Finally, knowledge of the underlying aetiology may affect the treatment in different ways. In patients with severe brain malformations such as hemimegalencephaly, or in patients diagnosed with Rasmussen's encephalitis, a decision is often made to operate rather than to continue attempts at medical therapy, based more on that diagnosis than on meticulously establishing criteria for medical intractability. Severe and medically refractory seizures occur in patients with a metabolic defect called glucose transporter defect 9 . These patients have impaired transport of glucose across the blood-brain barrier and their cerebrospinal fluid glucose level is one-third or less of the simultaneous value in plasma. These patients have been found to respond to the ketogenic diet much more readily than to anti-epileptic medications, and establishing this diagnosis is therefore crucial for optimal therapy. Pyridoxine dependency also causes medically intractable seizures, with atypical onset up to the...

The concept of medical intractability

Therapy, specifically epilepsy surgery, exceeds the benefit vs. risk ratio of any additional medical treatment, such as another AED or the ketogenic diet. The availability of epilepsy surgery has created the need to define medical intractability. Defining medical intractability and declaring a patient medically intractable serves no useful therapeutic purpose unless it is done in the context of defining the optimal point in time when a patient should be evaluated for the possibility of epilepsy surgery (see Chapter 2).

Diagnostic approach

Opinions regarding efficacious medications vary, and no single agent stands out Treatment with valproic acid along with a benzodiazepine is commonly initially advocated Stiripentol, vigabatrin, and topiramate have demonstrated some efficacy in limited trials or reports . Some authors prefer clonazepam to clobazam . Newer trials with much older agents such as potassium bromide have shown promise against convulsive episodes Other drugs such as carbamazepine and lamotrigine can aggravate seizures The ketogenic diet may help some patients Immunomodulation with

Movement Disorders of Glut1Deficiency Syndrome

It is important for physicians to recognize that impaired glucose transport across the blood-brain barrier results in Glut-1-deficiency syndrome. Classic cases are characterized by infantile seizures, developmental delay, acquired microcephaly, ataxia, and hypoglycorrhachia.73 As expected, in this relatively recently described genetic disorder, the associated phenotype is expanding. It includes individuals with mild or no learning disability, normal head circumference, and paroxysmal movement abnormalities such as ataxia, dystonia, and choreoathetosis. Diagnosis is based on finding an inappropriately low fasting CSF glucose (typical CSF blood glucose

Pharmacological treatment

Patients newly diagnosed with epilepsy should be started on a single AED, which will be effective in controlling their seizures in approximately 60 (41). Treatment may be safely withdrawn in some patients who have entered remission, particularly in children (59). There is still no consensus about the duration of remission before AED withdrawal should start. In children a period of six months has been advocated and in adults a period of at least two years. When two successive AEDs given as monotherapy have failed, most authorities would recommend combination therapy. Outcome studies suggest that after failure of two or three treatment schedules, the chance of subsequent remission with further drug manipulation is small. Between 30 and 40 of patients will continue to have seizures despite optimal AED therapy (48). These individuals with refractory epilepsy should be assessed for suitability of non-pharmacological management strategies, such as surgery, vagus nerve stimulation (VNS), or...

Availability of treatment

There is wide disparity in the availability of treatment modalities in different parts of the world. The reasons for these inequalities are complex and multifactorial. They may include both hardware factors (e.g. availability of technologies and a reliable drug supply) and software factors (e.g. availability of expertise and access to health care), which are often dictated by economic constraints. The treatment gap in developing countries is discussed separately in Section 12. EEG and brain imaging, which are considered essential for accurate classification of seizure types and epilepsy syndromes, are not available to the majority of patients living in developing countries. Phenobarbital carries the lowest cost among the AEDs and can be reliably supplied to rural areas. Phenytoin, carbamazepine and valproic acid can also be accessed in most countries. The newer agents are mostly neither affordable nor available for the majority of patients. Because of the high level of expertise...

Treatment and outcome

In desperation, her mother asked about the ketogenic diet, a therapy that had recently been resurrected following some attention in the national media. After some discussion, and shortly after the ketogenic diet became available at our center, J was hospitalized and underwent fasting. She was placed on the ketogenic diet at a 4 1 ratio of fat to carbohydrate and protein calories. Her seizures immediately decreased to only a few per day she had a slight exacerbation associated with an episode of otitis media and fever. She then became seizure-free for the first time in years. As weeks went by, her cognitive abilities improved. Her mother observed that the changes were 'like taking a veil off of her brain'. She exhibited improved abilities in reading and mathematics in school. After being seizure-free for 20 months, the ratio of her ketogenic diet was gradually decreased and a weaning process was started. After being seizure-free for 2 years, the diet was discontinued. A follow-up EEG...

Treatment strategy

Seizures may be difficult to control with antiepileptic medications . Broad-spectrum antiepileptic medications effective against partial seizures may prove helpful . In some patients, the disease appears to be progressive, and there is a view that early resective surgery may be effective in halting the progression It is not possible to predict who will develop medically intractable epilepsy Surgery should be considered when seizures are refractory to medical treatment Visually guided complete excision of the angiomatous cortex with or without the guidance of electrocorticography is the primary surgical procedure for epilepsy surgery Hemispherectomy is generally considered in children with extensive unilateral brain involvement and a fixed hemiparesis The ketogenic diet or vagus nerve stimulation may provide alternative treatment options for refractory patients, particularly in those with bilateral ictal onset zones. Aspirin 3-5 mg kg day is often recommended, with SWS, as primary...

Suggested reading

Expert Review of Neurotherapeutics 7(2), 179-193 . Keene, D. L . (2006) . A systematic review of the use of the ketogenic diet in childhood epilepsy. Pediatric. Neurol. 35(1), 1-5 . Malphrus, A .M . and Wilfong, A. A. (2007). Use of the newer antiepileptic drugs in pediatric

Medically Intractable Idiopathic Generalized Epilepsy

Many patients who appear to have medically intractable IGE are not truly intractable, but have been treated with inappropriate AEDs. Another possibility is that frontal lobe epilepsy with secondary bilateral synchrony is mistaken for IGE 1 . Once these possibilities have been ruled out, a small minority of patients with IGE remain refractory to medical treatment. These patients may benefit from different drug combinations including VPA, LTG, CZP, TPM, LVT and ZNS, as shown in trials which have included patients with refractory generalized seizure types. For some patients, vagal nerve stimulation (VNS) can be a good option. It seems that VNS has similar or greater efficacy in IGE than in partial epilepsy, but this is still an off-label use 93, 94 . Ketogenic diet could also be an option, although no solid data are available to support this.

Case presentation

And pushed to a level of 12 mg dL without change in his seizure control . Zonegran improved the myoclonic seizures briefly, but they later returned Convulsive seizures continued daily absences and myoclonic-astatic seizures were seen throughout the day. Up to this point he had been a normally developing child, but now his language regressed to where he was speaking in one- or two-word sentences or pointing . He was drooling . He would spend most of his day sitting, surrounded by pillows to avoid falls and head injury His motor function was also affected, and he walked wide-based and appeared ataxic At age 4. 5 years, he was started on the ketogenic diet (KD) . Within 1 week of KD therapy, all of his seizures abated . Within 6 months of KD therapy, he was successfully weaned off all his medications, and his language and balance returned to normal After 3 years of KD therapy, he was successfully weaned onto regular food without recurrence of his seizures . He is currently 8 years old...

What Are Essential Foods

Food is generally viewed by official sources as consisting of six basic elements (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

Medically Intractable

Majority of patients with IGE are fully controlled with AEDs. In addition, most patients with IGE that are not controlled are not truly intractable but instead have been treated with inadequate AEDs (37, 67, 68). Nevertheless, epilepsy centers encounter patients with clear IGE who are refractory to medications. For these patients, there is some preliminary evidence that vagus nerve stimulation (VNS) is a good option. VNS may have comparable efficacy against IGE as it does in localization-related epilepsy (69, 70), but this (like newer AEDs) is off-label use. One study in an animal model of absence epilepsy found no benefit of VNS (71). Another option in truly intractable IGE may the ketogenic diet, but no data are available to support this.

Therapeutic Approach

At all, it is also useful in deciding whether or not to add a second drug or to try experimental drugs in a child whose seizures are not fully controlled on the current therapeutic regimen, whether to consider epilepsy surgery for a child who is medically refractory, or to offer the ketogenic diet as a possible treatment modality. As more information and newer therapies become available, the risk benefit ratios may well change. In order to provide the best care available, the physician needs both to be aware of the available options and to individualize them to the needs of the specific patient.

James J Riviello Jr Stavros Hadjiloizou

Epilepsy Diagnossis Ilae

Regression in intellectual or cognitive abilities, associated with behavioral problems, is the hallmark of these syndromes, and regression may even be the presenting manifestation. In general, cognitive regression should always raise the suspicion of a sleep-activated epileptic encepha-lopathy, especially in those with underlying developmental or neurological disorders. LKS and CSWS may respond to treatment with the standard antiepileptic drugs (AEDs) but often require other therapies, such as corticosteroids (10-15), high dose benzodiazepine (16, 17), and other immune-modulating therapies such as intravenous immu-noglobulin (IVIG) (18-21), or the ketogenic diet (22, 23).

Ring Chromosome 20 Syndrome

Chawla and colleagues55 described success with VNS Therapy for intractable seizures associated with ring 20 chromosome syndrome in a girl of six years of age. She tried unsuccessfully with variations of AED and a ketogenic diet. This patient remained seizure free at nine months of follow up and became more social and

Articles in scientific journals

Fejerman N, Caraballo R, and Cersosimo R. 2005. Ketogenic diet in patients with Dravet syndrome and myoclonic epilepsies in infancy and early childhood. AdvNeurol, 95 299-305. Freeman JM, Vining EPG, Pillas DJ, et al. 1998. The efficacy of the ketogenic diet 1998 a prospective evaluation of intervention in 150 children. Pediatrics, 102 1358-63. Kang HC, Chung da E, Kim DW, et al. 2004. Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia, 45 1116-23. Kossoff EH, Pyzik PL, McGrogan JR, et al. 2002. Efficacy of the ketogenic diet for infantile spasms. Pediatrics, 109 780-3. Vining EPG. 1999. Clinical efficacy of the ketogenic diet. Epilepsy Res, 37 181-90. Vining EPG, Freeman JM, Ballaban-Gil K, et al. 1998. A multicentre study ofthe efficacy ofthe ketogenic diet. Arch Neurol, 55 1433 -7. Wheless JW. 2001. The ketogenic diet an effective medical therapy with side effects. J Child Neurol, 16 633-5.

The treatment of epilepsy between 1938 and 1945

Lennox's literature reviews and the summaries of epilepsy practice in the different countries (notably in the USA in these years) in Epilepsia provide an excellent vantage point to view the progress of epilepsy therapy in the years 1938-45. The first literature review was published in 1938 (actually a review of the year 1936). Thirteen articles on treatment were reviewed, and these were concerned with bromides, phenobarbital, prominal, antirabies vaccine, ergotamine tartrate, subarachnoid air injections, non-dehydrating doses of Epsom Salt, X-irradiation, atropine, fluid restriction and the keto-genic diet. In 1939, Lennox published his annual review of epilepsy in America 2 , He again described treatment. Barbiturate, bromide and borotartrate were still the mainstay of treatment, but he also reported the experimental results of other therapies. Of these, the most interest was in the effects of ketosis and the ketogenic diet (this had been of recurring interest throughout the 1930s),...

Special diets and nutritional supplements

The ketogenic diet is widely accepted now as main-line therapy for a few children with severe epilepsy (see p. 96). However, other diets are also used widely as complementary therapies. The Atkins diet (60 fat, 30 protein and 10 carbohydrate) has gained favour, no doubt because of its superficial resemblance to the ketogenic diet (typically 80 fat, 15 protein and 5 carbohydrate). In a small open study of six children and adults, 50 became seizurefree. The best results were seen in those who attained ketosis. Fasting also undoubtedly helps epilepsy, and on this basis, low carbohydrate diets have been attempted and have advocates. Oligoantigenic diets are widely used in paediatric practice, and have been the subject of limited scientific investigation. One interesting double-blind study in a 19-year-old woman with frequent seizures, a history of allergies and eosinophilia was carried out. She was found by an elimination diet to be sensitive to beef. Seizures occurred soon after taking...

Epilepsy Questions and Answers about Seizure Disorders

Summary Epilepsy Questions and Answers about Seizure Disorders is a brochure that provides general information about epilepsy to the public. Topics include (1) questions and answers about epilepsy (2) questions and answers about seizures (3) seizures that look like sleepwalking (4) most seizures do not injure the brain (5) seizures do not cause injuries to other people (6) questions and answers about first aid (7) simple first aid for epilepsy (8) how doctors treat epilepsy with drugs (9) surgery, the ketogenic diet, vitamin and mineral treatment, and biofeedback (10) questions and answers about daily living for individuals with epilepsy, including information on driving, employment, discrimination, drinking, serving in the armed forces, sports, swimming, insurance, aging, and mental illness and (11) how the Epilepsy Foundation of America helps people with epilepsy and the benefits of membership in the Foundation. A final section offers an annotated list of selected videos, pamphlets,...

Infantile sPAsMs AND west sYNDRoME

All patients were started on pyridoxine 3 days prior to and continued treatment during the 6-day double-blind period. Six of 20 (30 ) patients in the treatment group responded (cessation of spasms and resolution of hypsarrhythmia) and none in the placebo group (n 17). The three TS patients in the treatment group failed to respond. Somnolence was more commonly observed in the treatment group (4 out of 20 20 vs. 1 out of 17 6 ). None of the responders relapsed during the follow-up period (6-32 months, mean 16 months) 71 . The ketogenic diet is a further option in resistant cases and will be discussed later in this chapter.

Modeling to Test New Therapies

Alternative treatments for epilepsy also benefit from animal research. Vagus nerve stimulation (VNS), for instance, was first investigated with acute seizures in dogs and then with chronic epilepsy in monkeys before it was tried in humans (Schachter and Wheless, 2002). Animal research is also playing an important role in developing the techniques of deep brain stimulation as a treatment for epilepsy. Epilepsy surgery, gamma knife surgery, and the ketogenic diet (KD) have been used effectively in patients without preliminary studies in animals. However, animal research continues to be of value in our efforts to understand how these therapeutic interventions work, what might be done to improve them, and which patients are most likely to benefit from their use. Identifying appropriate animal models for testing therapeutic interventions is a prime concern. For example, because KD is principally used in children, understanding and improving KD-based approaches require comparable immature...

Editors

Kevin Chapman completed his residency training at Baylor College of Medicine and a clinical neurophysiology fellowship at the Cleveland Clinic Foundation . He served as faculty at Baylor College of Medicine before becoming faculty at the Barrow Neurologic Institute . Dr. Chapman's clinical and research areas of interest involve the surgical management of epilepsy, medical treatment of hypothalamic hamartoma, and the ketogenic diet

History

The child continued to develop satisfactorily until spasms recurred on vigabatrin at 12 months of age these spasms were associated with partial seizures. The spasms were again rapidly controlled using hydrocortisone, but partial seizures persisted. They were stereotyped in semiology the child hid her eyes with her right arm and cried for about 30 seconds, and then she recovered immediately. Ictal EEG showed paroxysmal activity over the right hemisphere, but the onset could not be localized more precisely. The seizures were refractory to antiepileptic drugs (carbamazepine, valproate, benzodiazepines, phenytoin, lamotrigine and stiripentol) and to the ketogenic diet. She had between five and 10 seizures a day until she was 7k years of age.

Conclusions

Dietary therapies are a useful treatment option for both children and adults with intractable epilepsy While diets can improve seizure control in many patients with epilepsy, certain particular epilepsy syndromes may respond better to the diet than others . Although often seen as a more natural treatment, side effects from the diets do occur and the complexity of the diets makes them difficult for some families . The recent emergence of alternative ketogenic diets such as the modified Atkins and low-glycemic index diets have also led to additional options for patients, especially adolescents and adults . Understanding the many advantages of dietary treatments for epilepsy is very important in the care of children and adults with refractory seizures, even in this era of plentiful new and old anticonvulsants

Efficacy in epilepsy

Cent had IQs under 70, 36 had tried the ketogenic diet and five had had callosotomies previously. The median seizure reduction at 3 months (n 43) was 58.2 and at 6 months was 57.9 (n 24). By 6 months there was a 50 decrease in 58 of patients. Drop attacks were reduced at 3 months by 55 and at 6 months by 88 . In the five patients with callosotomies, seizures were reduced by 73 at 3 months and 69 at 6 months 36 . Other smaller studies have reported similar results 37, 38 .

Other drug therapies

The value of antiepileptic therapy in West syndrome is difficult to assess, but most conventional antiepileptic drugs are relatively ineffective. Valproate and clonazepam control 25-30 of cases, but relapse rates are high. Carba-mazepine can worsen the spasms. Topiramate, lamotrigine, felbamate, and zonisamide have all been reported to help in small open-case series. Nitrazepam has been used but carries life-threatening side-effects. High-dose pyridoxine is often given and there are promising reports about IV immunoglobulin. The ketogenic diet and thyrotropin-releasing hormone have been reported to be occasionally helpful in refractory cases.

Outcome

Patients with TSC have a high prevalence of cognitive and behavioral difficulties, including autism Infantile spasms and early intractable epilepsy may increase this risk, and side effects of polytherapy with antiepileptic medications may play a role Many patients may respond to medical management with antiepileptic medications however, up to 40 of patients with early onset seizures may prove medically refractory. Epilepsy surgery may render more than 50 of appropriately selected patients seizure free A recent meta-analysis found that tonic seizures and moderate or severe intellectual disability were significant risk factors for seizure recurrence following surgery. For those that are not appropriate candidates, ketogenic diet or vagus nerve stimulation should be considered

Dietary Modification

In a paediatric population, the ketogenic diet is a recognized therapy for refractory epilepsy. It mimics the effects of starvation, with provision of high fat, low to moderate protein and very low carbohydrate diet. However, evidence to support its use in adult patients is very limited. One recent case series reported the use of the Atkins diet, which is akin to the ketogenic diet, with restriction of carbohydrates but not overall calories or proteins, in six patients aged between 7 and 52 years with refractory epilepsy 73 . Although three of the patients attained good seizure reduction, it was difficult to conclude whether or not the Atkins diet can be recommended as therapy for adult refractory epilepsy patients. In this cohort, only one of three adult patients (aged 18 years) maintained adherence to the diet, ketosis on urine testing and good seizure response to the therapy. By comparison, two of three paediatric patients (aged 18 years) attained good seizure response. The authors...

Longterm outcome

Once on a low-therapeutic dosage of oxcarbazepine, RM stopped having clinical seizures . However, after approximately 1 year, the seizures recurred and only transiently responded to sequential dosage increases . He was gradually changed to lamotrigine, to which topiramate was added due to persistent seizures RM was referred to a tertiary epilepsy center where he underwent a presurgical evaluation and was found to have seizures arising from the right temporal lobe. The literature reflects that only 50 of patients will remain seizure free with the first medication chosen, and only 60-70 of patients will have complete seizure control with multiple medication trials . Patients who fail two appropriately selected antiepileptic medications are diagnosed to have medically intractable or medically refractory epilepsy, and non-pharmacologic treatments should be considered These include resective epilepsy surgery, vagus nerve stimulation, and the ketogenic diet . Whenever possible, resec-tive...

Metabolic Disorders

Non-ketotic hyperglycaemia (NKH) usually occurs in older patients with non-insulin-dependent diabetes. It is associated with significant morbidity and mortality and often causes seizures. It may be precipitated by infection, surgery or other physiological stress. In contrast, ketotic hyperglycaemia rarely causes seizures, as ketosis is thought to have an anti-convulsant effect. Patients with NKH are often also hyponatraemic and may develop areas of potentially reversible focal cerebral damage 47 , both of which increase the risk of seizures. Treatment of NKH is with insulin, fluids and correction of the metabolic abnormalities.

Figure 242

Alternate treatments including immunoglobulins and the ketogenic diet have been tried, with case reports documenting efficacy, but long-term follow-up data are limited (18-22). MST has been performed in selected children who failed medical therapy, and it may provide benefit (62, 89).

Porphyria

Porphyria is a term used to describe a range of at least eight different diseases in which the hepatic production of haem is disordered. There is a marked geographical variation, and the highest frequency is in South Africa, where a founder effect has been traced to a Dutch orphan immigrant in 1688. Acute intermittent porphyria (AIP) is an autosomal dominant condition due to mutations in the porphobi-linogen deaminase gene. Symptoms (the acute attack) occur only intermittently, and are precipitated by hormones, low carbohydrate diet, and drugs. The drugs precipitate por-phyria by inducing P450 enzymes and this increases hepatic production of haem precursors. Certain antiepileptic drugs are quite unsafe in this regard in porphyria, and treatment of the epilepsy can be complicated by the risk of exacerbating symptoms (Table 1.25). In an acute attack, seizures occur with nausea, vomiting, pain in the back and limbs, urinary retention, muscle weakness, tachycardia, confusion and...

Safety

Figure Four Epilepsy

Patients of any age should be considered for VNS therapy if they experience seizures refractory to other therapies, including AEDs, the ketogenic diet, and epilepsy surgery Preliminary data suggest that patients treated with VNS therapy earlier in the course of their epilepsy (i .e . , when seizures fail to respond to treatment with two or three AEDs within 2 years of epilepsy onset) may have a higher response rate to treatment. 24

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