Lorazepam Nasal <5 min 15 \200\22360 min 12 \200\22316 hrs a Slow active metabolite. CHAPTER 12 non-pharmacological therapy of epilepsy 137 Seizure prodromes The term prodrome is used for \200\230warnings \200\231 that in some pat ients habitually precede a seizure for more than 1 hour. In the majority, they express mini mal or \200\230subclinical \200\231 status-like seizure activity such as absence status or aura status (8). Prodromes offer excellent conditions for ADA with an oral BZD. In practic e, it is often neces- sary to get relatives or carers involved because reduced awareness an d reactivity may be part of the prodromal symptoms. (PRE), and hot-water epilepsy (HWE) as re \202 ex epilepsies. These are summarized in Tabl e 12.3 , but there may be others. A variety of HWE in infants was described by Plouin and V igevano (48), and the large population of photosensitive subjects includes a small group wi th triggered GTCS only and no spontaneous seizures. These are generally not considered as r epresenting a separate syn- drome but may be therapeutically addressed differently from pat ients with both spontaneous and re \202 ex seizures. Pathophysiology of re \202 ex epileptic ictogenesis With elementary stimuli the latency fr om the stimulus onset to the clinical or EEG response is typically short (1 \200\2233 secon ds) and with complex stimuli, longer (usually some up to many minutes). Re \202 ex seizures and re \202 ex epilepsies The reproducibility of some patients \200 \231 seizures by well-de \201 ned trig- gers can sometimes provide possibilities of target ed prevention. A complex interaction between factors and stimuli from the endogenous (e.g. hormones, elect rolytes, state of consciousness, and body temperature) and exogenous environment (e.g. sens ory, electrical, and biochemical) may lower the seizure threshold, selec- tively activate i ctogenesis in speci \201 c hyperexcitable cortical systems or functional networks, and pro voke the initiation of a seizure (21, 49, 50). De \201 nition, precipitating stimuli, clinical manifestations, and diagnosis Re \202 ex seizures Re \202 ex, stimulus-sensitive, triggered, or sensory-evoked epileptic seizures a re synonyms (21) and they represent seizures that are \200\230objectively and consistently evoked by a speci \201 c afferent stimulus or by activity of the patient \200\231 (22). T he afferent stimuli may be elementary/unstructured (e.g. light \202 ashes) or elaborated/ struc- tured (e.g. a particular musical work). Activities may be elementary (e.g. a particu lar movement) or elaborate (e.g. involving visuomo- tor coordination) (22). Re \202 ex sei zures may occur in patients with focal and generalized epilepsy syndromes who also get spon tane- ous seizures. Isolated re \202 ex seizures can also occur in situations that do not necessarily require a diagnosis of epilepsy (21). Whereas the anatomical substrate of ictogenesis in many re \202 ex epilepsies remains poor ly understood, in others recent EEG and sophisticated neuroimaging studies (positron emissi on tomogra- phy, single-photon emission computed tomography, EEG/electro- myography-functio nal magnetic resonance imaging) have highlighted the important role of corticoreticular and corticocorti- cal circuitry, including the occipitotemporal regions in the genera- tion of seizures in PRE (41, 51), photoparoxysmal response generated in an hyperexcitable occipita l cortex and participation of frontorolandic regions in IPOLE (10, 24), ictal hypermetaboli c uptake in the medial temporal structures and hypothalamus in HWE (52), these areas corres pond only to a part of the neural net- work that underlies the function of reading, vision, or thermoregu- lation, which are complex processes that comprise different functions of th e brain and are integrated into a network that expands over different brain areas. Accordin g to Moeller et al. (53), the generation of spikes and waves in the photoparoxysmal respons e is an intracortical event different from the corticotha- lamic circuit producing spontane ous spikes and waves in absence epilepsies. Considering these aspects, re \202 ex epilepsi es could be considered excellent models of \200\230system epilepsies \200\231, in which se i- zures are the result of hyperexcitability of a network of either genetic or acquired ori gin, with possible age-related clinical expres- sion, and give rise to an epileptic process after the stimulus speci \201 c for that area is applied (30, 49, 54, 55). Visual stimuli are the most common external factors triggering seizures in humans. They may include: \202 ickering lights/intermittent photic stimulation, \202 ickering sunlight, arti \201 cial light, television, Pok mon cartoon, videogames; and also, speci \201 c v isual patterns (geometric), striped patterns as from Venetian blind, clothes (23 \200\22325 ). In addition, many other precipitating stimuli were also described: higher mental activit ies such as calculation, reading, speaking, writ- ing, and other language functions, praxis , thinking, decision- making, and neuropsychological electroencephalogram (EEG) activation (26 \200\22330); unexpected touch or noise and startle (31); somato- sensory or propriocept ive stimuli; micturition (32, 33); music (34); eating (35); tooth-brushing (36); and hot wa ter. Re \202 ex epileptic mech- anisms were recently extensively reviewed by Wolf and Koep p (9). The epileptic response may consist of clinical seizures \200\224 generalized (absences, my oclonia, GTCSs) or focal (e.g. visual, motor, or somatosensory) \200\224 or of epileptifor m EEG patterns (subclinical or ictal), alone or in combination. The role of the EEG is fund amental in establishing the relationship between the precipitating stimulus and the re \202 ex seizures (21). The importance of re \202 ex mechanisms recognition in the comprehensive treatment of pati ents with epilepsy The arrest of seizure activity at the stage of the aura (i.e. at the sta ge of locally restricted neuronal discharge) can be achieved both by non-speci \201 c (i.e . relaxation, concentration techniques or both, biofeedback, vagal nerve stimulation) and b y specific focus- targeted sensory or cognitive inputs. Speci \201 c focus-targeted inputs activate circumscribed cortical areas that are not yet involved in the epileptic discharge but are likely to become it during its spread from the primary epileptic focus to other ar eas and, eventually, both cerebral hemispheres (30, 49). Re \202 ex triggers of seizures need to be distinguished from factors that temporarily inc rease seizure propensity such as intense emo- tional stress, sleep deprivation and tirednes s, fever, menstruation, alcohol consumption, and many others. Re \202 ex epilepsies Re \202 ex epilepsies constitute epileptic syndromes in which all e pi- leptic seizures are precipitated by sensory stimuli, and the 2006 International League Against Epilepsy Commission on Clas- si \201 cation and Terminology Report (37) listed idi opathic photosen- sitive occipital lobe epilepsy (IPOLE), primary reading epilepsy oxford textbook of epilepsy and epileptic seizures 138 Table 12.3 Re \202 ex epilepsy syndromes recognized by the ILAE Commission on Classi \201 cation and Terminology Report (25) IPOLE (10, 21, 24, 37, 38) PRE (27, 39, 40) HWE (41 \200\22346) Synonyms \200\223 \200\223 Water-immersion epilepsy, bathing epilepsy First reported Guerrini et al. (1995) Bickford et al. (1956) Allen (1945) De \201 nition All seizures induced by photic stimuli, particularly videogames and TV Seizures occurring in relation to reading (especially aloud), progressing to a GTCS if stim ulus continued CFS precipitated by bathing with hot water (40 \200\22350 C) poured over the head Prevalence 0.4 % of all epilepsies Very low 6.9 % of all epilepsies in the Bangalore community (60/100,000) Age of onset Late childhood or puberty Late puberty 13.4 11.1 (SD) years (44) M:F 1:2 1.8:1 2 \200\2232.5:1 Seizures Auras of colorful elementary circular, bright or \202 ashing, visual hallucinations often associated with conscious tonic head and eye version. Blurring of vision or blindness has also been reported. Visual symptoms may be isolated, usually lasting for seconds, frequentl y 1 \200\2233 min and rarely longer (5 \200\22315 min) in which case other symptoms also oc cur (autonomic, mainly retching and ictal vomiting, and, rarely, secondary GTCS) SFS characterized by myoclonia in the jaw or orofacial muscles, sometimes with involvement of arms, progressing to a GTCS if reading continues. Occasionally, transient cognitive impa irment with the jerks. Rarely partial seizures with ictal dyslexia or alexia, speech arrest . Bilateral brachial myoclonia may also occur. Absences uncommon CFS with or without secondary GTCS, initiating with \201 xed look, fear, dysphasia, visua l and auditory hallucinations associated with complex automatisms, lasting 30 s to 3 min. P rimary GTCS have also been reported in 1/3 of cases Neurological examination Normal Normal Normal EEG Interictal: uni- or bilateral spontaneous synchronous or asynchronous occipital spikes or s pike-waves and/or generalized spike and wave discharges Ictal: IPS (5 \200\22340 Hz) elicit s abnormal EEG paroxysms of spikes or polyspikes con \201 ned to the occipital regions or generalized photoparoxysmal responses of spikes or polyspikes and slow waves that predomina te in the posterior regions Interictal: normal Ictal: very brief 3 \200\2236 Hz bilateral and synchronous spikes or spi ke-waves maximal in the dominant occipital and parietal areas, evoked paroxysmal rhythmic t heta activity or spikes over one or both frontocentral, centroparietal, or temporoparietal regions in association with jaw jerks. The left > right hemisphere is involved when activit y is unilateral, but bilateral jaw jerks may be associated with unilateral discharges. Also , uni-, bilateral or asymmetric myoclonia and bilaterally synchronous spike and wave activi ty may be associated Interictal: usually normal, but 15 \200\22320 % might show diffuse abnormalities, and later alized or localized spike discharges Ictal: left or right temporal rhythmic delta activity, sharp and slow waves in the left hemisphere or bilateral spikes Neuroimaging No structural lesions on MRI No structural lesions on MRI No structural lesions on MRI Genetics Unclear \200\224 probably genetically determined Unclear \200\224 probably genetically determined Two gene loci described in families with autosomal dominant occurrence (45, 46) Management Avoidance of precipitating factors is essential, particularly to videogames and TV. Avoid s troboscope lights, looking away, covering one eye, wearing polarized or colored glasses, wa tching TV from a distance of at least 2 m, viewing a 100 Hz television set are often effect ive. Sodium valproate, clonazepam, clobazam No deterioration in neurological status and goo d prognosis Avoidance of precipitating factors. Valproate or small doses (0.5 \200\2231 mg) of clonazep am No deterioration in neurological status and good prognosis Avoid precipitant stimuli (prefer warm water for a head bath or sponging with hot towels). Phenytoin or carbamazepine. Prophylaxis with benzodiazepines (clobazam 5 \200\22310 mg 1.5 \200\2232 h before a head bath) No deterioration in neurological status and good prognosis CF, complex focal seizures; EEG, electroencephalogram; F, female; GTCS, generalized tonic \200\223clonic seizures; HWE, hot-water epilepsy; ILAE, International League Against Epilep sy; IPOLE, idi- opathic photosensitive occipital lobe epilepsy; IPS, intermittent photic st imulation; M, male; MRI, magnetic resonance imaging; PRE, primary reading epilepsy; SD, sta ndard deviation; SFS, simple focal seizures CHAPTER 12 non-pharmacological therapy of epilepsy 139 Table 12.4 Non-pharmacological preventive measures for visually induced seizures In some patients, the same stimulus can both precipitate and abort a seizure. The type of r esponse to the stimulus largely depends on the state of cortical activation at the moment t he input is given: while an input meeting a pool of potentially ictogenic neurons in the re sting condition or at the intermediate state of activation of the neuronal membrane may pre cipitate a seizure; seizure inter- ruption may occur when epileptic discharge has already b egun or a critical mass of neurons responding to a stimulus strong enough may block the spr ead of seizure activity (49). \227\206 Looking away or avoiding the source of stimuli, such as discotheque lighting, str iped clothing, and other striped patterns; sunlight on water; \202 ickering sunlight; sud den changes in light and contrast; and \202 ashing TV programs and videogames (49) \227\206 Closing or monocular occlusion with the palm of a hand so as to prevent light rea ching the retina of one eye. Other alternative methods are the use of dark or colored glass es (dark blue/green or precision tints), or the use of polarized glasses which are effectiv e in reducing the diffusion of light (49, 50) \227\206 Use small TV, 12-inch set and viewi ng from a distance of at least three times Because of their variability from patient to patient, as well as their variability with tim e in the same patient, combined with the emphasis on AED therapy in modern epilepsy care, t he utility of these factors that may modify ictal susceptibility of patients has been negle cted in the current management of PWE (5). the width of the TV screen in a well-lit room (6, 49) \227\206 Use preferably liquid crystal display computers or TV; 100 Hz TV set (120 Hz in N orth America) will increase the frequency of the \202 ickering screen from 50 Hz (60 Hz i n North America) to 100 Hz (120 Hz in North America) and make sensitivity to whole-screen \202 icker or the pattern of vibrating lines less likely and the image more stable (51) Speci \201 c non-pharmacological measures for prevention and inhibition of re \202 ex sei zures and epilepsies Visually-induced seizures are by far the most common re \202 ex sei- zures. Changes in luminance, contrast, pattern, and color can provoke seizures in photosens itive individuals. Although no rand- omized controlled trials, or controlled comparative cl inical trials to evaluate pharmacological and non-pharmacological treatments have been perf ormed, data on ef \201 cacy depending on series of patients have allowed the implementatio n of diverse preventive measures for photosensitive epilepsies. The modern environment is a rich source of potentially seizure-triggering visual stimuli, to which people are increasi ngly exposed at all ages worldwide, such as televisions (TVs), computers, video games, disc otheque lights, Venetian blinds, striped walls, rolling stairs, striped clothing, and sunli ght re \202 ected from snow or the sea or interrupted by trees during a ride in a car or t rain, dysfunctioning \202 uorescent lighting, etc. (10, 23, 25). \227\206 Use of temporal optical \201 lters or video-hazard blocker to avoid TV \202 i cker- and pattern-induced seizures (52, 53) \227\206 Avoid adjusting the controls or fast-forwarding the video and keep at a distance from the screen by using remote control (49) in selected cases only and requires a tailored intervention taking care of the individual c ircumstances. Behavioral therapy : antistress, cognitive behavioral therapy, and relaxation programs were applied for preventing seizures precipitated by higher mental activities (64, 65). Stimulus avoidance : most patients with PRE get a series of orofacial myocloni before devel oping a GTCS. They can learn to stop reading at the \201 rst myoclonus and thus avoid maj or seizures. This can be used as a monotherapeutic approach (27), but for patients who have experienced rapid development of GTCSs or who need to read a lot this is not suf \201 cie nt and they will need pharmacotherapy. In these cases, avoidance of potentially provocative visual stimuli is the mainstay of trea tment. Protection against the stimulus by its modi \201 cation or attenuation has especial ly been used for photosen- sitivity. It was reviewed by Covanis et al. (56) and is summariz ed in Table 12.4 . Successful use of dark and colored glasses or \201 lters has been desc ribed by several authors (57 \200\22360). For TV-sensitive patients, a 100 Hz screen is les s provocative than a 50 Hz screen. (61).The effectiveness of stimulus avoidance and modi \201 cation will depend on the individual \200\231s degree of photosensitivity (Table 12.4 ). Patients with seizures exclusively triggered by visual stimuli, such as TV or \202 ick ering sunlight (also called \200\230pure photosensitive epi- lepsy \200\231), may be treat ed without AEDs. For most patients, however, non-pharmacological approaches are combined wi th AEDs, since avoidance of provocative visual stimuli in modern daily life is becoming inc reasingly dif \201 cult (56). Briefer and less vigorous tooth-brushing has been recommended for PWE with a slow precipita tion of seizures only by vigorous tooth-brushing (36), and the introduction of an urinary c atheter to suppress micturition-induced re \202 ex seizures (32). Stimulus attenuation and sensory protection : its role in photosen- sitivity is described i n an earlier section. Patients with the infantile type of HWE (48) are susceptible to water with a temperature above 37.5 C. As these infants don \200\231t have spontaneous seizur es and the condition is age-limited, treatment consisting in bathing them in water below th is temperature is suf \201 cient. In the variety of HWE in older children, adolescents, and adults (42, 43), the patients get seizures when hot water is poured over their head ( \200\230head bath \200\231). The non-p harmacological treatment con- sists of using lukewarm water for head bath or sponging the h ead with hot towels, avoiding pouring water over the head (66). Deconditioning : rather systematic attempts at treating re \202 ex epi- lepsies, such as p hotosensitive seizures, by deconditioning meth- ods were undertaken with some success by Fo rster (62), who applied standardized methods of deconditioning, e.g. by starting intermitte nt photic stimulation with reduced light intensity or with subthreshold \202 ickering fre quencies and then gradually increasing the intensity. However, his \201 ndings were not r eplicated and are today largely forgotten. Wolf and Dockweiler (63) reported suc- cessful d econditioning in a patient with tonic versive seizures pre- cipitated by touch. Decondition ing seems to be a useful approach Acute drug prevention : Dhanaraj and Jayavelu (47) reported 10 patients with the last-menti oned type of HWE who were suc- cessfully treated only by intake of 10 mg clobazam 1 hour before a head bath. However, with daily or quasi -daily application of clobazam, tolerance is likely to develop because of the accumula- tion of the active metabolite desmethylclobaz am with a half-life of about 50 hours. Midazolam seems to be a better choice for this condi tion where it could be applied orally since no immediate action is required. oxford textbook of epilepsy and epileptic seizures 140 Diets The history of the treatment of epilepsy starts many centuries before the advent of m odern pharmacotherapy. Diets were an important part of therapy, and still after the introdu ction of the \201 rst effective AED, bromide, diets were discussed in textbooks in relati on to theories about metabolic and nutritional causes of seizures (67). In a chronic condit ion with a substantial rate of pharmacoresistance, there will always be an interest in alte rnative treatments. On the Internet, always a mine of alternative approaches, recommendatio ns can be found, e.g. of glutamate aspartate restricted diet, and a detailed discussion of nutritional factors supposed to have an in \202 uence on epilepsy and their possi- ble con trol (68). One diet (with two variants) stands out because it is today scienti \201 cally well established. A ketogenic diet is effective in up to 54 \200\22360 % of patients with myoclonic-astatic e pilepsy (75 \200\22378). In the series of Oguni et al. (75), a signi \201 cant decrease in myoclonic and atonic seizures was observed in 15 out of 26 patients. In the study by Carab allo et al. (77), after 18 months after the diet initiation two of six children became seiz ure-free, two demonstrated seizure reduction of 75 % or more, and two patients of 50 \200 \22374 % reduction. In Dravet syndrome, as shown in one case series, the ketogenic diet resulted in greater tha n 75 % improvement in 50 % of patients, while another case series showed greater than 50 % improvement in seizure frequency in over 60 % of children (79 \200\22381). However, all the studies were retrospective and in none of them was a direct comparison of the diet ef \201 cacy and AEDs performed. A ketogenic diet might be also bene \201 cial in infantile spasms refractory to vigabatrin and corticosteroids (81 \200\22383). A compara- tive assessment of the ketogenic diet vers us adrenocorticotropic hormone (ACTH) demonstrated that complete seizure control after 1 mo nth of therapy was achieved in 62 % and 90 % of children respectively. The ketogenic diet h ad fewer side effects than ACTH but ACTH normalized EEG more rapidly (83). In their prospec tive study, Hong et al. (82) reported that greater than 50 % spasm improvement occurred in 64 % of patients at 6 months and 77 % after 1 \200\2232 years. Thirty-eight (37 % ) became spasm-free for at least a 6-month period within a median 2.4 months of starting the ketogen ic diet. The ketogenic diet The ketogenic diet is a high-fat, low-to-adequate protein, low- carbohyd rate diet which is used as a therapeutic alternative to AEDs in epilepsy treatment. Histori cally, fasting can be considered its precursor. The \201 rst modern use of starvation as a treatment for epilepsy was recorded in 1911 by two Parisian physicians, Guelpa and Marie, who treated 20 patients with epilepsy and reported the decrease of seizure severity during treatment. Later on, several sim- ilar attempts have been made in the US by Dr Hugh W. Con klin and Bernard Macfadden (69) Ketogenic diet is elective therapy for several metabolic conditions (71): glucose transport er type I (GLUT-I) de \201 ciency, pyruvate dehydrogenase de \201 ciency, phosphofruktoki nase de \201 ciency and glycogenosis type V (MacArdle disease). In these disorders the ket ogenic diet provides an alternative source of energy for the brain, in GLUT-I de \201 cien cy syndrome in the form of ketone bodies and beta-hydroxybutirate, in pyruvate dehydrogenas e de \201 ciency an alternative source of acetyl-CoA, thus controlling seizures and improv ing the general condition of patients (71, 84). The beginning of ketogenic diet use in epilepsy treatment was in 1921, when Dr Wilder in th e Mayo Clinic proposed producing ketonaemia by other means than fasting. He suggested that the diet should be as effective as fasting and could be maintained for a much longer period of time (69). However, further development of the new AEDs, such as pheny- toin and later valproate, was associated with a decline of interest in the ketogenic diet. Nevertheless, the ketogenic di et has experienced a re-emergence in recent years, and now it is available in more than 45 countries (69, 70). Contraindications Ketogenic diet is contraindicated in the following conditions (71): Types of ketogenic diet Three types of ketogenic diet are currently used for epilepsy treat - ment (71): the classical ketogenic diet, modi \201 ed Atkins diet, and ketogenic diet wi th medium-chain triglycerides. \227\206 Primary carnitine de \201 ciency \227\206 Carnitine palmitoyltransferase de \201 ciency type I or II \227\206 Carnitine translocase de \201 ciency \227\206 Defects of beta-oxidation The classical ketogenic diet is constituted from normal foods and involves utilization of t he long-chain triglycerides. It has a ratio of fat to protein plus carbohydrate of 4:1. The two other diets are less restrictive than the traditional ketogenic diet. The modi \201 e d Atkins diet has a ketogenic ratio of 0.9:1, and the ketogenic diet with medium-chain trig lycerides is a variant with the ketogenic ratio 1.2:1. It is an option for patients who can tolerate more calo- ries, have a large appetite, or who cannot accept the restrictions of the classical ketogenic diet. All three types of the ketogenic diet showed comparable ef \201 cacy in the treatment of childhood epilepsy (72 \200\22374). \227\206 Pyruvate carboxylase de \201 ciency \227\206 Porphyria. Initiating the ketogenic diet in patients with these conditions might cause a severe deteri oration or devastating catabolic crisis. Therefore, before diet administration, all patient s should be screened for disorders of fatty acid transportation and disturbances of beta-ox idation. Mechanisms of action The mechanisms underlying the ef \201 cacy of the ketogenic diet are still not completely understood. Many hypotheses have been developed and tested, however, n one of them gives complete explanation. One of the theories suggested is that ketone bodies could have a direct anticonvulsant effect but most studies have failed to observe it (85). The modulation of the neurotransmitter system by the ketogenic diet has also been discusse d. Nevertheless, data con \201 rming this Indications for use Although a ketogenic diet might be effective in a broad range of medica lly refractory epilepsies, it is most often used for the treat- ment of generalized epileps ies. The particular benefit of the ketogenic diet has been identi \201 ed in myoclonic-ast atic epilepsy, Dravet syndrome, and infantile spasms (71). CHAPTER 12 non-pharmacological therapy of epilepsy 141 creatinine). Between the visits, parents evaluate urine ketosis several times per week. hypothesis is lacking. There is evidence indicating that the ketogenic diet enhances energy production in the brain, and as a consequence the brain tissue becomes more resistant to m etabolic stress (86). The author proposed that enhancements in metabolism, induced by the k etogenic diet, compensate for metabolic de \201 cits exhibited within epileptic foci and t ransient failures of gamma-aminobutyric acidergic inhibition. Weinshenker (85) reported the involvement of noradrenaline to the anticonvulsant effect of the ketogenic diet, although noting that its presence is rather \200\230permissive \200\231 than an integral part of th e direct anticonvulsant mechanism. Adverse effects The most frequently observed side effects of the ketogenic diet are: gastro intestinal disturbances (constipation, vomiting, diarrhea, abdominal pain), hypercholestero laemia, kidney stones, and growth failure. Gastrointestinal symptoms have been reported in 12 \200\22350 % of children, and hypercholesterolemia in 14 \200\22359 % of patients (80, 8 9). Kidney stones occur in 5 \200\2237 % of children. Risk factors include young age, famil y history of kidney stones, and urine calcium/creatinine ratio of more than 0.2 (90). Oral potas- sium citrate signi \201 cantly decreases the risk of kidney stone forma- tion. A nu mber of studies have demonstrated the slowed growth of patients on the ketogenic diet. The majority of children were below the 10th percentile for height at diet follow-up (80, 91, 9 2). Growth problems were independent from the type of diet, mean age, diet duration, protei n, and energy intake per body weight (73, 92). However, one recent study, evaluating the lo ng-term outcomes of the ketogenic diet, reported the improvement of growth after diet disco ntinuation (93). Implementation and management of the ketogenic diet The International Ketogenic Diet Study Group has recently elabo- rated recommendations for the optimal clinical management of chil dren receiving the ketogenic diet (71). Before starting the ketogenic diet a clinical consu ltation is needed. The purpose of it is to give the family or carers complete information a bout the ketogenic diet, to review the current antiepileptic treatment, and determine carbo hydrate content, to make the decision regarding which type of diet should be chosen. The following laboratory tests are recommended to be per- Ketogenic diet discontinuation The ketogenic diet should not be discontinued before at leas t a mean of 3.5 months of use (71). In patients with more than 50 % seizure reduction the k etogenic diet can be discontinued after 2 years, whereas in patients with almost complete s eizure control it can be used for a longer period, up to 6 \200\22312 years (89). Typically the ketogenic diet is tapered off slowly, over 2 \200\2233 months. The ketogenic ratio gra dually decreases from 4:1 to 3:1 to 2:1. Ketogenic food is then continued with free \202 uid intake and amount of calories. Usual food can be reintroduced after the ketosis is lost . formed before diet initiation: \227\206 Complete blood count with platelets \227\206 Electrolytes (serum bicarbonate, total protein, calcium, zinc, selenium, magnesium, phosphate) \227\206 Liver and kidney tests (albumin, aspartate transaminase, alanine transaminase, blood urea nitrogen, creatinine) \227\206 Fasting lipid pro \201 le \227\206 Serum acylcarnitine level \227\206 Urinalysis References \227\206 Urine calcium and creatinine 1 . Fisher RS , van Emde Boas W , Blume W , Elger C , Genton P , Lee P , et al . Epileptic seizures and epilepsy: De \201 nitions proposed by the ILAE and IBE . Epilepsia 2005 ; 46 : 470 \200\223 2 . \227\206 Urine organic acids \227\206 Serum amino acids. 2 . Hauser WA , Annegers JF , Kurland LT . Prevalence of epilepsy in Rochester, Minnesota: 1940-1980 . Epilepsia 1991 ; 32 : 429 \200\223 45 . The procedure usually begins with an initial fasting period. In many countries this takes p lace at the hospital since the child can experience side effects, such as hypoglycaemia, ac idosis, vomiting. The fasting period varies from 12 \200\22348 hours. While staying at the hospital the parents/carers are taught to calculate, weigh, and prepare meals. However, som e studies demonstrated that fasting is not necessary to achieve ketosis, and the gradual in i- tiation of the ketogenic diet without fasting is associated with less side effects but t he same seizure control within the \201 rst 3 months (87, 88). 3 . Ad hoc Task Force of the ILAE Commission on Therapeutic Strategies . De \201 nition of drug resistant epilepsy: consensus proposal . Epilepsia 2010 ; 51 : 1069 \200\223 77 . 4 . Foldvary-Schaefer N , Falcone T . Catamenial epilepsy. Pathophysiology, diagnosis, and management . Neurology 2003 ; 61 (Suppl 2 ): S2 \200\223 S15 . 5 . Aird RB . The importance of seizure-inducing factors in the control of refractory forms of epilepsy . Epilepsia 1983 ; 24 : 567 \200\223 83 . 6 . Wolf P , Okujava N . Possibilities of non-pharmacological conservative treatment of epilepsy . Seizure 1999 ; 8 : 45 \200\223 52 . 7 . Trevorrow T . Air travel and seizure frequency for individuals with The concomitant AEDs are not changed in the \201 rst months after diet initiation, wherea s they can be reduced or sometimes with- drawn after several months of seizure control by t he ketogenic diet. Ketogenic diets contain limited quantities of fruits, vegetables, and in suf \201 cient amounts of calcium and vitamins D and B. Therefore, dietary supplementation is needed. A child on the ketogenic diet should be seen by a neurologist and a dietician a t least every 3 months during the \201 rst year on the diet. At each visit a labora- tory assessment should be performed (complete blood count with platelets, electrolytes, serum l iver and kidney parameters, fasting lipid pro \201 le, serum acylcarnitine, urinalysis, an d urine calcium and epilepsy . Seizure 2006 ; 15 : 320 \200\223 7 . 8 . Scaramelli A , Braga P , Avellanal A , Bogacz A , Camejo C , Rega I , et al . Prodromal symptoms in epileptic patients: clinical characterization of the pre-ictal phase . Seizure 2009 ; 18 : 246 \200\223 50 . 9 . Wolf P, Koepp M (2012). Re \202 ex epilepsies. In: Handbook of Clinical Neurology, Vol .107, Epilepsy , Part I (H Stefan & WH Theodore, eds). Edinburgh: Elsevier (in press). 10 . Kasteleijn-Nolst Trenit DGA . Photosensitivity, visually sensitive seizures and epilepsies . Epilepsy Res 2006 ; 70 (Suppl 1 ): 269 \200\223 79 . 11 . Beniczky S, Guaranha MSB, Conradsen I, Singh MB, Rutar V, Lorber B, Braga P, Bogacz Fressola A, Inoue Y, Yacubian EMT, Wolf P. oxford textbook of epilepsy and epileptic seizures 142 37 . Engel J Jr . Report of the ILAE Classi \201 cation Core Group . Epilepsia Modulation of epileptiform discharges in juvenile myoclonic epilepsy: An investigation of r e \202 ex epileptic traits. Epilepsia 2012; 53: 832 \200\2239. 12 . May TW , Pf f \202 i n M . The ef \201 cacy of an educational treatment program 2006 ; 47 ( 9 ): 1558 \200\223 68 . 38 . Guerrini R , Dravet C , Genton P , Bureau M , Bonanni P , Ferrari AR , et al . Idiopathic photosensitive occipital lobe epilepsy . Epilepsia 1995 ; 36 ( 9 ): 883 \200\223 91 . for patients with epilepsy (MOSES): results of a controlled, randomized study . Epilepsia 2 002 ; 43 : 539 \200\223 49 . 39 . Taylor I , Marini C , Johnson MR , Turner S , Berkovic SF , Scheffer IE . Juvenile myo clonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap? Br ain 2004 ; 127 ( 8 ): 1878 \200\223 86 . 40 . Bickford RG , Whelan JL , Klass DW , Corbin KB . Reading epilepsy: 13 . Wolf P . Acute drug administration in epilepsy. A review. CNS Neurosci Ther 2011 ; 17:442 \200\2238. 14 . Wolf P . Acute administration of benzodiazepines as part of treatment strategies for epilepsy . CNS Neurosci Ther 2011 ; 17 : 214 \200\223 20 . clinical and electrographic studies of a new syndrome . Trans Am Neurol Assoc 1956 ; 81 ( 1 ): 100 \200\223 2 . 15 . Paulson GW . Inhibition of seizures . Dis Nerv Syst 1963 ; 24 : 657 \200\223 64 . 16 . Cull CA , Fowler M , Brown SW . Perceived self-control of seizures in 41 . Koutroumanidis M , Koepp MJ , Richardson MP , Cam \201 eld C , young people with epilepsy . Seizure 1996 ; 5 : 131 \200\223 8 . Agathonikou A , Ried S , et al . The variants of reading epilepsy: a clinical and video-EEG study of 17 patients with reading-induced seizures . Brain 1998 ; 121 ( 8 ): 1409 \200 \223 27 . 17 . Lee SA , No YJ . Perceived self-control of seizures in patients with uncontrolled partial epilepsy . Seizure 2005 ; 14 : 100 \200\223 5 . 18 . Gowers WR . Epilepsy and other convulsive diseases . London : Churchill , 42 . Allen IM . Observation on cases of re \202 ex epilepsy . N Z Med J 1945 ; 1881 . 44 : 135 \200\223 42 . 19 . Efron R . The effect of olfactory stimuli in arresting uncinate \201 ts . 43 . Mani KS , Gopalakrishnan PN , Vyas JN , Pillai MS . Hot-water epilepsy: a peculiar typ e of re \202 ex epilepsy, a preliminary report . Neurology (India) 1968 ; 16 ( 3 ): 107 \200\223 10 . Brain 1956 ; 79 : 267 \200\223 81 . 20 . Efron R . The conditioned inhibition of uncinate \201 ts . Brain 1957 ; 80 : 251 \200\223 62 . 44 . Satishchandra P , Shivaramakrishnana A , Kaliaperumal VG , 21 . Panayiotopoulos CP . A clinical guide to epileptic syndromes and their treatment: base d on the new ILAE diagnostic scheme . Oxford: Bladon Medical Publishing , 2002 . Schoemberg BS . Hot-water epilepsy: A variant of re \202 ex epilepsy in Southern India . E pilepsia 1988 ; 29 : 52 \200\223 6 . 45 . Ratnapriya R , Satishchandra P , Dilip S, Gadre G, Anand A. Familial autosomal dominan t re \202 ex epilepsy triggered by hot water maps to 4q24 \200\223q28 . Hum Genet 2009 ; 1 26 : 677 \200\223 83 . 22 . Blume WT , L ders HO , Mizrahi E , Tassinari C , van Emde Boas W , Engel J Jr . Glossary of descriptive terminology for ictal semiology: report of the ILAE ta sk force on classi \201 cation and terminology . Epilepsia 2001 ; 42 : 1212 \200\223 8 . 46 . Ratnapriya R , Satishchandra P , Kumar SD , Gadre G , Reddy R , Anand A . A locus for autosomal dominant re \202 ex epilepsy precipitated by hot water map s at chromosome 10q21.3 \200\223q22.3 . Hum Genet 2009 ; 125 : 541 \200\223 9 . 23 . Wilkins AJ , Andermann F , Ives J . Stripes, complex cells and seizures: an attempt to determine the locus and nature of the trigger mechanism in pattern-sensitive epilepsy . Brain 1975 ; 98 : 365 \200\223 80 . 47 . Dhanaraj M , Jayavelu A . Prophylactic use of clobazam in hot water 24 . Parra J , Kalitzin SN , Silva FHL . Photosensitivity and visually induced epilepsy . J Assoc Physicians India 2003 ; 51 : 43 \200\223 4 . seizures . Curr Opin Neurol 2005 ; 18 : 155 \200\223 9 . 48 . Plouin P , Vigevano F . Re \202 ex seizures in infancy . In: Wolf P , Inoue Y , Zifki n B (eds) Re \202 ex epilepsies: progress in understanding , pp. 115 \200\223 22 . Montro uge : John Libbey Eurotext , 2004 . 25 . Kasteleijn-Nolst Trenit DGA , Van der Beld G , Heynderickx I , Groen P . Visual stimuli in daily life . Epilepsia 2004 ; 45( Suppl 1 ): 2 \200\223 6 . 26 . Wilkins AJ , Zifkin B , Andermann F , McGovern E . Seizures induced by 49 . Wolf P . From precipitation to inhibition of seizures: rationale of a thinking . Ann Neurol 1982 ; 11 : 608 \200\223 12 . therapeutic paradigm . Epilepsia 2005 ; 46 (Suppl 1 ): 15 \200\223 6 . 50 . Zifkin BG . So me lessons from re \202 ex seizures . Epilepsia 2010 ; 27 . Wolf P . Reading epilepsy . In: Roger J, Bureau M, Dravet CH, Dreifuss FE , Perret A , Wolf P (eds) Epileptic syndromes in infancy , childhood and adolescence (2nd edn), pp. 281 \200\22398 . London: J. Libbey , 1992 . 51 (Suppl 1 ): 43 \200\223 4 . 51 . Salek-Haddadi A , Mayer T , Hamandi K , Symms M , Josephs O , 28 . Inoue Y , Seino M , Tanaka M , Kubota H , Yamakaku K , Yagi K . Epilepsy with praxis-i nduced epilepsy . In: Wolf P (ed) Epileptic seizures and syndromes , pp . 81 \200\223 91 . London: John Libbey , 1994 . Fluegel D , et al . Imaging seizure activity: a combined EEG/EMG-fMRI study in reading epil epsy . Epilepsia 2009 ; 50 ( 2 ): 256 \200\223 64 . 52 . Satishchandra P , Kallur KG , Jayakumar PN . Inter-ictal and ictal 99m 29 . Matsuoka H , Takahashi T , Sasaki M , Matsumoto K , Yoshida S , TC ECD SPECT scan in hot-water epilepsy . Epilepsia 2001 ; 42 (Suppl 7 ), 158 . Numachi Y , et al . Neuropsychological EEG activation in patients with epilepsy . Brain 200 0, 123 ( 2 ): 318 \200\223 30 . 53 . Moeller F , Siebner HR , Ahlgrimm N, Wolff S, Muhle H, Granert O, 30 . Ferlazzo E , Zifkin BG , Andermann E , Andermann F . Cortical et al . fMRI activation during spike and wave discharges evoked by photic stimulation . Neu roImage 2009 ; 48 : 682 \200\223 95 . triggers in generalized re \202 ex seizures and epilepsies . Brain 2005 ; 128 ( 4 ): 700 \200\223 10 . 54 . Avanzini G, Manganotti P, Meletti S, Mosh SL, Panzica F, Wolf P, 31 . Alajouanine T , Gastaut H . La syncin sie-sursaut et l \200\231 pilepsie sursaut Capovilla G. The system epilepsies: A pathophysiological hypothesis. Epilepsia 2012; 53: 77 1 \200\2238. d clenchement sensoriel ou sensitif inopin . Les faits anatomo- cliniques (15 observation s) . Rev Neurol 1955 ; 93 : 29 \200\223 41 . 55 . Striano P , Striano S . Reading epilepsy and its variants: a model for 32 . Glass HC , Prieur B , Molnar C , Hamiwka L , Wirrell E . Micturition and system epilepsy . Epilepsy Behav 2011 ; 20 ( 3 ): 591 .