102 Archives ofDisease in Childhood 1996;75:102-107

ORIGINAL ARTICLES Arch Dis Child: first published as 10.1136/adc.75.2.102 on 1 August 1996. Downloaded from

Focal abnormalities detected by '8FDG PET in epileptic

Colin D Ferrie, Michael Maisey, Timothy Cox, Charles Polkey, Sally F Barrington, Chrystosomos P Panayiotopoulos, Richard 0 Robinson

Abstract cal treatment not only for control of A prospective study of 32 children with but possibly also to improve neurodevelop- epileptic encephalopathies 12 years or mental outcome.4 Seizures in the epileptic younger revealed a high incidence of focal encephalopathies are usually considered to be cortical metabolic defects on 18- primary generalised, arising from a cortex with fluorodeoxyglucose positron emission to- diffuse or multifocal abnormalities. Despite mography (PET) not suspected from this, cases are described in patients with readily clinical, EEG, or magnetic resonance detectable localised brain lesions including imaging findings. PET scans were normal tumours, porencephalic cysts, and severe mi- in all five children with typical de novo grational anomalies such as pachygyrias.' Lennox-Gastaut syndrome but showed Seizures are associated with pronounced cortical metabolic abnormalities in three changes in the metabolism of substrates such out of four with atypical de novo Lennox- as glucose. In partial focal reduction Gastaut syndrome, five out of six with (hypometabolism) and increase in glucose Lennox-Gastaut syndrome following in- consumption (hypermetabolism) in the epilep- fantile spasms, six out ofeight with severe togenic zone is characteristic of the interictal myoclonic in infancy, one out of and ictal states respectively.6 This can be two with epilepsy with myoclonic-astatic detected by positron emission tomography seizures, and four out of six with an (PET) using 18-fluorodeoxyglucose (FDG), a unclassified epileptic . radionucleotide labelled analogue of glucose. http://adc.bmj.com/ This suggests that some children with epi- Recently FDG PET studies have contributed leptic encephalopathies previously to the detection of subtle localised abnormali- thought to have primary generalised sei- ties of neuronal migration in children with cer- zures or seizures due to multifocal pathol- tain epileptic encephalopathies with apparently ogy may have unifocal cortical origin for generalised seizures.7-" In patients with infan- Department of their seizures. Such an origin may be tile spasms this has lead to cortical resections Paediatric , amenable to surgery. with excellent control and improved on September 26, 2021 by guest. Protected copyright. Guy's Hospital, London (Arch Dis Child 1996;75:102-107) development."214 C D Ferrie However, these studies used broad defini- R 0 Robinson Keywords: epilepsy, positron emission tomography, tions, particularly of the Lennox-Gastaut infantile spasms, Lennox-Gastaut syndrome. and often included with Clinical PET Centre, syndrome, patients UMDS, London clinical, EEG, or structural neuroimaging M Maisey evidence strongly indicative of focal brain S F Barrington The term 'epileptic encephalopathy' encom- passes various severe childhood epilepsies pathology, making the contribution of PET Department of characterised by multiple and dif- unclear. In earlier studies computer assisted Neurological Sciences, fusely slow EEG with generalised or multifocal tomography rather than magnetic resonance Guy's and St Thomas' imaging (MRI) scans was often used, and even Hospitals, London paroxysmal abnormalities. Psychomotor delay T Cox with onset preceding or following the onset of when MRI was employed, it is not clear if the seizures is usual.' 2 The best known of these technical specifications were sufficient to allow Maudsley Hospital, conditions are West's and the Lennox-Gastaut detection of subtle abnormalities. In this study London we aimed to establish whether FDG PET C Polkey syndromes (International League Against Epi- lepsy code 2.2).? Others include epilepsy with detects focal abnormalities in children with Department of Clinical myoclonic-astatic seizures (2.2) and severe epileptic encephalopathies in whom this is not Neurophysiology and clear from clinical examination, EEG, or high Epilepsy, St Thomas' myoclonic epilepsy in infancy (3.2).' Their Hospital, London intractable nature, associated developmental resolution MRI studies, and whether there are C P Panayiotopoulos problems, and frequent need for residential syndrome related differences in the PET find- schooling makes them important conditions ings. Correspondence to: Dr C D Ferrie, Newcomen both to paediatric neurologists and to general Centre, Guy's Hospital, and London SE1 9RT. community paediatricians. Current medi- Methods cal treatment is usually disappointing and has Children of 1 to 12 years of age with an epilep- Accepted 17 May 1996 prompted renewed interest in the role of surgi- tic encephalopathy of unknown aetiology were "8FDG PET in epileptic encephalopathies 103

studied prospectively. Treatment with at least discouraged. Intravenous diazepam was given three major had failed in all to patients with frequent paroxysmal EEG

and they were considered potential candidates activity before or during the first 10 minutes of Arch Dis Child: first published as 10.1136/adc.75.2.102 on 1 August 1996. Downloaded from for surgery. Epileptic encephalopathy was FDG uptake, and also to agitated patients. defined as the occurrence of mixed generalised Patients were scanned after 30 minutes of seizures (tonic, atonic, myoclonic, atypical FDG uptake, using a head holder to minimise absence, generalised tonic-clonic) with, in the movement. Six 5 minute consecutive frames fully evolved syndrome, a diffusely slow EEG were acquired with the data summed. Frames with generalised or multifocal interictal parox- with excessive movement were discarded. Fol- ysmal abnormalities and (if recorded) general- lowing correction for attenuation, images were ised ictal abnormalities. Patients with seizures smoothed and reconstructed to give 31, 3.4 which were difficult to classify but which did mm thick planes with an in plane spatial reso- not have localising or lateralising value and lution of 8 mm and a total axial field ofview of those with ictal symptoms of uncertain localis- 10.4 cm. The images were reconstructed in ing value-such as eye deviation during gener- axial and coronal planes and in the plane alised seizures-were included provided other parallel to the long axis of the temporal lobes. typical seizures were also present. Patients with MRI and PET images were inspected 'soft' or equivocal focal neurological signs were visually blind to the clinical information and to eligible. each other. Semiquantitative analysis of PET Patients with seizures with localising value data was performed using a template of multi- were excluded except if they occurred before ple 4 mm diameter circular regions of interest the onset of infantile spasms or in those classi- (ROI) placed in selected areas chosen by fied as severe myoclonic epilepsy in infancy in matching PET planes to an anatomical brain whom focal ictal symptoms are characteristic.3 atlas. ROI were placed on anatomical grounds Patients whose EEG showed consistent asym- rather than on functional imaging findings; metries or focal abnormalities were excluded, thus areas of apparent increased or decreased as were those with clear focal neurological FDG uptake were not preferentially selected. deficits and those in whom previous neuroim- Frontal, parietal, occipital, medial, and lateral aging showed focal abnormalities or other temporal and cerebellar cortices as well as len- abnormalities likely to preclude surgery. Spe- tiform and caudate nuclei, thalami, mid-brain, cific metabolic conditions were excluded by and pons were sampled. Control PET data for measurement of plasma biotinidase, lactate, normal children is lacking for ethical reasons. pyruvate, ammonia and amino acids, urine FDG PET studies in adults with partial organic acids, (CSF) lac- seizures suggest an asymmetry of 15% or more tate, pyruvate, and glycine, the CSF:blood glu- in homologous cortical regions is abnormal.23 cose ratio (for glucose carrier protein defi- Studies in children show important regional ciency),"6 and by a trial of oral pyridoxine. changes during development but did not

A detailed clinical review, examination find- suggest greater side to side asymmetries.24 We http://adc.bmj.com/ ings, and EEG including sleep and video used an asymmetry of greater than 15% to recordings was used to classify patients syndro- define unequivocal abnormality. Detection of mically according to recommendations of the bilateral and diffuse abnormalities on semi- International League Against Epilepsy supple- quantitative analysis is difficult. We report it mented by those of leading authorities.3 17-22 only when obvious on visual inspection. Close Additionally, patients were divided according observation of the patient and the EEG to whether they were typical or atypical of the recorded during radiotracer uptake was used to particular syndrome. Features leading to a des- classify scans as ictal (paroxysmal EEG activity on September 26, 2021 by guest. Protected copyright. ignation as atypical included onset of seizures generally acknowledged as ictal with or without outside the age limits considered normal for clinical events) or as interictal (no ictal-type the syndrome, clinical signs (for example, paroxysmal EEG activity and no clinical equivocal plantar responses, non-sustained events) 25 A degree of uncertainty must exist ankle clonus, or brief postictal Todd's paresis), with such classification, given the inherent dif- or ictal symptoms (for example, eye deviations, ficulty of clearly designating some patterns- limb posturing) of 'soft' localising value, or the such as bursts ofspike and wave-as being ictal presence of unclassified seizures without local- or interictal.25 When such abnormalities were ising features. Classification was blind to both unaccompanied by clinical events they were MRI and PET findings. considered as probably interictal. All patients underwent MRI (Phillips Gyro- scan ACS 1.5T) with 6 mm thick axial proton density and T2 weighted spin echo images of the whole head and 3 mm thick fast spin echo Results images and 4 mm thick Ti weighted coronal Thirty five patients were recruited to the study images orthogonal to the temporal lobes. In but two were excluded before PET because of patients without focal MRI findings or abnor- multiple cortical abnormalities on MRI. An malities which would preclude surgery, FDG additional patient did not proceed to MRI as PET (Siemens ECAT 951R PET scanner) seizures came under control. The median age with EEG monitoring during radiotracer up- of onset of seizures in the remaining 32 take was performed. Patients were fasted for patients was 11.5 months (range 3 weeks to 7 four hours before injection of 3.6 MBq/kg years); 18 were boys. The median age at PET FDG. During radiotracer uptake lights were study was 9 years (range 2 to 12). Unilateral dimmed and interactions with the child areas of abnormal cortical metabolism were 104 Ferrie, Maisey, Cox, Polkey, Barrington, Panayjotopoulos, Robinson

seen in 12 patients and bilateral or diffuse ties, compared with three of four with atypical hypometabolism in five. Scans were considered de novo Lennox-Gastaut syndrome (p < 0.05,

normal in 15 patients. Table 1 gives the Fisher's exact test). PET abnormalities were Arch Dis Child: first published as 10.1136/adc.75.2.102 on 1 August 1996. Downloaded from syndromic diagnosis of the patients along with seen in all the other syndromes investigated, the frequency of PET abnormalities in each. with no significant differences between those Unilateral focal PET abnormalities involved classified as typical and atypical. No syndrome the temporal lobes only (five cases) (see fig 1), related differences in the sites of focal meta- or included the frontal and/or parietal and/or bolic abnormalities was seen but on visual occipital lobes (six cases). After integration of inspection they generally appeared to be more uptake EEG and PET findings, one of these extensive in those with Lennox-Gastaut syn- scans was designated as ictal showing focal drome secondary to infantile spasms than in hypermetabolism. The others were designated the other syndromes. as interictal or predominantly interictal and showed hypometabolic focal abnormalities. Bitemporal hypometabolism occurred in two Discussion patients (asymmetrical in one). In three This study significantly extends that of previ- patients diffuse, bilateral hypometabolism was ous reports of FDG PET in patients with epi- seen, in each case being maximal on the right. leptic encephalopathies. It reports relatively By definition no patients had definite focal frequent focal cortical abnormalities in pa- abnormalities on MRI. However, five patients tients in whom clinical features, EEG, and high with focal metabolic defects had minor asym- quality MRI found either no suggestion of metries, but no signal abnormalities, in the focal pathology or only equivocal findings. temporal lobes. These were congruent with Re-examining MRI scans in the knowledge of PET findings in only three patients. Eleven PET findings did not improve detection. It also patients had seizures with 'soft'- or in those used a strict syndromic approach using the with severe myoclonic epilepsy in infancy, International League Against Epilepsy classifi- definite-focal features or had equivocal focal cation and found significant syndrome based neurological findings. Congruent unifocal or variations in the occurrence of cortical meta- bilateral but asymmetrical PET abnormalities bolic defects. were seen in six of these 11 patients. None had It is possible that newer techniques employ- abnormalities on the opposite side (p < 0.05). ing Ti volume acquisition and 3D rendering Eight patients had unclassified seizures. Seven would have detected more abnormalities.26 ofthese had abnormal PET scans with unifocal However, pathological studies suggest that or bilateral metabolic defects (p < 0.05). Four abnormalities involving neuronal misalign- out of eight patients with severe myoclonic epi- ments-'cerebral microdysgenesis'-rather than lepsy in infancy had lateralised seizures. One neuronal loss and gliosis are associated with had contralateral temporal lobe hypometabo- the epileptic encephalopathies.'7-31 This is

lism. Two others had asymmetrical temporal probably not detectable by any current struc- http://adc.bmj.com/ lobe FDG uptake, lower on the contralateral tural imaging technique. side. In both cases the side to side difference The patients we studied lacked clinical, was 13%, just lower than that required for sig- EEG, or neuroimaging evidence of focal nificance. The fourth patient had predomi- cerebral pathology. However, 'soft' ictal symp- nantly but not exclusively left sided clonic sei- toms or clinical signs were permitted and in zures. PET showed bilateral temporal lobe those with severe myoclonic epilepsy in infancy hypometabolism with suggestive asymmetry. clear ictal focal features were allowed, as these Sixteen patients had either equivocal focal had not previously been shown to have localis- on September 26, 2021 by guest. Protected copyright. neurological findings, focal ictal features, or ing value. These were not always associated unclassified seizures. Eleven of these had with definite cortical abnormalities but when normal scans (p > 0.05). they were there was significant congruence Clear syndrome related differences in PET between the site of the metabolic defect and findings were seen (table 1). No patient (out of contralateral clinical manifestations. Seizures five) with typical de novo Lennox-Gastaut syn- which were without localising or lateralising drome had focal cortical metabolic abnormali- features but which were difficult to classify

w . _ . Figure 1 Coronal MRI (T2 weighted) and FDG PETscansfrom a Oyear old boy with typical severe myoclonic epilepsy in infancy. Seizure types included clonic seizures which were predominantly left sided. Uptake in the right (R) medial temporal lobe was 33% less than in the left. 18FDG PET in epileptic encephalopathies 105

Table I Summary of the major PET abnormalities seen, according to epilepsy syndromes

Age at seizure onset Age at PET scan Classification No ofpatients [median (range)] [median, (range)] Sex (M:F) Major PETfindings Arch Dis Child: first published as 10.1136/adc.75.2.102 on 1 August 1996. Downloaded from Lennox-Gastaut syndrome following 3 6 m (3-6) 10 y (5-10) 1:2 *Normal - 1, Unilateral focal typical infantile spasms hypometabolism - 2 (TPO, TP) Lennox-Gastaut syndrome following 4 21/2 m (3 w - 8 10 y (7-12) 0:4 Normal - 1, Unilateral focal atypical infantile spasms m) hypometabolism - 2 (TF, T), Extensive unilateral hypermetabolism - I Typical de novo Lennox-Gastaut 5 3 y (2-5) 9 y (8-11) 4:1 Normal - 5 syndrome Atypical de novo Lennox-Gastaut 4 3 y (1-3) 7 y (5-10) 4:0 Normal - 1, Unilateral syndrome hypometabolism - 2 (TP, T), Bilateral, asymmetrical posterior hypometabolism - 1 Typical severe myoclonic epilepsy in 6 5 m (2-7) 10.5 y (3-12) 3:3 Normal - 3, Unilateral infancy hypometabolism - 1 (T), Bitemporal hypometabolism - 1, Marked, diffuse hypometabolism -l1 Atypical severe myoclonic epilepsy in 2 12 and 15 m 4 and 10 y 2:0 Normal - 1, Bilateral, asymmetrical infancy posterior hypometabolism - 1 Atypical myoclonic-astatic epilepsy 2 11 m and 2 y 11 and 12 y 1:1 Normal - 1, Unilateral focal hypometabolism - 1 (TP) Unclassified 6 20 m (5 m - 7 y) 5.5 y (2-12) 3:3 Normal - 2, Unilateral focal hypometabolism - 3 (T, T, TP), Bitemporal hypometabolism - 1 T = temporal lobe; P = parietal lobe; F = frontal lobe; o=occipital lobe; m = months; w = weeks; y = years. * Visual and semiquantative analysis failed to reveal asymmetries of > 15% between homologous cortical regions, and bilateral/global abnormalities were not seen on visual inspection.

were significantly associated with cortical partial seizures which rapidly generalise.' '71 metabolic defects, suggesting that some may The former condition may be caused by have been unusual complex partial seizures. non-structural abnormalities such as neuro- Totally normal neurological examination and transmitter, receptor, or membrane defects. typical seizure semiology is not predictive of a normal PET scan. INFANTILE SPASMS Patients with a previous history of cryptogenic LENNOX-GASTAUT SYNDROME infantile spasms, whether typical or atypical, The nosology of the childhood epileptic had a high incidence of cortical metabolic encephalopathies is controversial.' 2 Patients in defects in the present study. This is in agreement with previous reports.'2 131 Maeda

this study all had refractory generalised sei- http://adc.bmj.com/ zures, diffuse EEG abnormalities, and develop- et al suggested that such defects may be mental delay. According to some definitions, transient in patients responding to treatment including those used in some previous PET who subsequently developed normally.'5 In studies, most could have been classified as contrast, in patients with persisting PET Lennox-Gastaut syndrome. A stricter ap- abnormalities or those who developed such proach appears justified by this study. The abnormalities, seizures continued with ensuing likely presence of focal cortical metabolic developmental delay. When 11 of our patients defects in patients with atypical Lennox- with unifocal cortical metabolic defects were on September 26, 2021 by guest. Protected copyright. Gastaut syndrome and Lennox-Gastaut syn- rescanned at a median ofone year from the ini- drome following infantile spasms may be tial scan, 10 had similar abnormalities on the predicted by strict classification. No focal PET repeat scan (Parker A, et al. Consistency of abnormalities were found in the one previous focal abnormalities detected by '8FDG PET in study of patients with Lennox-Gastaut syn- epileptic encephalopathies. British Paediatric drome which used strict inclusion criteria Neurology Association XXII Annual Meeting, similar to this study.9 In studies in which focal 1996. Abstract, p 43.) Taken together, these abnormalities were seen,7 8 1011 application of studies suggest that there is a high incidence of the criteria used here would have lead in all focal cortical defects in refractory cryptogenic patients with such abnormalities to classifica- infantile spasms. Recent video-EEG studies tion as atypical Lennox-Gastaut syndrome or have shown that spasms are frequently asym- as syndromes other than Lennox-Gastaut syn- metrical or are preceded by focal seizures.2"33 drome. Conversely patients which we would Had video-EEG been done in our patients have designated as typical de novo Lennox- during active spasms more may have been clas- Gastaut syndrome all had normal PET scans sified as atypical. or on quantitative analysis globally reduced glucose metabolism. The latter may reflect fac- SEVERE MYOCLONIC EPILEPSY IN INFANCY tors unrelated to seizure aetiology such as anti- There are no previous reports on PET findings convulsant medication, the effect of uncon- in patients with severe myoclonic epilepsy in trolled seizures, or associated cognitive deficits. infancy. However, some patients classified as These findings appear to justify the previously Lennox-Gastaut syndrome in previous studies suggested separation of a 'genuine' or 'true' may have been examples ofthis syndrome. The Lennox-Gastaut syndrome from a clinically focal ictal symptoms which characterise it have similar (but not identical) condition with not previously been shown to have localising 106 Ferrie, Maisey, Cox, Polkey, Barrington, Panayiotopoulos, Robinson

value for cortical pathology. We showed a cor- cortical abnormalities in a significant number relation between focal ictal symptoms and con- of these patients and may help select candi-

tralateral PET abnormalities in some, suggest- dates for more invasive investigation. However, Arch Dis Child: first published as 10.1136/adc.75.2.102 on 1 August 1996. Downloaded from ing a focal onset of seizures with rapid bilateral it is premature to conclude that all such lesions synchrony. However, bilateral or diffuse defects are causative. In all our cases PET scans were were also seen. performed some years after the onset of seizures which were both extremely frequent and intractable. It is conceivable that this may EPILEPSY WITH MYOCLONIC-ASTATIC SEIZURES OR UNCLASSIFIED EPILEPTIC ENCEPHALOPATHIES lead to secondary focal cortical damage Two of our cases had frequent myoatonic reflected in PET studies. However, this is seizures and EEG features compatible with unlikely as mesial temporal sclerosis with neu- epilepsy with myoclonic-astatic seizures. How- ronal loss and gliosis rather than microdysgen- ever, many of the other features of the esis is associated with uncontrolled seizures. syndrome were lacking and an alternative des- Serial scans starting soon after the onset of ignation as myoclonic variant of Lennox- these epileptic encephalopathies along with Gastaut syndrome (that is, among the atypical pathology study of surgically resected material de novo Lennox-Gastaut syndrome cases) should resolve this issue. would have been possible. Given these reserva- This work was supported by grants from Marion Merrell Dow tions, the findings in these patients should not and Co and the Special Trustees of Guy's Hospital. be generalised to more typical examples of epi- 1 Aicardi J. Epileptic encephalopathies of early childhood. lepsy with myoclonic-astatic seizures. As in Curr Opin Neurol Neurosurg 1992;5:344-8. 2 Donat JF. The age-dependent epileptic encephalopathies. J previous studies, a significant minority of our Child Neurol 1992;7:7-21. patients did not fit into any of the currently 3 Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for recognised epilepsy syndromes. Given the high revised classification ofepilepsies and epileptic syndromes. frequency of metabolic defects in these pa- Epilepsia 1989;30:389-99. 4 Holmes GL. Surgery for intractable seizures in infancy and tients, they merit careful evaluation for possible early childhood. Neurology 1993;43(suppl 5):28-37. surgical foci. 5 Aicardi J. . New York: Raven Press, 1994. 6 Editorial. SPECT and PET in epilepsy. Lancet 1989; This study adds further evidence that appar- i:135-6. ently generalised refractory epilepsies are not 7 Gur RC, Sussman NM, Alavi A, et al. Positron emission tomography in two cases of childhood epileptic encepha- infrequently caused by focal cerebral abnor- lopathy (Lennox-Gastaut syndrome). Neurology 1982; malities. These arise by secondary bilateral 32:1191-4. 8 Chugani HT, Mazziotta JC, Engel J, Phelps ME. The synchrony from a unilateral cortical dis- Lennox-Gastaut syndrome: metabolic subtypes deter- charge."4 This can be apparent on scalp EEG mined by 2-deoxy-2fluro-D-glucose positron emission tomography. Ann Neurol 1987;21:4-13. but may require special techniques for its 9 Theodore WH, Rose D, Patronas N, et al. Cerebral glucose detection. Mesial frontal foci are often consid- metabolism in the Lennox-Gastaut syndrome. Ann Neurol 1987;21:14-21. ered to be most likely to give rise to secondary 10 Yanai K, Linuma K, Matsuzawa T, et al. Cerebral glucose bilateral synchrony. However, as in this study, it utilization in pediatric neurological disorders determined

by positron emission tomography. Eur J Nucl Med http://adc.bmj.com/ may be as likely, or more so, to arise in the 1987;13:292-6. temporal lobes."4 The metabolic abnormality 11 Miyauchi T, Nomura Y, Ohno S, Kishimoto H, Matsushita M. Positron emission tomography in three cases of in children with epileptic encephalopathies is Lennox-Gastaut syndrome. Jpn J Psychiatr Neurol 1988; usually larger than that seen in partial epilep- 42:795-804. 12 Chugani HT, Shields WD, Shewmon DA, Olson DM, sies, presumably reflecting a wider epilep- Phelps ME, Peacock WJ. Infantile spasms. I. PET togenic zone. Widely synchronous regional identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 1990;27:406-13. spike foci are more apt to produce secondary 13 Olson DM, Chugani HT, Shewmon A, Phelps ME, Peacock

bilateral synchrony than discrete foci.'5 Chil- WJ. Electrocorticographic confirmation of focal positron on September 26, 2021 by guest. Protected copyright. emission tomographic abnormalities in children with dren presenting with infantile spasms generally intractable epilepsy. Epilepsia 1990;31:731-9. appeared to have the largest focal cortical 14 Chugani HT, Shewmon DA, Shields WD, et al. Surgery for infantile spasms: neuroimaging perspectives. Epilepsia defects. If the focal hypometabolism suggests 1993;34:764-71. cerebral microdysgenesis it may be that those 15 Maeda N, Watanabe K, Negoro T, et al. Evoloutional changes of cortical hypometabolism in West's syndrome. with larger abnormalities present earlier with Lancet 1994;343: 1620-3. infantile spasms. 16 De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI. Defective glucose transport across Identification of focal areas of abnormality the blood-brain barrier as a cause ofpersistent hypoglycor- offers the prospect that some patients may be rhachia, seizures, and developmental delay. N Engl J Med 1991;325:703-9. candidates for resective surgical treatment. 17 Aicardi J, Levy Gomes A. Clinical and electroencephalo- PET cannot be used yet as the basis on which graphic symptomatology of the 'genuine' Lennox-Gastaut syndrome and its differentiation from other forms of to select for this.'6 Traditionally, scalp EEG has epilepsy ofearly childhood. In: Degan R, Dreifuss FE, eds. been the principal investigational technique in Benign localized and generalized epilepsies of early chidhood. (Epilepsy Res Suppl 6.) Amsterdam: Elsevier, 1992:185- identifying focal onset of seizures. However, its 93. value in the epileptic encephalopathies of 18 Beaumanoir A, Dravet C. The Lennox-Gastaut syndrome. In: Roger J, Bureau M, Dravet C, Dreifuss, Perret A, Wolf childhood is limited by the speed of secondary P, eds. Epileptic syndromes in infancy, childhood and bilateral synchrony and by the abundance of adolescence. London: John Libbey, 1992:115-34. 19 Dulac 0, N'Guyen T. The Lennox-Gastaut syndrome. Epi- generalised abnormalities masking focal abnor- lepsia 1993;34(suppl 7):7-17. malities. Additionally, the location of apparent 20 Dravet C, Bureau M, Guerrini R, Giraud N, RogerJ. Severe myoclonic epilepsy in infants. In: Roger J, Bureau M, focal or lateralising abnormalities frequently Dravet C, Dreifuss, Perret A, Wolf P, eds. Epileptic varies. MRI may identify structural abnormali- syndromes in infancy, childhood and adolescence. London: John Libbey, 1992:75-88. ties where EEG is non-contributory but even 21 Yakoub M, Dulac 0, Jambaque I, Chiron C, Ploin P. Early with optimal techniques will not detect subtle diagnosis of severe myoclonic epilepsy in infancy. Brain Dev 1992;14:299-303. abnormalities, such as cerebral microdysgen- 22 Doose H. Myoclonic-astatic epilepsy. In: Degan R, Dreifuss esis. PET appears sensitive in detecting focal FE, eds. Benign localised and generalised epilepsies ofearly '8FDG PET in epileptic encephalopathies 107

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