Background. Approximately one third of the parents of children with pervasive developmental disorders or autistic spectrum disorders reports an early regression of unknown cause in their children's language, sociability, and play. Seizures or an epileptiform electroencephalogram (EEG) are associated with language regression in acquired epileptic aphasia (Landau–Kleffner syndrome) and some other pediatric epileptic syndromes. The importance of epilepsy or epileptic EEGs as contributors to autistic regression is not known.
Method. Subjects were 482 boys and 103 girls on the autistic spectrum seen consecutively in consultation by one child neurologist. Data on autistic regression, seizures, sleep EEGs, and cognitive function were entered prospectively into a data base.
Results. Of the 585 children, 176 (30%) had a history of regression, and 66 children (11%) had a history of epilepsy, defined as two or more unprovoked seizures. Among 392 children with available sleep EEGs, the EEG was epileptiform in 59% of the 66 epileptic children and 8% of the 335 nonepileptic children. Regression had occurred equally among children without seizures and in those with epilepsy. Regression was associated with an epileptiform EEG in 14% of 155 nonepileptic children who had undergone a regression, as opposed to 6% of 364 children with neither regression nor epilepsy. Mean age at regression was 21 months. There was no difference in the proportion of children with epilepsy or epileptiform EEGs who had regressed before or after 2 years of age. Approximately half of the epileptiform discharges were centrotemporal, whether or not the child was epileptic or had regressed. Children with lower cognitive function were more likely to have undergone regression than those with better cognitive skills (34% vs 20%).
Conclusion. Epilepsy or epileptiform EEGs occur in a significant minority of autistic children with a history of regression and in a smaller minority without regression. Prompt recognition of regression and recording of prolonged sleep EEGs is recommended, even though information on the potential efficacy of antiepileptic treatment to improve language and behavior in autistic children with epilepsy or an epileptiform EEG is still lacking.
Pervasive developmental disorders (PDD) or autistic spectrum disorders (ASD) encompass a heterogeneous group of individuals with early childhood onset of deficits in social interaction and language proficiency, a restricted repertoire of interests and activities, and a wide range of cognitive competence. The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–IV) divides the PDD spectrum into five behaviorally defined subgroups: autistic disorder, Asperger syndrome, Rett syndrome, disintegrative disorder, and pervasive disorder not otherwise specified.1Delineating biologically valid subgroups within the autistic spectrum awaits better understanding of the neurobiologic basis of PDD, its etiologies, and pathophysiology.
Deficits, including impaired language, are present from the start in the majority of young children on the autistic spectrum. A significant minority (∼20% to 40%) of parents report an early regression in their children's language, associated with a deterioration in nonverbal communication and play skills, a worsening of behavior, and, in a proportion of children, a cognitive decline.2,3 Some of these children are stated to have been entirely normal before the regression, others to have had some preexisting autistic traits that clearly worsened.4 Regression typically takes place between 1 and 3 years of age. It may be passed off at first, especially if insidious, in children who spoke only a few words and continued to acquire gross motor milestones.
Disintegrative disorder refers to a subgroup of children on the PDD spectrum who were developing entirely normally, including speaking in sentences, in whom regression occurred after 2 years of age and, occasionally, as late as midchildhood.1 It remains to be seen whether autistic regression and disintegrative disorder are biologically distinct clinical entities or variants of the same disorder.1,5,6 In neither case is the etiology and pathophysiology of the regression understood.
Approximately one third of children on the autistic spectrum develop epilepsy.7-9 In addition, a significant minority of nonepileptic autistic children are found to have epileptiform discharges, especially during sleep, and many of these are centrotemporal.9,10 It is tempting to assume, as it has been in acquired epileptic aphasia (Landau–Kleffner syndrome, or LKS), that the clinical epilepsy or subclinical epilepsy indexed by the epileptiform electroencephalogram (EEG) is responsible for the autistic regression by disrupting the function of relevant neocortical systems.11,12 Indeed, there are individual case reports of improvement, although rarely complete recovery, with antiepileptic treatments in autistic children who had regressed.13-16
The relationship of epilepsy and epileptiform EEG abnormalities to language and behavioral regression in autism and, for that matter, in other pediatric syndromes such as LKS is far from straightforward, and it is not known how tightly epilepsy (clinical or subclinical) and autistic regression are coupled. Therefore, we undertook this study of a large unselected group of children with PDD to provide additional information on the relationship of epilepsy to autistic regression.
MATERIALS AND METHODS
Among 869 consecutive children with developmental disabilities evaluated clinically by R.F.T. between July 1990 and August 1995, 589 children were identified as having PDD. Children were referred for neurological assessment or neurobehavioral evaluation from pediatricians, pediatric neurologists, allied health professionals, and parents. Children with Rett syndrome, deafness, progressive neurologic illness, spastic quadriparesis, and diagnosed brain malformations were excluded from the study sample, as were 5 otherwise eligible children because of inadequate data on regression. We did not exclude 10 children (2%) with cytogenetic abnormalities: 5 with fragile X, 2 with 47XYY, 1 with 46XY-14+T (14q21q), 1 with 46XX del15(q11q13), and 1 with 18p+. We also did not exclude 105 children (18%) who had relatively minor motor deficits, among whom 87 (83%) were hypotonic, 10 had spastic diplegia, 3 were hemiparetic, 1 mildly ataxic, and 4 had bradykinesia or rigidity. All of these deficits were mild, and none were the major problem interfering with the individuals progress.
Children were diagnosed as being on the autistic spectrum on the basis of their history and by clinical observation of qualitative impairments in social interactions, verbal and nonverbal communication, and a restricted, repetitive and stereotyped pattern of interests and behaviors. Thus, they encompassed autistic disorder, pervasive disorder not otherwise specified, Asperger syndrome, and disintegrative disorder of DSM IV.1 Although children in this study encompassed the various subgroups delineated in the DSM–IV, they were all grouped together as ASD. All assessments and neurologic examinations took place in a clinical office setting, with particular attention to verbal output, responses to verbal commands, play skills, and reciprocal interactions. Language regression was deemed to have occurred if a child who had developed at least three or more words stopped using them for a period >3 months. All children with regression of language were using these words with communicative intent. Language regression was based exclusively on parental report. Children were considered to be high functioning if they exhibited age-appropriate or near age-appropriate cognitive skills, and not high functioning if they had few or inconsistent age-appropriate skills.
Epilepsy and EEG Data
Following the criteria of the International League Against Epilepsy, children with more than one unprovoked seizure by well-documented clinical history were considered to have epilepsy, and those with only provoked seizures such as febrile seizures or a single unprovoked seizure were considered to be nonepileptic.17EEGs were performed at various locations and read by different electroencephalographers. EEG studies were classified as epileptiform if spikes, sharp waves, or spike/slow wave complexes were recorded during a minimum of 1 h recording in sleep. Nonepileptiform EEGs included those with abnormalities such as slowing of the background or other nonepileptic patterns. Data on regression were obtained on all 585 children, including the 392 children (67%) in whom EEG data were available. All parents provided information about the occurrence of seizures.
Data Acquisition and Analysis
Data regarding regression, age at the time of regression, EEG findings, history of seizures, and an estimate of cognitive competence were entered prospectively into a database at the time of the initial visit. We studied the patients' data retrospectively, but they were seen and the data entered prospectively. All data in this study reflect findings at the time of this first visit and data available at the first visit or generated by the first visit.
Data were analyzed using standard statistical methods provided by the Statview 4.2 statistical package.18 Percents of EEGs in subgroups presented in the tables were calculated on the basis of the entire cohort so as not to inflate the proportion with abnormal EEGs, under the assumption that children in whom no EEGs had been obtained were more likely than not to have normal EEGs. Differences in relative proportions within subgroups were based on univariate analyses. AllP values were computed using two-tailed distributions, and probabilities of <.05 were considered significant.
These 585 children on the PDD spectrum included 482 boys and 103 girls (4.7:1), a ratio similar to that in other studies.19-21 Their ages at the time of the first visit ranged from 19 months to 28 years (mean age: 70 months) (Fig1). Of the parents, 176 (30%) reported that their children underwent a regression in their language, sociability, and behavior, a proportion similar to that in other studies.4,22 Age at regression ranged from 12 months to 42 months (mean: 21 months) (Fig 2). A similar proportion of the boys (29%) and girls (33%) had regressed.
Regression and Epilepsy or Epileptiform EEGs
There was no difference in the frequency of reported regression among the 66 children with epilepsy and the 519 who did not experience epilepsy (Table 1). As expected, there was a strong correlation between a history of seizures and an epileptiform sleep EEG, whether one included all children in the calculation or only those with available EEG data. In the entire cohort, the proportion of epileptiform EEGs in the 66 children with epilepsy was 59%, compared with 8% of the 519 children without epilepsy (P= .0001). Among the 392 children with available EEGs, 68% of 57 children with epilepsy had an epileptiform EEG, compared with 15% of 335 children without epilepsy (P < .0001).
The proportion of children who had an epileptiform EEG was unrelated to whether they had experienced a regression (18% vs 12% in the entire cohort and 25% vs. 19% among the 392 children with EEG data) (Table2). To assess the relationship between regression and an epileptiform EEG, we then removed from the analysis the 66 epileptic children, because their rate of epileptiform EEGs was so much higher than that in children without epilepsy. Among 335 children without epilepsy with available EEG data, the proportion of children with an epileptiform sleep EEG was almost twice as high: 21 of 113 (19%) with regression compared with 22 of 222 (10%) without regression (P = .02).
Regression and Localization of Epileptiform EEG Abnormalities
Because centrotemporal epileptiform activity is assumed to contribute to or even be responsible for language regression in LKS, we examined whether there was a difference in the localization of epileptiform activity in the autistic children with and without language regression. We divided the 82 children with epileptiform activity into four groups (Table 3). Among 32 children with regression, 59% of EEGs had centrotemporal spikes, compared with 43% of those without seizures. The proportion of children with and without epilepsy among those who had centrotemporal epileptiform activity was also examined. Among 39 children with epilepsy, 38% had centrotemporal spikes, compared with 58% of those without epilepsy. There was no difference among the groups in the localization of paroxysmal EEG discharges depending on whether the children had experienced regression or had epilepsy. The highest percent of perisylvian epileptiform abnormalities occurred in group 2, the children who regressed but did not have epilepsy.
Age at Regression
On average, children were seen 4 years after they had regressed. As can be seen in Figures 1 and 2, only 3% of children were seen before 2 years of age and 20% by 3 years of age, whereas regression was reported to have occurred in 64% of children before 2 years of age and in 95% by 3 years of age. Parents who brought in their children closer to the time of the regression were more likely to report a regression than those who brought in their children later, inasmuch as 46 (40%) of 115 children who were <3 years of age at the time of the visit were said to have regressed, compared with 130 (28%) of 470 children seen at an older age (P = .001).
We examined whether regression before or after 2 years of age influenced the prevalence of seizures or epileptiform EEGs, keeping in mind the serious limitation of evaluating this question retrospectively rather than at the time of the regression and given the lack of accurate ages at which the EEGs had been recorded. In the cohort of 170 children in whom age at regression was specified, there was no significant difference between groups in the proportion of those with epilepsy (9% if regression occurred before 2 years of age vs 11% if regression occurred at or after age 2 years of age) or with epileptiform EEGs (16% in those with regression before 2 years of age vs 21% after 2 years of age). There was also no difference in the proportion of epileptiform EEGs among the 153 children without epilepsy who regressed before or after 2 years of age (11% vs. 18%).
There were only 9 children (5%) in the cohort of 170 children in whom age of regression was specified whose parents reported that regression had occurred after 3 years of age and who could be considered classic examples of disintegrative disorder. Seven of these children were considered low-functioning and 2 were high-functioning. Only 1 of these 9 children had epilepsy, and his EEG was nonepileptiform. Among the other 8 nonepileptic children with late regression, 1 had an epileptiform EEG, 5 had normal EEGs, and 2 had no EEG data. There were 53 children (31%) who regressed between 2 and 3 years of age who may also have met criteria for disintegrative disorder, because their parents stated that their development had been of no concern before the regression.
Regression and Cognition
There was a significant association between regression and more severe cognitive dysfunction in that regression was reported in 20% of 158 children considered to have adequate cognitive function, as compared with 34% of 427 of the lower-functioning group (P = .002; Table 4). Epilepsy or epileptiform EEGs were more prevalent in the lower-functioning children (22% vs 9%, p = .003), but there was no difference between the two cognitive groups in the number of children who had no regression, epilepsy, or a paroxysmal EEG (33% vs 38%).
The two major findings in this study are the lack of a close link between a history of language regression and epilepsy and the equal proportion of children with epilepsy or an epileptiform EEG among those with a history of regression and those without. It is also important to note that there were almost twice as many children in the sample with epileptiform EEGs (21%) as there were with clinical epilepsy (11%), which indexes a significant proportion with subclinical epilepsy. Perhaps because of the high association of epileptiform EEGs with clinical seizures, it was only in children without epilepsy that regression seemed to be a risk factor for an epileptiform EEG (19% in those with regression vs 10% in those without). These data must be interpreted with caution, however, in that the EEGs were not all performed at the same center, varied in number, were not independently reviewed, and may have differed in quality even though only reports with documentation of sleep were accepted. Whether autistic children with clinical seizures and those who have an epileptiform EEG without clinical epilepsy represent two overlapping but distinct groups remains to be seen. The figures in this study underline the importance of obtaining sleep EEGs in autistic children, especially those with regression, even if there are no clinical seizures.
The reported overall prevalence of epilepsy among autistic children ranges from 11% to 42%.7,9,23 One of the reasons for the rather low figure (11%) in this study may be that the children were still young (50% <5 years of age) and that the cumulative probability of seizures in autism increases throughout childhood to reach approximately 30% in adults.24-26 Another reason may be that the cohort included the entire autistic spectrum (with the exception of Rett syndrome) and that 27% of children in the sample were considered not to be low functioning. Higher-functioning children, who are probably overlooked in many studies of autism, are at much lower risk for epilepsy than are more classically autistic children. In a study that controlled for risk factors for epilepsy such as severity of cognitive function and motor deficits, the rate of epilepsy was only 7% among children without either of these deficits, a figure close to the 9% among the children with better cognitive skills in this study.9
LKS and electrical status epilepticus in slow wave sleep (ESES) are two other epileptic syndromes of childhood in which epileptiform EEGs may or may not be associated with clinical seizures and in which regression of language and behavior occurs.27 No child in this sample met strict criteria for ESES or LKS. By strict definition, LKS is associated with language regression but not with major behavioral or cognitive regression, whereas in ESES, behavioral correlates may range from a severe global regression compatible with a diagnosis of disintegrative disorder or autistic disorder to minimal or absent behavioral correlates.28 There are reports of behavioral problems in children with LKS, but most are not of the magnitude of those in autism, are assumed to represent the child's emotional reaction to the frustration of being unable to communicate adequately, and tend not to be the focus of published reports. Whether one should broaden LKS to encompass all the children who fit the criterion of language regression with epilepsy or an epileptiform EEG, including those with autism such as those in groups 1 and 2 in this study (see Table 3) or whether to keep the strict definition of LKS as involving only language loss is controversial.29 Whether epilepsy (clinical or subclinical) provides a fully adequate pathophysiologic explanation for the language loss of LKS and ESES or whether both the epilepsy and the language loss reflect a common underlying process is still de-bated.30
The type of language disorder, the location of the epileptiform activity, and the developmental period in which the regression occurs may be important in attempting to understand the relationship of autistic regression to epilepsy or epileptiform EEG activity. Unfortunately, we do not have adequate data with regard to the type of language abnormality in the children in this study. The type of language disorder may be an important variable to consider in future studies in that a majority of children with LKS have severe receptive (and, therefore, expressive) deficits amounting to verbal auditory agnosia (VAA).11,31 This particular language disorder is associated with the highest rate of epilepsy, both among children with PDD and those with developmental language disorders.9 VAA is a receptive aphasia or dysphasia for acoustically, but not visually, presented language.32 VAA arises from inadequate auditory or phonologic processing that engages activity in the primary or secondary auditory cortices.11,32,33 These cortical areas underlie the centrotemporal epileptiform EEG activity characteristic of LKS and of almost half of the children in this sample.16,34,35 Thus far, no pathologic changes have been found in these neocortical areas in either LKS or autism.36
The recording of paroxysmal EEG activity from temporal leads has been invoked as evidence for interference with auditory or phonologic processing by epileptic activity.32,35,37 Epileptiform activity from the centrotemporal leads is assumed to contribute to or be responsible for language regression in LKS. The epileptic activity in LKS resembles the EEG findings in benign Rolandic epilepsy in its morphology and distribution.12 Although both are activated by sleep and both may cause seizures that are easily controlled with anticonvulsants and that tend to abate in older children and adolescents, their behavioral correlates differ radically. Rolandic seizures have little or no consequence for language, cognition, or behavior, whereas the language deficit in LKS may persist for years, even after the EEG has improved and the seizures have remitted. In addition, it is much more resistant to anticonvulsant therapy than are the seizures.12,38 In ESES, the epileptiform abnormalities are much more diffuse and correspond to more global dysfunction affecting both language and behavior, and it has been proposed that the continuous spike and wave activity during sleep accounts for the loss of previous knowledge and the impairment of acquisition of new knowledge.39 In this study, localization of the epileptiform activity did not differentiate between those children with PDD and regression and those without regression. It may be that autistic regression associated with epilepsy or an epileptiform EEG represents a similar but more widespread process than in LKS and, as such, is more similar to ESES, inasmuch as ESES is likely to affect other aspects of cognition and behavior besides language. In autism, this study suggests that epilepsy or sub-clinical epileptiform EEG activity is responsible for regression and persistent deficits in behavior, language, and socio-communicative skills in a significant minority of children. The size of this minority remains to be determined.
Autistic regression tends to occur in younger children than does LKS. Indeed, 90% of the children in this autistic cohort underwent regression before 3 years of age, whereas Bishop40 and Dugas and colleagues41 reported that only 12.5% and 14% of children with LKS they culled from the literature had regressed before that age. Bishop found that prognosis for recovery is worse in children with LKS who regress earlier. Because complete recovery is so rare in autistic regression and is not guaranteed in LKS, autistic regression in the context of an epileptiform EEG in some ways parallels infantile spasms and Lennox–Gastaut syndrome.42 These malignant epileptic syndromes of infants and toddlers are even more likely to be associated with permanent cognitive deficits and, in a significant proportion of cases, autism, than of older children.43
This study indicates that younger age at autistic regression does not always presage a worse prognosis inasmuch as an equal proportion of children who had regressed before 2 years of age and between 2 and 3 years of age were among those with poorer cognition. Disintegrative disorder, in which by definition regression occurs later than in autism, is stated to be associated with a particularly severe cognitive and behavioral regression.5,6,44 We were uncertain that the 62 children who regressed after 2 years of age had been completely normal before the regression and, therefore, we do not know how many of them fulfilled criteria for disintegrative disorder. In the 9 children who regressed after 3 years of age and who could be considered likely examples of disintegrative disorder, 7 were among those with poorer cognition. Whether disintegrative disorder and autistic regression are discrete disorders is not settled.
Cognition is not a defining feature of PDD, even though mental deficiency is linked to the severity of the autistic features and underlying brain dysfunction. The observation in this study that autistic regression carried with it a heightened probability of cognitive incompetence, compared with autism without regression, may signal a somewhat greater degree of underlying brain dysfunction among children who regress. These findings are consonant with those of Kurita (1985), Rogers and DiLalla (1990), and Burack and Volkmar (1992), all of whom reported greater cognitive impairment in autistic children with regression than in those without regression.2-4 Better understanding of the brain mechanisms responsible for the regression may shed light on the basis for the cognitive compromise that so frequently accompanies it.
The prevalence of regression in this sample (30%) is commensurate with that in other studies.3,4,22 We found, however, that parents of children seen for the first time before 3 years of age reported regression significantly more often than parents of children seen in later childhood (40% vs 28%). Perhaps the parents of older children had forgotten or overlooked an insidious early regression by the time the history was obtained several years later.
The fact that only 2% of the children presented for evaluation when <2 years of age, whereas regression was reported to have occurred in children <2 years of age in 64% of the sample, indicates that language regression, if detected early, may be dismissed as a trivial developmental fluctuation rather than an observation with potentially ominous consequences that requires prompt investigation. Parents and physicians may interpret pathologically oppositional behavior as the “terrible twos” and lack of sociability as “independence” rather than as symptoms of concern. The regrettable failure to seek neurologic consultation while regression is in progress precludes a reliable estimate of the contributory role of epilepsy or epileptiform EEGs without seizures to its occurrence.
This study highlights how much remains to be learned about the role of clinical and subclinical epilepsy in autistic regression, as well as in the LKS and other pediatric epileptic syndromes with deleterious developmental consequences. All children with language loss require prompt referral for prolonged EEG recordings during sleep, ideally with overnight monitoring, because the epileptiform discharges are enhanced in slow wave sleep and may not occur during a brief nap.45This necessary first step toward evaluating the potential benefit of antiepileptic therapy will require a controlled prospective study at the time of the regression or as soon as possible thereafter. Such a study is needed if we are ever to understand the relationship of epilepsy with or without clinical seizures to language loss and to the worsening or appearance of the so far irreversible autistic traits and cognitive deficits that regression all too often leaves in its wake.
This work was supported in part by grant NS 20489 from the National Institute of Neurological Diseases and Stroke, the US Public Health Service, and a grant from the Jack and Mimi Leviton Amsterdam Foundation to Dr Rapin. We express our gratitude to Dr Shlomo Shinnar, who reviewed the data and the manuscript and made valuable suggestions.
- Received July 25, 1996.
- Accepted September 6, 1996.
Reprint requests to (R.F.T.) Department of Neurology, Miami Children's Hospital, Solomon Klein Pavilion, 3200 SW 60 Court, Suite 302, Miami, FL 33155.
- PDD =
- pervasive developmental disorders •
- ASD =
- autistic spectrum disorders •
- DSM–IV =
- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition •
- LKS =
- Landau–Kleffner syndrome •
- EEG =
- electroencephalogram •
- ESES =
- electrical status epilepticus in slow wave sleep •
- VAA =
- verbal auditory agnosia
- ↵American Psychiatric Association. Pervasive Developmental Disorders. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:65–78
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- Tuchman R,
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- ↵Beaumanoir A. The Landau-Kleffner syndrome. In: Roger J, Dravet C, Bureau M, Dreifuss FE, Wolf P, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence. London, England: John Libbey; 1985:181–191
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- ↵Haycock K, Roth J, Gagnon J, Finzer W, Soper C. Statview. 4.02. ed. Berkeley, CA: Abacus Concepts; 1992
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- ↵Beaumanoir A, Bureau M, Deonna T, Mira L, Tassinari C. Continuous spikes and waves during slow sleep, electrical status epilepticus during slow sleep, acquired epileptic aphasia and related conditions. In: Majno M, ed. Mariani Foundation Paediatric Neurology Series. London, England: John Libbey; 1995:260
- ↵Hirsch E, Maquet P, Metz-Lutz M, Motte J, Finck S, Marescaux C. The eponym “Landau-Kleffner syndrome” should not be restricted to childhood-acquired aphasia with epilepsy. In: Beaumanoir A, Bureau M, Deonna T, Mira L, Tassinari CA, eds. Continuous Spikes and Waves During Slow Sleep, Electrical Status Epilepticus During Slow Sleep, Acquired Epileptic Aphasia and Related Conditions. London, England: John Libbey; 1995:57–62
- ↵Aicardi J. Syndrome of acquired aphasia with seizure disorder: epileptic aphasia, Landau-Kleffner syndrome, verbal auditory agnosia with convulsive disorder. In: French J, Prichard JS, Rapin I, eds. Epilepsy in Children. New York, NY: Raven Press; 1986:176–182
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- ↵Bauman M, Kemper T. Neuroanatomic observations of the brain in autism. In: Bauman M, Kemper T, eds. The Neurobiology of Autism. Baltimore, MD: John Hopkins University Press; 1994:119–145
- ↵Niedermeyer E. Epileptic seizure disorders. In: Niedermeyer E, Lopes da Silva F, eds. Electroencephalography: Basic Principles, Clinical Applications and Related Fields. 2nd ed. Baltimore, MD: Urban & Schwarzenberg; 1987:405–510
- ↵Van Dongen H, De Wijngaert E, Wennekes M. The Landau-Kleffner syndrome: diagnostic considerations. In: Pavao Martins I, Castro-CaldasA, van Dongen HR, van Hout A, eds. Acquired Aphasia in Children. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1991:253–261
- ↵Tassinari A, Daniele O, Bernardina B. The problem of “continuous spikes and waves during slow wave sleep” or “electrical status epilepticus during slow wave sleep.” In: Beaumanoir A, Bureau M, Deonna T, Mira L, Tassinari CA, eds. Continuous Spikes and Waves During Slow Sleep, Electrical Status Epilepticus During Slow Sleep, Acquired Epileptic Aphasia and Related Conditions. London, England: John Libbey; 1995:251–255
- ↵Dugas M, Gerard C, Franc S, Sagar D. Natural history, course and prognosis of the Landau and Kleffner syndrome. In: Pavao Martins I, Castro-Caldas A, van Dongen HR, van Hout A, eds. Acquired Aphasia in Children. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1991:263–277
- Tuchman RF
- ↵Yaylali I, Tuchman R, Jayakar P. Comparison of the utility of routine versus prolonged EEG recordings in children with language regression. Presented at the American Clinical Neurophysiology Society Annual Meeting, 1996. Abstract
- Copyright © 1997 American Academy of Pediatrics