The Epilepsy Aphasias: Landau Kleffner Syndrome and Rolandic Epilepsy

Clinics in Developmental Medicine

THE EPILEPSY-APHASIA SPECTRUM

FROM LANDAU-KLEFFNER SYNDROME TO ROLANDIC EPILEPSY

Clinics in Developmental Medicine

The Epilepsy-Aphasia Spectrum

From Landau-Kleffner Syndrome to Rolandic Epilepsy

by

THIERRY DEONNA

Pediatric Neurology and Neurorehabilitation Unit, Department of Pediatric Medicine and Surgery, Lausanne University Hospital, (Centre Hospitalier Universitaire Vaudois), Switzerland

and

ELIANE ROULET-PEREZ

Pediatric Neurology and Neurorehabilitation Unit, Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois); Faculty of Biology and Medicine, University of Lausanne, Switzerland

with contributions from

XAVIER DE TIÈGE, SERGE GOLDMAN and PATRICK VAN BOGAERT,

Laboratoire de Cartographie fonctionnelle du Cerveau, The ULB Neuroscience Institute, Université libre de Bruxelles, Belgium

2016

Mac Keith Press

© 2016 Mac Keith Press

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First published in this edition in 2016

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ISBN: 978-1-909962-76-7

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CONTENTS

AUTHORS’ APPOINTMENTS

FOREWORDS

PREFACE

ACKNOWLEDGEMENTS

1.INTRODUCTION

2.HISTORY OF THE LANDAU–KLEFFNER SYNDROME

3.CLASSIFICATION ISSUES

4.SPEECH PERCEPTION AND BRAIN ORGANIZATION OF LANGUAGE: RELEVANT FEATURES FOR LANDAU–KLEFFNER SYNDROME AND THE EPILEPSY-APHASIA SPECTRUM

5.THE DIFFERENT CLINICAL FACETS OF LANDAU–KLEFFNER SYNDROME

6.DEVELOPMENTAL ASPECTS OF LANDAU–KLEFFNER SYNDROME AND THE EPILEPSY-APHASIA SPECTRUM AND THE OVERLAP WITH DEVELOPMENTAL LANGUAGE DISORDERS AND AUTISM SPECTRUM DISORDER

7.EVOLUTION OF LANDAU–KLEFFNER SYNDROME: SHORT-, MID- AND LONG-TERM OUTCOMES

8.FROM ROLANDIC EPILEPSY TO LANDAU–KLEFFNER SYNDROME

9.LABORATORY INVESTIGATIONS IN LANDAU–KLEFFNER SYNDROME AND THE EPILEPSY-APHASIA SPECTRUM

10.PHYSIOPATHOLOGY OF SPEECH, LANGUAGE AND OTHER PROLONGED EPILEPTIC DYSFUNCTION IN LANDAU–KLEFFNER SYNDROME, EPILEPSY WITH CONTINUOUS SPIKE WAVES DURING SLEEP AND RELATED SYNDROMES

11.FUNCTIONAL NEUROIMAGING INVESTIGATIONS IN IDIOPATHIC FOCAL EPILEPSIES OF CHILDHOOD WITH COGNITIVE AND BEHAVIOURAL IMPAIRMENT

Xavier De Tiège, Serge Goldman, and Patrick Van Bogaert

12.DRUG MANAGEMENT OF COGNITIVE IMPAIRMENTS IN LANDAU–KLEFFNER SYNDROME AND OTHER EPILEPSY APHASIA SPECTRUM SYNDROMES

13.SPEECH AND LANGUAGE, EDUCATIONAL AND PSYCHOLOGICAL REMEDIATION

14.PERSONAL TESTIMONIES AND UNPUBLISHED CASES

15.SUMMARY AND CONCLUSIONS

REFERENCES

INDEX

AUTHORS’ APPOINTMENTS

FOREWORD

It is rare to find a book that one can recommend with equal enthusiasm to clinicians and researchers, but The Epilepsy-Aphasia Spectrum; From Landau-kleffner syndrome to Rolandic Epilepsy is just such a volume. The overarching topic–the relationship between childhood epilepsy and cognition, especially language–is a fascinating one that holds many intellectual puzzles. Why do some children deteriorate after a period of normal development, losing skills they once had? What is the relationship between the aphasia and the epilepsy—does one cause the other, or are they separate consequences of a common underlying cause? Can we predict which children will regain their lost skills?

There are several features of acquired epileptic aphasia that make these questions particularly difficult. Heterogeneity at both clinical and aetiological levels is a major challenge, especially given the rarity of these disorders, which can make it difficult to draw generalisations from a group of cases. Deonna and Roulet-Perez point out how an over-narrow conceptualisation of Landau–Kleffner syndrome (for which, I discovered, I was in part, unwittingly, responsible!) led to the neglect of research on children whose speech and language problems went beyond the classic picture of verbal auditory agnosia. They present a wealth of clinical case histories that show just how variable the presentation can be. Variability characterises not just the initial presentation but also the course of the disorder. Children can recover after a substantial regression only to regress again months or years later. Careful longitudinal studies can be helpful in studying the vexed question of the causal relationship between epilepsy and cognition, but it is clear that there can be a far more neurophysiological abnormality than may be evident from a simple observation of seizures. Drugs that control the seizures may leave language deficits untouched, and indeed may even make the condition worse.

This book notes the fluid boundaries between classic ‘Landau–Kleffner syndrome’ and other childhood epilepsies. It is noted that rolandic epilepsy has many features in common with Landau–Kleffner syndrome, but with a focus on the centro-temporal rather than posterior-temporal cortex.

In the midst of this scholarly account of the nature and manifestations of these epileptic syndromes, we never lose sight of the family and child whose lives can be turned upside down by a sudden change in cognition and behaviour. As Deonna and Roulet-Perez put it: ‘How can a young human being cope with a prolonged loss of language while keeping otherwise preserved intellectual and emotional abilities and adapt without losing his essential self?’ Chapters on drug treatment, surgery, and educational approaches are illustrated with carefully documented case histories, and there is a particularly thoughtful account of the benefits of sign language for many children with a verbal auditory agnosia. This book ends with some vivid first-hand accounts of the impact of language loss by adults who have grown up with Landau–Kleffner syndrome.

Dorothy Bishop

Professor, Department of Developmental Neuropsychology, University of Oxford, UK

FOREWORD

The Landau–Kleffner syndrome (LKS) is not a common condition. There are, however, many reasons why a book should be devoted to it.

The diagnosis should come to mind when confronted by a child with comparatively mild epilepsy who has difficulty in understanding verbal requests to carry out non-linguistic tasks, but when he or she has grasped what he or she is being asked to do, he or she does it. A properly conducted sleep EEG should follow revealing electrical status epilepsia in sleep (ESES). Appropriate treatment should then ensue.

Sometimes psychological deficits manifest with surgical precision. I recall a 12-year-old boy who was unable to understand speech and had age appropriate reading and writing skills. In other children, inability to understand language extends to incomprehension of environmental sounds. There is frequently an accompanying behavioural disorder that seems greater than a reaction to a world that has become confusing.

Other epilepsies also carry this signature EEG. What is the relationship between LKS and, for example, rolandic epilepsy or the epileptic frontal and opercular syndrome? Classic LKS arises in a previously normal child. What are the taxonomic implications for a child with a pre-existing language disorder—and do they matter?

These and other issues are fully explored in this book, which the authors, after many years’ experience and reflection, are uniquely qualified to write. They consider the recently proposed concept of the ‘epilepsy-aphasia spectrum’, in which conditions share involvement of the perisylvian networks of speech and language, which may be permanently affected. They explore the nature of this involvement. Does abnormal electrical activity directly damage circuitry or is some process affecting neuronal excitability and the primary pathology (or both in some malignant spiral)? They point out that the phenotype, especially with LKS of early onset, may mimic autistic spectrum disorder and address the relationship between autism and LKS.

They describe how management will involve not only the child neurologist but also professionals in the communication sciences, behavioural management and teachers of the deaf. Language as well as speech may be variably affected from one child to another, and management will have to be tailored accordingly.

They demonstrate how LKS can teach us much about the relationship between other epilepsies and cognitive function. We are fortunate that the authors’ experience enables them to give a historical account of the development of our understanding of LKS, and also draw lessons from the pitfalls we have encountered along the way.

The reader will gain not only an understanding of LKS and related syndromes, but also a deeper appreciation of the relationship between epilepsy and related neuropsychological difficulties.

Richard Robinson

Emeritus Professor of Paediatric Neurology

Guys, Kings and St Thomas Hospital

London, UK

PREFACE

It was in the early 1970s that I first met a child who presented with loss of language comprehension, mutism and cognitive regression. He had only a few seizures, but severe epileptiform discharges on his EEG. He was thought to have an unusual kind of viral encephalitis until the unexpected course of the disorder, literature search, and discussion with colleagues prompted the recognition of similar cases in our community. We were faced with a mysterious combination of aphasia and epilepsy, without any evident cause, about which little had been written after the initial paper published by Landau and Kleffner in 1957. The prevailing hypothesis was that the epilepsy was an epiphenomenon of one or several different brain diseases, although the search for them remained elusive. During the same period, like many child neurologists around the world, we were busy in Lausanne trying to better identify the ‘idiopathic focal epilepsies of childhood’, a group of focal epilepsies without any identified structural lesion and a self-limited ‘benign’ course that seemed to occur quite frequently in otherwise typically developing children. While doing so, we became increasingly aware, like several others, of the many, but long unsuspected common features between rolandic epilepsy (or childhood epilepsy with centro-temporal spikes) and ‘acquired epileptic aphasia’ that unfortunately became known as Landau–Kleffner syndrome, an eponym that Landau and Kleffner themselves disapproved. The often remittent-relapsing course and, at times, spectacular remission of clinical and epileptiform EEG abnormalities (most prominent in sleep) with antiepileptic drugs or steroids clearly pointed to a direct role of the epileptic activity. Affected children exemplified the fact that an epilepsy can manifest with an acquired, insidious and puzzling disruption of language as well as other cognitive and behavioural functions. The latter can sometimes present like a developmental language disorder or an autistic spectrum disorder, whereas epileptic seizures can be rare or even absent. In short, epilepsy can no longer be regarded only as a paroxysmal disorder with various seizures types but can also present as a continuous slow progressive disorder with no evident paroxysmal features.

This prompted us to focus our research on longitudinal studies of children whose epilepsy was accompanied by a cognitive regression, developmental arrest or behavioural disruption. The aim was to try to disentangle a possible direct role of the epilepsy from all other factors that may affect cognitive function, and this in any epilepsy, regardless of type, cause or age at onset. This was a tedious, unspectacular approach, involving often single or only a few cases, each child being his or her own control. Such cases are often dismissed as anecdotal, but we thought, and still think, that their study is justified given the paucity of relevant data that emerge from many group studies and their tendency to disregard exceptional but informative cases. This led us to our first book titled Cognitive and Behavioural Disorders of Epileptic Origin (Deonna and Roulet-Perez 2005). Since then, several new tools in the domain of electrophysiology, functional imaging, genetics, neurometabolism and neuro-immunology became increasingly used in children with epilepsy, including Landau–Kleffner syndrome and rolandic epilepsy. They contributed to show that despite their many differences, these syndromes belonged to a continuum.

This diversity of the ‘epilepsy-aphasia spectrum’ is mirrored by that of the numerous medical and non-medical professionals who studied children at various points in the course of the disease, usually focusing on one selected aspect and published in a multitude of different periodicals or book chapters in the past 50 years or so.

About 10 years after my encounter with my first patient and involvement in this topic, I was fortunate to be joined by Eliane Roulet-Perez who became a life-long collaborator and my successor as the head of child neurology in Lausanne University Hospital. She became from the start an enthusiastic partner on all childhood epilepsy issues that we studied. She carried out pioneering studies of epilepsy with continuous spike-waves during sleep, on sign language in Landau–Kleffner syndrome, cognitive development of young children after successful epilepsy surgery and epilepsy in glucose transporter deficiency. This background and her fully active clinical and scientific involvement were decisive for me to dare to undertake the long-considered project to bring together the old and the new of the vast but scattered information on Landau–Kleffner syndrome and its continuum after my retirement. We both believe that the cognitive consequences of epilepsy are the most important aspect of childhood epilepsy in general and that the study of the children with epilepsies in the epilepsy-aphasia spectrum provides a helpful model for approaching many other epilepsies, including those with structural lesions.

It was also a last opportunity for me to bring to light forgotten and unpublished case histories and long-term follow-ups and describe the evolution of some older patients with Landau–Kleffner syndrome whose fate constitutes a now partly closed chapter in the history of this disorder. The dramatic loss of verbal comprehension and speech that has puzzled our forefathers in psychiatry and neurology has also allowed us to explore the history of ideas on many aspects of cognitive and social development of children and its disorders. It also allowed us to admire the adaptation of children to these extreme circumstances including the world of the deaf and the use of sign language.

There is a growing awareness that a full understanding of the consequences of brain disease on cognition and behaviour requires also an analysis ‘at the first person’ level. This subject-oriented approach is obviously difficult with children who either may not have enough insights or enough verbal understanding or ability to engage in a dialogue about their experience and emotions or even may have forgotten (or suppressed) memories of painful events. When possible, and with the help of their parents, we tried to give them a voice throughout this book and in the testimonies at the end, a dimension that cannot be found in short scientific papers.

Thierry Deonna

March, 2016

REFERENCE

Deonna T, Roulet-Perez E. Cognitive and Behavioural Disorders of Epileptic Origin in Children. Clinics in Developmental Medicine No. 168. London: Mac Keith Press, 2005.

ACKNOWLEDGEMENTS

Who, in our ‘e-days’, still supports the idea of writing a medical book, the more so on a complex and poorly understood topic in which new data accumulate constantly? A few colleagues and friends thought there was still room for such an endeavour and challenge, and their early encouragement was decisive: Jean Aicardi (now deceased), Peter Baxter, Claude Chevrie-Muller, Mary Coleman, Marie-Noelle Metz-Lutz, Isabelle Rapin and Patrick Van Bogaert. Our gratitude goes to all of them.

Most of the neuropsychological data on our patients were obtained by Claire Mayor-Dubois, the head neuropsychologist of our unit. Thanks also to her training in speech therapy and a great interest in language and Landau–Kleffner syndrome, we were able to investigate our patients in depth and follow them up over many years. Her contribution to several unpublished personal case reports is specifically mentioned throughout this book. We thank her for all her inestimable work and stimulating discussions during the preparation of this book.

We are indebted and thankful to Xavier De Tiège, Patrick Van Bogaert and Serge Goldman and their colleagues who wrote an important chapter on functional neuroimaging in the epilepsy-aphasia spectrum. We very much appreciate their willingness to contribute with their unique expertise in an otherwise personal book. They share with us the belief that the close integration of clinical and highly technical and sophisticated data is of paramount importance.

Several colleagues around the world whom we know personally or from their writings were kind enough to comment and go back to their own often old articles for a requested clarification or follow-up data: Claude Chevrie-Muller, Ine Cockerell, Alexander Datta, Peter Huppke, Mariko Kaga, Mary King, Sara Kivity, Christian Korff, Catherine Labasse, Peter Marien, Marie-Noelle Metz-Lutz, Juan Narbona, Geneviève Offermans, Costanza Pagano, Gunilla Rejnö-Habte-Selassié, Peter Ulldall, Patrick Van Bogaert and Paolo Veggiotti. Some of them and others, Prakash Kotagal, Sarah von Spickaz, Ulrich Stephani and Peter Uvebrandt, also provided us with the unpublished observations presented in Chapter 14. We are very grateful and indebted to them for the hard work they did to go back into their files.

Many of those mentioned above also read and made invaluable comments on the whole or selected chapters of our manuscript, as did Anne O’Hare, Richard Robinson, Anne-Claude Prélaz, Ingrid Scheffer and last but not least Anne-Lise Ziegler, an essential contributor in our initial projects. Many collaborators from our team and from the EEG and Neuroradiology of le Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne who cannot be all named helped obtain invaluable data on our patients and we are grateful to them.

It is a great pleasure to also thank all the parents and children for their willingness to collaborate and accept investigations that they knew were not always for their direct benefit. This always makes a huge difference. Several patients were not children anymore, but adults accompanied at times by their elderly parents, when they accepted a late first or follow-up encounter and sometimes to be the subject of a special investigation.

We are indebted to CHUV, Lausanne and especially to Professor Pierre-François Leyvraz, the general director, for a grant that helped to support our project. We also thank Fabrice Weyermann for his very helpful local technical assistance.  Finally, we would like to warmly thank our editors, Udoka Ohuonu and Ann-Marie Halligan, for their patience, encouragement and editorial guidance and our families and friends for their understanding when we were absorbed in our work.

TD and E R-P

1

INTRODUCTION

The idea that LKS is a rare condition that does not deserve a whole book has been gradually challenged over the years. Actually, language loss which is the hallmark of Landau-Kleffner syndrome (LKS) is only the most obvious and dramatic among a wide range of cognitive disturbances that can occur in the course of idiopathic focal epilepsies (IFE) of childhood, which are the most frequent childhood epilepsies. It has taken almost half a century to understand that LKS was due or closely related to a bioelectrical dysfunction of the brain, - ie. an epilepsy-even if it did not appear so at first glance. LKS has thus opened the way to the concept of epilepsies with cognitive symptomatology or cognitive epilepsies, denoting those epilepsies that manifest mainly or exclusively in the cognitive or/and behavioural sphere without (or only rare) seizures. (Deonna, 1993a; 1996; Deonna and Roulet, 2005).

LKS gradually emerged as a ‘new’ form of childhood aphasia following the publication of Landau and Kleffner in 1957 entitled ‘Syndrome of acquired aphasia with convulsive disorder in children’. These authors reported six previously normal children who rapidly or more insidiously lost their language without any evident cause. However, they all had epileptic seizures except one and severe epileptiform abnormalities on their electroencephalogram (EEG). These disappeared after a few years and the aphasia recovered to various degrees. There was no other sign of brain dysfunction or evidence of a demonstrable acquired brain pathology. The language deficit involved mainly comprehension and was prolonged, unlike typical childhood aphasias due to focal brain lesions in language areas. Whereas antiepileptic drugs controlled the rather rare seizures, they seemed to have no effect on the language disorder or on the EEG, an observation that delayed the recognition of the direct role of the epilepsy. However, Landau and Kleffner already suggested that ‘persistent convulsive discharge in brain tissue largely concerned with linguistic communication results in the functional ablation of these areas for normal linguistic behaviour’. A number of similar cases were subsequently recognized worldwide and assessed with new imaging techniques as they emerged. With rare exceptions, the latter never revealed a structural brain lesion. The eponym ‘Landau–Kleffner syndrome’ was introduced as an epilepsy syndrome equivalent to ‘acquired epileptic aphasia’ for the first time in the 1989 International League Against Epilepsy (ILAE) proposal for revised classification of epilepsies and epileptic syndromes. Over the years, the increasing recognition of new patients, follow-up of the early ones and an enlarged perspective on the age-variability, severity and role of the epilepsy have gradually led to the present view of LKS, which is summarized in Table 1.1. LKS is now considered to be at the severe end of a spectrum of epilepsy syndromes with neuropsychological deficits belonging to the idiopathic focal epilepsies of childhood (IFE), rolandic epilepsy being at its mild end (see Chapter 3 for further discussion). Now brought together under the broader label of epilepsy-aphasia spectrum (EAS), these epilepsies share an age-related, self-limited course, sleep activated interictal discharges (IED), response to similar medications and absence of a structural lesion. They are likely to be related to and linked together by a complex genetically determined alteration of maturation of the perisylvian networks supporting speech and language functions. Symptoms mainly consist in acquired, sometimes subtle language impairments. Other cognitive functions may also be affected when the focal epileptic activity shifts or spreads beyond the perisylvian region. Patients may thus present with executive deficits or a global intellectual, behavioral and even motor regression, that often correlate with the finding of intensely sleep activated diffuse and ample interictal epileptiform discharges (IEDs) on the EEG, called continuous spike waves during sleep (see chapter 3). The latter seem to sustainably modify the activity of more remote functionnally connected cortical areas such as the prefrontal regions via the thalamo-cortical circuitry (chapter 11).

TABLE 1.1

The early (1980–1990) and present (2015) views of Landau Kleffner syndrome

ACTH, adrenocorticotrophic hormone; AEDs, antiepileptic drugs; CSWS, continuous spike waves during slow sleep; EAS, epilepsy-aphasia spectrum; FSW, focal sharp waves; IFE, idiopathic focal epilepsies of childhood; PET, positron emission tomography

Occasionnally, when an EAS syndrome starts very early in development, it can mimick a developmental language disorder or an autistic spectrum disorder (see chapter 6).

Beyond its status as an epilepsy syndrome, LKS has also helped clinicians understand that an acquired language disturbance in a child is not necessarily a sign of global cognitive regression or deafness, and it can have a neurophysiological rather than a psychological origin. Because of the affected cognitive functions and their consequences on the child’s communication and intellectual development, the expertise of professionals outside the child neurology and epileptology fields is required, the management of the epilepsy being often only part of the story. LKS has, therefore, also captured the minds of specialists in communication sciences, speech pathology, neuropsychology and child development. It has also led to more fundamental questions. For instance, whether and how the different components of developing language can be selectively and temporarily disrupted and compensated for later on? How can a young human being cope with a prolonged loss of language while keeping otherwise preserved intellectual and emotional abilities and adapt without losing his or her essential self? What are the best ways to help the child to recover? If the child does not, how to maintain communication? Will he or she be able to learn a visual form of language, and if yes, how should it be taught? How did patients who recovered live the unique experience of being part of two different worlds, that of the ‘deaf’ and that of the hearing?

We believe that a historical review and a synthesis of the extensive but scattered research of the past 50 years on LKS and related epilepsy syndromes represent a fascinating journey into what is probably the most important aspect of childhood epilepsy, that is, its impact on developing higher cerebral functions. Many clinical and theoretical issues relating to LKS constitute an excellent introduction to this topic that has become a major preoccupation in childhood epilepsy and generates extensive research. The thinking about LKS proposed here can to a large extent be generalized to many epilepsies, including lesional epilepsies in which developmental stagnation, regression and various cognitive and behavioural impairments can occur beyond what is expected from the underlying aetiology and that propagate within one or both hemispheres and become activated by sleep.

Recounting the slow evolution of ideas, conceptual errors and late recognition of retrospectively obvious facts about LKS is a lesson of humility for all, a lesson that can apply to many other medical conditions. In this book we also report the tragic case histories and pay tribute to the early patients diagnosed with severe forms of LKS who we have met personally or read about in the literature. They were born when LKS was still unrecognized or diagnosed late and were badly managed. Some of these children have never spoken again and did not recover language comprehension either. It was difficult to find a place for them in schools, as they were not intellectually disabled or psychiatrically disturbed and were rarely accepted or at ease in schools for the deaf and the deaf community. In fact, they belonged to neither world. Such patients are now fortunately the exception, thanks to improved diagnosis, better drugs and better management. But so that the earlier patients might be forgotten by younger generations, we have given their stories a separate place at the end of the book.

2

THE HISTORY OF LANDAU–KLEFFNER SYNDROME

The Landau–Kleffner syndrome (LKS) represents a unique opportunity to look at early ideas about language and particularly its development and acquired deficits. It is often only when we are faced with a new or exceptional phenomenon that we start to think about what we normally take for granted. There is no reason to believe that LKS was a new condition that appeared at the mid-turn of the twentieth century. In other words, it certainly always existed, and descriptions of children who became mute for a long time or for the rest of their lives can be found in the medical or related literature. They must have intrigued the first psychiatrists, neurologists or other curious and compassionate men, who were willing to record their encounter with such an incomprehensible and tragic situation. The ways they tried to explain the cognitive disturbance of a patient, which we now would label as ‘severe LKS’, provides an insight into the history of ideas about complex brain function, and into the development of specific neuropsychiatric disciplines in the past hundred years. It is thus worth starting our journey as early as possible, looking at published cases whose description suggests a diagnosis of LKS, and see how they were interpreted before the advent of electroencephalography (EEG) in the early fifties.

The historical period before LKS was recognized

Table 2.1 shows the different diagnostic labels given by the emerging psychiatric and neurological fields for children with LKS