Paul R. Dyken

Changing character of subacute sclerosing panencephalitis in the United States

We analyzed National Registry data from 575 patients with subacute sclerosing panencephalitis (SSPE) in the United States to assess changes in patient characteristics and SSPE epidemiology. Racial proportions have changed in recent years with an increasing number of Hispanic patients reported in relation to a constant black:white ratio; however, the male:female ratio of approximately 2:1 has remained. The most striking feature of the data is the rapid decline in SSPE incidence. Corresponding to this decrease is an increase in the proportion of cases following measles vaccination. There also is a shorter incubation period for SSPE following vaccination than after measles infection.

Review Article: The Neuronal Ceroid Lipofuscinoses

The neuronal ceroid lipofuscinoses are clinical disorders associated with the accumulation of autofluorescent waxy pigments within cells of several different tissues. Such syndromes always have neurological manifestations. Variations in clinical course, genetics, pathogenesis, and possibly treatment occur in each of the several forms listed under this category. Ten subtypes have now been recognized: (1) chronic, juvenile (Batten type); (2) acute, late infantile (Bielschowsky type); (3) subacute-chronic, adult (Kufs type); (4) acute, infantile (Santavuori-Haltia type); (5) congenital (Norman-Wood type); (6) acute, adult (Zeman-Dyken type); (7) acute-subacute childhood (Bielschowsky variant); (8) chronic, childhood with pervasiveness (Edathodu-Dyken type); (9) chronic, infantile with autism (Dyken type); and (10) chronic, juvenile with ataxia and spasticity (Dyken type). By far the most common of these are the first four disorders listed. It is proposed that this present classification of neuronal ceroid lipofuscinosis is more comprehensive than previous ones and fails to support the hypothesis that this disorder represents a unitary disease process, rather than different diseases with similar characteristics. At present, each of the neuronal ceroid lipofuscinosis types are of unknown etiology. (J Child Neurol 1989;4:165-174).

Short term effects of valproate on infantile spasms

Although valproic acid (VPA) is used to treat infantile spasms, VPAs efficacy in infantile spasms has not been determined in a controlled study. This study evaluated the effect of VPA on infantile spasms in patients who had not responded to adrenocorticotropin (ACTH) and corticosteroid therapy. The hypotheses were tested using a double-blind, randomized controlled crossover design. Twenty-one patients were randomly assigned to either the baseline-valproate-placebo treatment or the baseline-placebo-valproate treatment groups. Based on a repeated measures analysis of variance test, the valproate group had lower total mean spasm frequency levels than the placebo group. However, this difference did not remain after the crossover; the difference was due to the initial administration of valproate and placebo. When the spasm index was analyzed, the valproate treatment was found to have lower mean spasm index scores than the baseline treatments (p less than 0.03). No short-term toxic effects were observed in any patient. We conclude that short-term VPA therapy has a beneficial effect even on chronic infantile spasm patients who have failed to respond to ACTH/corticosteroid therapy.

Magnetic resonance and CT imaging correlated with clinical status in SSPE

Five patients afflicted with subacute sclerosing panencephalitis were studied with computed tomography and magnetic resonance imaging. Computed tomography documented changes of nonspecific cerebral atrophy and low attenuation in the subcortical white matter. Magnetic resonance imaging revealed bilateral, symmetric, and diffuse abnormal increased signal in the white matter of the cerebral hemispheres with normal posterior fossa structures in 4 of 5 patients. Magnetic resonance imaging was superior to computed tomography in demonstrating the total extent of abnormality and may be the imaging modality of choice for this childhood disease.

Magnetic resonance imaging in neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinosis is a group of neurodegenerative disorders characterized by accumulation of lipofuscin and/or ceroid within the tissues of the body. These entities are manifest by visual, intellectual, and motor deterioration as well as recurrent seizures. Computed tomography has been shown to demonstrate changes of cerebral atrophy in more severely affected patients. Seven patients with neuronal ceroid lipofuscinosis were examined with both computed tomography and magnetic resonance imaging, and the results were correlated with the clinical severity of the disorder. Two less severely affected patients had normal results on computed tomography and magnetic resonance imaging studies. Varying degrees of cerebral atrophy were seen in the remaining five patients with both computed tomography and magnetic resonance imaging. Severity of atrophy correlated with the severity of disability in these patients. Abnormal white matter was seen in the two most severely affected patients only with magnetic resonance imaging. Although the findings in patients with neuronal ceroid lipofuscinosis were nonspecific, the increased sensitivity of magnetic resonance imaging for subtle white matter abnormalities over computed tomography may prove helpful in monitoring the progression of this rare disorder.

Profound Infantile Neuroretinal Dysfunction in a Heterozygote for the CLN3 Genetic Defect

The neuronal ceroid-lipofuscinoses are a group of diseases that are characterized by progressive neuroretinal symptomatology, progressive accumulation of autofluorescing waxy lipopigments (ceroid-lipofuscin) within the brain and other tissues, and cerebral atrophy. Juvenile neuronal ceroid-lipofuscinosis, or Batten disease, is a form of neuronal ceroid-lipofuscinosis that is characterized by onset of neuroretinal symptoms between 4 and 10 years. Juvenile neuronal ceroid-lipofuscinosis is the most common type of neuronal ceroid-lipofuscinosis in the United States and Europe and is inherited as an autosomal recessive genetic disorder. Research in the last decade has led to the identification of the responsible gene for juvenile neuronal ceroid-lipofuscinosis, which is designated as CLN3. CLN3 is located on chromosome 16p11.2-12.1. The major mutation is a 1.02 kb deletion, which removes exons 7 and 8. Both homozygotic and heterozygotic deletions at the CLN3 gene site have been associated with the clinical syndromes of juvenile neuronal ceroid-lipofuscinosis. We report a possible atypical case of neuronal ceroid-lipofuscinosis, an infant, who presented at 5 months of age with a lack of developmental milestones, poor vision, severe retinopathy, intractable seizures, and progressive cerebral atrophy. Extensive laboratory investigations, including thorough metabolic evaluations, were unremarkable except for neuroimaging studies, electroencephalography, and electroretinography, all of which showed abnormalities confirming both cerebral and retinal degeneration. Although skin and conjunctival biopsies did not show classic fingerprint cytosomes by electron microscopic study, which characterize juvenile neuronal ceroid-lipofuscinosis, a diagnosis of an atypical form of juvenile neuronal ceroid-lipofuscinosis was suspected on the basis of the clinical picture. The retinal abnormalities, surprisingly, were those believed to be diagnostic of juvenile-onset neuronal ceroid-lipofuscinosis, or Batten disease. Subsequently, a heterozygous mutation for the common 1.02 kb deletion characteristic of juvenile neuronal ceroid-lipofuscinosis was established. (J Child Neurol 2004;19:42—46).

From the National SSPE Registry

It has been increasingly apparent that the numbers of patients with subacute sclerosing panencephalitis (SSPE) reported to the National SSPE Registry is declining in the United States. These statistics undoubtedly reflect the result of the extensive national immunization program against measles in the United States. This country is the first in the world to show a decreased incidence of SSPE. Collecting meaningful data concerning the effect of treatments in rare, chronic, debilitating, neurologic diseases is well known. As an example, multiple authors have reported beneficial effects of drug Others have claimed that there is no statistical proof of benefit and therefore the treatments are assumed, falsely, to be ineffective. Extreme care must be taken in studying the effects of treatment in such uncommon diseases as SSPE, however. The most important element counteracting SSPE has been the prevention of the development of natural measles and its subsequently developing neurologic complication. Although SSPE in the USA may be seen at a slightly higher rate than would be expected from the occurrence of natural measles here, many patients with SSPE reported in the United States are immigrants who have not had measles immunization. Such an example seems to exist in the patient reported in the Clinical/Scientific Note by Mitchell and Crawford in this issue of Ne~rology.~ Curative therapeutic measures must be developed for such patients in the United States and in the world. Mitchell and C r a ~ f o r d , ~ in a simple case, report many interesting points about the problems faced in obtaining meaningful data on SSPE treatment. They correct one bias by measuring the neurologic disability of the disease in their patient, using a method for measuring changes in disease disability by standard clinical as~essment.~ Such a simple approach eliminates considerable subjective bias. The authors also accept the fact that the results of treatment in only a few cases may be meaningless. They suggest an appropriate manner of correcting the latter situation. They suggest establishing a tracking station, such as the National SSPE Registry, to act as a conduit to accumulate data. to standardize the usefulness of various forms of treatment. When the National SSPE Registry was first formed in 1969, its primary objective was not to follow treatment protocols specifically. This, however, was based on the fact that, at this time, no treatments really existed. As the years have passed, many of the earlier concepts about SSPE have changed dramatically as have the forms of treatment. In support of the suggestion by Mitchell and Crawford, the National SSPE Registry has recently, and will in the future, closely track the results of treatment in this disease. The National SSPE Registry is now located in Mobile, Alabama, within the University of South Alabama College of Medicine and the Department of Neurology. Individuals are encouraged to communicate all information on this now rare disease to these offices.

In Memoriam: William Erl DeMyer (1924-2008)

A n exceptional neurologist died in the fall of last year. His name was Bill DeMyer (Figures 1 and 2). This traditional neuroscientist was both an expert clinical neurologist and a gifted neuroanatomist who had a deep-seated interest in the neurological disorders of children. He was extremely self-disciplined and focused on excellence in all aspects of his life. Bill will probably be remembered by most child neurologists primarily for his many studies on the malformation group of disorders known as holoprosencephaly, a name he coined. Yet, holoprosencephaly was only one of his many contributions to the field of child neurology and, although he identified himself as a child neurologist, his accomplishments were varied and extensive. Bill received his MD degree from Indiana University in 1952 followed by a rotating internship at the University of Michigan from 1952 to 1953. He took his residency in neurology at Indiana University from 1953 to 1956 and then attended the Medical Faculty Training Program at the University of Pennsylvania (19561957). He returned to Indiana University as a faculty member in 1957. These were in the days before child neurology was recognized as a subspecialty. Because of his interests and extensive work in child neurology practice, teaching, and research between 1956 and 1968, he was one of the first to become certified by the American Board of Psychiatry and Neurology in the subspecialty of Child Neurology in 1968. In addition to holoprosencephalies and median facial anomalies, Bill made many other original contributions to medical science. During his residency, he developed innovative techniques and stains as methods for identifying and counting nerve fibers. These led to a classic study that established the number and origin of axons and myelin sheaths in the medullary pyramids. He published definitive papers on Pelizaeus-Merzbacher disease. With Alexander Ross, he conclusively established the anatomical side of the medial longitudinal fasciculus lesion in an isolated syndrome in man. With his wife, Marian DeMyer, a renowned child psychiatrist, he was one of the first to define autism as an organic disease. These are only a few examples of his original studies. Despite Bill’s many major contributions to neuroscience, it is perhaps his teaching that will remain his Received January 14, 2009. Accepted for publication January 14, 2009.

The Beginnings of the Southern Child/Pediatric Neurology Society:

The founding and early development of the Southern Pediatric Neurology Society was in many ways parallel to that of the Child Neurology Society. The organization started out as the Southern Child Neurology Society but the name was changed at the time of incorporation so as to avoid confusion of identity and purpose with the larger Child Neurology Society. Although there are archives of early days and the later development of the Southern Pediatric Neurology Society, the details have never been set down in a narrative explaining the events that led to the development of the organization. In this paper, we try to produce a written record of the history of the founding and early development of the Southern Pediatric Neurology Society.

De Lange's Syndrome: Facial Features of Pediatric Neurologic Syndromes

Received April 14, 1999. Accepted for publication April 14, 1999. Address correspondence to Dr Paul R. Dyken, Director, Institute for Research in Childhood Neurodegenerative Diseases, 283 Wingfield Drive, Mobile, AL 36607.Tel: 334-471-3765; fax: 334-476-8277. This interesting syndrome, although reasonably uncommon, represents one of the classic facial abnormality syndromes seen in the neurologic practice of children. The syndrome was first described by Brachmann in 1916, yet it was not until l