Periventricular low attenuations: a normal finding in computerized tomographic scans of neonates?

Twenty-five of the initial computerized tomographic (CT) scans of 63 neonates had "definite" abnormalities. These abnormalities included dilated ventricles, advanced hypodensities extending beyond the periventricular areas, and varieties of hemorrhage. Thirty-six, with otherwise normal intracranial structures, were found to have localized periventricular frontal or frontooccipital areas of low attenuation. These areas were confined to the white matter of the periventricular area and have been identified by others as indicating "periventricular leukomalacia." In follow-up clinical studies on 26 of this latter groups, only two showed neurological abnormalities. Seven CT scans were repeated; only one was abnormal. In this case, the attenuations had disappeared, but were replaced by mild deep and cortical atrophy. The patient then showed findings suggesting a mild spastic diparesis and psychomotor delay. Our findings suggest that periventricular low attenuations in an otherwise normal CT scan are usually due to incomplete myelination or, at least, a transient abnormality. Periventricular low attenuation cannot be used as a diagnostic sign of periventricular leukomalacia, nor does it necessarily suggest an unfavorable prognosis.

Cerebrospinal fluid cytology: practical clinical usefulness.

Sedimentation cytomorphology is a simple, inexpensive technique of collecting cells from cerebrospinal fluid and is of great clinical value. Important variables such as blood contamination, age of the patient, and general clincial condition must be considered. Specific conditions for which cerebrospinal fluid cytomorphology shows clinical usefulness include central nervous system leukemia, hemorrhage, immunopathies, infections, and brain tumors. Clinical examples of each of these conditions and their correlated cytograms are presented.

Hereditary nonprogressive athetotic hemiplegia: a new syndrome.

A family with four affected members showed a stereotyped unilateral neurologic deficit. The disorder was characterized in each member by congenital left hemiparesis, with subsequent development of left hemihypoplasia and athetoid posturing of the left hand. Although the proband was initially considered a "cerebral palsy" victim, the autosomal dominant pattern and the stereotyped clinical features in all affected family members suggest a hereditary process. Hereditary factors may be an uncommon cause of static unilateral neurologic motor defects.

The effect of inosiplex on the survival of subacute sclerosing panencephalitis.

We studied the probability of survival of subacute sclerosing panencephalitis (SSPE) patients prognostically stratified into rapidly and slowly developing SSPE, nontreatment, and inosiplex-treated groups. Based on life table analysis, survival did not differ between treated and untreated patients with rapidly developing SSPE. The cumulative survival rates were significantly (p less than 0.05) higher and the mortality rate significantly lower in the slowly developing inosiplex-treated group.

Serum clonazepam concentrations in children with absence seizures.

Clonazepam, a chlorinated derivative of nitrazepam, was administered to 10 children with absence seizures. Serum concentrations were measured after 8 weeks of treatment, at steady state. Seizure frequency reports and the 12-hour telemetered electroencephalogram were studied before and after 8 weeks of treatment to determine the frequency and duration of generalized spike-wave paroxysms. The clonazepam dosage ranged from 0.028 to 0.111 mg per kilogram and was reflected in serum levels ranging from 13 to 72 ng per milliliter, with an excellent correlation between dose and serum level. Eight of the 10 patients showed a significant decrease in seizure frequency, with three experiencing no seizures at all. Six patients had side effects, predominantly drowsiness and ataxia. This preliminary study shows clonazepam to be useful in the treatment of absence seizures in children and to merit further study.

Opsoclonus in Hemophilus influenzae meningitis.

We studied a 3-month-old boy who had opsoclonus in association with acute bacterial meningitis. The CSF IgG and IgM were elevated acutely, gradually returning to normal with clinical improvement. Correspondingly, CSF cytomorphology showed excessive plasmocytosis and a higher proportion of reactive lymphocytes than expected in an acute bacterial meningitis. These abnormalities in CSF cytology are effects of an abnormal immune response in the CNS, and provide evidence to support an immunopathic basis to opsoclonus.

Ethosuximide in the treatment of absence (peptit mal) seizures.

Thirty-seven patients with previously untreated absence seizures were treated with ethosuximide. Seizures were completely controlled in 7 patients (19 percent); 90 to 100 percent control was achieved in 18 patients (49 percent) and 50 to 100 percent control in 35 (95 percent). Plasma ethosuximide concentration increased with dose, but variability in the plasma concentration produced by a given ethosuximide dose made it impossible to predict a patient's plasma concentration from the dose. The therapeutic range of plasma ethosuximide concentration was 40 to 100 mug per milliliter. Patients with evidence of structural central nervous system abnormalities responded as well or better to the drug as patients without such evidence. Ethosuximide did not impair psychometric performance, but rather resulted in improved performance in 17 cases. The side effects of ethosuximide were minor, and rarely required withdrawal of the drug.

Classification of the neuronal ceroid-lipofuscinoses: expansion of the atypical forms.

The neuronal ceroid-lipofuscinoses (NCL) are a group of different genetic diseases. The major types of NCL are expressed by six forms which represent different clinicopathologic and genetic forms. These are CLN-1, Infantile; CLN-2, Late Infantile; CLN-3, Juvenile; CLN-4, Adult-Recessive; CLN-5, Adult-Dominant; and CLN-6, Early Juvenile. The distinction between CLN-4 and CLN-5 is still disputatious. CLN-6 has been called CLN-5. A seventh classification of NCL represents from 12 to 20% of those afflicted. This group consists of an extensive array of atypical types of ceroid-lipofuscin accumulation in the secondary lysosomes of neurons and cells of other tissues (e.g., skin, conjunctiva, and lymphocytes) or by presumed clinical and genetic relationships. The authors have identified 15 atypical subtypes of NCL. These as a group are here described as a seventh form. Further biochemical, molecular, and genetic studies will identify more precisely the phenotypic and genotypic expression of these "minor" forms of NCL.

Cellular distribution of lesions in Batten disease.

One of the characteristic manifestations of chronic neuronal lipofuscinosis (Batten disease) is a marked predisposition for epileptic seizures. The management of these seizures is very difficult. The present study was initiated to determine what mechanisms could account for the seizure disorder. Tissue was examined from a patient with a history of Batten disease that was histologically verified. Reduced silver and Golgi impregnations were done on the parietal cortex of the patient. There was no evidence of the marked dendritic abnormalities seen in classic epileptic foci. Instead there was marked swelling and dilatation of the axon hillock and initial segment. This finding suggested that inhibition of these pyramidal neurons was markedly attenuated due to disruption of initial segment inhibitory synapses. Studies are continuing to determine if the GABA decreases seen in Batten disease may in part be due to trophic sequences brought about by loss of these critical inhibitory synapses.

Translocation 10;18 in a patient with juvenile neuronal ceroid-lipofuscinosis (Batten disease).

We report the first observation of a chromosome abnormality in a patient with typical juvenile ceroid-lipofuscinosis (NCL), who was found to have an apparently balanced translocation between chromosomes 10 and 18 [t(10;18)(q22.1;q21.1)]. Since juvenile NCL was previously mapped to 16p12, this report raises the possibility of heterogeneity in this form of NCL.

Free radicals, anticonvulsants, and the neuronal ceroid-lipofuscinoses.

The relationship between free radicals and scavenger enzymes, and the disorders called the neuronal ceroid-lipofuscinoses, has long been an argumentative one. Recent evidence would seem to support the fact that such a relationship might exist but that it is indirect. The relationship does not seem due to an inborn error of free radical scavenger enzyme metabolism. Anticonvulsants play a role, as they influence free radical generating systems. At this juncture, no one has studied the relationship of anticonvulsant therapy, neuronal ceroid-lipofuscinosis, and the free radical-scavenging enzyme system, and their interplay. We have studied a large number of patients with epilepsy who are on either monotherapeutic or polytherapeutic regimens of most of the common anticonvulsants. We have found excessive free radical production in many of these patients, ranging from minor effects in the simpler anticonvulsants when used monotherapeutically, to more complex changes in polytherapeutic combinations. Likewise, we have found subtle and inconsistent findings in the free radical-scavenging enzyme system in a variety of examples of neuronal ceroid-lipofuscinosis. When refractory seizure disorders stimulate the vigorous use of polytherapy with a variety of free radical-facilitating anticonvulsants, free radical production becomes deleterious. Likewise, in certain types of neuronal ceroid-lipofuscinosis, polypharmacy with anticonvulsants, by enhancing the production of free radicals or suppressing scavenging enzymes, tends to be deleterious and induces a worsening in the disease process.

Subacute sclerosing panencephalitis. Current status.

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease of childhood that is due to a persistent measles infection. Owing to a nationwide immunization program in the United States, the incidence has decreased considerable, coexistent with the decline in natural measles infection. The disease, now fully understood, still represents a great international problem. Clinical presentation, etiology, pathogenesis, prevention, and treatment are updated in this 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.

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.

Infantile spasms: ictal phenomena.

Ictal phenomena were studied during three separate six-hour video/polygraphic recording sessions in 10 patients with infantile spasms; 1,079 spasms occurred. Frequency during wakefulness (7.7 spasms/hour) was greater than that during sleep (2.5 spasms/hour); 46.6% of spasms occurred in clusters. Spasms were composed of one or more of three phases: a myoclonic contraction, a tonic contraction, and/or an arrest of activity. The most common types were myoclonic-tonic (40.3%) and myoclonic alone (36.3%). When classified by postural motor phenomena, 41.6% were "flexor", 16.3% "extensor", 39.0% "mixed", and 3.1% "arrest" alone. Electrographic monitoring revealed that myoclonic contractions were associated with an initial paroxysmal event. Tonic contractions and arrests were usually associated with suppression of electroencephalographic activity with or without rhythmic activity. Knowledge of these clinical and electrographic features is important for diagnosis and evaluation of proposed treatments.

Short term effects of valproate on infantile spasms.

Although valproic acid (VPA) is used to treat infantile spasms, VPA's 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.

Comparison of cytocentrifugation and sedimentation techniques for CSF cytomorphology.

Two methods of processing cerebrospinal fluid (CSF) cells for morphologic study were compared. The newer cytocentrifugation method, using the Shandon Cytospin apparatus, allowed slightly quicker processing of cells but did not appreciably influence the total time needed to fully study the cells. The preservation of cells, as measured by observation of cellular detail, was better after the use of older, more gentle, sedimentation technique. The sedimentation technique was generally found to yield a higher number of total cells. The loss of small cells by the sedimentation method was not statistically greater than with the cytocentrifugation method, but large cell collection was significantly better. The older sedimentation method is concluded to be preferable to the newer cytocentrifugation method for CSF cytomorphology.

Subacute sclerosing panencephalitis. Clinical aspects and prognosis. The Brazilian registry.

Subacute sclerosing panencephalitis (SSPE) is an inflammatory neurodegenerative disease related to the persistence of measles virus. Although its frequency is declining because of measles eradication, we still have some cases being diagnosed. With the aim to describe epidemiological aspects of SSPE in Brazil, we sent a protocol to Child Neurologists around the country, 48 patients were registered, 27 (56%) were from the southeast region, 34 (71%) were male and 35 (73%) white, 27 (56%) had measles, 9 (19%) had measles and were also immunized, 7 (14%) received only immunization, 1 patient had a probable neonatal form. Mean time between first symptoms and diagnosis was 12 months (22 started with myoclonus or tonic-clonic seizures, 7 (14%) with behavioral disturbances); 36 patients (75%) had EEG with pseudoperiodic complexes. Follow up performed in 28 (58%) patients showed: 12 died, 2 had complete remission and the others had variable neurological disability. Our data shows endemic regions in the country, a high incidence of post-immunization SSPE and a delay between first symptom and diagnosis.