Absence of the septum pellucidum with porencephalia. A neuroradiologic syndrome with variable clinical expression.

We studied 12 patients with absence of the septum pellucidum associated with porencephalies. Seven patients had bilateral and five apparently unilateral defects of the cerebral mantle. The clinical manifestations were relatively mild in half of the patients and limited to isolated partial seizures in one. In one case, extensive calcification was present adjacent to the defects. In two cases, the presence of a cleft was demonstrated only by magnetic resonance imaging, although it had been suspected by computed tomography in one.

The juvenile and chronic forms of GM2 gangliosidosis: clinical and enzymatic heterogeneity.

We report the cases of 5 patients from 2 sibships with the "adult" or chronic form of GM2 gangliosidosis and 2 patients from another sibship with the juvenile form. We demonstrated hexosaminidase A deficiency in all cases but in 1 sibship the enzymatic profile was identical to that in Tay-Sachs disease, whereas in the remaining 2 families it was that of the B1 variant. There was no correlation between the clinical features and the enzymatic profile. Hexosaminidase A deficiency should be considered in unexplained progressive neurologic disorders of childhood and adolescence, including isolated dementia. EMG evidence of anterior horn cell involvement in association with neurologic or cognitive deterioration may be a diagnostic clue in the juvenile forms.

Extensive macrogyri or no visible gyri: distinct clinical, electroencephalographic, and genetic features according to different imaging patterns.

We studied 43 children with extensive brain gyral anomalies diagnosed radiologically and defined by (a) the absence or paucity of sulci over cortical areas affecting at least two lobes in each hemisphere, and (b) the absence or reduction of interdigitation between gray and white matter. We correlated the clinical, EEG, and genetic findings with the imaging features. A seemingly homogeneous group of patients (group A, n = 30) presented a common imaging pattern characterized by four features: (1) a thickened neocortex, (2) widened lateral ventricles, (3) apparent verticalization and widening of sylvian fissures, and (4) bilateral and symmetric distribution of the abnormalities. Another group of patients (group B, n = 13) exhibited heterogeneous imaging anomalies, termed "nonlissencephalic brain malformation," differing in at least one of the following four ways from the radiologic criteria defining group A: absence of verticalization of sylvian fissures (n = 12), thin neocortex (n = 2), normal-size lateral ventricles (n = 2), and asymmetric brain defects (n = 3). In group A, some clinical features had a significantly lower frequency (p < or = 0.01) than in group B: microcephaly, a complete lack of postural development, and intractable epilepsy. There was a significant relationship, but only in group A, between the degree of gyral anomalies and the extent of neurodevelopmental delay. Some EEG patterns (rapid rhythms and delta-theta rhythms) were highly specific for the group A patients. There was lower risk of familial recurrence in group A (recurrence of convolutional anomalies was 3.5% of sibship in group A versus 44% of sibship in group B, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse cortical dysplasia, or the 'double cortex' syndrome: the clinical and epileptic spectrum in 10 patients.

Diffuse neuronal migration disorders associated with epilepsy can now be recognized by modern neuroimaging techniques, particularly high-resolution MRI. We report 10 patients with a recently described MRI picture of continuous or generalized band heterotopia underlying the cortical mantle, giving the appearance of a "double cortex." They have epilepsy, and almost all have mental retardation. The epileptic disorder varies in nature and degree of severity. Patients may present with infantile spasms, a Lennox-Gastaut syndrome, or other forms of secondary generalized or multifocal epilepsy. Response to medical treatment is variable. Callosotomy may lead to considerable reduction of drop attacks, present in 60%. Mental retardation is usually mild or moderate, and only rarely severe. It correlates with the type of epileptic syndrome, and is greater in patients with more disorganized cortex overlying the heterotopia. Recognition of this entity by MRI is important for appropriate diagnosis of the epileptic disorder, planning of therapeutic strategy, and prognosis.

Extensive brain calcifications, leukodystrophy, and formation of parenchymal cysts: a new progressive disorder due to diffuse cerebral microangiopathy.

A new cerebral disorder, described in three unrelated children, has recognizable clinical, radiologic, and neuropathologic findings. The onset occurs from early infancy to adolescence with slowing of cognitive performance, rare convulsive seizures, and a mixture of extrapyramidal, cerebellar, and pyramidal signs. CT shows progressive calcifications in the basal and cerebellar gray nuclei and the central white matter. MRI reveals diffuse abnormal signals of the white matter on T2-weighted sequences. A special feature is the development of parenchymal cysts in the cerebellum and the supratentorial compartment, leading to compressive complications and surgical considerations. Neuropathologic examination of surgically removed pericystic samples reveals angiomatous-like rearrangements of the microvessels, together with degenerative secondary changes of other cellular elements. Both the anatomic findings and the course of the disease suggest a constitutional, diffuse cerebral microangiopathy resulting in microcystic, then macrocystic, parenchymal degeneration.

Acute measles encephalitis in children with immunosuppression.

Four cases of encephalitis occurring in children treated for lymphatic malignancies by immunosuppressive drugs are reported. Measles virus was isolated from the brain in one case and identified immunologically in another. Nucleocapsids identical to those seen in subacute sclerosing panencephalitis were demonstrated in three cases. Severe immunosuppression was evidenced in two patients by failure of rosette formation and low phytohemagglutinin tests. Pathologically, the inflammatory reaction was absent in one brain and moderate in two. Clinically, epilepsia partialis continua was a prominent feature in three patients. A history of measles or of contact was elicited in three cases, five weeks to three months before onset. All cases ran an acute fatal course. Measles virus can behave as an opportunistic invader of the central nervous system in children and the diagnosis of measles encephalitis should be considered in immunosuppressed patients.

Schilder's myelinoclastic diffuse sclerosis.

The term "Schilder's disease" has been used to describe conditions as disparate as adrenoleukodystrophy, myelinoclastic diffuse sclerosis, and postinfectious and postvaccinal encephalomyelitis. The eponymic designation should be reserved for instances of myelinoclastic diffuse sclerosis that correspond to the case described by Schilder in 1912. The diagnosis cannot be made unless adrenoleukodystrophy has been ruled out by analysis of the long-chain fatty acids of plasma cholesterol esters. Schilder's myelinoclastic diffuse sclerosis, a variant of multiple sclerosis, is a very rare disease that occurs in children and adults of both sexes and appears to respond to vigorous treatment with corticosteroids and/or corticotropin. A case of this disease is reported and the recent literature of cases that have been called Schilder's disease is reviewed.

Three new cases of the Schinzel-Giedion syndrome and review of the literature.

Three fetuses with normal chromosomes were found to have uni- or bilateral hydronephrosis during the third trimester of pregnancy. At birth, they presented with coarse face, hypertelorism, and a deep groove under the eyes. Fontanelles and sutures were wide open. Genital abnormalities were present in 2 cases. Skeletal radiographs showed delayed bone maturation, broad and dense ribs, and a wide synchondrosis between the exoccipital and supraoccipital bones. The combination of such findings suggested the diagnosis of Schinzel-Giedion syndrome. Two patients died soon after birth, whereas the third one developed severe mental and motor retardation with seizures and spasticity, and died at 18 months. Schinzel-Giedion syndrome is rare and likely to be inherited as an autosomal recessive trait. So far, 13 well-documented cases have been reported allowing major and minor traits of the syndrome to be distinguished. Since no genetic marker is available, the prenatal diagnosis of Schinzel-Giedion syndrome relies on ultrasound examination, especially detection of renal abnormalities.

Ullrich's congenital atonic sclerotic muscular dystrophy. A case report.

A 5-year old girl with Ullrich's atonic-sclerotic muscular dystrophy is reported and 16 previously reported cases are reviewed. The clinical features, in particular proximal contractures, distal hyperextensibility, mild dysmorphism and hyperhidrosis, allow recognition of this subtype of congenital muscular dystrophy, which has no specific pathological characteristics. There is evidence in favour of an autosomal recessive mode of inheritance.

Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy.

IFN-alpha was detected in cerebrospinal fluid and/or sera from 7 of 8 patients with a progressive familial encephalopathy associated with calcifications of the basal ganglia and white matter alterations. The secretion of IFN-alpha was prolonged, as shown by its presence at different times between birth and 5 years, and was not associated with IFN-gamma. Virological investigations excluded various congenital infections. In only 2 patients, high levels of Epstein-Barr virus antibodies were observed, indicating the possibility of an abnormal response to viral infection rather than a congenital infection. Further investigations are required for characterization of the recessive autosomal trait of this syndrome and its relation to the IFN system.

Surgery of epilepsy associated with focal lesions in childhood.

OBJECT: Surgery in children with epilepsy is a new, evolving field. The important practical issues have been to define strategies for choosing the most suitable candidates and the type and optimal timing of epilepsy surgery. This study was undertaken to elucidate these points. METHODS: To identify the factors that correlated with outcome, the authors analyzed a series of 200 children (aged 1-15 years (mean 8.7 years) who underwent surgery between 1981 and 1996 at the Hôpital Necker-Enfants Malades. In 171 cases (85.5%) the epilepsy was medically refractory and was associated with focal cortical lesions. Surgery consisted of resection of the lesion without specifically attempting to identify and remove the "epileptogenic area. "In the group of children whose seizures were medically refractory, the mean follow-up period was 5.8 years. According to Engel's classification, 71.3% of these children became seizure free (Class 1a,) whereas 82% were in Class I. A multivariate statistical analysis revealed that among all the factors studied, the success of surgery in a patient in whom there was a good clinical/electroencephalogram/imaging correlation depended on the patient's having undergone a minimally traumatic operation, a complete resection of the lesion, and a short preoperative seizure duration. After the surgical control of epilepsy, behavior disorders were more improved (31% of all patients) than cognitive function (25%). The patient age at onset, duration and frequency of seizures, intractability of the disease to therapy, and seizure characteristics were correlated with cognitive, behavioral, and academic performance pre- and postoperatively. Multivariate statistical analysis revealed that cognitive dysfunction correlated highly with the duration of epilepsy prior to surgery, whereas behavioral disorders correlated more with seizure frequency. CONCLUSIONS: These data must be taken into account when selecting patients for surgical treatment and when deciding the timing of surgery. Early surgical intervention allows for optimum brain development.

Ischemic strokes in children.

Of 44 infants and children (neonates excluded) with ischemic strokes of arterial origin documented by CT scan and/or cerebral angiography, idiopathic strokes, occurring in 22 cases, accounted for half the total. Eight of these patients had basal ganglia and/or capsular infarcts without cortical involvement. The outcome in the idiopathic group was favorable: after an average follow-up duration of 48 months, no child had recurrence, two children developed secondary epilepsy, and only two were severely mentally retarded. However, residual dystonia and dyskinesia constituted an incapacitating handicap, having been observed in 14 children of the idiopathic group and in 18 of the whole series. It may be concluded from the present study that the long-term prognosis of ischemic strokes in children is excellent except for the risk of secondary evolutive dystonia in the absence of any detectable cause.

Leukoencephalopathy, megalencephaly, and mild clinical course. A recently individualized familial leukodystrophy. Report on five new cases.

Five children presented in the first months of life with progressive megalencephaly and leukodystrophy characterized by diffuse swelling of the white matter, cystic cavitations in frontal and temporal lobes, and a slow progressive course contrasting with the intensity of the leukodystrophic process. Four had epilepsy. Two were brothers and three had consanguineous parents. No metabolic defect was detected. The clinical and magnetic resonance imaging features are similar to those of patients previously reported. These five new cases add arguments to delineate a new type of leukodystrophy with megalencephaly in infancy and autosomal recessive inheritance.

Rett syndrome: clinical presentation and laboratory investigations in 12 further French patients.

Twelve French patients with the Rett syndrome collected since July 1982 are reported. They confirm the stereotyped clinical presentation of the syndrome which represented 22% of the whole progressive encephalopathies referred to our hospital in the same period and 55% of the progressive encephalopathies of unknown etiology. Metabolic investigations have been constantly negative.

New experience with Rett syndrome in France: the problem of atypical cases.

Thirty-five patients with typical Rett syndrome have been observed by the authors. Fourteen patients with behavioral features suggestive of RS but who lacked some of the diagnostic criteria are reported. They were divided into 3 groups: 1) abnormal development from birth, 2) acute post-epileptic onset, and 3) encephalopathy with a known etiology different from RS. These 14 patients included 3 boys. In none of these cases was there an obvious history of acquired, progressive deterioration. The latter is essential for the diagnosis of RS.

Rett syndrome: criteria for inclusion and exclusion.

In the absence of discriminatory laboratory tests for accurate diagnosis of the Rett syndrome, the authors have tried to give as precise clinical criteria as possible for use particularly for research purposes.

Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome.

We report 2 sisters with a degenerative neurological disorder presenting clinically as a leukodystrophy. CT scan and MRI demonstrated small symmetrical foci of necrosis in the substentia nigra and in the basal ganglia typical of Leigh syndrome and diffuse cerebral white matter abnormalities. In these patients a deficiency in complex II of the respiratory chain was demonstrated in isolated mitochondria from muscle, as well as in fibroblasts and lymphocytes.

Hemifacial spasm or subcortical epilepsy?

A child with Goldenhar's syndrome presented at about one week of age with stereotyped, repetitive paroxysmal episodes of hemifacial contraction, suggestive of partial seizures or hemifacial spasm. Later in life he also developed independent, permanent abnormal eye and chin movements identical in rhythm to those seen in myorhythmias, suggesting involvement of the dentato-olivary pathway. MRI demonstrated a hamartomatous lesion at the level of the pontomedullary junction. We speculate that the nature of the lesion could be responsible for the partial seizures mimicking hemifacial spasm and that because of its location, this same lesion could also be implicated in the genesis of myorhythmias. The presence of a hamartomatous lesion in a region affected by the abnormal development of the first and second branchial arches is not fortuitous.

[Dopa-sensitive dystonia]. / Dystonies dopa-sensibles.

Dopa-sensitive dystonia has been recognised for twenty years. It may occur in the first years of life. It first affects the lower limbs, then generalized becomes, as in torsion dystonia. Eight clinical cases are presented in five boys and three girls. The absence of the disorder in the parents, but its presence in siblings in three cases suggests that it might be recessively inherited. The symptoms are severe enough to cause major functional disability. In some cases, the intensity of the motor disorder varies during the days being, less pronounced in the morning or after a nap and more marked in the evening. Nonetheless, this feature is not constant and thus cannot be considered as an essential diagnostic criterion. Treatment with levodopa gives remarkable and durable results, but it must be continued indefinitely. Abnormal movements accompany an overdose but regress when the dosage is decreased. Unlike Parkinson's disease, it is not necessary to increase or fragment doses to avoid fluctuations in the efficacy of treatment during the day. On the contrary, after several years of the illness a decrease in daily dosage sometimes to a single dose is possible. Discontinuing treatment leads to reappearance of dystonia after two or three days. There are no established biological criteria to aid diagnosis. However, a decrease in urine levels of homovanillic acid was observed in two cases. Dopa-sensitive dystonia should be regarded as distinct from juvenile Parkinson's disease, firstly because of its symptomatology and secondly, and more importantly, because of its particular course, since fluctuations in therapeutic efficacy are never observed. It is the only known example of dopaminergic insufficiency that is chronically almost completely controlled by a modest exogenous supply of levodopa.

[GM2-Gangliosidosis variant B1 disclosed during adolescence by an isolated multi-systemic involvement of the central and peripheral nervous systems]. / Gangliosidose à GM2 variant B1. Révélation à l'adolescence par une atteinte isolée et plurisystématisée du système nerveux central et périphérique.

The authors report on a Portuguese family with 3 adult brothers affected with GM2-gangliosidosis (B1 variant) in a sibship of 4, and more specifically on one of these brothers with neurological onset at the age of 17. Psychosis, lower motoneuron involvement and dysarthria were predominant in two of the cases; the third had a cerebellar symptomatology. Hexosaminidase A activity, studied in leukocytes, was profoundly deficient when measured using the specific sulfated substrate, but nearly normal using a conventional assay (non-sulfated substrate). These results established the diagnosis of the unusual enzymological form of GM2-gangliosidosis known as the B1 variant, which had so far not been associated with an adult phenotype. Molecular studies are in progress to study genotype/phenotype correlations in this family in comparison with known mutations in the B1 variant and in adult GM2-gangliosidosis. This report also emphasizes that a metabolic etiology, leading to genetic counselling, should be considered in some familial degenerative neurological disorders.