Eleftherios E. Kontopoulos

Characteristics and prognosis of epilepsy in children with cerebral palsy.

The aims of the study were to describe the prevalence and characteristics of epilepsy in a population of patients with cerebral palsy in a university referral center and to determine the rate of relapse caused by discontinuation of antiepileptic drugs after a 3-year seizure-free period. A total of 178 consecutive patients with cerebral palsy and epilepsy were prospectively followed for 9.2 ± 2.4 years after onset of seizures and compared to a control group of 150 epileptic patients without cerebral palsy (median follow-up period, 10.5 years). The overall prevalence of epilepsy was 36.1%. Patients with atonic-diplegic, dystonic, tetraplegic, and hemiplegic cerebral palsy had a higher incidence of epilepsy (87.5%, 87.1%, 56.5%, and 42%, respectively). In all, 134 (75.3%) patients were seizure free for more than 3 years and could discontinue therapy, whereas 44 patients (24.7%) were still on antiepileptic drugs. Eighteen of 134 patients relapsed after a 3-year seizure-free period and subsequent discontinuation of antiepileptic drugs, thus giving a relapse rate of 13.4%. First seizures occurred during the first year of life in 69.7% of the patients with epilepsy and cerebral palsy. Complete control of seizures could be achieved in 65.2% of the patients with cerebral palsy and epilepsy; however, regardless of the prognosis of seizures, epilepsy was a major prognostic factor regarding both the presence of mental retardation and the motor development of children with cerebral palsy. (J Child Neurol 1999;14:289-294).

Neurophysiologic and intellectual evaluation of beta-thalassemia patients.

In order to detect involvement of the central and peripheral nervous system in beta-thalassemic patients, 32 children and young adults (mean age 14.5 +/- 6.4 years) participated in a systematic neurophysiologic and intellectual prospective study. All patients were in a regular transfusion program, receiving subcutaneous desferrioxamine chelation and maintaining a mean serum ferritin level of 2,101.56 +/- 986.32 ng/ml. Study patients underwent neurophysiologic evaluation consisting of brainstem auditory, visual and somatosensory evoked potential examination (BAEP, VEP, SEP) as well as motor and sensory nerve conduction velocity studies (MCV, SCV). Additionally, the verbal, performance and total IQ were assessed in patients under 16 years of age using the Weschler Intelligence Scale for Children (WISC-III). The incidence of abnormal BAEP, VEP, SEP and NCVs was 0, 3.12, 3.12 and 18.75%, respectively, findings comparative to or better than previously reported. On the contrary, the prevalence of abnormal total IQ score was considerably high (36.4%), not correlating, however, to any of the parameters assessed (age, sex, ferritin level, BAEP, VEP, SEP, NCV). Factors associated with chronic illness, rather than the disease per se, could play a potential role in the development of cognitive dysfunction in beta-thalassemia patients.

Serial MRI and neurophysiological studies in late-infantile Krabbe disease

We report serial clinical, radiological, and neurophysiological findings of a patient with late-infantile Krabbe disease. At age 13 months, the patient was hospitalized for sudden stiffness and irritability and a diagnosis of spastic diplegia was made. At age 24 months, he was readmitted because of further psychomotor deterioration; neurologically, he manifested severe spastic tetraplegia with optic atrophy. MRI disclosed diffuse high intensity in the cerebral white matter on T2-weighted images. Nerve conduction velocity and evoked potential studies were markedly abnormal, as were the EEG and the EMG. Assay of galactocerebroside beta-galactosidase activity in leukocyte culture disclosed a marked deficiency of the enzyme, confirmatory of the diagnosis of late-infantile Krabbe disease. Serial MRI and neurophysiological studies performed every 6 months for 18 months demonstrated the progressive nature of the disorder, correlating with the clinical deterioration.

Early infantile Krabbe disease: deceptively normal magnetic resonance imaging and serial neurophysiological studies

Early infantile Krabbe disease is a progressive neurodegenerative disease caused by deficiency of lysosomal enzyme galactocerebroside beta-galactosidase, with onset before the age of 6 months. We present serial clinical, radiological and neurophysiological findings of a patient with early infantile Krabbe disease, presenting at the third day of life with hypotonia, macrocephaly and neonatal seizures. The patient had a deceptively normal initial magnetic resonance imaging examination at the age of 3 months, with progression of the white matter disease over the following 9 months, showing a clinical picture of profound hypotonia with pyramidal and pseudobulbar signs, as well as mild optic atrophy. Assay of galactocerebroside beta-galactosidase activity in leukocyte culture disclosed a marked deficiency of the enzyme (0.00 nmol/mg protein per h with normal values > 0.7 nmol/mg protein per h), thus confirming the diagnosis of Krabbe disease. Nerve conduction velocity and evoked potential studies, as well as the electroencephalogram, were abnormal at the age of 6 months, while serial neurophysiological studies at the age of 12 and 18 months demonstrated the progressive nature of the disease.

Protracted course of N-acetylaspartic aciduria in two non-Jewish siblings: identical clinical and magnetic resonance imaging findings

Canavan disease (CD) or N-acetylaspartic aciduria (NAA) is a severe, progressive, autosomal recessive leukodystrophy, occurring mainly among Ashkenazi Jewish individuals. We report clinical and MRI findings in two, non-Jewish, Greek siblings, 7 and 5 years, respectively, with a protracted form of NAA. The constellation of identical clinical course and identical MRI findings with involvement of the basal ganglia, the brainstem, the dentate nucleus and the subcortical white matter in both siblings, as well as the absence of the three commonest mutations found in both Jewish and non-Jewish CD patients, give support to the existence of a protracted form of NAA with a milder clinical course, presumably genetically determined.

Neurophysiologic Evaluation of Long-Term Desferrioxamine Therapy in Beta-Thalassemia Patients

Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age and maintained on long-term desferrioxamine (DFO) treatment, were examined by evoked potential and nerve conduction velocity studies to investigate a possible involvement of the auditory, visual, somatosensory, or peripheral nervous pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory-evoked potentials, and nerve conduction velocity studies were demonstrated in 25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated involvement of multiple neural pathways. Subclinical involvement of the auditory pathway was statistically associated with higher mean daily DFO dose and longer duration of DFO therapy, whereas abnormalities regarding the somatosensory pathways were related to older age, longer mean duration of DFO therapy, and lower serum copper levels. Involvement of the peripheral nervous system was related to lower serum copper levels. Multiple involvement of neural pathways was related to longer mean duration of DFO therapy. We conclude that risk factors related to long-term DFO treatment are only partly responsible for the subclinical involvement of neural pathways demonstrated in beta-thalassemia major patients.

Neurophysiology and MRI in late-infantile metachromatic leukodystrophy

We present serial clinical, radiologic, and neurophysiologic findings of a patient with late-infantile metachromatic leukodystrophy who was first admitted at 30 months of age because of gait disturbance. The neurologic findings were consistent with mild spastic diplegia (occasionally with toe walking). Magnetic resonance imaging disclosed diffuse high intensity in the cerebral white matter on T2-weighted images. Nerve conduction velocity studies and evoked-potential studies were markedly abnormal. Assay of arylsulfatase A activity in leukocyte culture disclosed a marked deficiency of the enzyme, confirming the diagnosis of late-infantile metachromatic leukodystrophy. Serial neurophysiologic studies demonstrated a marked decrease of nerve conduction velocities, both motor and sensory, as well as prolongation or disappearance of brainstem auditory-, visual-, and somatosensory-evoked potential latencies. Magnetic resonance imaging studies revealed initially diffuse increased signal intensity of periventricular and subcortical white matter on T2-weighted images, progressing to cortical atrophy with involvement of the arcuate fibers and the cerebellar white matter, correlating with the clinical deterioration (severe spastic tetraplegia with optic atrophy and epilepsy).

Benign congenital hemifacial spasm

Hemifacial spasm (HFS) is characterized by involuntary, irregular contraction of the muscles innervated by one facial nerve. Usually, it is caused by facial nerve injury either due to microvascular compression or a posterior fossa tumor, but it also occurs without apparent cause. It is rare in children; no congenital cases have yet been reported. We report the first case of congenital HFS in a term newborn delivered by forceps after a normal labor. Multimodal evoked potentials, electroencephalogram, computed tomography of the petrous bone, as well as brain magnetic resonance imaging and angiography disclosed no abnormalities. Serial neurodevelopmental examinations and video recordings performed until 8 months of age documented a normal neurodevelopmental status and a tendency for spontaneous diminution of the HFS. An intrauterine facial nerve injury as the causative factor of HFS, being responsible for its benign course, is proposed.

Plantar Response Profile of High-Risk Infants at One Year of Life

To clarify the plantar reflex profile at 1 year of life in different categories of neurodevelopmental abnormalities, plantar responses were examined prospectively in 204 high-risk infants, of whom 58 developed cerebral palsy, 22 had developmental retardation without motor disturbance, and 124 were normal at a follow-up examination at 3 years of age. The plantar response was extensor in 82.3% of infants subsequently found to be neurologically normal at the first month of life, becoming flexor at the age of 9 and 11 months in 68.5% and 86.3%, respectively. Twenty-one (42.9%) of 49 patients with various types of spastic cerebral palsy demonstrated a combined extensor response (ie, dorsiflexion of the great toe with fanning of the remaining toes) as early as the first month of life. Children with spastic quadriplegia and hemiplegia more frequently demonstrated a combined extensor response compared to diplegic patients. The combined extensor plantar response remains a reliable prognostic clinical tool that contributes to an earlier diagnosis of spastic cerebral palsy as early as the first month of life. (J Child Neurol 1999;14:514-517).

Prospective study of ankle clonus at the first year of life

We read with great interest the article by Futagi et al. [ 1 ] about the prognosis of infants with ankle clonus within the first year of life. We would like to add our own experience in this field. As part of a prospective study regarding the prognostic significance of primitive reflex profiles in the early diagnosis of cerebral palsy (CP) [2], ankle clonus was prospectively examined in a series of 204 high-risk infants at 1, 3, 5, 7, 9 and 11 months of life. At follow-up at 3 years of age, 58 children developed CP (49 spastic CP, 7 athetoid CP and 2 ataxic CP), 22 had developmental retardation without motor disturbance (DR) and 124 children had a normal development. Ankle clonus was elicited using the same method as described by Futagi et al. [1] and was defined as present only when the reactivity was more than 10 beats. The results are summarized in Table 1. The presence of ankle clonus was significantly higher in children with spastic CP already from the third month of life (P < 0.001) compared to normal children. There was no significant difference at any age between athetoid and normal children regarding ankle clonus, while children with DR demonstrated a statistical significance (P < 0.05) compared to normal children, only at the first month of life. It is also worth mentioning that although 78 out of 124 normal children (62.9%) exhibited ankle clonus at the first month of life, it almost disappeared at the fifth month of life (4.5% of the children). The above results suggest that ankle clonus is often present in high-risk infants at the first year of life, especially at the first month. However, only its presence beyond the third month of life should be interpreted as a Table 1