Warwick J. Peacock

Surgery for intractable infantile spasms: neuroimaging perspectives.

Summary: Twenty‐three infants and children underwent cortical resection (n= 15) or hemispherectomy (n =8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow‐up (range 4–67 months; mean 28.3 months), 15 children were seizure‐free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.

Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy

Objective: Sodium-coupled transporters remove extracellular neurotransmitters and alterations in their function could enhance or suppress synaptic transmission and seizures. This study determined hippocampal gamma-aminobutyric acid (GABA) and glutamate transporter immunoreactivity (IR) in temporal lobe epilepsy (TLE) patients. Methods: Hippocampal sclerosis (HS) patients (n = 25) and non-HS cases (mass lesion and cryptogenic; n = 20) were compared with nonseizure autopsies (n = 8). Hippocampal sections were studied for neuron densities along with IR for glutamate decarboxylase (GAD; presynaptic GABA terminals), GABA transporter-1 (GAT-1; presynaptic GABA transporter), GAT-3 (astrocytic GABA transporter), excitatory amino acid transporter 3 (EAAT3; postsynaptic glutamate transporter), and EAAT2-1 (glial glutamate transporters). Results: Compared with autopsies, non-HS cases with similar neuron counts showed: 1) increased GAD IR gray values (GV) in the fascia dentata outer molecular layer (OML), hilus, and stratum radiatum; 2) increased GAT-1 OML GVs; 3) increased astrocytic GAT-3 GVs in the hilus and Ammon’s horn; and 4) no IR differences for EAAT3-1. HS patients with decreased neuron densities demonstrated: 1) increased OML and inner molecular layer GAD puncta; 2) decreased GAT-1 puncta relative to GAD in the stratum granulosum and pyramidale; 3) increased GAT-1 OML GVs; 4) decreased GAT-3 GVs; 5) increased EAAT3 IR on remaining granule cells and pyramids; 6) decreased glial EAAT2 GVs in the hilus and CA1 stratum radiatum associated with neuron loss; and 7) increased glial EAAT1 GVs in CA2/3 stratum radiatum. Conclusions: Hippocampal GABA and glutamate transporter IR differ in TLE patients compared with autopsies. These data support the hypothesis that excitatory and inhibitory neurotransmission and seizure susceptibility could be altered by neuronal and glial transporters in TLE patients.

Cerebral Palsy Spasticity. Selective Posterior Rhizotomy

We have performed selective posterior rhizotomies on 60 children with cerebral palsy. The procedure involves lumbar laminectomy with stimulation of the rootlets (fascicles) of the second lumbar to the first sacral posterior roots bilaterally; those rootlets associated with an abnormal motor response, as evidenced by sustained or diffused muscular contraction, are divided leaving intact rootlets associated with a brief localized contraction. The patients were between 20 months and 19 years of age representing all degrees of physical handicap and ranging from profoundly retarded to normal intelligence. Follow-up has been from 1 to 5 years. Each child was assessed pre- and postoperatively and graded in the following categories: muscle tone, power, sitting, standing, walking, upper limb function, and speech. The patients whose function improved most dramatically following rhizotomy were purely spastic and intelligent, were significantly more affected by spasticity in the lower than the upper limbs, had some degree of forward locomotion, and could side-sit independently. Patients with severe athetosis or marked contractures improved least.

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

Summary: Purpose: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long‐term seizure control.

Surgical treatment of intractable neonatal‐onset seizures The role of positron emission tomography

We have performed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) in eight infants and children (aged 18 days to 5 years) with medically refractory epilepsy of neonatal onset. It was hypothesized that in at least some of these infants a surgical approach (focal resection, cerebral hemispherectomy) might be of benefit in achieving seizure control, and that PET might assist in surgical selection. In three of the eight subjects, interictal PET revealed unilateral diffuse hypometabolism; following cerebral hemispherectomy in these three patients, all seizures ceased and there were no adverse effects. In one child, ictal PET showed hypermetabolism in the left frontal cortex, left striatum, and right cerebellum; a partial left cerebral hemispherectomy guided by intraoperative electrocorticography was performed, following which all seizures ceased. One infant had relative hypermetabolism in the right temporal and occipital lobes, right thalamus, and left frontal lobe on ictal PET, and EEG telemetry revealed a right occipitotemporal epileptic focus; this infant died from anesthetic complications following right occipitotemporal cortical resection. Of the three unoperated patients, one is a potential candidate for right frontal lobectomy, but the other two were not considered to be surgical candidates due to bilateral epileptogenicity. Neuropathologic correlation in our series revealed that PET is a sensitive test capable of detecting cytoarchitectural disturbances whereas CT and MRI failed in this regard. In addition, PET provides a very unique and important assessment of the functional integrity of brain regions outside the area of potential resection.

Children with severe epilepsy: evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation

Surgically resected hippocampi from children with extrahippocampal seizures and structurally non-atrophic brains were examined to determine the relationship of neuron losses and aberrant mossy fiber (MF) sprouting to the postnatal migration and differentiation of the fascia dentata (FD) granule cells (GC). Percent neuron loss compared to age-matched autopsy controls was determined by quantitative cell densities, and aberrant MF sprouting by neo-Timm histochemistry. Postnatal immature GC migration and differentiation was demonstrated by the transient but GC-specific expression of the immature form of neural cell adhesion molecule (NCAM-H). Results showed that the hippocampi from children with seizures appeared microanatomically intact without focal areas of damage. However, significant neuron losses were found by neuron counts in the fascia dentata (P < 0.01), CA4 (P < 0.01), and CA2 (P < 0.05). Aberrant supragranular inner molecular layer MF sprouting was found in hippocampi of children with seizures, and the MFs showed smaller puncta in specimens resected under 2 years of age (n = 3) compared to the larger puncta in older children (n = 5). Hippocampi from children under 2 years of age also demonstrated NCAM-H positive primitive cells in the infragranular and stratum granulosum of the fascia dentata consistent with the postnatal migration and differentiation of GCs, the parent neurons of the MFs. These results indicate that seizures in the immature but structurally intact human hippocampus are associated with decreased neuron densities and aberrant MF sprouting very early in postnatal development. The data also show that aberrant MF sprouting is found during postnatal migration, differentiation and axogenesis of GCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective posterior rhizotomy: a long-term follow-up study

Fifty-one spastic children who had undergone selective posterior lumbar rhizotomy between 1981 and 1984 were re-examined to determine whether the gains achieved had persisted and to look at other aspects that had not previously been explored in detail. The reduction of tone was maintained in all cases, while motor function continued to improve in 42 cases. Functional gains were greatest in children operated on under the age of 8, but pleasing results were also achieved in older children. Forty-five children continued to receive physiotherapy, particular attention being paid to building up muscle strength. Sensory disturbances were minimal, and there was no evidence of spinal instability. Post-rhizotomy orthopaedic surgery for fixed-joint contractures generally brought further improvement. Parents and older children were also questioned and almost all were enthusiastic about the outcome. Rhizotomy can be of considerable benefit to spastic children, but great care must be taken in the selection of suitable cases.

The surgical treatment of spasticity

Many neurosurgical procedures have been designed for or applied to the treatment of spasticity arising from different disorders, including cerebral palsy; traumatic, ischemic, or hypoxic brain injury, multiple sclerosis, and spinal cord injury. Neurosurgical procedures are primarily aimed at reducing spasticity by interrupting the stretch reflex at various sites along the spinal reflex arc or attempting to increase the centrally mediated inhibitory influence on the pool of motor neurons in the anterior horn. Surgical interventions for spasticity can be classified into peripheral ablative procedures, such as rhizotomy or peripheral neurectomy, and central ablative procedures, such as cordectomy, myelotomy, or stereotactic procedures. Non‐ablative procedures include peripheral nerve or motor point blocks, the implantation of cerebellar or spinal stimulators, and the implantation of subdural catheters for infusion of pharmacologic agents to increase inhibitory activity. Several proposed mechanisms for spasticity are reviewed so that the rationale for the various surgical interventions for spasticity described may be better understood.

ELECTROCORTICOGRAPHIC CONFIRMATION OF FOCAL POSITRON EMISSION TOMOGRAPHIC ABNORMALITIES IN CHILDREN WITH INTRACTABLE EPILEPSY

Summary: The relationship between focal disturbances of glucose utilization demonstrated by positron emission tomography (PET) and electrophysiologic abnormalities defined by intraoperative electrocorticography (ECoG) was studied in eight children (aged 13 months to 12 years) who underwent cortical resection because of intractable seizures. None of the children had pure temporal lobe epilepsy. Computed tomography (CT) and/or magnetic resonance imaging (MRI) were normal in four of the eight children. The scalp electroencephalogram (EEG) showed lateralized interictal epileptiform abnormalities in all eight and lateralized ictal onset in five of eight. In seven children, interictal PET showed focal hypometabolism; the eighth child had focal, ictal hypermetabolism. ECoG at the time of surgery showed epileptiform spiking, slowing, and/or suppression of normal background activity that in every case corresponded to the focus on PET scan. The ECoG findings support the notion that in children with epilepsy focal metabolic abnormalities on PET correspond to electrophysiologically abnormal areas of cortex, which are presumably also the epileptogenic regions. Such areas can appear normal on anatomic imaging studies (CT and MRI). When ictal scalp EEG data are ambiguous or contradictory, PET provides a less invasive means than chronic grid or depth electrode recording for evaluating whether a localized epileptogenic area exists.

Temporal and Extended Temporal Resections for the Treatment of Intractable Seizures in Early Childhood

In our series of 33 children who underwent temporal and extended temporal lobe resections because of seizures, the average age at surgery was 7 years, 11 months. Sixteen cases (48%) were diagnosed as having tumors: low-grade astrocytoma (6), hamartoma (5), and ganglioglioma/neuroma (5). Other pathologic diagnoses included one or more cytoarchitectural abnormalities and/or reactive changes. Due to a more aggressive and early radiologic and electrophysiologic investigation of children with seizures, a resectable focus, e.g. neoplasm or structural abnormality, was found in a much younger age group of patients than previously reported. In children who had intractable seizures but normal radiologic studies, positron emission tomography was of great value in localizing the seizure focus. In a group of children with infantile spasms, seizures were controlled following the identification and resection of a focal lesion. Prompt detection and precise localization of lesions in the temporal lobe in the pediatric population may lead to surgical management and seizure control.