The epileptogenic zone: general principles.
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Cerebral Cortex↗
Biomedical subjects
Dileep Nair
Publications and source records attributed to Dileep Nair.
Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord.
Peripherally conditioned sensory neurons have an increased capacity to regenerate their central processes. However, even conditioned axons struggle in the presence of a hostile CNS environment. We hypothesized that combining an aggressive conditioning strategy with modification of inhibitory reactive astroglial-associated extracellular matrix could enhance regeneration. We screened potential treatments using a model of the dorsal root entry zone (DREZ). In this assay, a gradient of inhibitory chondroitin sulfate proteoglycans (CSPGs) stimulates formation of dystrophic end bulbs on adult sensory axons, which mimics regeneration failure in vivo. Combining inflammation-induced preconditioning of dorsal root ganglia in vivo before harvest, with chondroitinase ABC (ChABC) digestion of proteoglycans in vitro allows for significant regeneration across a once potently inhibitory substrate. We then assessed regeneration through the DREZ after root crush in adult rats receiving the combination treatment, ChABC, or zymosan pretreatment alone or no treatment. Regeneration was never observed in untreated animals, and only minimal regeneration occurred in the ChABC- and zymosan-alone groups. However, remarkable regeneration was observed in a majority of animals that received the combination treatment. Regenerated fibers established functional synapses, as demonstrated electrophysiologically by the presence of an H-reflex. Two different postlesion treatment paradigms in which the timing of both zymosan and ChABC administration were varied after injury were ineffective in promoting regeneration. Therefore, zymosan pretreatment, but not posttreatment, of the sensory ganglia, combined with ChABC modification of CSPGs, resulted in robust and functional regeneration of sensory axons through the DREZ after root injury.
Animals↗
Mapping prosody: correlation of functional magnetic resonance imaging with intraoperative electrocorticography recordings in a patient with a right-sided temporooccipital glioma. Case illustration.
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Adult↗
Epileptogenicity of focal malformations due to abnormal cortical development: direct electrocorticographic-histopathologic correlations.
PURPOSE: Malformations due to abnormal cortical development (MCDs) are common pathologic substrates of medically intractable epilepsy. The in situ epileptogenicity of these lesions as well as its relation to histopathologic changes remains unknown. The purpose of this study was to correlate the cellular patterns of MCDs with the expression of focal cortical epileptogenicity as assessed by direct extraoperative electrocorticographic (ECoG) recordings by using subdural grids. METHODS: Fifteen patients with drug-resistant focal epilepsy due to pathologically confirmed MCD who underwent subdural electrode placement for extraoperative seizure localization and cortical mapping between 1997 and 2000 were included in the study. Areas of interictal spiking and ictal-onset patterns were identified and separated during surgery for further pathologic characterization (cellular and architectural). Three pathologic groups were identified: type I; architectural disorganization with/without giant neurons, type IIA; architectural disorganization with dysmorphic neurons, and type IIB; architectural disorganization, dysmorphic neurons, and balloon cells (BCs). The focal histopathologic subtypes of MCDs in cortical tissue resected were then retrospectively correlated with in situ extraoperative ECoG patterns. RESULTS: Cortical areas with histopathologic subtype IIA showed significantly higher numbers of slow repetitive spike pattern in comparison with histopathologic type I (p = 0.007) and normal pathology (p = 0.002). The ictal onset came mainly from cortical areas with histopathologic type IIA (nine of 15 patients). None of the seizures originated from neocortical areas that showed BC-containing MCD (type IIB). CONCLUSIONS: This study shows that areas containing BCs are less epileptogenic than are closely located dysplastic regions. These results suggest a possible protective effect of BCs or a severe disruption in the neuronal networks in BCs containing dysplastic lesions. Further studies are needed to elucidate the nature and the potential role(s) of balloon cells in MCD-induced epileptogenicity.
Adolescent↗
A novel technique for peripheral nerve repair.
OBJECTIVE: To evaluate a novel technique for the repair of neural deficits using a single fascicle to bridge an injury in the rat sciatic nerve. STUDY DESIGN: Twenty-four male Lewis rats were divided into four groups as follows: group 1 (control group), 1.5-cm deficit without repair; group 2, conventional epineural repair with autografts (100% diameter); group 3, nerve repair with large single autograft fascicle (50% diameter); and group 4, nerve repair with small single autograft fascicle (25% diameter). METHODS: Nerve regeneration was evaluated at 3, 6, and 12 weeks by somatosensory evoked potential (SSEP) evaluation and standardized pin-prick and toe-spread tests. Nerve samples were harvested at 12 weeks and stained with toluidine blue to assess the total number of myelinated axons, axon area, and myelin sheath thickness. RESULTS: In group I, the pin-prick and toe-spread tests showed no response at 3, 6, and 12 weeks. Rats in groups 3 and 4 demonstrated significantly better pin-prick test results and a trend toward better toe-spread test responses compared with conventional-repair animals. The SSEP evaluations displayed nondiagnostic waves in rats in group 1 rats. There was no evidence that the other surgery groups differed significantly in median SSEP latencies. Histological evaluation revealed fibrosis in rats in group 1 rats and a significantly higher median number of axons and myelin thickness in the small single fascicle (1296 axons and 4.22 microm, respectively) and large fascicle (2682 axons and 4.62 microm, respectively) groups compared with the conventional autograft group (630 axons and 2.93 microm, respectively). The small fascicle group had a significantly greater mean axon area (58.59 micro m2) than the large fascicle (29.66 micro m2) and conventional autograft (25.35 micro m2) groups. CONCLUSIONS: Peripheral nerve repair using a single fascicle graft resulted in better functional recovery and morphometric outcome without a significant difference in electrophysiological status compared with conventional nerve repair. This technique may provide expanded sources of nerve autografts and alleviate the morbidity of harvesting peripheral nerves from multiple sites for individuals with extensive peripheral nerve injuries.
Animals↗
EEG and evoked potential recording from the subthalamic nucleus for deep brain stimulation of intractable epilepsy.
OBJECTIVES: The substantia nigra in the animal model has been implicated in the control of epilepsy. The substantia nigra pars reticulata (SNpr) receives afferents from the subthalamic nucleus (STN), which thus may have an effect on the control of epilepsy. There is evidence in the animal model of a direct connection from the cortex to the STN. High-frequency STN stimulation is being used in experimental trial for the management of intractable epilepsy. Our primary objective in this study was to determine if there was epileptiform activity recorded from the STN in association with scalp recorded epileptiform activity to support the presence of a pathway from the cortex to the STN in humans as described in animals that may be important for the management of epilepsy. This article describes the interictal and ictal electroencephalographic (EEG) findings as well as evoked potential recordings from the STN in these patients with intractable epilepsy. METHODS: Four patients (3 males) ranging from 19 to 45 years with intractable focal epilepsy refractory to anti-epileptic drugs were studied. Two patients failed vagal nerve stimulation and one patient had previous epilepsy surgery. Depth electrodes were implanted stereotactically in the STN bilaterally. A comparative analysis of the interictal and ictal activities recorded from the scalp and STN electrodes was performed. Median nerve somatosensory evoked potentials (SEPs) and auditory evoked potentials (AEPs) were also recorded. RESULTS: Interictal sharp waves recorded in the scalp EEG were always negative in polarity. These sharp waves were always associated with sharp waves recorded at the ipsilateral STN electrode contacts that were always positive in polarity. In addition repetitive spikes were recorded independently at the left or right STN electrode contacts, with no reflection at the scalp. These spikes were extremely stereotyped, of high amplitude and short duration, and were positive or negative in polarity. Focal scalp EEG seizures were also recorded at the ipsilateral STN electrodes. In 3 patients SEPs were recorded from the contralateral STN electrodes corresponding to the P14/N18 far-field complex. In two patients AEPs were recorded, and wave V (near-field) and wave VII (far-field) from the contralateral STN electrodes. CONCLUSIONS: This study demonstrates that scalp recorded epileptiform activity is reflected at the ipsilateral STN either following or preceding the scalp sharp waves. The STN sharp waves are most probably an expression of the direct cortico-STN glutamatergic pathways that have been demonstrated previously in animals. This pathway in man may be important with regard to a possible mechanism for the treatment of epilepsy with STN stimulation.
Action Potentials↗
Focal cortical dysplasias in eloquent cortex: functional characteristics and correlation with MRI and histopathologic changes.
PURPOSE: Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features. METHODS: Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics. RESULTS: Language or motor areas were colocalized with epileptogenic regions (n=6 of 8, 75%), but were not mapped in regions of increased signal on fluid-attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n=5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells. CONCLUSIONS: We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.
Adolescent↗