Characteristics and surgical outcomes for medial temporal post-traumatic epilepsy.

A common post-traumatic location of epileptogenesis is the medial temporal lobe despite evidence of associated diffuse or remote cerebral injury. We undertook a review of post-traumatic medial temporal lobe epilepsy (MTLE) patients as part of an overall post-traumatic epilepsy population to assess the extent of cerebral injury sustained by this subpopulation and to establish whether surgical outcome differed from that of a non-traumatically-induced epilepsy population. A retrospective review of 57 patients operated for post-traumatic epilepsy (PTE) over a 10-year period (1993-2003) was undertaken with particular attention to those undergoing medial temporal resection. Preoperative magnetic resonance imaging (MRI) was assessed for the type and location of abnormalities. Postoperative outcomes were compared with those of patients with MTLE of non-traumatic origin operated by the same surgeon. Of the 57 patients operated, 30 cases underwent medial temporal lobe resection. The most common mechanism of injury was blunt trauma attributable to motor vehicle accidents with imaging abnormalities characterized by medial temporal sclerosis (MTS; 16 cases), T2/FLAIR hyperintensities (nine cases), periventricular gliosis (seven cases), diffuse cerebral atrophy (five cases) and focal encephalomalacia (three cases). Six patients had normal MRI studies. No significant differences in postoperative outcomes were found between post- and non-traumatic MTLE epilepsy groups. The presence of histopathological change in the medial temporal lobe varied greatly and provided no indication of a favourable postoperative outcome. Patients with post-traumatic medial temporal lobe epilepsy respond favourably to surgical treatment. In the case of medial temporal sclerosis, there is substantial variation of histopathological findings which correlate poorly with current imaging applications. The favourable outcomes obtained following surgery in this group attest to a commonality with other risk factors in the genesis of epilepsy in this location.

Auditory cortex stimulation for tinnitus.

Functional imaging techniques have demonstrated a relationship between the intensity of tinnitus and the degree of reorganization of the primary auditory cortex. Studies in experimental animals and humans have revealed that tinnitus is associated with a synchronized hyperactivity in the auditory cortex and proposed that the underlying pathophysiological mechanism is thalamocortical dysrhythmia; hence, decreased auditory stimulation results in decreased firing rate, and decreased lateral inhibition. Consequently, the surrounding brain area becomes hyperactive, firing at gamma band rates; this is considered a necessary precondition of auditory consciousness, and also tinnitus. Synchronization of the gamma band activity could possibly induce a topographical reorganization based on Hebbian mechanisms. Therefore, it seems logical to try to suppress tinnitus by modifying the tinnitus-related auditory cortex reorganization and hyperactivity. This can be achieved using neuronavigation-guided transcranial magnetic stimulation (TMS), which is capable of modulating cortical activity. If TMS is capable of suppressing tinnitus, the effect should be maintained by implanting electrodes over the area of electrophysiological signal abnormality on the auditory cortex. The results in the first patients treated by auditory cortex stimulation demonstrate a statistically significant tinnitus suppression in cases of unilateral pure tone tinnitus without suppression of white or narrow band noise. Hence, auditory cortex stimulation could become a physiologically guided treatment for a selected category of patients with severe tinnitus.

Enhanced excitability induced by ionizing radiation in the kindled rat.

Evidence derived from both clinical and experimental investigations has suggested an influence of ionizing radiation on focal epileptogenicity. To better characterize this influence we applied focal ionizing radiation to a kindled epileptic focus in the rat amygdala. The right and left basolateral amygdala and right frontal cortex were implanted with concentric bipolar electrodes. Rats were kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold electrostimulation of the left amygdala, after which generalized seizure thresholds were determined prior to irradiation. The left amygdala was exposed to single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months. We observed no significant changes in seizure threshold during the postirradiation interval; however, we did observe persistent changes in seizure dynamics manifesting within the first week postirradiation. These consisted of an increased tendency for seizure activity to propagate into brain stem circuits during the primary ictus (i.e., "running fits") and an increased tendency for secondary convulsions to emerge postictally. These effects involving seizure dynamics have not been reported previously and appear to represent a radiation-induced disinhibition of one or more neural circuits. The disparity between these effects and earlier reports of seizure-suppressive effects resulting from analogous radiation exposures is discussed in relation to kindling and status epilepticus-induced pathogenesis within the hippocampus.

Transient hemifacial sensory loss with xerophthalmia following temporal lobectomy.

OBJECTIVE AND IMPORTANCE: The occurrence of a unilateral sensory loss in the second trigeminal distribution and the inability to tear following an ipsilateral temporal lobectomy has not been noted despite a number of reports of cranial nerve compromise under similar situations. CLINICAL PRESENTATION: A 48-year-old woman experienced complex partial seizures over three years attributable to the presence of cavernous malformations of the right temporal lobe. INTERVENTION: An anterior temporal extrahippocampal resection was performed. The surgery was marked by the need for electrocoagulation of the dural base of the temporal lobe where numerous bleeding points were encountered. Postoperatively, the patient experienced an ipsilateral maxillary division sensory loss, absence of tearing, and diminished nasal congestion for an eight-month period until resolution. CONCLUSION: Injury of the fibers of the maxillary division of the trigeminal nerve and the adjacent greater superficial petrosal nerve appears to be the cause. No prior account of such an occurrence has been published.

Effects of vagus nerve stimulation on progressive myoclonus epilepsy of Unverricht-Lundborg type.

PURPOSE: A 34-year-old woman with progressive myoclonus epilepsy of Unverricht-Lundborg type was considered for vagus nerve stimulation (VNS) therapy. METHODS: After demonstration of intractability to multiple antiepileptic regimens and progressive deterioration in cerebellar function, the patient was implanted with a vagus nerve stimulator and followed for 1 year. Neurological status, seizure frequency, and parameter changes were analyzed. RESULTS: VNS therapy resulted in reduction of seizures (more than 90%) and a significant improvement in cerebellar function demonstrated on neurological examination. The patient reported improved quality of life based in part on her ability to perform activities of daily living. CONCLUSIONS: VNS therapy may be considered a treatment option for progressive myoclonus epilepsy. The effects of VNS on seizure control and cerebellar dysfunction may provide clues to the underlying mechanism(s) of action.

A direct brain interface based on event-related potentials.

Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERP's. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.

Ictal spiking patterns recorded from temporal depth electrodes predict good outcome after anterior temporal lobectomy.

PURPOSE: Investigators have shown that the presence of ictal spiking (IS) recorded from temporal depth electrodes is associated with mesial temporal sclerosis (MTS). We investigated the relation of IS to seizure control and pathology after anterior temporal lobectomy (ATL). METHODS: All patients undergoing intracranial ictal monitoring from a single institution since 1989 were identified. Those who did not undergo ATL or had postoperative follow-up of <1 year were excluded. All received at a minimum bilateral temporal depth electrodes. Ictal recordings were reviewed for the presence of IS, and the proportion of seizures with IS was determined for each patient. Outcome was determined by using Engel's classification. Surgical specimens were reviewed for pathology. Statistics used were chi2, Fisher exact test, and Wilcoxon rank sum. RESULTS: Forty patients with 571 seizures were reviewed. In 292 seizures from 32 patients, IS was seen. Outcomes were 24 class I (22 with IS), five class II (four with IS), three class III (one with IS), seven class IV (four with IS), and one lost to follow-up (with IS). Pathologic review revealed 25 with MTS, 22 of whom had IS. The presence of IS was associated with class I outcomes (p = 0.04), but not MTS (p = 0.06). Patients with class I outcomes had a significantly greater proportion of seizures with IS (mean, 0.58 +/- 0.3) compared with other outcomes (mean, 0.30 +/- 0.3, p = 0.02). CONCLUSIONS: The presence of IS and higher proportion of seizures with IS correlated with good seizure outcome after ATL. This information may be used in preoperative counseling.

Detection of event-related potentials for development of a direct brain interface.

The study presented here is part of an ongoing effort to develop a direct brain interface based on detection of event-related potentials (ERPs). In a study presented in a companion article, averaged ERP templates were identified from electrocorticograms recorded during repetition of voluntary motor actions. Here the authors report on the detection of individual motor ERPs within the electrocorticogram using cross-correlation. An averaged ERP template was created from the first half of each electrocorticogram and then cross-correlated with the continuous electrocorticogram from the second half. Points where the cross-correlation value exceeded an experimentally determined detection threshold were considered to be detection points. A detection point was considered to be a valid "hit" if it occurred between 1 second before and 0.25 second after the recorded time of a voluntary action. The difference between the hit and false-positive percentages (HF-difference) was used as a metric of detection accuracy. HF-differences greater than 90 were found for 5 of 15 subjects, HF-differences greater than 75 were found for 8 of 15 subjects, and HF-differences greater than 50 were found for 12 of 15 subjects. The three other subjects with HF-differences less than 50 had electrode locations not well suited for recording movement-related ERPs. Recordings from sensorimotor and supplementary motor areas produced the highest yield of channels with HF-difference greater than 50; however, a number of channels with good performance were found in other areas as well. The results demonstrate the likely prospect of using ERP detection as the basis of a single-switch direct brain interface and that furthermore, there is a good possibility of obtaining multiple control channels using this approach.

Morbidity and infection in combined subdural grid and strip electrode investigation for intractable epilepsy.

The coverage of large surface areas of the brain for electrographic monitoring purposes necessitates a craniotomy to achieve comprehensive sampling. We undertook a review and prospective analysis over 3 years of 38 patients undergoing craniotomy for electrode implantation. The indication for invasive monitoring was to determine candidacy for resective surgery in patients whose seizure focus was not well localized by scalp electroencephalography and other noninvasive testing. Prophylactic cultures from the epidural space were obtained at electrode removal. There were five positive epidural cultures. All five patients went on to seizure-free status. Two positive cultures occurred in patients without obvious infection and who were not treated with antibiotics. Other complications included individual cases of atrial fibrillation, pulmonary edema, postoperative fever, and epidural hematoma. There was no mortality or permanent neurologic morbidity related to craniotomy for electrode placement. There was a 7.9% rate of clinical infection per patient and a 5.7% rate per craniotomy side. This study has identified several factors that significantly correlate with positive epidural culture results: > 100 electrodes, more than ten cables, more than 14 days of implantation, and more than one cable exit site.

Developing an effective program to complete ictal SPECT in the epilepsy monitoring unit.

With the availability of more stable radiopharmaceuticals, the ictal single photon emission computed tomography (SPECT) perfusion study has emerged as a useful noninvasive functional neuroimaging tool in the presurgical evaluation of patients with medically intractable partial epilepsy. The purpose of this study was to determine whether the development of a program using trained electroencephalography (EEG) technologists to perform ictal injections in the epilepsy monitoring unit enabled a more efficient delivery of radiopharmaceuticals and therefore a higher specificity and sensitivity of outcome. All patients admitted to the epilepsy monitoring unit for prolonged video/EEG monitoring as part of the presurgical evaluation were eligible for completion of an ictal SPECT study using a three-way needle-free apparatus. Over a 19-month period, 85 (77%)) of 110 eligible patients were successfully injected during typical partial seizures. Various factors were analyzed including latency of ictal injection (27.3+/-20.8 [S.D.] s), radiopharmaceutical wastage (40% dose utilization), radiation safety parameters (1.6% contamination rate), and preliminary data of localizing value. Our results show that ictal SPECT can be a safe, noninvasive procedure completed on a routine basis in the epilepsy monitoring unit when appropriately trained support staff are utilized as part of a structured multidisciplinary program.

Test-retest stability and short-term habituation of the N1 and gamma band response.

The gamma band response (GBR) is an exogenous, cortically generated, event-related potential that occurs between 20- and 170-msec post-stimulus onset. The auditory GBR is superimposed on the transient evoked middle and long latency cortical auditory evoked potentials and demonstrates a peak spectral frequency between 30 and 40 Hz. The present investigations were conducted to evaluate the test-retest stability and short-term habituation of the GBR. Both the GBR and N1 were recorded from six normal-hearing, neurologically intact subjects (Investigation 1, test-retest stability) and two subjects with intractable epilepsy with implanted subdural electrode grid arrays (Investigation 2, short-term habituation characteristics). For Investigation 1, the test-retest interval was 1 month. For Investigation 2, 300 samples were acquired per stimulus block (a 10-minute interval) and then subaveraged in blocks of 25 to 50 samples each. Results suggest that (1) like N1, the GBR shows high repeatability (qualitative) and test-retest stability (quantitative) and (2) the GBR does not demonstrate evidence of short-term habituation.

SPARC: a signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas.

In an attempt to identify genetic alterations occurring early in astrocytoma progression, we performed subtractive hybridization between astrocytoma and glioblastoma cDNA libraries. We identified secreted protein acidic and rich in cysteine (SPARC), a protein implicated in cell-matrix interactions, as a gene overexpressed early in progression. Northern blot and immunohistochemical analyses indicated that transcript and protein were both elevated in all tumor specimens (grades II-IV) examined when compared with levels in normal brain. The level of SPARC expression was found to be tumor-dependent rather than grade-related. Immunohistochemically, SPARC protein was found to be overexpressed in 1) cells in the less cellularly dense regions within the tumor mass, 2) histomorphologically neoplastic-looking cells in adjacent normal brain at the tumor/brain interface, 3) neovessel endothelial cells in both the tumor and adjacent normal brain, and 4) reactive astrocytes in normal brain adjacent to tumor. Using a combination of DNA in situ hybridization and protein immunohistochemical analyses of the human/rat xenograft, SPARC expression was observed in the human glioma cells within the tumor mass, and in cells that invaded along vascular basement membranes and individually into the rat brain parenchyma, suggesting it may be an invasion-related gene. While it remains to be determined whether SPARC functionally contributes to tumor cell invasion, these data suggest that the early onset of increased SPARC expression, though complex, may serve as a signal indicative of neoplastic astrocytic transformation and reactive response to tumor-induced stress.

Surgical treatment of intractable epilepsy attributable to multiple sclerosis.

Surgically removing a focus of epileptogenicity attributable to a multiple sclerosis (MS) plaque has not previously been considered a treatment option. Medically intractable partial epilepsy due to a chronically situated MS plaque is uncommon because most cases are self-limiting or managed with antiepileptic medication. We report a case of partial epilepsy resulting from such a plaque situated at the gray-white interface in the anterior parahippocampal gyrus. A favorable outcome was achieved by resection of the epileptogenic area.

High resolution recording of late cortical surface potentials N1 and gamma band response (GBR).

The present investigation was conducted to help determine whether source activity of the direct recorded N1 response differed from that of the gamma band response (GBR). Auditory evoked cortical potential data from two patients with intractable epilepsy undergoing prolonged video EEG monitoring after implantation of subdural electrodes is reported in this investigation. Evoked responses were recorded to 1000-Hz tone bursts. The data were then filtered digitally to resolve the GBR. The voltage fields were subsequently viewed topographically. Although both responses originated in the supratemporal cortex, the N1 and GBR voltage field patterns differed. These results are consistent with the view that the sources of N1 and the GBR are different, suggesting that these components emanate from functionally distinct neuronal pools.

Temporal profile of connexin 43 mRNA expression in a tetanus toxin-induced seizure disorder.

The messenger ribonucleic acid (mRNA) of gap junction protein connexin 43 was quantified in the tetanus toxin rat model of focal epilepsy following injection of toxin into the left amygdala. Animals were monitored electrographically at weekly intervals with bilateral amygdala electrodes. Cohorts of 3 rats were sacrificed at weeks 1, 2, 3, 4, 6, 8, and 10, and bilateral regions containing the amygdala and posterior cerebral cortex were sampled, frozen, and later pooled for northern blot analysis. Spike generation was manifest in all animals during the first 4 wk followed by variable attenuation and cessation by 10 wk. Electrode implantation alone was shown by regression analysis to cause significant (p < 0.05) elevation of connexin mRNA in weeks 1-4. Injection of toxin diminished connexin mRNA expression in the amygdala when compared to electrode implantation alone. No trend in connexin mRNA expression was established over time in either amygdala or cerebral cortex in the acute epileptic or chronic postepileptic phase. No association between connexin 43 mRNA expression and the development of epileptogenicity was found in the context of a self-limiting animal model of focal epilepsy.

Hippocampal connexin 43 expression in human complex partial seizure disorder.

An increase in the cellular production of gap junction proteins and increased numbers of gap junctions in the neuronoglial syncytium of an epileptic focus have been proposed as a possible mechanism underlying synchronization of discharge. To study this issue, both Northern and Western blot analyses of the gap junction protein connexin 43 mRNA and protein abundance were performed on hippocampal tissue resected from patients presenting with a complex partial seizure disorder arising from the medial temporal area and the hippocampus in particular. Samples from 15 patients with medically intractable seizures were compared to those from 5 nonepileptic patients requiring temporal lobectomy in life-threatening situations. Six of the 15 epileptic patients underwent noninvasive electrographic recording, whereas the remaining 9 patients required intracerebral electrodes for extraoperative recording and therefore showed a more discrete focality than the noninvasive recordings. A decline in the mean levels of connexin 43 mRNA expressed predominantly in astrocytes was noted in the epileptic patient groups, particularly for those cases requiring intracranial electrode placement where ictal onset was more clearly established to be intrahippocampal. Quantitation of connexin 43 protein in both epileptogenic and nonepileptogenic hippocampal tissues showed no significant differences in expression. Although mean values for mRNA showed a decline, clinical outcomes postoperatively showed no correlation with either mRNA or protein expression individually in our epileptic population. The findings indicate that there is effectively no upregulation of mRNA and no increased production of connexin 43 protein in response to the development of epileptogenicity. Rather it appears the influence of gap junctions as a substrate of epileptogenicity in any mechanism(s) underlying synchrony or electrical propagation may be a function of the dynamic state (open versus closed) of the membrane-bound gap junction.

Connexin 43 mRNA expression in two experimental models of epilepsy.

The expression of mRNA for connexin 43, a gap junction protein putatively found in astrocytes, is studied in two experimental models of epilepsy: the electrically kindled rat and the tetanus-toxin-injected rat. Rats were kindled by electrical stimulation of the amygdala to Racine class 5 seizures and divided into cohorts of three to undergo 3, 6, or 10 such events, respectively. Another two cohorts of rats received injections of tetanus toxin at strengths of 3 and 9 MLD50, respectively, into the amygdala. Features of epileptogenicity were identified electrographically in both cohorts during the first 4 wk following toxin injection with spontaneous ictal events recorded in the latter cohort. All rats were sacrificed 4 wk after electrode or cannula implantation, except for two toxin-injected cohorts that were sacrificed at wk 8 or 10. The epileptogeonic area in the region of the amygdala was harvested and pooled by cohort for Northern blot analysis. These were compared with control nonimplanted tissues. In the tetanus-toxin-injected animals, at time-points of 4, 8, and 10 wk, connexin 43 mRNA expression in epileptogenic tissues is found to be decreased or unchanged relative to control cases. Kindled rats demonstrated reductions of connexin mRNA with a trend toward normalizing levels with increasing numbers of stimulations when compared to control animals. Connexin 43 immunostained sections of the basolateral amygdala showed a similar trend in protein expression. Both experimental models of epilepsy show no connexin 43 mRNA upregulation despite varying degrees of epileptogenicity. This study therefore does not support the hypothesis that an increase in transcription is the basis for any proposed increase in gap junction communication involving connexin 43 in the context of epileptogenicity or as a reaction to increased neuronal excitability.

Hodgkin's disease of the orbit with intracranial extension.

A rare presentation of intraorbital Hodgkin's lymphoma in a patient without prior history of systemic disease who complained of episodic monocular visual loss with minimal proptosis is reviewed. The case is further distinguished by intracranial extension of the tumor. A literature review highlights such an unusual event against the background of prior experience. Despite the fact Hodgkin's disease accounts for about 30% of systemic lymphomas, it rarely occurs in the orbit, where non-Hodgkin's lymphomas account for practically all lymphomas studied. Hodgkin's disease has occurred in patients with known systemic disease in its terminal stages and usually with proptosis as the presenting symptom. We present the case of a young man with intraorbital Hodgkin's disease whose presenting symptom was recurrent transient episodes of complete monocular visual loss. His condition was further distinguished by seeding of the skull base and dura by tumor.

Effect of ionizing radiation on partial seizures attributable to malignant cerebral tumors.

Empirical evidence in the clinical literature suggests that ionizing radiation influences human epileptic behavior. A group of patients with tumor-associated epilepsy, biopsy-proven malignancy, and primary antineoplastic treatment with ionizing radiation was selected to evaluate this observation. The antiepileptic effect of ionizing radiation was examined in 9 patients presenting with malignant cerebral tumor and medically refractory partial seizures during at least 2 months. Tissue diagnosis was obtained by stereotactic biopsy without further surgery. Histological categories included anaplastic astrocytoma (5 cases), glioblastoma (2), lymphoma (1), and metastatic non-small cell carcinoma of the lung (1). All patients had medically refractory simple partial seizures with or without secondary generalization with frequencies of 3/week to 8/day for 2-7 months before completion of therapy. Fractionated radiation therapy by parallel opposed fields was delivered with a cumulative dose range of 3,000-6,600 cGy. One patient also had 125I brachytherapy with implant removal after 6 months. Five patients had a seizure-free outcome for periods lasting 2-12 months, whereas the remainder experienced a reduction in frequency of greater than 75% during a follow-up period of 3 months to 6 years. One patient with a glioblastoma remained seizure-free for 3 months and experienced 2 generalized seizures during tumor progression and clinical deterioration but otherwise remained under good anticonvulsant control until his death after 1 year. This review of cases of partial seizures attributable to an unresected malignant cerebral tumor indicates that ionizing radiation may have a favorable effect upon medically refractory partial seizures with significant reduction or elimination of seizures. Moreover, the effect lasts beyond the immediate and early postradiation period. The therapy may thus also lessen the propensity for cerebral tissue towards later epileptogenicity that gives rise to a partial seizure disorder.

Size estimation and magnification error in radiographic imaging: implications for classification of arteriovenous malformations.

PURPOSE: To assess magnification error in digital subtraction angiography as it pertains to arteriovenous malformation (AVM) size. METHODS: A rectangular grid phantom with equally spaced markers mounted in a stereotactic frame was imaged with digital angiographic equipment. The location and orientation of the grid was altered relative to the central plane of the phantom. Both linear and area measurements were made according to the perceived location of phantom markers using a standard catheter calibration technique and compared with stereotactically derived estimates. Finally, a single case example of an angiographically imaged rolandic AVM was used to compare linear dimensions obtained with both described techniques. RESULTS: The determination of location and size with standard angiographic imaging is subject to error because of the divergent geometry of the incident x-ray beam. The resulting nonconstant geometric magnification causes errors in linear measurements of 10% to 13% at depths of 7 cm from the calibration plane. Errors in area measurements at the same position increase by 20% to 25%. Measurements of maximum diameter or cross-sectional area may have an additional error when nonspherical objects are inclined to the viewing direction (40% at 45 degrees inclination). These errors are reduced to less than 1 mm using the stereotactic technique. Some commercial angiographic systems have internal software to enable a spatial calibration based on known distances in the image or on the diameter of a catheter. The catheter technique was accurate in the calibration direction (perpendicular to the catheter axis) but had a 12% error in the direction parallel to the catheter because of a nonunity aspect ratio in the video system. Measurement of the dimensions of a rolandic AVM using the catheter calibration technique had an error that ranged from -3% to +26% (standard error, 20%) with respect to the stereotactic technique. CONCLUSIONS: Numerous nonstereotactic referential systems for determining linear distances are inherently erroneous by varying degrees compared with the stereotactic technique. Area and volume determinations naturally increase this error further. To the extent that no standardized method for determining linear distances exists, significant variations in estimation of AVM size result. Classification schemes for AVMs have been hampered by this technical error.