Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n = 16), non-HS (n = 10), and autopsy hippocampi (n = 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.

Foot contact pattern following selective dorsal rhizotomy.

Fourteen ambulatory patients with spastic cerebral palsy were evaluated prior to and 6 months following selective dorsal rhizotomy. An instrumented gait analysis identified significant improvements in foot contact patterns, velocity and stride length. The high incidence of postoperative valgus, excessive dorsiflexion and persistent knee flexion during gait was attributed to significant weakness and hypotonicity in the plantar flexors, as well as residual hamstring spasticity (p < 0.05). Sectioning of fewer S-1 rootlets may preserve plantar flexion strength and enhance stance stability by preventing postoperative increases in dorsiflexion and knee flexion. Orthotic prescription for ankle instability should be a routine postoperative consideration.

Postmortem changes in the levels and localization of microtubule-associated proteins (tau, MAP2 and MAP1B) in the rat and human hippocampus.

The neuronal cytoskeleton is disrupted in neurodegenerative disorders such as Alzheimer's disease. Due to the lack of suitable animal models, studies examining the events involved in the neurodegeneration have relied on postmortem human brain tissue obtained from individuals with the disease and from normal controls. However, it is uncertain if the neuronal cytoskeleton is stable during the postmortem interval. Immunohistochemistry and immunoblots were used to examine the microtubule-associated proteins tau, MAP2, and MAP1B in the rat hippocampus at various times after death. Shortly after death, tau immunoreactivity was lost from axons and accumulated in somatodendritic compartments. MAP2 and MAP1B also accumulated in neuronal cell bodies prior to a loss of immunostaining in some regions, notably subiculum. Immunoblots confirmed a loss of MAP2 and MAP1B within a few hours after death. Tau levels remained constant during the 8-hour postmortem interval examined, although the electrophoretic mobility of some tau bands was altered. Human brain tissue obtained at autopsy and at surgery demonstrated similar cytoskeletal alterations in postmortem tissue. These results demonstrate that microtubules and associated proteins are not stable postmortem.

Instrumented gait analysis after selective dorsal rhizotomy.

In an attempt to assess quantitatively the effects of selective dorsal rhizotomy on ambulatory patients with cerebral palsy, instrumental gait analysis was used to document and compare changes following surgery. Stride characteristics, dynamic surface electromyography, foot-floor contact patterns and motion of the thigh, knee and ankle were analysed. 14 patients (seven independent ambulators, seven using assistive devices) aged between 4.6 and 23.5 years were tested before surgery and again six to 14 months later. After surgery, the seven independent walkers retained the same level of function and one of the assisted walkers had progressed to independent walking, but the other six still used the same device as before surgery. Selective dorsal rhizotomy reduces spasticity and improves gait dynamics, but does not change patterns of muscle activation during walking.

Altered distribution of excitatory amino acid receptors in temporal lobe epilepsy.

In temporal lobe epilepsy, excitatory amino acid receptors in the hippocampus and temporal lobe may contribute to both increased excitability and vulnerability to excitotoxic damage. We used receptor autoradiography to examine the density of N-methyl-D-aspartate (NMDA) and kainic acid (KA) receptors in the hippocampus and parahippocampal gyrus obtained from five patients who had undergone anterior temporal lobectomy for the treatment of intractable seizures and from six control individuals, in which the hippocampus was obtained postmortem. Within the hippocampal formation, loss of [3H]KA and NMDA-sensitive L-[3H]glutamate binding was apparent in the sclerotic regions CA3, hilus, and CA1. In the subiculum and molecular layer of the denate gyrus, binding densities were maintained or even increased in some of the epileptic patients. A two-fold increase in L-[3H]glutamate binding, along with an increase in [3H]KA binding, was observed in the parahippocampal gyrus obtained from the epileptic patients. The results suggest that the vulnerability of the hippocampus in temporal lobe epilepsy may result, at least in part, from the presence of aberrant excitatory circuits in the parahippocampal gyrus.

Excitotoxic amino acid receptors in human complex partial epilepsy.

It has long been recognized that mesial temporal sclerosis is the most common pathologic finding in temporal lobes removed for the treatment of medically refractory complex partial epilepsy. The regions of the hippocampus most vulnerable contain the highest densities of excitatory amino acid receptors in the brain. We used receptor autoradiography to determine the density of N-methyl-D-aspartate (NMDA) and kainic acid (KA) receptors from 5 patients undergoing such surgery and compared the findings with 6 specimens obtained at postmortem. A 2-fold increase in the density of NMDA receptors and an increased density of KA receptors was found in entorhinal cortex in epileptic specimens. Loss of NMDA and KA receptor density was apparent in the sclerotic regions CA3 and CA1, but not in other areas of the hippocampus or dentate gyrus. These findings suggest that damage in the hippocampus may result, at least in part, from the presence of aberrant excitatory circuits in the entorhinal cortex.

Focal functional anatomy of dorsolateral frontocentral seizures.

We compared 6 patients with dorsolateral frontocentral seizures to 7 patients with temporal lobe seizures. We determined general seizure location by structural lesions in 7 patients, bilateral depth electrodes in 4, and EEG and semiology in 2. We then mapped seizure cortex and essential cortex using chronic ECoG arrays. Two ECoG patterns were similar in frontal and temporal seizures. Focal patterns were near lesions and resections. Regional patterns were distant from lesions but not associated with worse surgical outcome. "Dipolar" seizure patterns occurred in one-half of frontal patients with maps like somatosensory evoked responses, consistent with focal seizure anatomy and involvement of sensorimotor cortex. Dipole location estimates were near centers of seizure cortex determined by lesions, semiology, and outcome. Six temporal patients had focal excisions that gave significant seizure reduction in all. All frontocentral patients had focal excisions that significantly reduced seizures except in 1 patient with progressive disease. We conclude that dorsolateral frontocentral seizures have focal functional anatomy that can be predicted by ictal ECoG.

Transluminal angioplasty for treatment of intracranial arterial vasospasm.

Percutaneous transluminal angioplasty for treatment of intracerebral arterial vasospasm is now being performed in selected cases. Thirty-six vascular territories in 13 patients, ranging in age from 15 to 73 years, have been treated with a new silicone microballoon device. This balloon has allowed mechanical dilatation of segmental and diffuse areas of spastic intracerebral blood vessels less than 1 mm in diameter with return to normal luminal diameter. Follow-up angiography has documented improved cerebral perfusion without return of spasm. In 10 patients (77%), vasospasm was due to subarachnoid hemorrhage following rupture of an intracranial aneurysm. In three patients (23%), spasm with resultant neurological decline occurred during detachable balloon embolization therapy for treatment of an aneurysm. In each case, the vessel caliber returned to normal size following balloon dilatation. In nine (69%) of the 13 cases, balloon dilatation resulted in improvement of neurological function within minutes to hours following the procedure. Transluminal angioplasty techniques may offer an alternative form of therapy in the management of symptomatic arterial vasospasm.

Detachable balloon embolization therapy of posterior circulation intracranial aneurysms.

Treatment of complex and surgically difficult intracranial aneurysms of the posterior circulation is now being performed with intravascular detachable balloon embolization techniques. The procedure is carried out under local anesthesia from a transfemoral arterial approach, which allows continuous neurological monitoring. Under fluoroscopic guidance, the balloon is propelled by blood flow through the intracranial circulation and in most cases, can be guided directly into the aneurysm, thus preserving the parent vessel. If an aneurysm neck is not present, test occlusion of the parent vessel is performed and, if tolerated, the balloon is detached. Twenty-six aneurysms in 25 patients have been treated by this technique. The aneurysms have involved the distal vertebral artery (five cases), the mid-basilar artery (six cases), the basilar artery (11 cases), and the posterior cerebral artery (four cases). The aneurysms varied in size and included three small (less than 12 mm), 15 large (12 to 25 mm), and eight giant (greater than 25 mm). Fifteen patients (60%) presented with hemorrhage and 10 patients (40%) with mass effect. In 17 cases (65%) direct balloon embolization of the aneurysm was achieved with preservation of the parent artery. In nine cases (35%), because of aneurysm location and size, occlusion of the parent vessel was performed. Complications from therapy included three cases of transient cerebral ischemia which resolved, three cases of stroke, and five deaths due to immediate or delayed aneurysm rupture. The follow-up period has ranged from 2 months to 43 months (mean 22.5 months). In cases where posterior circulation aneurysms have been difficult to treat by conventional neurosurgical techniques, intravascular detachable balloon embolization may offer an alternative therapeutic option.

Relief of seizures from a predominantly posterior temporal tumor with anterior temporal lobectomy.

We report the relief of intractable complex partial seizures in a patient with a posteromesial temporal lobe hamartoma after anterior temporal lobectomy, despite minimal tumor removal. We suggest that the key to successful treatment is the mainly medial, or limbic, location of the tumor, which apparently requires anterior limbic structures for full clinical expression of seizures. We conclude that excision anterior to a posterior temporal lesion can result in seizure relief and that a medial tumor location may be important for successful treatment.

The magnetic field of epileptic spikes agrees with intracranial localizations in complex partial epilepsy.

The magnetoencephalogram (MEG) and electroencephalogram (EEG) were measured during interictal epileptic spikes in nine patients with complex partial seizures. The MEG localization estimates were compared with localizations by intraoperative cortical electrodes, subdural electrodes, stereotaxic depth electrodes, anatomic imaging, postoperative pathologic analysis, and postoperative follow-up. In all patients, MEG localization estimates were in the same lobe as the epileptic focus determined by invasive methods and EEG. In two patients, it was possible to quantify precisely the accuracy of MEG localization by mapping a spike focus that was visually indistinguishable on MEG and cortical recordings. In both patients, MEG localization was approximately 12 mm from the center of the cortical spike focus on intracranial recordings. In eight patients, MEG showed tangential dipolar field patterns on the spontaneous record, but EEG did not. In one patient, a cortical epileptic discharge was detected only on MEG for some discharges and only on EEG for other discharges. The MEG did not detect deep spikes with present levels of environmental noise.

Intraoperative digital subtraction neuroangiography: a diagnostic and therapeutic tool.

We report our experience with intraoperative digital subtraction neuroangiography to demonstrate its application as a diagnostic and therapeutic technique. Intraoperative neuroangiography was performed on 53 occasions in 43 patients using a portable imaging system. Thirty-two procedures were performed for diagnostic purposes after resection of arteriovenous malformations, clipping of aneurysms, or carotid endarterectomy. Unexpected problems were disclosed in seven cases and were surgically remedied immediately in four. In addition, angiography was used as a therapeutic tool in 21 cases to facilitate intraoperative embolization of a vascular lesion or to enable the angioplasty of a vessel inaccessible without direct surgical exposure. We found that by allowing a combined interventional neuroangiographic and neurosurgical approach, intraoperative angiography opened new avenues for treatment of intracranial vascular abnormalities.

The magnetic field of complex partial seizures agrees with intracranial localizations.

The magnetoencephalogram (MEG) was recorded during 63 complex partial seizures in 4 patients. The MEG showed large biomagnetic signals occurring at the same time as discharges recorded from scalp electroencephalogram (EEG). These MEG signals had the same morphology and frequency as the discharges from the EEG. The location of the seizure focus was verified by depth electrode recordings in 2 patients and by lesions shown on computed tomographic scan and magnetic resonance imaging in the other 2. In each patient, MEG localization estimates were consistent with the location of the seizure focus shown by other methods. When seizures were recorded repeatedly and mapped with a single-channel magnetometer placed at different scalp locations in a single patient, the MEG localization agreed with the electrographic seizure focus localized from depth electrodes. In the maps, the MEG resolved an ambiguity in the scalp EEG and therefore increased the confidence of localization. MEG recordings of seizures may help localize epileptic foci noninvasively.

Variants of radiculomeningeal vascular malformations of the spine.

In recent years, it has become evident that the most common form of arteriovenous malformation to involve the spinal cord in adults is a low-flow fistula with its nidus located on the dura in relation to the dorsal nerve root. This lesion, termed "radiculomeningeal fistula" (RMF), is drained by the intradural coronal venous system and most likely causes neurological deficits due to raised venous pressure within the spinal cord. The therapy that was formerly recommended was multilevel laminectomy with microsurgical stripping of the intradural vessels. However, that procedure focused on the draining veins rather than the nidus, and it has been replaced by direct treatment of the nidus or by disconnecting the nidus from the coronal venous system. This paper reports variants of RMF's that show a wider spectrum of the clinical and radiological findings than has been previously reported. Three patients presenting with extradural venous drainage, intraspinal hemorrhage, and/or sudden non-hemorrhagic neurological decline are reported. A more complete understanding of RMF facilitates the radiological and clinical evaluation of these patients and enables the surgeon to modify the therapy in a significant way.

Electrophysiologic studies in selective dorsal rhizotomy for spasticity in children with cerebral palsy.

A group of 20 children with spastic cerebral palsy underwent selective dorsal rhizotomy for alleviation of spasticity. Pre- and postoperatively, cortical somatosensory evoked responses (cSSEP), H reflex and F wave studies were done. Clinically there was dramatic reduction of tone without noticeable sensory loss. The electrophysiologic studies showed several findings: (1) many children have abnormal cSSEP preoperatively; (2) surgery seldom leads to a loss of cSSEP; (3) in many patients, there is a noteworthy improvement in the cSSEP wave form; (4) some children have electrophysiologic evidence of spinal cord dysfunction preoperatively and (5) Hmax/Mmax ratio decreases after surgery confirming decrease in tone.

Surgery for epilepsy: a review.

This year marks the centennial of the first surgical resection for epilepsy performed by Horsley. While epilepsy is generally considered a disease best treated with anticonvulsant medications, surgical therapy is of significant benefit to some patients in whom medical therapy has proved ineffective. Anterior temporal lobectomy has been the single most successful operation commonly performed today. In this paper we review current techniques of preoperative evaluation, the role of scalp and intracranial electrophysiologic monitoring, as well as the contribution of PET and MRI scanning to improving the selection of patients for surgical therapy. The role of focal cortical excisions, hemispherectomy, and corpus callosotomy in the surgical armamentarium is also outlined. A plea is made for establishment of additional regionalized centers for epilepsy surgery in which close collaboration among neurologists, neuropsychologists, neurosurgeons and neurophysiologists can enhance patient care and advance our knowledge of the partial epilepsies and human cerebral function.

Intraoperative angiography using a portable digital subtraction unit. Technical note.

A portable digital subtraction unit has been used in the operating room as an important improvement in obtaining high-quality intraoperative angiograms. This digital subtraction system offers several advantages over previously described techniques for intraoperative studies. Not only are the images of good quality, but also the dose of contrast medium is reduced and a real-time imaging capability allows the surgeon to visualize the passage of contrast agent dynamically. Arterial injections may be performed by selective femoral cerebral catheterization, puncture of the cervical carotid artery, retrograde catheterization via the superficial temporal artery, or puncture of an intracranial vessel at the time of surgery.

Spontaneous arteriovenous fistulas of cerebral vessels in association with fibromuscular dysplasia.

Four cases of spontaneous arteriovenous fistula seen in association with fibromuscular dysplasia of the parent artery are presented. In two patients, the fistula was between the carotid artery and cavernous sinus; in two others, the fistula involved the vertebral artery and paravertebral veins. It is postulated that the angiopathy was responsible for the fistula. Treatment by detachable balloon embolization was successful in each case; however, the presence of the fibromuscular dysplasia made treatment more difficult.

Immunogenicity of melanoma-associated gangliosides in cancer patients.

The immunogenicity of gangliosides found on human melanoma cells was determined from sera of 26 melanoma patients who were immunized every 1-4 weeks for 4 months with tumor-cell vaccine (TCV) prepared from cultured melanoma cells. Total lipid-bound sialic acid in the gangliosides isolated from TCV was 0.38 mumol/10(8) cells, and was distributed as follows: 44.8% to GM3, 44.2% to GD3, 5.6% to GM2, and 4.6% to GD2. Sera were tested at monthly intervals for antibodies to each ganglioside by ELISA with purified gangliosides as the antigen source. The immunologic specificity of the antibody was confirmed by absorption tests. None of the 26 patients had detectable anti-GM3, anti-GD3, or anti-GD2 antibodies before immunization, although anti-GM2 antibody was detected in 3 patients. After immunization, 2 patients developed IgM anti-GD2, 10 developed IgM anti-GM2, and 2 developed IgG anti-GM2 antibodies. No patient developed detectable anti-GM3 or anti-GD3 antibodies. These results indicate that both GD2 and GM2 expressed on human melanoma cells are immunogenic in humans, although GM2 appears to be more immunogenic. The other two gangliosides, GM3 and GD3, are present in human sera and in human normal tissues, and thus immunologic tolerance may have been established against these gangliosides. Alternatively, circulating GM3 and GD3 may have neutralized anti-GM3 and anti-GD3 antibodies, if any were induced by TCV immunization.