A.C. van Huffelen

Measurement of the Conductivity of Skull, Temporarily Removed During Epilepsy Surgery

The conductivity of the human skull plays an important role in source localization of brain activity, because it is low as compared to other tissues in the head. The value usually taken for the conductivity of skull is questionable. In a carefully chosen procedure, in which sterility, a stable temperature, and relative humidity were guaranteed, we measured the (lumped, homogeneous) conductivity of the skull in five patients undergoing epilepsy surgery, using an extended four-point method. Twenty-eight current configurations were used, in each of which the potential due to an applied current was measured. A finite difference model, incorporating the geometry of the skull and the electrode locations, derived from CT data, was used to mimic the measurements. The conductivity values found were ranging from 32 mS/m to 80 mS/m, which is much higher than the values reported in other studies. Causes for these higher conductivity values are discussed.

Combined use of subdural and intracerebral electrodes in preoperative evaluation of epilepsy.

For intracranial recording of partial seizures considered to originate from one of the temporal or frontal lobes, the team in the Utrecht Academic Hospital has used subdural, multicontact, flexible electrodes since 1972. These are introduced through bilateral, frontocentral trephine holes and are manipulated under fluoroscopy to cover most of the cerebral convexity. It became evident that in many patients, additional placements to record from intracerebral structures were indispensable. Therefore, using the same trephine holes, an additional 2 to 4 depth electrodes were stereotactically implanted in the mesial temporal and/or frontal structures, as appropriate. An extensive intra- and extracerebral spatial representation of the epileptogenic zone was thus obtained. We report here the methods for manufacturing and applying these electrodes and our clinical experience with 28 patients. The results obtained so far stress the value of combining subdural and depth electroencephalographic monitoring in the presurgical selection of patients suffering from medically refractory complex partial seizures. By miniaturizing the electrodes, extensive areas of the brain can be investigated without craniotomy or multiple burr holes.

Recurrent ischemia in symptomatic carotid occlusion Prognostic value of hemodynamic factors

Objective: To identify hemodynamic factors that predict recurrence of ipsilateral cerebral ischemic events in patients with symptomatic carotid artery occlusion (CAO). Patients and Methods: The authors studied 117 consecutive patients with CAO and corresponding recent (≤6 months) ischemic symptoms of the brain or eye that were transient or at most mildly disabling. They determined, using Cox proportional hazards analysis, the prognostic value for recurrence of ipsilateral cerebral ischemic events of 1) clinical features believed to indicate hemodynamic compromise, 2) collateral blood flow pattern, and 3) transcranial Doppler CO2-reactivity. Results: None of the 24 patients with symptoms of retinal ischemia alone had a recurrent cerebral ischemic event. In the 93 patients with cerebral ischemic symptoms on entry, recurrence of these symptoms was independently predicted by 1) the nature of the initial symptoms being of purported hemodynamic origin (limb-shaking, precipitation of symptoms by rising, exercise or low blood pressure, retinal claudication) (hazard ratio [HR] 3.8, 95% CI 1.5 to 9.5), 2) continuing symptoms after the CAO had been documented, but before inclusion in the study (HR 5.9, 95% CI 2.2 to 16.1), and 3) the presence of collateral blood flow via leptomeningeal vessels (HR 4.1, 95% CI 1.3 to 13.1). CO2-reactivity did not predict recurrence of cerebral ischemic events. Conclusions: Having cerebral in contrast to retinal ischemia, clinical features suggestive of hemodynamic compromise, continuing symptoms after demonstration of the CAO, and presence of leptomeningeal collaterals may help to identify patients with symptomatic CAO at high risk of future cerebral ischemia.

Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy?

OBJECTIVE: To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures. METHODS: Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI. RESULTS: Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C-flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C-flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non-lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET. CONCLUSION: In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery.

A Longitudinal Study of Collateral Flow Patterns in the Circle of Willis and the Ophthalmic Artery in Patients With a Symptomatic Internal Carotid Artery Occlusion

BACKGROUND AND PURPOSE The purpose of the present study was to assess whether the direction of flow via the circle of Willis and the ophthalmic artery (OphA) changed over time in patients with a symptomatic occlusion of the internal carotid artery (ICA) who did not experience recurrent cerebral ischemic symptoms. METHODS Sixty-two patients with a symptomatic ICA occlusion were investigated within 6 months after symptoms occurred. The investigations were repeated after 6 and 12 months. The directions of flow in the A1 segment and the posterior communicating artery (PCoA), both on the side of the symptomatic ICA occlusion, were assessed with the use of magnetic resonance angiography. The pattern of collateral flow via the circle of Willis was categorized as via the A1 segment only, via the PCoA only, via the A1 segment plus the PCoA, or no collateral flow via the circle of Willis. The direction of flow in the OphA was investigated with transcranial Doppler sonography. CO(2) reactivity was determined with transcranial Doppler sonography to investigate whether changes in flow patterns were accompanied by changes in cerebrovascular reactivity. RESULTS There were no statistically significant changes over time in the direction of blood flow in the A1 segment and the PCoA or in the pattern of collateral flow via the circle of Willis. On average, 72% of patients with a unilateral ICA occlusion (n=41) had willisian collateral flow compared with 37% of patients with a bilateral ICA occlusion (n=21; P<0.05). Patients with a unilateral ICA occlusion tended to a lower prevalence of reversed flow via the OphA over time. CO(2) reactivity did not change significantly in any patient group. In patients with a unilateral ICA occlusion, decreased CO(2) reactivity was associated with a higher prevalence of absent willisian collateral flow and a lower prevalence of collateral flow via the A1 segment plus the PCoA. CONCLUSIONS The absence of recurrent cerebral ischemic symptoms in patients with a symptomatic ICA occlusion is not associated with an improvement in collateral flow via the circle of Willis or the OphA during 1.5-year follow-up.

Quantitative EEG changes due to cerebral vasoconstriction. Indomethacin versus hyperventilation-induced reduction in cerebral blood flow in normal subjects

Hyperventilation leads to an increase in slow EEG activity as well as to a decrease in alpha activity. These effects may be considered a result of reduction in cerebral blood flow due to vasoconstriction, but metabolic factors, such as alkalosis and the increased formation of cerebral lactate, may also have to be taken into account. As indomethacin decreases cerebral blood flow it is possible to study cerebral vasoconstriction, without concomitant metabolic alkalosis or cerebral lactate formation. Two parallel groups of 12 healthy male subjects (age 20-25) were studied with quantitative EEG (qEEG) and cerebral blood flow velocity as parameters. In the first group the effect of 100 mg indomethacin was studied. In the parallel group a standardized hyperventilation procedure was performed. In the indomethacin group the blood flow velocity decreased to 60% of the initial value; the qEEG showed a 0.5 Hz slowing of the alpha peak frequency (P less than 0.01) and a decrease in the power of the alpha band without any change in the delta or theta band. In the hyperventilation group the blood flow velocity decreased to 63% of the initial value and the qEEG showed a marked increase in delta and theta activity (P less than 0.01), but a non-significant change in alpha peak frequency. Indomethacin and hyperventilation caused similar degrees of vasoconstriction; however, the increase in qEEG slow wave activity, which was observed only in the hyperventilation group, is apparently related to metabolic rather than haemodynamic factors.

Collateral Circulation via the Ophthalmic Artery or Leptomeningeal Vessels Is Associated with Impaired Cerebral Vasoreactivity in Patients with Symptomatic Carotid Artery Occlusion

Background and Purpose: In patients with carotid artery occlusion (CAO), collateral flow may reduce the risk of ischemic stroke. Collateral flow via the ophthalmic artery (OphthA) and flow via leptomeningeal vessels have been considered secondary collaterals, which are recruited only if the primary collateral circulation via the circle of Willis is insufficient. The aim of this study was to investigate whether patients with symptomatic CAO who have secondary in addition to primary collaterals have a worse flow state of the brain than those without secondary collaterals, as measured by vascular reactivity testing. Methods: We studied 70 patients with symptomatic CAO who were independent for their daily activities. In all patients, collateral circulation through the circle of Willis was present. Vascular reactivity, measured by means of transcranial Doppler sonography with carbogen inhalation, was compared between patients with and without secondary collaterals. Results: CO2 reactivity was lower in 64 patients with (mean ± standard deviation 8 ± 14%) than in 6 patients without secondary collaterals (33 ± 18%) resulting in a mean difference of 24% (95% confidence interval 12–37%; p < 0.01). Conclusions: Patients with symptomatic CAO with collateral circulation through the OphthA or through leptomeningeal vessels in addition to collaterals via the circle of Willis have a worse hemodynamic status of the brain than those with Willisian collaterals only. Therefore the presence of these collaterals may indicate insufficiency of collateral blood flow via the circle of Willis.

Estimation of the number of motor units based on macro-EMG

The technique of the macro-EMG was used to estimate the number of motor units in the tibialis anterior muscles of healthy subjects in a wide range of ages, and of patients with myasthenia gravis and patients with amyotrophic lateral sclerosis or spinal muscular atrophy. The results obtained suggest a decrease in the number of motor units in the tibialis anterior muscle with increasing age in normal subjects. In myasthenic patients the motor unit count was within the normal range for their age group. Patients with motor neuron disorders on the average had a very low number of motor units.

Quantitative EEG changes due to hypobaric hypoxia in normal subjects.

A condition of hypobaric hypoxia was created in a low pressure chamber by reducing the atmospheric pressure to 46.5 kPa. Thirty-six subjects were exposed to hypobaric hypoxia during 19 min with a recovery period of 25 min. In 13 subjects the experiment was repeated after 1 week. Four EEG channels, HbSaO2, PeCO2, heart and respiration rate were continuously monitored. Quantitative EEG (qEEG) samples for the derivation P4-O2 were taken in normobaric normoxic (A), hypobaric normoxic (B) and hypobaric hypoxic (C) conditions and mutually compared. Subtraction spectra and standard qEEG parameters were studied, in an attempt to select those which are most reliable to detect hypoxia. Hypobaric normoxia caused no significant qEEG changes. Hypobaric hypoxia resulted in a significant increase in slow activity, a significant decrease in alpha activity and a non-significant decrease in beta activity. Two clusters of non-related standard qEEG parameters were found to be sensitive to hypoxia. The differences between the parameters within each cluster are too small to permit a definite choice of one of them. For the description of qEEG changes due to hypoxia at least one parameter from each cluster has to be taken into account.

Collateral flow and ischemic brain lesions in patients with unilateral carotid artery occlusion

Objective: To investigate the association between ischemic brain lesions and intracranial collateral blood flow in patients with unilateral occlusion of the internal carotid artery (ICA). Methods: Sixty-eight consecutive patients were included. Ischemic lesions on MRI were identified on hard copies, and volume measurements of the lesions were performed on an MR workstation. Intracranial collateral pathways were studied with MR angiography, digital subtraction angiography, and transcranial Doppler sonography. Results: The presence of collateral flow via the anterior communicating artery (ACoA) was associated with a reduction in prevalence (p = 0.01) and volume (p = 0.008) of internal border zone infarcts in the hemisphere ipsilateral to the occluded ICA. Absence of collateral blood flow via the circle of Willis was associated with an increase in prevalence (p = 0.007) and volume (p = 0.005) of internal border zone infarcts. No association between any collateral flow pattern in the circle of Willis and periventricular lesions or lacunar, territorial, or external border zone infarcts was found. No association between collateral flow via the ophthalmic artery or leptomeningeal vessels with any type of ischemic lesion was found. Conclusion: Collateral flow via the ACoA is associated with a reduction of the prevalence and volume of internal border zone lesions but not with any other type of ischemic lesion. The presence of a functional posterior communicating artery or secondary collateral pathways is not associated with the prevalence of any type of ischemic lesion.