Ictal and interictal electric source imaging in pre-surgical evaluation: a prospective study.

BACKGROUND AND PURPOSE: Accurate localization of the epileptic focus is essential for surgical treatment of patients with drug-resistant epilepsy. Electric source imaging (ESI) is increasingly used in pre-surgical evaluation. However, most previous studies have analysed interictal (II) discharges. Prospective studies comparing the feasibility and accuracy of II and ictal (IC) ESI are lacking. METHODS: We prospectively analysed long-term video-electroencephalography recordings (LTM) of patients admitted for pre-surgical evaluation. We performed ESI of II and IC signals using two methods, i.e. equivalent current dipole (ECD) and a distributed source model (DSM). LTM recordings employed the standard 25-electrode array (including inferior temporal electrodes). An age-matched template head model was used for source analysis. Results were compared with intracranial recordings, conventional neuroimaging methods [magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT)] and outcome at 1 year after surgery. RESULTS: A total of 87 consecutive patients were analysed. ECD gave a significantly higher proportion of patients with localized focal abnormalities (94%) compared with MRI (70%), PET (66%) and SPECT (64%). Agreement between the ESI methods and intracranial recording was moderate to substantial (k = 0.56-0.79). A total of 54 patients were operated (47 patients more than 1 year ago) and 62% of them became seizure-free. The localization accuracy of II-ESI was 51% for DSM and 57% for ECD, and that for IC-ESI was 51% for DSM and 62% for ECD. The differences between the ESI methods were not significant. Differences in localization accuracy between ESI and MRI (55%), PET (33%) and SPECT (40%) were not significant. CONCLUSIONS: The II-ESI and IC-ESI of LTM data have high feasibility and their localization accuracy is similar to that of conventional neuroimaging methods.

Two-dimensional fusion imaging of planar bone scintigraphy and radiographs in patients with clinical scaphoid fracture: an imaging study.

BACKGROUND: Although magnetic resonance imaging (MRI) is now considered the gold standard in second-line imaging of patients with suspected scaphoid fracture and negative radiographs, bone scintigraphy can be used in patients with pacemakers, metallic implants, or other contraindications to MRI. Bone scintigraphy is highly sensitive for the detection of fractures, but exact localization of scintigraphic lesions may be difficult and can negatively affect diagnostic accuracy. PURPOSE: To investigate the influence of image fusion of planar bone scintigraphy and radiographs on image interpretation in patients with suspected scaphoid fracture. MATERIAL AND METHODS: In 24 consecutive patients with suspected scaphoid fracture, a standard planar bone scintigraphy of both hands was supplemented with fusion imaging of the injured wrist. Standard and fusion images were evaluated independently by three experienced nuclear medicine physicians. In addition to the diagnosis, the degree of diagnostic confidence was scored in each case. RESULTS: The addition of fusion images changed the interpretation of each of the three observers in seven, four, and two cases, respectively, reducing the number of positive interpretations of two of the observers from 11 and nine cases to six and seven cases, respectively. The degree of diagnostic confidence increased significantly in two observers, and interobserver agreement increased in all three pairs of observers from 0.83, 0.57, and 0.73 to 0.89, 0.8, and 0.9, respectively. CONCLUSION: Image fusion of planar bone scintigrams and radiographs has a significant influence on image interpretation and increases both diagnostic confidence and interobserver agreement.

Quantitative in vivo studies of soluble simian virus 40 tumor-specific transplantation antigens of the mouse.

Quantitative studies have been performed on the immunogenicity of a membrane-bound antigen of a simian virus 40 (SV40) -induced sarcoma in syngeneic BALB/c mice and of subcellular fractions derived from this tumor. The objectives of the investigation were: a) to develop a quantitative in vivo assay of the tumor-specific transplantation antigen (TSTA) and b) to compare the distribution of histocompatibility antigens, H-2, with that of the SV40 TSTA during several fractionation steps. The immunogenicity of the TSTA-containing fractions was assessed from dose-response curves relating tumor size and the amount of protein used for immunization. After digestion of the tumor cell membranes with a limited amount of papain, H-2 as well as TSTA were present in a soluble form. A single immunization with only 2 microng of the solubilized TSTA reduced the tumor size by 70% compared to that in nonimmunized control animals. The results of several fractionation steps suggest that H-2 and the TSTA are not tightly associated in the solubilized immunogenic material.

Biological and biochemical properties of soluble tumor-specific transplantation antigen of a simian virus 40-induced neoplasm.

We have solubilized by limited papain digestion and partially purified the tumor rejection antigen, tumor-specific transplantation antigens (TSTA), from membranes of a simian virus 40-induced sarcoma. Uniform-sized materials with a molecular weight range of 50,000 have retained their tumor rejection activities through the purification procedures. The simian virus 40 TSTA have been separated from H-2 activity by affinity chromatography on concanavalin A columns and no evidence was found for H-2 antigens in the unbound fraction (I) of concanavalin A containing TSTA activity. A reduced yield from the crude soluble fraction was observed with Fraction I of concanavalin A material and this may indeed represent fragmentation of antigen during papain digestion. These results stand in contrast to purification of histocompatibility antigens (H-2alpha) using the same methods and techniques. Low concentrations of simian virus 40 TSTA crude soluble materials were nervertheless biologically active. A concentration as low as 4 mug protein provided 50% tumor rejection and 0.1 mug protein provided lymphocyte stimulation. Both assays reflected specificity of response.

Decreased norepinephrine concentration in normal tissue neighboring a malignant tumor.

We observed in five adenocarcinomas that norepinephrine as well as nerve fibers were absent from tumor tissue. The number of nerve fibers in normal tissue neighboring the tumor was normal. In contrast, norepinephrine concentration was decreased in normal tissue immediately surrounding tumor and increased in a stepwise fashion with the distance from tumor. Since there is evidence that some catecholamines possess antitumor activity, we suggest that depletion of catecholamines and perhaps other neurotransmitters in normal tissue neighboring a tumor may be of importance for invasion and accelerated malignant growth.

Hepatic metabolism during constant infusion of fructose; comparative studies with 31P-magnetic resonance spectroscopy in man and rats.

A protocol of constant infusion of fructose has been carried out both in human volunteers and in the perfused rat liver, aiming at a steady-state blood fructose concentration of 6-8 mM. Localized 31P-NMR spectroscopy and biochemical analyses were used to evaluate the metabolic changes. Comparison of the model experiment and the clinical study allowed an evaluation of this protocol as a clinically relevant assessment of the metabolic function of the liver. The time course of change, as well as the quasi steady-state levels reached during fructose infusion, for phosphomonoesters (PME), ATP and inorganic phosphate (Pi) provided the following results: During fructose infusion, ATP and Pi reached a steady-state level of 74.0 +/- 5.9 and 54.6 +/- 3.3% of control respectively, in the human volunteers. The corresponding data in the rat liver was 71.3 +/- 4.3 and 54.4 +/- 4.3%. Hepatic clearance of fructose was 0.53 and 0.52 ml.g liver-1.min-1 for volunteers and rats, respectively. The time course of intracellular metabolite recovery after fructose could be approximated by a first order kinetic. The rate constants for PME and ATP change were similar during fructose infusion and recovery, while after the discontinuation of fructose infusion, Pi increased with a rate constant significantly greater than during its fructose-induced depletion in human liver (P < 0.005). Thus, this relatively simple clinically applicable protocol seems to be verifiable in the well controlled perfused rat liver model, and it is argued that it may be useful in the clinical evaluation of the metabolic functional capacity of the human liver.

Maintenance of high-energy brain phosphorous compounds during insulin-induced hypoglycemia in men. 31P nuclear magnetic resonance spectroscopy study.

31P nuclear magnetic resonance (NMR) spectroscopy allows noninvasive studies of cerebral energy-rich phosphorous compounds in humans. In an attempt to characterize the relationship between peripheral blood glucose concentrations and whole-brain phosphate metabolism during insulin-induced hypoglycemia, 31P NMR spectra were obtained before and after intravenous injection of insulin (0.15 IU/kg body wt) in six men. Compared with prehypoglycemic measurements, no significant changes were found in brain content of Pi, sugar phosphates, phosphocreatine, phosphodiesters, and ATP, and brain pH remained constant during the experiment. These results show that the integrated brain profile of energy-rich phosphorous compounds is unaffected by experimental insulin-induced hypoglycemia in humans.

Effect of heel-raising exercise upon collateral resistance in patients with occlusion of the superficial femoral artery.

Invasive blood pressure measurements were performed in the common femoral- and popliteal artery of six limbs with occlusion of the superficial femoral artery during upright exercise (heel raising) and intraarterial alpha-receptor blockade. Femoral blood flow was obtained by an indicator dilution method injecting 131 RISA into the femoral artery and sampling from the popliteal artery. Exercise increased femoral blood flow from an average of 184 (SE +/- 27) cm3 . min-1 at rest to 531 (SE +/- 61) cm3 . min-1 during a 40 degrees head up tilt. Intraarterially induced alpha-receptor blockade caused a further increase in blood flow to 685 (SE +/- 86) cm3 . min-1 during exercise. Changes in collateral arterial resistance was calculated relative to the supine resting value. During exercise a decrease of 24% (SE +/- 13) was observed. After alpha-receptor blockade and exercise collateral resistance decreased by 46% (SE +/- 12). The results indicate that the passive head-up tilt induced a constriction of the collateral arteries which is abolished by heel raising exercise (ie standing on tip toe). It seems, however, that during these circumstances there still remains some alpha-receptor mediated constriction of the collateral arteries which is blocked by intraarterially injected alpha-receptor blocking agents.

Local regulation of subcutaneous forefoot blood flow during orthostatic changes in normal subjects, in sympathetically denervated patients and in patients with occlusive arterial disease.

Local blood flow regulation was studied on the forefoot by the 133-Xenon wash-out method. In 21 normal limbs blood flow decreased 36% when the foot was lowered 40 cm below heart (local vasoconstrictor response). During elevation blood flow was constant to 20 cm, and flow decreased only 10% at further elevation to 40 cm, corresponding to a drop in vascular resistance of 15% (autoregulation of blood flow). In six sympathetically denervated limbs blood flow decreased only 6%, significantly less than in the normal limbs. Autoregulation of blood flow was preserved in these limbs. In 22 limbs with intermittent claudication blood flow decreased only 19%, significantly less than in the normal limbs. However, taking into account the additional increase in arterial pressure that occurs, when a limb with arterial occlusion is lowered there was no significant difference (p = 0.26) in the increase in vascular resistance between the two groups. During elevation vascular resistance decreased significantly in the claudicants indicating preservation of autoregulation. In limbs with rest pain blood flow increased 28% during lowering, and when the additional increase in arterial blood pressure was accounted for, a significant increase in vascular resistance of 21% was noted. During elevation blood flow decreased significantly, and the estimated vascular resistance in this group did not decrease significantly. The study suggests that the increase in blood flow and the relief of ischaemic rest pain induced by lowering are due to an additional increase in arterial pressure rather than due to dilatation of arterioles.

Mechanism of the tilt induced increase in collateral arterial resistance in patients with occlusion of the superficial femoral artery.

Resistance in collateral arteries bypassing an occlusion of the superficial femoral artery was studied in five patients before and during epidural blockade. The patients were placed on a tilt table and the measurements were performed with the patients both in supine and tilted position (40 degrees head up). Arterial blood pressure was measured directly in the brachial, common femoral and popliteal artery. Relative and absolute blood flows were calculated as the relative change in arteriovenous oxygen difference and by an indicator dilution technique. Tilting caused a decrease in relative leg blood flow of 28%. The relative pressure gradient between the femoral and popliteal artery did not change significantly. Calculated relative collateral resistance increased by 49%. During epidural blockade blood flow increased by 39% in supine position corresponding to a decrease in collateral resistance of 22%. During blockade tilting caused a decrease in relative blood flow of 22% compared with the value in supine position. The relative pressure gradient over the occluded superficial femoral artery decreased by 14%. The corresponding calculated relative collateral resistance increased by 14%. The results indicate that the tilt induced constriction of the collateral arteries is mainly neurogenically mediated via the lumbar sympathetic chain, whereas local mechanisms only seems to play a minor role.

Capillary permeability of 131I-albumin in the resting human forearm.

STUDY OBJECTIVE: The aim was to examine capillary permeability of 131I-albumin in the normal, resting human forearm. DESIGN: A bolus injection of 131I-albumin was injected into the brachial artery, and the residue function was measured by external registration over the forearm tissues. The results were analysed by indicator kinetic "black box" theory using the single injection, residue detection method which is based on indicator diffusion principles. SUBJECTS: Seven normal volunteers participated in the study. MEASUREMENTS AND MAIN RESULTS: The mean capillary extraction fraction of 131I-albumin was 0.023 (SD 0.0056), n = 7, at a mean plasma flow rate of 2.1 (0.34) ml.100 g-1.min-1. At an estimated capillary surface area of 70 cm.g-1 the permeability coefficient was 11.10(-8) cm.s-1. CONCLUSIONS: According to the theories of restricted diffusion and equivalent pores the results are compatible with an equivalent pore radius estimate of 113 A using additional previously published results from experiments with 51Cr-EDTA.

Constriction of collateral arteries induced by "head-up tilt" in patients with occlusive arterial disease of the legs.

The effect of head-up tilt on leg blood flow and segmental arterial blood pressures was studied in 21 patients with occlusion or severe stenosis of the common or superficial femoral artery. Arterial pressure was measured directly in the brachial artery, common femoral artery and popliteal artery. Relative change in blood flow in the leg during tilt was estimated by changes in arterio-venous oxygen differences and by the indicator dilution technique in nine patients. Head-up tilt caused a decrease in leg blood flow of 36% corresponding to an increase in total vascular resistance of 57%. Tilt did not change the pressure gradient from femoral to popliteal artery in the patients with occlusion of the superficial femoral artery, indicating that the flow resistance offered by the collateral arteries had increased. In a bilateral sympathectomised patient the increase in collateral resistance was almost absent indicating that the constriction of the collateral arteries is mainly mediated via sympathetic vasoconstrictor fibres.

Distensibiltiy of the papaverine-induced passive vascular bed in dermis of generalized scleroderma.

Passive distensibility of of the vascular bed in cutaneous tissue of the hand was examined in 7 normal persons and 15 patients suffering from generalized scleroderma of the acrosclerosis type. Paralysis of vascular smooth muscle cells was obtained by locally injected papaverine. Increase in vascular transmural pressure was induced by lowering the limb. Blood flow was estimated by the local Xenon wash-out technique. There was no significant difference between the patients and the normals in relative blood flow during lowering, when injection volumes of 0.005 and 0.02 ml were used, indicating that distensibility of the vascular bed in cutaneous tissue in generalized scleroderma is not diminished. However, in generalized scleroderma an injection volume of 0.1 ml caused a significant decrease in relative blood flow during lowering. This phenomenon observed in the patients probably reflects changes in total tissue pressure opposing distension of the vascular bed. This suggests an altered pressure-volume relationship of the interstitial fluid spaces in cutaneous tissue of generalized scleroderma.

Distensibility of the vascular bed in subcutaneous tissue in generalized scleroderma.

Passive distensibility of resistance vessels in subcutaneous tissue of hand and leg was examined in 6 normals and 8 patients suffering from generalized scleroderma of the acrosclerosis type. Local paralysis of smooth muscle was obtained by injection of papaverine and increase in transmural pressure by lowering the limb. Blood flow was estimated by the local 133Xenon wash-out method. Distensibility of blood vessels in subcutaneous tissue in generalized scleroderma was not decreased to a significant degree, whereas, both in patients and normals, the blood vessels of the leg exhibited diminished distensibility compared to blood vessels of the hand. The findings suggest that the morphologic changes of vascular and extravascular tissue observed in sclerodermic skin do not affect distensibility of the vascular bed in subcutaneous tissue.

Local regulation of blood flow in subcutaneous tissue in generalized scleroderma.

The effect of orthostatic changes in vascular transmural pressure on blood flow in subcutaneous tissue was studied in 10 patients with the acrosclerotic type of generalized scleroderma. Blood flow was measured on the back of the hand by the local 133xenon washout technique. The blood flow remained constant when the hand was elevated 20 cm above the jugular notch, indicating that there is autoregulation of blood flow, When the hand was lowered 40 cm below by 50% observed in normals. Thus, intrinsic vascular reactions responsible for the autoregulator response are present, whereas the normal "vasoconstrictor response" to an increase in venous transmural pressure is almost abolished in tissues with sclerodermic changes. The abolition of the vasoconstrictor response is probably due to sympathetic neuropathy associated with the sclerodermic changes.

Epilepsy surgery: non-invasive versus invasive focus localization. What is needed from a neurological point of view?

Epilepsy surgery should be performed as early as possible when intractable seizures are diagnosed together with a well-defined focus in a resectable part of the brain. All patients with epilepsy, and especially all children with epilepsy, should therefore be followed by a neurologist or a child neurologist specially trained in epileptology.

Surgical treatment of epilepsy. Clinical aspects in children.

Neurosurgery, mainly temporal lobectomy, has given substantial relief of serious seizure problems in two-thirds of children with intractable epilepsy. Since the prognoses of children with an intractable epilepsy is poor, surgery should be considered. To prevent sequela of a long standing seizure disorder and side effects of antiepileptic medication as well as the development of mirror foci, surgery should be considered at an early age. The age at which surgery should be undertaken depends upon several factors, for instance: the seizure problem, the EEG findings--are they persistently focal and do they fit with the seizures? Is there a malignant development of the epilepsy and little or no chance of remission? And especially, if there is brain pathology in concordance with the clinical findings and EEG signs, neurosurgery should not be postponed. It is of great advantage for children with an intractable epilepsy to be evaluated at an epilepsy center. Both the children and their parents will profit from the evaluation and information gained as well as education by a multiprofessional team. This will optimise the difficult decision process which may lead to neurosurgery.

24-hour lithium concentration in human brain studied by Li-7 magnetic resonance spectroscopy.

Brain and serum lithium concentrations were measured every second hour during a 24-hr period following lithium intake, and again 48-hr later in two normal subjects in steady state lithium treatment receiving lithium carbonate (Priadel Synthelabo) once every evening. The brain-lithium concentration was measured by 7Li magnetic resonance spectroscopy (MRS). The brain lithium level was found to undulate in a peak-trough pattern that followed the serum lithium profile, although in an attenuated form. The brain/serum lithium concentration ratio varied considerably during the 48-hr period, ranging from 0.5 to 1.3, but the ratio was independent of the serum-lithium concentration. The median half-life for lithium was 28 hr in the brain, and 16 hr in serum. The brain lithium concentration in the morning was about 75% of the clinically relevant standard 12-hr serum lithium concentration. The finding that brain lithium undulates during the day means that MRS measurements of brain lithium can only be compared if carried out under standard conditions that include a fixed interval following lithium intake and an identical treatment regimen.

Neuronal pH regulation: constant normal intracellular pH is maintained in brain during low extracellular pH induced by acetazolamide--31P NMR study.

The intracellular pH in the brain was studied in six healthy volunteers before and immediately after the administration of 2 g of acetazolamide. Phosphorus-31 nuclear magnetic resonance spectroscopy by a 1.5 tesla whole-body scanner was used. The chemical shift between the inorganic phosphate and the phosphocreatine resonance frequencies was used for indirect assessment of the intracellular pH. The mean baseline intracellular pH was 7.05 +/- 0.04 (SD). The mean pH changes obtained at 15-min intervals within the first hour of acetazolamide administration were -0.03 +/- 0.04 (SD), -0.02 +/- 0.03 (SD), and 0.00 +/- 0.04 (SD), i.e., no statistically significant pH decrease was observed during the period where extracellular pH is known to drop markedly. Although several factors contribute to the lack of change of the intraneuronal pH, we will discuss that this observation in addition might suggest a direct intracerebral effect of acetazolamide.

Peripheral neuropathy in systemic lupus erythematosus.

We studied 33 consecutive patients with systemic lupus erythematosus (SLE) for neuropathy by employing the Neuropathy Symptom Score (NSS), Neurological Disability Score (NDS), EMG and nerve conduction velocity (NCV) studies, and determinations of vibration thresholds (VT). Polyneuropathy defined as NCV abnormalities of two or more nerves occurred in seven patients (21%). Neuropathic symptoms showed a poor correlation with NCV and VT, while clinical neuropathic signs, VT, and NCV correlated with each other in most instances. When reporting frequencies of neuropathy in SLE, NCV studies should be used as a basis. NSS, NDS, and VT give additional quantifiable information and can be useful in the follow-up of patients and for evaluating the response to therapy.