New NMR measurements in epilepsy. T2 relaxometry and magnetic resonance spectroscopy.
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Animals↗
Biomedical subjects
G D Jackson
Publications and source records attributed to G D Jackson.
Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients.
BACKGROUND: Prognosis and treatment of the first seizure depends on identification of a specific epilepsy syndrome, yet patients with first seizures are generally regarded as a homogeneous group. We studied whether it is possible to diagnose specific epilepsy syndromes promptly by use of standard clinical methods, electroencephalography (EEG) and magnetic resonance imaging (MRI). METHODS: 300 consecutive adults and children presented with unexplained seizures. We systematically collected clinical data from patients and witnesses, and attempted to obtain an EEG within 24 h of the seizure. Where the EEG was negative, a sleep-deprived EEG was done. MRI was done electively. FINDINGS: A generalised or partial epilepsy syndrome was clinically diagnosed in 141 (47%) patients. Subsequent analysis showed that only three of these clinical diagnoses were incorrect. Addition of the EEG data enabled us to diagnose an epilepsy syndrome in 232 (77%) patients. EEG within 24 h was more useful in diagnosis of epileptiform abnormalities than later EEG (51 vs 34%). Neuroimaging showed 38 epileptogenic lesions, including 17 tumours. There were no lesions in patients for whom generalised epilepsy was confirmed by EEG. Our final diagnoses were: generalised epilepsy (23% of patients); partial epilepsy (58%); and unclassified (19%). INTERPRETATION: An epilepsy syndrome can be diagnosed in most first-seizure patients. Ideally, an EEG should be obtained within 24 h of the seizure followed by a sleep deprived EEG if necessary. MRI aids diagnosis and should be done for all patients except for those with idiopathic generalised epilepsies and for children with benign rolandic epilepsy.
Adolescent↗
In vitro comparison of the biologic activities of monoclonal monomeric IgA, polymeric IgA, and secretory IgA.
Secretory IgA (S-IgA), a major humoral mediator of mucosal immunity, is a polymeric Ig containing an unusual extra polypeptide, secretory component (SC), added during transcytosis through epithelial cells. Polymeric S-IgA is more effective than monomeric IgA (mIgA) and IgG in neutralizing viruses. It is not known whether this increased efficacy is due solely to the polymeric structure of the molecule or whether SC itself makes S-IgA more efficient; a quantitative in vitro comparison of the biologic activities of S-IgA and pIgA has not been reported. We prepared purified pIgA and mIgA mAbs directed toward the H1 hemagglutinin of PR8 influenza virus and purified monoclonal S-IgA (made from monoclonal pIgA injected into a Lewis rat and collected as S-IgA from bile) and compared their abilities to carry out hemagglutination inhibition (HI) and neutralization of the infectivity of PR8 influenza virus in vitro. The polymeric Igs (pIgA and S-IgA) were 5 times more effective than mIgA in HI and 7 to 10 times more effective than mIgA in virus neutralization. Addition of SC to pIgA did not modify its ability to mediate HI and had only a minimal effect (S-IgA was 1.4 times more effective) on its ability to neutralize influenza virus in vitro. Trypsin preincubation partially abolished mIgA- or pIgA-mediated, but not S-IgA-mediated, viral neutralization. Thus, although S-IgA is more stable functionally than pIgA, the addition of SC does not influence, positively or negatively, the biologic activity associated with the Fab of S-IgA.
Animals↗
Twins with different temporal lobe malformations: schizencephaly and arachnoid cyst.
The etiology and relationships between different forms of malformations of cortical development are poorly understood. Schizencephaly is generally regarded as unrelated to arachnoid cysts. As part of a systematic study of epilepsy in twins we observed a monozygotic twin pair discordant for temporal lobe epilepsy where the twin with epilepsy had unilateral temporal schizencephaly and periventricular heterotopia. The twin without epilepsy had an arachnoid cyst in the same temporal lobe. Although an incidental association is possible, this observation, together with occasional reports of schizencephaly and arachnoid cysts within one individual, suggests a shared pathogenic mechanism. Schizencephaly can be caused by both genetic and acquired factors. We propose that our observations in this twin pair are best explained by a genetic factor present in both twins, with an additional environmental insult resulting in schizencephaly in only one of the pair.
Adult↗
Effect of tear secretory IgA on chemotaxis of polymorphonuclear leucocytes.
PURPOSE: The aim of the present study was to examine the effect of tear and purified colostrum secretory IgA (sIgA) on polymorphonuclear leucocyte (PMN) chemotaxis. METHODS: The chemotactic effect of tear and purified sIgA for PMN was studied using a modified Boyden chamber. Tears treated with anti-human IgA, complement-inactivated tears and albumin were used as controls. RESULTS: The data indicate that both tear and purified sIgA are highly chemotactic for PMN. Anti-sIgA antibodies reduced the chemotactic effect of closed-eye tears (34%) and tear collected during ocular inflammation. CONCLUSION: The massive recruitment of PMN in tears during sleep may be partially attributed to the increased levels of tear sIgA. This may play an important role in protecting the eye against bacterial infection.
Chemotaxis, Leukocyte↗
Hemicranial volume deficits in patients with temporal lobe epilepsy with and without hippocampal sclerosis.
PURPOSE: In patients with refractory temporal lobe epilepsy, studies have suggested volume deficits measured by MRI of brain structures outside the epileptogenic hippocampus. Hippocampal sclerosis (HS) is a frequent, but not obligate, finding in such patients. The present study examines the influence of the presence of HS on quantitative magnetic resonance imaging (MRI) measurements. METHODS: We analyzed 47 patients and 30 controls by quantitative MRI, including intracranial volume (ICV), hemicranial volume, hippocampal volume (HCV), and T2 relaxometry. MRI results were compared with histological findings in the resected temporal lobe. RESULTS: Histology documented HS in 35 patients (HS group) and other findings in 12 patients (no-HS group). In both groups, the hemicranial volume ipsilateral to the epileptogenic focus was significantly smaller than on the contralateral side (p < 0.004). The HCV on both sides was smaller in the HS group compared with patients without HS (p < or = 0.004). Unilateral hippocampal atrophy and increased T2 value were found in 71% of patients with HS, and bilaterally normal HCV and T2 value were found in 67% of patients without HS. CONCLUSIONS: The smaller hemicranial volume on the focus side, irrespective of the presence or absence of HS suggests a different pathogenic mechanism for the additional hemicranial volume deficit, compared to HS itself. The contralateral HCV deficit depends on the presence of HS, indicating a pathogenic connection between damage to both hippocampi.
Adult↗
Hippocampal sclerosis studied in identical twins.
OBJECTIVE: To test both the genetic and acquired hypotheses for the etiology of hippocampal sclerosis (HS) by studying with optimized and quantitative MRI three monozygous (MZ) twin pairs in which the index twin had temporal lobe epilepsy and HS. BACKGROUND: There is conflicting evidence in the literature regarding whether HS is genetic or acquired prenatally, perinatally, or as a consequence of prolonged childhood seizures. METHODS: We compared three MZ pairs with 30 age-matched control subjects who had no history of a neurologic disorder; we also used the twins as matched samples to assess subtle differences between the affected and the unaffected twins. RESULTS: All of the affected twins had prolonged seizures with fever in early childhood, which stood out as the unique factor common to all affected twins and was absent in all the unaffected twins. HS was present in all affected twins but was absent in the unaffected twin on visual, volumetric, and T2 relaxometry criteria. Comparison of the affected twin with the co-twin revealed that intracranial volume ipsilateral to the HS was relatively small in two of three affected twins. CONCLUSIONS: The absence of HS in the unaffected twin is strong evidence against a genetic hypothesis for HS. Neither perinatal problems nor birth order were factors in determining the presence of HS. This twin study supports the notion of HS as an acquired lesion secondary to prolonged seizures in early childhood and suggests that regional abnormalities of intracranial volume are associated with HS.
Adult↗
The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study.
One hundred patients with intractable temporal lobe epilepsy and 22 control subjects were scanned on a 1.5-T Siemens SP63 Magnetom scanner. A combination of hippocampal T2 mapping, hippocampal volume measurement corrected for intracranial volume, and inspection of hippocampal morphology on a hippocampal volume distribution graph compared with a control graph revealed previously undetected forms of bilateral hippocampal sclerosis and four false-positive diagnoses of hippocampal sclerosis made on visual inspection of the scans. A physiological asymmetry in the position of the hippocampi in 41% of control subjects and focal hippocampal atrophies in patients made measurement of the whole length of the hippocampus mandatory. The extent of hippocampal damage in patients with hippocampal sclerosis correlated with the number of secondary generalized seizures during a patient's lifetime. In contrast to patients with unilateral hippocampal sclerosis, patients with severe bilateral hippocampal sclerosis had no history of febrile convulsions. Twenty-six patients with intractable temporal lobe epilepsy had normal hippocampal magnetic resonance imaging measures and as a group were significantly older at the onset of habitual epilepsy than were patients with hippocampal sclerosis. In conclusion, a combination of quantitative magnetic resonance imaging techniques revealed a spectrum of hippocampal sclerosis and optimally defined boundaries of hippocampal normality. The spectrum of hippocampal sclerosis is related to the etiology, the number of secondary generalized seizures, and the age at onset of habitual epilepsy.
Adolescent↗
Bile regulates the expression of major histocompatibility complex class II molecules on rat intestinal epithelium.
BACKGROUND & AIMS: Major histocompatibility complex (MHC) class II molecules are expressed on intestinal epithelial cells, and the intensity of this expression is regulated. The aim of this study was to test the hypothesis that bile regulates the expression of MHC class II molecules on intestinal epithelium. METHODS: Rats were deprived of intestinal bile by external drainage for 24 or 48 hours, and their intestines were collected, sectioned, and stained with the anti-MHC class II monoclonal antibodies OX4 and OX6. For one group of rats, bile flow was deviated from its usual entry point to the ileum. RESULTS: Compared with intact animals, MHC class II expression was observed to be diminished within 24 hours and totally absent after 48 hours of bile drainage. For the group in which bile flow was deviated to the ileum, staining was only observed in the region distal to the entry point. Analysis by bioassay and enzyme-linked immunosorbent assay of bile showed the presence of tumor necrosis factor and interferon gamma, respectively. CONCLUSIONS: It is concluded that the presence of bile is required for the expression of MHC class II molecules on gut epithelium and that the cytokine components of bile may be the inducing agents.
Animals↗
Detection and specificity of anti-Staphylococcus intermedius secretory IgA in human tears.
PURPOSE: Secretory IgA (sIgA) is the predominant immunoglobulin present in tears that protects the ocular surface against various antigens. Staphylococcus intermedius is a member of the normal ocular microbiota. METHODS: The presence and the specificity of immunoglobulin A to S. intermedius was determined by fluorescent assay, ELISA and western blots. RESULTS: Three immunodominant antigens of S. intermedius were detected of 145, 127 and 61 kDa. Staphylococcus intermedius-specific IgA cross reacted with Staphylococcus aureus but not with Gram negative bacteria. CONCLUSIONS: This indicates that specific IgA may play an important role in the protection of the eye by limiting the levels of Gram positive normal microbiota and defending against the more pathogenic S. aureus.
Antibodies, Bacterial↗
Interictal 99Tc(m) HMPAO SPECT and 1H MRS in children with temporal lobe epilepsy.
PURPOSE: To understand the pathological basis of focal hypoperfusion seen on interictal 99Tc(m) hexamethylpropyleneamine oxime (HMPAO) single-photon-emission computed tomography (SPECT) in intractable temporal lobe epilepsy, and to determine why the technique may be misleading in the localization and lateralization of the seizure focus in some cases. METHODS: Interictal 99Tc(m) HMPAO SPECT and proton magnetic resonance spectroscopy (1H MRS) of the mesial temporal regions were performed in 14 children with intractable temporal lobe epilepsy not caused by a foreign tissue lesion. RESULTS: Hypoperfusion of one temporal lobe ipsilateral to the seizure focus was demonstrated in 10 (71%) of the children; 1H MRS correctly lateralised in eight of these 10. No asymmetry of perfusion of the anterior temporal regions was seen in the remaining four children; on 1H MRS, three of these were bilaterally abnormal but nonlateralising. Repeated SPECT and 1H MRS in three children demonstrated changes over time, the findings from the two techniques being consistent with each other on both the initial and the repeated scans. CONCLUSIONS: Abnormalities demonstrated by 1H MRS correlate well with those seen on interictal SPECT and can help to understand the pathologic basis of these SPECT abnormalities. Furthermore, the presence of bilateral damage can result in an absence of perfusion asymmetry on interictal SPECT.
Adolescent↗
Bacterial lipopolysaccharides induce peripheral nerve disturbances in rats that mimic human immune-mediated polyneuropathies.
A single injection of Escherichia coli lipopolysaccharide (LPS; i.v. and i.p.) reliably induced peripheral nerve disturbances in male Australian albino Wistar (AaW) rats. Signs developed 6 to 24 h after LPS inoculation and persisted only transiently. Most AaW rats had variable degrees of bilateral hind limb impairment, and rarely had forelimb, tail, or central impairment. Signs included gait abnormalities, proprioceptive loss, and to a lesser extent hind limb weakness and sensory deficits. Signs were more severe in male than female AaW rats and were induced in a number of genetically related rat strains (e.g., AaW and outbred Wistar and inbred Lewis rats, but not Sprague Dawley or inbred Fischer 344 rats). Development and severity of these signs were found not be related to animal body weight, but were dependent on LPS dose. Signs were not associated with LPS-induced alterations in pain perception, or occurrence of spontaneous pain, as indexed by tail-flick and hot-plate tests. Taken together, these data indicate that LPS induced transient peripheral nerve disturbances in rats, the severity of which was influenced by genetic, sex-related, and dose-related factors.
Animals↗
Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy.
We performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N-acetylaspartate to choline plus creatine (NAA/[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean 18%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.
Adolescent↗
A classification scheme for malformations of cortical development.
Malformations of the cerebral cortex are being recognized more frequently as a cause of epilepsy, developmental delay, neurological deficits, and mental retardation. Nonetheless, a standard nomenclature and classification system of these malformations, based upon state-of-the art knowledge derived from genetics, embryology, imaging, and pathology, has not been devised. In this manuscript, we propose such a classification system. Moreover, we have constructed the system such that both the framework and the classifications themselves are flexible and can be adapted as our knowledge of the embryology, genetics, imaging, and pathology of these disorders advances. We believe that the use of this classification system will help both clinicians and researchers to understand and think about these disorders and their causes better. In turn, we hope that this improved understanding will lead to further refinements in classification, to advances in our knowledge and, ultimately, to improvements in therapy.
Brain Damage, Chronic↗
Magnetic resonance imaging and spectroscopy.
In the past year, magnetic resonance has assumed an increasingly important role in the study of patients with epilepsy that now extends beyond its demonstration of neuroanatomy and neuropathology into the fields of neurochemistry, neurometabolism and neurophysiology. For proper use of this information, epileptologists, neurologists and neuroradiologists need to understand the limitations as well as the strengths of this technology. Magnetic resonance literacy will increasingly become an essential part of all of these disciplines.
Child, Preschool↗
Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy.
We used proton magnetic resonance spectroscopy (1H MRS) for the assessment of focal brain pathology in 22 right-handed children with a diagnosis of intractable temporal lobe epilepsy, and we related this pathology to cognitive dysfunction. Cognitive assessment was based on measurements of verbal IQ, performance IQ, and the Paired Associate Learning subtest of the Wechsler Memory Scale. Five of the 22 children showed no abnormalities of the temporal lobes on 1H MRS, seven showed unilateral pathology, and 10 showed bilateral abnormalities. We found that left-sided pathology is associated with a loss of verbal cognitive functions, whereas right-sided pathology is associated with a loss of nonverbal functions. These findings are consistent with the pattern of lateralization of brain function that has been observed in adults.
Adolescent↗
Functional magnetic resonance imaging and the supplementary sensorimotor area.
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Animals↗
The diagnosis of hippocampal sclerosis: other techniques.
Pathologically, hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis affecting particularly the pyramidal neurons of CA1, CA3, and CA4 with relative sparing of the CA2 neurons. This can be identified in vivo with magnetic resonance (MR) imaging techniques that can reveal both morphological and signal abnormalities. The morphological changes are atrophy and loss of the normal internal architecture of the hippocampus as seen in coronal section. There is also T1- and T2-weighted signal abnormality in the hippocampus. Quantitative techniques are very good at measuring any single one of these features, but the spectrum of HS includes cases in which a single feature can occasionally be misleading. Also, quantitation focuses entirely on the hippocampus, and it is becoming clear that HS may exist in the presence of other brain pathology that may affect proper management of the patient. Therefore, quantitative measures should always be interpreted in the context of optimised imaging sequences and visual inspection. For routine clinical purposes, the relative reliance on quantitation (hippocampal volume or T2 measurements) depends entirely on the yield of visual inspection in any institution. This, in turn, depends on whether optimised imaging is performed and on the familiarity of the reporting specialist with the MRI features of HS. A technique which approaches 95-100% compared with pathology is essential in any epilepsy centre, and optimised visual analysis can achieve this. There are some cases where quantitation of a single feature can be misleading, so visual analysis should always be performed, and complements any quantitative study.
Atrophy↗