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Biomedical subjects

G D Jackson

Publications and source records attributed to G D Jackson.

At least 37 records · Page 2Linked to original sources

TLE patients with postictal psychosis: mesial dysplasia and anterior hippocampal preservation.

The authors studied six patients with refractory temporal lobe epilepsy and postictal psychosis using quantitative MRI and histopathology, and compared the results with 45 patients with temporal lobe epilepsy without postictal psychosis. Total hippocampal volumes were not different between the two groups. However, patients with postictal psychosis had a relatively preserved anterior hippocampus, and temporal lobe dysplasia was more frequent (p = 0.006, chi-square test). These findings may be associated with the clinical symptoms.

Adult↗

APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy.

The authors analyzed the association between APOE epsilon4 genotype and clinical and MRI findings in 43 refractory temporal lobe epilepsy patients. The distribution of the alleles were normal. Ten patients (23%) had an APOE epsilon 4 allele and had an earlier onset of habitual seizures (with epsilon4 5 +/- 5 years; without epsilon4 15 +/- 10 years). Quantitative MRI findings were not influenced by the APOE epsilon4 genotype. APOE epsilon4 may shorten the latency between an initial injury and seizure onset.

Adult↗

Components of verbal learning and hippocampal damage assessed by T2 relaxometry.

We studied a group of 31 temporal lobe epilepsy patients (25 left, 6 right) with unilateral hippocampal sclerosis evident on magnetic resonance imaging. Single slice T2 relaxation times were acquired for the left and right hippocampi. Principal components analysis of preoperative memory data resulted in two factors that reflect a distinction between arbitrary and semantic forms of verbal recall. The former component correlated with left hippocampal T2 relaxation time, while the latter component did not. This study suggests that variation in left hippocampal integrity is more related to the acquisition of arbitrary associates than semantically structured material, and reinforces the possibility that the left temporal lobe is functionally heterogeneous with respect to memory.

Adolescent↗

Lipopolysaccharide-induced biliary factors enhance invasion of Salmonella enteritidis in a rat model.

In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 10(6) to 10(7) CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 microg/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P < 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-alpha) concentrations were measured by bioassay. Biliary concentrations of TNF-alpha rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-alpha cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

Animals↗

Bile mediates intestinal pathology in endotoxemia in rats.

Intestinal pathology frequently accompanies experimental endotoxic shock and is mediated by proinflammatory cytokines. Our hypotheses are that hepatobiliary factors operating from the luminal side of the gut make a major contribution to this damage and that tumor necrosis factor alpha (TNF-alpha) is involved in the pathology. We treated rats with lipopolysaccharide (LPS) intravenously and found that external drainage of bile totally protected the gastrointestinal tract, macroscopically and microscopically, 4 h after LPS administration and dramatically improved survival of the animals for 48 h after LPS administration. The concentration of TNF-alpha in bile increased markedly after LPS administration and was over 30 times higher in bile than in serum. Tissue damage and the biliary TNF-alpha response were abrogated when animals were pretreated with gadolinium chloride to eliminate Kupffer cells. TNF-alpha infusion into the duodenal lumen caused intestinal damage similar to that elicited by intravenous LPS. In rats treated with LPS, survival was significantly increased during the first 36 h in animals given an infusion of anti-TNF-alpha antibody into the duodenum. These results demonstrate that in endotoxemia, intestinal damage is mediated by factors derived from the bile. The findings indicate that luminally acting TNF-alpha contributes to the intestinal damage.

Albinism↗

Motor cortex localization using functional MRI and transcranial magnetic stimulation.

OBJECTIVE: Congenital brain lesions producing focal seizures may be accompanied by reorganization of the areas responsible for motor and sensory functions within the brain due to a phenomenon that has been termed "neuronal plasticity." This can be studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Using either method, the motor cortex can be localized noninvasively, but to date there have been few studies correlating the level of agreement between the two techniques. METHODS: We used fMRI and TMS to localize the motor cortex in a young woman with intractable focal seizures, congenital left arm weakness, and a dysplastic right hemisphere on MRI. RESULTS: There was excellent agreement in the localization of motor representation for each hand. Both were predominantly located in the left hemisphere. fMRI also showed an area of posterior activation in the right hemisphere, but there was no evidence of descending corticospinal projections from this site using TMS, direct cortical stimulation, and Wada testing. CONCLUSIONS: Functional MRI (fMRI) and transcranial magnetic stimulation (TMS) were successfully used to localize cortical motor function before epilepsy surgery. Each technique demonstrated migration of motor function for the left hand to the left motor cortex. After resection of the dysplastic right precentral gyrus there was no permanent increase in weakness or disability. The two techniques are complementary; fMRI indicates all cortical areas activated by the motor task, whereas TMS identifies only those areas giving rise to corticospinal projections.

Adult↗

Clinical and imaging features of cortical malformations in childhood.

OBJECTIVE: To determine the types, relative frequencies, clinical features, and MRI characteristics of malformations of cortical development (MCD) occurring in a cohort of children referred to a tertiary pediatric center. METHODS: Original MR images were reviewed by two investigators, who were blinded to clinical details, to determine the elemental imaging features of each malformation and to label these malformations according to an existing system of classification. Clinical information was collected by a review of hospital records. RESULTS: A total of 109 children with MCD were identified. There were 58 boys and 51 girls, age 8 days to 18 years at initial imaging (mean age, 5 years). Seizures were present in 75%, developmental delay or intellectual disability in 68%, abnormal neurologic findings in 48%, and congenital anomalies apart from the CNS malformation in 18%. The main malformations identified were heterotopic gray matter (19%), cortical tubers (17%), focal cortical dysplasia (16%), polymicrogyria (16%), agyria/pachygyria (15%), schizencephaly/cleft (5%), transmantle dysplasia (5%), and hemimegalencephaly (4%). Eight patients had features of more than one malformation. Most lesions were multilobar (47%), with the frontal lobe being the most common lobe involved (78%). A total of 68% of patients had other cerebral malformations including ventricular dilatation or dysmorphism (46%) and abnormalities of the corpus callosum (29%). CONCLUSIONS: This study illustrates the spectrum of MCD in a pediatric cohort and highlights some of the differences between pediatric and adult patients. Patients with MCD presenting in childhood have a wider spectrum of malformations and more varied, often more severe, clinical manifestations. The lesions are frequently multifocal or generalized and many are associated with noncortical developmental brain anomalies.

Brain↗

Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study.

OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.

Adolescent↗

Reorganization of verbal memory and language: a case of dissociation.

Left-to-right reorganization of verbal memory following early left hemisphere damage has been reported in patients whose expressive language is governed by the right hemisphere. We present a case in which verbal memory performance was intact, despite severe left mesial temporal damage, and despite aphasia on left internal carotid sodium amytal ablation. The distribution and degree of left mesial temporal damage was assessed visually and quantitatively on MRI. These findings raise the possibility that verbal memory may shift to the language-nondominant hemisphere as a result of early left mesial temporal damage.

Brain Damage, Chronic↗

A role for the hepatobiliary system in IgE-mediated intestinal inflammation in the rat.

BACKGROUND: For many years the central focus of research into gastrointestinal hypersensitivity reactions has been the mast cell population of the intestinal lamina propria. Since bile is known to deliver immunological mediators to the gastrointestinal tract, the possibility arises that extra-intestinal populations of mast cells may also contribute to IgE-mediated intestinal damage. OBJECTIVES: To characterize hepatic mast cells in the rat and to investigate the role of the hepatobiliary system in a model of IgE-mediated reactivity to dietary antigen. METHODS: Wistar rats were passively sensitized with monoclonal antidinitrophenyl (DNP) IgE antibodies, and were later challenged orogastrically with DNP-HSA. Additional animals were sensitized, then bile duct-cannulated prior to antigen challenge. At various time points, liver and intestinal samples were collected for histological examination, and bile was collected and assayed for histamine and TNFalpha. RESULTS: Hepatic mast cells display a mucosal mast cell-like phenotype, and are closely associated with the vessels of the portal triads. Orogastric antigen challenge led to a rapid and significant decline (P<0.0001) in detectable mast cells as a result of anaphylactic degranulation. The median number of granulated mast cells associated with each portal triad in liver sections declined from six per portal triad to one per portal triad post-antigen challenge. After 15 min, biliary histamine concentrations rose above background levels (P<0.01). TNFalpha was also detectable in the majority (4/6) of bile samples within 15 min of challenge. Histological examination of the gastrointestinal mucosa revealed disruption to the villous epithelium ranging from oedematous changes to gross destruction. Such damage was not seen in animals in which bile had been externally drained. CONCLUSION: The data indicate that biliary products are major contributors to the gastrointestinal damage arising from IgE-mediated hypersensitivity reactions in the rat, and such hypersensitivity reactions may involve a population of mast cells which reside in the liver.

Animals↗

Occurrence of hippocampal sclerosis: is one hemisphere or gender more vulnerable?

PURPOSE: We analyzed a large group of patients investigated for suspected seizures to test whether gender or side are important factors in the origins of hippocampal sclerosis (HS). METHODS: We studied 996 consecutive patients (48% men, 52% women) by using standard hippocampal T2-relaxometry methods. RESULTS: HS was associated with a highly abnormal T2 time (< or =113 ms). Categoric analysis showed that hippocampal T2 time was independent of gender and side. T2 time was bilaterally normal in 81% of men and in 79% of women; it was unilaterally abnormal in 15% of both men and women; and bilaterally abnormal in 4% of men and in 6% of women. Highly abnormal T2 relaxometry, suggesting HS, occurred with equal frequency in men and women and on the right and left sides. Quantitative analysis of hippocampal T2 times showed values not differing significantly between men and women or between the right and left hemispheres. There was no significant interaction between gender and side. CONCLUSIONS: In patients with seizure disorders, hippocampal T2 relaxometry is not different in adult men and women and in the right and left hemispheres.

Adult↗

Presurgical evaluation of the motor hand area with functional MR imaging in patients with tumors and dysplastic lesions.

PURPOSE: To test an optimized functional magnetic resonance (MR) imaging procedure to depict the motor hand representation area (HRA) in patients with epilepsy lesions near the central sulcus. MATERIALS AND METHODS: Fast low-angle shot MR imaging was performed with an oblique single-section imaging technique in eight control subjects (10 hemispheres) and six patients (12 hemispheres). Three series of five activation images (obtained while subjects performed repetitive finger-to-thumb opposition movements) and five rest images were acquired. Each hemisphere was studied in three adjacent sections. Difference maps (obtained with simple subtraction between activation and rest images) were compared with t-test maps. RESULTS: In control subjects, the HRA was visible in 27 of 30 sections. Qualitatively, activation was seen better on t-test maps in 14 and on difference maps in four of these sections. In all patients, motor activation could be seen in the hemisphere that contained the lesion. This activation was considered normal in four patients. In two patients, the HRA was deformed. Functional MR imaging activation in the motor area was confirmed with Penfield stimulation in five patients. CONCLUSION: Functional MR imaging findings in the preoperative assessment of dysplastic lesions around the central sulcus are the same as for tumors. t-test maps are superior to difference maps in the treatment of motor functional MR imaging data.

Adult↗

Hippocampal T(2) abnormalities correlate with antecedent events and help predict seizure intractability.

INTRODUCTION: We performed hippocampal T(2) relaxometry as part of a routine magnetic resonance imaging (MRI) examination in 50 normal controls and 127 consecutive patients referred because of suspected seizures. METHODS: On the basis of T(2) values in controls (100.2 +/- 4.2 ms) we defined normal as <110 ms ( 113 ms (>mean + 3 SD). RESULTS: After detailed investigation, 103 of these 127 patients had epilepsy and 24 did not. In the nonepilepsy group, none had abnormal hippocampal T(2) values. Twenty-seven of the 103 patients in the epilepsy group had abnormal values, 7 were borderline and 69 were normal. Only 5 patients with abnormal T(2) values did not have temporal lobe epilepsy: 1 had extratemporal lobe epilepsy, 1 had generalized epilepsy and 3 had unclassified epilepsy. Twenty-two of 27 (81%) patients with abnormal hippocampal T(2) values had intractable epilepsy [compared with 32 of 69 (46%) patients with normal values; p < 0.05, chi(2) test]. Two thirds of patients with abnormal values had a history of a major antecedent event (compared to only 7% of those with normal values, p < 0.05, chi(2) test). CONCLUSION: Abnormal T(2) relaxometry is significantly associated with intractable epilepsy as well as with major antecedent events.

Adult↗

Hippocampal sclerosis: development in adult life.

Hippocampal sclerosis (HS) is the most common pathological lesion underlying intractable temporal lobe epilepsy. It is not known whether HS exists before the onset of epilepsy or whether it is caused by seizures. Its has been proposed that childhood seizures cause HS. Optimized magnetic resonance imaging (MRI), hippocampal volumes and T(2) signal quantitation were performed 2 weeks and 8 months following at tonic-clonic seizure in a 23-year-old man. MRI 14 days after the seizure showed symmetrical hippocampal volumes (ratio R/L = 1.03) with intact internal architecture bilaterally but marked signal change in the right hippocampus (T(2) right = 121, T(2) left = 103, normal < or = 108 ms). Eight months later this hippocampus showed severe atrophy with a volume ratio of 0.65 and T(2) values of 117 (right) and 109 ms (left). High-resolution imaging showed that volume loss occurred mainly in the CA1 region which showed high signal in the initial study. Characteristic MRI features of HS can develop in adults and HS cannot always be assumed to have its origins in childhood. Hypoxia in the context of seizures may be an important component in hippocampal damage. HS may be a preventable lesion and MRI signal change seen in the neuronal layers of the hippocampus may be an indication for neuroprotection.

Adult↗

Bacterial lipopolysaccharide induces a conduction block in the sciatic nerves of rats.

A single injection of Escherichia coli lipopolysaccharide (LPS; intraperitoneally [i.p.] and intravenously [i.v.]) reliably induces peripheral nerve disturbances in the hindlimbs of inbred Australian albino Wistar (AaW) rats. In the series of experiments presented here, we aimed to characterize this syndrome by examining electrophysiologic, immunologic, and immunochemical features. The LPS-induced neurologic sequelae in AaW rats were transient, at least partly reversible by drug treatment, and were not associated with any detectable neuropathologic findings by light microscopy. Neurologic sequelae were prevented by administration of dexamethasone and by pretreatment with the macrophage inhibitor gadolinium chloride, suggesting that they were caused by LPS-induced activation of peripheral macrophages. Sequelae were associated with early decreases in compound muscle-action potential amplitudes, indicating impaired functioning of either proximal sciatic nerve axons and/or neuromuscular synapses. Spinal somatosensory-evoked potential latencies also were increased, indicating impaired somatosensory function at the sciatic nerve, dorsal roots, spinal cord, and/or postsynaptic interneurons, although the precise location of impairment could not be delineated. Similarities between this syndrome and immune-mediated polyneuropathies in humans are discussed.

Animals↗