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E W Mee

Publications and source records attributed to E W Mee.

9 recordsLinked to original sources

Changes in the mRNAs encoding voltage-gated sodium channel types II and III in human epileptic hippocampus.

Studies with animal seizure models have indicated that changes in temporal and spatial expression of voltage-gated sodium channels may be important in the pathology of epilepsy. Here, by using in situ hybridisation with previously characterised subtype-selective oligonucleotide probes [Whitaker et al. (2000) J. Comp. Neurol. 422, 123-139], we have compared the cellular expression of all four brain alpha-subunit sodium channel mRNAs in "normal" and epileptic hippocampi from humans. Neuronal cell loss was observed in all regions of the hippocampus of diseased patients, indicating that sclerosis had occurred. Losses of up to 40% compared to post-mortem controls were observed which were statistically significant in all regions studied (dentate gyrus, hilus, and CA1-3). To assess mRNA levels of the different alpha-subtypes in specific subregions, control and diseased tissue sections were hybridised to subtype-specific probes. To quantify any changes in expression while allowing for cell loss, the sections were processed for liquid emulsion autoradiography and grain counts were performed on populations of individual neurones in different subregions. No significant differences were found in the expression of type I and VI mRNAs. In contrast, a significant down-regulation of type II mRNA was observed in the epileptic tissue in the remaining pyramidal cells of CA3 (71+/-7% of control, P<0.01), CA2 (81+/-8% of control, P<0.05) and CA1 (72+/-6% of control, P<0.05) compared with control tissue. Additionally, a significant up-regulation in type III mRNA in epileptic CA4 pyramidal cells (145+/-7% of control, P<0.05) was observed. It is not clear whether these changes play a causal role in human epilepsy or whether they are secondary to seizures or drug treatment; further studies are necessary to investigate these alternatives. However, it is likely that such changes would affect the intrinsic excitability of hippocampal neurones.

Adolescent↗

Too little, too late: does tirilazad mesylate reduce fatigue after subarachnoid hemorrhage?

OBJECTIVE: Trials assessing drug effectiveness for treatment of subarachnoid hemorrhage (SAH) often use mortality rates and Glasgow Outcome Scale scores as outcome measures. Neuropsychological and psychosocial measures might be more sensitive to outcomes, especially for patients of better-grade status. METHODS: Eighteen of a total of 31 patients enrolled in the New Zealand arm of the Upjohn international, double-blind, therapeutic trial of tirilazad mesylate for women with SAH were assessed neuropsychologically and psychosocially 3 months after SAH. The 13 not assessed either had died or remained vegetative (9 patients), did not speak English (1 patient), or did not consent (3 patients). The drug code was broken after all assessments had been scored. RESULTS: Sixteen of the 31 patients had received the drug and 15 the vehicle. There were no differences between the two groups with respect to age, grades assessed at admission and 14 weeks after SAH, Glasgow Outcome Scale scores assessed at 3 months, or mortality rates. In the subgroup assessed neuropsychologically, nine patients were in each of the drug- and vehicle-treated groups. No differences were found with respect to grades, Glasgow Outcome Scale scores, or values for an index that measured cognitive impairment in all tests, but vehicle-treated patients were more impaired with respect to measures of concentration, sustained attention, and psychomotor speed (P < 0.02), as well as debilitating fatigue (P < 0.01). CONCLUSION: The finding that the patients in the drug-treated group exhibited fewer impairments typical of diffuse cortical damage could be viewed as being consistent with the hypothesis that tirilazad mesylate protects neurons. Given the small size of this study, these results require confirmation with larger patient groups. Future drug trials should consider including neuropsychological tests in assessments of outcomes after SAH. If this is too costly, questions regarding fatigue levels might prove worthwhile.

Adult↗

Neurological and psychosocial outcome 4 to 7 years after subarachnoid hemorrhage.

OBJECTIVE: Previous studies have demonstrated that many patients with good neurological outcomes still experience excessive fatigue, cognitive impairments, and lowered work status 1 year after subarachnoid hemorrhage (SAH). Does recovery continue for many years or are survivors of SAH left with permanent disabilities? We describe the long-term outcome. METHODS: Approximately 50% (n = 123) of the patients who survived SAH for more than 3 years from a population of 1.5 million and who had participated in research studies at the time of their SAH were interviewed 4 to 7 years later by telephone or questionnaire. Participants did not differ from the 126 unsurveyed survivors in age, gender, SAH grades, aneurysm sites, or complications. RESULTS: Most patients thought their recovery to be satisfactory to good, although some reported memory problems (41%), headaches (16.5%), daytime sleepiness (35%), problems sleeping at night (26%), a reduced ability to work (20%), and a changed personality (48.3%). Many had reduced their smoking and drinking. Each of 24 of the 121 participants for whom seizure data were available (all with clipped aneurysms) had suffered at least one seizure, but only each of 10 had suffered two or more seizures since hospital discharge. Relative youth was the only significant predictor of seizures, with strong trends observed between seizures and a poor Glasgow Outcome Scale score at 10 weeks or between seizures and an ischemic neurological deficit. No evidence for the effectiveness of prophylactic anticonvulsants was demonstrated. CONCLUSION: Survivors of SAH continue to recover for years and develop good coping skills and a positive attitude toward their recovery, even when they experience ongoing problems. Few are left with disabling headaches or epilepsy.

Activities of Daily Living↗

Loss of A1 adenosine receptors in human temporal lobe epilepsy.

Using quantitative receptor autoradiographic methods we have examined A1 adenosine receptors, adenosine uptake sites, benzodiazepine receptors, NMDA, AMPA, and kainic acid receptors in temporal lobes removed from patients suffering from complex partial seizures and in normal control post-mortem temporal cortex. Binding to A1 adenosine receptors and NMDA receptors was reduced in epileptic temporal cortex, while the other neurochemical parameters were unchanged. The reason for this A1 receptor loss is unclear as it occurred in both idiopathic and symptomatic cases and thus may be a consequence rather than an initial cause of seizures. However, because adenosine is a powerful anticonvulsant substance, loss of anticonvulsant A1 receptors may contribute to the human epileptic condition. It is also possible that the observed differences in A1 binding are due to autopsy vs. biopsy changes in the levels of A1 adenosine receptors.

Adolescent↗

A prospective study of impairment of cognition and memory and recovery after subarachnoid hemorrhage.

In this prospective study, a series of 89 patients with subarachnoid hemorrhage (SAH), most of whom had a "good" neurological outcome, were assessed with a range of tests of memory and cognition as inpatients and at 10 weeks and 12 months after SAH. On tests of verbal cognition and memory, most patients had scores in the normal range 12 months after SAH. However, a significant number of patients still showed impairment on tests of visuospatial construction and memory, mental flexibility, and psychomotor speed at the 12-month assessment. Statistical analyses were carried out for each test score to see whether aneurysm site, location of blood on the admission computed tomographic scan, vasospasm, ischemia, hydrocephalus, grades at admission to and at discharge from hospital, and Glasgow Outcome Scale score at follow-up were associated with test scores. Aneurysm site was not shown to be associated with performance on any test at any time, and the other complications of SAH had only minimal predictive value. The grade at discharge proved to be the best predictor of impairment of cognition and memory at both follow-up assessments. Older subjects did not recover to the same extent as younger subjects by the 12-month assessment. The authors conclude that the diffuse effects of SAH are more important than focal neuropathology in relation to cognitive impairment in this group of patients.

Adolescent↗

Vertebral artery occlusion associated with closed head injury: report of three cases.

Vertebral artery occlusion associated with closed head injury is an uncommon clinical entity. Three cases are presented with discussion of the mechanisms of injury, pathology, diagnosis, possible treatment modalities and autopsy findings in the two fatalities. Angiography is essential for diagnosis and in fatal cases post-mortem examination of the entire length of the vertebral arteries should be routine.

Adult↗

Multiple brain abscesses secondary to dental caries and severe periodontal disease.

A case is reported in which an intra-oral focus of sepsis is thought to have resulted in the patient developing multiple brain abscesses without the presence of lung infection or cardiac valvular disease. The link between the two sites of infection is supported by the isolation of two Streptococcus viridans species normally associated with dental caries and periodontal disease. The management of multiple brain abscesses is discussed.

Adult↗