Predictive value of electroencephalography and computed tomography in childhood non-traumatic coma

Objectives: To study value of electroencephalogram (EEG) and computed tomography (CT Scan) in predicting outcome of non-traumatic coma in children.Methods: 100 consecutive children, between 2 months to 12 years, with nontraumatic coma, (Glasgow Coma Scale score <-8). Demographic and clinical data was recorded at admission. EEG and CT scan were done within 24 hours of admission. Etiologic diagnosis was assigned on basis of clinical data and relevant laboratory investigations. The outcome was recorded as survived and died. Among survivors it was graded as no disability, or mild, moderate, or severe disability. Odds ratio and/or relative risk (RR) with 95% confidence interval (CI) were calculated.Results: EEG could be done in 60 patients (43 survived; 7 were normal, 8 had mild, 17 moderate and 11 severe disability) CT scan in 93 patients (60 survived; 11 were normal, 14 had mild, 21 moderate and 14 severe disability). A normal/borderline EEG was associated with good outcome (P = 0.001); 11 of 12 survived and of survivors 55% had no or mild disability. Electrocerebral silence on EEG was a predictor of death (OR = 44; 95% CI -1.5-7372; P =0.01). An abnormal EEG was associated with significant increase in risk of disability among survivors (RR=2.6, 95% CI= 1.2–5.4, P=0.03). Among CT abnormalities intracranial bleed suggested increased risk of death (RR = 2.1; 95% CI-0.8-5.3; P = 0.058), while, hydrocephalus was associated with better survival (RR = 0.7; 95% CI-0.5 to 0.96; P = 0.029). However, hydrocephalus when compared with other abnormal CT scan findings, was associated with higher risk of moderate and severe disability among survivors (P= 0.046)Conclusion: A normal CT scan and EEG, and some of the specific findings could be helpful in predicting outcome in children with non-traumatic coma. EEG and CT scan should be done at admission in all patients with non-traumatic coma if feasible     

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

Forebrain activation patterns in normal and spinal-injured Sprague-Dawley (SD) rats were determined by measuring regional cerebral blood flow as an indicator of neuronal activity. Data are compared to our previously published findings from normal and spinal-injured Long-Evans (LE) rats and reveal a striking degree of overlap, as well as differences, between strains in the basal (unstimulated) forebrain activation in normal animals. Specifically, 81% of the structures sampled showed similar activation in both strains, suggesting a consistent and identifiable pattern of basal cerebral activation in the rat. LE controls showed significantly greater basal activation in the remaining structures compared to SD control group, including the anterior dorsal thalamus, basolateral amygdala, SII cortex, and the hypothalamic paraventricular nucleus. In contrast, spinal cord injury (SCI) resulted in strain-specific changes in forebrain activation categorized by structures that showed significant increases in: (1) only LE SCI rats (posterior, ventrolateral, and ventroposterolateral thalamic nuclei); (2) only SD SCI rats (anterior-dorsal and medial thalamus, basolateral amygdala, cingulate and retrosplenial cortex, habenula, interpeduncular nucleus, hypothalamic paraventricular nucleus, periaqueductal gray); or (3) both strains (arcuate nucleus, ventroposteromedial thalamus, SI and SII somatosensory cortex). These results provide information related to the remote, i.e. supraspinal, effects of spinal cord injury and suggest that genetic differences play an important part in the forebrain response to such injury. Brain activation studies therefore provide a useful tool in understanding the full extent of secondary consequences following spinal injury and for identifying potential central mechanism responsible for the development of pain.     

Co-activation of the amygdala, hippocampus and inferior frontal gyrus during autobiographical memory retrieval

Functional MRI was used to investigate the role of medial temporal lobe and inferior frontal lobe regions in autobiographical recall. Prior to scanning, participants generated cue words for 50 autobiographical memories and rated their phenomenological properties using our autobiographical memory questionnaire (AMQ). During scanning, the cue words were presented and participants pressed a button when they retrieved the associated memory. The autobiographical retrieval task was interleaved in an event-related design with a semantic retrieval task (category generation). Region-of-interest analyses showed greater activation of the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval relative to semantic retrieval. In addition, the left inferior frontal gyrus showed a more prolonged duration of activation in the semantic retrieval condition. A targeted correlational analysis revealed pronounced functional connectivity among the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval but not during semantic retrieval. These results support theories of autobiographical memory that hypothesize co-activation of frontotemporal areas during recollection of episodes from the personal past.     

Sustained involvement of a frontal-parietal network for spatial response selection with practice of a spatial choice-reaction task

With practice, performance on a task typically becomes faster, more accurate, and less prone to interference from competing tasks. Some theories of this performance change suggest it reflects a qualitative reorganization of the cognitive processing required for successful task performance. Other theories suggest this change in performance reflects a more quantitative change in the amount of processing required to perform the task. Neuroimaging research results provide some support for both of these broad theories. This inconsistency may reflect the complex nature of the effect of practice on cognitive and neural processing. Our current experiment addresses this issue by investigating the effect of practice of a relatively easy perceptual-motor task on the frontal-parietal brain network for a specific cognitive process (viz. spatial response selection). Participants were scanned during three functional magnetic resonance imaging sessions on separate days within 4 days while they performed a relatively easy spatial perceptual-motor task. We found sustained activity with practice in right dorsal prefrontal cortex; and sustained but decreasing activity in bilateral dorsal premotor, left superior parietal, and precuneus cortices, supporting a quantitative decrease in difficulty of response selection with practice. Conversely, we found a qualitative change in activity with practice in left dorsal prefrontal cortex. This brain region is outside the response selection network for this task and showed activity only during novel task performance. These results suggest that practice produces both qualitative and quantitative changes in processing. The particular effect of practice depends on the cognitive process in question.     

Dissociable correlates of recollection and familiarity within the medial temporal lobes

Regions in the medial temporal lobes (MTL) have long been implicated in the formation of new memories for events, however, it is unclear whether different MTL subregions support different memory processes. Here, we used event-related functional magnetic resonance imaging (fMRI) to examine the degree to which two recognition memory processes-recollection and familiarity-were supported by different MTL subregions. Results showed that encoding activity in the rhinal cortex selectively predicted familiarity-based recognition, whereas, activity in the hippocampus and posterior parahippocampal cortex selectively predicted recollection. Collectively, these results support the view that different subregions within the MTL memory system implement unique encoding processes that differentially support familiarity and recollection.     

Brain areas engaged during visual judgments by involuntary access to novel semantic information

Theories of visual recognition place different emphasis on the role of non-stimulus factors. Previously, we showed that arbitrary semantic associations influenced visual recognition of novel objects. Here, the neural substrate of this effect was investigated. During a visual task, novel objects associated with arbitrary semantic features produced more activation in frontal and parietal cortex than objects associated with names. Because the task required no semantic retrieval, access to semantics appears to be involuntary. The brain regions involved have been implicated in semantic processing, thus recently acquired semantics activate a similar network to semantics learned over a lifetime.     

Pharmacological characterisation of novel alpha 2-adrenoceptor antagonists as potential brain imaging agents

Development of suitable imaging ligands to facilitate in vivo characterisation of alpha(2)-adrenoceptors has been limited in its success. In the present study, a series of iodinated derivatives and a fluorinated derivative of the classical alpha(2)-adrenoceptor antagonist, idazoxan, have been evaluated as potential imaging ligands. These compounds are based on the structure of idazoxan but more closely resemble the selective alpha(2)-adrenoceptor antagonists 2-methoxy-idazoxan (RX821002) and 2-ethoxy-idazoxan (RX811059). Preliminary studies, investigating their affinities at alpha(2)-adrenoceptors, using brain membranes prepared from a variety of species, and their ability to antagonise UK14, 304-induced inhibition of twitch in mouse vas deferens highlighted 2-iodopropoxy-idazoxan and 2-fluoroethoxy-idazoxan as the most promising candidates. Further characterisation of these two compounds showed they had a good selectivity for alpha(2)-adrenoceptors compared with imidazoline(2)-binding sites and beta-adrenoceptors. Additional functional studies also showed a lack of intrinsic activity at alpha(2)-adrenoceptors. Following intravenous injection, both compounds were able to cross the blood brain barrier when tested using an ex vivo binding assay. These data show that both 2-iodopropoxy-idazoxan and 2-fluoroethoxy-idazoxan have binding and functional properties suitable for imaging ligands. Further studies using radiolabelled forms of these ligands and a more extensive characterisation of their binding profiles are necessary but these initial evaluations demonstrate their potential.     

Activation of the prefrontal cortex to trauma-related stimuli measured by near-infrared spectroscopy in posttraumatic stress disorder due to terrorism

To develop a noninvasive method for psychophysiological assessment of posttraumatic stress disorder (PTSD), 34 victims of the Tokyo Subway Sarin Attack in 1995 including 8 diagnosed as PTSD and 12 controls were examined by a multichannel near-infrared spectroscopy (NIRS) system. Hemodynamic response in the prefrontal cortex was monitored during the presentation of trauma-related and control stimuli by video images. Skin conductance response (SCR) was also examined. Oxygenated hemoglobin significantly increased during the trauma-related image in the victims with or without PTSD. Deoxygenated hemoglobin significantly decreased only in victims with PTSD. No significant alteration was found in controls. Significantly enhanced SCR was also observed in the victims with PTSD during trauma-related stimuli. The findings suggest that measurement of cerebral hemodynamic response by NIRS is useful for psychophysiological assessment of PTSD.     

Adult Leigh syndrome with mitochondrial DNA mutation at 8993

Adult onset Leigh syndrome with a nucleotide (nt) 8993 mutation in mitochondrial (mt) DNA is reported. A 43-year-old woman with a 6-year-history of insulin-resistant diabetes mellitus developed muscular weakness, intractable nausea and vomiting, and anemia. These were followed vertigo, blindness, and deafness with nystagmus. Magnetic resonance imaging (MRI) revealed abnormal high intensities in the bilateral medial regions of the thalamus and periaqueductal gray matters. Autopsy disclosed well-demarcated necrotizing lesions with prominent capillaries in the areas detected by MRI, which were sufficiently diagnostic for Leigh syndrome. MtDNA analysis performed on DNAs extracted from formalin-fixed tissues including liver, heart, brain, muscle, kidney and pancreas showed a T→G mutation at nt 8993. This is the first case of adult Leigh syndrome demonstrating on mtDNA mutations. Received: 24 August 1998 / Revised, accepted: 21 October 1998     

Diagnosis of brain death with technetium 99m hexamethylpropylene amine oxime

We report on the utility of technetium 99m hexamethylpropylene amine oxime (^99mTc-HMPAO) to diagnose brain death following cardiac surgery on a 49-year-old man with triple-vessel coronary artery disease. The imaging parameters and criteria to diagnose irreversible brain damage (brain death) with ^99m-TcHMPAO are outlined. Brain imaging with this tracer seems to be more reliable than classic radionuclide angiography and has a potential value to confirm the diagnosis of brain death at an early stage. In addition, it may be used to evaluate the perfusion pattern to other vital organs with potential for transplantation.Partially presented as a poster demonstration to the 19th Annual Meeting of the BNMS. Offprint requests to: D.C. Costa