Do apparent diffusion coefficient measurements predict outcome in children with neonatal hypoxic-ischemic encephalopathy?

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) permits early detection and quantification of hypoxic-ischemic (HI) brain lesions. Our aim was to assess the predictive value of DWI and apparent diffusion coefficient (ADC) measurements for outcome in children with perinatal asphyxia. MATERIALS AND METHODS: Term neonates underwent MR imaging within 10 days after birth because of asphyxia. MR imaging examinations were retrospectively evaluated for HI brain damage. ADC was measured in 30 standardized brain regions and in visibly abnormal areas on DWI. In survivors, developmental outcome until early school age was graded into the following categories: 1) normal, 2) mildly abnormal, and 3) definitely abnormal. For analysis, category 3 and death (category 4) were labeled "adverse," 1 and 2 were "favorable," and 2-3 and death were "abnormal" outcome. Differences in outcome between infants with and without DWI abnormalities were analyzed by using chi(2) tests. The nonparametric Mann-Whitney U test analyzed whether ADC values in visible DWI abnormalities correlated with age at imaging. Logistic regression analysis tested the predictive value for outcome of the ADC in each standardized brain region. Receiver operating characteristic analysis was used to find optimal ADC cutoff values for each region for the various outcome scores. RESULTS: Twenty-four infants (13 male) were included. Mean age at MR imaging was 4.3 days (range, 1-9 days). Seven infants died. There was no difference in outcome between infants with and without visible DWI abnormalities. Only ADC of the posterior limb of the internal capsule correlated with age. ADC in visibly abnormal DWI regions did not have a predictive value for outcome. Of all measurements performed, only the ADC in the normal-appearing basal ganglia and brain stem correlated significantly with outcome; low ADC values were associated with abnormal/adverse outcome, and higher ADC values, with normal/favorable outcome (basal ganglia: P = .03 for abnormal, P = .01 for adverse outcome; brain stem: P = .006 for abnormal, P = .03 for adverse outcome). CONCLUSIONS: ADC values in normal-appearing basal ganglia and brain stem correlated with outcome, independently of all MR imaging findings including those of DWI. ADC values in visibly abnormal brain tissue on DWI did not show a predictive value for outcome.

Is there a way to predict outcome in (near) term neonates with hypoxic-ischemic encephalopathy based on MR imaging?

BACKGROUND AND PURPOSE: It has previously been demonstrated that comparison of signal intensity (SI) between selected brain structures on T1-weighted images enables distinction between the absence or presence of hypoxic-ischemic (HI) brain injury in young infants. The aim of the present study was to assess whether this method of brain structure T1-weighted SI comparison also enables prediction of outcome. MATERIALS AND METHODS: Survivors of a group of 57 children with neonatal HI encephalopathy (HIE) grade 2 or 3 according to Sarnat and Sarnat and controls who underwent neonatal MR imaging were retrospectively assigned to 1 of 3 outcome groups at 5 years of age, depending on developmental outcome: 1) normal, 2) mildly abnormal, and 3) definitely abnormal. Gestational age was not significantly different between the HIE group (range, 35 + 5-42 + 5 weeks; mean, 39 + 4 weeks) and control group (range, 35 + 0-42 + 1 weeks; mean, 39 + 2 weeks). We calculated the predictive values of the neonatal clinical HIE classification according to Sarnat and Sarnat for outcome (neonatal death and developmental outcome in survivors). We assessed which brain structure T1-weighted SI comparison scored best for outcome prediction. Predictive values of that comparison for outcome were calculated for the entire group and for the HIE grade 2 group only, a patient group with highly variable outcome. RESULTS: Of the 57 children, 6 died. Outcome group 1 consisted of 31; group 2, of 14; and group 3, of 6 children. The positive predictive value of the neonatal clinical classification for adverse outcome (outcome group 3 and death) was 52%; and negative predictive value, 100%. These were respectively 45% and 0% in children with HIE grade 2. Of all brain structure T1-weighted SI comparisons, that of the posterior limb of the internal capsule versus the posterolateral putamen scored best for outcome prediction. The positive predictive value for adverse outcome was 69%; and negative predictive value, 98%. In children with HIE grade 2, the positive predictive value and negative predictive value for adverse outcome were 67% and 88%. CONCLUSIONS: Brain structure T1-weighted SI comparisons are helpful to predict outcome in (near) term neonates with HIE. This finding adds to the current knowledge and clinical practice. If the SI in the posterolateral putamen is less than the SI in the posterior limb of the internal capsule, favorable outcome is very likely, whereas if the SI in the posterolateral putamen is equal to or greater than the SI in the posterior limb of the internal capsule, adverse outcome is very likely. In neonates with HIE grade 2 according to Sarnat and Sarnat, prediction of outcome is substantially improved by using these brain structure T1-weighted SI comparisons.

Differentiating normal myelination from hypoxic-ischemic encephalopathy on T1-weighted MR Images: a new approach.

BACKGROUND AND PURPOSE: Hypoxic-ischemic cerebral changes can be difficult to distinguish from normal myelination on T1-weighted images. We hypothesized that comparing signal intensity (SI) of brain structures on T1-weighted images enables differentiation of myelination from hypoxic-ischemic brain damage. MATERIALS AND METHODS: T1-weighted images, obtained in 57 infants aged 1-104 days and born after a gestational age of 35 weeks or older, were retrospectively evaluated. Subjects were assigned to a patient (n = 23, with perinatal hypoxic-ischemic encephalopathy [HIE] stage 2/3) or a control group (n = 34). In each subject, an SI score was assigned to 19 brain structures on the basis of pairwise comparisons with the other 18 structures. In both groups, mean total SI scores were calculated for the 19 structures. Independent samples t tests assessed whether the mean total score of a structure differed significantly between the 2 groups. Logistic regression assessed which comparison was best to distinguish between the groups and to predict the presence of hypoxic-ischemic injury. RESULTS: In patients, mean total SI scores for posterolateral putamen (PP) and peri-Rolandic cortex (PC) were significantly higher (P = .000 for both). Mean total SI scores of the posterior limb of internal capsule (PLIC) and the corona radiata (CR) were significantly lower in patients (P = .000 and 0.005, respectively). Two comparisons (PLIC versus CR, PP versus PC) were best to distinguish patients and controls and to predict absence or presence of HIE (P < .0001). CONCLUSION: SI changes due to hypoxia-ischemia can be differentiated from normal myelination by comparing SI of 4 brain structures on T1-weighted images.

Prediction of short-term neurological outcome in full-term neonates with hypoxic-ischaemic encephalopathy based on combined use of electroencephalogram and neuro-imaging.

BACKGROUND: In infants with hypoxic-ischaemic encephalopathy (HIE), prediction of the prognosis is based on clinical, neuro-imaging and neurophysiological parameters. METHODS: EEG, cranial ultrasound, MRI and follow-up findings of 23 infants (GA 35-42 weeks) with HIE were studied retrospectively to assess 1) the contribution of ultrasound, MRI and EEG in predicting outcome, 2) the accuracy of ultrasound as compared to MRI, and 3) whether patterns of brain damage and EEG findings are associated. RESULTS: An abnormal EEG background pattern was highly predictive of adverse outcome [positive predictive value (PPV) 0.88]. If combined with diffuse white and deep and/or cortical grey matter changes on ultrasound or MRI, the PPV increased to 1.00. Abnormal neuro-imaging findings were also highly predictive of adverse outcome. Abnormal signal intensity in the posterior limb of the internal capsule, and diffuse cortical grey matter damage were associated with adverse outcome. MRI showed deep grey matter changes more frequently than ultrasound. Severely abnormal neuro-imaging findings were always associated with abnormal EEG background pattern. CONCLUSIONS: Both early EEG and neuro-imaging findings are predictive of outcome in infants with HIE. The predictive value of EEG is strengthened by neuro-imaging.

Hyperechogenicity of the thalamus and basal ganglia in very preterm infants: radiological findings and short-term neurological outcome.

Cerebral ultrasound of preterm infants may show diffuse, bilateral, hyperechogenic "haze" over the thalami and basal ganglia (hyperechogenicity BGT). We explored whether this could be a pathological phenomenon. All cerebral ultrasound examinations performed in 2001 on infants < 35 weeks of age were reviewed. This resulted in a hyperechogenicity and non-hyperechogenicity group. The character of the hyperechogenicity BGT and the presence of concomitant brain lesions were noted. Detailed clinical and follow-up data from a selected group of infants < 32 weeks were reviewed and compared between the 2 groups. The incidence of hyperechogenicity BGT was 11 % (39/359) in infants < 35 weeks and 26 % (37/143) in infants < 32 weeks. Birth weight and gestational age were significantly lower and clinical course was more complicated in the hyperechogenicity group. Concomitant brain lesions were always present. In 12/39 infants with hyperechogenicity BGT, MRI (always performed for other reasons) was available, showing signal intensity changes in thalamic region in 5 infants. The neurological outcome at term was less favorable in the hyperechogenicity group, but similar at 1 year. Thus hyperechogenicity BGT mainly occurred in very small, sick infants and was always associated with cerebral pathology. MRI did not consistently show abnormalities in the thalamic region. It was not associated with a poorer outcome at 1 year.

Laparoscopy for the treatment of women with endometrial cancer.

OBJECTIVE: To evaluate the use of a laparoscopic approach for the management of endometrial cancer. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. SUBJECTS AND METHODS: Individual medical records of patients with preoperative histological diagnosis of endometrial carcinoma from January 2000 to December 2001 were reviewed and the data analysed. MAIN OUTCOME MEASURES: Success of laparoscopic-assisted surgical staging, intra-operative and postoperative morbidity, and length of hospital stay. RESULTS: Laparoscopic surgery was successful for 93.3% (28 of 30) patients. Two patients were converted to laparotomy. The mean operating time was 102 minutes (standard deviation, 16 minutes) and the mean operative blood loss was 280 mL (standard deviation, 137 mL). The mean hospital stay was 5 days (standard deviation, 2.3 days). The intra-operative and postoperative complication rate was 16.7%, including vaginal tear, injury to the inferior epigastric vessel, lymphocyst, and pulmonary embolism. CONCLUSION: This study illustrated that a laparoscopic approach is feasible for endometrial cancer surgery and may be considered as the primary treatment modality in skilled hands. This approach should be offered to women with endometrial cancer without contraindications for laparoscopic surgery if experienced endoscopic surgeons are available. Prophylaxis for venous thromboembolism and the use of retroperitoneal drainage may be helpful in decreasing the perioperative morbidity.

MR angiography of the intracranial venous system.

PURPOSE: To compare the effectiveness of different imaging planes at time-of-flight (TOF) magnetic resonance (MR) angiography and phase-contrast MR angiography in the visualization of the normal intracranial venous system. MATERIALS AND METHODS: In 12 healthy volunteers, two-dimensional (2D) TOF MR angiography and three-dimensional (3D) phase-contrast MR angiography were performed in transverse, sagittal, and coronal planes. All data were displayed as maximum intensity projection (MIP) images. Four neuroradiologists assessed the visibility of 28 intracranial venous structures on the MIP images. Statistical analysis was performed by using the Friedman two-way analysis of variance and the Cochran Q test. RESULTS: Visualization of the normal intracranial venous system was better with 3D phase-contrast and coronal 2D TOF MR angiography than with transverse or sagittal 2D TOF MR angiography (P < .05, Friedman test) for each observer and the group of observers. Differences were found between each of the 2D TOF and 3D phase-contrast MR angiographic sequences in the visualization of individual venous structures (Cochran Q test). The kappa values ranged from 0.36 to 0.71, which indicated a moderate to good agreement between observers. CONCLUSION: The normal intracranial venous system is adequately visualized with 3D phase-contrast and coronal 2D TOF MR angiography.

Optic nerve glioma mimicking an optic nerve meningioma.

The case is described of an optic nerve glioma, mimicking an optic nerve meningioma in a man aged 41 years. CT, MRI and DSA revealed an enhancing tumor surrounding the optic nerve. Histopathologic examination of the removed optic nerve revealed a centrally located glioma surrounded by normal optic nerve fibres.

Dysphagia in ambulant patients with Parkinson's disease: common, not dangerous.

To assess the frequency of subjective and objective dysphagia and its possible pulmonary sequelae, we prospectively studied 22 out-patients with Parkinson's disease; 15 spouses served as controls. All subjects answered a standard questionnaire concerning swallowing and respiratory functions and underwent barium swallow videofluoroscopy. Possible pulmonary infection was investigated by recordings of body temperature, ESR, leucocyte count, and chest X-ray. Patients had significantly more symptoms than controls, especially choking, piece-meal deglutition and regurgitation. Videofluoroscopy revealed tracheal aspiration in one patient, vestibular aspiration in one patient and in one control. Non-fluent swallowing movements were common in patients: abnormal bolus formation, delayed swallowing reflex, vallecular stasis, and piriform sinus residue. None of the subjects had signs of pulmonary infection. Both subjective and objective oro-pharyngeal dysfunction is frequent in ambulant Parkinson patients, but apparently does not produce demonstrable pulmonary infection.

Influence of bolus volume on hyoid movements in normal individuals and patients with Parkinson's disease.

The swallowing movements of 22 ambulant patients with Parkinson's disease were examined by videofluoroscopy, 15 spouses serving as controls. The relation between bolus volume and movement of the hyoid bone was studied in the lateral view to assess the adaptation of the pharynx musculature. Although movement characteristics of the hyoid varied considerably both intra- and interindividually, mean values followed typical patterns. In controls, the position of the hyoid before the start of the swallow tended to be lower as the bolus volume increased, apparently to create space in the oral cavity by lowering the floor of the mouth. This trend was not seen in the group of Parkinson patients. We suppose that this specific lack of adaptation represents hypokinesia. The amplitude of the hyoid movement did not change with increasing bolus volumes, either in patients or in controls. Moreover, Parkinson patients had many more aborted swallowing movements ("hesitations") than controls, probably representing defective switching from the voluntary phase of swallowing to the involuntary, automatic phase.

Carbamazepine (CBZ) controlled release compared with conventional CBZ: a controlled study of attention and vigilance in children with epilepsy.

To compare the effects on attention and vigilance of conventional carbamazepine (CBZ) and CBZ controlled release (CBZ-CR), 15 schoolchildren with epilepsy and normal intelligence receiving CBZ were switched to CBZ-CR. Psychological examination was performed on the day before (day A) and 1 month after substitution (day B). Measurements of attention and vigilance were repeated throughout the day at 2-h intervals. Both on days A and B, CBZ plasma levels were monitored during a 12-h period. Fifteen matched healthy controls were submitted to identical test programs, allowing comparisons within subjects as well as between patients and control children. Variability of performance over sessions was neither increased nor decreased with CBZ-CR. Consistent differences over sessions did not exist between patients and controls with either drug. No relation was noted between reaction time and CBZ plasma level. The pharmacologic data confirm results of earlier studies in children. We noted a reduction in intradose fluctuations of CBZ level with CBZ-CR as compared with conventional CBZ. The neuropsychological results do not show a difference between the drugs. Neither were differences noted with respect to antiepileptic efficacy and side effects. At the end of the study, all but one of the children (and their parents) opted to receive CBZ-CR for ease of dosage administration and overall satisfaction.

Effect of vitamin A on the growth and differentiation of rat external auditory canal epithelium in organ culture.

Intact rat external ear canal explants were maintained either in retinoid-deficient or retinoid-supplemented medium for 7, 10, 14, and 21 days. The morphology of the external ear canal epidermis was well maintained, including the presence of sebaceous glands even after 21 days in culture with retinoid-deficient medium. However, after culturing in retinoid-supplemented medium, the external ear canal epithelium showed both a loss of keratohyalin granules and the formation of keratin. Extensive microvilli formation occurred, even though the desquamation process continued from the superficial layer after 7, 10, and 14 days in culture with retinoid-enriched medium. After 21 days in culture with retinoid-supplemented medium, the ear canal epithelium contained well-developed Golgi apparatus and secretory granules as well. It was concluded that the ear canal epithelium was transformed into a secretory-like mucosal epithelium by retinoid supplementation.

A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.

Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.

A clinical and biochemical assessment of prinomide in patients with rheumatoid arthritis.

Prinomide (CGS-10787B), a potential disease modifying drug, was evaluated clinically and biochemically in 15 patients with active rheumatoid arthritis. The single group study design included monthly assessments of 7 clinical measures and 22 laboratory measures. Twelve patients completed 24 weeks' therapy with prinomide 1.2 g/day. All clinical variables showed improvement which consistently reached statistical significance for articular index from Week 8 (p less than 0.01), for summated change score from Week 12 (p less than 0.01) and for pain score from Week 16 (p less than 0.05). Sustained significant improvement in laboratory variables was seen by Week 2 for erythrocyte sedimentation rate and platelet count (both p less than 0.05), and by Week 4 for plasma viscosity (p less than 0.01), IgG, IgA, IgM (all p less than 0.05).

The effects of diclofenac sodium on arachidonic acid metabolism.

Evidence has been presented that inhibition by diclofenac sodium of the production of leukotrienes by cells participating in the inflammatory process is due to a decreased availability of intracellular arachidonic acid which results from enhanced uptake of the substrate into triglyceride pools. The diminished leukotriene production does not result from direct inhibition of 5-lipoxygenase or phospholipase A2. Reduced availability of arachidonic acid would also limit production of prostaglandins, although in this case manifestation is obscured by the potent inhibitory effect of diclofenac sodium on cyclooxygenase. This recently discovered action of diclofenac sodium, which has been characterized by studies on isolated leukocytes, appears to be operative in vivo. Consistent with this mechanism, and not explainable by classical cyclooxygenase inhibition, diclofenac sodium inhibited leukotriene production in whole blood from drug-treated animals and also suppressed leukocyte infiltration of subcutaneously implanted sponges. The latter effect contrasts with increased infiltration frequently obtained with other NSAIDs and thought to reflect enhanced production of leukotrienes. In conclusion, the findings suggest that patient acceptance or preference for diclofenac sodium is not merely subjective but has a logical scientific basis.