Predictive value of proton magnetic resonance spectroscopy in pediatric closed head injury.

We studied 26 infants (1-18 months old) and 27 children (18 months or older) with acute nonaccidental (n = 21) or other forms (n = 32) of traumatic brain injury using clinical rating scales, a 15-point MRI scoring system, and occipital gray matter short-echo proton MRS. We compared the differences between the acutely determined variables (metabolite ratios and the presence of lactate) and 6- to 12-month outcomes. The metabolite ratios were abnormal (lower NAA/Cre or NAA/Cho; higher Cho/Cre) in patients with a poor outcome. Lactate was evident in 91% of infants and 80% of children with poor outcomes; none of the patients with a good outcome had lactate. At best, the clinical variables alone predicted the outcome in 77% of infants and 86% of children, and lactate alone predicted the outcome in 96% of infants and 96% of children. No further improvement in outcome prediction was observed when the lactate variable was combined with MRI ratios or clinical variables. The findings of spectral sampling in areas of brain not directly injured reflected the effects of global metabolic changes. Proton MRS provides objective data early after traumatic brain injury that can improve the ability to predict long-term neurologic outcome.

1H-magnetic resonance spectroscopy-determined cerebral lactate and poor neurological outcomes in children with central nervous system disease.

By using proton magnetic resonance spectroscopy ((1)H-MRS), cerebral lactate has been shown to be elevated in a wide variety of pediatric and adult neurological diseases. In this study we compared 36 newborns, infants, and children with elevated lactate peaks on (1)H-MRS with 61 patients without an identifiable lactate signal. (1)H-MRS was acquired from the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with echo time = 20 msec, repetition time = 3.0 seconds) and data were expressed as ratios of different metabolite peak areas (N-acetylaspartate [NA]/creatine [Cr], NA/choline [Ch], and Ch/Cr) and the presence of a characteristic lactate doublet peak at 1.3 ppm. Outcomes (Pediatric Cerebral Performance Category Scale score; PCPCS) were assigned 6 to 12 months after injury. Patients with lactate peaks were more likely to have suffered a cardiac arrest, were more often hyperglycemic, and had lower Glasgow Coma Scale scores on admission. They were also more likely to have abnormal metabolite ratios when compared with age-matched controls or with patients without detectable lactate. Of prognostic importance, patients with increased lactate were more likely to be severely disabled (39% vs 10%), survive in a persistent vegetative state (13% vs 2%), or have died (39% vs 7%). In contrast, patients with similar conditions without increased lactate were more likely to have had a good outcome (23% vs 3%) or recovered to a mild (38% vs 6%) or moderate disability (20% vs 0%). Our data suggest that (1)H-MRS is useful in the prediction of long-term outcomes in children with neurological disorders. Patients with elevated cerebral lactate are more likely to die acutely or are at greater risk for serious long-term disability.

Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children.

PURPOSE: To evaluate the usefulness of proton magnetic resonance (MR) spectroscopy in predicting 6-12-month neurologic outcome in children after central nervous system injuries. MATERIALS AND METHODS: Localized single-voxel, 20-msec-echo-time MR spectra (including N-acetylaspartate [NAA], choline [Ch], creatine and phosphocreatine [Cr]) were obtained in the occipital gray matter in 82 patients and 24 control patients. Patient age groups were defined as neonates (< or = 1 month [n = 23]), infants (1-18 months [n = 31]), and children (> or = 18 months [n = 28]). Metabolite ratios and the presence of lactate were determined. Linear discriminant analysis-with admission clinical data, proton MR spectroscopy findings, and MR imaging score (three-point scale based on severity of structural neuroimaging changes)-was performed to help predict outcome in each patient. Findings were then compared with the actual 6-12-month outcome assigned by a pediatric neurologist. RESULTS: Outcome on the basis of proton MR spectroscopy findings combined with clinical data and MR imaging score was predicted correctly in 91% of neonates and in 100% of infants and children. Outcome on the basis of clinical data and MR imaging score alone was 83% in neonates, 84% in infants, and 93% in children. The presence of lactate was significantly higher in patients with poor outcome than in patients with good-moderate outcomes in all three age groups (neonates, 38% vs 5%; infants, 87% vs 5%; children, 64% vs 10% [chi 2 test, P < .02]). In children with poor outcomes, NAA/Cr ratios were significantly lower in infants (P = .006) and children (P < .001), and NAA/Ch ratios were significantly lower in infants (P = .001) and neonates (P = .05). CONCLUSION: Findings at proton MR spectroscopy helped predict long-term neurologic outcomes in children after central nervous system injury.

Proton magnetic resonance spectroscopy in children with acute central nervous system injury.

Single voxel proton magnetic resonance spectroscopy (1H-MRS) was used in 30 infants and children with acute central nervous system injuries to determine the value of changes in specific metabolite ratios in predicting outcome. The mean age of all patients was 38 +/- 52 months and the mean time of study after insult was 7 +/- 5 days. 1H-MRS was determined in the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with TE = 20 ms, TR = 3,000 ms). Data were expressed as ratios of different metabolite peak areas including N-acetylaspartate (NA), choline-containing compounds (Ch), creatine and phosphocreatine (Cr), and lactate (Lac). Statistically significant differences were observed when patients with good/moderate (G/M) outcomes (n = 17; mean age: 46 months) were compared to patients with bad outcomes (n = 10; mean age: 26 months). NA/Cr and NA/Ch were significantly lower in the bad outcome group (NA/Cr = 1.15 +/- 0.38; NA/Ch = 1.18 +/- 0.52) compared to the G/M group (NA/Cr = 1.41 +/- 0.28, P < .05; NA/Ch = 1.98 +/- 0.81, P < .01). Lactate was present in 80% of bad outcome patients and in none of the G/M group (P < .0001). Using a linear discriminant analysis and combining 4 clinical variables (Glasgow Coma Scale score, initial pH and glucose, number of days unconscious at time of 1H-MRS) allows classification of 94% of patients into their correct outcome group. Use of spectroscopy variables (NA/Cr, NA/Ch, Ch/Cr, presence of lactate) alone correctly classified 81% of patients. The combination of clinical and 1H-MRS variables correctly classified 100% of patients. Our findings suggest that 1H-MRS adds information which, in combination with clinical examination, may be useful in outcome assessment in children with serious acute central nervous system injury.

CBF and CBF/PCO2 reactivity in childhood strangulation.

Four children with self-inflicted strangulation injuries had cerebral blood flow determined by stable xenon computed tomography (XeCTCBF) within 24 hours of admission. All had suffered a severe hypoxic-ischemic cerebral injury; 3 initially had fixed pupils, all were apneic with varying bradyarrhythmias, and the initial mean arterial pH was 7.26 (+/- 0.18). The initial blood glucose values were greater than 300 mg/dl (334 and 351 mg/dl) in the 2 patients who died compared to the 2 who survived (104 and 295 mg/dl). The cardiac index was depressed during the first several days of hospitalization in the 2 patients who died (less than 2.0 L/min/m2) compared to the 2 who survived. Total CBF was normal (63 +/- 8 ml/min/100 gm) and local variations in CBF were present. PCO2 reactivity was determined by hyperventilating the 4 patients for 20 min from an end tidal PCO2 of 39 +/- 3 torr to 29 +/- 1 torr and then repeating the XeCTCBF study. Marked regional variability in the CBF/PCO2 response was observed, ranging from 0.5-5.5 ml/min/100 gm/torr PCO2. In the 2 patients who died, the CBF/PCO2 was decreased (1.2 ml/min/100 gm/torr PCO2) compared to the 2 patients who survived (2.1 ml/min/100 gm/torr PCO2). Although CBF was normal in these 4 children, the hyperventilation response was depressed, variable, and even paradoxical which may be important in the evolution of further brain injury and is a critical factor in deciding whether hyperventilation may be of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Anencephaly: clinical determination of brain death and neuropathologic studies.

Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.

A distinctive neurologic syndrome after induced profound hypothermia.

Four patients suffered a distinctive neurologic syndrome after undergoing profound hypothermia and complete circulatory arrest for congenital heart lesion repair. Symptom onset was delayed 24-120 hours postoperatively. The syndrome consists of choreoathetosis and oral-facial dyskinesias, hypotonia, affective changes, and pseudobulbar signs (CHAP). Precise anatomic localization is uncertain. Magnetic resonance imaging of 2 patients did not reveal basal ganglia lesions. Pathogenesis is obscure.

The diminishing incidence of hypsarrhythmia.

The incidence of hypsa over a 40-year period in 667 pts was noted to rise to a peak in 1958 and then to fall so that relatively few cases appeared in the early 1970's, with hypsa seen only rarely in the past 10 years. This diminishing incidence was confirmed in a major children's hospital. The incidence curve of rubeola is seen to follow a similar course; the possibility is discussed that subclinical infectious disease, and rubeola in particular as a prototype, may have played a more prominent role in the etiology of hypsa than has been considered in the past.

Reversibility of human myopathy caused by vitamin E deficiency.

Although a neuromuscular syndrome has been induced experimentally by vitamin E deficiency, a human syndrome has not yet been documented. This report describes a 7-year-old boy with severe malabsorption since birth who presented with progressive external ophthalmoplegia, proximal muscle weakness, peripheral neuropathy, hyporeflexia, and bilateral Babinski signs. Abnormalities on neurologic examination included elevated creatine phosphokinase and aldolase, slowed distal sensory latencies, type II muscle fiber atrophy, and a plasma vitamin E level of 8 microgram per deciliter (normal, 550-1500 microgram per deciliter). Treatment with oral water-solubilized vitamin E (400 IU daily; greater than 50 times the normal daily intake) was begun, with repeat laboratory studies at 3-month intervals. Over a 16-month period, plasma vitamin E content gradually increased to 350 microgram per deciliter, associated with declining sarcoplasmic enzyme activities and clinical improvement.

Ophthalmoplegia and bulbar palsy in variant form of maple syrup urine disease.

This is the third reported case of a neonate with ophthalmoplegia in whom the diagnosis of maple syrup urine disease (MSUD) was delayed into infancy. In this case, the demonstration of significant residual branched-chain ketoacid decarboxylase activities suggests that this atypical presentation may be characteristic of the MSUD variant form.

Purtscher retinopathy in the battered child syndrome.

Purtscher retinopathy is a hemorrhagic angiopathy that occurs after sudden compression of the thorax. Virtually all reported cases have been in adults who have decreased visual acuity, retinal hemorrhages and exudates, and no other neurological signs. By contrast, in infants, hemorrhagic retinopathy is rarely benign, and generally is considered to indicate intracranial hemorrhage, usually an acute subdural hematoma. Two battered infants had seizures and associated chest injury. There were retinal hemorrhages and exudates, unaccompanied by clinically important intracranial hemorrhage. At follow-up, the hemorrhagic retinopathy had resolved without sequelae; development was normal, and seizures had not recurred. Purtscher retinopathy thus should be added both to the differential diagnosis of hemorrhagic retinopathy in infancy and to the list of physical signs suggesting child abuse.

Changes in the distribution of a histone in dorsal root ganglion neurons during development.

The isolation and cellular localization of a basic protein (histone) from central nervous tissue have been previously reported. In the tissues previously studied (nervous tissue, testis, liver, spleen, kidney, ovary), the basic protein was restricted in distribution to the nuclei of neurons and spermatogonia. In the present study, the temporal appearance of the histone within neurons and the changes in its distribution during ontogenesis were examined. The reaction between a fluorescent immune gamma-globulin prepared against this purified tissue-specific histone and the neurons from the dorsal root ganglia of the rat was investigated. The dorsal root ganglia examined were those from fetuses, 2-, 10-, and 40-day-old rats, and from adult rats. At the earliest stages, only the nucleoli reacted. Subsequently, threads of fluorescent material were seen to emerge from the nucleoli. The extent of this reaction between the immune globulin and the threads within the nuclei continued to increase with maturation. No changes in fluorescence localization during development could be seen in the nuclei of neurons in the cerebellum or brain stem. The role that this tissue-specific histone may play in cell function is discussed.