Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand.

We describe use of a bidirectional neuromyoelectric prosthetic hand that conveys biomimetic sensory feedback. Electromyographic recordings from residual arm muscles were decoded to provide independent and proportional control of a six-DOF prosthetic hand and wrist-the DEKA LUKE arm. Activation of contact sensors on the prosthesis resulted in intraneural microstimulation of residual sensory nerve fibers through chronically implanted Utah Slanted Electrode Arrays, thereby evoking tactile percepts on the phantom hand. With sensory feedback enabled, the participant exhibited greater precision in grip force and was better able to handle fragile objects. With active exploration, the participant was also able to distinguish between small and large objects and between soft and hard ones. When the sensory feedback was biomimetic-designed to mimic natural sensory signals-the participant was able to identify the objects significantly faster than with the use of traditional encoding algorithms that depended on only the present stimulus intensity. Thus, artificial touch can be sculpted by patterning the sensory feedback, and biologically inspired patterns elicit more interpretable and useful percepts.

Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder.

To determine whether circadian profiles of various plasma hormones are abnormal in patients with winter seasonal affective disorder (SAD), we obtained 24-hour profiles of plasma cortisol, prolactin, and thyrotropin in subsets of a sample of 22 depressed patients with SAD on and off light therapy and in subsets of a sample of 24 normal controls. Cortisol levels did not differ between patients and controls, and levels in patients were not affected by light therapy. Prolactin levels were lower in patients than in controls throughout the day (p < 0.03) but were unaffected by light therapy. Independent of patient vs. control status, prolactin levels were higher in women than in men throughout the day (p < 0.003). Thyrotropin levels were no different in patients and controls, but levels in patients were lower following light therapy (p < 0.05).

Effects of bright light on resting metabolic rate in patients with seasonal affective disorder and control subjects.

Many of the symptoms of seasonal affective disorder (SAD) could be construed as having an energy-conserving function. We predicted that SAD patients would have abnormally low resting metabolic rates (RMR), which would be increased to normal levels by light therapy. To test this hypothesis we measured RMR in 10 patients on and off light treatment and 9 normal controls. Contrary to our prediction we found that SAD patients had significantly higher RMR values compared with the normal population (p less than 0.02) and these values were significantly lowered by light treatment (p less than 0.05). The possible implications of these findings are discussed.

Delayed hemorrhagic infarction. A cause of late neonatal germinal matrix and intraventricular hemorrhage.

Although a single perinatal or postnatal event may be directly correlated to intraventricular hemorrhage (IVH) in some infants, in other infants IVH may be related to a series of insults. Asphyxia, hypotension, and a pressure-passive low cerebral blood flow (CBF) may lead to an infarction. Subsequent events known to cause sudden rises in the CBF may then produce a hemorrhage into damaged tissues. We report two cases of this proposed model for delayed hemorrhage into infarcted tissues, or late IVH. Both neonates were severely asphyxiated, and both experienced profound hypotension and a low CBF on the first postnatal day. Late IVH was found in both neonates; at 2 to 3 months of age, one neonate was found to have computed tomographic evidence for diffuse encephalomalacia, and the other neonate was noted to have an occipital porencephalic cyst.

Beagle puppy model of intraventricular hemorrhage: randomized indomethacin prevention trial.

The newborn beagle puppy has been demonstrated to provide a good model for neonatal intraventricular hemorrhage (IVH). By randomized computerized design, indomethacin, a known inhibitor of prostaglandin synthetase, was administered to newborn beagle puppies, all of which underwent the experimental model of hemorrhagic hypotension followed by volume reexpansion for the production of IVH, to determine whether indomethacin can prevent intraventricular hemorrhage in this model. Nine percent of all pups receiving indomethacin experienced intraventricular hemorrhage, compared with 80% of animals who received the saline vehicle. In addition, significant alterations in the blood pressure responses to the hemorrhagic hypotension/volume reexpansion insult were noted in this group when compared with control animals.

Alterations in cerebral blood flow in preterm infants with intraventricular hemorrhage.

Xenon-133 inhalation hemispheric cerebral blood flow (HCBF) determinations at one to two days and four to six days postnatally and at 37 weeks postconceptual age have been correlated with computed tomography (CT) scan and autopsy findings in 15 preterm infants weighing less than 1,250 gm at birth. Ten of these infants had germinal matrix hemorrhages (GMH) or intraventricular hemorrhages (IVH). Although HCBF obtained at one to two days showed no mean difference between the GMH/IVH group and the nonhemorrhage infants, hemispheric flow ratios showed significant discrepancies in the GMH/IVH group. In addition, in four of five patients in whom the hemorrhage appeared asymmetric on CT scan, the side of higher flow correlated with the hemorrhage. At four to six days HCBF showed a lower mean value in the GMH/IVH patients than in the nonhemorrhage patients and differences in the interhemispheric ratios in the GMH/IVH group persisted. There were no differences in the mean HCBF values or hemispheric ratios between the two groups of infants at 37 weeks postconceptual age.

Outcome of children in the indomethacin intraventricular hemorrhage prevention trial.

BACKGROUND: For preterm infants, intraventricular hemorrhage (IVH) may be associated with adverse neurodevelopmental outcome. We have demonstrated that early low-dose indomethacin treatment is associated with a decrease in both the incidence and severity of IVH in very low birth weight preterm infants. In addition, we hypothesized that the early administration of low-dose indomethacin would not be associated with an increase in the incidence of neurodevelopmental handicap at 4.5 years of age in our study children. METHODS: To test this hypothesis, we provided neurodevelopmental follow-up for the 384 very low birth weight survivors of the Multicenter Randomized Indomethacin IVH Prevention Trial. Three hundred thirty-seven children (88%) were evaluated at 54 months' corrected age, and underwent neurodevelopmental examinations, including the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Peabody Picture Vocabulary Test-Revised (PPVT-R), and standard neurologic examinations. RESULTS: Of the 337 study children, 170 had been randomized to early low-dose indomethacin therapy and 167 children had received placebo. Twelve (7%) of the 165 indomethacin children and 11 (7%) of the 158 placebo children who underwent neurologic examinations were found to have cerebral palsy. For the 233 English-monolingual children for whom cognitive outcome data follow, the mean gestational age was significantly younger for the children who received indomethacin than for those who received placebo. In addition, although there were no differences in the WPPSI-R or the PPVT-R scores between the 2 groups, analysis of the WPPSI-R full-scale IQ by function range demonstrated significantly less mental retardation among those children randomized to early low-dose indomethacin (for the indomethacin study children, 9% had an IQ <70, 12% had an IQ of 70-80, and 79% had an IQ >80, compared with the placebo group, for whom 17% had an IQ <70, 18% had an IQ of 70-80, and 65% had an IQ >80). Indomethacin children also experienced significantly less difficulty with vocabulary skills as assessed by the PPVT-R when compared with placebo children. CONCLUSIONS: These data suggest that, for preterm neonates, the early administration of low-dose indomethacin therapy is not associated with adverse neurodevelopmental function at 54 months' corrected age.

Minimal head trauma in children revisited: is routine hospitalization required?

OBJECTIVE: Children with a question of occult head injury are routinely hospitalized despite having both normal central nervous system (CNS) and computed tomographic (CT) scan examinations. We determined the incidence of significant CNS morbidity after occult head injury to determine whether or not hospital admission was necessary in children after minimal head trauma. METHODS: We reviewed the records of children admitted to a level I trauma center with a question of closed head injury, an initial Glasgow Coma Scale equal to 15, a normal neurologic exam, and a normal head CT scan. Children with associated injuries requiring admission were excluded. The endpoints were deterioration in CNS exam, new CT findings, and the need for a prolonged hospital stay. RESULTS: Sixty-two patients were studied with a mean age of 7 years (range, 1 month to 15 years), and 65% were male. The primary mechanisms of injury were fall (45%) and vehicular crash (23%). The mean injury severity score was 4 +/- 2. The mean length of stay was 1.2 days (range, 1 to 3 days). Prolonged hospitalization occurred in 9 patients (15%). No child developed significant CNS sequelae warranting hospital admission. Total charges for these hospitalizations were $177 874. CONCLUSIONS: Children undergoing emergency department work-up of occult head injury, who have a normal CNS exam and a normal head CT scan, do not seem to be at risk for significant CNS sequelae. These patients can be discharged home with parental supervision and avoid unnecessary and costly hospitalization.

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.

Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial.

OBJECTIVES: Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelopmental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). METHODS: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. RESULTS: Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo. CONCLUSIONS: Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

Human eastern equine encephalitis. Electron microscopic study of a brain biopsy.

An electron microscopic study was done on brain biopsy tissue from an eight-month-old female with acute eastern equine encephalitis diagnosed by indirect immunofluorescence. Rare clusters of round virions were found almost exclusively in the extracellular space. All virions observed had spiked envelopes, and their sizes averaged approximately 55 nm. Also found were rare enveloped virions along with degenerate organelles in a membrane-bound structure in the cytoplasm of macrophages. Intracytoplasmic development of virions was not found. Tubuloreticular complexes were seen in the endothelial cells and macrophages. This is the first report of an electron microscopic study on biopsy material from a case of human eastern equine encephalitis. It will extend the usefulness of brain biopsy in the diagnosis of acute encephalitis.

Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia.

Patients with schizophrenia appear to have abnormalities in both brain structures and information processing. Several recent reports have suggested that correlations exist between such measures. We examined the volume of several brain regions using magnetic resonance imaging (MRI), and also assessed both information processing, using brain event-related potentials (ERPs), and clinical symptomatology in sixteen medicated patients with schizophrenia. Subjects were tested using auditory and visual discrimination tasks. From the ERPs elicited by stimuli presented with relative probabilities of 0.1, the N100, N200, and P300 components were identified and measured. All subjects also had MRI scans that included 12 contiguous coronal sections, each 1 cm thick. From these scans, the following structures were identified and the volume or area quantified: third ventricle, lateral ventricles (partial), amygdala and hippocampus (one slice), partial brain volume (in one slice through the parietal lobe), and total prefrontal and temporal lobe gray and white matter in both cortical regions. Significant correlations were found between hippocampal area and the amplitude of the auditory and visual N200, and between the right hippocampus and the visual P300. Lower but significant correlations were seen between auditory P300 and measures of left temporal lobe structures. Auditory P300 amplitude correlated inversely with positive symptoms of schizophrenia. These preliminary results suggest that the ERP abnormalities in patients with schizophrenia are associated with temporal lobe pathology.

A nosology of disorders of attention.

The trailblazing research on sleep mechanisms and petit mal epilepsy, conducted during the period from 1940 through 1970, illuminated the brain substrate for normal consciousness and attention, as well as their disorders. This research helped inform and structure our neuropsychologically based model of the "elements" of attention. The model has been used to assess attention in the research laboratory and clinic, and has led to a "nosology of disorders of attention," which is presented here in preliminary form. The nosology reviews the possible causes of the symptom(s) of impaired attention, as well as suggesting a blueprint for future research in this area.

Event-related brain potentials: a window on information processing in schizophrenia.

The application of the P300 component of the event-related brain potential to the study of attentional impairment in schizophrenia is discussed, and two recent studies are described. In one, the relative effects on P300 of stimulus modality and probability were evaluated. The data showed that the P300 is smaller in schizophrenic patients relative to normal controls for low-probability auditory stimuli. Next is described a preliminary report that evaluated whether this P300 reduction reflects a core deficit (trait marker) or clinical symptomatology (state marker). To pursue this question, a group of schizophrenic patients was studied on and off neuroleptic medication. The data showed that improvement in clinical state was highly correlated with increased visual P300 but was uncorrelated with auditory P300. These findings suggest that P300 elicited in the visual modality has the characteristics of a state marker of schizophrenia. In contrast, auditory P300 remains a candidate for a vulnerability trait marker of schizophrenia. The core deficit in schizophrenia thus appears to involve the auditory information-processing system, whereas fluctuations in clinical state may be reflected in the visual processing system.

Evaluation of level of consciousness by the Glasgow coma scale in children with Reye's syndrome.

The Glasgow Coma Scale, which was designed to evaluate level of consciousness after head trauma, has been compared to the Lovejoy scale in 21 patients with Reye's syndrome. Like other investigators, we have noted a poorer prognosis in those patients with higher peak NH3 levels and rapid progression of disease. However, we have also noted that the Glasgow coma scale provides a better, earlier indicator of progressive central nervous system disease than the Lovejoy scale and, therefore, helps physicians caring for such patients to institute intracranial pressure (ICP) monitoring and vigorous measures for the control of elevated ICP earlier than they might otherwise.

Cranial asymmetry and lambdoid synostosis in a sibship.

In craniosynostosis, as in all congenital diseases, the interaction of hereditary and neonatal environmental factors can be separated only in rare cases. Four siblings with an asymmetry of the posterior right portion of the skull are presented. The youngest of the four suffered from severe cyanotic congenital heart diseases and secondarily suffered from ischemic/hypoxic cerebral injury. This child had complete synostosis of the right lambdoid and posterior sagittal sutures by the age of 5 1/2 months. The cranial asymmetry was less pronounced in each of the older children and was nearly undetectable in the oldest, a 7 1/2-year-old girl. True synostosis was not present in any of the older siblings. It is suggested that an autosomal-dominant hereditary condition caused a hypotrophic mesenchymal relationship of occipitotemporal ontogenesis. This condition was compensated for through childhood by the molding effect of the brain in the older three siblings. The systemic disease and delayed cerebral growth in the youngest probably led to the complete picture of craniosynostosis.

Petit mal epilepsy: a review and integration of recent information.

Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy.

Management of proximal shunt obstruction. Technical note.

Proximal shunt obstruction or obstruction of the ventricular catheter may present with signs and symptoms of shunt failure with either no cerebrospinal fluid flow or a falsely low intracranial pressure (ICP) upon shunt tap. The author reports a technique for lowering the ICP and for measuring the pressure in patients with such obstruction by cannulation of the reservoir and ventricular catheter to penetrate into the ventricle with a 3 1/2-in. No. 22 spinal needle. The findings in 20 cases in which this approach was utilized are summarized.

Removal of retained ventricular shunt catheters without craniotomy. Technical note.

A technique is described in which insulated suction is used to extract infected retained ventricular catheters in cases of shunt infection. This procedure allows safe removal without craniotomy. Retained catheters are pulled through an insulated No. 11F or 13F suction tube attached to an electrocoagulation unit used for resection and coagulation of adhesions. The technique has been successful in two cases with retained catheters.

Benign enlargement of the subarachnoid spaces in the infant.

The authors report 18 infants with benign enlargement of the subarachnoid spaces seen at their institution during a 1-year time interval. This condition is characterized by the computerized tomography findings of dilatation of the subarachnoid spaces, normal or slightly enlarged ventricular size, and prominence of the basilar cisterns. Most cases were found in children referred for the evaluation of abnormally increasing head circumference measurements. Although it was not possible to document the development, and, in several cases, improvement of this process, in these patients enlargement of the subarachnoid spaces was a benign diagnosis, not associated with serious neurological dysfunction.