The First Examination of Diagnostic Performance of Automated Measurement of the Callosal Angle in 1856 Elderly Patients and Volunteers Indicates That 12.4% of Exams Met the Criteria for Possible Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Many patients with dementia may have comorbid or misdiagnosed normal pressure hydrocephalus, a treatable neurologic disorder. The callosal angle is a validated biomarker for normal pressure hydrocephalus with 93% diagnostic accuracy. Our purpose was to develop and evaluate an algorithm for automatically computing callosal angles from MR images of the brain. MATERIALS AND METHODS: This article reports the results of analyzing callosal angles from 1856 subjects with 5264 MR images from the Open Access Series of Imaging Studies and the Alzheimer's Disease Neuroimaging Initiative databases. Measurement variability was examined between 2 neuroradiologists (n = 50) and between manual and automatic measurements (n = 281); from differences in simulated head orientation; and from real-world changes in patients with multiple examinations (n = 906). We evaluated the effectiveness of the automatic callosal angle to differentiate normal pressure hydrocephalus from Alzheimer disease in a simulated cohort. RESULTS: The algorithm identified that 12.4% of subjects from these carefully screened cohorts had callosal angles of <90°, a published threshold for possible normal pressure hydrocephalus. The intraclass correlation coefficient was 0.97 for agreement between neuroradiologists and 0.90 for agreement between manual and automatic measurement. The method was robust to different head orientations. The median coefficient of variation for repeat examinations was 4.2% (Q1 = 3.1%, Q3 = 5.8%). The simulated classification of normal pressure hydrocephalus versus Alzheimer using the automatic callosal angle had an accuracy, sensitivity, and specificity of 0.87 each. CONCLUSIONS: In even the most pristine research databases, analyses of the callosal angle indicate that some patients may have normal pressure hydrocephalus. The automatic callosal angle measurement can rapidly and objectively screen for normal pressure hydrocephalus in patients who would otherwise be misdiagnosed.

Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.

A soluble monomeric form of Alzheimer's amyloid-beta (1-40) peptide (sAbeta1-40) is present in the circulation and could contribute to neurotoxicity if it crosses the brain capillary endothelium, which comprises the blood-brain barrier (BBB) in vivo. This study characterizes endothelial binding and transcytosis of a synthetic peptide homologous to human sAbeta1-40 using an in vitro model of human BBB. 125I-sAbeta1-40 binding to the brain microvascular endothelial cell monolayer was time dependent, polarized to the apical side, and saturable with high- and low-affinity dissociation constants of 7.8+/-1.2 and 52.8+/-6.2 nM, respectively. Binding of 125I-sAbeta1-40 was inhibited by anti-RAGE (receptor for advanced glycation end products) antibody (63%) and by acetylated low density lipoproteins (33%). Consistent with these data, transfected cultured cells overexpressing RAGE or macrophage scavenger receptor (SR), type A, displayed binding and internalization of 125I-sAbeta1-40. The internalized peptide remains intact > 94%. Transcytosis of 125I-sAbeta1-40 was time and temperature dependent, asymmetrical from the apical to basolateral side, saturable with a Michaelis constant of 45+/-9 nM, and partially sensitive to RAGE blockade (36%) but not to SR blockade. We conclude that RAGE and SR mediate binding of sAbeta1-40 at the apical side of human BBB, and that RAGE is also involved in sAbeta1-40 transcytosis.

Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization.

PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. METHODS: MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. RESULTS: Taurine (Tau) was significantly elevated in medulloblastomas (P < .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentration, in pineal germinomas. Creatine (Cr) was significantly reduced in pilocytic astrocytomas, distinguishing them from All Other (P < .000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P < .01) concentrations; however, myoinositol was elevated (P < .01) and total choline (tCho) (P < .0001) was reduced relative to All Other. Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors studied. Guanidinoacetate was reduced in low-grade astrocytomas and anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P < .00001 versus All Other). CONCLUSION: Quantitative proton MR spectroscopy reveals features of pediatric brain tumors that are likely to improve preoperative diagnoses.

Kinetics of arginine-vasopressin uptake at the blood-brain barrier.

Uptake of arginine-vasopressin, VP, at the luminal side of the blood-brain barrier (BBB) was studied by means of an in situ brain perfusion technique in the guinea-pig. Kinetic experiments revealed a saturable peptide influx into the parietal cortex, caudate nucleus and hippocampus with Km between 2.1 and 2.7 microM, and Vmax ranging from 4.9 to 5.6 pmol.min-1.g-1. The non-saturable component, Kd, was not significantly different from zero. Influx of VP into the brain was not altered by the presence of the peptide fragments: VP-(1-8), pressinoic acid and [pGlu4,Cyt6]VP-(4-9) at 4.5 microM, nor yet by the aminopeptidase inhibitor, bestatin (0.5 mM) and the L-amino acid transport system substrates, L-tyrosine and L-phenylalanine at 5 mM. At a perfusate concentration of 4.5 microM, the V1-vasopressinergic receptor antagonist, d(CH2)5[Tyr(Me)2]VP, reduced VP influx; regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 4.7 and 8.5 microM. It is concluded that there is an apparent cerebrovascular permeability to circulating VP due to the presence of a carrier-mediated transport system for the peptide located at the luminal side. The mechanism for VP BBB uptake exhibits no affinity for peptide fragments and large neutral amino acids, but requires reception of the intact molecule, which may be the same initial step for both the BBB VP transporter and the V1-receptor.

Current and emerging MR imaging techniques for the diagnosis and management of CSF flow disorders: a review of phase-contrast and time-spatial labeling inversion pulse.

This article provides an overview of phase-contrast and time-spatial labeling inversion pulse MR imaging techniques to assess CSF movement in the CNS under normal and pathophysiologic situations. Phase-contrast can quantitatively measure stroke volume in selected regions, notably the aqueduct of Sylvius, synchronized to the heartbeat. Judicious fine-tuning of the technique is needed to achieve maximal temporal resolution, and it has limited visualization of CSF motion in many CNS regions. Phase-contrast is frequently used to evaluate those patients with suspected normal pressure hydrocephalus and a Chiari I malformation. Correlation with successful treatment outcome has been problematic. Time-spatial labeling inversion pulse, with a high signal-to-noise ratio, assesses linear and turbulent motion of CSF anywhere in the CNS. Time-spatial labeling inversion pulse can qualitatively visualize whether CSF flows between 2 compartments and determine whether there is flow through the aqueduct of Sylvius or a new surgically created stoma. Cine images reveal CSF linear and turbulent flow patterns.

Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy.

Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector-transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100% HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day) in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87% compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7 increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and periphery, respectively. We conclude that RMP-7 could be an important adjunctive treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV combination may also have a significant antitumor effect in untransfected gliomas.

The effect of cerebrospinal fluid pressure on the size of drainage pathways.

The cerebrospinal fluid drainage pathways were studied using labeled molecules of different sizes. Following determination of the limiting size, the cerebrospinal fluid pressure was raised above the normal range and changes in transfer were measured. These data show that molecules smaller than the limiting size will transfer at an increased rate in response to elevated pressures. Larger molecules did not demonstrate an increased transfer with raised cerebrospinal fluid pressures, suggesting that the pathways did not enlarge.

Galactose-induced cataract formation in guinea pigs: morphologic changes and accumulation of galactitol.

PURPOSE: To develop and characterize a new model of galactose-induced cataract formation in young, 3- to 4-week-old Hartley guinea pigs. METHODS: Experimental animals were fed 50% galactose in powdered guinea pig chow containing 0.5 g ascorbate/kg diet. Control animals were fed normal powdered guinea pig chow (0.5 g ascorbate/kg diet). Lenses from all animals were subjected to photo-slit-lamp examination, light microscopic analysis, and high-pressure liquid chromatography (HPLC) analysis of polyol content. RESULTS: Photo-slit-lamp examination indicated initial opacities in equatorial subcapsular region between 3 and 5 days in all galactose-fed animals (20/20); opacities progressed toward the anterior pole when diet was extended to 14 days. Histologic analysis of the equatorial changes confirmed progressive cataract formation consisting of small intra-fibrillar vacuoles in the pre-equatorial region (3 days), an increased number of enlarged and coalesced vacuoles (6 days), and progressive tissue swellings with cellular disruption and signs of epithelial multilayering (14 days). The anterior epithelium showed increased cell height and swelling after 3 days of the galactose diet. HPLC analysis of lens tissue indicated progressive accumulation of galactitol, 18 mM after 3 days, which plateaued to about 30 mM between 6 and 14 days. The level of myo-inositol dropped from a control value of 2.8 +/- 0.7 mM to 1.5 +/- 0.7 mM after 3 days, and was nearly undetectable after 14 days of the galactose diet. CONCLUSIONS: The current study suggests that the guinea pig model may serve as a valuable new tool to study sugar-induced cataract formation and to characterize the early morphologic and biochemical events in cataractogenesis.

Further studies on the difference between ventricular and subarachnoid perfusion.

In order to study the exchanges between the subarachnoid fluid and the adjacent cortical tissue independently of the choroid plexus, artificial cerebrospinal fluid (CSF) was perfused from the supracallosal cistern to the cisterna magna in the rabbit. Test substances were introduced into the blood and held at a constant level. The degree of penetration by the blood-borne test substances into the artificial CSF perfused into the cortical subarachnoid space was noted. The degree of penetration of these test substances into the artificial CSF does not solely reflect rates of exchange between this fluid and the exposed cortex for it was shown histologically as well as physiologically that the artificial CSF does not remain in the subarachnoid space but also enters the subdural space to exchange with the blood via the dural capillaries. Thus this experimental model routinely produces an artefactual situation which restricts its use in the study of CSF-brain relations.

Blood-cerebrospinal fluid barrier alteration following intraventricularly administered cholera toxin.

Cholera toxin (CT) has been reported to double cerebrospinal fluid (CSF) formation following its introduction into the ventricular system of cats and dogs. In our laboratory we noted that CT used in a similar fashion in rabbits and cats resulted in only a slight increase in CSF formation and was associated with a steadily rising protein content in the cisterna magna effluent. To further investigate this finding, rabbits and cats underwent ventriculo-cisternal perfusions, one group with CT introduced into the ventricles and the other without. In the rabbit only, radioiodinated serum albumin (125I-RISA) was given i.v. Other groups of rabbits had 125I-RISA or 125I-CT injected into the ventricles. The group of rabbits receiving intraventricular CT experienced a 4-10-fold elevation in the amount of both protein and 125I-RISA in the cisterna magna effluent compared with the control group. Electrophoretic pattern of the protein present in the effluent was similar to that of rabbit plasma. Autoradiography of the brains of those animals given intraventricular 125I-CT were found to have a very high uptake of 125I-CT in the choroid plexus and along all exposed ventricular surfaces, a finding not evident when 125I-RISA alone was given intraventricularly. It is concluded that CT altered the blood-CSF barriers allowing the reference marker to penetrate these barriers and plasma to leak into the CSF. These findings appear to account for most if not all of what was thought to be an increase in CSF formation in response to intraventricular CT.

Transport, uptake, and metabolism of blood-borne vasopressin by the blood-brain barrier.

Transport, binding, and metabolism of [phenylalanyl-3,4,5,-3H(N)]arginine vasopressin (AVP) by the blood-brain barrier (BBB) was studied in adult guinea-pigs by means of a novel vascular brain perfusion (VBP)/capillary depletion technique and HPLC. A time-dependent, progressive brain uptake of 3H-radioactivity was measured over the 10 min period of VBP both in brain homogenates and in brain tissue depleted of cerebral microvessels. The unidirectional blood-to-brain transport constant, K(IN), estimated by multiple-time tissue uptake analysis of the homogenate and postcapillary supernatant, indicated that the BBB transfer rate for [3H]AVP (K(IN) = 2.37 +/- 0.25 microliters min-1 per gram brain homogenate) was almost 10 times higher than for simultaneously perfused [14C]sucrose, a cerebrovascular space marker. In contrast to homogenate and postcapillary supernatant, the [3H]radioactivity determined in the vascular pellet after dextran density centrifugation of the brain homogenate was very low and only somewhat higher than for [14C]sucrose. HPLC analysis of the perfused brain tissue revealed time-dependent degradation of the blood-borne neuropeptide. The percentage of intact [3H]AVP as determined in the postcapillary supernatant progressively declined during brain perfusion, from 49% at 1 min to 11.9% at 10 min. The major detectable labeled metabolite was [3H]phenylalanine, the labeled amino acid residue of [3H]AVP. The aminopeptidase inhibitor bestatin (0.5 mM), perfused simultaneously with [3H]AVP by the VBP technique, did not alter tissue uptake of [3H]AVP, indicating that there was no significant hydrolysis of peptide by the luminal BBB surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid beta in guinea pigs.

An intracarotid brain infusion/capillary depletion technique was used in guinea pigs to examine cerebral capillary sequestration and transport into brain parenchyma of sA beta 1-40 and sA beta 1-42, synthetic peptides identical to two forms of the amyloid beta peptide found in Alzheimer's disease lesions: the 40 residue form, found primarily in vascular deposits, and the 42 residue form, found primarily in senile plaques. The peptides crossed well into the brain parenchyma via a specific transport mechanism for which sA beta 1-40 had an approximately two-fold greater affinity than sA beta 1-42. There was significant capillary sequestration of sA beta 1-40, but retention by the microvasculature of sA beta 1-42 was negligible. These data suggest that the level of the 40 residue peptide in cerebral vasculature and of the 42 residue peptide in parenchyma could be regulated by blood-brain barrier sequestration and transport of their respective circulating precursors.

Early CT detection of intracranial seeding from medulloblastoma.

Since 1975, intracranial subarachnoid metastases of medulloblastoma have been detected in seven of 23 initial contrast-enhanced computed tomographic (CT) scans in children with proven medulloblastoma. Furthermore, four of the seven cases with subarachnoid seeding were diagnosed after the introduction of high-resolution contrast-enhanced CT. Only three cases of seeding had been detected in the previous 17 low-resolution cases studied with CT. Thus, it is quite likely that the incidence of subarachnoid metastases may be substantially more than the overall figure of 30% indicated by this series. This may have an impact on the treatment of these patients, since the frequent appearance of metastases may indicate the need for more vigorous chemotherapeutic regimens. One should be aware of the possibility of early intracranial subarachnoid seeding and that it can be demonstrated by contrast-enhanced CT. This is particularly true when using high-resolution scanners in conjunction with 5 mm sections through the posterior fossa.

Integration of a variable action suction adapter into ultrasonic aspirators.

PURPOSE: Use of ultrasonic aspirators has become a mainstay in the neurosurgical armamentarium. The handpiece design and ultrasonic parameters have evolved to maximize its safe and efficacious use. Despite these modifications, continuous suction through the tip of the aspirator can result in neurovascular damage, especially when the aspirator is working in the cavernous sinus region or cerebellopontine angle. CONCEPT: We describe the integration of a variable suction adapter into the existing handpiece of an ultrasonic aspirator to minimize potential injury from the continuous forceful suction normally associated with the use of these devices. RATIONALE: The integration of such an adapter can reduce the potential for suction injury to cranial nerves or microvascular structures or smaller-caliber arteries and veins. DISCUSSION: This variable action suction adapter can decrease suction injuries to cranial nerves or the microvasculature.

Intracranial pressure monitoring in severe pediatric near-drowning.

Between April 1979 and April 1981, 20 near-drowned children admitted to Childrens Hospital of Los Angeles with a Glasgow coma score of 3 underwent intracranial pressure (ICP) monitoring and brain resuscitative therapy. By the 3rd hospital day, 14 patients had developed ICP elevation above 20 torr, and 11 of these had sustained intracranial hypertension above 30 torr. Ten of these children died, and 4 remain in a persistent vegetative state. Of 6 patients whose ICP never exceeded 20 torr, 3 recovered completely, 1 died, and 2 remain without any cognitive function. The salvage rate for patients with normal ICP after near-drowning accidents is significantly better than that for patients in whom the ICP is elevated (P = 0.017). Intracranial hypertension is associated with a uniformly bad outcome and is frequent in patients who die or suffer permanent, severe central nervous system damage after near-drowning.

C1-C2 fusion in children with atlantoaxial instability and spinal cord compression: technical note.

Children with atlantoaxial instability and subluxation that will not reduce with extension of the cervical spine often present with clinical and/or radiographic evidence of spinal cord compression at the C1-C2 level. If the patient requires a laminectomy at the C1 level, occipital fusion is necessitated with associated reduction in mobility and high incidence of nonunion, as compared with a C1-C2 fusion. Also, passing wires under the intact lamina at C1 can further compromise an already compressed cervical cord. To address the problems associated with either of the above options, we used a C1-C2 fusion with removal of the mid 2 cm of the lamina of C1. Another option is the application of a transarticular screw fixation of C1-C2, which does not require the posterior element of C1. The current study was performed before the introduction of this type of fixation. Over a 10-year period, we have used the described technique to treat 13 patients. After decompression and fusion at the C1 and C2 levels as described, all patients had resolution of their preoperative neurological symptoms and all have achieved a stable fusion. Partial removal of the lamina at C1 and then C1-C2 fusion are safe and effective procedures to treat children with atlantoaxial instability and spinal cord compression.

To shunt or to fenestrate: which is the best surgical treatment for arachnoid cysts in pediatric patients?

The treatment options for intracranial arachnoid cysts are either craniotomy and fenestration of the cyst into the cerebrospinal fluid spaces or shunting of the cyst contents extracranially. Fenestration may eliminate the need to shunt, but it is a major operative procedure and is not always successful. To determine which treatment provides the greatest benefit with the fewest complications, the records of 31 patients with 34 arachnoid cysts treated at the Children's Hospital of Los Angeles between 1976 and 1986 were reviewed. The mean age of the patients was 4.4 years, with a range of 0 to 15.5 years. The most common location was the middle fossa (14 cases), followed by the posterior fossa (7 cases), the suprasellar region (5 cases), and hemispheric (5 cases) and other locations (3 cases). Signs and symptoms were related to abnormally rapid head growth in infants and to increased intracranial pressure and seizures in older children. The initial treatment of 29 cysts was fenestration. Twenty-two (76%) procedures were successful, with no additional treatment needed for the cyst. The other 7 cysts required the subsequent placement of a cystoperitoneal shunt. In 5 cases, the cysts were treated initially with cystoperitoneal shunts. Of the total 12 cystoperitoneal shunts, 5 have required revisions on one or more occasions. No significant difference in morbidity was noted between the two treatment options. Because we consider shunt independence to be a major goal of therapy, we suggest that patients with arachnoid cysts be divided into two categories, those presenting with associated hydrocephalus and those without hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS)

Extraneural metastatic medulloblastoma during childhood.

From 1960 to 1977, 59 patients with histologically confirmed medulloblastoma were initially treated at Childrens Hospital of Los Angeles. Of this group, 49 have died and, of these, 34 were autopsied. Among the autopsied cases, 2 infants had neck masses that proved to be medulloblastoma that had spread from the cerebellar vermis before any surgical intervention. Four additional patients who had undergone a posterior fossa craniectomy without either the pre- or postoperative placement of a cerebrospinal fluid-diverting shunt were found to have extraneural metastatic medulloblastoma at autopsy. The extraneural metastatic medulloblastoma rate in the autopsied cases was 17.6% (6 of 34). Our series shows that the incidence of the extraneural spread of medulloblastoma is associated with being young, being male, and having diffuse tumor involvement of the subarachnoid space.

Management of symptomatic chronic extra-axial fluid collections in pediatric patients.

The records of 103 pediatric patients having symptomatic chronic extra-axial fluid collections treated at Children's Hospital of Los Angeles from 1977 to 1988 were reviewed. Patients were treated with observation, serial percutaneous needle drainage, drainage through burr holes, drainage into a closed external drainage system, or subdural to peritoneal shunt. If the initial treatment was not effective, additional forms of treatment were instituted. Shunts, ultimately used in 73% of the patients, proved to be the most effective treatment. Of the group with shunts, the extra-axial fluid was unilateral in 20% and bilateral in 80%. In those patients with bilateral effusions, no difference in efficacy of shunts was seen in patients treated with bilateral versus unilateral shunts. Of the 75 patients with shunts, 12% required a shunt revision for progressive or recurrent symptoms. Shunt infections occurred in 3% of the patients, necessitating removal of the shunt and treatment with antibiotics. Eosinophilia in the subdural fluid was associated with shunt obstruction requiring revision. The shunt was never removed in 51% of patients with no untoward effects. This study demonstrates that the most efficacious treatment of symptomatic chronic extra-axial fluid collections in children is a unilateral subdural to peritoneal shunt. The shunt need not be removed after resolution of the fluid collections.

Neuropsychological outcome after severe pediatric near-drowning.

Between April 1979 and August 1983, 49 nearly drowned children in serious condition were admitted to Childrens Hospital of Los Angeles (CHLA) with Glasgow coma scores of 3, 4, or 5 and underwent intracranial pressure monitoring and brain resuscitative therapy. Of the 49 patients, 29 (59%) died in the hospital 1 day to 3 months after admission, 13 (27%) were discharged in vegetative states, and 7 (14%) made good recoveries. No patient made a partial neurological recovery. The sustained mean highest intracranial pressure was significantly higher and the sustained lowest cerebral perfusion pressure was significantly lower for those who died than for survivors (P less than 0.05), but these data did not significantly distinguish between intact and vegetative survivors. Pupillary reactivity noted on arrival at CHLA also significantly discriminated survivors and fatalities (P less than 0.05), but not between intact and vegetative survivors. The presence of any motor activity after arrival at CHLA, even posturing or twitching, indicated a significant chance for intact survival (P less than 0.05), although such activity did not discriminate between death and vegetative survival. Extensive neuropsychological testing indicated that the apparently intact recovered patients generally showed nearly average levels of cognitive functioning, with mild residual gross motor and coordination deficits.