A Retrospective Study of Cervical Spine MRI Findings in Children with Abusive Head Trauma.

BACKGROUND/AIMS: Increasing attention has been given to the possible association of cervical spine (c-spine) injuries with abusive head trauma (AHT). The aims of this study were to describe c-spine MRI findings in hospitalized AHT patients. METHODS: This is a retrospective study of children under the age of 5 years with AHT admitted to hospital in 2004-2013. Those with c-spine MRI were identified, and the images were reviewed. RESULTS: 250 AHT cases were identified, with 34 (14%) undergoing c-spine MRI. Eleven patients (32%) had 25 findings, including hematoma in 2, occiput-C1-C2 edema in 3, prevertebral edema in 6, facet edema in 2, and interspinous and/or muscular edema in 10. No patients had a clinically evident c-spine injury, a clinically unstable c-spine, or required c-spine surgery. CONCLUSIONS: C-spine MRI may identify abnormalities not apparent upon physical examination and the procedure should therefore be considered in cases of suspected AHT.

Radiologic common data elements rates in pediatric mild traumatic brain injury.

OBJECTIVE: The nosology for classifying structural MRI findings following pediatric mild traumatic brain injury (pmTBI) remains actively debated. Radiologic common data elements (rCDE) were developed to standardize reporting in research settings. However, some rCDE are more specific to trauma (probable rCDE). Other more recently proposed rCDE have multiple etiologies (possible rCDE), and may therefore be more common in all children. Independent cohorts of patients with pmTBI and controls were therefore recruited from multiple sites (New Mexico and Ohio) to test the dual hypothesis of a higher incidence of probable rCDE (pmTBI > controls) vs similar rates of possible rCDE on structural MRI. METHODS: Patients with subacute pmTBI (n = 287), matched healthy controls (HC; n = 106), and orthopedically injured (OI; n = 71) patients underwent imaging approximately 1 week postinjury and were followed for 3-4 months. RESULTS: Probable rCDE were specific to pmTBI, occurring in 4%-5% of each sample, rates consistent with previous large-scale CT studies. In contrast, prevalence rates for incidental findings and possible rCDE were similar across groups (pmTBI vs OI vs HC). The prevalence of possible rCDE was also the only finding that varied as a function of site. Possible rCDE and incidental findings were not associated with postconcussive symptomatology or quality of life 3-4 months postinjury. CONCLUSION: Collectively, current findings question the trauma-related specificity of certain rCDE, as well how these rCDE are radiologically interpreted. Refinement of rCDE in the context of pmTBI may be warranted, especially as diagnostic schema are evolving to stratify patients with structural MRI abnormalities as having a moderate injury.

The relationship between cavum septum pellucidum and psychopathic traits in female offenders.

Cavum Septum Pellucidum (CSP) is a common anatomical variant of the septum pellucidum. CSP is considered a marker for abnormal limbic brain development, but its functional consequences are non-specific. In a recent report (Crooks et al., 2018), CSP size was significantly positively correlated with the affective/interpersonal traits of psychopathy in male offenders (N = 1742). Here we test the hypothesis that CSP is related to psychopathic traits in incarcerated females (N = 355). We examine continuous relationships as well as categorical assignments for CSP size corresponding to a number of prior reports. We also compare female offenders to healthy female controls (N = 385). Consistent with our reported findings in males, a positive association was observed between the interpersonal psychopathic traits and CSP size. In contrast to findings among males, an association between CSP and antisocial psychopathic traits was apparent in females. There was no significant difference in CSP size (in mm) or CSP presence/absence between incarcerated and non-incarcarated groups. However, categorical rates of medium and large CSP were more common in female inmates than in controls. This is the first systematic investigation of these variables in a female inmate sample. In combination with our prior study, these findings demonstrate that limbic abnormalities, as indexed by CSP, are related to psychopathic traits in both female and male inmates.

The relationship between cavum septum pellucidum and psychopathic traits in a large forensic sample.

Cavum septum pellucidum (CSP) is a neuroanatomical variant of the septum pellucidum that is considered a marker for disrupted brain development. Several small sample studies have reported CSP to be related to disruptive behavior, persistent antisocial traits, and even psychopathy. However, no large-scale samples have comprehensively examined the relationship between CSP, psychopathic traits, and antisocial behavior in forensic samples. Here we test hypotheses about the presence of CSP and its relationship to psychopathic traits in incarcerated males (N = 1432). We also examined the incidence of CSP in two non-incarcerated male control samples for comparison (N = 208 and 125). Ethnic and racial composition was varied with a mean age of 33.1, and an average IQ of 96.96. CSP was evaluated via structural magnetic resonance imaging. CSP was measured by length (number of 1.0 mm slices) in continuous analyses, and classified as absent (0) or present (1+ mm), as well as by size (absent (0), small (1-3), medium (4-5), or large (6+ mm)) for comparison with prior work. The Wechsler Adult Intelligence Scale (WAIS-III), Structured Clinical Interview (SCID-I/P), and Hare Psychopathy Checklist-Revised (PCL-R) were used to assess IQ, substance dependence, and psychopathy, respectively. CSP length was positively associated with PCL-R total, Factor 1 (interpersonal/affective) and Facets 1 (interpersonal) and 2 (affective). CSP was no more prevalent among inmates than among non-incarcerated controls, with similar distributions of size. These results support the hypotheses that abnormal septal/limbic development may contribute to dimensional affective/interpersonal traits of psychopathy, but CSP is not closely associated with antisocial behavior, per se.

Sporadic pediatric meningiomas: a neuroradiological and neuropathological study of 15 cases.

OBJECTIVE Sporadic meningiomas have been classified in many different ways. Radiographically, these lesions can be described as occurring in either typical or atypical locations. The purpose of this study was to determine if there are any histopathological differences between sporadic meningiomas that arise in these varying locations in children. METHODS The neuroimaging, histopathological findings, and clinical records in patients with sporadic pediatric meningiomas not associated with neurofibromatosis Type 2 or prior radiation therapy were retrospectively reviewed. Tumors were classified by radiological findings as either typical or atypical, and they were categorized histopathologically by using the latest WHO nomenclature and grading criteria. RESULTS Fifteen sporadic meningiomas in pediatric patients were biopsied or resected at the authors' institution between 1989 and 2013. Five (33%) were typical in radiographic appearance and/or location and 10 (67%) were atypical. Four (80%) typical meningiomas were WHO Grade I tumors. Most (60%) of the atypical meningiomas were WHO Grade II or III. CONCLUSIONS This study is the largest series of sporadic pediatric meningiomas in atypical locations to date. Although sporadic meningiomas are relatively infrequent in children, those with atypical imaging, specifically those with apparently intraparenchymal and intraosseous locations, may be more common than previously recognized. In this study, pediatric sporadic meningiomas arising in atypical locations, in particular intraparenchymal meningiomas, may be of higher histopathological grade. The authors' findings should alert clinicians to the potential for more aggressive clinical behavior in these tumors.

Brain Lesions among Orally Fed and Gastrostomy-Fed Dysphagic Preterm Infants: Can Routine Qualitative or Volumetric Quantitative Magnetic Resonance Imaging Predict Feeding Outcomes?

INTRODUCTION: The usefulness of qualitative or quantitative volumetric magnetic resonance imaging (MRI) in early detection of brain structural changes and prediction of adverse outcomes in neonatal illnesses warrants further investigation. Our aim was to correlate certain brain injuries and the brain volume of feeding-related cortical and subcortical regions with feeding method at discharge among preterm dysphagic infants. MATERIALS AND METHODS: Using a retrospective observational study design, we examined MRI data among 43 (22 male; born at 31.5 ± 0.8 week gestation) infants who went home on oral feeding or gastrostomy feeding (G-tube). MRI scans were segmented, and volumes of brainstem, cerebellum, cerebrum, basal ganglia, thalamus, and vermis were quantified, and correlations were made with discharge feeding outcomes. Chi-squared tests were used to evaluate MRI findings vs. feeding outcomes. ANCOVA was performed on the regression model to measure the association of maturity and brain volume between groups. RESULTS: Out of 43 infants, 44% were oral-fed and 56% were G-tube fed at hospital discharge (but not at time of the study). There was no relationship between qualitative brain lesions and feeding outcomes. Volumetric analysis revealed that cerebellum was greater (p < 0.05) in G-tube fed infants, whereas cerebrum volume was greater (p < 0.05) in oral-fed infants. Other brain regions did not show volumetric differences between groups. CONCLUSION: This study concludes that neither qualitative nor quantitative volumetric MRI findings correlate with feeding outcomes. Understanding the complexity of swallowing and feeding difficulties in infants warrants a comprehensive and in-depth functional neurological assessment.

Utility of Neurodiagnostic Studies in the Diagnosis of Autoimmune Encephalitis in Children.

BACKGROUND: Autoimmune encephalitis is currently a clinical diagnosis without widely accepted diagnostic criteria, often leading to a delay in diagnosis. The utility of magnetic resonance imaging (MRI) and electroencephalography (EEG) in this disease is unknown. The objective of this study was to identify disease-specific patterns of neurodiagnostic studies (MRI and EEG) for autoimmune encephalitis in children. METHODS: We completed a retrospective chart review of encephalopathic patients seen at a large pediatric hospital over a four year interval. Clinical presentation, autoantibody status, and MRI and EEG findings were identified and compared. Individuals with autoantibodies were considered "definite" cases, whereas those without antibodies or those with only thyroperoxidase antibodies were characterized as "suspected." RESULTS: Eighteen patients met the inclusion criteria and autoantibodies were identified in nine of these. The patients with definite autoimmune encephalitis had MRI abnormalities within limbic structures, most notably the anteromedial temporal lobes (56%). Only individuals with suspected disease had nontemporal lobe cortical lesions. Sixteen patients had an EEG and 13 (81%) of these were abnormal. The most common findings were abnormal background rhythm (63%), generalized slowing (50%), focal slowing (43%), and focal epileptiform discharges (31%). Sleep spindle abnormalities occurred in 38% of patients. There were no specific differences in the EEG findings between the definite and suspected cases. Focal EEG findings only correlated with a focal lesion on MRI in a single definite case. CONCLUSIONS: Pediatric patients with definite autoimmune encephalitis have a narrow spectrum of MRI abnormalities. Conversely, EEG abnormalities are mostly nonspecific. All patients in our cohort had abnormalities on one or both of these neurodiagnostic studies.

Comparison of reorganization of the somatosensory system in rats that sustained forelimb removal as neonates and as adults.

Studies of sensory pathways in several species indicate that the extent and form of reorganization resulting from deafferentation early in life vs. adulthood are not the same. The reasons for such differences are not well understood. To gain further insight into age-dependent mechanisms of reorganization, this study compared the consequences of neonatal vs. adult forelimb amputation in rats at multiple levels of the sensory pathway, including primary somatosensory cortex, brainstem, and dorsal root ganglia. At the cortical level, the average area of the functional forelimb-stump representation from rats amputated as adults was significantly smaller (P < 0.05) than that of neonatally amputated rats (4.3 +/- 1.3 mm(2) vs. 6.6 +/- 1.5 mm(2), respectively). At the brainstem level, neonatally amputated rat cuneate neurons possessed the following responsivities: 20% stump responsive, 40% responsive to both stump and hindlimb, 30% responsive to another body region, and 10% unresponsive. In contrast, cuneate neurons of adult amputated rats were 70% stump responsive, 2% responsive to both stump and hindlimb, and 30% unresponsive. A significantly (P < 0.001) greater percentage of the C(6)-C(8) dorsal root ganglia neurons of adult amputated rats were unresponsive to peripheral stimulation vs. neurons from neonatally amputated rats (48% vs. 16%, respectively). These results indicate that the reorganization that occurs in response to forelimb amputation at birth vs. adulthood is distinctly different at each of these levels of the dorsal column-medial lemniscal pathway. Possible mechanisms to account for these differences are considered.

Does reorganization in the cuneate nucleus following neonatal forelimb amputation influence development of anomalous circuits within the somatosensory cortex?

Neonatal forelimb amputation in rats produces sprouting of sciatic nerve afferent fibers into the cuneate nucleus (CN) and results in 40% of individual CN neurons expressing both forelimb-stump and hindlimb receptive fields. The forelimb-stump region of primary somatosensory cortex (S-I) of these rats contains neurons in layer IV that express both stump and hindlimb receptive fields. However, the source of the aberrant input is the S-I hindlimb region conveyed to the S-I forelimb-stump region via intracortical projections. Although the reorganization in S-I reflects changes in cortical circuitry, it is possible that these in turn are dependent on the CN reorganization. The present study was designed to directly test whether the sprouting of sciatic afferents into the CN is required for expression of the hindlimb inputs in the S-I forelimb-stump field. To inhibit sprouting, neurotrophin-3 (NT-3) was applied to the cut nerves following amputation. At P60 or older, NT-3-treated rats showed minimal sciatic nerve fibers in the CN. Multiunit electrophysiological recordings in the CN of NT-3-treated, amputated rats revealed 6.3% of sites were both stump/hindlimb responsive, compared with 30.5% in saline-treated amputated animals. Evaluation of the S-I following GABA receptor blockade, revealed that the percentage of hindlimb responsive sites in the stump representation of the NT-3-treated rats (34.2%) was not significantly different from that in saline-treated rats (31.5%). These results indicate that brain stem reorganization in the form of sprouting of sciatic afferents into the CN is not necessary for development of anomalous hindlimb receptive fields within the S-I forelimb/stump region.

Modulation of dopamine release by striatal 5-HT2C receptors.

Previous work has demonstrated that dopamine (DA) transmission is regulated by serotonin-2C (5-HT2C) receptors but the site(s) in the brain where these receptors are localized is not known. The present work utilized in vivo microdialysis to investigate the modulation of DA release by 5-HT2C receptors localized in the nerve terminal regions of the mesocortical and nigrostriatal DA pathways. Microdialysis probes implanted in the striatum or the prefrontal cortex (PFC) measured dialysate DA concentrations, while the selective 5-HT2B/2C inverse agonist SB 206553 was given locally by reverse dialysis into these terminal regions. Additionally, the effects of the 5-HT2C agonist mCPP on striatal DA were measured. Local administration of SB 206553 (0.1-100 microM) into the striatum increased DA efflux in a concentration-dependent manner. Systemic administration of mCPP (1.0 mg/kg i.p.) decreased striatal DA and attenuated the SB 206553-induced increase. In contrast, infusion of SB 206553 (0.1-500 microM) by reverse dialysis into the PFC had no significant effect on basal DA efflux in this region. Additionally, high concentrations of SB 206553 had no effect on high potassium (K(+))-stimulated DA release in the PFC. These data contribute to a body of evidence indicating that 5-HT2C receptors inhibit nigrostriatal dopaminergic transmission. In addition, the results suggest that the nigrostriatal system is regulated by 5-HT2C receptors localized in the dorsal striatum. Elucidating the mechanisms by which serotonin (5-HT) modulates striatal and prefrontocortical DA concentrations may lead to improvements in the treatment of diverse syndromes such as schizophrenia, Parkinson's disease, anxiety, drug abuse, and/or depression.

Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats.

In adult rats that sustained forelimb amputation on the day of birth, >30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA(A+B) receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimb-stump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in approximately 60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats.

Local GABA receptor blockade reveals hindlimb responses in the SI forelimb-stump representation of neonatally amputated rats.

In adult rats that sustained forelimb amputation on the day of birth, there are numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to cutaneous stimulation of the hindlimb when cortical receptors for GABA are blocked. These normally suppressed hindlimb inputs originate in the SI hindlimb representation and synapse in the dysgranular cortex before exciting SI forelimb-stump neurons. In our previous studies, GABA (A + B) receptor blockade was achieved by topically applying a bicuculline methiodide/saclofen solution (BMI/SAC) to the cortical surface. This treatment blocks receptors throughout SI and does not allow determination of where along the above circuit the GABA-mediated suppression of hindlimb information occurs. In this study, focal injections of BMI/SAC were delivered to three distinct cortical regions that are involved in the hindlimb-to-forelimb-stump pathway. Blocking GABA receptors in the SI hindlimb representation and in the dysgranular cortex was largely ineffective in revealing hindlimb inputs ( approximately 10% of hindlimb inputs were revealed in both cases). In contrast, when the blockade was targeted at forelimb-stump recording sites, >80% of hindlimb inputs were revealed. Thus GABAergic interneurons within the forelimb-stump representation suppress the expression of reorganized hindlimb inputs to the region. A circuit model incorporating these and previous observations is presented and discussed.

Role of development in reorganization of the SI forelimb-stump representation in fetally, neonatally, and adult amputated rats.

Rats that sustain forelimb removal on postnatal day (P) 0 exhibit numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to hindlimb stimulation when cortical GABAA+B receptors are blocked. Most of these hindlimb inputs originate in the medial SI hindlimb representation. Although many forelimb-stump sites in these animals respond to hindlimb stimulation, very few respond to stimulation of the face (vibrissae or lower jaw), which is represented in SI just lateral to the forelimb. The lateral to medial development of SI may influence the capacity of hindlimb (but not face) inputs to "invade" the forelimb-stump region in neonatal amputees. The SI forelimb-stump was mapped in adult (>60 days) rats that had sustained amputation on embryonic day (E) 16, on P0, or during adulthood. GABA receptors were blocked and subsequent mapping revealed increases in nonstump inputs in E16 and P0 amputees: fetal amputees exhibited forelimb-stump sites responsive to face (34%), hindlimb (10%), and both (22%); neonatal amputees exhibited 10% face, 39% hindlimb, and 5% both; adult amputees exhibited 10% face, 5% hindlimb, and 0% both, with approximately 80% stump-only sites. These results indicate age-dependent differences in receptive-field reorganization of the forelimb-stump representation, which may reflect the spatiotemporal development of SI. Results from cobalt chloride inactivation of the SI vibrissae region and electrolesioning of the dysgranular cortex suggest that normally suppressed vibrissae inputs to the SI forelimb-stump area originate in the SI vibrissae region and synapse in the dysgranular cortex.