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1.
Pediatr Neurol ; 151: 21-28, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38091919

ABSTRACT

BACKGROUND: Drowning is a leading cause of brain injury in children. Long-term outcome data for drowning survivors are sparse. This study reports neurocognitive outcomes for 154 children hospitalized following drowning. METHODS: A survey for parent caregivers was distributed online. Likert scale items assessed 10 outcome variables in four domains: motor (three), perception (three), language (three), and social/emotional (one). Cluster analysis, outcome relative risk, and descriptive statistics were applied. RESULTS: Of 208 surveys received, 154 met inclusion criteria. Coma was the most common admission status (n = 137). Cluster analysis identified three outcome groups: Mild (n = 39), Moderate (n = 75), and Severe (n = 40). Motor impairment with cognitive and perceptual sparing (deefferentation) was present in Moderate (P < 1 × 10-26) and Severe (P < 1 × 10-12) but absent in Mild. Locked-in state was endorsed in both Moderate (83%) and Severe (70%). The strongest predictor of good outcome (Mild) was hospitalization with no medical intervention (relative risk [RR] = 6.7). Responsivity on admission (RR = 4.2) or discharge (RR = 12.22) also predicted good outcome. In-hospital prognostication and counseling predicted outcome weakly (RR = 1.3) or not at all. CONCLUSIONS: Long-term outcomes in pediatric drowning ranged widely. Overall, motor impairments exceeded perceptual or cognitive (P < 1 × 10-18), with "locked-in state" endorsed in most (93 of 154). The strongest predictors of good outcome were the lack of necessity for interventions and responsivity on admission or discharge. The eponym "Conrad syndrome" is proposed for locked-in state following nonfatal drowning in children.


Subject(s)
Brain Injuries , Drowning , Child , Humans , Caregivers , Hospitalization
2.
J Neurosurg ; 140(6): 1799-1809, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38157521

ABSTRACT

OBJECTIVE: Medial thalamotomy has been shown to benefit patients with neuropathic pain, but widespread adoption of this procedure has been limited by reporting of clinical outcomes in studies without a control group. This study aimed to minimize confounders associated with medial thalamotomy for treating chronic pain by using modern MRI-guided stereotactic lesioning and a rigorous clinical design. METHODS: This prospective, double-blinded, randomized controlled trial in 10 patients with trigeminal neuropathic pain used sham procedures as controls. Participants underwent assessments by a pain psychologist and pain management clinician, including use of the following measures: the Numeric Pain Rating Scale (NPRS); patient-reported outcome measures; and patient's impression of improvement at baseline, 1 day, 1 week, 1 month, and 3 months postprocedure. Patients in the treated group underwent bilateral focused ultrasound (FUS) medial thalamotomy targeting the central lateral nucleus. Patients in the control group underwent sham procedures with energy output disabled. The primary efficacy outcome measure was between-group differences in pain intensity (using the NPRS) at baseline and at 3 months postprocedure. Adverse events were measured for safety and included MRI analysis. Exploratory measures of connectivity and metabolism were analyzed using diffusion tensor imaging, functional MRI, and PET, respectively. RESULTS: There were no serious complications from the FUS procedures. MRI confirmed bilateral medial thalamic ablations. There was no significant improvement in pain intensity from baseline to 3 months, either for patients undergoing FUS medial thalamotomy or for sham controls; and the between-group change in NPRS score as the primary efficacy outcome measure was not significantly different. Patient-reported outcome assessments demonstrated improvement (i.e., a decrease) only in pain interference with enjoyment of life at 3 months. There was a perception of benefit at 1 week, but only for patients treated with FUS and not for the sham cohort. Advanced neuroimaging showed that these medial thalamic lesions altered structural connectivity with the postcentral gyrus and demonstrated a trend toward hypometabolism in the insula and amygdala. CONCLUSIONS: This randomized controlled trial of bilateral FUS medial thalamotomy did not reduce the intensity of trigeminal neuropathic pain, although it should be noted that the ability to estimate the magnitude of treatment effects is limited by the small cohort.


Subject(s)
Thalamus , Trigeminal Neuralgia , Humans , Male , Female , Trigeminal Neuralgia/surgery , Trigeminal Neuralgia/diagnostic imaging , Middle Aged , Double-Blind Method , Aged , Thalamus/surgery , Thalamus/diagnostic imaging , Prospective Studies , Treatment Outcome , Pain Measurement , Adult , Magnetic Resonance Imaging , Patient Reported Outcome Measures
3.
J Pain ; 24(12): 2283-2293, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37468022

ABSTRACT

Variability in pain sensitivity arises not only from the differences in peripheral sensory receptors but also from the differences in central nervous system (CNS) pain inhibition and facilitation mechanisms. Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation but is susceptible to confounding when elicited with the skin-contact thermode, which adds the responses of touch-related Aß low-threshold mechanoreceptors to nociceptive receptors. In the present study, we evaluate an alternative method involving the use of a contactless cutaneous laser for TSP assessment. We show that repetitive laser stimulations with a one second inter-stimulus interval evoked reliable TSP responses in a significant proportion of healthy subjects (N = 36). Female subjects (N = 18) reported greater TSP responses than male subjects confirming earlier studies of sex differences in central nociceptive excitability. Furthermore, repetitive laser stimulations during TSP induction elicited increased time-frequency electroencephalography (EEG) responses. The present study demonstrates that repetitive laser stimulation may be an alternative to skin-contact methods for TSP assessment in patients and healthy controls. PERSPECTIVE: Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation. We show that contactless cutaneous laser stimulation is a reliable alternative to the skin contact approaches during TSP assessment.


Subject(s)
Pain Threshold , Pain , Humans , Male , Female , Pain Measurement/methods , Pain Threshold/physiology , Skin , Sensory Receptor Cells
4.
World Neurosurg ; 165: e242-e250, 2022 09.
Article in English | MEDLINE | ID: mdl-35724884

ABSTRACT

OBJECTIVE: Changes to neurosurgical practices during the coronavirus disease 2019 (COVID-19) pandemic have not been thoroughly analyzed. We report the effects of operative restrictions imposed under variable local COVID-19 infection rates and health care policies using a retrospective multicenter cohort study and highlight shifts in operative volumes and subspecialty practice. METHODS: Seven academic neurosurgery departments' neurosurgical case logs were collected; procedures in April 2020 (COVID-19 surge) and April 2019 (historical control) were analyzed overall and by 6 subspecialties. Patient acuity, surgical scheduling policies, and local surge levels were assessed. RESULTS: Operative volume during the COVID-19 surge decreased 58.5% from the previous year (602 vs. 1449, P = 0.001). COVID-19 infection rates within departments' counties correlated with decreased operative volume (r = 0.695, P = 0.04) and increased patient categorical acuity (P = 0.001). Spine procedure volume decreased by 63.9% (220 vs. 609, P = 0.002), for a significantly smaller proportion of overall practice during the COVID-19 surge (36.5%) versus the control period (42.0%) (P = 0.02). Vascular volume decreased by 39.5% (72 vs. 119, P = 0.01) but increased as a percentage of caseload (8.2% in 2019 vs. 12.0% in 2020, P = 0.04). Neuro-oncology procedure volume decreased by 45.5% (174 vs. 318, P = 0.04) but maintained a consistent proportion of all neurosurgeries (28.9% in 2020 vs. 21.9% in 2019, P = 0.09). Functional neurosurgery volume, which declined by 81.4% (41 vs. 220, P = 0.008), represented only 6.8% of cases during the pandemic versus 15.2% in 2019 (P = 0.02). CONCLUSIONS: Operative restrictions during the COVID-19 surge led to distinct shifts in neurosurgical practice, and local infective burden played a significant role in operative volume and patient acuity.


Subject(s)
COVID-19 , Neurosurgery , Cohort Studies , Humans , Neurosurgical Procedures/methods , Pandemics
5.
NPJ Parkinsons Dis ; 8(1): 59, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35550514

ABSTRACT

Focused ultrasound (FUS) thalamotomy is an emerging treatment for tremor-dominant Parkinson's disease (PD). We report the first postmortem neuropathologic study of FUS thalamotomy in a 68-year-old man with tremor-dominant PD, which was performed seven months before he died. Although the peak voxel temperature at the target was <54 °C, his tremor improved on intraoperative and postoperative assessments. Additionally, postoperative MRI demonstrated a thalamic lesion. Lewy body-related pathology consistent with PD was detected. There was also a 5-mm lesion in the ventral lateral thalamus characterized by demyelination and neuropil loss, with many lipid-laden macrophages, but no lymphocytic infiltrates and relatively preserved neurons and axons. Additional pathological assessments after FUS thalamotomy are needed to determine if the observed brain changes are typical of this procedure.

6.
Neurotrauma Rep ; 2(1): 391-398, 2021.
Article in English | MEDLINE | ID: mdl-34901938

ABSTRACT

Skull bone graft failure is a potential complication of autologous cranioplasty after decompressive craniectomy (DC). Our objective was to investigate the association of graft size with subsequent bone graft failure after autologous cranioplasty. This single-center retrospective cohort study included patients age ≥18 years who underwent primary autologous cranioplasty between 2010 and 2017. The primary outcome was bone flap failure requiring graft removal. Demographic, clinical, and radiographic factors were recorded; three-dimensional (3D) reconstructive imaging was used to perform accurate measurements. Univariate and multi-variate regression analysis were performed to identify risk factors for the primary outcome. Of the 131 patients who underwent primary autologous cranioplasty, 25 (19.0%) underwent removal of the graft after identification of bone flap necrosis on computed tomography (CT); 16 (64%) of these were culture positive. The mean surface area of craniectomy defect was 128.5 cm2 for patients with bone necrosis and 114.9 cm2 for those without bone necrosis. Linear regression analysis demonstrated that size of craniectomy defect was independently associated with subsequent bone flap failure; logistic regression analysis demonstrated a defect area >125 cm2 was independently associated with failure (odds ratio [OR] 3.29; confidence interval [CI]: 0.249-2.135). Patient- and operation-specific variables were not significant predictors of bone necrosis. Our results showed that increased size of antecedent DC is an independent risk factor for bone flap failure after autologous cranioplasty. Given these findings, clinicians should consider the increased potential of bone flap failure after autologous cranioplasty among patients whose initial DC was >125 cm2.

7.
J Craniofac Surg ; 32(1): 155-158, 2021.
Article in English | MEDLINE | ID: mdl-33074976

ABSTRACT

ABSTRACT: Numerous methods for surgical correction of sagittal synostosis have been described in the literature, yielding similar outcomes. At the authors' institution, surgical approaches to correct this condition have evolved over the past few decades, including Π, H-type craniectomies (Renier), endoscopic suturectomy, and our current technique, the FLAG procedure. Our aim is to review the evolution of these surgical techniques at our institution and compare patient outcomes. A retrospective review was performed on consecutive patients undergoing correction for craniosynostosis from 2008 to 2018. All patients with a diagnosis of nonsyndromic isolated sagittal craniosynostosis were included and classified into one of 4 groups by the type of surgical correction performed (H-type, FLAG, endoscopic, other). The authors identified 166 consecutive patients with a mean age at time of surgery of 6.7 ± 4.0 months. 91 (54.8%) carried a diagnosis of nonsyndromic sagittal synostosis. 63 patients underwent H-type procedures, 9 underwent FLAG procedures, 5 underwent endoscopic procedures, and 14 were classified as other (distraction or other implant). Perioperatively, the FLAG group had the shortest ICU stay (1.3 days, P < 0.05), postoperative transfusion requirement (42cc pRBC, P < 0.001), and complication rate (0.0%). The endoscopic group had the shortest surgical time at 2.00 hours (p < 0.001). No statistically significant difference in cranial index or revision procedures between the four groups was identified. Overall, the mean length of follow-up was 25.3 months. All procedures had similar results for cranial index with decreased surgical time, transfusion volume, and hospital stay seen in FLAG and endoscopic groups.


Subject(s)
Craniosynostoses , Plastic Surgery Procedures , Craniosynostoses/surgery , Craniotomy , Endoscopy , Humans , Retrospective Studies , Skull/surgery , Treatment Outcome
8.
World Neurosurg ; 119: 209-214, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30096499

ABSTRACT

BACKGROUND: Hydrocephalus and intracranial hypertension are rare signs of spinal tumors when presenting in isolation, particularly with benign tumors. CASE DESCRIPTION: Herein reported is a case of a 53-year-old woman who presented with headache, blurry vision, communicating hydrocephalus, and intracranial hypertension. No primary intracranial pathology was identified, and there were no clinical signs or symptoms of intraspinal pathology. Lumbar puncture revealed elevated opening pressure, cerebrospinal fluid protein, and suspected tumor cells in the cerebrospinal fluid, thus prompting spinal imaging. A primary lumbar schwannoma was subsequently determined to underlie her symptoms, which resolved with tumor resection. CONCLUSIONS: Clinical suspicion of spinal pathology should be maintained in patients with unexplained intracranial hypertension, even in the absence of localizing signs of spinal pathology.


Subject(s)
Intracranial Hypertension/diagnosis , Intracranial Hypertension/etiology , Neurilemmoma/complications , Neurilemmoma/diagnosis , Spinal Cord Diseases/complications , Spinal Cord Diseases/diagnosis , Diagnosis, Differential , Female , Humans , Intracranial Hypertension/surgery , Lumbar Vertebrae , Middle Aged , Neurilemmoma/pathology , Neurilemmoma/surgery , Spinal Cord Diseases/pathology , Spinal Cord Diseases/surgery
9.
Neurosurg Focus ; 43(3): E10, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28859557

ABSTRACT

Throughout history, neurosurgical procedures have been fundamental in advancing neuroscience; however, this has not always been without deleterious side effects or harmful consequences. While critical to the progression of clinical neuroscience during the early 20th century, yet, at the same time, poorly tolerated by patients, pneumoencephalography is one such procedure that exemplifies this juxtaposition. Presented herein are historical perspectives and reflections on the role of the pneumoencephalography in the diagnosis and treatment of neuropsychiatric illnesses.


Subject(s)
Mental Disorders/history , Neurosurgical Procedures/history , Pneumoencephalography/history , Cerebral Ventricles/diagnostic imaging , History, 19th Century , History, 20th Century , Humans , Mental Disorders/diagnostic imaging , Mental Disorders/surgery , Neurosurgical Procedures/methods , Pneumoencephalography/methods
10.
Hum Brain Mapp ; 38(10): 4813-4831, 2017 10.
Article in English | MEDLINE | ID: mdl-28759710

ABSTRACT

Drowning is a leading cause of accidental injury and death in young children. Anoxic brain injury (ABI) is a common consequence of drowning and can cause severe neurological morbidity in survivors. Assessment of functional status and prognostication in drowning victims can be extremely challenging, both acutely and chronically. Structural neuroimaging modalities (CT and MRI) have been of limited clinical value. Here, we tested the utility of resting-state functional MRI (rs-fMRI) for assessing brain functional integrity in this population. Eleven children with chronic, spastic quadriplegia due to drowning-induced ABI were investigated. All were comatose immediately after the injury and gradually regained consciousness, but with varying ability to communicate their cognitive state. Eleven neurotypical children matched for age and gender formed the control group. Resting-state fMRI and co-registered T1-weighted anatomical MRI were acquired at night during drug-aided sleep. Network integrity was quantified by independent components analysis (ICA), at both group- and per-subject levels. Functional-status assessments based on in-home observations were provided by families and caregivers. Motor ICNs were grossly compromised in ABI patients both group-wise and individually, concordant with their prominent motor deficits. Striking preservations of perceptual and cognitive ICNs were observed, and the degree of network preservation correlated (ρ = 0.74) with the per-subject functional status assessments. Collectively, our findings indicate that rs-fMRI has promise for assessing brain functional integrity in ABI and, potentially, in other disorders. Furthermore, our observations suggest that the severe motor deficits observed in this population can mask relatively intact perceptual and cognitive capabilities. Hum Brain Mapp 38:4813-4831, 2017. © 2017 Wiley Periodicals, Inc.


Subject(s)
Brain Injuries/etiology , Brain Injuries/physiopathology , Brain/physiopathology , Drowning/physiopathology , Brain/diagnostic imaging , Brain Injuries/diagnostic imaging , Brain Mapping/methods , Child , Child, Preschool , Disability Evaluation , Drowning/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging/methods , Male , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Neurologic Examination , Rest
11.
Neuroimage Clin ; 11: 167-172, 2016.
Article in English | MEDLINE | ID: mdl-26937385

ABSTRACT

Drowning is a leading cause of neurological morbidity and mortality in young children. Anoxic brain injury (ABI) can result from nonfatal drowning and typically entails substantial neurological impairment. The neuropathology of drowning-induced pediatric ABI is not well established. Specifically, quantitative characterization of the spatial extent and tissue distribution of anoxic damage in pediatric nonfatal drowning has not previously been reported but could clarify the underlying pathophysiological processes and inform clinical management. To this end, we used voxel-based morphometric (VBM) analyses to quantify the extent and spatial distribution of consistent, between-subject alterations in gray and white matter volume. Whole-brain, high-resolution T1-weighted MRI datasets were acquired in 11 children with chronic ABI and 11 age- and gender-matched neurotypical controls (4-12 years). Group-wise VBM analyses demonstrated predominantly central subcortical pathology in the ABI group in both gray matter (bilateral basal ganglia nuclei) and white matter (bilateral external and posterior internal capsules) (P < 0.001); minimal damage was found outside of these deep subcortical regions. These highly spatially convergent gray and white matter findings reflect the vascular distribution of perforating lenticulostriate arteries, an end-arterial watershed zone, and suggest that vascular distribution may be a more important determinant of tissue loss than oxygen metabolic rate in pediatric ABI. Further, these results inform future directions for diagnostic and therapeutic modalities.


Subject(s)
Basal Ganglia Cerebrovascular Disease/pathology , Drowning/physiopathology , Gray Matter/pathology , Hypoxia, Brain/etiology , Hypoxia, Brain/pathology , Basal Ganglia Cerebrovascular Disease/diagnostic imaging , Basal Ganglia Cerebrovascular Disease/etiology , Case-Control Studies , Child, Preschool , Female , Gray Matter/diagnostic imaging , Humans , Hypoxia, Brain/diagnostic imaging , Imaging, Three-Dimensional , Infant , Magnetic Resonance Imaging , Male , White Matter/diagnostic imaging , White Matter/pathology
12.
J Ovarian Res ; 6(1): 2, 2013 Jan 04.
Article in English | MEDLINE | ID: mdl-23289505

ABSTRACT

BACKGROUND: There is a clinical need for routinely available genomic biomarker testing in newly diagnosed ovarian cancer. In the current study we performed molecular cytogenetics using a validated array based comparative genomic hybridization (array CGH) assay to screen for the presence of predictive and prognostic biomarkers in archival diagnostic tissue from ovarian cancer patients. We hypothesized that biomarkers of high-risk disease would be detectable in tumor samples from patients with treatment refractory, advanced disease, and would be detected less frequently in tumor samples from patients with more favorable outcomes. In addition, we predicted that the use of a genome-wide copy number analysis (CNA) testing platform would enable us to identify novel potentially targetable chromosomal alterations of therapeutic significance in a percentage of cases. METHODS: Formalin-fixed paraffin-embedded tissue (FFPE) tumor bank specimens were retrieved from the initial surgical resection for 18 ovarian cancer patients. Molecular cytogenetics was performed by array CGH for the detection of somatic chromosomal alterations associated with high-risk disease including amplifications of the CCNE1 and HER2 genes. Genomic risk stratification results were correlated with available clinical data. CGH data from each patient's tumor genome was also surveyed for the presence of potentially targetable aberrations. Relevant therapeutic agents and open studies for investigational drugs were reported for each patient. RESULTS: High-risk genomic alterations were identified in 12/18 (67%) of cases and all patients with high-risk markers had advanced, treatment refractory disease. Three tumors with minimal genomic changes had no high-risk markers and were from patients with Stage I/II disease that had been completely resected and under surveillance for recurrence. Eleven patients (61%) had at least one potentially targetable genomic alteration including CCNE1, HER2, KRAS gene amplifications, and somatic BRCA1 and/or BRCA2 gene deletions. Bi-allelic PTEN gene deletion was detected in one patient's tumor. CONCLUSIONS: Clinical genomic profiling of ovarian tumors by array CGH augments pathologic grade and stage to help stratify newly diagnosed ovarian cancer into high and low-risk disease. This personalized genomic information can also help guide treatment planning and disease monitoring by identifying novel potentially targetable genomic alterations that can be used by clinicians to choose rational directed therapies for patients with chemo-resistant disease.

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