Robert Greenwood | University of North Carolina at Chapel Hill (original) (raw)

Papers by Robert Greenwood

Research paper thumbnail of Proton MR spectroscopy in a possible enhancing hamartoma in a patient with neurofibromatosis type 1

AJNR. American journal of neuroradiology, 1995

A patient with neurofibromatosis type 1 was found to have an enhancing lesion in the cerebellum. ... more A patient with neurofibromatosis type 1 was found to have an enhancing lesion in the cerebellum. Proton MR spectroscopy was performed and showed findings similar to those seen in healthy volunteers. A 3-year follow-up MR study showed the lesion was unchanged. Proton MR spectroscopy might prove useful in the diagnosis of hamartomas.

Research paper thumbnail of Möbius syndrome in infant exposed to cocaine in utero

Pediatric Neurology, 1993

The pathophysiology of Miibius syndrome has been debated for decades. A vascular etiology is curr... more The pathophysiology of Miibius syndrome has been debated for decades. A vascular etiology is currently favored because it explains the wide clinical spectrum of this syndrome. An infant is reported who was born with Miibius syndrome after a pregnancy complicated by heavy maternal use of cocaine and alcohol. We speculate that cocaine-induced vasoconstriction at a critical time of cerebrovascular development produced a vascular disruption sequence leading to the Miibius syndrome.

Research paper thumbnail of Diagnostic pitfalls associated with amoxapine overdose: A case report

The American Journal of Emergency Medicine, 1990

Amoxapine is a second-peneration antidepressant that has been reported to cause seixures, severe ... more Amoxapine is a second-peneration antidepressant that has been reported to cause seixures, severe acidosis, cardiac dysrhythmias, hypotension, renal failure, coma, and cardiorespiratoty arrest in polsoning exposures. This is a report of a previously normal 9-year-old child who presented with generalized tonic clonic seizures that led to an extensive workup for primary generalized epilepsy. Nothing in the patient's history or laboratow test results su99ested innestion of a toxin. It was not until 48 hours after admission, when the child admitted taking several of her mother's amoxapine tablets, that the correct dlapnosis was made. Because of the risks and the diannostlc pitfalls associated with inoestlon of amoxapine, clinicians should be mindful of the lessons tau9ht by this case. (Am J Emery Med 1990;8:335-337. 0 1990 by W.9. Saunders Company.) Antidepressants are a leading cause of death due to poison exposure in the United States.' Newer, second generation antidepressants, ie, amoxapine, a dibenzoxazepine tricyclic compound, and maprotiline, a tetracyclic compound, have been reported to cause convulsions more commonly than traditional, first generation tricyclic antidepressants (TCAS).~*' In a retrospective review of 1,3 13 cases of cyclic antidepressant ingestions, the incidence of seizures was 24.5% in the amoxapine group and 12.2% in the maprotiline group, compared with 3.0% in the TCA group (P < 0.01).2 Amoxapine-induced seizures have been reported in nonepileptic adults who were taking doses recommended for the treatment of depression.4" The risk of death secondary to amoxapine overdose may also be greater than with other cyclic antidepressants.' Although amoxapine has somewhat less anticholinergic effect than other cyclic antidepressants,8 the clinical features of amoxapine poisoning are reported to be similar to those suggested for classical TCA overdose.2,9 The diagnostic considerations are also similar. However, we report a case that illustrates the diagnostic problems and pitfalls associated with amoxapine poisoning.

Research paper thumbnail of F1000Prime recommendation of Next generation sequencing methods for diagnosis of epilepsy syndromes

F1000 - Post-publication peer review of the biomedical literature, 2020

Research paper thumbnail of Clinical spectrum of individuals with pathogenic N F1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1

Human Mutation, 2019

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of Proton MR Spectroscopic Characteristics of a Presumed Giant

Summary: A newborn presented with a mass replacing the left cerebral hemisphere. Although the int... more Summary: A newborn presented with a mass replacing the left cerebral hemisphere. Although the internal signal characteris-tics of the lesion were suggestive of disorganized gray and white matter, a true neoplasia such as a ganglioglioma could not be totally excluded. Biopsy is not recommended in these cases since the results may be misleading. Proton MR spectroscopy was used; this technique also suggested the hamartomatous nature of the lesion. Based on the clinical course and the imaging features, conservative therapy and observation were undertaken instead of surgery. At 6 months of age, the patient is stable and the lesion is unchanged. Index terms: Magnetic resonance, spectroscopy; Brain neo-plasms, in infants and children; Migration anomalies Rarely, gray matter heterotopias attain a very large size and simulate true masses both clinically and radiographically (1). The large size of these lesions and the shift of the intracranial structures may lead to surgical excision and / o...

Research paper thumbnail of Faculty Opinions recommendation of Voxel-based magnetic resonance image postprocessing in epilepsy

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Objective: Although the general utility of voxel-based processing of structural magnetic resonanc... more Objective: Although the general utility of voxel-based processing of structural magnetic resonance imaging (MRI) data for detecting occult lesions in focal epilepsy is established, many differences exist among studies, and it is unclear which processing method is preferable. The aim of this study was to compare the ability of commonly used methods to detect epileptogenic lesions in magnetic resonance MRI-positive and MRI-negative patients, and to estimate their diagnostic yield. Methods: We identified 144 presurgical focal epilepsy patients, 15 of whom had a histopathologically proven and MRI-visible focal cortical dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure origin, 27 of whom had resections. We applied four types of voxel-based morphometry (VBM), three based on T1 images (gray matter volume, gray matter concentration, junction map [JM]) and one based on normalized fluid-attenuated inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy controls. Results: The four maps had different sensitivity and specificity profiles. All maps showed detection rates for focal cortical dysplasia patients (MRI positive and negative) of >30% at a strict threshold of p < 0.05 (family-wise error) and >60% with a liberal threshold of p < 0.0001 (uncorrected), except for gray matter volume (14% and 27% detection rate). All maps except nFSI showed poor specificity, with high rates of falsepositive findings in controls. In the MRI-negative patients, absolute detection rates were lower. A concordant nFSI finding had a significant positive odds ratio of 7.33 for a favorable postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and nFSI was rare, yet showed good specificity throughout the thresholds. Significance: All VBM variants had specific diagnostic properties that need to be considered for an adequate interpretation of the results. Overall, structural postprocessing can be a useful tool in presurgical diagnostics, but the low specificity of some maps has to be taken into consideration.

Research paper thumbnail of Neurology workforce deficits

Neurology, 2019

There is a shortfall of neurologists in the United States. One physician recruitment site found n... more There is a shortfall of neurologists in the United States. One physician recruitment site found neurology to be the most in-demand specialty in 2018, with fewer candidates per job posted than any other field.1 This shortfall is projected to worsen in the coming years, exacerbating clinic wait times and reducing patient access to neurologic care.2 A stable minority of allopathic medical students choose to train in neurology each year, with ≈3.1% matching into a neurology residency in 2018.3 The assumption is that if more students go into neurology, the field would be better equipped to serve the burgeoning population of patients with neurologic disorders.

Research paper thumbnail of Changing Child Neurology Training

Journal of Child Neurology, 2012

Child neurology training must change as our understanding of the diseases of the developing nervo... more Child neurology training must change as our understanding of the diseases of the developing nervous system increases. A proposed child neurology training path leading to certification in child neurology would eliminate all but 3 months of adult neurology training; however gaining approval for a new Accreditation Council for Graduate Medical Education (ACGME) training program would be an arduous task. I review why this change would add significant administrative and financial burdens and how this change in training could negatively affect the education of child neurology residents. I believe that modifications of the current training requirements already underway could achieve the same aims with fewer losses.

Research paper thumbnail of Extradural Hematomas of the Posterior Fossa

Research paper thumbnail of Faculty Opinions recommendation of Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associate... more Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify diseasecausing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsyassociated genes (KCNQ2,

Research paper thumbnail of Faculty Opinions recommendation of Systematic review: syndromes, early diagnosis, and treatment in autoimmune encephalitis

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Epilepsy genetics: Current knowledge, applications, and future directions

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Spatiotemporal mapping of epileptic spikes using simultaneous EEG-functional MRI

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Investigation of neuronal auto-antibodies in children diagnosed with epileptic encephalopathy of unknown cause

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization.... more The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization. Here, we demonstrate in human cells and zebrafish that the F-BAR domain containing proteins PACSIN1 and-2 play an essential role in ciliogenesis, similar to their binding partner and membrane reorganizer EHD1. In mature cilia, PACSINs and EHDs are dynamically localized to the ciliary pocket membrane (CPM) and transported away from this structure on membrane tubules along with proteins that exit the cilium. PACSINs function early in ciliogenesis at the ciliary vesicle (CV) stage to promote mother centriole to basal body transition. Remarkably, we show that PACSIN1 and EHD1 assemble membrane tubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel (EMC) to the outside of the cell.

Research paper thumbnail of Faculty Opinions recommendation of Clinical and genetic spectrum of a large cohort of children with epilepsy in China

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Advances in Autoimmune Epilepsy Associated with Antibodies, Their Potential Pathogenic Molecular Mechanisms, and Current Recommended Immunotherapies

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of The new definition and classification of seizures and epilepsy

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of F1000Prime recommendation of Systematic review: syndromes, early diagnosis, and treatment in autoimmune encephalitis

F1000 - Post-publication peer review of the biomedical literature, 2020

Research paper thumbnail of Proton MR spectroscopy in a possible enhancing hamartoma in a patient with neurofibromatosis type 1

AJNR. American journal of neuroradiology, 1995

A patient with neurofibromatosis type 1 was found to have an enhancing lesion in the cerebellum. ... more A patient with neurofibromatosis type 1 was found to have an enhancing lesion in the cerebellum. Proton MR spectroscopy was performed and showed findings similar to those seen in healthy volunteers. A 3-year follow-up MR study showed the lesion was unchanged. Proton MR spectroscopy might prove useful in the diagnosis of hamartomas.

Research paper thumbnail of Möbius syndrome in infant exposed to cocaine in utero

Pediatric Neurology, 1993

The pathophysiology of Miibius syndrome has been debated for decades. A vascular etiology is curr... more The pathophysiology of Miibius syndrome has been debated for decades. A vascular etiology is currently favored because it explains the wide clinical spectrum of this syndrome. An infant is reported who was born with Miibius syndrome after a pregnancy complicated by heavy maternal use of cocaine and alcohol. We speculate that cocaine-induced vasoconstriction at a critical time of cerebrovascular development produced a vascular disruption sequence leading to the Miibius syndrome.

Research paper thumbnail of Diagnostic pitfalls associated with amoxapine overdose: A case report

The American Journal of Emergency Medicine, 1990

Amoxapine is a second-peneration antidepressant that has been reported to cause seixures, severe ... more Amoxapine is a second-peneration antidepressant that has been reported to cause seixures, severe acidosis, cardiac dysrhythmias, hypotension, renal failure, coma, and cardiorespiratoty arrest in polsoning exposures. This is a report of a previously normal 9-year-old child who presented with generalized tonic clonic seizures that led to an extensive workup for primary generalized epilepsy. Nothing in the patient's history or laboratow test results su99ested innestion of a toxin. It was not until 48 hours after admission, when the child admitted taking several of her mother's amoxapine tablets, that the correct dlapnosis was made. Because of the risks and the diannostlc pitfalls associated with inoestlon of amoxapine, clinicians should be mindful of the lessons tau9ht by this case. (Am J Emery Med 1990;8:335-337. 0 1990 by W.9. Saunders Company.) Antidepressants are a leading cause of death due to poison exposure in the United States.' Newer, second generation antidepressants, ie, amoxapine, a dibenzoxazepine tricyclic compound, and maprotiline, a tetracyclic compound, have been reported to cause convulsions more commonly than traditional, first generation tricyclic antidepressants (TCAS).~*' In a retrospective review of 1,3 13 cases of cyclic antidepressant ingestions, the incidence of seizures was 24.5% in the amoxapine group and 12.2% in the maprotiline group, compared with 3.0% in the TCA group (P < 0.01).2 Amoxapine-induced seizures have been reported in nonepileptic adults who were taking doses recommended for the treatment of depression.4" The risk of death secondary to amoxapine overdose may also be greater than with other cyclic antidepressants.' Although amoxapine has somewhat less anticholinergic effect than other cyclic antidepressants,8 the clinical features of amoxapine poisoning are reported to be similar to those suggested for classical TCA overdose.2,9 The diagnostic considerations are also similar. However, we report a case that illustrates the diagnostic problems and pitfalls associated with amoxapine poisoning.

Research paper thumbnail of F1000Prime recommendation of Next generation sequencing methods for diagnosis of epilepsy syndromes

F1000 - Post-publication peer review of the biomedical literature, 2020

Research paper thumbnail of Clinical spectrum of individuals with pathogenic N F1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1

Human Mutation, 2019

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Research paper thumbnail of Proton MR Spectroscopic Characteristics of a Presumed Giant

Summary: A newborn presented with a mass replacing the left cerebral hemisphere. Although the int... more Summary: A newborn presented with a mass replacing the left cerebral hemisphere. Although the internal signal characteris-tics of the lesion were suggestive of disorganized gray and white matter, a true neoplasia such as a ganglioglioma could not be totally excluded. Biopsy is not recommended in these cases since the results may be misleading. Proton MR spectroscopy was used; this technique also suggested the hamartomatous nature of the lesion. Based on the clinical course and the imaging features, conservative therapy and observation were undertaken instead of surgery. At 6 months of age, the patient is stable and the lesion is unchanged. Index terms: Magnetic resonance, spectroscopy; Brain neo-plasms, in infants and children; Migration anomalies Rarely, gray matter heterotopias attain a very large size and simulate true masses both clinically and radiographically (1). The large size of these lesions and the shift of the intracranial structures may lead to surgical excision and / o...

Research paper thumbnail of Faculty Opinions recommendation of Voxel-based magnetic resonance image postprocessing in epilepsy

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Objective: Although the general utility of voxel-based processing of structural magnetic resonanc... more Objective: Although the general utility of voxel-based processing of structural magnetic resonance imaging (MRI) data for detecting occult lesions in focal epilepsy is established, many differences exist among studies, and it is unclear which processing method is preferable. The aim of this study was to compare the ability of commonly used methods to detect epileptogenic lesions in magnetic resonance MRI-positive and MRI-negative patients, and to estimate their diagnostic yield. Methods: We identified 144 presurgical focal epilepsy patients, 15 of whom had a histopathologically proven and MRI-visible focal cortical dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure origin, 27 of whom had resections. We applied four types of voxel-based morphometry (VBM), three based on T1 images (gray matter volume, gray matter concentration, junction map [JM]) and one based on normalized fluid-attenuated inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy controls. Results: The four maps had different sensitivity and specificity profiles. All maps showed detection rates for focal cortical dysplasia patients (MRI positive and negative) of >30% at a strict threshold of p < 0.05 (family-wise error) and >60% with a liberal threshold of p < 0.0001 (uncorrected), except for gray matter volume (14% and 27% detection rate). All maps except nFSI showed poor specificity, with high rates of falsepositive findings in controls. In the MRI-negative patients, absolute detection rates were lower. A concordant nFSI finding had a significant positive odds ratio of 7.33 for a favorable postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and nFSI was rare, yet showed good specificity throughout the thresholds. Significance: All VBM variants had specific diagnostic properties that need to be considered for an adequate interpretation of the results. Overall, structural postprocessing can be a useful tool in presurgical diagnostics, but the low specificity of some maps has to be taken into consideration.

Research paper thumbnail of Neurology workforce deficits

Neurology, 2019

There is a shortfall of neurologists in the United States. One physician recruitment site found n... more There is a shortfall of neurologists in the United States. One physician recruitment site found neurology to be the most in-demand specialty in 2018, with fewer candidates per job posted than any other field.1 This shortfall is projected to worsen in the coming years, exacerbating clinic wait times and reducing patient access to neurologic care.2 A stable minority of allopathic medical students choose to train in neurology each year, with ≈3.1% matching into a neurology residency in 2018.3 The assumption is that if more students go into neurology, the field would be better equipped to serve the burgeoning population of patients with neurologic disorders.

Research paper thumbnail of Changing Child Neurology Training

Journal of Child Neurology, 2012

Child neurology training must change as our understanding of the diseases of the developing nervo... more Child neurology training must change as our understanding of the diseases of the developing nervous system increases. A proposed child neurology training path leading to certification in child neurology would eliminate all but 3 months of adult neurology training; however gaining approval for a new Accreditation Council for Graduate Medical Education (ACGME) training program would be an arduous task. I review why this change would add significant administrative and financial burdens and how this change in training could negatively affect the education of child neurology residents. I believe that modifications of the current training requirements already underway could achieve the same aims with fewer losses.

Research paper thumbnail of Extradural Hematomas of the Posterior Fossa

Research paper thumbnail of Faculty Opinions recommendation of Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associate... more Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify diseasecausing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsyassociated genes (KCNQ2,

Research paper thumbnail of Faculty Opinions recommendation of Systematic review: syndromes, early diagnosis, and treatment in autoimmune encephalitis

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Epilepsy genetics: Current knowledge, applications, and future directions

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Spatiotemporal mapping of epileptic spikes using simultaneous EEG-functional MRI

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Investigation of neuronal auto-antibodies in children diagnosed with epileptic encephalopathy of unknown cause

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization.... more The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization. Here, we demonstrate in human cells and zebrafish that the F-BAR domain containing proteins PACSIN1 and-2 play an essential role in ciliogenesis, similar to their binding partner and membrane reorganizer EHD1. In mature cilia, PACSINs and EHDs are dynamically localized to the ciliary pocket membrane (CPM) and transported away from this structure on membrane tubules along with proteins that exit the cilium. PACSINs function early in ciliogenesis at the ciliary vesicle (CV) stage to promote mother centriole to basal body transition. Remarkably, we show that PACSIN1 and EHD1 assemble membrane tubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel (EMC) to the outside of the cell.

Research paper thumbnail of Faculty Opinions recommendation of Clinical and genetic spectrum of a large cohort of children with epilepsy in China

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of Advances in Autoimmune Epilepsy Associated with Antibodies, Their Potential Pathogenic Molecular Mechanisms, and Current Recommended Immunotherapies

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of Faculty Opinions recommendation of The new definition and classification of seizures and epilepsy

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, 2019

Research paper thumbnail of F1000Prime recommendation of Systematic review: syndromes, early diagnosis, and treatment in autoimmune encephalitis

F1000 - Post-publication peer review of the biomedical literature, 2020