Neel Madan | Tufts Medical Center (original) (raw)

Papers by Neel Madan

Seminars in fetal & neonatal medicine, Apr 1, 2024

Developmental Medicine & Child Neurology, Oct 7, 2010

Tubers are the most common brain lesions in tuberous sclerosis complex (TSC), and typically remai... more Tubers are the most common brain lesions in tuberous sclerosis complex (TSC), and typically remain stable in size and appearance. We present the case of a young male with global developmental impairment and autistic features as well as multiple and mixed daily seizures. The patient had a prominent right frontal cortical tuber characterized by a calcified component, which changed on consecutive magnetic resonance imaging between the age of 4 and 11 years, at which time the patient underwent a lesionectomy. A poor long-term outcome is reported since the patient presents an intractable mixed seizure disorder status post-epilepsy surgery and no significant neuropsychological improvements. Histopathology findings show typical characteristics of tubers in TSC as well as numerous calcifications within the resected nodular lesion. This case supports the notion that tubers with calcified components are not necessarily static lesions and can change with time. Investigation of the relationship between the presence of calcification in tubers and epileptogenecity in a large group of patients would provide insights into the pathogenesis of the seizures and cognitive impairment and hopefully, eventually provide better treatment options for patients with TSC. Tuberous sclerosis complex (TSC) is a genetic disorder, which can affect multiple organs including the central nervous system. Several cerebral abnormalities are characteristic of TSC, including subependymal nodules (SEN) and white matter abnormalities, but tubers are the most common lesions of TSC. 1 Tubers have been reported in 82 to 100% of patients and are often epileptogenic. 2-4 They vary widely in size, location, and appearance, 5,6 but in contrast to SENs, tubers are thought to remain stable in size over time. We report the case of a young patient whose magnetic resonance imaging (MRI) detected a prominent right frontal cortical tuber with a calcified component that changed over time in both size and appearance. This cerebral lesion was resected and we describe both radiological and histological findings of this unusual lesion. The Massachusetts General Hospital institutional review board approved this study and informed consent was obtained from the patient's parents.

PLOS ONE, Feb 24, 2022

Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, charact... more Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Postacquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4-24.0) and 23.9 (20.6-29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI

medRxiv (Cold Spring Harbor Laboratory), Jun 12, 2023

doi: medRxiv preprint Background: Two RCTs demonstrated efficacy and safety of IV alteplase for p... more doi: medRxiv preprint Background: Two RCTs demonstrated efficacy and safety of IV alteplase for patients with acute ischemic stroke (AIS) who awaken with symptoms or with last known well (LKW) more than 4.5 hours prior to arrival. However, real world experience using CT perfusion (CTP) or DWI-MRI for patient selection in the U.S. is limited. We developed the Tufts Late Presenter Thrombolysis (LPT) protocol to offer alteplase to patients with wakeup stroke, known LKW more than 4.5 hours, or unknown LKW likely more than 4.5 hours and less than 24 hours, using CTP or DWI-MRI to aid patient selection. Methods: We reviewed ED stroke codes from our Comprehensive Stroke Center between 1/1/20-12/31/22 to identify patients treated with alteplase. Data were collected on demographics, comorbidities, LKW-to-treatment time (LTT), imaging modality, imaging findings, NIHSS, vessel occlusions, endovascular therapy (EVT), symptomatic ICH, and 90 days mRS. Outcomes for comparative analyses included process times (door to needle, door to CT) and clinical outcomes (90 day mRS, symptomatic ICH). Results: Forty-three of 118 patients (36%) presenting with AIS and treated with thrombolysis were treated between 4.5-24 hours after LKW. Patients treated in the 4.5 hour window and the later window had similar demographics, comorbidities, NIHSS, and EVT rates. CTP was used in the majority of LPT cases. The median penumbra was 45.04 mL (11.55-83.21), and the median core infarct was 5.92 mL (1.89-16.7). Symptomatic intracranial hemorrhage occurred in one LPT case (2.3%). Favorable mRS (0-1) was achieved by 36% of LPT patients with documented 90 day mRS.

Pediatric Research, Oct 24, 2022

Background:Preclinical data demonstrate that opioids modulate brain reward signaling through an i... more Background:Preclinical data demonstrate that opioids modulate brain reward signaling through an inflammatory cascade, but this relationship has yet to be studied in opioid-exposed neonates.Methods:Saliva samples of 54 opioid-exposed and sex- and age-matched non-exposed neonates underwent transcriptomic analysis of inflammatory and reward genes. A subset of 22 neonates underwent brain magnetic resonance imaging (MRI) to evaluate white matter injury commonly associated with inflammatory response. Gene expression and brain MRI were compared between opioid- and non-exposed neonates and further stratified by sex and pharmacotherapy need.Results:Opioid-exposed females regardless of pharmacotherapy need had higher expression of inflammatory genes than their male counterparts, with notable differences in the expression of CCL2 and CXCL1 in females requiring pharmacotherapy (p=0.01 and 0.06, respectively). Opioid-exposed males requiring pharmacotherapy had higher expression of DRD2 than exposed females (p=0.07), validating our prior research. Higher expression of IL1β, IL6, TNFα, and IL10 was seen in opioid-exposed neonates with T1 white matter hyperintensity (WMH) compared to exposed neonates without WMH (p<0.05).Conclusion:Prenatal opioid exposure may promote inflammation resulting in changes in reward signaling and white matter injury in the developing brain, with unique sex-specific effects. The actions of opioids through non-neuronal pathways need further investigation.

Amyloid, Nov 20, 2013

Systemic immunoglobulin light-chain primary amyloidosis (AL) is the most common type of systemic ... more Systemic immunoglobulin light-chain primary amyloidosis (AL) is the most common type of systemic amyloidosis. Recent advances in AL amyloidosis include the use of definitive proteomic typing, confirming the type of amyloid in patients with two possible amyloid-forming proteins. Laser microdissection followed by mass spectrometry (LMD/MS) can correctly identify the amyloid type with over 95% sensitivity and specificity. We report the case of a 68-year-old man with a history of IgA lambda monoclonal gammopathy and peripheral neuropathy who was diagnosed with pelvic nodal and psoas amyloidosis. The amyloid was found to be AL kappa type by LMD/MS. While LMD/MS has been effective in distinguishing among AL, secondary amyloidosis and hereditary forms of amyloidosis, our case demonstrates that typing can also identify unusual instances of discordance between light chain isotypes associated with clonal processes.

IEEE Journal of Biomedical and Health Informatics, Jun 1, 2021

The coronavirus (COVID-19) pandemic has been adversely affecting people's health globally. To dim... more The coronavirus (COVID-19) pandemic has been adversely affecting people's health globally. To diminish the effect of this widespread pandemic, it is essential to detect COVID-19 cases as quickly as possible. Chest radiographs are less expensive and are a widely available imaging modality for detecting chest pathology compared with CT images. They play a vital role in early prediction and developing treatment plans for suspected or confirmed COVID-19 chest infection patients. In this paper, a novel shape-dependent Fibonacci-p patterns-based feature descriptor using a machine learning approach is proposed. Computer simulations show that the presented system (1) increases the effectiveness of differentiating COVID-19, viral pneumonia, and normal conditions, (2) is effective on small datasets, and (3) has faster inference time compared to deep learning methods with comparable performance. Computer simulations are performed on two publicly available datasets; (a) the Kaggle dataset, and (b) the COVIDGR dataset. To assess the performance of the presented system, various evaluation parameters, such as accuracy, recall, specificity, precision, and f1-score are used. Nearly 100% differentiation between normal and COVID-19 radiographs is observed for the three-class classification scheme using the lung area-specific Kaggle radiographs. While Recall of 72.65 ± 6.83 and specificity of 77.72 ± 8.06 is observed for the COVIDGR dataset.

Cerebral Cortex, Jul 2, 2019

Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause... more Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7∼35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6∼33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P < 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.

Military Medicine, 2021

A 56-year-old female with 2 prior Chiari decompressions presented with rapidly progressive cognit... more A 56-year-old female with 2 prior Chiari decompressions presented with rapidly progressive cognitive decline. Brain magnetic resonance imaging, computed tomography myelogram, and prone digital subtraction myelography revealed signs of brain sag and left T9 perineural cysts but no cerebrospinal fluid leaks. Symptoms improved after multilevel blood patches but recurred. Lateral decubitus digital subtraction myelography revealed a spinal cerebrospinal fluid venous fistula (SCVF), which resolved after neurosurgeons ligated the nerve root. Rebound headaches with papilledema occurred on postoperative day 9 and then resolved 2 months after acetazolamide was started. A hyperintense paraspinal vein was seen retrospectively on T2-weighted magnetic resonance imaging with Dixon fat suppression sequencing. This case is unique in the acuity of cognitive decline secondary to SCVF. Acetazolamide at the time of treatment may potentially be used as prophylaxis for rebound intracranial hypertension. The hyperintense paraspinal vein may have utility in future diagnosis of SCVF.

Medical Physics, Jun 1, 2009

ABSTRACT Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns... more ABSTRACT Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about proton therapy. It leads to cautious treatment plans that partially neutralize the dosimetric advantage of protons. Vertebral bone marrow responds to radiation with fatty replacement that is visible on post‐treatment MRI. This presents a unique opportunity to visualize radiation effects in vivo. We have developed a method that uses spine MRI changes to precisely localize the distal dose edge in spinal proton radiation patients. Method and Materials: We carefully registered treatment planning CT scans and follow‐up T1‐weighted MRI scans from 10 proton spinal radiation patients. A radiation dose‐MRI signal intensity curve was created using the lateral beam penumbra in the sacrum. This curve was then used to quantitatively examine possible systematic or spatially varying proton range errors. Results: In the lateral penumbra there was a gradual increase in signal intensity with higher dose throughout the full dose range of 0–37.5 Gy. In the distal dose fall‐off region, the beam appeared to penetrate farther than planned in the central part of the vertebral bodies. The mean overshoot in five patients was 2.71 mm (95% confidence interval 1.13–4.28 mm). These errors are probably not clinically significant with current treatment planning procedures. Conclusion: We have demonstrated in vivo proton range verification based on post‐treatment spine MRI changes. Our analysis indicates that if range errors occur in spine treatments, their magnitude is at most a few millimeters in the majority of patients. It may be possible to extend our technique to MRI sequences that show early bone marrow changes. It could then be used for adaptive modification of spine radiation plans in order to reduce radiation dose to bone marrow and other normal tissues.

NeuroImage: Clinical, 2023

Cambridge University Press eBooks, May 5, 2013

Journal of Neurosurgery, May 1, 2013

S tent assistance for coil embolization of cerebral aneurysms is increasingly used during endovas... more S tent assistance for coil embolization of cerebral aneurysms is increasingly used during endovascular procedures involving wide-necked, small blistertype, and dissecting aneurysms. Although stents are considered to be effective in the treatment of wide-necked aneurysms through prevention of coil herniation into the parent artery lumen, 18,31 recent reports are suggesting that stents may play a role in flow remodeling that promotes further occlusion of aneurysms 14,17,20,30 and may also alter the underlying angular geometry of the stent-treated target vessel. 9 One of the major concerns limiting the uniform adoption of stent-mediated treatment, especially in ruptured lesions, relates to their associated risk of thromboembolic complications and the attendant requirement Incomplete stent apposition in Enterprise stent-mediated coiling of aneurysms: persistence over time and risk of delayed ischemic events Clinical article

International Journal of Radiation Oncology Biology Physics, Sep 1, 2010

Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about pr... more Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about proton therapy. It leads to cautious treatment plans that partially neutralize the dosimetric advantage of protons. Vertebral bone marrow responds to radiation with fatty replacement that is visible on post-treatment MRI. This presents a unique opportunity to visualize radiation effects in vivo. We have developed a method that uses spine MRI changes to precisely localize the distal dose edge in spinal proton radiation patients. Method and Materials: We carefully registered treatment planning CT scans and follow-up T1-weighted MRI scans from 10 proton spinal radiation patients. A radiation dose-MRI signal intensity curve was created using the lateral beam penumbra in the sacrum. This curve was then used to quantitatively examine possible systematic or spatially varying proton range errors. Results: In the lateral penumbra there was a gradual increase in signal intensity with higher dose throughout the full dose range of 0-37.5 Gy. In the distal dose fall-off region, the beam appeared to penetrate farther than planned in the central part of the vertebral bodies. The mean overshoot in five patients was 2.71 mm (95% confidence interval 1.13-4.28 mm). These errors are probably not clinically significant with current treatment planning procedures. Conclusion: We have demonstrated in vivo proton range verification based on post-treatment spine MRI changes. Our analysis indicates that if range errors occur in spine treatments, their magnitude is at most a few millimeters in the majority of patients. It may be possible to extend our technique to MRI sequences that show early bone marrow changes. It could then be used for adaptive modification of spine radiation plans in order to reduce radiation dose to bone marrow and other normal tissues.

Epilepsia, Oct 1, 2009

SummaryNeuroimaging is essential in the work‐up of patients with intractable epilepsy. In pediatr... more SummaryNeuroimaging is essential in the work‐up of patients with intractable epilepsy. In pediatric patients with medically refractory epilepsy, cortical dysplasias account for a large percentage of the epileptogenic substrate. Unfortunately, these are also the most subtle lesions to identify. For this reason, there has been ongoing interest in utilizing new advanced magnetic resonance imaging (MRI) techniques to improve the ability to identify, diagnose, characterize, and delineate cortical dysplasias. Technologic gains such as multichannel coils (32 phased array and beyond) and higher field strengths (3T, 7T, and greater) coupled with newer imaging sequences such as arterial spin labeling (ASL), susceptibility weighted imaging (SWI) and diffusion tensor/spectrum imaging (DTI/DSI) are likely to increase yield. Improved MRI techniques coupled with a multimodality approach including magnetoencephalography (MEG), positron emission tomography (PET), and other techniques will increase sensitivity and specificity for identifying cortical dysplasias.

Rivista Di Neuroradiologia, Jun 4, 2019

Background and purposeCervical spine tapering affects cerebrospinal fluid dynamics. Cervical spin... more Background and purposeCervical spine tapering affects cerebrospinal fluid dynamics. Cervical spine taper ratios derived from anteroposterior diameters reportedly differ between patients with syringomyelia and controls. We attempted to verify the differences in diameter and to show differences in cross-sectional area between syringomyelia and controls.MethodsCervical spine magnetic resonance images in syringomyelia patients (idiopathic or Chiari I related) and control patients were examined. In each subject, the anteroposterior diameter of the spinal canal was measured at each cervical level, and C1–C4, C4–C7, and C1–C7 taper ratios were calculated. Differences in taper ratio between groups were tested for statistical significance with the t-test. Cross-sectional areas of the spinal canal were measured at each cervical spinal level, and tapering was calculated.ResultsEighteen patients with idiopathic syringomyelia, 28 with Chiari I, and 29 controls were studied. Chiari and syringomyelia patients had significantly steeper diameter-based taper ratios than controls. The dural sac areas tapered proportionally with the diameter-based taper ratio in all groups.ConclusionsCervical spine anteroposterior diameter tapering and dural sac cross-sectional areas tapering differ between syringomyelia patients and controls.

Journal of Perinatology, Jun 18, 2022

Journal of Neuroimaging, Sep 18, 2022

Background and PurposePituitary macroadenomas and meningiomas are common neoplasms arising within... more Background and PurposePituitary macroadenomas and meningiomas are common neoplasms arising within the cavernous sinus. Imaging characteristics on MRI can often distinguish these tumors from one another; however, some cases may be more difficult to differentiate. This study compares patterns of cavernous segment internal carotid artery (CS‐ICA) stenosis between the two tumor types to establish a novel radiographic method of differentiation.MethodsA retrospective analysis of patients with pathology‐confirmed meningioma and pituitary adenomas at Tufts Medical Center was performed. The diameter of the CS‐ICA at the narrowest point within the cavernous sinus was measured and compared to the ipsilateral petrous segment ICA and contralateral CS‐ICA. The mean and range of percent stenosis and frequency of cases of CS‐ICA stenosis >15% were determined. Statistical analysis to compare the groups was conducted using the Chi‐squared test, Fisher's exact test, and t‐test.ResultsThere were a total of 78 out of 231 patients who were included in the study. The mean % ICA stenosis for all meningiomas was 9.3%, with increasing stenosis with increasing World Health Organization grade. Of all meningioma cases, 13 (33%) had greater than 15% ICA stenosis. Mean ICA stenosis for pituitary adenomas was –1.48%. There were no cases of pituitary adenomas causing ICA stenosis >15%.ConclusionsDifferentiating pituitary adenomas and intracavernous meningioma tumors can have important implications on surgical approach and outcome. Our study found that stenosis of the CS‐ICA greater than 15% is highly specific to meningiomas and can serve as a radiologic sign to distinguish between these two tumors.