Nicholas Boulis - Academia.edu (original) (raw)

Papers by Nicholas Boulis

Spinal muscular atrophy is a genetic neurodegenerative disorder affecting muscle tone and functio... more Spinal muscular atrophy is a genetic neurodegenerative disorder affecting muscle tone and function, primarily in children. Disease onset varies from in utero to adult, and its progression and severity differ significantly among individuals. Clinicians have documented and categorized the disease for over a century, but no cure has been found to date. Recent breakthroughs in the understanding of the disease’s genetic underpinnings and mechanism have ushered in the promise of new treatments for the first time.

Nature Reviews Neurology, May 14, 2013

In the version of this article initially published, HSV-1-thymidine kinase was incorrectly referr... more In the version of this article initially published, HSV-1-thymidine kinase was incorrectly referred to as tyrosine kinase in Table 4, and as HSV1-tyrosine kinase on page 288. The error has been corrected for the HTML and PDF versions of the article.

Experimental Neurology, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

American Journal of Roentgenology, Dec 1, 2018

In the 1940s, Seddon [8, 9] popularized a three-tier classification of nerve injury. According to... more In the 1940s, Seddon [8, 9] popularized a three-tier classification of nerve injury. According to Seddon, neuropraxia occurs after disruption of the myelin sheath, but without distal Wallerian degeneration. Axonotmesis denotes complete axonal injury, resulting in distal Wallerian degeneration, but the continuity of the endoneurium or perineurium is maintained. Neurotmesis implies complete disruption of essential parts of a nerve with or without gross anatomic nerve discontinuity. Sunderland's classification [10] more precisely describes and predicts recovery, although there are varying opinions as to which is more important for surgical planning. Sunderland's first-degree injury [10] is equivalent to Seddon's neuropraxia [8, 9] and a complete and rapid recovery is expected. Axonotmesis (Sunderland's second-degree injury) involves axonal injury and resultant Wallerian degeneration, but the endoneurial tubes are intact. With a short gap, complete recovery is expected because the axons regenerate in the correct orientation as a result of endoneurial tube guidance [10]. Neurotmesis is further split into third-through fifthdegree injuries with increasing connective tissue injuries, beginning from the endoneurium and continuing peripherally to the epineurium. In third-degree injury, the endoneurial tubes are disrupted, allowing the chance of axonal mismatch and resulting in functional loss. Fourth-degree injuries are characterized by additional perineurium damage and

Neurosurgery, Jul 1, 2010

OBJECTIVE-The purpose of Clinical Problem Solving articles is to present management challenges to... more OBJECTIVE-The purpose of Clinical Problem Solving articles is to present management challenges to give practicing neurosurgeons insight into how field leaders address these dilemmas. This illustration is accompanied by a brief review of the literature on the topic. PRESENTATION-The case of a 16-year-old boy presenting with headaches is presented. The patient is found to have a typical colloid cyst at the foramen of Monro. Bilateral ventriculoperitoneal shunt placement had been performed as an initial treatment of the patient before presentation. RESULTS-Surgeons experienced in open and endoscopic surgery discuss their individual approaches to colloid cysts, in the context of previous shunting, providing a varied perspective on the clinical challenges posed by these lesions. CONCLUSION-Both open and endoscopic options remain viable for excision of a colloid cyst. Each has associated potential complications, as illustrated by the current case.

PLOS ONE, Oct 6, 2009

Background: Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by mus... more Background: Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by muscle weakness and atrophy due to progressive motoneuron loss. The death of motoneuron is preceded by the failure of neuromuscular junctions (NMJs) and axonal retraction. Thus, to develop an effective ALS therapy you must simultaneously preserve motoneuron somas, motor axons and NMJs. A conditioning lesion has the potential to accomplish this since it has been shown to enhance neuronal survival and recovery from trauma in a variety of contexts. Methodology/Principal Findings: To test the effects of a conditioning lesion in a model of familial ALS we administered a tibial nerve crush injury to presymptomatic fALS G93A rats. We examined its effects on motor function, motoneuron somas, motor axons, and NMJs. Our experiments revealed a novel paradigm for the conditioning lesion effect. Specifically we found that the motor functional decline in fALS G93A rats that received a conditioning lesion was delayed and less severe. These improvements in motor function corresponded to greater motoneuron survival, reduced motor axonopathy, and enhanced NMJ maintenance at disease end-stage. Furthermore, the increased NMJ maintenance was selective for muscle compartments innervated by the most resilient (slow) motoneuron subtypes, but was absent in muscle compartments innervated by the most vulnerable (fast fatigable) motoneuron subtypes. Conclusions/Significance: These findings support the development of strategies aimed at mimicking the conditioning lesion effect to treat ALS as well as underlined the importance of considering the heterogeneity of motoneuron sub-types when evaluating prospective ALS therapeutics.

Annals of Biomedical Engineering, Nov 17, 2017

The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results in the death of motor n... more The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results in the death of motor neurons in voluntary muscles. There are no cures for ALS and few available treatments. In studies with small animal models, injection of cellular therapeutics into the anterior horn of the spinal cord has been shown to inhibit the progression of ALS. It was hypothesized that spinal injection could be made faster and less invasive with the aid of a robot. The robotic system presented-SpinoBot-uses MRI guidance to position a needle for percutaneous injection into the spinal cord. With four degrees of freedom (DOF) provided by two translation stages and two rotational axes, SpinoBot proved capable of advanced targeting with a mean error of 1.12 mm and standard deviation of 0.97 mm in bench tests, and a mean error of 2.2 mm and standard deviation of 0.85 mm in swine cadaver tests. SpinoBot has shown less than 3% signal-to-noise ratio reduction in 3T MR imaging quality, demonstrating its compliance to the MRI environment. With the aid of SpinoBot, the length of the percutaneous injection procedure is reduced to less than 60 minutes with 10 minutes for each additional insertion. Although SpinoBot is designed for ALS treatment, it could potentially be used for other procedures that require precise access to the spine.

Brain Research, Jun 1, 1990

The present study investigated the individual contributions of spinal cord N-methyl-D-aspartate (... more The present study investigated the individual contributions of spinal cord N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the acoustic startle reflex in rats. The first experiment measured whole body acoustic startle before and after intrathecal infusion of various doses of either the NMDA receptor antagonist, D.L-2-amino-5-phosphonovaleric acid (AP-5), or the non-NMDA antagonist, 6-cyano-7nitroquinoxaline-2,3-dione (CNQX). Both compounds depressed startle in a dose-dependent fashion with similar potencies. A second experiment measured startle electromyographically (EMG) in the quadriceps femoris muscle complex in the hindlimbs during auditory stimulation to characterize the effects of these two compounds on the early (-8 ms) or late (-15 ms) EMG components of the startle response. CNQX preferentially blocked the early EMG component of startle, whereas AP-5 preferentially blocked the late component. These results suggest that the acoustic startle reflex involves an early EMG component mediated by spinal non-NMDA receptors, and a late EMG component mediated by spinal NMDA receptors.

Frontiers in Aging Neuroscience, Dec 7, 2020

Current Gene Therapy, Aug 1, 2007

ACS Applied Materials & Interfaces, Mar 30, 2017

Seeding nerve guidance conduits with Schwann cells can improve the outcome of peripheral nerve in... more Seeding nerve guidance conduits with Schwann cells can improve the outcome of peripheral nerve injury repair. Bone marrow stem cells (BMSCs) represent a good choice of cell source as they can differentiate into Schwann cells under appropriate conditions. In this work, we systematically investigated the differentiation of BMSCs into Schwann cells on scaffolds comprising electrospun fibers. We changed the alignment, diameter, and surface properties of the fibers to optimize the differentiation efficiency. The uniaxial alignment of fibers not only promoted the differentiation of BMSCs into Schwann cells but also dictated the morphology and alignment of the derived cells. Coating the surface of aligned fibers with laminin further enhanced the differentiation and thus increased the secretion of neurotrophins. When co-cultured with PC12 cells or chick dorsal root ganglion, the as-derived Schwann cells were able to promote the outgrowth of neurites from cell bodies and direct their extension along the fibers, demonstrating the positive impacts of both the neurotrophic effect and the morphological contact guidance. This work offers a promising strategy for integrating fiber guidance with stem cell therapy to augment peripheral nerve injury repair.

Surgical Neurology, Jun 1, 1994

A unique case of a suprasellar hamartoma in a 29-year-old woman is presented. The lesion was disc... more A unique case of a suprasellar hamartoma in a 29-year-old woman is presented. The lesion was discovered in the context of a work-up for amenorrhea that had lasted 1 year and was resistant to clomiphene and medroxyprogesterone acetate treatment. Magnetic resonance imaging (MRI) revealed a 1.2-cm anterior suprasellar lesion with no apparent connection to the hypothalamus or hypophysis. She underwent surgical resection of the mass. Pathologic examination revealed randomly arranged mature neurons, glial tissue, and myelinated fibers. There was no evidence of gonadotropin-releasing hormone producing neurons on immunohistochemical studies. Postoperative MRI showed complete resection of the lesion, and 1 year later mensus resumed off medication.

World Neurosurgery, Dec 1, 2020

Neurosurgery, Jul 1, 2011

BACKGROUND AND IMPORTANCE: Harlequin syndrome is a rare neurological condition involving various ... more BACKGROUND AND IMPORTANCE: Harlequin syndrome is a rare neurological condition involving various degrees of unilateral hyperhidrosis and erythema of the head and neck. We present a clinical presentation and description of curative therapy in a patient with a sudden onset of Harlequin syndrome following a thoracotomy. CLINICAL PRESENTATION: A 42-year-old female with a history of mastectomy for rightsided breast cancer subsequently had a left partial pneumonectomy for a metastasis. Postoperatively, she had onset of contralateral neck and facial flushing and sweating. Flushing was triggered by emotion and exercise, but also occurred spontaneously at random intervals. Magnetic resonance imaging of the brain, cervical spine, and thoracic spine were negative for pathology. Because of the patient's surgical history and negative workup, she was given a diagnosis of Harlequin syndrome. Surgical intervention consisted of a partial right T3 costotransversectomy with T2 sympathectomy. Postoperatively, the patient's symptoms of Harlequin syndrome resolved. The procedure was complicated by T1 radicular pain, which responded well to Gabapentin. CONCLUSION: The diagnosis of Harlequin syndrome is relatively new, and the majority of the scientific literature is concerned with descriptive case presentations. We present a surgical technique for the treatment of Harlequin syndrome.

Neuron, Jul 1, 2020

GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause amyotrophic lateral sclerosis (AL... more GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and lead to the production of aggregating dipeptide repeat proteins (DPRs) via repeat associated non-AUG (RAN) translation. Here, we show the similar intronic GGCCTG HREs that causes spinocerebellar ataxia type 36 (SCA36) is also translated into DPRs, including poly(GP) and poly(PR). We demonstrate that poly(GP) is more abundant in SCA36 compared to c9ALS/FTD patient tissue due to canonical AUG-mediated translation from intron-retained GGCCTG repeat RNAs. However, the frequency of the antisense RAN translation product poly(PR) is comparable between c9ALS/FTD and SCA36 patient samples. Interestingly, in SCA36 patient tissue, poly(GP) exists as a soluble species, and no TDP-43 pathology is present. We show that aggregate-prone chimeric DPR (cDPR) species underlie the divergent DPR pathology between c9ALS/FTD and SCA36. These findings reveal key differences in translation, solubility, and protein aggregation of DPRs between c9ALS/FTD and SCA36.

Stem Cell Research & Therapy, Jul 9, 2012

Neurosurgical Focus, Jun 1, 2007

ERIPHERAL nerve tumors comprise both benign and malignant variants. Benign tumors are predominant... more ERIPHERAL nerve tumors comprise both benign and malignant variants. Benign tumors are predominantly either schwannomas or neurofibromas. The former represent approximately 5% of all benign tumors of the soft tissue. Absence of the NF2 gene is required for tumor development. The gene is located on chromosome 22 and is variably called schwannomin or merlin. When not present in isolation, the tumors are associated with either NF2 or schwannomatosis, indicating the presence of a germline mutation and subsequent LOH. Tumors have been isolated intracranially and extracranially, in both major peripheral nerve complexes and in small distal branches, and in somatic as well as autonomic nerves. Because they arise endoneurally, they are encapsulated by the outer layers of the nerve sheath, the perineurium and fibrous epineurium. Neurofibromas may be localized in up to 90% of cases and are usually solitary but are most commonly associated with the phacomatosis, NF1, when diffuse. 142 This autosomal dominant condition is associated with a variety of occult findings related to inactivation of the NF1 tumor suppressor gene found on chromosome 17. Clinically, the conditions are stratified into localized, diffuse, and plexiform variants. It is particularly from this

Neurosurgery, Apr 3, 2020

BACKGROUND Facial pain syndromes can be refractory to medical management and often need neurosurg... more BACKGROUND Facial pain syndromes can be refractory to medical management and often need neurosurgical interventions. Neuromodulation techniques, including percutaneous trigeminal ganglion (TG) stimulation, are reversible and have emerged as alternative treatment options for intractable facial pain. OBJECTIVE To report the complication rates and analgesic effects associated with TG stimulation and identify potential predictors for these outcomes. METHODS A retrospective chart review of 59 patients with refractory facial pain who underwent TG stimulation was conducted. Outcomes following trial period and permanent stimulation were analyzed. Patients with >50% pain relief during trial stimulation received permanent implantation of the stimulation system. RESULTS Successful trial stimulation was endorsed by 71.2% of patients. During the trial period, 1 TG lead erosion was identified. History of trauma (facial/head trauma and oral surgery) was the only predictor of a failed trial compared to pain of idiopathic etiology (odds ratio: 0.15; 95% CI: 0.03-0.66). Following permanent implantation, approximately 29.6% and 26.5% of patients were diagnosed with lead erosion and infection of the hardware, respectively. TG lead migrations occurred in 11.7% of the patients. The numeric rating scale score showed a statistically significant reduction of 2.49 (95% CI: 1.37-3.61; P = .0001) at an average of 10.8 mo following permanent implantation. CONCLUSION TG stimulation is a feasible neuromodulatory approach for the treatment of intractable facial pain. Facial/head trauma and oral surgery may predict a nonsuccessful trial stimulation. Future development of specifically designed electrodes for stimulation of the TG, and solutions to reduce lead contamination are needed to mitigate the relatively high complication rate.

Neurosurgery, Apr 1, 2001

OBJECTIVE: The mechanisms underlying neural injury in intracerebral hemorrhage (ICH) remain uncer... more OBJECTIVE: The mechanisms underlying neural injury in intracerebral hemorrhage (ICH) remain uncertain. The present two-part study investigated cell death in the region of ICH and its association with caspase-3 activation. METHODS: ICH was produced in adult rats by injection of 100 l of autologous blood or saline into the right basal ganglia. The animals' brains were removed at 6 hours or at 1, 3, 7, or 14 days after hemorrhage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin in situ nick end-labeling (TUNEL) was used to detect deoxyribonucleic acid (DNA) fragmentation. TUNEL-positive cells were quantified. Caspase-3 activation was measured by Western blotting and immunohistochemistry. Double labeling was used to compare TUNEL with caspase-3 distribution and to identify the cell types affected. TUNEL-positive cells were also quantified at 6 hours, 1 day, and 3 days after injection of 5 U of thrombin into the right basal ganglion. RESULTS: At 6 hours, TUNEL-positive cells appeared in the ICH model (but not in the saline control brains) and were present for more than 2 weeks after ICH, peaking at 3 days. Western blot analysis revealed that the increase in immunoreactivity for the activated caspase-3 precedes that of DNA fragmentation, peaking at 1 day after ICH and declining thereafter. Immunohistochemistry analysis showed nucleus translocation of caspase-3 after ICH. Double-labeling studies demonstrated that both neurons and astrocytes surrounding the clot were TUNELpositive. In addition, TUNEL and caspase-3 were colocalized in the same cells. Intracerebral thrombin injection elicited DNA fragmentation similar to that observed after the injection of blood. CONCLUSION: Double-strand breaks in genomic DNA and induction of caspase-3 were demonstrated adjacent to parenchymal hematoma in the animals' brains. These results provide evidence that cell loss after ICH is associated with activation of caspase-3. (Neurosurgery 48:875-883, 2001)