Publications by authors named "Sunil Manjila"

99 Publications

Editorial. Long-term solutions in neurosurgery using extended reality technologies.

Neurosurg Focus 2021 08;51(2):E2

6Department of Neurosurgery, Mountain View Regional Medical Center, Las Cruces, New Mexico.

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http://dx.doi.org/10.3171/2021.5.FOCUS21235DOI Listing
August 2021

Radiomics and radiogenomics in gliomas: a contemporary update.

Br J Cancer 2021 Aug 6;125(5):641-657. Epub 2021 May 6.

Neuroradiology Division, Department of Radiology, Columbia University Medical Center, New York City, NY, USA.

The natural history and treatment landscape of primary brain tumours are complicated by the varied tumour behaviour of primary or secondary gliomas (high-grade transformation of low-grade lesions), as well as the dilemmas with identification of radiation necrosis, tumour progression, and pseudoprogression on MRI. Radiomics and radiogenomics promise to offer precise diagnosis, predict prognosis, and assess tumour response to modern chemotherapy/immunotherapy and radiation therapy. This is achieved by a triumvirate of morphological, textural, and functional signatures, derived from a high-throughput extraction of quantitative voxel-level MR image metrics. However, the lack of standardisation of acquisition parameters and inconsistent methodology between working groups have made validations unreliable, hence multi-centre studies involving heterogenous study populations are warranted. We elucidate novel radiomic and radiogenomic workflow concepts and state-of-the-art descriptors in sub-visual MR image processing, with relevant literature on applications of such machine learning techniques in glioma management.
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http://dx.doi.org/10.1038/s41416-021-01387-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405677PMC
August 2021

Expanded endoscopic endonasal approach for extending suprasellar and third ventricular lesions.

Acta Neurochir (Wien) 2020 10 9;162(10):2403-2408. Epub 2020 May 9.

Department of Neurological Surgery, The Ohio State University Medical Center, Columbus, OH, USA.

Background: Expanded endonasal approaches can provide direct access to the midline skull base from the anterior cranial fossa to the ventral foramen magnum. Surgical strategies of bone drilling, dural opening, and intradural dissection can determine the area of surgical exposure and instrument handling, affecting the safety of devascularizing/debulking suprasellar tumors.

Methods: We describe an expanded endoscopic endonasal approach for suprasellar lesions, with stepwise image-guided dissections highlighting surgical pearls and pitfalls to enhance surgical safety. This article presents transnasal intra-third-ventricular anatomy from trans-tuber cinereum, and trans-lamina terminalis approaches, comparing subchiasmatic and suprachiasmatic trajectories.

Conclusion: The rostral extension via endoscopic endonasal transsellar-transtubercular-transplanum approaches can provide a safe and feasible route for suprasellar lesions, in subchiasmatic, suprachiasmatic, and intraventricular regions.
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http://dx.doi.org/10.1007/s00701-020-04368-9DOI Listing
October 2020

Focused endoscopic endonasal craniocervical junction approach for resection of retro-odontoid lesions: surgical techniques and nuances.

Acta Neurochir (Wien) 2020 06 8;162(6):1275-1280. Epub 2020 Apr 8.

Department of Neurological Surgery, The Ohio State University Medical Center, N-1049 Doan Hall, 410 West 10th, Avenue, Columbus, OH, 43210, USA.

Background: Lesions posterior to the odontoid process pose a surgical challenge. Posterolateral approaches to this region are considerably risky for the spinal cord. Transoral approaches are limited in terms of exposure and can also carry morbidity.

Methods: We describe a focused endoscopic endonasal approach (EEA) for removing an osteochondroma located dorsal to the odontoid process. The surgical pearls and pitfalls using stepwise image-guided EEA cadaveric dissections are highlighted defining the importance of various craniocervical junction (CCJ) lines on imaging.

Conclusion: EEA to CCJ can be offered, with lower morbidity than other approaches, even for lesions that extend posterior and caudal to the odontoid process. Radiologic predictors of exposure and intraoperative techniques to enhance endoscopic visualization are discussed.
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http://dx.doi.org/10.1007/s00701-020-04319-4DOI Listing
June 2020

Surgical nuances of the expanded endoscopic anterior skull base craniectomy for hyperostotic meningioma resection.

Acta Neurochir (Wien) 2020 06 15;162(6):1269-1274. Epub 2020 Mar 15.

Department of Neurological Surgery, The Ohio State University Medical Center, N-1049 Doan Hall, 410 West 10th, Avenue, Columbus, OH, 43210, USA.

Background: The rostral expanded endoscopic approach (EEA) to anterior cranial fossa (ACF) has several advantages over transcranial/craniofacial surgery, providing early access to the vascular supply of tumors and reducing morbidities of craniotomy especially that of brain retraction. This article presents endoscopic landmarks and nuances for a wide ACF corridor, with stepwise image-guided dissections highlighting surgical tricks and techniques to enhance surgical safety.

Methods: We describe an expanded endoscopic endonasal anterior skull base craniectomy for a recurrent large olfactory groove hyperostotic meningioma, with correlated cadaveric dissections.

Conclusion: The widening of rostral EEA can provide a safe and feasible route to access ACF. This article highlights the specific landmarks in endoscopic anatomy with reference to the angle of visualization and bayonetted instruments.
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http://dx.doi.org/10.1007/s00701-020-04277-xDOI Listing
June 2020

Techniques and challenges of the expanded endoscopic endonasal access to the ventrolateral skull base during the "far-medial" and "extreme medial" approaches.

Acta Neurochir (Wien) 2020 03 13;162(3):597-603. Epub 2020 Jan 13.

Department of Neurological Surgery, The Ohio State University, Wexner Medical Center, N-1049 Doan Hall, 410 West 10th Avenue, Columbus, OH, 43210, USA.

Background: Expanding the ventrolateral skull base corridor from the midline of lower clivus to the petroclival fissure is a challenging endonasal surgical task. Resection of lytic lesions like chondrosarcoma can cause cranial nerve morbidities and injury of ICA, necessitating accurate knowledge of correlative endoscopic anatomy with stereotactic landmarks.

Methods: We describe an extended endoscopic endonasal approach (EEA) for a right petroclival chondrosarcoma with the demonstration of ipsilateral surgical landmarks with contralateral normal correlates, using a stepwise comparative image-guided cadaveric dissection study.

Conclusion: EEA for lytic lesions like chondrosarcomas needs to address brain shift and displacement of ICA, posing a chance for cranial nerve morbidities and ICA injury. Meticulous utilization of intraoperative stereotactic landmarks can help avoid and mitigate surgical complications.
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http://dx.doi.org/10.1007/s00701-019-04204-9DOI Listing
March 2020

History of cerebral localization and the emigration plight of three neuroscience giants from Nazi Germany: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann.

Neurosurg Focus 2019 09;47(3):E14

4Department of Neurosurgery, McLaren Bay Regional Medical Center, Bay City, Michigan.

The Nazi regime held power for well over a decade in Germany and were steadfast in their anti-Semitic agenda. Among the massive cohort of immigrants to America were approximately 5056 Jewish physicians, including several highly esteemed neurologists and neuroscientists of the time. Emigrating to a new world proved difficult and provided new challenges by way of language barriers, roadblocks in medical careers, and problems integrating into an alien system of medical training and clinical practice. In this article, the authors examine the tumultuous and accomplished lives of three Jewish German and Austrian neurologists and neuroscientists during the time of the Third Reich who shaped the foundations of neuroanatomy and neuropsychology: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann. The authors first examine the successful careers of these individuals in Germany and Austria prior to the Third Reich, followed by their journeys to and lives in the United States, to demonstrate the challenges an émigré physician faces for career opportunities and a chance at a new life. This account culminates in a description of these scientists' eponymous syndromes.Although their stories are a testimony to the struggles in Nazi Germany, there are intriguing and notable differences in their ages, ideologies, and religious beliefs, which highlight a spectrum of unique circumstances that impacted their success in the United States. Furthermore, in this account the authors bring to light the original syndromic descriptions: Gerstmann discovered contralateral agraphia and acalculia, right-left confusion, and finger agnosia in patients with dominant angular gyrus damage; Wallenberg described a constellation of symptoms in a patient with stenosis of the posterior inferior cerebellar artery; and Kallmann identified an association between hypogonadotropic hypogonadism and anosmia based on family studies. The article also highlights the unresolved confusions and international controversies about these syndromic descriptions. Still, these unique cerebral syndromes continue to fascinate neurologists and neurosurgeons across the world, from residents in training to practicing clinicians and neuroscientists alike.
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http://dx.doi.org/10.3171/2019.6.FOCUS19340DOI Listing
September 2019

Contemporary Updates on Clinical Trials of Antiangiogenic Agents in the Treatment of Glioblastoma Multiforme.

Asian J Neurosurg 2018 Jul-Sep;13(3):546-554

Metrohealth Medical Center, Case Western Reserve University School of Medicine, OH, USA.

Glioblastoma multiforme (GBM) has the highest rate of vascular proliferation among solid tumors. Angiogenesis is the central feature of rapid tumor growth in GBM and therefore remains an appealing therapeutic target in the treatment of these highly malignant tumors. Antiangiogenic therapy is emerging as an important adjuvant treatment. Multiple antiangiogenic agents targeting various sites in vascular endothelial growth factor (VEGF) and integrin pathways have been tested in clinical trials of newly diagnosed and recurrent GBMs. These include bevacizumab, enzastaurin, aflibercept, cediranib, and cilengitide. In this review, we discuss the current status and challenges facing clinical application of antiangiogenic treatment including anti-VEGF therapy and integrin pathway agents' therapy in glioblastoma. Here, we highlight a strong biologic rationale for this strategy, also focusing on integrin pathways. PubMed-indexed clinical trials published in English on antiangiogenic treatment of glioblastomas in the past 5 years were reviewed. The results of the current clinical trials of these agents are presented.
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http://dx.doi.org/10.4103/ajns.AJNS_266_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159033PMC
October 2018

Intratumoral Rathke's Cleft Cyst Remnants Within Craniopharyngioma, Pituitary Adenoma, Suprasellar Dermoid, and Epidermoid Cysts: A Ubiquitous Signature of Ectodermal Lineage or a Transitional Entity?

Neurosurgery 2019 08;85(2):180-188

Department of Neurological Surgery, The Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Background: The authors present cystic epithelial masses in the suprasellar region which on histopathology revealed 4 mixed tumors having simple cuboidal epithelium of Rathke's Cleft Cyst (RCC) elements trapped within pituitary adenoma, epidermoid cyst, dermoid cyst, and papillary craniopharyngioma respectively.

Objective: To highlight the developmental theory of ectodermal continuum in the realm of suprasellar epithelial cystic lesions and examines the cardinal aspects that distinguish RCC from its confounder, ciliary craniopharyngioma.

Methods: The authors performed a medical chart review on 4 patients who had coexisting RCC with craniopharyngioma, pituitary adenoma, suprasellar dermoid, and epidermoid cysts.

Results: This series of unique suprasellar lesions elucidate the spectrum of cases from Rathke's cyst to other suprasellar epithelial cysts including a recently identified clinical entity called ciliary craniopharyngioma, which authors feel is a misnomer. The authors also report the first case of ruptured dermoid cyst admixed with elements of Rathke's cyst elements and xanthogranuloma in neurosurgical literature.

Conclusion: We propose that the new entity of ciliary craniopharyngioma could be just another variant of RCC elements nested within a typical papillary or adamantinomatous lesion. Further study is warranted to understand the implications of natural history with tumors containing RCC elements.
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http://dx.doi.org/10.1093/neuros/nyy285DOI Listing
August 2019

Jugular bulb and skull base pathologies: proposal for a novel classification system for jugular bulb positions and microsurgical implications.

Neurosurg Focus 2018 07;45(1):E5

3Department of ENT, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

OBJECTIVE There is no definitive or consensus classification system for the jugular bulb position that can be uniformly communicated between a radiologist, neurootologist, and neurosurgeon. A high-riding jugular bulb (HRJB) has been variably defined as a jugular bulb that rises to or above the level of the basal turn of the cochlea, within 2 mm of the internal auditory canal (IAC), or to the level of the superior tympanic annulus. Overall, there is a seeming lack of consensus, especially when MRI and/or CT are used for jugular bulb evaluation without a dedicated imaging study of the venous anatomy such as digital subtraction angiography or CT or MR venography. METHODS A PubMed analysis of "jugular bulb" comprised of 1264 relevant articles were selected and analyzed specifically for an HRJB. A novel classification system based on preliminary skull base imaging using CT is proposed by the authors for conveying the anatomical location of the jugular bulb. This new classification includes the following types: type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (SCC), subclassified as type 2a (without dehiscence into the middle ear) or type 2b (with dehiscence into the middle ear); type 3, between the inferior margin of the posterior SCC and the inferior margin of the IAC, subclassified as type 3a (without dehiscence into the middle ear) and type 3b (with dehiscence into the middle ear); type 4, above the inferior margin of the IAC, subclassified as type 4a (without dehiscence into the IAC) and type 4b (with dehiscence into the IAC); and type 5, combination of dehiscences. Appropriate CT and MR images of the skull base were selected to validate the criteria and further demonstrated using 3D reconstruction of DICOM files. The microsurgical significance of the proposed classification is evaluated with reference to specific skull base/posterior fossa pathologies. RESULTS The authors validated the role of a novel classification of jugular bulb location that can help effective communication between providers treating skull base lesions. Effective utilization of the above grading system can help plan surgical procedures and anticipate complications. CONCLUSIONS The authors have proposed a novel anatomical/radiological classification system for jugular bulb location with respect to surgical implications. This classification can help surgeons in complication avoidance and management when addressing HRJBs.
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http://dx.doi.org/10.3171/2018.5.FOCUS18106DOI Listing
July 2018

A review of extraaxial developmental venous anomalies of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, venous varices or aneurysmal malformations, and enlarged emissary veins.

Neurosurg Focus 2018 07;45(1):E9

3Department of Medical Imaging, University of Arizona College of Medicine, Tucson, Arizona.

This paper is a narrative review of extraaxial developmental venous anomalies (eDVAs) of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, enlarged emissary veins, and venous varices or aneurysmal malformations. The article highlights the natural history, anatomy, embryology, imaging, clinical implications, and neurosurgical significance of these lesions, which the authors believe represent a continuum, with different entities characterized by distinct embryopathologic features. The indications and surgical management options are discussed for these individual intracranial pathologies with relevant illustrations, and a novel classification is proposed for persistent falcine sinus (PFS). The role of neurointervention and/or microsurgery in specific cases such as sinus pericranii and enlarged emissary veins of the skull is highlighted. A better understanding of the pathophysiology and developmental anatomy of these lesions can reduce treatment morbidity and mortality. Some patients, including those with vein of Galen malformations (VOGMs), can present with the added systemic morbidity of a high-output cardiac failure. Although VOGM is the most studied and classified of the above-mentioned eDVAs, the authors believe that grouping the former with the other venous anomalies/abnormalities listed above would enable the clinician to convey the exact morphophysiological configuration of these lesions, predict their natural history with respect to evolving venous hypertension or stroke, and extrapolate invaluable insights from VOGM treatment to the treatment of other eDVAs. In recent years, many of these symptomatic venous malformations have been treated with endovascular interventions, although these techniques are still being refined. The authors highlight the broad concept of eDVAs and hope that this work will serve as a basis for future studies investigating the role of evolving focal venous hypertension/global intracranial hypertension and possibilities of fetal surgical intervention in these cases.
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http://dx.doi.org/10.3171/2018.5.FOCUS18107DOI Listing
July 2018

Minimally Invasive Bilateral Anterior Cingulotomy via Open Minicraniotomy Using a Novel Multiport Cisternoscope: A Cadaveric Demonstration.

Oper Neurosurg (Hagerstown) 2019 02;16(2):217-225

Department of CV Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Bilateral anterior cingulotomy has been used to treat chronic pain, obsessive compulsive disorder, and addictions. Lesioning of the target area is typically performed using bilateral stereotactic electrode placement and target ablation, which involves transparenchymal access through both hemispheres.

Objective: To evaluate an endoscopic direct-vision lesioning using a unilateral parasagittal minicraniotomy for minimally invasive bilateral anterior cingulotomy using a novel multiport endoscope through the anterior interhemispheric fissure.

Methods: A novel multiport magnetic resonance imaging (MRI)-compatible neuroendoscope prototype is used to demonstrate cadaveric cingulate lesioning through a lateral imaging port while simultaneously viewing the pericallosal arteries as landmarks through a tip imaging port. The lateral port enables extended lesioning of the gyrus while rotation of the endoscope about its axis provides access to homologous areas of both hemispheres.

Results: Cadaver testing confirmed the capability to navigate the multiport neuroendoscope between the hemispheres using concurrent imaging from the tip and lateral ports. The lateral port enabled exploration of the gyrus, visualization of lesioning, and subsequent inspection of lesions. Tip-port imaging provided navigational cues and allowed the operator to ensure that the endoscope tip did not contact tissue. The multiport design required instrument rotation in the coronal plane of only 20° to lesion both gyri, while a standard endoscope necessitated a rotation of 54°.

Conclusion: Multiport MRI-compatible endoscopy can be effectively used in cisternal endoscopy, whereby a unilateral parasagittal minicraniotomy can be used for endoscopic interhemispheric bilateral anterior cingulotomy.
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http://dx.doi.org/10.1093/ons/opy083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215753PMC
February 2019

From Hypothermia to Cephalosomatic Anastomoses: The Legacy of Robert White (1926-2010) at Case Western Reserve University of Cleveland.

World Neurosurg 2018 May 27;113:14-25. Epub 2018 Feb 27.

Department of Neurosurgery, Metro Health Medical Center, Cleveland, Ohio, USA.

Dr. Robert J. White (1926-2010) was an eminent neurosurgeon and bioethicist, renowned for his classic work in hypothermia and pioneering mammalian head transplant experiments. He founded the Division of Neurosurgery at the Cleveland Metropolitan General Hospital (currently MetroHealth Medical Center, a level 1 trauma county hospital) and became the youngest full professor at the Case Western Reserve University in Cleveland, Ohio. With over 500 research articles to his credit, he founded the Brain Research Laboratory at what was then the Cleveland Metropolitan General Hospital, which was also home to future leaders in neurosurgery, neurosciences, and allied specialties. He transferred a healthy monkey head onto a surgically beheaded monkey body under deep hypothermic conditions drawing both laurels and criticisms alike. Despite a largely controversial neurosurgical research career, his original contributions to deep hypothermia have found profound clinical applications in modern trauma and vascular neurosurgery. The new fusogens and myelorrhaphy methods being tried in Europe hold promise for a future of reanastomosing 2 homologous or heterologous tracts in the neuraxis.
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http://dx.doi.org/10.1016/j.wneu.2018.01.175DOI Listing
May 2018

Bedside optical coherence tomography for Terson's syndrome screening in acute subarachnoid hemorrhage: a pilot study.

J Neurosurg 2018 02;130(2):517-524

2Department of Ophthalmology, University Hospitals, Case Western Reserve University, Cleveland, Ohio.

Objective: Approximately 10% of patients with subarachnoid hemorrhage (SAH) become permanently, legally blind. The average cost of lifetime support and unpaid taxes for each blind person amounts to approximately $900,000. This study evaluates the feasibility and potential role of bedside optical coherence tomography (OCT) in Terson’s syndrome (TS) in patients with acute SAH (aSAH) and its potential role in blindness prevention.

Methods: The authors conducted an open-label pilot study, in which 31 patients with an angiographic diagnosis of aSAH were first screened for TS with dilated funduscopy and then with OCT in the acute phase and at 6-week followup visits. Outpatient mood assessments (Patient Health Questionnaire–depression module, Hamilton Depression Scale), and quality of life general (NIH Patient-Reported Outcomes Measurement Information System) and visual scales (25-item National Eye Institute Visual Functioning Questionnaire) were measured at 1 and 6 weeks after discharge. Exclusion criteria included current or previous history of severe cataracts, severe diabetic retinopathy, severe macular degeneration, or glaucoma.

Results: OCT identified 7 patients with TS, i.e., a 22.6% incidence in our aSAH sample: 7 in the acute phase, including a large retinal detachment that was initially missed by funduscopy and diagnosed by OCT in follow-up clinic. Dilated retinal funduscopy significantly failed to detect TS in 4 (57.1%) of these 7 cases. Intraventricular hemorrhage was significantly more common in TS cases (85.7% vs 25%). None of the participants experienced any complications from OCT examinations. Neither decreased quality of life visual scale scores nor a depressed mood correlated with objective OCT pathological findings at the 6-week follow-up after discharge. There were no significant mood differences between TS cases and controls.

Conclusions: OCT is the gold standard in retinal disease diagnosis. This pilot study shows that bedside OCT examination is feasible in aSAH. In this series, OCT was a safe procedure that enhanced TS detection by decreasing false-negative/inconclusive funduscopic examinations. It allows early diagnosis of macular holes and severe retinal detachments, which require acute surgical therapy to prevent legal blindness. In addition, OCT aids in ruling out potential false-positive visual deficits in individuals with a depressed mood at follow-up.
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http://dx.doi.org/10.3171/2017.7.JNS171302DOI Listing
February 2018

In vivo tissue regeneration with robotic implants.

Sci Robot 2018 01;3(14)

Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Robots that reside inside the body to restore or enhance biological function have long been a staple of science fiction. Creating such robotic implants poses challenges both in signaling between the implant and the biological host, as well as in implant design. To investigate these challenges, we created a robotic implant to perform in vivo tissue regeneration via mechanostimulation. The robot is designed to induce lengthening of tubular organs, such as the esophagus and intestines, by computer-controlled application of traction forces. Esophageal testing in swine demonstrates that the applied forces can induce cell proliferation and lengthening of the organ without a reduction in diameter, while the animal is awake, mobile, and able to eat normally. Such robots can serve as research tools for studying mechanotransduction-based signaling and can also be used clinically for conditions such as long-gap esophageal atresia and short bowel syndrome.
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http://dx.doi.org/10.1126/scirobotics.aaq0018DOI Listing
January 2018

Acute Bilateral Ophthalmoplegia Due to Vertebrobasilar Dolichoectasia: A Report of Two Cases.

Am J Case Rep 2017 Dec 7;18:1302-1308. Epub 2017 Dec 7.

Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.

BACKGROUND Vertebrobasilar dolichoectasia (VBD) is a complex progressive arterial disease characterized by dilation, elongation, and tortuosity of the vertebral and basilar arteries, and may be congenital or acquired. VBD may lead to progressive compression of the brainstem, cranial nerve abnormalities, and intracranial hemorrhage, but may also be associated with arterial thrombosis, with ischemic stroke as the most common clinical outcome. CASE REPORT Two cases of VBD are presented, both with acute bilateral ophthalmoplegia and cranial nerve palsies, and vertebrobasilar arterial thrombosis that resulted in ischemic stroke. CONCLUSIONS VBD is a complex arterial disease with a variety of clinical manifestation, with bilateral ophthalmoplegia being a rare presentation. Clinical management of VBD is a challenge as there are no current management guidelines. Therefore, clinical management of cases of VBD should be individualized to balance the risks and benefits of treatment options for each patient.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729801PMC
http://dx.doi.org/10.12659/ajcr.904395DOI Listing
December 2017

A low-cost bioprosthetic semilunar valve for research, disease modelling and surgical training applications.

Interact Cardiovasc Thorac Surg 2017 11;25(5):785-792

Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.

Objectives: This paper provides detailed instructions for constructing low-cost bioprosthetic semilunar valves for animal research and clinical training. This work fills an important gap between existing simulator training valves and clinical valves by providing fully functioning designs that can be employed in ex vivo and in vivo experiments and can also be modified to model valvular disease.

Methods: Valves are constructed in 4 steps consisting of creating a metal frame, covering it with fabric and attaching a suture ring and leaflets. Computer-aided design files are provided for making the frame from wire or by metal 3D printing. The covering fabric and suturing ring are made from materials readily available in a surgical lab, while the leaflets are made from pericardium. The entire fabrication process is described in figures and in a video. To demonstrate disease modelling, design modifications are described for producing paravalvular leaks, and these valves were evaluated in porcine ex vivo (n = 3) and in vivo (n = 6) experiments.

Results: Porcine ex vivo and acute in vivo experiments demonstrate that the valves can replicate the performance of clinical valves for research and training purposes. Surgical implantation is similar, and echocardiograms are comparable to clinical valves. Furthermore, valve leaflet function was satisfactory during acute in vivo tests with little central regurgitation, while the paravalvular leak modifications consistently produced leaks in the desired locations.

Conclusions: The detailed design procedure presented here, which includes a tutorial video and computer-aided design files, should be of substantial benefit to researchers developing valve disease models and to clinicians developing realistic valve training systems.
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http://dx.doi.org/10.1093/icvts/ivx189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388656PMC
November 2017

Prolonged Intracisternal Papaverine Toxicity: Index Case Description and Proposed Mechanism of Action.

World Neurosurg 2018 Jan 7;109:251-257. Epub 2017 Oct 7.

Department of Neurology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:

Background: Intracisternal papaverine (iPPV) is a vasodilator used for prophylaxis of intraoperative vasospasm during aneurysmal clipping. Postoperative side effects of iPPV include transient cranial nerve palsies, most commonly mydriasis owing to oculomotor nerve involvement, with rapid resolution.

Methods: We critically reviewed current literature on the adverse effects of iPPV in aneurysmal surgery with a focus on oculomotor nerve involvement. We also present the index case of prolonged bilateral mydriasis secondary to iPPV irrigation toxicity and its putative underlying mechanism.

Results: Papaverine toxicity occurs in the setting of its antimuscarinic action and blood-cerebrospinal fluid and blood-brain barrier compromise owing to acute subarachnoid hemorrhage and direct effect of papaverine. Our patient also experienced severe vasospasm and a minor stroke, both contributing to further blood-brain barrier disruption, and relatively acidic pH of the subarachnoid hemorrhage milieu.

Conclusions: We propose that these factors perpetuate phase dynamics of papaverine crystals and facilitate a sustained slow release of papaverine within the cisternal system. Were it indicated, 0.3% iPPV would reasonably diminish the risk for neurotoxicity.
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http://dx.doi.org/10.1016/j.wneu.2017.09.196DOI Listing
January 2018

Cardioscopically Guided Beating Heart Surgery: Paravalvular Leak Repair.

Ann Thorac Surg 2017 Sep;104(3):1074-1079

Department of Cardiovascular Surgery, Boston Children's Hospital, Boston, Massachusetts. Electronic address:

Purpose: There remains a paucity of direct visualization techniques for beating-heart intracardiac procedures. To address this need, we evaluated a novel cardioscope in the context of aortic paravalvular leaks (PVLs) localization and closure.

Description: A porcine aortic PVL model was created using a custom-made bioprosthetic valve, and PVL presence was verified by epicardial echocardiography. Transapical delivery of occlusion devices guided solely by cardioscopy was attempted 13 times in a total of three pigs. Device retrieval after release was attempted six times. Echocardiography, morphologic evaluation, and delivery time were used to assess results.

Evaluation: Cardioscopic imaging enabled localization of PVLs via visualization of regurgitant jet flow in a paravalvular channel at the base of the prosthetic aortic valve. Occluders were successfully placed in 11 of 13 attempts (84.6%), taking on average 3:03 ± 1:34 min. Devices were cardioscopically removed successfully in three of six attempts (50%), taking 3:41 ± 1:46 min. No damage to the ventricle or annulus was observed at necropsy.

Conclusions: Cardioscopy can facilitate intracardiac interventions by providing direct visualization of anatomic structures inside the blood-filled, beating-heart model.
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http://dx.doi.org/10.1016/j.athoracsur.2017.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572817PMC
September 2017

A morphometric survey of the parasellar region in more than 2700 skulls: emphasis on the middle clinoid process variants and implications in endoscopic and microsurgical approaches.

J Neurosurg 2018 07 11;129(1):60-70. Epub 2017 Aug 11.

1Case Western Reserve University School of Medicine.

OBJECTIVE The middle clinoid process (MCP) is a bony projection that extends from the sphenoid bone near the lateral margin of the sella turcica. The varied prevalence and morphological features of the MCP in populations stratified by age, race, and sex are unknown; however, the knowledge of its anatomy and preoperative recognition on CT scans can aid greatly in complication avoidance and management. The aim of this study was to further illustrate the surgical anatomy of the parasellar region and to quantify the incidence of MCP and caroticoclinoid rings (CCRs) in dried preserved human anatomical specimens. METHODS The presence, dimensions, morphological classification (incomplete, contact, and CCR), and intracranial relations of the MCP were measured in 2726 dried skull specimens at the Hamann-Todd Osteological Collection at the Cleveland Museum of Natural History. Specific morphometric data points were recorded from each of these hemiskulls, and categorized based on age, sex, and ethnicity. Linear and logistic regressions were used to determine associations between explanatory variables and MCP morphology. Computed tomography scans of the skull specimens were obtained to explore radiological landmarks for different types of MCPs. Illustrative intraoperative videos were also analyzed in the light of these crucial surgical landmarks. RESULTS The sample included 2250 specimens from males and 476 from females. Specimens were classified as either "white" (60.5%) or "black" (39.2%). An MCP was found in 42% of specimens, with 60% of those specimens presenting bilaterally. Fully ossified CCR comprised 27% of all MCPs, and contact (defined as contact without ossification between MCP and anterior clinoid process) comprised 4% of all MCPs. White race (relative to black race) and increasing age were significant predictors of MCP presence (p < 0.001). White race was significantly associated with greater average MCP height (p < 0.001). Among skulls with CCR, both male sex and older age (> 70 years relative to < 50 years) were associated with increased CCR diameter (p < 0.001). No other significant predictors or associations were observed. The CT scans of skulls replicated and validated the authors' morphometric observations on incomplete, contact, and CCR patterns adequately. The surgical strategies of clinoid bone removal are validated, with appropriate video illustrations. CONCLUSIONS Variations in the patterns of bony MCPs can pose a significant risk for injury to the internal carotid artery during parasellar procedures, especially those involving clinoidectomy and optic strut drilling. Understanding parasellar anatomy, especially on skull-base CT imaging, may be integral to surgical planning and preoperative risk counseling in both transcranial and extended endonasal procedures, as well as to preparing for complications management perioperatively.
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http://dx.doi.org/10.3171/2017.2.JNS162114DOI Listing
July 2018

Endovascular plug for internal carotid artery occlusion in the management of a cavernous pseudoaneurysm with bifrontal subdural empyema: technical note.

J Neurosurg Pediatr 2017 Sep 16;20(3):239-246. Epub 2017 Jun 16.

Division of Pediatric Neurosurgery, Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, Maryland.

The authors demonstrate the use of an endovascular plug in securing a carotid artery pseudoaneurysm in an emergent setting requiring craniotomy for a concurrent subdural empyema. They describe the case of a 14-year-old boy with sinusitis and bifrontal subdural empyema who underwent transsphenoidal exploration at an outside hospital. An injury to the right cavernous segment of the ICA caused torrential epistaxis. Bleeding was successfully controlled by inflating a Foley balloon catheter within the sphenoid sinus, and the patient was transferred to the authors' institution. Emergent angiography showed a dissection of the right cavernous carotid artery, with a large pseudoaneurysm projecting into the sphenoid sinus at the site of arterial injury. The right internal carotid artery was obliterated using pushable coils distally and an endovascular plug proximally. The endovascular plug enabled the authors to successfully exclude the pseudoaneurysm from the circulation. The patient subsequently underwent an emergent bifrontal craniotomy for evacuation of a left frontotemporal subdural empyema and exenteration of both frontal sinuses. He made a complete neurological recovery. Endovascular large-vessel sacrifice, obviating the need for numerous coils and antiplatelet therapy, has a role in the setting of selected acute neurosurgical emergencies necessitating craniotomy. The endovascular plug is a useful adjunct in such circumstances as the device can be deployed rapidly, safely, and effectively.
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http://dx.doi.org/10.3171/2017.3.PEDS16370DOI Listing
September 2017

Pial Arteriovenous Fistula and Capillary Malformation-Arteriovenous Malformation Associated with RASA1 Mutation: 2 Pediatric Cases with Successful Surgical Management.

Pediatr Neurosurg 2017 31;52(4):261-267. Epub 2017 May 31.

Division of Pediatric Epilepsy, Department of Pediatric Neurology, Rainbow Babies and Children's Hospital, and Department of Neurology and Neurosurgery, The Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

We present case reports of 2 pediatric patients who were both found to have pial arteriovenous fistulas (AVFs) with subsequent genetic analysis revealing mutations in the RASA1 gene. Considering their family history of distinct cutaneous lesions, these mutations were likely inherited as opposed to de novo mutations. Patient 1 had large capillary malformations on the left side of the face and neck, associated with macrocephaly, and presented at the age of 32 months with speech delay, right-sided weakness, and focal seizures involving the right side of the body. Patient 2 presented with proptosis at the age of 9 months, but was otherwise neurologically intact. Given the chance for definitive single-stage control of vascular shunt (obviating chances for radiation exposure with endovascular treatment) and surgically accessible location of these intracranial lesions, both patients were treated with surgery with excellent clinical and radiological outcome. In general, given the high mortality secondary to severe congestive heart failure when treated conservatively, the goal of treatment in cortical AVF in young children, even when asymptomatic, is rapid control of the shunt. This was achieved successfully in our cases - both patients experienced significant symptomatic improvement following surgery and remained neurologically stable in the subsequent follow-up visits.
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http://dx.doi.org/10.1159/000474942DOI Listing
May 2018

A Novel Cause of Inferior Olivary Hypertrophy.

Neurohospitalist 2017 Apr 19;7(2):NP5-NP6. Epub 2016 Sep 19.

Department of Neurological Surgery, The Neurological Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.

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http://dx.doi.org/10.1177/1941874416665761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382652PMC
April 2017

Real-Time Ultrasound-Guided Catheter Navigation for Approaching Deep-Seated Brain Lesions: Role of Intraoperative Neurosonography with and without Fusion with Magnetic Resonance Imaging.

Pediatr Neurosurg 2017 20;52(2):80-86. Epub 2017 Jan 20.

Department of Neurosurgery, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.

Background/aims: Brain shift during the exposure of cranial lesions may reduce the accuracy of frameless stereotaxy. We describe a rapid, safe, and effective method to approach deep-seated brain lesions using real-time intraoperative ultrasound placement of a catheter to mark the dissection trajectory to the lesion.

Methods: With Institutional Review Board approval, we retrospectively reviewed the radiographic, pathologic, and intraoperative data of 11 pediatric patients who underwent excision of 12 lesions by means of this technique.

Results: Full data sets were available for 12 lesions in 11 patients. Ten lesions were tumors and 2 were cavernous malformations. Lesion locations included the thalamus (n = 4), trigone (n = 3), mesial temporal lobe (n = 3), and deep white matter (n = 2). Catheter placement was successful in all patients, and the median time required for the procedure was 3 min (range 2-5 min). There were no complications related to catheter placement. The median diameter of surgical corridors on postresection magnetic resonance imaging was 6.6 mm (range 3.0-12.1 mm).

Conclusions: Use of real-time ultrasound guidance to place a catheter to aid in the dissection to reach a deep-seated brain lesion provides advantages complementary to existing techniques, such as frameless stereotaxy. The catheter insertion technique described here provides a quick, accurate, and safe method for reaching deep-seated lesions.
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http://dx.doi.org/10.1159/000454838DOI Listing
March 2017

Ominous Etiology of Blurry Vision.

Neurohospitalist 2017 Jan 11;7(1):53-54. Epub 2016 May 11.

Department of Neurosurgery, Case Medical Center, Cleveland, OH, USA.

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http://dx.doi.org/10.1177/1941874416648196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167092PMC
January 2017

Local Coverage for Acute Severely Herniated Brain Using Scalp and Forehead Flaps in a Pediatric Patient With Head Trauma.

J Craniofac Surg 2017 Jan;28(1):231-235

*Division of Plastic Surgery †Department of Neurosurgery, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH.

A 4-year-old-boy required emergent craniectomy and drainage of a large right-sided acute subdural hematoma after head trauma, during which massive sinus hemorrhage with brain swelling occurred. Acute intraoperative management entailed dural cover using synthetic dural membrane substitute and scalp coverage over the herniated brain using acellular dermal matrix. After intensive monitoring and control of raised intracranial pressure over the next few days, the exposed brain was then covered by scalp and forehead flaps with cadaveric skin grafting to the donor site. This temporary coverage continued until adequate resolution of the intracranial swelling and control of the hydrocephalus using a ventriculoperitoneal shunt. Ultimately, the flaps were derotated and the craniectomy site was reconstructed with autologous banked bone. The child had a significant functional recovery with some residual left-sided weakness. This case is the first report of local tissue flaps used for temporary coverage of malignant brain herniation in a pediatric head trauma patient and highlights their effective use. Through serial surgical procedures the brain was successfully covered without significant blood loss and the patient's local tissues returned to their original donor sites with good cosmetic outcome, without sacrifice of the patient's own skin or free flap options.
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http://dx.doi.org/10.1097/SCS.0000000000002782DOI Listing
January 2017

Beyond the Cyst: The Many Contributions of Isadore Tarlov (1905-1977) to Contemporary Neurosurgical Practice.

Neurosurgery 2016 Nov;79(5):758-764

The Neurological Institute, University Hospital Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

: Isadore Max Tarlov (1905-1977) is primarily remembered for his 1938 description of the eponymous perineural "Tarlov cyst." However, during his long career as a neurosurgeon and researcher, he was responsible for many other observations and inventions that influenced the development of neurosurgery in the 20th century. While studying at Johns Hopkins Medical School he was acquainted with Walter Dandy, and he became the first resident to study under Wilder Penfield at the newly formed Montreal Neurological Institute. He made many novel observations about peripheral and cranial nerve anatomy, pioneered nerve anastomosis and grafting techniques, and introduced the concept of fibrin glue. He developed an animal model of spinal cord injury and used it to establish for the first time that functional neurological reserve is proportional to rapidity of injury, because gradual onset of compression is better tolerated by neural tissue than acute compression. He was the first to describe the use of the knee-chest position for lumbar spine surgery to minimize increases in epidural venous pressure due to abdominal compression. Finally, near the end of his career, he published a collection of thoughtful, philosophical essays entitled The Principle of Parsimony in Medicine and Other Essays, in which he advocated for a humanistic and restrained approach to medical practice. In this article, we discuss the contributions of Tarlov to the field of neurosurgery, including many of his lesser-known accomplishments that have become part of neurosurgery's collective legacy.
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http://dx.doi.org/10.1227/NEU.0000000000001379DOI Listing
November 2016

Mature salivary gland rests within sonic hedgehog-positive medulloblastoma: case report and insights into the molecular genetics and embryopathology of ectopic intracranial salivary gland analogs.

J Neurosurg Pediatr 2016 Dec 16;25(6):708-712. Epub 2016 Sep 16.

Department of Neurological Surgery, The Neurological Institute, and.

Intracranial ectopic salivary gland rests within dural-based lesions are reported very infrequently in the literature. The authors report the unique case of a 12-year-old boy with a cerebellar medulloblastoma positive for sonic hedgehog (Shh) that contained intraaxial mature ectopic salivary gland rests. The patient underwent clinical and radiological monitoring postoperatively, until he died of disseminated disease. An autopsy showed no evidence of salivary glands within disseminated lesions. The intraaxial presence of salivary gland rests and concomitant Shh positivity of the described tumor point to a disorder in differentiation as opposed to ectopic developmental foci, which are uniformly dural based in the described literature. The authors demonstrate the characteristic "papilionaceous" appearance of the salivary glands with mucicarmine stain and highlight the role of Shh signaling in explaining the intraaxial presence of seromucous gland analogs. This article reports the first intraaxial posterior fossa tumor with heterotopic salivary gland rests, and it provides molecular and embryopathological insights into the development of these lesions.
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http://dx.doi.org/10.3171/2016.6.PEDS15575DOI Listing
December 2016

IgG4-related disease causing facial nerve and optic nerve palsies: Case report and literature review.

Am J Otolaryngol 2016 Nov - Dec;37(6):567-571. Epub 2016 Aug 18.

Ear, Nose, and Throat Institute, University Hospitals Case Medical Center, Cleveland, OH, USA.

IgG4-related disease (IgG4-RD) is increasingly being recognized as an entity effecting the head and neck region. Although most commonly seen with salivary gland or paranasal sinus involvement, IgG4-RD may also involve the temporal bone and skull base. We report a rare care of a 61-year-old female with IgG4-RD presenting as synchronous lesions of the middle ear and middle cranial fossa with polyneuropathy of cranial nerves II, VI, and VII. Initial histopathological evaluation of her resected ear mass suggested a benign inflammatory process but no specific diagnosis. Her symptoms progressed over 10months prompting re-evaluation of the specimen and consideration of the IgG4-RD diagnosis. Key pathologic features included prominent lymphoplasmacytic population, storiform fibrosis, obliterative phlebitis, and IgG4 specific staining. The patient was treated with high-dose intravenous and oral steroids but was transitioned to azathioprine secondary to steroid-induced myopathy. Radiographic studies before and after treatment reveal marked improvement of the intracranial and extracranial disease. Correspondingly, her cranial neuropathies resolved. A high degree of clinical suspicion is necessary to diagnosis IgG4-RD. The diagnosis can be supported by elevated serum IgG, elevated IgG index, and pathognomonic histopathological findings. Primary treatment is with corticosteroids. However, immunotherapy using azathioprine or rituximab can be utilized in recurrent disease or patients with steroid intolerance.
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http://dx.doi.org/10.1016/j.amjoto.2016.08.005DOI Listing
September 2017
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