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Timothy W. Vogel, Sunil Manjila and Alan R. Cohen

Giant occipitoparietal encephaloceles are rare forms of neurodevelopmental defects whose etiologies remain uncertain. Their occurrence can lead to variable neurological outcomes depending on the extent of cerebral cortex involved and the ability to repair the defect. In addition, encephaloceles may be associated with various genetic syndromes and familial inheritance. Here, the authors describe a unique constellation of malformations associated with the case of a giant occipitoparietal meningoencephalocele with herniation of cortical tissue and continuity with the ventricular system. The patient had a cleft lip and palate, hemivertebrae of the thoracic spine, a patent ductus arteriosus, a ventricular septal defect, and coarctation of the aorta. To identify the genetic underpinnings of these malformations, fluorescence in situ hybridization and microarray analysis were performed and revealed an 80.65-kb gain within chromosome band 2p11.2. Duplications of this region involving RMND5A, whose product contains a C-terminal to lis homology (LisH) domain, have not previously been associated with a defined phenotype but may present insight into encephalocele formation. Surgical repair and follow-up for the neurological malformations are also discussed.

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Michael Fana, Eleanor C. Smith, Jessica L. Gable, Nihal Manjila and Sunil Manjila

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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Sunil Manjila, Gagandeep Singh, Ayham M. Alkhachroum and Ciro Ramos-Estebanez

Edward Muybridge was an Anglo-American photographer, well known for his pioneering contributions in photography and his invention of the “zoopraxiscope,” a forerunner of motion pictures. However, this 19th-century genius, with two original patents in photographic technology, made outstanding contributions in art and neurology alike, the latter being seldom acknowledged. A head injury that he sustained changed his behavior and artistic expression. The shift of his interests from animal motion photography to human locomotion and gait remains a pivotal milestone in our understanding of patterns in biomechanics and clinical neurology, while his own behavioral patterns, owing to an injury to the orbitofrontal cortex, remain a mystery even for cognitive neurologists. The behavioral changes he exhibited and the legal conundrum that followed, including a murder of which he was acquitted, all depict the complexities of his personality and impact of frontal lobe injuries. This article highlights the life journey of Muybridge, drawing parallels with Phineas Gage, whose penetrating head injury has been studied widely. The wide sojourn of Muybridge also illustrates the strong connections that he maintained with Stanford and Pennsylvania universities, which were later considered pinnacles of higher education on the two coasts of the United States.

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Efrem M. Cox, Kathleen E. Knudson, Sunil Manjila and Alan R. Cohen

The authors present the first report of spinal congenital dermal sinus with paramedian dual ostia leading to 2 intradural epidermoid cysts. This 7-year-old girl had a history of recurrent left paramedian lumbosacral subcutaneous abscesses, with no chemical or pyogenic meningitis. Admission MRI studies demonstrated bilateral lumbar dermal sinus tracts and a tethered spinal cord. At surgery to release the tethered spinal cord the authors encountered paramedian dermal sinus tracts with dual ostia, as well as 2 intradural epidermoid cysts that were not readily apparent on MRI studies. Congenital dermal sinus should be considered in the differential diagnosis of lumbar subcutaneous abscesses, even if the neurocutaneous signatures are located off the midline.

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Osmond C. Wu, Sunil Manjila, Nima Malakooti and Alan R. Cohen

Among the families that have influenced the development of modern medicine into what it is today, the Monro lineage stands as one of the most notable. Alexander Monro primus (1697–1767) was the first of 3 generations with the same name, a dynasty that spanned 126 years occupying the Chair of Anatomy one after the other at the University of Edinburgh. After becoming Professor of Anatomy at the University of Edinburgh in 1719, Monro primus played a principal role in the establishment of the University of Edinburgh School of Medicine and the Edinburgh Royal Infirmary. In 1726, he published The Anatomy of the Humane Bones, of which 8 editions were printed during his lifetime. His son, Alexander Monro secundus (1733–1817), arguably the most notable of the 3 men, succeeded him as Professor of Anatomy. A highly regarded lecturer and anatomist, Monro secundus studied under many great physicians, including William Hunter and Johann Friedrich Meckel the Elder, and was also teacher to other well-known figures at the time, such as Joseph Black and Thomas Trotter. His most notable contributions include his work with the lymphatic system, the interventricular foramen (of Monro), and the Monro-Kellie doctrine. Alexander Monro tertius (1773–1859), the last of the dynasty, also succeeded his father as Professor of Anatomy. His work included insights into abdominal aortic aneurysms and the anatomy of the genitourinary system. The prominent association of the Monro family with the University of Edinburgh and the effects of a tenured professorship under the concept of “Ad vitam aut culpam” over successive generations are also described. To the best of the authors' knowledge, this historical review of the Monro family is among the few published in neurosurgical literature. A vivid historical overview of the medical contributions of the most famous and influential dynasty of physicians in Edinburgh at that time is provided, with relevant excerpts from original publications.

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Sunil Manjila, Shakeel A. Chowdhry, Nicholas C. Bambakidis and David J. Hart

The authors present a case of traumatic, complete, high cervical spine injury in a patient with gradual worsening deformity and neck pain while in rigid cervical collar immobilization, ultimately resulting in coronal-plane spondyloptosis. Due to the extent of lateral displacement of the spinal elements, preoperative evaluation included catheter angiography, which revealed complete right vertebral artery (VA) occlusion. A prophylactic arterial bypass graft from the right occipital artery to the extradural right VA was fashioned to augment posterior circulation blood supply prior to reduction and circumferential instrumented fusion. Following surgery, the patient was able to participate in an aggressive rehabilitation program allowing early mobilization, and he ceased to be ventilator-dependent following implantation of a diaphragmatic pacer. The authors review factors leading to progression of this type of injury and suggest technical pearls as well as highlight specific management pitfalls, including operative risks.

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Biji Bahuleyan, Sunil Manjila, Shenandoah Robinson and Alan R. Cohen


Surgery for medically intractable epilepsy secondary to unihemispheric pathology has evolved from more aggressive hemispherectomy to less aggressive variations of hemispherotomy. The authors propose a novel minimally invasive endoscopic hemispherotomy that should give results comparable to conventional open craniotomy and microsurgery.


Endoscopic transventricular hemispherotomy was performed in 5 silicon-injected cadaveric heads in the authors' minimally invasive neurosurgery laboratory. The lateral ventricle was accessed endoscopically through a frontal and occipital bur hole. White matter disconnections were performed to unroof the temporal horn and to disconnect the frontobasal region, corpus callosum, and fornix.


Using an endoscopic transventricular approach, all white matter disconnections were successfully performed in all 5 cadavers.


The authors have demonstrated the feasibility of endoscopic transventricular hemispherotomy in a cadaveric model. The technique is simple and could be useful in a subgroup of patients with parenchymal volume loss and ventriculomegaly.

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Harvey Chim, Sunil Manjila, Alan R. Cohen and Arun K. Gosain

The interplay of signals between dura mater, suture mesenchyme, and brain is essential in determining the fate of cranial sutures and the pathogenesis of premature suture fusion leading to craniosynostosis. At the forefront of research into suture fusion is the role of fibroblast growth factor and transforming growth factor–β, which have been found to be critical in the cell-signaling cascade involved in aberrant suture fusion. In this review, the authors discuss recent and ongoing research into the role of fibroblast growth factor and transforming growth factor–β in the etiopathogenesis of craniosynostosis.

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Sunil Manjila, Margherita Mencattelli, Benoit Rosa, Karl Price, Georgios Fagogenis and Pierre E. Dupont


Rigid endoscopes enable minimally invasive access to the ventricular system; however, the operative field is limited to the instrument tip, necessitating rotation of the entire instrument and causing consequent tissue compression while reaching around corners. Although flexible endoscopes offer tip steerability to address this limitation, they are more difficult to control and provide fewer and smaller working channels. A middle ground between these instruments—a rigid endoscope that possesses multiple instrument ports (for example, one at the tip and one on the side)—is proposed in this article, and a prototype device is evaluated in the context of a third ventricular colloid cyst resection combined with septostomy.


A prototype neuroendoscope was designed and fabricated to include 2 optical ports, one located at the instrument tip and one located laterally. Each optical port includes its own complementary metal-oxide semiconductor (CMOS) chip camera, light-emitting diode (LED) illumination, and working channels. The tip port incorporates a clear silicone optical window that provides 2 additional features. First, for enhanced safety during tool insertion, instruments can be initially seen inside the window before they extend from the scope tip. Second, the compliant tip can be pressed against tissue to enable visualization even in a blood-filled field. These capabilities were tested in fresh porcine brains. The image quality of the multiport endoscope was evaluated using test targets positioned at clinically relevant distances from each imaging port, comparing it with those of clinical rigid and flexible neuroendoscopes. Human cadaver testing was used to demonstrate third ventricular colloid cyst phantom resection through the tip port and a septostomy performed through the lateral port. To extend its utility in the treatment of periventricular tumors using MR-guided laser therapy, the device was designed to be MR compatible. Its functionality and compatibility inside a 3-T clinical scanner were also tested in a brain from a freshly euthanized female pig.


Testing in porcine brains confirmed the multiport endoscope's ability to visualize tissue in a blood-filled field and to operate inside a 3-T MRI scanner. Cadaver testing confirmed the device's utility in operating through both of its ports and performing combined third ventricular colloid cyst resection and septostomy with an endoscope rotation of less than 5°.


The proposed design provides freedom in selecting both the number and orientation of imaging and instrument ports, which can be customized for each ventricular pathological entity. The lightweight, easily manipulated device can provide added steerability while reducing the potential for the serious brain distortion that happens with rigid endoscope navigation. This capability would be particularly valuable in treating hydrocephalus, both primary and secondary (due to tumors, cysts, and so forth). Magnetic resonance compatibility can aid in endoscope-assisted ventricular aqueductal plasty and stenting, the management of multiloculated complex hydrocephalus, and postinflammatory hydrocephalus in which scarring obscures the ventricular anatomy.

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Prachi Mehndiratta, Sunil Manjila, Thomas Ostergard, Sylvia Eisele, Mark L. Cohen, Cathy Sila and Warren R. Selman

Amyloid angiopathy–associated intracerebral hemorrhage (ICH) comprises 12%–15% of lobar ICH in the elderly. This growing population has an increasing incidence of thrombolysis-related hemorrhages, causing the management of hemorrhages associated with cerebral amyloid angiopathy (CAA) to take center stage. A concise reference assimilating the pathology and management of this clinical entity does not exist. Amyloid angiopathy–associated hemorrhages are most often solitary, but the natural history often progresses to include multifocal and recurrent hemorrhages. Compared with other causes of ICH, patients with CAA-associated hemorrhages have a lower mortality rate but an increased risk of recurrence. Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical vessels, CAA-associated hemorrhages are superficial in location due to preferential involvement of vessels in the cerebral cortex and meninges. This feature makes CAA-associated hemorrhages easier to access surgically. In this paper, the authors discuss 3 postulates regarding the pathogenesis of amyloid hemorrhages, as well as the established clinicopathological classification of amyloid angiopathy and CAA-associated ICH. Common inheritance patterns of familial CAA with hemorrhagic strokes are discussed along with the role of genetic screening in relatives of patients with CAA. The radiological characteristics of CAA are described with specific attention to CAA-associated microhemorrhages. The detection of these microhemorrhages may have important clinical implications on the administration of anticoagulation and antiplatelet therapy in patients with probable CAA. Poor patient outcome in CAA-associated ICH is associated with dementia, increasing age, hematoma volume and location, initial Glasgow Coma Scale score, and intraventricular extension. The surgical management strategies for amyloid hemorrhages are discussed with a review of published surgical case series and their outcomes with a special attention to postoperative hemorrhage.