Chen Jingrun (1933–1996), perhaps the most prodigious mathematician of his time, focused on the field of analytical number theory. His work on Waring's problem, Legendre's conjecture, and Goldbach's conjecture led to progress in analytical number theory in the form of “Chen's Theorem,” which he published in 1966 and 1973. His early life was ravaged by the Second Sino-Japanese War and the Chinese Cultural Revolution. On the verge of solving Goldbach's conjecture in 1984, Chen was struck by a bicyclist while also bicycling and suffered severe brain trauma. During his hospitalization, he was also found to have Parkinson's disease. Chen suffered another serious brain concussion after a fall only a few months after recovering from the bicycle crash. With significant deficits, he remained hospitalized for several years without making progress while receiving modern Western medical therapies. In 1988 traditional Chinese medicine experts were called in to assist with his treatment. After a year of acupuncture and oxygen therapy, Chen could control his basic bowel and bladder functions, he could walk slowly, and his swallowing and speech improved. When Chen was unable to produce complex work or finish his final work on Goldbach's conjecture, his mathematical pursuits were taken up vigorously by his dedicated students. He was able to publish Youth Math, a mathematics book that became an inspiration in Chinese education. Although he died in 1996 at the age of 63 after surviving brutal political repression, being deprived of neurological function at the very peak of his genius, and having to be supported by his wife, Chen ironically became a symbol of dedication, perseverance, and motivation to his students and associates, to Chinese youth, to a nation, and to mathematicians and scientists worldwide.
Ting Lei, Evgenii Belykh, Alexander B. Dru, Kaan Yagmurlu, Ali M. Elhadi, Peter Nakaji and Mark C. Preul
Ali M. Elhadi, Samuel Kalb, Nikolay L. Martirosyan, Abhishek Agrawal and Mark C. Preul
Within a few months of Wilhelm Conrad Röntgen's discovery of x-rays in 1895, Fedor Krause acquired an x-ray apparatus and began to use it in his daily interactions with patients and for diagnosis. He was the first neurosurgeon to use x-rays methodically and systematically. In 1908 Krause published the first volume of text on neurosurgery, Chirurgie des Gehirns und Rückenmarks (Surgery of the Brain and Spinal Cord), which was translated into English in 1909. The second volume followed in 1911. This was the first published multivolume text totally devoted to neurosurgery. Although Krause excelled in and promoted neurosurgery, he believed that surgeons should excel at general surgery. Importantly, Krause was inclined to adopt technology that he believed could be helpful in surgery. His 1908 text was the first neurosurgical text to contain a specific chapter on x-rays (“Radiographie”) that showed roentgenograms of neurosurgical procedures and pathology. After the revolutionary discovery of x-rays by Röntgen, many prominent neurosurgeons seemed pessimistic about the use of x-rays for anything more than trauma or fractures. Krause immediately seized on its use to guide and monitor ventricular drainage and especially for the diagnosis of tumors of the skull base. The x-ray images contained in Krause's “Radiographie” chapter provide a seminal view into the adoption of new technology and the development of neurosurgical technique and are part of neurosurgery's heritage.
M. Yashar S. Kalani, Ali M. Elhadi, Wyatt Ramey, Peter Nakaji, Felipe C. Albuquerque, Cameron G. McDougall, Joseph M. Zabramski and Robert F. Spetzler
Aneurysms are relatively rare in the pediatric population and tend to include a greater proportion of large and giant lesions. A subset of these large and giant aneurysms are not amenable to direct surgical clipping and require complex treatment strategies and revascularization techniques. There are limited data available on the management of these lesions in the pediatric population. This study was undertaken to evaluate the outcome of treatment of large and giant aneurysms that required microsurgical revascularization and vessel sacrifice in this population.
The authors retrospectively identified all cases in which pediatric patients (age < 18 years) with aneurysms were treated using cerebral revascularization in combination with other treatment modalities at their institution between 1989 and 2013.
The authors identified 27 consecutive patients (19 male and 8 female) with 29 aneurysms. The mean age of the patients at the time of treatment was 11.5 years (median 13 years, range 1–17 years). Five patients presented with subarachnoid hemorrhage, 11 with symptoms related to mass effect, 2 with stroke, and 3 with seizures; in 6 cases, the aneurysms were incidental findings. Aneurysms were located along the internal carotid artery (n = 7), posterior cerebral artery (PCA) (n = 2), anterior cerebral artery (n = 2), middle cerebral artery (MCA) (n = 14), basilar artery (n = 2), vertebral artery (n = 1), and at the vertebrobasilar junction (n = 1). Thirteen were giant aneurysms (45%). The majority of the aneurysms were fusiform (n = 19, 66%), followed by saccular (n = 10, 34%). Three cases were previously treated using microsurgery (n = 2) or an endovascular procedure (n = 1). A total of 28 revascularization procedures were performed, including superficial temporal artery (STA) to MCA (n = 6), STA to PCA (n = 1), occipital artery to PCA (n = 1), extracranial-intracranial (EC-IC) bypass using radial artery graft (n = 3), EC-IC using a saphenous vein graft (n = 7), STA onlay (n = 3), end-to-end anastomosis (n = 1), and in situ bypasses (n = 6). Perioperative stroke occurred in 4 patients, but only one remained dependent (Glasgow Outcome Scale [GOS] score 3). At a mean clinical follow-up of 46 months (median 14 months, range 1–232 months), 26 patients had a good outcome (GOS score 4 or 5). There were no deaths. Five patients had documented occlusion of the bypass graft. The majority of aneurysms (n = 24) were obliterated at last follow-up. There was a single case of a residual aneurysm and one case of recurrence. Angiographic follow-up was unavailable in 3 cases.
Cerebral revascularization remains an essential tool in the treatment of complex cerebral aneurysms in children.
Ali M. Elhadi, Joseph M. Zabramski, Kaith K. Almefty, George A. C. Mendes, Peter Nakaji, Cameron G. McDougall, Felipe C. Albuquerque, Mark C. Preul and Robert F. Spetzler
Hemorrhagic origin is unidentifiable in 10%–20% of patients presenting with spontaneous subarachnoid hemorrhage (SAH). While the patients in such cases do well clinically, there is a lack of long-term angiographic followup. The authors of the present study evaluated the long-term clinical and angiographic follow-up of a patient cohort with SAH of unknown origin that had been enrolled in the Barrow Ruptured Aneurysm Trial (BRAT).
The BRAT database was searched for patients with SAH of unknown origin despite having undergone two or more angiographic studies as well as MRI of the brain and cervical spine. Follow-up was available at 6 months and 1 and 3 years after treatment. Analysis included demographic details, clinical outcome (Glasgow Outcome Scale, modified Rankin Scale [mRS]), and repeat vascular imaging.
Subarachnoid hemorrhage of unknown etiology was identified in 57 (11.9%) of the 472 patients enrolled in the BRAT study between March 2003 and January 2007. The mean age for this group was 51 years, and 40 members (70%) of the group were female. Sixteen of 56 patients (28.6%) required placement of an external ventricular drain for hydrocephalus, and 4 of these subsequently required a ventriculoperitoneal shunt. Delayed cerebral ischemia occurred in 4 patients (7%), leading to stroke in one of them. There were no rebleeding events. Eleven patients were lost to followup, and one patient died of unrelated causes. At the 3-year follow-up, 4 (9.1%) of 44 patients had a poor outcome (mRS > 2), and neurovascular imaging, which was available in 33 patients, was negative.
Hydrocephalus and delayed cerebral ischemia, while infrequent, do occur in SAH of unknown origin. Long-term neurological outcomes are generally good. A thorough evaluation to rule out an etiology of hemorrhage is necessary; however, imaging beyond 6 weeks from ictus has little utility, and rebleeding is unexpected.
Nikolay L. Martirosyan, Joseph Georges, Jennifer M. Eschbacher, Daniel D. Cavalcanti, Ali M. Elhadi, Mohammed G. Abdelwahab, Adrienne C. Scheck, Peter Nakaji, Robert F. Spetzler and Mark C. Preul
The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models.
Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H & E–stained tissues were reviewed.
Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well.
Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.
Ali M. Elhadi, Hasan A. Zaidi, Kaan Yagmurlu, Shah Ahmed, Albert L. Rhoton Jr., Peter Nakaji, Mark C. Preul and Andrew S. Little
Endoscopic transmaxillary approaches (ETMAs) address pathology of the anterolateral skull base, including the cavernous sinus, pterygopalatine fossa, and infratemporal fossa. This anatomically complex region contains branches of the trigeminal nerve and external carotid artery and is in proximity to the internal carotid artery. The authors postulated, on the basis of intraoperative observations, that the infraorbital nerve (ION) is a useful surgical landmark for navigating this region; therefore, they studied the anatomy of the ION and its relationships to critical neurovascular structures and the maxillary nerve (V2) encountered in ETMAs.
Endoscopic anatomical dissections were performed bilaterally in 5 silicone-injected, formalin-fixed cadaveric heads (10 sides). Endonasal transmaxillary and direct transmaxillary (Caldwell-Luc) approaches were performed, and anatomical correlations were analyzed and documented. Stereotactic imaging of each specimen was performed to correlate landmarks and enable precise measurement of each segment.
The ION was readily identified in the roof of the maxillary sinus at the beginning of the surgical procedure in all specimens. Anatomical dissections of the ION and the maxillary branch of the trigeminal nerve (V2) to the cavernous sinus suggested that the ION/V2 complex has 4 distinct segments that may have implications in endoscopic approaches: 1) Segment I, the cutaneous segment of the ION and its terminal branches (5–11 branches) to the face, distal to the infraorbital foramen; 2) Segment II, the orbitomaxillary segment of the ION within the infraorbital canal from the infraorbital foramen along the infraorbital groove (length 12 ± 3.2 mm); 3) Segment III, the pterygopalatine segment within the pterygopalatine fossa, which starts at the infraorbital groove to the foramen rotundum (13 ± 2.5 mm); and 4) Segment IV, the cavernous segment from the foramen rotundum to the trigeminal ganglion (15 ± 4.1 mm), which passes in the lateral wall of the cavernous sinus. The relationship of the ION/V2 complex to the contents of the cavernous sinus, carotid artery, and pterygopalatine fossa is described in the text.
The ION/V2 complex is an easily identifiable and potentially useful surgical landmark to the foramen rotundum, cavernous sinus, carotid artery, pterygopalatine fossa, and anterolateral skull base during ETMAs.
Luis Perez-Orribo, Laura A. Snyder, Samuel Kalb, Ali M. Elhadi, Forrest Hsu, Anna G. U. S. Newcomb, Devika Malhotra, Neil R. Crawford and Nicholas Theodore
Craniovertebral junction (CVJ) injuries complicated by transverse atlantal ligament (TAL) disruption often require surgical stabilization. Measurements based on the atlantodental interval (ADI), atlas lateral diameter (ALD1), and axis lateral diameter (ALD2) may help clinicians identify TAL disruption. This study used CT scanning to evaluate the reliability of these measurements and other variants in the clinical setting.
Patients with CVJ injuries treated at the authors' institution between 2004 and 2011 were evaluated retrospectively for demographics, mechanism and location of CVJ injury, classification of injury, treatment, and modified Japanese Orthopaedic Association score at the time of injury and follow-up. The integrity of the TAL was evaluated using MRI. The ADI, ALD1, and ALD2 were measured on CT to identify TAL disruption indirectly.
Among the 125 patients identified, 40 (32%) had atlas fractures, 59 (47.2%) odontoid fractures, 31 (24.8%) axis fractures, and 4 (3.2%) occipital condyle fractures. TAL disruption was documented on MRI in 11 cases (8.8%). The average ADI for TAL injury was 1.8 mm (range 0.9–3.9 mm). Nine (81.8%) of the 11 patients with TAL injury had an ADI of less than 3 mm. In 10 patients (90.9%) with TAL injury, overhang of the C-1 lateral masses on C-2 was less than 7 mm. ADI, ALD1, ALD2, ALD1 – ALD2, and ALD1/ALD2 did not correlate with the integrity of the TAL.
No current measurement method using CT, including the ADI, ALD1, and ALD2 or their differences or ratios, consistently indicates the integrity of the TAL. A more reliable CT-based criterion is needed to diagnose TAL disruption when MRI is unavailable.
Luis Perez-Orribo, Samuel Kalb, Laura A. Snyder, Forrest Hsu, Devika Malhotra, Richard D. Lefevre, Ali M. Elhadi, Anna G. U. S. Newcomb, Nicholas Theodore and Neil R. Crawford
The rule of Spence is inaccurate for assessing integrity of the transverse atlantal ligament (TAL). Because CT is quick and easy to perform at most trauma centers, the authors propose a novel sequence of obtaining 2 CT scans to improve the diagnosis of TAL impairment. The sensitivity of a new CT-based method for diagnosing a TAL injury in a cadaveric model was assessed.
Ten human cadaveric occipitocervical specimens were mounted horizontally in a supine posture with wooden inserts attached to the back of the skull to maintain a neutral or flexed (10°) posture. Specimens were scanned in neutral and flexed postures in a total of 4 conditions (3 conditions in each specimen): 1) intact (n = 10); either 2A) after a simulated Jefferson fracture with an intact TAL (n = 5) or 2B) after a TAL disruption with no Jefferson fracture (n = 5); and 3) after TAL disruption and a simulated Jefferson fracture (n = 10). The atlantodental interval (ADI) and cross-sectional canal area were measured.
From the neutral to the flexed posture, ADI increased an average of 2.5% in intact spines, 6.25% after a Jefferson fracture without TAL disruption, 34% after a TAL disruption without fracture, and 25% after TAL disruption with fracture. The increase in ADI was significant with both TAL disruption and TAL disruption and fracture (p < 0.005) but not in the other 2 conditions (p > 0.6). Changes in spinal canal area were not significant (p > 0.70).
This novel method was more sensitive than the rule of Spence for evaluating the integrity of the TAL on CT and does not increase the risk of further neurological damage.
Ali M. Elhadi, Samuel Kalb, Luis Perez-Orribo, Andrew S. Little, Robert F. Spetzler and Mark C. Preul
The field of anatomy, one of the most ancient sciences, first evolved in Egypt. From the Early Dynastic Period (3100 bc) until the time of Galen at the end of the 2nd century ad, Egypt was the center of anatomical knowledge, including neuroanatomy. Knowledge of neuroanatomy first became important so that sacred rituals could be performed by ancient Egyptian embalmers during mummification procedures. Later, neuroanatomy became a science to be studied by wise men at the ancient temple of Memphis. As religious conflicts developed, the study of the human body became restricted. Myths started to replace scientific research, squelching further exploration of the human body until Alexander the Great founded the city of Alexandria. This period witnessed a revolution in the study of anatomy and functional anatomy. Herophilus of Chalcedon, Erasistratus of Chios, Rufus of Ephesus, and Galen of Pergamon were prominent physicians who studied at the medical school of Alexandria and contributed greatly to knowledge about the anatomy of the skull base. After the Royal Library of Alexandria was burned and laws were passed prohibiting human dissections based on religious and cultural factors, knowledge of human skull base anatomy plateaued for almost 1500 years. In this article the authors consider the beginning of this journey, from the earliest descriptions of skull base anatomy to the establishment of basic skull base anatomy in ancient Egypt.