Inflammatory pseudotumor of the trigeminal nerve: a neoplastic mimic you do not want to miss.

Inflammatory pseudotumor is a rare non-neoplastic mass that may clinically and radiologically mimic a spectrum of benign and malignant neoplasms. It is uncommon in the head and neck and particularly rare at the skull base. We present a case of pseudotumor originating from the trigeminal nerve in a patient who presented with headache and facial numbness. A high index of suspicion is necessary to diagnose this benign but locally aggressive entity.

Arterial spin-labeling and MR spectroscopy in the differentiation of gliomas.

BACKGROUND AND PURPOSE: Noninvasive grading of gliomas remains a challenge despite its important role in the prognosis and management of patients with intracranial neoplasms. In this study, we evaluated the ability of cerebral blood flow (CBF)-guided voxel-by-voxel analysis of multivoxel proton MR spectroscopic imaging ((1)H-MRSI) to differentiate low-grade from high-grade gliomas. MATERIALS AND METHODS: A total of 35 patients with primary gliomas (22 high grade and 13 low grade) underwent continuous arterial spin-labeling perfusion-weighted imaging (PWI) and (1)H-MRSI. Different regions of the gliomas were categorized as "hypoperfused," "isoperfused," and "hyperperfused" on the basis of the average CBF obtained from contralateral healthy white matter. (1)H-MRSI indices were computed from these regions and compared between low- and high-grade gliomas. Using a similar approach, we applied a subgroup analysis to differentiate low- from high-grade oligodendrogliomas because they show different physiologic and genetic characteristics. RESULTS: Cho(glioma (G)/white matter (WM)), Glx(G/WM), and Lip+Lac(G)/Cr(WM) were significantly higher in the "hyperperfused" regions of high-grade gliomas compared with low-grade gliomas. Cho(G/WM) and Lip+Lac(G)/Cr(WM) were also significantly higher in the "hyperperfused" regions of high-grade oligodendrogliomas. However, metabolite ratios from the "hypoperfused" or "isoperfused" regions did not exhibit any significant differences between high-grade and low-grade gliomas. CONCLUSION: The results suggest that (1)H-MRSI indices from the "hyperperfused" regions of gliomas, on the basis of PWI, may be helpful in distinguishing high-grade from low-grade gliomas including oligodendrogliomas.

A new fractionator principle with varying sampling fractions: exemplified by estimation of synapse number using electron microscopy.

The quantification of ultrastructure has been permanently improved by the application of new stereological principles. Both precision and efficiency have been enhanced. Here we report for the first time a fractionator method that can be applied at the electron microscopy level. This new design incorporates a varying sampling fraction paradigm. The method allows for systematic random sampling from blocks of variable slab thickness, thereby eliminating the need for exhaustive serial sectioning through an entire containing space. This novel approach acknowledges the inaccuracy inherent in estimating the total object number using section sampling fractions based on the average thickness of sections of variable thicknesses. As an alternative, this approach estimates the correct particle section sampling probability based on an estimator of the Horvitz-Thompson type, resulting in a theoretically more satisfying and accurate estimate of the expected number of particles for the defined containing space.

Regional hippocampal alteration associated with cognitive deficit following experimental brain injury: a systems, network and cellular evaluation.

Cognitive deficits persist in patients who survive traumatic brain injury (TBI). Lateral fluid percussion brain injury in the mouse, a model of human TBI, results in hippocampal-dependent cognitive impairment, similar to retrograde amnesia often associated with TBI. To identify potential substrates of the cognitive impairment, we evaluated regional neuronal loss, regional hippocampal excitability and inhibitory synaptic transmission. Design-based stereology demonstrated an approximate 40% loss of neurons through all subregions of the hippocampus following injury compared with sham. Input/output curves recorded in slices of injured brain demonstrated increased net synaptic efficacy in the dentate gyrus in concert with decreased net synaptic efficacy and excitatory postsynaptic potential-spike relationship in area CA1 compared with sham slices. Pharmacological agents modulating inhibitory transmission partially restored regional injury-induced alterations in net synaptic efficacy. Both evoked and spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in surviving dentate granule neurons were smaller and less frequent in injured brains than in uninjured brains. Conversely, both evoked and spontaneous mIPSCs recorded in surviving area CA1 pyramidal neurons were larger in injured brains than in uninjured brains. Together, these alterations suggest that regional hippocampal function is altered in the injured brain. This study demonstrates for the first time that brain injury selectively disrupts hippocampal function by causing uniform neuronal loss, inhibitory synaptic dysfunction, and regional, but opposing, shifts in circuit excitability. These changes may contribute to the cognitive impairments that result from brain injury.

Mild traumatic brain injury induces apoptotic cell death in the cortex that is preceded by decreases in cellular Bcl-2 immunoreactivity.

Although mild traumatic brain injury is associated with behavioral dysfunction and histopathological alterations, few studies have assessed the temporal pattern of regional apoptosis following mild brain injury. Anesthetized rats were subjected to mild lateral fluid-percussion brain injury (1.1-1.3 atm), and brains were evaluated for the presence of in situ DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, TUNEL) and morphologic characteristics of apoptotic cell death (nuclear and cytoplasmic condensation, presence of apoptotic bodies). Significant numbers of apoptotic TUNEL(+) cells were observed in the injured parietal cortex and underlying white matter up to 72 h post-injury (P<0.05 compared to sham-injured-injured), with maximal numbers present at 24 h. Apoptosis was confirmed by the presence of 180-200 bp nuclear DNA fragments in tissue homogenates. The appearance of apoptotic TUNEL(+) cells in the injured cortex was preceded by a marked decrease in immunoreactivity for the anti-cell death protein, Bcl-2, as early as 2 h post-injury. This decrease in cellular Bcl-2 staining was not accompanied by a concomitant loss of staining for the pro-cell death Bax protein, suggesting that post-traumatic neuronal death in the cortex may be dependent on altered cellular ratios of Bcl-2:Bax. In the hippocampus, no significant increase in apoptotic TUNEL(+) cells was observed compared to sham-injured-injured animals. However, selective neuronal loss was evident in the CA3 region at 24 h post-injury, that was preceded by an overt loss of neuronal Bcl-2 immunoreactivity at 6 h. No changes in either cellular Bcl-2 or Bax expression were observed in the thalamus or white matter at any time post-injury. Taken together from these data, we suggest that apoptosis contributes to cell death in both gray and white matter, and that decreases in cellular Bcl-2 may, in part, be associated with both apoptotic and non-apoptotic cell death following mild brain trauma.

A review and rationale for the use of genetically engineered animals in the study of traumatic brain injury.

The mechanisms underlying secondary cell death after traumatic brain injury (TBI) are poorly understood. Animal models of TBI recapitulate many clinical and pathologic aspects of human head injury, and the development of genetically engineered animals has offered the opportunity to investigate the specific molecular and cellular mechanisms associated with cell dysfunction and death after TBI, allowing for the evaluation of specific cause-effect relations and mechanistic hypotheses. This article represents a compendium of the current literature using genetically engineered mice in studies designed to better understand the posttraumatic inflammatory response, the mechanisms underlying DNA damage, repair, and cell death, and the link between TBI and neurodegenerative diseases.

Mild head injury increasing the brain's vulnerability to a second concussive impact.

OBJECT: Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI. METHODS: Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury. observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta-amyloid or tau were observed in any brain-injured animal. CONCLUSIONS: On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.

Effects of chronic, post-injury Cyclosporin A administration on motor and sensorimotor function following severe, experimental traumatic brain injury.

PURPOSE: Cyclosporin A (CsA) is widely used in clinical situations to attenuate graft rejection following organ and central nervous system transplantation. Previous studies demonstrated that CsA administration is neuroprotective in models of traumatic brain injury (TBI). However, no studies, to date, have evaluated the influence of post-injury CsA administration on behavioral recovery after TBI. METHODS: Rats (n = 33) were anesthetized and subjected to severe, lateral fluid percussion brain injury. Fifteen minutes thereafter, animals were randomized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgically prepared without injury and treated daily either with CsA or saline. Motor and sensorimotor functions were assessed at one day before and two days after injury, and weekly thereafter up to 4 wks post-injury. Cognition was assessed at 1 and 4 wks post-injury using a Morris Water Maze test. RESULTS: Injured animals showed significant impairments in motor, sensorimotor and cognitive function over the 4-week post-injury period. Injured animals treated with CsA showed a significant improvement in motor function assessed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on cognitive function were observed following CSA administration. CONCLUSION: These data suggest that daily post-injury treatment with CsA improves certain aspects of motor and sensorimotor function following experimental TBI.

The cause of infant and toddler subdural hemorrhage: a prospective study.

OBJECTIVE: To determine the frequency of child abuse and unintentional injury as a cause of infant and toddler subdural hemorrhage (SDH). METHODS: A prospective case series of a level I regional trauma center, regional children's hospital, and county medical examiner's office assessed consecutive children who were

Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model.

BACKGROUND AND PURPOSE: Histopathologic studies indicate that aneurysms treated with Guglielmi detachable coils (GDCs) have avascular centers with fibrosis mostly at the aneurysm periphery. We hypothesized that vascular endothelial growth factor (VEGF) released from a coil promotes clot organization, hyperplasia, and endothelial proliferation to facilitate closure of the aneurysm neck. METHODS: GDC segments were inserted into ligated common carotid arteries (CCAs) of adult male rats for 14 days. Coil segments (4-mm) were unmodified, modified with type I collagen (2.4 mg/mL), or modified with type I collagen and recombinant human VEGF-165 (rhVEGF; 500 microg/mL). CCA segments were harvested and coils removed for scanning electron microscopy (SEM). RESULTS: Collagen/rhVEGF coils (n = 11) resulted in marked reductions in CCA lumen area (0.03 mm(2)) compared with coils (n = 9, 0.21 mm(2), P <.001) and collagen coils (n = 5, 0.13 mm(2), P <.001). Collagen/rhVEGF coils (n = 11) also resulted in marked reductions in CCA diameter (0.19 mm) compared with coils (n = 9, 0.50 mm, P <.001) and collagen coils (n = 5, 0.40 mm, P <.001). Wall thickness was greater for the collagen/rhVEGF coil segments (0.22 mm) compared with coils (0.09 mm, P <.001), and the collagen coils (0.15 mm, P =.06). CCA segments containing collagen/rhVEGF coils also displayed Factor VIII positivity and were completely encapsulated in fibrotic tissue, while the unmodified and collagen coils were essentially smooth, as seen by SEM. CONCLUSION: These results suggest that rhVEGF may be beneficial in promoting endothelialization, clot organization, and tissue integration of the coils. This is the first study to hypothesize that rhVEGF may be useful as a surface modification to GDCs for enhancing their therapeutic effects in the treatment of cerebral aneurysms.

Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury.

OBJECT: Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. METHODS: Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). CONCLUSIONS: This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.

Acute cytoskeletal alterations and cell death induced by experimental brain injury are attenuated by magnesium treatment and exacerbated by magnesium deficiency.

Traumatic brain injury results in a profound decline in intracellular magnesium ion levels that may jeopardize critical cellular functions. We examined the consequences of preinjury magnesium deficiency and post-traumatic magnesium treatment on injury-induced cytoskeletal damage and cell death at 24 h after injury. Adult male rats were fed either a normal (n = 24) or magnesium-deficient diet (n = 16) for 2 wk prior to anesthesia and lateral fluid percussion brain injury (n = 31) or sham injury (n = 9). Normally fed animals were then randomized to receive magnesium chloride (125 micromol, i.v., n = 10) or vehicle solution (n = 11) at 10 min postinjury. Magnesium treatment reduced cortical cell loss (p < 0.05), cortical alterations in microtubule-associated protein-2 (MAP-2) (p < 0.05), and both cortical and hippocampal calpain-mediated spectrin breakdown (p < 0.05 for each region) when compared to vehicle treatment. Conversely, magnesium deficiency prior to brain injury led to a greater area of cortical cell loss (p < 0.05 compared to vehicle treatment). Moreover, brain injury to magnesium-deficient rats resulted in cytoskeletal alterations within the cortex and hippocampus that were not observed in vehicle- or magnesium-treated animals. These data suggest that cortical cell death and cytoskeletal disruptions in cortical and hippocampal neurons may be sensitive to magnesium status after experimental brain injury, and may be mediated in part through modulation of calpains.

Medical management and adjuvant therapies in spinal metastatic disease.

Metastatic spinal tumors are an increasingly common and difficult problem encountered by neurosurgeons and orthopedic surgeons. To improve therapies and increase life expectancy for patients with tumors such as those of the breast and prostate, a global, systematic approach is required to maximize the preservation of neurological function, maintenance of spinal stability, and relief of pain, all with the ultimate goal of improved functional capacity and quality of life (QOL). Although radiotherapy and surgery are still the primary therapeutic options, several new adjuvant therapies initially implemented to control pain more effectively have also been shown to reduce overall skeleton-related complications (pathological fractures and hypercalcemia) and may ultimately improve and extend QOL. This more global approach to spinal metastases also includes optimizing each patient's overall medical condition and potential for healing (that is, nutrition), as well as avoiding potential complications associated with metastatic disease (such as deep vein thrombosis), including excessive blood loss in the case of renal metastasis. A thorough knowledge and understanding of these therapeutic adjuvants is required to optimize care and to respond to our increasingly medically knowledgable patient population whose access to prevalent medical information has been increased because of the internet.

Biodegradable polyglycolide endovascular coils promote wall thickening and drug delivery in a rat aneurysm model.

OBJECTIVE: We designed biodegradable polyglycolide coils (BPCs) and compared the histopathological response to the coils with that to platinum Guglielmi detachable coils (GDCs), after insertion into ligated common carotid arteries (CCAs) of adult rats. BPCs were also tested for use in local drug delivery. METHODS: Segments (4-mm) of unmodified BPCs, unmodified GDCs, or BPCs coated with Type I bovine collagen and recombinant human vascular endothelial growth factor-165 (500 microg/ml) were inserted into ligated CCAs of adult rats for 14 days, and specimens were compared with contralateral CCA control specimens. RESULTS: Arterial segments with BPCs exhibited substantially increased wall thickening, compared with GDCs (0.33 mm versus 0.10 mm, P < 0.005), which reduced the luminal diameter by 40%, relative to untreated contralateral control specimens (P < 0.05, n = 6). Arterial segments with BPCs also exhibited a marked reduction (P < 0.05, n = 6) in luminal area (0.72 +/- 0.93 mm(2)), with marked cellular proliferation within the coil diameter, indicating coil integration. Arterial segments with collagen/recombinant human vascular endothelial growth factor-coated BPCs also exhibited a marked 2.9-fold increase (P < 0.005, n = 5) in wall thickness (0.29 +/- 0.11 mm) and a 34% reduction in luminal diameter, compared with contralateral control vessels. There was marked proliferation of cells within the coil lumen of vessels treated with BPCs with collagen/recombinant human vascular endothelial growth factor. CONCLUSION: In this feasibility study, BPCs enhanced the vascular response of CCA segments, compared with GDCs, and were also suitable for local protein delivery to the vessel lumen, under conditions of stasis and arterial pressurization of vascular cells.

Topic review: surface modifications enhancing biological activity of guglielmi detachable coils in treating intracranial aneurysms.

BACKGROUND: Endovascular therapy with Guglielmi detachable coils is an accepted treatment option for patients with intracranial aneurysms. However, an emerging technology in the realm of endovascular tools is the use of traditional Guglielmi detachable coils with biologically active substances complexed to the coil surface to enhance aneurysm occlusion. METHODS: We review the literature and current trends in modified Guglielmi detachable coils. Surface modifications with extracellular matrix proteins, growth factors, ion impregnation, and genetically altered cells have been used in animal studies to improve the cellular response of Guglielmi detachable coils. Similarly, coronary artery stents have been modified in several different ways to maintain vessel patency, contrary to the goal of endovascular therapy. We comparatively reviewed this literature to add insight into the evolution of the research on modified Guglielmi detachable coils. CONCLUSIONS: Guglielmi detachable coil modifications have the potential to enhance aneurysm obliteration with directed cellular responses. This may allow aneurysm occlusion with coils in less time than untreated coils, thus decreasing the risks of aneurysm enlargement and hemorrhage.

Experimental study of the magnetic stereotaxis system for catheter manipulation within the brain.

OBJECT: The magnetic stereotaxis system (MSS) is a device designed to direct catheter tips through magnetic forces. In this study the authors tested the safety and performance of the MSS in directing catheters through a nonlinear path to obtain biopsy specimens in pig brains. METHODS: Sixteen pigs underwent biopsy of the frontal brain region with the aid of an MSS (11 pigs) or a standard stereotactic biopsy tool (five pigs). Surgical preparation consisted of placement of six fiducial markers in the skull and the creation of a burr hole for attachment of a cranial bolt and passage of the biopsy catheter. The pigs underwent magnetic resonance (MR) imaging of the head to define a biopsy target and to plan a nonlinear path. Guided by the MSS, which used nearly real-time fluoroscopic imaging fused to the preoperative MR image, the authors advanced a catheter to the biopsy target. A biopsy tool was passed through the catheter and a tissue sample was obtained. The animals were observed for 3 to 5 days postoperatively, when they were assessed for neurological abnormalities or other signs of morbidity. Actual catheter placement was within 1.5 mm of the planned path to the biopsy site, using a minimum path radius of 30 mm. The registration error associated with the use of the MSS x-ray fluoroscopy and MR imaging averaged 1.7 mm. Tissue disruption caused by the MSS was similar to that of standard stereotactic procedures. CONCLUSIONS: The MSS affords accurate and safe guidance of brain catheters in animals. The application tested here, brain biopsy, is one of a number of potential catheter-guided procedures.

Bilateral growth-related protein expression suggests a transient increase in regenerative potential following brain trauma.

The potential of mature central nervous system (CNS) neurons to regenerate after injury represents a fundamental issue in neurobiology. The regional expression of proteins associated with axonal elongation, such as microtubule-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM), was examined using immunohistochemistry from 24 hours to 2 months following lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected to anesthesia alone. Within the site of maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased immunoreactivity was observed bilaterally for all growth-related proteins that were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the cortex (P < 0.01) and the hippocampus (P < 0.001), whereas MAP1B-P also was elevated in the thalamus (P < 0.05). Within the dentate gyrus, increased immunoreactivity was observed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated bilaterally within the inner molecular layers of the dentate gyrus (P < 0.005) and within the stratum lacunosum moleculare (P < 0.01), the stratum radiatum (P < 0. 005), and the stratum oriens (P < 0.05) of the hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P < 0.0005). The bilateral nature of increased expression of growth-related proteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Taken together, these results suggest the existence of a temporary posttraumatic state in which the CNS may have increased regenerative potential. Enhancement of such a response may be one therapeutic strategy in treating CNS injury.

Use of structural allografts in spinal osteomyelitis: a review of 47 cases.

OBJECT: The use of structural allografts in spinal osteomyelitis remains controversial because of the perceived risk of persistent infection related to a devitalized graft and spinal hardware. The authors have identified 47 patients over the last 3.5 years who underwent a surgical decompression and stabilization procedure in which fresh-frozen allografts were used after aggressive removal of infected and devitalized tissue. The patients subsequently underwent 6 weeks of postoperative antibiotic therapy (12 months for those with tuberculosis [TB]). METHODS: Follow-up data included results of serial clinical examinations, radiography, laboratory analysis (erythrocyte sedimentation rate and white blood cell count), and clinical outcome questionnaires. Of the original 47 patients (14 women and 33 men, aged 14-83 years), 39 were available for follow up. The average follow-up period at the time this article was submitted was 17 +/- 9 months (median 14 months, range 6-45 months). In the majority of cases (57%), a Staphylococcus species was the infectious organism. Predisposing risk factors included intravenous drug abuse (IVDA), previous surgery, diabetes, TB, and concurrent infections. During the follow-up period only two patients suffered recurrent infection at a contiguous level; both had a history of IVDA and one also had a chronic excoriating skin condition. No other recurrent infections have been identified, and no patient has required reoperation for persistent infection or allograft/hardware failure. CONCLUSIONS: It is the authors' opinion that the use of structural allografts in combination with aggressive tissue debridement and adjuvant antibiotic therapy provide a safe and effective therapy in cases of spinal osteomyelitis requiring surgery.

Neurosurgery at the University of Pennsylvania Medical Center.

The University of Pennsylvania Medical School was the nation's first medical school, and its Department of Neurosurgery is one of the nation's oldest. The history of the Department of Neurosurgery at Penn is recounted, beginning with the pioneer surgeon Charles Harrison Frazier. The evolution of the current department, its contemporary status, and its residency program are described.