Spinal cord perfusion pressure correlates with breathing function in patients with acute, cervical traumatic spinal cord injuries: an observational study.

OBJECTIVE: This study aims to determine the relationship between spinal cord perfusion pressure (SCPP) and breathing function in patients with acute cervical traumatic spinal cord injuries. METHODS: We included 8 participants without cervical TSCI plus 13 patients with cervical traumatic spinal cord injuries, American Spinal Injury Association Impairment Scale grades A-C. In the TSCI patients, we monitored intraspinal pressure from the injury site for up to a week and computed the SCPP as mean arterial pressure minus intraspinal pressure. Breathing function was quantified by diaphragmatic electromyography using an EDI (electrical activity of the diaphragm) nasogastric tube as well as by ultrasound of the diaphragm and the intercostal muscles performed when sitting at 20°-30°. RESULTS: We analysed 106 ultrasound examinations (total 1370 images/videos) and 198 EDI recordings in the patients with cervical traumatic spinal cord injuries. During quiet breathing, low SCPP (< 60 mmHg) was associated with reduced EDI-peak (measure of inspiratory effort) and EDI-min (measure of the tonic activity of the diaphragm), which increased and then plateaued at SCPP 60-100 mmHg. During quiet and deep breathing, the diaphragmatic thickening fraction (force of diaphragmatic contraction) plotted versus SCPP had an inverted-U relationship, with a peak at SCPP 80-90 mmHg. Diaphragmatic excursion (up and down movement of the diaphragm) during quiet breathing did not correlate with SCPP, but diaphragmatic excursion during deep breathing plotted versus SCPP had an inverse-U relationship with a peak at SCPP 80-90 mmHg. The thickening fraction of the intercostal muscles plotted versus SCPP also had inverted-U relationship, with normal intercostal function at SCPP 80-100 mmHg, but failure of the upper and middle intercostals to contract during inspiration (i.e. abdominal breathing) at SCPP < 80 or > 100 mmHg. CONCLUSIONS: After acute, cervical traumatic spinal cord injuries, breathing function depends on the SCPP. SCPP 80-90 mmHg correlates with optimum diaphragmatic and intercostal muscle function. Our findings raise the possibility that intervention to maintain SCPP in this range may accelerate ventilator liberation which may reduce stay in the neuro-intensive care unit.

Duroplasty for injured cervical spinal cord with uncontrolled swelling: protocol of the DISCUS randomized controlled trial.

BACKGROUND: Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone. METHODS: This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results). DISCUSSION: We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care. TRIAL REGISTRATION: IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021).

Adverse Effect of Neurogenic, Infective, and Inflammatory Fever on Acutely Injured Human Spinal Cord.

This study aims to determine the effect of neurogenic, inflammatory, and infective fevers on acutely injured human spinal cord. In 86 patients with acute, severe traumatic spinal cord injuries (TSCIs; American Spinal Injury Association Impairment Scale (AIS), grades A-C) we monitored (starting within 72 h of injury, for up to 1 week) axillary temperature as well as injury site cord pressure, microdialysis (MD), and oxygen. High fever (temperature ≥38°C) was classified as neurogenic, infective, or inflammatory. The effect of these three fever types on injury-site physiology, metabolism, and inflammation was studied by analyzing 2864 h of intraspinal pressure (ISP), 1887 h of MD, and 840 h of tissue oxygen data. High fever occurred in 76.7% of the patients. The data show that temperature was higher in neurogenic than non-neurogenic fever. Neurogenic fever only occurred with injuries rostral to vertebral level T4. Compared with normothermia, fever was associated with reduced tissue glucose (all fevers), increased tissue lactate to pyruvate ratio (all fevers), reduced tissue oxygen (neurogenic + infective fevers), and elevated levels of pro-inflammatory cytokines/chemokines (infective fever). Spinal cord metabolic derangement preceded the onset of infective but not neurogenic or inflammatory fever. By considering five clinical characteristics (level of injury, axillary temperature, leukocyte count, C-reactive protein [CRP], and serum procalcitonin [PCT]), it was possible to confidently distinguish neurogenic from non-neurogenic high fever in 59.3% of cases. We conclude that neurogenic, infective, and inflammatory fevers occur commonly after acute, severe TSCI and are detrimental to the injured spinal cord with infective fever being the most injurious. Further studies are required to determine whether treating fever improves outcome. Accurately diagnosing neurogenic fever, as described, may reduce unnecessary septic screens and overuse of antibiotics in these patients.

Fat in the Fossa and the Sphenoid Sinus: A Simple and Effective Solution to CSF Leaks in Transsphenoidal Surgery. Cohort Study and Systematic Review.

Objectives Cerebrospinal fluid (CSF) leak following endoscopic transsphenoidal surgery (TSS) remains a challenge and is associated with high morbidity. We perform a primary repair with f at in the pituitary f ossa and further fat in the s phenoid sinus (FFS). We compare the efficacy of this FFS technique with other repair methods and perform a systematic review. Design, Patients, and Methods This is a retrospective analysis of patients undergoing standard TSS from 2009 to 2020, comparing the incidence of significant postoperative CSF rhinorrhea (requiring intervention) using the FFS technique compared with other intraoperative repair strategies. Systematic review of current repair methods described in the literature was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results In all, there were 439 patients, with 276 patients undergoing multilayer repair, 68 patients FFS repair, and 95 patients no repair. No significant differences were observed in baseline demographics between the groups. Postoperative CSF leak requiring intervention was significantly lower in the FFS repair group (4.4%) compared with the multilayer (20.3%) and no repair groups (12.6%, p < 0.01). This translated to fewer reoperations (2.9% FFS vs. 13.4% multilayer vs. 8.4% no repair, p < 0.05), fewer lumbar drains (2.9% FFS vs. 15.6% multilayer vs. 5.3% no repair, p < 0.01), and shorter hospital stay (median days: 4 [3-7] FFS vs. 6 (5-10) multilayer vs. 5 (3-7) no repair, p < 0.01). Risk factors for postoperative leak included female gender, perioperative lumbar drain, and intraoperative leak. Conclusion Autologous fat on fat graft for standard endoscopic transsphenoidal approach effectively reduces the risk of significant postoperative CSF leak with reduced reoperation and shorter hospital stay.

Removal or retention of minimally invasive screws in thoracolumbar fractures? Systematic review and case-control study.

BACKGROUND: There is uncertainty regarding delayed removal versus retention of minimally invasive screws following percutaneous fixation for thoracolumbar fractures. We conducted a systematic review and case-control study to test the hypothesis that delayed metalwork removal following percutaneous fixation for thoracolumbar fractures improves outcome. METHODS: A systematic review was performed in accordance with the PRISMA guidelines. Our case-control study retrospectively evaluated 55 consecutive patients with thoracolumbar fractures who underwent percutaneous fixation in a single unit: 19 with metalwork retained (controls) and 36 with metalwork removed. Outcomes were the Oswestry Disability Index (ODI), a supplemental questionnaire, and complications. RESULTS: The systematic review evaluated nine articles. Back pain was reduced in most patients after metalwork removal. One study found no difference in the ODI after versus before metalwork removal, whereas three studies reported significant improvement. Six studies noted no significant alterations in radiological markers of stability after metalwork removal. Mean complication rate was 1.7% (0-6.7). Complications were superficial wound infection, screw breakage at the time of removal, pull-out screw, and a broken rod. In the case-control study, both groups were well matched. For metalwork removal, mean operative time was 69.5 min (range 30-120) and length of stay was 1.3 days (0-4). After metalwork removal, 24 (68.6%) patients felt better, 10 (28.6%) the same and one felt worse. Two patients had superficial hematomas, one had a superficial wound infection, and none required re-operation. Metalwork removal was a significant predictor of return to work or baseline household duties (odds ratio 5.0 [1.4-18.9]). The ODI was not different between groups. CONCLUSIONS: The findings of both the systematic review and our case-control study suggest that removal of metalwork following percutaneous fixation of thoracolumbar fractures is safe and is associated with improved outcome in most patients.

Chronic relapsing ascending myelopathy: a treatable progressive neurological syndrome following traumatic spinal cord injury.

BACKGROUND: We describe a novel progressive neurological syndrome complicating traumatic spinal cord injury (TSCI). Based on clinical and radiological features, we propose the term 'Chronic Relapsing Ascending Myelopathy' (CRAM). We distinguish between the previously described sub-acute progressive ascending myelopathy (SPAM) and post-traumatic syringomyelia (PTS), which may lie on a spectrum with CRAM. CASE REPORT: A 60-year-old man sustained a T4 ASIA-A complete TSCI. Four months post-injury, he developed a rapidly progressive ascending sensory level to C4. Clinical and radiological evaluation revealed ascending myelopathy with progressive T2 hyper-intense cord signal change. He underwent cord detethering and expansion duroplasty. Following an initial dramatic resolution of symptoms, the patient sustained two relapses, each 1-month post-discharge characterised by recurrence of disabling ascending sensory changes, each correlating with the radiological recurrence of cord signal change. Symptoms and radiological signal change permanently resolved with more extensive detethering and expansion duroplasty. There is radiological and clinical resolution at 1-year follow-up. CONCLUSION: Acute neurological deterioration post-TSCI may be due to SPAM or may occur after years due to PTS. We propose CRAM as a previously unrecognised phenomenon. The radiological characteristics overlap with SPAM. However, CRAM presents later and, clinically, behaves like PTS, but without cord cystic change. Cord detethering with expansion duroplasty are an effective treatment.

Spinal myxomas: review of a rare entity.

Intramuscular myxomas are rare, benign mesenchymal tumours, occurring predominantly in large skeletal muscles as large, slow-growing and painless masses. Spinal occurrence is rare, and may present incidentally, or diagnosed via localized symptoms secondary to local infiltration of surrounding structures. Differential diagnosis based on imaging includes sarcomas, meningiomas and lipomas. We discuss two contrasting cases presenting with well-circumscribed cystic paraspinal lesions indicative of an infiltrative tumour and discuss the radiological and histological differences that distinguish myxomas from similar tumours. Surgical resection of the tumour was performed in both cases, however one patient required surgical fixation due to bony erosion secondary to tumour infiltration. Immuno-histopathological analysis confirmed the diagnosis of a cellular myxoma. Follow up imaging at 6 months confirmed no symptomatic or tumour recurrence in both cases. Histological analysis is the definitive means for diagnosis to differentiate myxomas from other tumours. Recurrence is rare if full resection is achieved.

Monitoring Spinal Cord Tissue Oxygen in Patients With Acute, Severe Traumatic Spinal Cord Injuries.

OBJECTIVES: To determine the feasibility of monitoring tissue oxygen tension from the injury site (pscto2) in patients with acute, severe traumatic spinal cord injuries. DESIGN: We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and pscto2. We analyzed 2,213 hours of such data. Follow-up was 6-28 months postinjury. SETTING: Single-center neurosurgical and neurocritical care units. SUBJECTS: Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A-C. Probes were inserted within 72 hours of injury. INTERVENTIONS: Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter. MEASUREMENTS AND MAIN RESULTS: pscto2 was significantly influenced by ISP (pscto2 26.7 ± 0.3 mm Hg at ISP > 10 mmHg vs pscto2 22.7 ± 0.8 mm Hg at ISP ≤ 10 mm Hg), SCPP (pscto2 26.8 ± 0.3 mm Hg at SCPP < 90 mm Hg vs pscto2 32.1 ± 0.7 mm Hg at SCPP ≥ 90 mm Hg), tissue glucose (pscto2 26.8 ± 0.4 mm Hg at glucose < 6 mM vs 32.9 ± 0.5 mm Hg at glucose ≥ 6 mM), tissue LPR (pscto2 25.3 ± 0.4 mm Hg at LPR > 30 vs pscto2 31.3 ± 0.3 mm Hg at LPR ≤ 30), and fever (pscto2 28.8 ± 0.5 mm Hg at cord temperature 37-38°C vs pscto2 28.7 ± 0.8 mm Hg at cord temperature ≥ 39°C). Tissue hypoxia also occurred independent of these factors. Increasing the Fio2 by 0.48 increases pscto2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in pscto2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26). CONCLUSIONS: This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy.

Recurrent terminal ventricle cyst: a case report.

The terminal ventricle (TV) of Krause is a rare cystic dilation of the conus' central canal. Due to limited understanding surrounding its pathophysiology, optimal management remains controversial. We report a 25-year-old female presenting with acute paraparesis. Magnetic resonance imaging spine revealed a cystic conus medullaris lesion in keeping with an incidental TV cyst. However, the patient experienced a rapid resolution of symptoms. We hypothesize that the TV cyst spontaneously ruptured and auto-decompressed. To our knowledge, this is the first reported case of an enlarging symptomatic TV cyst with spontaneous rupture and resolution of symptoms, highlighting the variable natural history of this condition.

Low-Grade Glioma Case Series: Lessons Learned from an Evolving 10-Year Single-Institution Multidisciplinary Team Practice.

BACKGROUND: Low-grade gliomas are a heterogeneous group with significant changes in their management during the last decade. OBJECTIVE: To assess how our multidisciplinary team approach to the management of low-grade glioma has evolved over the past 10 years and its implications for outcomes. METHODS: Retrospective single-center cohort study of adult patients with a pathologically confirmed diagnosis of World Health Organization grade II glioma between 2009 and 2018. Demographic, clinical, and pathologic data were collected. RESULTS: Ninety-five patients were included. There was a statistically significant difference in the surgical approach, with more patients having gross total resection (45.7% vs. 18.4%) and fewer patients having a biopsy (21.8% vs. 49.0%) (P = 0.002) after 2014. There was a significantly better overall survival after 2014 (<2014, 16.3%; ≥2014, 0 deaths; P = 0.010) measured at the mean time of follow-up. The use of adjuvant chemotherapy (P = 0.045) and radiotherapy (P = 0.001) significantly decreased after 2014. A subgroup analysis showed that the impact of extent of surgical resection was the greatest for survival in the 1p19q noncodeleted tumors (P = 0.029) and for seizure outcomes in the 1p19q codeleted group (P = 0.018). There was no statistically significant increase in neurologic disability with more radical surgery, incorporating intraoperative neuromonitoring, as measured by modified Rankin Scale score (P > 0.05). CONCLUSIONS: More radical surgery was associated with increased survival, less need for postoperative adjuvant therapy and better seizure control, without significant morbidity. Molecular markers are useful tools for stratification of benefits after such surgery.

Reliability of Intraoperative Monitoring in Patients with a Preexisting Motor Deficit: Case Report and Literature Review.

BACKGROUND: The use of intraoperative monitoring (IOM) in glioma surgery is a widely adopted and clinically validated adjunct to define safe zones of resection for the neurosurgeon. However, the role of IOM in cases of a significant preexisting motor deficit is questionable. CASE DESCRIPTION: We describe a case of a 25-year-old with a recurrent presentation of a left paracentral glioblastoma, admitted with intratumoral hemorrhage and subsequent acute severe right-sided weakness. The patient underwent a redo left parietal craniotomy and 5-aminolevulinic acid-guided resection with IOM. The severity of the weakness was not reflected by the pre- and intraoperative cortical motor evoked potentials (MEPs) that were reassuring. The patient's hemiparesis recovered to full power postoperatively. CONCLUSIONS: Preoperative weakness is traditionally accepted as a relative contraindication to IOM and therefore its usefulness is questioned in this context. Our case challenges this assumption. We present the clinical course, review the cranial and spinal literature including the reliability of IOM in cases of preoperative motor deficit, and discuss the need for tailor-made IOM strategies.

Spinal Cord Compression Caused by Fibroblastic Reticular Cell Tumor (FRCT) Originating from Thoracic Spine.

BACKGROUND: The authors present the first reported case of a fibroblastic reticular cell tumor (FRCT) presenting with spinal cord compression. FRCTs are the rarest subset of dendritic cell tumors, a specific group of hematologic malignancies. FRCTs reportedly behave similar to low-grade sarcomas as opposed to malignant tumors. CASE DESCRIPTION: A 45-year-old female patient presented with a 2-and-a-half week history of a flu-like illness and 1 week history of lower limb imbalance. Magnetic resonance imaging revealed an extradural lesion at T3/4 compressing the spinal cord. Initially, the patient was presumed to have metastatic spinal cord compression, and she underwent a decompressive thoracic laminectomy with debulking of the lesion with follow-up adjuvant radiotherapy. However, histology identified a unique primary FRCT originating from spine, not secondary metastatic spinal cord compression. There were no histologically aggressive features likely contributing to the favorable outcome following surgery and adjuvant radiotherapy. Her postoperative recovery was unremarkable, and she recovered fully. CONCLUSIONS: Although rare, we report the first case of FRCT originating in the spine causing spinal cord compression. The clinical presentation of the case, histologic features of FRCT, and the treatment options are reviewed.

Is There a Difference in Hospital Stay between Patients undergoing Translabyrinthine or Retrosigmoid Surgery for Vestibular Schwannoma Stratified by Tumor Size?

Objective To date, no European study has compared approach-specific outcome data in vestibular schwannoma (VS) surgery stratified by tumor size. We analyzed hospital length of stay (LOS), intensive therapy/high-dependency unit (ITU/HDU) LOS, and complications in patients undergoing VS surgery via the translabyrinthine (TL) versus retrosigmoid (RS) approaches, stratifying for tumor size. Design Prospective database undergoing retrospective review. Setting Tertiary center. Participants A total of 117 patients with VS undergoing TL ( n = 71) or RS ( n = 46) surgical resection from 2011 to 2016 were analyzed. Data including age, gender, surgical approach, tumor size, hospital, and ITU/HDU LOS and postoperative complications were evaluated. Intervention(s) Therapeutic-VS surgery via either TL or RS approach. Main Outcome Measure(s) LOS (hospital/intensive care unit). Results Hospital LOS was significantly greater in patients undergoing the RS approach versus TL approach in VS between 31 and 40 mm (11 versus 7 days, p < 0.0006). The mean ITU/HDU LOS was greater in the RS group compared with the TL group (4.6 versus 1, p > 0.05). Reported complications were higher in the RS group ( n = 40 versus 22). A post hoc analysis of the 31 to 40 mm group revealed no statistically significant difference in the American Society of Anesthesiologists grade or preoperative performance status. Conclusions In our practice, in VS sized 31 to 40 mm patients stay 4 days longer post RS compared with TL surgery. This translates to £1600 extra per patient in the UK. Our data may inform decision-making during the skull base multidisciplinary team and the consent process to help decide the ideal operative approach for the patient.

Drug-induced paraspinal myositis mimicking acute bilateral sciatica.

Although cocaine induced myopathy and myotoxicity are described in the literature, we report a rare case of cocaine induced paraspinal myositis presenting with acute sciatic symptoms. A 35-year-old man presented with acute left-sided sciatica and was discharged from the emergency department (ED). He subsequently attended ED the following day in severe pain and bilateral sciatic symptoms, but denied symptoms of neurogenic bowel/bladder disturbance. Clinical examination was limited by severe pain: focal midline lumbar tenderness was elicited on palpation, per rectal and limb examinations were within normal limits with no significant neurological deficit. He was admitted for observation and pain management. His blood tests revealed a leucocyte count of 21.5×109/L, C reactive protein of 89 mg/L and deranged renal function with creatinine of 293 µmol/L. An urgent lumbar spine MRI was arranged to rule out a discitis or epidural abscess. Lumbar MRI did not demonstrate any features of discitis but non-specific appearances of paraspinal inflammation raised the suspicion of a paraspinal myositis. Creatinekinase (CK) was found to be 66329 IU/L and a detailed history revealed he was a cocaine user. Paraspinal muscle biopsy confirmed histological features compatible with myositis. Other serological tests were negative, including anti-GBM, ANCA, ANA, Rheumatoid factor, Hep B, Hep C, myositis specific ENA, Treponema pallidum, Borrelia burgdorferi, Rickettsia, Leptospira, EBV and CMV. There was good clinical response to treatment with prednisolone 20 mg OD with an improvement in renal function, CK levels and CRP. He had resumed normal activities and return to work at 6-week follow-up. A detailed social history including substance misuse is important in patients presenting to the ED-especially in cases of severe musculoskeletal pain with no obvious localising features. Drug induced myotoxicity, although rare, can result in symptomatic patients with severe renal failure.

Subclinical meningoventriculitis as a cause of obstructive hydrocephalus.

Communicating hydrocephalus may complicate infantile bacterial meningitis, typically presenting with systemic features of infection. We report a rare case of 'subclinical meningoventriculitis' causing obstructive hydrocephalus and its challenging management. A healthy 10-week-old immunocompetent male patient presented with failure to thrive and vomiting, secondary to presumed gastro-oesophageal reflux. The child was neurologically alert, afebrile with normal inflammatory markers. Progressive macrocephaly prompted an MRI confirming triventricular hydrocephalus secondary to aqueductal stenosis. An endoscopic third ventriculostomy was performed however abandoned intraoperatively due to the unexpected finding of intraventricular purulent cerebrospinal fluid. A 6-week course of intravenous ceftriaxone was commenced for Escherichia coli meningoventriculitis. However, the child was readmitted 18 days postoperatively with acute hydrocephalus requiring a ventricular washout and staged ventriculoperitoneal shunt insertion at 4 weeks. Serial head circumference measurements are paramount in the assessment of a paediatric patient. In an immunocompetent child, a subclinical fibropurulent meningoventriculitis can result in several management challenges.

Joseph Buford Pennybacker, C.B.E., M.D., F.R.C.S. (1907-1983): Continuing Sir Hugh Cairns' Oxford Legacy and Pioneer of the Modern Management of Cerebral Abscesses.

The authors examine the life and contribution of Joseph Buford Pennybacker to British neurosurgery and the modern management of cerebral abscesses. Pennybacker's inspirational journey began with him aspiring to follow in the footsteps of the pioneering surgeon, Ephraim McDowell. It saw him cross the Atlantic, learn medicine at Edinburgh, train in neurology at Queen Square in London, and study neurosurgery under Sir Hugh Cairns in Oxford. Pennybacker navigated a successful career through World War II and together with Cairns established the Radcliffe Infirmary in Oxford as a highly esteemed neurosurgical unit. By increasing the operative tempo yet uncompromising the meticulousness of his operative technique, Pennybacker challenged the Halstedian and Cushing traditions. The pioneering Pennybacker system of managing cerebral abscesses stood the test of time and the ethos of preoperative imaging, intervention, and postoperative monitoring-clinically, biochemically, and with imaging results-remains today. Pennybacker contributed significantly to British neurosurgery and the training of both home-grown and international neurosurgeons and he was also a remarkably kind-hearted and calm individual. These qualities inspired many of his contemporaries and junior colleagues, and we hope will continue to do so for generations to come.

H1N1 triggered recurrent acute necrotizing encephalopathy in a family with a T653I mutation in the RANBP2 gene.

A 28-month-old infant presented with fever, vomiting and encephalopathy. Magnetic resonance imaging findings and family history confirmed a diagnosis of recurrent familial acute necrotizing encephalopathy (ANE1). We believe that this is the first description implicating the H1N1 viral strain as a trigger and the second report of a T653I mutation in the RANBP2 gene described in relation to ANE1.