Publications by authors named "Josephine Jung"

15 Publications

  • Page 1 of 1

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

World Neurosurg 2021 Mar 26. Epub 2021 Mar 26.

Department of Neurosurgery, King's College Hospital Foundation Trust, London.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.03.101DOI Listing
March 2021

Neurosurgery and coronavirus: impact and challenges-lessons learnt from the first wave of a global pandemic.

Acta Neurochir (Wien) 2021 02 21;163(2):317-329. Epub 2020 Nov 21.

Department of Neurosurgery, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Introduction And Objectives: The novel severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic has had drastic effects on global healthcare with the UK amongst the countries most severely impacted. The aim of this study was to examine how COVID-19 challenged the neurosurgical delivery of care in a busy tertiary unit serving a socio-economically diverse population.

Methods: A prospective single-centre cohort study including all patients referred to the acute neurosurgical service or the subspecialty multidisciplinary teams (MDT) as well as all emergency and elective admissions during COVID-19 (18th March 2020-15th May 2020) compared to pre-COVID-19 (18th of January 2020-17th March 2020). Data on demographics, diagnosis, operation, and treatment recommendation/outcome were collected and analysed.

Results: Overall, there was a reduction in neurosurgical emergency referrals by 33.6% and operations by 55.6% during the course of COVID-19. There was a significant increase in the proportion of emergency operations performed during COVID-19 (75.2% of total, n=155) when compared to pre-COVID-19 (n = 198, 43.7% of total, p < 0.00001). In contrast to other published series, the 30-day perioperative mortality remained low (2.0%) with the majority of post-operative COVID-19-infected patients (n = 13) having underlying medical co-morbidities and/or suffering from post-operative complications.

Conclusion: The capacity to safely treat patients requiring urgent or emergency neurosurgical care was maintained at all times. Strategies adopted to enable this included proactively approaching the referrers to maintain lines of communications, incorporating modern technology to run clinics and MDTs, restructuring patient pathways/facilities, and initiating the delivery of NHS care within private sector hospitals. Through this multi-modal approach we were able to minimize service disruptions, the complications, and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00701-020-04652-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680211PMC
February 2021

Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading.

Neurosurgery 2020 12;88(1):183-192

Neurosurgical Department, King's College Hospital Foundation Trust, London, United Kingdom.

Background: Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown.

Objective: To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS).

Methods: Retrospective cohort study of patients admitted for surgery with diffuse gliomas within motor eloquent areas. Demographic, clinical, and nTMS-related variables were collected. The Cortical Excitability Score (CES 0 to 2 according to the number of abnormal interhemispheric resting motor threshold (RMT) ratios) was calculated for patients where bilateral upper and lower limb mapping was performed.

Results: A total of 45 patients were included: 9 patients had a low-grade glioma and 36 patients had a high-grade glioma. The unadjusted analysis revealed an increase in the latency of the motor evoked potential of the lower limb with an increase of the WHO grade (P = .038). The adjusted analysis confirmed this finding (P = .013) and showed a relation between the increase in the WHO and a decreased RMT (P = .037) of the motor evoked responses in the lower limb. When CES was calculated, an increase in the score was related with an increase in the WHO grade (unadjusted analysis-P = .0001; adjusted analysis-P = .001) and in isocitrate dehydrogenase (IDH) wild-type tumors (unadjusted analysis-P = .020).

Conclusion: An increase in the WHO grading system and IDH wild-type tumors are associated with an abnormal excitability of the motor eloquent areas in patients with diffuse gliomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyaa354DOI Listing
December 2020

Management evaluation of metastasis in the brain (MEMBRAIN)-a United Kingdom and Ireland prospective, multicenter observational study.

Neurooncol Pract 2020 Jun 6;7(3):344-355. Epub 2019 Dec 6.

Department of Neurosurgery, King's College Hospital, London, UK.

Background: In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making.

Methods: A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database.

Results: A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, < .001) as well as sentinel location and tumor histology ( < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases.

Conclusions: This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nop/npz063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274191PMC
June 2020

Patient-reported experience measures in patients undergoing navigated transcranial magnetic stimulation (nTMS): the introduction of nTMS-PREMs.

Acta Neurochir (Wien) 2020 07 25;162(7):1673-1681. Epub 2020 Feb 25.

Department of Neurosurgery, King's College Hospital Foundation Trust, London, UK.

Background: Patient-reported experience measures (PREMs) are a unique measure of experience of patients which can help address the quality of care of the patients.

Objective: Our aim of the study is to collect quality of care outcomes with our newly navigated transcranial magnetic stimulation patient-reported experience measure (nTMS-PREMs) questionnaire among neurosurgical patients undergoing nTMS.

Methods: A single-centre prospective nTMS-PREMs 19-item questionnaire study was performed between February 2018 and December 2018 on patient referred for nTMS at our hospital. The Data was analysed using Likert scale, linear and logistic regression using statistical software (STATA 13.0®).

Results: Fifty patient questionnaires were collected (30 males, 20 females, mean age of 47.6 ± 2.1 years) among which 74% of patients underwent both motor and language mapping with a mean duration of 103.3 ± 5.1 min. An overall positive response was noted from the results of the questionnaire, tiredness and anxiety being the common effects noted. Patients with the left-sided disease appreciated more the conditions provided in our laboratory (Q4, p = 0.040) and increasing age was related to less confidence and trust (Q6, p = 0.038) in the staff performing the exam. Younger patients tolerated nTMS better than older patients (> 65 years). PubMed literature search resulted in no relevant articles on the use of PREMs in nTMS patients.

Conclusion: nTMS is a well-tolerated non-invasive tool and nTMS-PREMS provides a promising role in identifying the unmet needs of the patients and improving the quality of their care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00701-020-04268-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295840PMC
July 2020

Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma.

Int J Mol Sci 2019 Jul 9;20(13). Epub 2019 Jul 9.

Brain Tumour Research Centre, Institute of Biological and Biomedical Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.

Glioblastoma is the most common and malignant primary brain tumour in adults, with a dismal prognosis. This is partly due to considerable inter- and intra-tumour heterogeneity. Changes in the cellular energy-producing mitochondrial respiratory chain complex (MRC) activities are a hallmark of glioblastoma relative to the normal brain, and associate with differential survival outcomes. Targeting MRC complexes with drugs can also facilitate anti-glioblastoma activity. Whether mutations in the mitochondrial DNA (mtDNA) that encode several components of the MRC contribute to these phenomena remains underexplored. We identified a germ-line mtDNA mutation (m. 14798T > C), enriched in glioblastoma relative to healthy controls, that causes an amino acid substitution F18L within the core mtDNA-encoded cytochrome b subunit of MRC complex III. F18L is predicted to alter corresponding complex III activity, and sensitivity to complex III-targeting drugs. This could in turn alter reactive oxygen species (ROS) production, cell behaviour and, consequently, patient outcomes. Here we show that, despite a heterogeneous mitochondrial background in adult glioblastoma patient biopsy-derived cell cultures, the F18L substitution associates with alterations in individual MRC complex activities, in particular a 75% increase in MRC complex II_III activity, and a 34% reduction in CoQ10, the natural substrate for MRC complex III, levels. Downstream characterisation of an F18L-carrier revealed an 87% increase in intra-cellular ROS, an altered cellular distribution of mitochondrial-specific ROS, and a 64% increased sensitivity to clomipramine, a repurposed MRC complex III-targeting drug. In patients, F18L-carriers that received the current standard of care treatment had a poorer prognosis than non-carriers (373 days vs. 415 days, respectively). Single germ-line mitochondrial mutations could predispose individuals to differential prognoses, and sensitivity to mitochondrial targeted drugs. Thus, F18L, which is present in blood could serve as a useful non-invasive biomarker for the stratification of patients into prognostically relevant groups, one of which requires a lower dose of clomipramine to achieve clinical effect, thus minimising side-effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20133364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651022PMC
July 2019

Symptomatic Idiopathic Spinal Epidural Lipomatosis in 9 Patients: Clinical, Radiologic, and Pathogenetic Features.

World Neurosurg 2019 Jun 29;126:e33-e40. Epub 2019 Jan 29.

The Atkinson Morley Neurosurgical Department, St. George's Hospital, Tooting, England.

Background: Symptomatic spinal epidural lipomatosis (SSEL) is characterized by hypertrophy of adipose tissue within the spinal canal and consequent neural compromise. The exact pathogenesis remains enigmatic. The authors describe a retrospective case series, define the full clinical spectrum, and discuss possible pathogenetic mechanisms.

Methods: The medical notes and imaging of 9 patients with SSEL undergoing surgery from 2008-2018 were analyzed. Seven patients presented secondary to lumbosacral spinal epidural lipomatosis (SEL); 3 patients with chronic incomplete cauda equina syndrome (CES), 3 patients with acute CES (including a 25-week gravid patient and a 40-year-old patient with intravenous leiomyomatosis, both of whom had mild SEL) and 1 patient with chronic lumbar radiculopathy. In addition, 2 patients presented with progressive myelopathy secondary to thoracic SEL.

Results: Patients presenting with acute CES had a mean age of 37 years (range 23-49 years) and mean extradural fat (EF)-to-spinal canal (SC) ratio of 47% (range 41%-58%), in comparison with patients with chronic CES; mean age 61 years (range 58-65 years) and EF:SC ratio 72% (range 65%-80%). Patients underwent laminectomy and resection of EF at compressive levels. All patients with CES experienced complete resolution of symptoms at follow-up (range 1-48 months).

Conclusions: The clinician should be astute to the radiologic features of SEL, particularly in patients presenting with CES in the absence of acute disk herniation. The outcome of patients with CES and SEL after surgery is excellent regardless of symptom duration. Venous impedance related to increased body mass index and EF deposition may play the predominant role in addition to mechanical compression in the pathogenesis of SSEL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.01.098DOI Listing
June 2019

First United Kingdom Experience of Navigated Transcranial Magnetic Stimulation in Preoperative Mapping of Brain Tumors.

World Neurosurg 2019 Feb 23;122:e1578-e1587. Epub 2018 Nov 23.

Department of Neurosurgery, King's College Hospital, London, United Kingdom.

Background: Surgery for lesions in eloquent brain areas remains challenging owing to the risk of permanent neurological deficits. To date, direct electrical stimulation (DES) and intraoperative neuromonitoring represent the reference standard. Recently, navigated transcranial magnetic stimulation (nTMS) has emerged as a mapping tool to optimize surgical planning. Our aim was to correlate nTMS with the intraoperative findings and assess its effects on surgical decision-making.

Methods: We retrospectively reviewed our series of patients who had undergone craniotomy for removal of a brain tumor at our institution with preoperative nTMS, intraoperative neuromonitoring, and DES from February 2017 to February 2018. Demographic data, tumor entity and location, extent of resection, change in surgical approach, and neurological outcome were collected.

Results: Of 35 patients, 24 (68.6%) had undergone preoperative motor mapping and 11 (31.4%) had undergone mapping for language. Histopathological examination demonstrated glioma in 88.6% (high grade, n = 24; low grade, n = 6), metastasis (n = 2), epidermoid cyst (n = 1), and cavernoma (n = 1). nTMS resulted in change in the surgical strategy in 31.5% (craniotomy size, n = 7; access pathway, n = 3; surgical indication, n = 1). The specificity of nTMS for language was 66.7%, with a negative predictive value of 74.1%. nTMS motor mapping correlated with DES in all cases, with a mean abductor pollicis brevis hotspot distance of 3.50 ± 0.66 mm (n = 9).

Conclusions: nTMS is a safe, noninvasive adjunctive tool for preoperative mapping of brain tumors in eloquent areas. Furthermore, nTMS can influence the surgical decisions in up to one third of patients in our experience.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2018.11.114DOI Listing
February 2019

Navigated Transcranial Magnetic Stimulation in Patient with Cranioplasty in Situ: Safe and Accurate Procedure.

World Neurosurg 2019 Feb 6;122:176-179. Epub 2018 Oct 6.

Department of Neurosurgery, King's College Hospital, London, United Kingdom.

Background: Navigated transcranial magnetic stimulation (nTMS) is a nonsurgical mapping technique used in mapping of motor and language eloquent areas within and/or surrounding brain tumors. Previous reports support this as a safe technique with minor side effects associated with minor headaches and discomfort around the stimulation area. Currently there are no published reports concerning the accuracy and safety of this procedure in patients with a titanium cranioplasty in situ.

Case Presentation: A 59-year-old lady was diagnosed with a recurrent glioma in the context of increasing seizure frequency, left-sided numbness, and weakness. She was diagnosed with a World Health Organization grade 2 oligodendroglioma 10 years before her presentation, which was initially treated with radiotherapy and then surgical resection of this lesion 5 years later. The procedure was complicated with a wound infection, treated with a craniectomy and wound washout, followed by a titanium cranioplasty. Before proceeding with surgery for recurrence, nTMS was performed for motor mapping. No complications were identified. She underwent a craniotomy for tumor resection with aminolevulinic acid HCl (Gliolan), and the tumor was completely removed. Intraoperatively, the direct cortical stimulation correlated with the preoperative nTMS. The pathologic diagnosis on recurrence was an anaplastic oligodendroglioma grade III, and the patient is currently undergoing adjuvant chemotherapy.

Conclusion: This report confirms that nTMS is a safe and accurate procedure in patients who have a titanium cranioplasty in situ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2018.09.198DOI Listing
February 2019

Refusal of Vitamin K Injection: Survey of the Current Literature and Practical Tips for Pediatricians.

Pediatr Ann 2018 Aug;47(8):e334-e338

Vitamin K refusal and associated sequelae of vitamin K deficiency bleed (VKDB) in the newborn period is becoming a more common occurrence. We present six recent cases from a 4-month period in 2017 of parent refusal of vitamin K and describe the reasons for refusal and the clinical outcomes of these infants. There have been a number of case reports citing the rising incidence of VKDB and the reasons why parents refuse. However, there is a gap in the literature and clinical practice guidelines describing how a physician should approach a refusal in the hospital and in the office, and the need to report a refusal to child welfare. In addition, we describe a scenario in which the caregivers provide a religious reason for refusal of vitamin K that, to the best of our knowledge, has yet to be cited in the literature. [Pediatr Ann. 2018;47(8):e334-e338.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3928/19382359-20180709-02DOI Listing
August 2018

Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and Management.

Pediatr Ann 2018 Jan;47(1):e36-e40

Lead toxicity is the result of lead ingestion, one of the most common ingestions in the pediatric population. Nationwide and statewide efforts to recognize and curtail this epidemic have led to declining rates of toxicity. In patients with sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to overlapping symptom profiles, and inconsistent follow-up with a primary care physician can make the diagnosis even more difficult. In this article, two illustrative cases of lead toxicity in patients with SCD are described. The discussion reviews the current risk factors, screening, and inpatient management of lead toxicity, as well as describing the unique and sometimes confounding presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann. 2018;47(1):e36-e40.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3928/19382359-20171218-01DOI Listing
January 2018

Conus Medullaris Arteriovenous Malformation Presenting with Acute Dysphagia and Intractable Hiccups.

World Neurosurg 2018 Mar 2;111:261-263. Epub 2018 Jan 2.

Department of Neurosurgery, King's College Hospital, London, UK; Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.

Background: Conus medullaris arteriovenous malformations (AVMs) are rare spinal vascular malformations presenting most frequently with features of myelopathy (Foix-Alajounine syndrome), radiculopathy, bowel/bladder dysfunction, or acute spinal hemorrhage (Coup de poignard of Michon) causing profound neurological deficit. Here we present the case of a young patient with progressive dysphagia and intractable hiccups as a rare first presentation symptom of later verified conus medullaris AVM.

Case Description: A 21-year-old male patient presented with acute onset of dysphagia and persistent hiccups. His magnetic resonance imaging of the spine demonstrated a lesion at the T11 and T12 levels with an associated holocord syrinx and syringobulbia to the level of the medulla. The patient underwent a decompressive suboccipital craniectomy and C1 (atlas) laminectomy with wide myelotomy of the medulla followed by T11 and T12 laminectomy and AVM reduction. Two days after partial AVM occlusion the patient developed transient worsening of his symptoms. Repeat magnetic resonance imaging showed recurrence of dilatation of the central canal. A syringo-subarachnoid shunt was sited at the level of the previous myelotomy of the medulla, after which his neurological symptoms resolved completely.

Conclusions: This is the first case report in the English literature to date of a conus AVM presenting with intractable hiccups. These are extremely rare sporadic vascular malformations, and although their natural history is poorly understood, symptomatic patients generally deteriorate, culminating in severe disability. Management requires a multimodality approach including combined endovascular and microsurgical treatment. The patient in our case made a full recovery confirmed at 2-year follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2017.12.144DOI Listing
March 2018

How does the publication fate of abstracts presented at the Society of British Neurological Surgeons meetings differ five years on?

Br J Neurosurg 2017 06 7;31(3):291-292. Epub 2017 May 7.

b Department of Neurosurgery , King's College London , London , UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02688697.2017.1319462DOI Listing
June 2017