Publications by authors named "Gordan Grahovac"

41 Publications

Patient-Reported Bladder, Bowel, and Sexual Function After Cauda Equina Syndrome Secondary to a Herniated Lumbar Intervertebral Disc.

Top Spinal Cord Inj Rehabil 2020 20;26(4):290-303. Epub 2021 Jan 20.

Department of Neurosurgery, Kings College London, London.

Background: Cauda equina syndrome (CES) is rare neurosurgical emergency requiring emergent surgical decompression to prevent bladder, bowel, and sexual dysfunction that can have significant impact on quality of life. There is a paucity of data relating to the prevalence of these long-term complications.

Objective: The aim of this observational study was to evaluate the long-term prevalence of CES-related bladder, bowel, and sexual dysfunction and impact on quality of life to inform service provision.

Methods: Participants were selected through coding of operative records of patients who underwent lumbar decompression for CES secondary to a herniated intervertebral disc at two large UK neurosurgical departments between 2011 and 2015 inclusive. A telephone-based survey including both validated and modified tools was used to collect data pertaining to bladder, bowel, and sexual function and impact on quality of life both before development of CES and at the time of the survey, at least 1 year postoperatively.

Results: Of 135 patients contacted, 71 (42 male, 29 female) responded. Post-CES compared to pre-CES, there was higher prevalence and significant intrarespondent deterioration of bowel dysfunction, bladder dysfunction, perception of bladder function, sexual function, effect of back pain on sex life, and activities of daily living/quality of life ( < .0001 for all). Significant differences in individual questions pre-CES versus post-CES were also found.

Conclusion: We show high prevalence of long-term bowel, bladder, and sexual dysfunction post-CES, with functional and psychosocial consequences. Our results demonstrate the need for preoperative information and subsequent screening and long-term multidisciplinary support for these complications.
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http://dx.doi.org/10.46292/sci19-00065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831285PMC
March 2021

Risk Factor Analysis and Surgical Outcomes of Acute Spontaneous Spinal Subdural Hematoma. An Institutional Experience of Four Cases and Literature Review.

World Neurosurg 2021 Feb 24;146:e384-e397. Epub 2020 Oct 24.

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

Objective: Spontaneous spinal subdural hematoma (SSSDH) is exceedingly rare, with significant morbidity in most patients. Acute neurologic deficit in the context of a SSSDH is considered a neurosurgical emergency. We performed a literature review and compared the results with our institutional experience to evaluate the risk factors and neurologic outcomes of SSSDH.

Methods: We retrospectively collected the medical, radiologic, and surgical information of 4 patients with SSSDH who were operated on in our neurosurgical unit. A literature review of surgically managed patients with SSSDH and their neurologic outcomes was performed. Ordered logistic regression statistics were used to study the risk factors influencing the postoperative Domenicucci grade.

Results: A total of 112 patients were evaluated, with a female/male ratio of 1.3:1. Mean patient age was 60.25 years. Our analysis of the data showed that the cohort of patients presenting with bladder dysfunction in addition to paraparesis were found to have worse neurologic outcomes postoperatively. Adjusted analysis identified 3 clinical characteristics that influenced surgical outcome: cervical SSSDH (P = 0.029), neurologic deficit (P < 0.001), and anticoagulation medication (P < 0.001).

Conclusions: This review shows that patients aged ≥60 years and on anticoagulation are at an increased risk of sustaining a spontaneous subdural spinal hematoma without history of trauma. To our knowledge, this is also the first study to show a presenting symptom of bladder dysfunction as a significant risk factor for poor surgical outcome in SSSDH. Our study supports surgical evacuation of acute SSSDH in the presence of these risk factors.
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http://dx.doi.org/10.1016/j.wneu.2020.10.096DOI Listing
February 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.
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http://dx.doi.org/10.1007/s00701-020-04652-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680211PMC
February 2021

Inter-dural spinal cyst with acute thoracic compressive myelopathy: anatomical aspects of spinal dura, case report and literature review.

Br J Neurosurg 2020 Oct 14:1-5. Epub 2020 Oct 14.

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

Introduction: Inter-dural juxta-facet spinal cysts occur rarely. They form as part of the degenerative spinal disease process and can be misdiagnosed as synovial cysts or ganglion cysts. We report the case of a thoracic inter-dural juxta-facet spinal cyst causing acute compressive thoracic myelopathy.

Methods: The data was collected retrospectively from patient records. The literature review was performed in PubMed.

Results: We report a case of symptomatic inter-dural juxta-facet thoracic spinal cyst. The literature review showed a variety of different spinal cysts including arachnoid cyst, discal cyst, ganglion cyst, epidermoid cyst and synovial cysts. Micro-instability and repeated microtrauma associated with degenerative changes are most likely contributors to its formation. Asymptomatic cysts can show spontaneous resolution. When symptomatic, they can be managed with surgical excision with good patient outcome.

Conclusion: Inter-dural spinal cysts can be diagnosed and surgically excised to produce excellent post-operative outcome. High pre-operative index of suspicion of this diagnosis together with good understanding of the intraoperative anatomy are essential to avoid inadvertent dural breach.
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http://dx.doi.org/10.1080/02688697.2020.1834507DOI Listing
October 2020

Reducing neurosurgical theatre start time delays by seventy minutes through application of the 'Golden Patient' initiative.

Br J Neurosurg 2020 Oct 8:1-8. Epub 2020 Oct 8.

King's College Hospital, London, UK.

Background: This project's focus was on improving neurosurgical theatre efficiency through the application of Javed et al's Golden Patient initiative to the emergency theatre setting. This initiative has not previously been used in neurosurgery, so we have had to consider how to adapt it. Phase I's primary objective was to quantify theatre start time delays. Phase II assessed whether introducing the initiative reduced the delays.

Methodology: We performed an observational retrospective service evaluation project. Data was collected on weekday theatre start times over 12-week periods pre- and post-initiative. We quantified the delay in theatre start times and recorded the reasons for delays. Following the initiative's introduction, we repeated the evaluation process. Mean and median theatre start times were compared. An ANOVA test was used to confirm statistical significance.

Results: Data was collected on 49 days and on 48 days over 12-week periods in both Phase I and II respectively. Phase I of this project identified that there was on average an 86.7 minute delay in starting the theatre each day. The theatre start time was delayed in 91.7% of cases. A 72.3 minute reduction in the theatre start time delay was noted following the initiative's introduction ( < .0005), with an improvement in the average emergency theatre start time from 09:56 to 08:44 (08:30 is the recognised theatre start time). We have identified hospital-wide and doctor-related contributing factors which require further attention, most notably, relating to issues around transferring patients from the ward to theatre.

Conclusions: We have identified a statistically significant improvement in reducing theatre start time delays following the introduction of the initiative. This relatively simple intervention improved communication amongst the multidisciplinary team and led to a notable improvement in the service provided to patients by reducing start time delays. Through tackling identified areas, we hope to further reduce theatre start time delays leading not only to financial savings but also to further improvements in the quality of care provided to our neurosurgical patients.
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http://dx.doi.org/10.1080/02688697.2020.1822513DOI Listing
October 2020

Conservative Management of Type II Odontoid Fractures in Older People: A Retrospective Observational Comparison of Osseous Union Versus Nonunion.

Neurosurgery 2020 Jun 22. Epub 2020 Jun 22.

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

Background: Type II odontoid fractures are a common cervical fracture in older people. Lower osseous-union rates are reported in those treated conservatively compared to surgically; however, the clinical relevance of a nonunion is unknown.

Objective: To compare pain, disability, and quality of life in older people following conservative management of type II odontoid fractures demonstrating osseous-union and nonunion.

Methods: Electronic records were searched from 2008 to 2018 for adults ≥65 yr with type II odontoid fracture, managed in a semi-rigid collar. Clinical and demographic data were retrieved from electronic patient notes. Surviving patients were invited to complete questionnaires to assess pain, disability, and quality of life. Ethical approval was granted.

Results: A total of 125 patients were identified: 36 (29%) demonstrated osseous-union, 89 (71%) had nonunion, of which 33 (40%) had radiological instability. Mean age at fracture was 84 yr (osseous-union 83 yr; nonunion 84 yr). A total of 53 had deceased (41 nonunion). Median length of survival was 77 mo for osseous-union vs 50 mo for nonunion; P = .02. No patient developed myelopathy during the follow-up period. Questionnaire response rate was 39 (58%). There were no statistically significant differences between the groups in terms of pain, disability, or quality of life (P > .05). Both groups reported mild disability and pain but low quality of life.

Conclusion: Management with a semi-rigid collar in older people with type II odontoid fracture is associated with low levels of pain and disability without statistically significant differences between those demonstrating osseous-union or stable or unstable nonunions. Conservative management appears to be a safe treatment for older people with type II fractures.
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http://dx.doi.org/10.1093/neuros/nyaa256DOI Listing
June 2020

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

World Neurosurg 2020 09 1;141:20-24. Epub 2020 Jun 1.

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

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.
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http://dx.doi.org/10.1016/j.wneu.2020.05.190DOI Listing
September 2020

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

Posterior longitudinal ligament and its implications in intradural cervical disc herniation: Case report and review of the literature.

Surg Neurol Int 2018 18;9:119. Epub 2018 Jun 18.

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

Background: Intradural disc herniations (IDH) are rare, particularly in the cervical spine, where they account for less than 5% of all discs. Adhesions between the ossified/calcified posterior longitudinal ligament (OPLL), dura, and ossified/calcified disc herniations increase the complexity of resecting these cervical lesions.

Case Description: A 42-year-old male presented with a rapidly progressive cervical myelopathy over a 2-month period. This was attributed to an ossified/calcified intradural cervical disc herniation in conjunction with OPLL. The anterior cervical discectomy and fusion (ACDF) resulted in a dural defect but there was no cerebrospinal fluid (CSF) fistula as the arachnoid membrane remained intact. Had there been a CSF leak, it would have warranted both wound-peritoneal (WP) and lumbo-peritoneal shunts (LP). The surgeons should have anticipated that a CSF leak would likely occur prior to performing the ACDF, and should have prophylactically prepared and draped the abdomen for a potential WP, followed by a LP shunt. Three months postoperatively, the patient's proprioceptive deficit improved, and he almost completely recovered motor function.

Conclusion: Performing an ACDF for resection of an intradural calcified/ossified disc with OPLL often results in both a dural defect and CSF fistula. As the arachnoid membrane rarely remains intact, the spine surgeon should be prepared to immediately perform both a WP shunt, and subsequently, an LP. In this case, following an ACDF, resection of an intradural ossified disc with OPLL resulted in an isolated dural defect without a CSF fistula and did not require no dural repair or shunting procedures.
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http://dx.doi.org/10.4103/sni.sni_29_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024507PMC
June 2018

Chiari type I malformation of infants and toddlers.

Childs Nerv Syst 2018 06 2;34(6):1169-1176. Epub 2018 Feb 2.

Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E. Chicago Avenue, Chicago, IL, 60611, USA.

Objectives: Chiari I malformation has been a well-recognized clinical entity; however, its occurrence among infants and toddlers is unusual. Their clinical presentations may be different from other age groups due to their lack of effective verbal communication. The authors analyze their personal series of patients focusing on symptomatology and MRI characteristics. Treatment methods, results, and outcome are analyzed in order to identify appropriate surgical management among infants and toddlers with Chiari I malformation.

Methods: The authors retrospectively reviewed 16 patients who were diagnosed and surgically treated between 2007 and 2014 during the first 3 years of life with minimum follow-up of 3 years. We focused on the presenting symptoms, magnetic resonance imaging findings, and surgical techniques used for posterior fossa decompression (PFD) and their postoperative outcome.

Results: Twelve patients (75%) presented with signs of headaches such as irritability, inconsolable crying, head grabbing, and/or arching back. Ten patients (62.5%) presented with oropharyngeal and/or respiratory symptoms such as emesis, choking, gagging, snoring, sleep apnea, breathing pause, and/or vocal cord palsy. Only one patient had segmental cervical hydromyelia. At the first surgery, ten patients had PFD with dural scoring (Type 1 procedure), while six others had PFD with duraplasty (Type 2 procedure) with thermal reduction of the cerebellar tonsils in four. Following the first operation, all initially had varying degrees of symptomatic improvement; however, seven patients subsequently had symptomatic recurrence. Persistent crowding at the PFD site on the postoperative imaging indicated greater risk of recurrences in both Type 1 procedure and Type 2 procedure groups. Of seven patients who needed a second operation, fivewere after Type 1 procedure and the two were after Type 2 procedure. The difference of recurrence rates between these two groups is not significant. CSF-related complications occurred in 4 out of 11 patients who had Type 2 procedure (one after primary decompression and three after the second decompression for recurrence).

Conclusion: Young patients lacking effective verbal communication often present their Chiari I malformation differently from olderage groups. Behavioral changes indicative of headaches/irritability and oropharyngeal/respiratory symptoms are the primary presenting symptoms. The recurrence rate tends to be higher among the patients after Type 1 procedure (particularly those younger than 18 months) than after Type 2 procedure. We observed that duraplasty at primary or at redo PFD provides for better decompression and long-term outcome. However, one should keep it in mind that there is risk of CSF-related complications following duraplasty, particularly higher tendency after redo PFD.
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http://dx.doi.org/10.1007/s00381-017-3712-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978832PMC
June 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.
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http://dx.doi.org/10.1016/j.wneu.2017.12.144DOI Listing
March 2018

Spontaneous cervical intradural disc herniation presenting with Brown-Séquard and Horner's syndrome: lesson learned from a very unique case.

Eur Spine J 2017 05 25;26(Suppl 1):218-221. Epub 2017 Mar 25.

Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust, Queen Square, London, WC1N 3BG, UK.

Purpose: Cervical spontaneous intradural disc herniation (IDH) is an extremely rare condition. We describe a unique case of a patient presenting with a Brown-Séquard syndrome (BSS) and Horner's syndrome (HS). This study aimed to report an unusual case of spontaneous cervical intradural disc herniation that presented with Horner's and Brown-Séquard syndrome (BSS) and discuss difficulties in preoperative diagnosis and treatment difficulties of intradural cervical disc.

Methods: Notes and images review, and analysis of the relevant literature.

Results: A 45-year old female presented with acute Horner's syndrome and Brown-Séquard syndrome. The magnetic resonance imaging of cervical spine revealed C4-5 disc extrusion with cord compression. The patient underwent urgent decompression through an anterior cervical corpectomy and fusion. Patient fully recovered 6 months after disease onset.

Conclusion: We would like to emphasize that prompt and anterior cervical decompression is the treatment of choice, as it directly address the problem and allows dura repair in spontaneous cervical disc herniation.
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http://dx.doi.org/10.1007/s00586-017-5044-4DOI Listing
May 2017

Mixed pineal mature teratoma and germinoma in two brothers of the fraternal triplets.

Childs Nerv Syst 2017 May 24;33(5):859-863. Epub 2017 Feb 24.

Department of Pathology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 60611, USA.

Introduction: Intracranial teratomas are rare germ cell neoplasms that contain tissues derived from all three germ cell layers and most commonly occurring during childhood. This is the first report of pineal region mixed mature teratoma and germinoma in two fraternal brothers of fraternal triplets.

Case Presentation: We report the case of a mixed mature teratoma and germinoma of the pineal region in two brothers of fraternal triplets. Older brother was initially diagnosed at the age of 11 years with the pure teratoma of the pineal region but the review of the pathology 3 years after initial surgery revealed the mixed mature teratoma with 5% germinomatous component. The younger brother was diagnosed at the age of 13 years with the mixed mature teratoma with 10% germinomatous component tumor of the pineal region. Younger brother has been treated with adjuvant chemo-radiotherapy and older brother was treated without adjuvant therapy. Both brothers had no recurrence.

Conclusion: Pineal mature teratomas have a good prognosis, in contrast to their immature or mixed counterparts. A rigorous histological examination of the tumor samples is mandatory, in order to not omit a mixed contingent within the tumor.
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http://dx.doi.org/10.1007/s00381-017-3349-6DOI Listing
May 2017

Targeting CD133 improves chemotherapeutic efficacy of recurrent pediatric pilocytic astrocytoma following prolonged chemotherapy.

Mol Cancer 2017 01 31;16(1):21. Epub 2017 Jan 31.

Falk Brain Tumor Center, Division of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, 225 E Chicago Ave, PO Box #28, Chicago, IL, 60611, USA.

Background: Pilocytic astrocytomas (PAs) are the most common pediatric central nervous system neoplasms. In the majority of cases these tumors are benign and receive favorable prognosis following gross total surgical resection. In patients with progressive or symptomatic tumors, aggressive surgical resection is generally not feasible, thus radiation or chemotherapy are accepted initial or adjuvant interventions. Due to serious long-lasting side-effects, radiation is limited in young children; therefore, chemotherapy is widely practiced as an adjuvant treatment for these patients. However, chemotherapy can promote the emergence of multidrug resistant tumor cells that are more malignant than those of the original tumor. CD133, a putative stem cell marker in normal tissue and malignant brain tumors, enhances multidrug resistant gene 1 (MDR1) expression following chemotherapy in adult malignant glioblastomas. This study examines the relationship between CD133 and MDR1 in pediatric PAs exposed to chemotherapy, with the goal of identifying therapeutic targets that manifest as a result of chemotherapy.

Methods: Slides were obtained for 15 recurrent PAs, seven of which had received chemotherapy prior to surgical treatment for the recurrent tumor. These samples, as well as primary tumor tissue slides from the same patients were used to investigate CD133 and MDR1 expression via immunofluorescence. Archived frozen tissue samples from the same patients were used to examine CD133, MDR1 and PI3K-Akt-NF-κB signaling mediators, via western blot. Two drug resistant pediatric PA cell lines Res186 and Res199 were also used to evaluate the role of CD133 on cell response to cytotoxic therapy.

Results: CD133 and MDR1 were co-expressed and their expression was elevated in recurrent PAs from patients that had received chemotherapy, compared to patients that had not received chemotherapy. PI3K-Akt-NF-κB signaling mediator expression was also elevated in recurrent, chemotherapy-treated PA. Suppressing CD133 expression with siCD133 decreased levels of PI3K-Akt-NF-κB signaling mediators and MDR1, while increasing cell chemosensitivity, as indicated by quantification of apoptotic cells following chemotherapy.

Conclusions: CD133 contributes to multidrug resistance by regulating MDR1 levels via the PI3K-Akt-NF-κB signal pathway not only in adult glioblastomas, but also in pediatric PAs. Targeting CD133, adjuvant to conventional chemotherapy may improve outcomes for children with recurrent PA.
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http://dx.doi.org/10.1186/s12943-017-0593-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282778PMC
January 2017

Effect of an Annular Closure Device (Barricaid) on Same-Level Recurrent Disk Herniation and Disk Height Loss After Primary Lumbar Discectomy: Two-year Results of a Multicenter Prospective Cohort Study.

Clin Spine Surg 2016 12;29(10):454-460

*Department of Neurosurgery, Vanderbilt University School of Medicine, Nashville, TN †Department of Neurosurgery, University Hospital Dubrava, Zagreb ‡Localitet Susak Neurosurgery, Rijeka, Croatia §Department of Orthopedics, Stanford University, Stanford, CA.

Study Design: A prospective cohort study.

Objective: To evaluate whether an annular closure device could be implanted safely to reduce same-level recurrent disk herniation, or attenuate disk height loss and improve the outcome after lumbar discectomy.

Summary Of Background Data: Same-level recurrent disk herniation, disk height loss, and progressive degeneration are common complications and sequelae after lumbar discectomy. Techniques to reduce these consequences may improve outcomes.

Methods: Forty-six consecutive patients undergoing lumbar discectomy for single-level herniated disk at 2 institutions were followed prospectively with clinical and radiographic evaluations at 6 weeks and 3, 6, 12, and 24 months (control cohort). A second consecutive cohort of 30 patients undergoing 31 lumbar discectomies with implantation of an annular closure device was followed similarly. Incidence of recurrent disk herniation, disk height loss, the leg and back pain visual analog scale (VAS), and the Oswestry Disability Index were assessed at each follow-up.

Results: Cohorts were well matched at baseline. By 2 years of follow-up, symptomatic recurrent same-level disk herniation occurred in 3 (6.5%) patients in the control cohort versus 0 (0%) patients in the annular repair cohort (P=0.27). A trend of greater preservation of disk height was observed in the annular repair versus the control cohort 3 months (7.9 vs. 7.27 mm, P=0.08), 6 months (7.81 vs. 7.18 mm, P=0.09), and 12 months (7.63 vs. 6.9 mm, P=0.06) postoperatively. The annular closure cohort reported less leg pain (VAS-LP: 5 vs. 16, P<0.01), back pain (VAS-BP: 13 vs. 22, P<0.05), and disability (Oswestry Disability Index: 16 vs. 22, P<0.05) 1 year postoperatively.

Conclusions: Implantation of a novel annular repair device was associated with greater maintenance of disk height and improved 1-year leg pain, back pain, and low-back disability. Recurrent disk herniation did not occur in any patient after annular repair. Closure of annular defect after lumbar discectomy may help preserve the physiological disk function and prevent long-term disk height loss and associated back and leg pain.
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http://dx.doi.org/10.1097/BSD.0b013e3182956ec5DOI Listing
December 2016

Cerebellopontine angle tumors in infants and children.

Childs Nerv Syst 2015 Oct 9;31(10):1739-50. Epub 2015 Sep 9.

Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Chicago, IL, 60611, USA.

Objective: Cerebellopontine angle (CPA) and cerebellomedullary fissure (CMF) tumors are rare in children and information is scarce in the literature. This retrospective study reports their histological distribution and tumor origin, and describes surgical resections and post-operative outcome based upon the authors' consecutive personal series.

Methods: Clinical data of infants and children 16 years old or younger of age treated from 2001 to 2012 by a single surgeon was retrospectively reviewed. All had histologically verified CPA/CMF tumors and underwent radical tumor resection through craniotomy except for two children who had a stereotactic biopsy for malignant tumors (glioblastoma and primitive neuroectodermal tumor (PNET)). Tumors' pathological distributions, tumors' origin, surgical approaches, and patients' outcome were reviewed.

Results: There were 44 infants and children with the age at diagnosis ranging from 11 weeks to 16 years; 32 were predominantly in the CPA and/or CMF whereas 12 showed an extension to the fourth ventricle. Pathology showed 14 ependymomas, 12 benign gliomas (11 pilocytic astrocytomas, 1 ganglioglioma), 4 atypical teratoid rhabdoid tumors (ATRTs), 4 epidermoids, 3 primitive neuroectodermal tumors (PNETs), 3 meningiomas, 3 nerve sheath tumors, and 1 glioblastoma. The anatomical site of tumor origin was the lateral recess of the fourth ventricle in 13 patients, the ventral cerebellar hemisphere in 8, the cerebellar peduncle in 7, and the brain stem in 6. Others were from embryonal nest, cranial nerve, or meninges. For 42 tumor resections, 38 were approached through a posterior fossa craniotomy and 4 through a temporal craniotomy and transtentorial approach. At tumor resection, 26 had a gross total or near total resection, 12 subtotal resection, and 4 partial resection. There were no mortalities. The most significant morbidity was ninth and tenth nerve palsy; 15 patients had unilateral vocal cord palsy or dysphagia. Of these, nine were treated with nasogastric (NG) feeding tube, five with a combination of gastrostomy (G-tube) and tracheotomy, and one with G-tube. All had successful removal of NG feeding from 1 month to 2 years (average 6 months). The tracheostomy and G-tube were removed between 4 months and 2 years (average 14 months) in all.

Conclusion: A plethora of tumor types occur in childhood at the CPA/CMF and our review indicated 50 % were benign in histology. High rates of lower cranial nerve morbidity were experienced but their dysfunctions were often recovered or compensated in 2 years. However, one should be cognizant of these complications and conduct resection with appropriate surgical approach, intraoperative monitoring, and surgical microscope.
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http://dx.doi.org/10.1007/s00381-015-2747-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564453PMC
October 2015

Atypical teratoid rhabdoid tumors of the posterior fossa in children.

Childs Nerv Syst 2015 Oct 9;31(10):1717-28. Epub 2015 Sep 9.

Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

Purpose: Atypical teratoid rhabdoid tumors (AT/RT) are rare, aggressive, central nervous system neoplasms that typically affect children under 3 years of age and have a very poor prognosis. Early case series consistently demonstrated rapid recurrence with progression to death, but more recent experience has shown significant improvements in progression free and overall survival.

Methods: A retrospective analysis of the clinical data of children diagnosed with AT/RT at the Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital) between 2000 and 2014 was performed. Overall survival (OS) was used to describe outcome. Our small sample size and the utilization of different adjuvant regimens over the study period precluded a detailed statistical analysis.

Results: Eight children with AT/RT of the posterior fossa were included in our report. Gross total resection (GTR) was achieved in five children (63 %), two children underwent subtotal resection (25 %), and there was one who underwent biopsy. Patients were treated with various combinations of chemotherapy with or without conformal radiation therapy (RT). Median overall survival was 5 months (range 1 to 107 months) with two patients achieving sustained responses to 45 and 107 months.

Conclusions: Our experience is in line with prior reports that show that children diagnosed with AT/RT of the posterior fossa have a poor prognosis, but that long-term survival is possible. These tumors provide many challenges, but contemporary series are beginning to show improvements in survival.
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http://dx.doi.org/10.1007/s00381-015-2844-xDOI Listing
October 2015

Solid hemangioblastoma of vestibular nerve mimicking vestibular schwannoma.

Authors:
Gordan Grahovac

Neurol Sci 2015 Aug 22;36(8):1537-9. Epub 2015 Apr 22.

Department of Neurosurgery, Clinical Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia,

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http://dx.doi.org/10.1007/s10072-015-2216-zDOI Listing
August 2015

Effect of anular closure on disk height maintenance and reoperated recurrent herniation following lumbar diskectomy: two-year data.

J Neurol Surg A Cent Eur Neurosurg 2015 May 14;76(3):211-8. Epub 2015 Jan 14.

Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.

Objective: To assess the potential benefits of disk reherniation reduction and disk height maintenance in limited diskectomy combined with the implantation of the anular closure device.

Summary And Background Data: Postoperative disk height loss is apparent in most patients undergoing lumbar diskectomy for herniated nucleus pulposus. Less favorable patient outcomes are associated with significant loss in disk height that can occur after aggressive disk tissue removal. More conservative disk removals, however, are often burdened by the increased risk of recurrent disk herniation.

Methods: Two prospective single-arm studies on patients treated with limited diskectomy and an anular closure device were conducted. Outcome measures included disk height maintenance relative to preoperative values, Oswestry Disability Index, back pain, leg pain, and complications such as reherniations. Patients were evaluated preoperatively and postoperatively at 6 weeks and at 3-, 6-, 12-, and 24-month time points.

Results: A total of 75 patients were included in this cohort consisting of 40 men and 35 women with an average age of 40 years. Disk height maintenance within the group overall was 90% at 24 months. Overall, 97% of the treated disks demonstrated disk height maintenance of at least 75% of preoperative levels at 12 months and 92% at 24 months. Disk height maintenance was correlated with less nucleus removal. Patient disability, back pain, and leg pain were significantly improved from preoperative levels at 6 weeks and maintained over the course of study. There was a single symptomatic reherniation requiring surgical intervention within this series.

Conclusions: Limited lumbar diskectomy combined with the use of an anular closure device provided very low rates of disk reherniation and exhibited excellent disk height maintenance and sustained disability, leg pain, and back pain improvement within a 24-month postoperative study period. As with prior diskectomy studies, disk height maintenance was correlated with lower nucleus removal, although recurrence was less than in prior reports of limited diskectomy. Anular closure may allow for achievement of both objectives.
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http://dx.doi.org/10.1055/s-0034-1393930DOI Listing
May 2015

Should MS be treated by escalation or induction therapy?

Coll Antropol 2014 Mar;38(1):385-93

MS is a chronic, increasingly disabling disease whose long-term outcomes determine the key social, medical and economic impact of this disease. Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are prescribed to delay disease progression and to protect a patient's functional capability. The concepts of escalation and induction immunotherapy in MS represent different therapeutic strategies for the treatment of MS. Both strategies may be valuable options for patients starting on DMT, however, induction therapy mainly focuses on patients with very aggressive course of MS from the onset. Using a patient unique approach to selection of treatment, MS can be effectively control disease and may delay or even prevent the development of secondary progressive MS.
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March 2014

Tongue somatosensory-evoked potentials in microvascular decompression treated trigeminal neuralgia.

Acta Neurol Belg 2014 Mar 26;114(1):55-8. Epub 2013 Nov 26.

Department of Neurology, Referral Center for Demyelinating Diseases of the Central Nervous System, Zagreb School of Medicine and University Hospital Center, Kišpatićeva 12, 10000, Zagreb, Croatia.

Somatosensory-evoked potentials of the tongue (tSSEP) provide useful information about trigeminal-afferent pathway. The aim of this study was to evaluate tSSEP in trigeminal neuralgia (TN) treatment with microvascular decompression. Two patients with trigeminal neuralgia refractory to conservative treatment underwent microvascular decompression of the trigeminal nerve. tSSEP was performed a month prior to surgery and in the month after the surgery in both patients. Pain frequency and tSSEP were analyzed before and after surgery. In both patients, a complete resolution of pain occurred. In patient 1, tSSEP latencies became shorter than before surgery and wave N1 appeared. The intensity of stimulation necessary to reach the threshold was 4 mA before the surgery and 1 mA after the surgery. A complete recovery of tSSEP after the operation was achieved in patient 2. The results of present study demonstrate potential value of tSSEP in pre-surgery evaluation and post-surgery follow-up of TN patients.
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http://dx.doi.org/10.1007/s13760-013-0260-0DOI Listing
March 2014

Clinical outcomes in patients after lumbar disk surgery with annular reinforcement device: two-year follow up.

Acta Clin Croat 2013 Mar;52(1):87-91

Department of Neurosurgery, Rijeka University Hospital Center, Rijeka, Croatia.

Annular Reinforcement Device represents a modification of operative treatment of intervertebral disk herniation. It is a prosthesis that is anchored into the body of the vertebra. The intradiscal part of the implant is placed in the inner part of the annulus fibrosus defect. The aim of this technique is to reduce the incidence of reherniation and the degree of intervertebral space collapse, which is the most frequent adverse effect of diskectomy. Clinical outcomes of the treatment group indicated a statistically significant improvement with respect to the control group. Furthermore, over the period of two years, no cases of symptomatic reherniation were recorded. Considering that no serious complications occurred during the procedures, it would appear that this is an implant that, given its encouraging results, should be further verified in carefully designed future studies.
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March 2013

Cost savings associated with prevention of recurrent lumbar disc herniation with a novel annular closure device: a multicenter prospective cohort study.

J Neurol Surg A Cent Eur Neurosurg 2013 Sep 13;74(5):285-9. Epub 2013 May 13.

Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA.

Objective: Same-level recurrent disc herniation is a well-defined complication following lumbar discectomy. Reherniation results in increased morbidity and health care costs. Techniques to reduce these consequences may improve outcomes and reduce cost after lumbar discectomy. In a prospective cohort study, we set out to evaluate the cost associated with surgical management of recurrent, same-level lumbar disc herniation following primary discectomy.

Methods: Forty-six consecutive European patients undergoing lumbar discectomy for a single-level herniated disc at two institutions were prospectively followed with clinical and radiographic evaluations. A second consecutive cohort of 30 patients undergoing 31 lumbar discectomies with implantation of an annular closure device was followed at the same hospitals and same follow-up intervals. Cost estimates for reherniation were modeled on Medicare national allowable payment amounts (direct cost) and patient work-day losses (indirect cost).

Results: Annular closure and control cohorts were matched at baseline. By 2 years follow-up, symptomatic recurrent same-level disc herniation occurred in three (6.5%) patients in the control cohort versus zero (0%) patients in the annular closure cohort. For patients experiencing recurrent disc herniation, mean estimated direct and indirect cost of management of recurrent disc herniation was $34,242 and $3,778, respectively. Use of an annular closure device potentially results in a cost savings of $222,573 per 100 primary discectomy procedures performed (or $2,226 per discectomy), based solely on the reduction of reoperated reherniations when modeled on U.S. Medicare costs.

Conclusions: Recurrent disc herniation did not occur in any patients after annular closure within the 12-month follow-up. The reduction in the incidence of reherniation was associated with potentially significant cost savings. Development of novel techniques to prevent recurrent lumbar disc herniation is warranted to decrease the associated morbidity and health care costs associated with this complication.
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http://dx.doi.org/10.1055/s-0033-1341416DOI Listing
September 2013

Sinus pericranii in the left frontal region involving the superior eyelid: a case report.

J Neurol Surg A Cent Eur Neurosurg 2013 Dec 20;74 Suppl 1:e166-9. Epub 2013 Feb 20.

Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.

Background: Sinus pericranii is a rare asymptomatic communication between the intracranial and extracranial venous drainage pathways. The venous flow in this condition circulates through abnormal dilated veins in both directions.

Patient/methods: We describe an unusual location of an accessory sinus pericranii that involved the left frontal bone along with the superior orbital rim and the upper eyelid, with special focus on therapy.

Results: The patient did not have any complication during the first and second surgery. Final outcome was excellent. The patient did not show any evidence of disease recurrence 1 year after the surgery.

Conclusion: We propose a multidisciplinary approach in the treatment of such lesions with a two-step surgery. Excision of the sinus pericranii is possible if the sinus pericranii is not a major venous outflow channel of the brain, which can be evaluated by angiography.
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http://dx.doi.org/10.1055/s-0032-1333423DOI Listing
December 2013

Multiple cystic brain metastases from papillary thyroid carcinoma mimicking neurocysticercosis.

Int J Surg Pathol 2013 Aug 24;21(4):390-3. Epub 2013 Jan 24.

Department of Neurology, University Hospital Dubrava, Avenija Gojka Šuška 6, 10000 Zagreb.

The papillary carcinoma of the thyroid gland is the most common type of tumor of the thyroid gland with good prognosis and low incidence of distant metastasis. The brain metastases of thyroid gland carcinoma are extremely rare. We report a patient with multiple cystic brain lesions and satisfying criteria for diagnosis of neurocysticercosis. Brain biopsy revealed brain metastases from papillary thyroid carcinoma. The tumor originated from mediastinal thyroid tissue. Even in cases when neuroimaging suggests neurocysticercosis with great accuracy, it is important to exclude metastasis. Extensive brain metastases of primary papillary thyroid carcinoma are extremely rare.
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http://dx.doi.org/10.1177/1066896912473353DOI Listing
August 2013

Primary spinal malignant melanoma of spinal cord and conus medullaris.

Can J Neurol Sci 2013 Jan;40(1):104-5

Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.

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http://dx.doi.org/10.1017/s0317167100013068DOI Listing
January 2013

Implantation metastasis of malignant fibrous histiocytoma along the stereotactic biopsy tract.

Clin Neurol Neurosurg 2013 Jul 3;115(7):1160-1. Epub 2012 Oct 3.

Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.

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http://dx.doi.org/10.1016/j.clineuro.2012.09.018DOI Listing
July 2013

An unexpected obstacle: a retrorectal mass went undetected until the patient was in labor.

Am J Obstet Gynecol 2011 Dec 20;205(6):578.e1-2. Epub 2011 Oct 20.

Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.

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http://dx.doi.org/10.1016/j.ajog.2011.10.856DOI Listing
December 2011