Publications by authors named "Marina Raguz"

21 Publications

  • Page 1 of 1

Structural Changes in the Cortico-Ponto-Cerebellar Axis at Birth are Associated with Abnormal Neurological Outcomes in Childhood.

Clin Neuroradiol 2021 May 4. Epub 2021 May 4.

Croatian Institute for Brain Research, Centre of Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, Croatia.

White matter lesions in hypoxic-ischemic encephalopathy (HIE) are considered to be the important substrate of frequent neurological consequences in preterm infants. The aim of the study was to analyze volumes and tractographic parameters of the cortico-ponto-cerebellar axis to assess alterations in the periventricular fiber system and crossroads, corticopontine and corticospinal pathways and prospective transsynaptic changes of the cerebellum.Term infants (control), premature infants without (normotypic) and with perinatal HIE (HIE) underwent brain magnetic resonance imaging at term-equivalent age (TEA) and at 2 years. Cerebrum, cerebellum, brainstem divisions and ventrodorsal compartments volumetric analysis were performed, as well as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of corticopontine, corticospinal pathways and middle cerebellar peduncles. Amiel-Tison scale at TEA and the Hempel test at 2 years were assessed.Cerebellum, brainstem and its compartments volumes were decreased in normotypic and HIE groups at TEA, while at 2 years volumes were significantly reduced in the HIE group, accompanied by decreased volume and FA and increased ADC of corticopontine and corticospinal pathways. Negative association of the brainstem, cerebellum, mesencephalon, pons, corticopontine volumes and corticospinal pathway FA at TEA with the neurological score at 2 years. Cerebellum and pons volumes presented as potential prognostic indicators of neurological outcomes.Our findings agree that these pathways, as a part of the periventricular fiber system and crossroads, exhibit lesion-induced reaction and vulnerability in HIE. Structural differences between normotypic and HIE group at the 2 years suggest a different developmental structural plasticity.
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http://dx.doi.org/10.1007/s00062-021-01017-1DOI Listing
May 2021

Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes that are involved in cadherin switch, and , play a role in meningioma progression. Increased N-cadherin expression in relation to E-cadherin was recorded. In meningioma, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-cadherin. The expression of SNAIL and SLUG was significantly associated with higher grades ( = 0.001), indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form ( = 0.000). This research brings the results of genetic and protein analyzes of important molecules that are involved in Wnt and EMT signaling pathways and reveals their role in intracranial meningioma. The results of this study offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.
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http://dx.doi.org/10.3390/cancers13071633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037732PMC
April 2021

Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.

Sci Rep 2021 Feb 23;11(1):4401. Epub 2021 Feb 23.

Department of Neurosurgery, Dubrava University Hospital, Avenija Gojka Suska 6, 10000, Zagreb, Croatia.

Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients. Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures. Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase. Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.
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http://dx.doi.org/10.1038/s41598-021-83873-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902623PMC
February 2021

The Accuracy of Direct Targeting Using Fusion of MR and CT Imaging for Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson's Disease.

J Neurol Surg A Cent Eur Neurosurg 2021 Feb 22. Epub 2021 Feb 22.

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

Introduction:  In 33 consecutive patients with Parkinson's disease (PD) undergoing awake deep brain stimulation (DBS) without microelectrode recording (MER), we assessed and validated the precision and accuracy of direct targeting of the subthalamic nucleus (STN) using preoperative magnetic resonance imaging (MRI) and stereotactic computed tomography (CT) image fusion combined with immediate postoperative stereotactic CT and postoperative MRI, and we report on the side effects and clinical results up to 6 months' follow-up.

Materials And Methods:  Preoperative nonstereotactic MRI and stereotactic CT images were merged and used for planning the trajectory and final lead position. Immediate postoperative stereotactic CT and postoperative nonstereotactic MRI provided the validation of the final electrode position. Changes in the Unified Parkinson's Disease Rating Scale III (UPDRS III) scores and the levodopa equivalent daily doses (LEDD) and appearance of adverse side effects were assessed.

Results:  The mean Euclidian distance (ED) error between the planned position and the final position of the lead in the left STN was 1.69 ± 0.82 mm and that in the right STN was 2.12 ± 1.00. The individual differences between planned and final position in each of the three coordinates were less than 2 mm. The UPDRS III scores improved by 75% and LEDD decreased by 45%. Few patients experienced complications, such as postoperative infection (= 1), or unwanted side effects, such as emotional instability ( = 1).

Conclusion:  Our results confirm that direct targeting of an STN on stereotactic CT merged with MRI could be a valid method for placement the DBS electrode. The magnitude of our targeting error is comparable with the reported errors when using MER and other direct targeting approaches.
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http://dx.doi.org/10.1055/s-0040-1715826DOI Listing
February 2021

Frameless stereotactic brain biopsy: A prospective study on robot-assisted brain biopsies performed on 32 patients by using the RONNA G4 system.

Int J Med Robot 2021 Feb 16. Epub 2021 Feb 16.

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

Background: We present a novel robotic neuronavigation system (RONNA G4), used for precise preoperative planning and frameless neuronavigation, developed by a research group from the University of Zagreb and neurosurgeons from the University Hospital Dubrava, Zagreb, Croatia. The aim of study is to provide comprehensive error measurement analysis of the system used for the brain biopsy.

Methods: Frameless stereotactic robot-assisted biopsies were performed on 32 consecutive patients. Post-operative CT and MRI scans were assessed to precisely measure and calculate target point error (TPE) and entry point error (EPE).

Results: The application accuracy of the RONNA system for TPE was 1.95 ± 1.11 mm, while for EPE was 1.42 ± 0.74 mm. The total diagnostic yield was 96.87%. Linear regression showed statistical significance between the TPE and EPE, and the angle of the trajectory on the bone.

Conclusion: The RONNA G4 robotic system is a precise and highly accurate autonomous neurosurgical assistant for performing frameless brain biopsies.
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http://dx.doi.org/10.1002/rcs.2245DOI Listing
February 2021

Transient structural MRI patterns correlate with the motor functions in preterm infants.

Brain Dev 2021 Mar 22;43(3):363-371. Epub 2020 Nov 22.

Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience, Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia.

Aim: To explore the relationships between transient structural brain patterns on MRI at preterm and at term-equivalent age (TEA) as a predictor of general movements (GMs) and motor development at 1-year corrected age (CA) in very preterm infants.

Methods: In this prospective study, 30 very preterm infants (median = 28wks; 16 males) had structural magnetic resonance imaging (MRI) at preterm (median = 31wks + 6d) and at TEA (median = 40wks) and neuromotor assessments. The quality of GMs was assessed by Prechtl's general movements assessment and a detailed analysis of the motor repertoire was performed by calculating a motor optimality score (MOS), both at term age and at 3 months post-term. Motor development at 1-year CA was evaluated with the Infant Motor Profile (IMP). Associations between qualitative MRI findings and neuromotor scores were investigated.

Results: Abnormal GMs and low motor performance at 1-year CA were associated with the poor visibility of transient structural pattern, that is with sagittal strata.

Interpretation: Transient structural MRI pattern, sagittal strata, at preterm age is related to the quality of GMs and later motor development in preterm infants. This transient fetal brain compartment may be considered as a component of neurobiological basis for early neuromotor behavior, as expressed by GMs.
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http://dx.doi.org/10.1016/j.braindev.2020.11.002DOI Listing
March 2021

Stereotactic Neuro-Navigation Phantom Designs: A Systematic Review.

Front Neurorobot 2020 23;14:549603. Epub 2020 Oct 23.

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

Diverse stereotactic neuro-navigation systems are used daily in neurosurgery and novel systems are continuously being developed. Prior to clinical implementation of new surgical tools, methods or instruments, experiments on phantoms should be conducted. A stereotactic neuro-navigation phantom denotes a rigid or deformable structure resembling the cranium with the intracranial area. The use of phantoms is essential for the testing of complete procedures and their workflows, as well as for the final validation of the application accuracy. The aim of this study is to provide a systematic review of stereotactic neuro-navigation phantom designs, to identify their most relevant features, and to identify methodologies for measuring the target point error, the entry point error, and the angular error (α). The literature on phantom designs used for evaluating the accuracy of stereotactic neuro-navigation systems, i.e., robotic navigation systems, stereotactic frames, frameless navigation systems, and aiming devices, was searched. Eligible articles among the articles written in English in the period 2000-2020 were identified through the electronic databases PubMed, IEEE, Web of Science, and Scopus. The majority of phantom designs presented in those articles provide a suitable methodology for measuring the target point error, while there is a lack of objective measurements of the entry point error and angular error. We identified the need for a universal phantom design, which would be compatible with most common imaging techniques (e.g., computed tomography and magnetic resonance imaging) and suitable for simultaneous measurement of the target point, entry point, and angular errors.
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http://dx.doi.org/10.3389/fnbot.2020.549603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644893PMC
October 2020

Hemoglobin A1c in Patients with Glioblastoma-A Preliminary Study.

World Neurosurg 2020 09 31;141:e553-e558. Epub 2020 May 31.

Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia; Department of Surgery, Zagreb University School of Medicine, Zagreb, Croatia.

Background: Glioblastomas are among the most common primary brain tumors with an abysmal prognosis. The significance of glucose metabolism in glioblastoma cell metabolism and proliferation is well-known. However, a significant correlation between the systemic metabolic status of the patient and the cellular proliferation of the glioblastoma has not yet been established.

Methods: Our aim was to observe and analyze for a possible correlation between glioblastoma cellular proliferation and patients' glycated hemoglobin (HbA1c) levels as a marker of chronic systemic glycemia. We analyzed the data from 25 patients and compared their Ki-67 values with their preoperative HbA1c values.

Results: We observed a statistically significant correlation (P < 0.03) between chronic glycemia (measured using HbA1c) and the cellular proliferation of glioblastoma (measured by cellular Ki-67 expression).

Conclusions: These results imply a possible positive correlation between glioblastoma cell proliferation and chronic systemic glycemia, a correlation that, to the best of our knowledge, has not yet been reported. Further research in this area could not only lead to a better understanding of glioblastoma but also have significant clinical applications in treating this devastating disease.
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http://dx.doi.org/10.1016/j.wneu.2020.05.231DOI Listing
September 2020

Brain tissue volumes at term-equivalent age are associated with early motor behavior in very preterm infants.

Int J Dev Neurosci 2020 May 20. Epub 2020 May 20.

Croatian Institute for Brain Research, Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience, School of Medicine, University of Zagreb, Zagreb, Croatia.

Preterm birth is associated with a wide range of adverse developmental outcomes, including sensory, motor, cognitive and language impairments, and behavioral or attention problems. Subtle motor deficits that might emerge in premature infants with no evident or with mild brain injury encompass qualitative and quantitative aspects of motor behavior. This prospective cohort study provided an evaluation of the relationship between brain tissue volumes revealed by magnetic resonance imaging (MRI) at term-equivalent age and motor behavior in infancy in very preterm infants (total number = 40; mean gestational age = 28 weeks + 4 days; mean birth weight = 1190 g) without evident or with mild brain injury. Infants were recruited at birth and assessed at 12 months corrected age using the tool for qualitative and quantitative assessment of motor behavior, infant motor profile. The brain tissue was segmented first using advanced segmentation techniques and the volumes were measured by summing the volumes of all voxels belonging to a particular tissue class. The associations between volumetric brain MRI measures with motor behavior were explored using linear regression analyses. Results showed that larger total brain volumes were associated with higher motor score. Similar relationships were documented for parietal lobe, deep gray matter, and cerebellum volumes. Volumetric quantitative data of brain structures may serve as biomarkers for subtle motor deficits described in very preterm born infants without or with mild brain lesions apparent on MRI.
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http://dx.doi.org/10.1002/jdn.10039DOI Listing
May 2020

A biphasic tumor in posterior cranial fossa and the pineal region in young adult.

Surg Neurol Int 2020 11;11:64. Epub 2020 Apr 11.

Departments of Neurosurgery, University Hospital Dubrava, Zagreb, Croatia.

Background: Biphasic tumors of the central nervous system are rarely described and mainly consisted out of the glial and mesenchymal component. The tumor originated out of both astrocytes and pinealocytes, best to our knowledge, has not been described. We present a case of a brain tumor consisted out of pilocytic astrocytoma (PA) and pineocytoma as components situated in the pineal region and posterior cranial fossa in young adult.

Case Description: We present a 21-year-old patient with a history of intermittent headache, followed by nausea and vomiting, double vision, and dextropulsion. Magnetic resonance imaging revealed an extensive cystic-solid expansive formation in the posterior cranial fossa with a solid part in the area of the pineal gland. The patient underwent surgical resection. The pathohistological analysis showed two types of tumor cells; the major part of tumor showed features of PA, while minor part corresponded to pineocytoma.

Conclusion: PA accounts for 5% of all gliomas and is most common in children and young adults. It usually occurs in the cerebellum, the optic pathway, third ventricular region, etc. Pineocytomas are rare, accounting up to 1% of all intracranial tumors. Since tumors origin is different, there must be complex molecular events or mutations that can lead to cell rearrangements and generation of two histologically different tissues in the same tumor mass. The course of treatment options is different for PA and pineocytoma; therefore, the case of brain mass consisted out of two different tissues can be helpful when deciding about the treatment of tumors in posterior cranial fossa and pineal region.
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http://dx.doi.org/10.25259/SNI_288_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193197PMC
April 2020

Dynamics of inflammatory factors expression in ischemic brain tissue injury.

Neurol Int 2019 Nov 2;11(4):8282. Epub 2019 Dec 2.

Department of Neurosurgery, University Hospital Dubrava, Zagreb.

Ischemic stroke is one of the most common cause of mortality and disability in the modern world. Still, therapeutic options remain modest. Aim of the study was to present dynamics of inflammatory factors expression (C reactive protein, procalcitonin, interleukin 10) in patients after ischemic stroke. Our study included 101 patients divided in thrombolised and nonthrombolised groups. Inflammatory factors concentration in serum was determinate at admission, 24, 48 hours and seven days after the initial onset, while neurological assessment was measured at the admission, 24 hours, seven days and three months after the initial onset using National Institute of Health Stroke Scale and Rankin Scale. Certain pattern was observed in dynamics of inflammatory factors: intensive increase in first and second day after the stroke, followed by decrease till day seven in both groups. Additionally, thrombolised group showed significant neurological improvement. Although well investigated, the role of inflammatory factors in the ischemic stroke still stays controversial. High association of C reactive protein and interleukin 10 values suggest potential prognostic role in patient's follow-up, while the role of procalcitonin values still remains unclear.
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http://dx.doi.org/10.4081/ni.2019.8282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908952PMC
November 2019

Specific cognitive deficits in preschool age correlated with qualitative and quantitative MRI parameters in prematurely born children.

Pediatr Neonatol 2020 04 23;61(2):160-167. Epub 2019 Sep 23.

Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, Croatia; Department of Radiology, University Hospital Centre Zagreb, Zagreb, Croatia.

Background: Cognitive deficits after perinatal brain lesion in preterm infants are among the most common neurodevelopmental disturbances. The relationship between structural changes on at term magnetic resonance imaging (MRI) and cognitive deficits in the preschool age should be a special focus due to timely intervention. The aim of this study was to correlate qualitative and quantitative MRI parameters of perinatal brain lesion in preterm children, on early neonatal MRI and follow up MRI, with general and specific cognitive functions in the preschool age.

Methods: Twenty-one preterm infants with verified perinatal lesions based on clinical and ultrasound data underwent a brain MRI at term-equivalent age and a second MRI between 3 and 5 years of age. Qualitative and quantitative MRI analyses were done. All subjects underwent cognitive assessment (3-5 years) using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Developmental Neuropsychological Assessment (NEPSY-II).

Results: Results show that many structural changes on at term MRI and on follow up MRI in preterm born children moderately correlate with specific cognitive deficits in preschool age. At term equivalent MRI, white matter changes and cortical thickness correlate to general and specific cognitive functions in infants born preterm. By analyzing follow up MRI at preschool age, structural changes of different white matter segments, corpus callosum, cortical thickness and lobe volume correlate to some specific cognitive functions.

Conclusion: Besides general cognitive delay, specific cognitive deficits in preterm children should be targeted in research and intervention, optimally combined with MRI scanning, providing timely and early intervention of cognitive deficits after perinatal brain lesion. Our results, as well as previously published results, suggest the importance of detailed preschool neuropsychological assessment, prior to enrolment in the school system. Although preliminary, our results expand our understanding of the relationship between early brain developmental lesions and cognitive outcome following premature birth.
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http://dx.doi.org/10.1016/j.pedneo.2019.09.003DOI Listing
April 2020

The Dubrava Model-A Novel Approach in Treating Acutely Neurotraumatized Patients in Rural Areas: A Proposal for Management.

J Neurosci Rural Pract 2019 Jul 7;10(3):446-451. Epub 2019 Oct 7.

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

Neurotrauma is one of the leading causes of death and disabilities nowadays and represents one of the largest socioeconomic problems in rich countries, as well as developing ones. A satisfying, medically viable, and cost-effective model of managing acutely neurotraumatized patients, especially ones who come from distant and/or rural areas, has yet to be found. Patient outcome after acute neurotrauma depends on many factors of which the possibility of urgent treatment by an experienced specialist team has a crucial role. Here, we present our own way of managing acutely neurotraumatized patients from distant places which is unique in Croatia, the Dubrava model. We present our 5-year experience cooperating with general hospitals in four neighboring cities (Ĉakovec, Bjelovar, Sisak, and Koprivnica) in managing, operating, and taking care of acutely neurotraumatized patients. More than 300 surgeries have been performed in these hospitals through the Dubrava model. Our experience so far provides encouraging results that this system could also be successfully implemented in other institutions. Furthermore, we recorded an increased number of surgeries each year, as well as a good mutual cooperation with the local general hospitals. This trauma managing model is one of a kind in Croatia. We argue that it is not only better for the patients, providing them with better chances of survival, and disability-free recovery, but is also far superior in many ways to the dominant and currently prevalent way of treating these patients in other parts of Croatia. The Dubrava model of treating patients in rural and distant areas is a reliable and proven model with many benefits and as such its implementation should be considered in other institutions as well.
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http://dx.doi.org/10.1055/s-0039-1697777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779563PMC
July 2019

Intracranial Mature Teratoma in an Adult Patient: A Case Report.

J Neurol Surg Rep 2019 Jan 3;80(1):e14-e17. Epub 2019 Apr 3.

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

: Primary intracranial teratoma is a subtype of germ cell tumors, classified into three subtypes. They occur very rarely, with only several reported individual cases in adults.  We present a patient with an intermittent headache in the right frontal region. Magnetic resonance imaging (MRI) revealed a right sided high frontal parasagittal mass that compressed the falx, the right lateral ventricle, as well as the brain parenchyma. Patient underwent surgical treatment. Histopathological analysis described mature teratoma. Four months after the surgical treatment there were no signs of residual intracranial mass or relapse.  Primary intracranial teratoma in adults has a nonspecific clinical presentation. MRI reveals a solitary irregular mass with multilocularity and mixed signals derived from different tissues. The patients age, biochemical markers, and patohistological analysis are necessary to confirm the diagnosis.  Teratoma treatment strategy still remains controversial. It includes radical resection whenever possible. Since the residual portion of mature teratoma may contain part of immature or malignant tissue, tumor recurrence after surgical removal is possible. Also, new tumor mass could occur at other sites intracranial after the initial one was removed. Thus, although patients usually recover, they should be followed-up for a long period of time.
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http://dx.doi.org/10.1055/s-0039-1685213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447400PMC
January 2019

Intraspinal calcinosis mimicking intervertebral disc extrusion: A clinical and surgical case report.

Surg Neurol Int 2018 14;9:166. Epub 2018 Aug 14.

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

Background: Subcutaneous calcinosis is a well-recognized manifestation of systemic sclerosis that usually involves multiple pressure points and may also be found in the paraspinal or intraspinal regions. In this case, intraspinal calcinosis uniquely led to a severe neurological deficit.

Case Description: A patient with severe systemic sclerosis/calcinosis exhibited left greater than right lower extremity radiculopathy attributed to intraspinal left-sided L4-L5 calcinosis. On examination, the patient exhibited bilateral positive Lasegue signs, distal lower extremity weakness (left greater than right), and bilaterally decreased Achilles responses. When the magnetic resonance imaging (MRI) revealed a significant intracanalicular mass on the left side at the L4-L5 level, the patient underwent a left-sided L4-L5 decompressive laminectomy. The MRI scan 5 years later revealed no recurrence of the calcinosis, and the patient had no residual neurological deficit.

Conclusions: Spinal calcinosis rarely involves the lumbar spinal canal. Here, a patient with a large left-sided L4-L5 focus of intraspinal calcinosis, mimicking a disc herniation, required a laminectomy to resect the lesion. Lumbar calcinosis should be radiologically evaluated utilizing using X-ray, MRI, and computed tomography studies to adequately document the pathology. Patients, when symptomatic, may require surgical decompression and excision of these lesions.
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http://dx.doi.org/10.4103/sni.sni_147_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108162PMC
August 2018

Primary dural lymphoma mimicking meningioma: a clinical and surgical case report.

J Surg Case Rep 2018 Aug 6;2018(8):rjy189. Epub 2018 Aug 6.

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

Introduction: Primary central nervous system lymphoma and its subtype, primary dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the central nervous system without any dissemination. They are extremely rare cases of extra nodal lymphomas accounting for 1--5% of intracranial tumors.

Case Report: We present a patient diagnosed with primary dural lymphoma in right frontal brain region who underwent surgical resection. Histopathological analysis revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative, no signs of newly onset infiltration were present.

Discussion: Primary dural lymphoma most likely presents with unusual radiological signs, which can easily be mistaken for meningioma, the main differential diagnosis. A thorough immunological, histopathological and clinical patients profile should be conducted in order to establish the certainty of diagnosis. Although there are few treatment options: surgery, radiotherapy or chemotherapy, there is no established treatment protocol.
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http://dx.doi.org/10.1093/jscr/rjy189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077807PMC
August 2018

Spatiotemporal Relationship of Brain Pathways during Human Fetal Development Using High-Angular Resolution Diffusion MR Imaging and Histology.

Front Neurosci 2017 11;11:348. Epub 2017 Jul 11.

Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical SchoolBoston, MA, United States.

In this study, we aimed to identify major fiber pathways and their spatiotemporal relationships within transient fetal zones in the human fetal brain by comparing postmortem high-angular resolution diffusion MR imaging (HARDI) in combination with deterministic streamline tractography and histology. Diffusion weighted imaging was performed on postmortem human fetal brains [ = 9, age = 18-34 post-conceptual weeks (PCW)] that were grossly normal with no pathologic abnormalities. After HARDI was performed, the fibers were reconstructed using Q-ball algorithm and deterministic streamline tractography. The position of major fiber pathways within transient fetal zones was identified both on diffusion weighted images and on histological sections. Our major findings include: (1) the development of massive projection fibers by 18 PCW, as compared to most association fibers (with the exception of limbic fibers) which have only begun to emerge, (2) the characteristic laminar distribution and sagittal plane geometry of reconstructed fibers throughout development, (3) the protracted prenatal development shown of the corpus collosum and its' associated fibers, as well as the association fibers, and (4) the predomination of radial coherence in the telencephalon (i.e., majority of streamlines in the telencephalic wall were radially oriented) during early prenatal period (24 PCW). In conclusion, correlation between histology and HARDI (in combination with Q-ball reconstruction and deterministic streamline tractography) allowed us to detect sequential development of fiber systems (projection, callosal, and association), their spatial relations with transient fetal zones, and their geometric properties.
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http://dx.doi.org/10.3389/fnins.2017.00348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504538PMC
July 2017

Diameters and bone thickness at the margin of the foramen magnum in dry skulls from pediatric population: a cross-sectional anatomical study.

Childs Nerv Syst 2017 May 21;33(5):819-823. Epub 2017 Mar 21.

Department of Anatomy and Clinical Anatomy, University of Zagreb School of Medicine, Zagreb, Croatia.

Purpose: The purpose of the study was to estimate the size and bone thickness at the margin of the foramen magnum in a pediatric population.

Methods: Sixty occipital bone specimens from the collection of macerated skulls at the Department of Anatomy, University of Zagreb, were examined and measured using a vernier scale/caliper. For the purpose of analysis, specimens were divided into two age groups: 1-6 years and 7-18 years of age (before and after the fusion of ossification centers in the occipital bone). We measured the following: antero-posterior and transverse diameters of the foramen magnum, bone thicknesses at the basion, opisthion, two paramedial points on the anterior and posterior margins, and at the occipito-squamous junction.

Results: Data presented in this study show that diameters of the foramen magnum increase with age, whereas bone thickness shows variable behavior depending on the measured area.

Conclusions: Increases in diameters in specimens from the younger age group and their absence in specimens from older subjects reflect the growth pattern of the basilar part of occipital bone. Variability of bone thickness at the margin of the foramen magnum and lack of its association with age of the subjects may be attributed to various factors and may potentially affect the clinical presentation of compression syndromes at the level of foramen magnum.
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http://dx.doi.org/10.1007/s00381-017-3374-5DOI Listing
May 2017

Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development.

Front Neuroanat 2016 24;10:11. Epub 2016 Feb 24.

Department of Developmental Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb Zagreb, Croatia.

The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13-40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries.
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http://dx.doi.org/10.3389/fnana.2016.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764715PMC
March 2016

Volumetric analysis of cerebrospinal fluid and brain parenchyma in a patient with hydranencephaly and macrocephaly--case report.

Croat Med J 2014 Aug;55(4):388-93

Marijan Klarica, University of Zagreb, School of Medicine, Department of Pharmacology and Croatian Institute for Brain Research, Šalata 11, 10 000 Zagreb, Croatia,

The aim of this study was to perform for the first time the intracranial volumetric analysis of cerebrospinal fluid (CSF) and brain parenchyma in the supratentorial and infratentorial space in a 30-year-old female patient with hydranencephaly and macrocephaly. A head scan performed using a 3T magnetic resonance was followed by manual segmentation of the brain parenchyma and CSF on T2 coronal brain sections. The volume of CSF and brain parenchyma was measured separately for the supratentorial and infratentorial space. The total volume of the intracranial space was 3645.5 cm3. In the supratentorial space, the volume of CSF was 3375.2 cm3 and the volume of brain parenchyma was 80.3 cm3. In the infratentorial space, the volume of CSF was 101.3 cm3 and the volume of the brain parenchyma was 88.7 cm3. In the supratentorial space, there was severe malacia of almost all brain parenchyma with no visible remnants of the choroid plexuses. Infratentorial structures of the brainstem and cerebellum were hypoplastic but completely developed. Since our patient had no choroid plexuses in the supratentorial space and no obstruction between dural sinuses and CSF, development of hydrocephalus and macrocephaly cannot be explained by the classic hypothesis of CSF physiology with secretion, unidirectional circulation, and absorption as its basic postulates. However, the origin and turnover of the enormous amount of intracranial CSF volume, at least 10-fold larger than normal, and the mechanisms of macroencephaly development could be elucidated by the new hypothesis of CSF physiology recently published by our research team.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157378PMC
http://dx.doi.org/10.3325/cmj.2014.55.388DOI Listing
August 2014

Influence of congenital central nervous system malformations on postoperative complications following placement of cerebrospinal fluid shunts in pediatric and adolescent patients.

Wien Klin Wochenschr 2014 Jan 29;126(1-2):2-8. Epub 2013 Oct 29.

University Hospital Centre Zagreb, Kispaticeva 12, 10000, Zagreb, Croatia.

Background: This retrospective study was designed to evaluate whether patients with hydrocephalus associated with central nervous system (CNS) anomalies, compared with patients with hydrocephalus and absent CNS anomalies, present with significantly higher rate of postoperative complications, including more serious clinical presentation, increased life threat, and higher postoperative or late mortality rate.

Methods: We performed a retrospective study using medical records of 100 patients of pediatric and adolescent age (0-18 years) between 2004 and 2010 treated with operative cerebrospinal fluid (CSF) shunt placement.

Results: In both groups of patients, there were 43 postoperative complications, including 12 mechanical obstructions of the CSF drainage systems, 13 disconnections, 11 dislocations of proximal catheter, 6 inflammatory complications (meningitis), and 1 latex allergy. Patients with hydrocephalus associated with CNS anomalies were presented with statistically higher rate of postoperative complications (U = 303.5, z = -3.27, p = 0.001), higher number of operations, at least one complication more per patient, more complicated clinical course, higher life threat, and higher late mortality rate.

Conclusions: After installing the CSF drain system, children and adolescents with hydrocephalus associated with anomalies of the CNS require regular and careful follow-up.
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http://dx.doi.org/10.1007/s00508-013-0427-yDOI Listing
January 2014