Publications by authors named "Dimitrios Panagopoulos"

37 Publications

A diagnostic challenge in an unresponsive refugee child improving with neurosurgery-a case report.

Oxf Med Case Reports 2021 May 24;2021(5):omab020. Epub 2021 May 24.

Medical Department, Médecins Sans Frontières-Operational Centre Brussels, Lesvos, Greece.

An unresponsive paediatric patient may present a diagnostic challenge for health professionals, as rapid identification of the cause is needed to provide proper interventions. The following report details a challenging diagnosis of unresponsiveness in a refugee child. In the migratory context, observed unresponsiveness states are frequently attributed to psychologic factors, and overlapping psychiatric classifications (resignation syndrome, functional coma and catatonia) are common. Our patient fell into an unresponsive state for 6 months after witnessing a traumatic event. Diagnostic workup for multiple medical comorbidities led to surgical intervention for tethered cord syndrome. Shortly after that, the patient's responsiveness improved, putting to question her condition's underlying cause. This case highlights the need for a biopsychosocial approach in such cases, reflected in thorough clinical examination and diagnostic investigations. A multidisciplinary perspective and expertise proved crucial and may help in the rehabilitation of children in similar situations.
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http://dx.doi.org/10.1093/omcr/omab020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143662PMC
May 2021

Polycystin-1 modulates RUNX2 activation and osteocalcin gene expression via ERK signalling in a human craniosynostosis cell model.

J Cell Mol Med 2021 Apr 3;25(7):3216-3225. Epub 2021 Mar 3.

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Craniosynostosis refers to the premature fusion of one or more cranial sutures leading to skull shape deformities and brain growth restriction. Among the many factors that contribute to abnormal suture fusion, mechanical forces seem to play a major role. Nevertheless, the underlying mechanobiology-related mechanisms of craniosynostosis still remain unknown. Understanding how aberrant mechanosensation and mechanotransduction drive premature suture fusion will offer important insights into the pathophysiology of craniosynostosis and result in the development of new therapies, which can be used to intervene at an early stage and prevent premature suture fusion. Herein, we provide evidence for the first time on the role of polycystin-1 (PC1), a key protein in cellular mechanosensitivity, in craniosynostosis, using primary cranial suture cells isolated from patients with trigonocephaly and dolichocephaly, two common types of craniosynostosis. Initially, we showed that PC1 is expressed at the mRNA and protein level in both trigonocephaly and dolichocephaly cranial suture cells. Followingly, by utilizing an antibody against the mechanosensing extracellular N-terminal domain of PC1, we demonstrated that PC1 regulates runt-related transcription factor 2 (RUNX2) activation and osteocalcin gene expression via extracellular signal-regulated kinase (ERK) signalling in our human craniosynostosis cell model. Altogether, our study reveals a novel mechanotransduction signalling axis, PC1-ERK-RUNX2, which affects osteoblastic differentiation in cranial suture cells from trigonocephaly and dolichocephaly patients.
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http://dx.doi.org/10.1111/jcmm.16391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034462PMC
April 2021

Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics*.

ChemMedChem 2021 Apr 4;16(7):1116-1125. Epub 2021 Mar 4.

Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, Suite 700, 101 College Street, Toronto, ON M5G 1L7, Canada.

Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure-activity relationships for this class of compounds.
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http://dx.doi.org/10.1002/cmdc.202100018DOI Listing
April 2021

Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies.

Clin Med (Lond) 2021 Jan 26;21(1):e63-e67. Epub 2020 Nov 26.

Hammersmith Hospital, London, UK.

The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.
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http://dx.doi.org/10.7861/clinmed.2020-0896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850225PMC
January 2021

Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma.

J Med Chem 2020 05 5;63(9):4978-4996. Epub 2020 May 5.

Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, Room 4207, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.

Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Analysis of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant. Initial efforts resulted in the discovery of , an analogue of the previously reported ALK2 inhibitor . Although highly selective for ALK2 over the TGF-βR1 receptor ALK5, is also moderately active against the hERG potassium channel. Varying the substituents of the trimethoxyphenyl moiety gave rise to an equipotent benzamide analogue with reduced off-target affinity for the ion channel. Additional modifications yielded 2-fluoro-6-methoxybenzamide derivatives (), which possess high inhibitory activity against ALK2, excellent selectivity, and superior pharmacokinetic profiles.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00395DOI Listing
May 2020

Post-Traumatic Status Epilepticus Masquerading as Acute Ischemic Stroke: A Case Report and Literature Review.

Am J Case Rep 2020 May 4;21:e922679. Epub 2020 May 4.

Department of Neurosurgery, Pediatric Hospital of Athens, Agia Sophia, Athens, Greece.

BACKGROUND Advanced imaging is one of the main modalities utilized in the diagnostic investigation of a first-time epileptic ictus, as well as in the evaluation of a patient suspected of having an ischemic stroke. CASE REPORT We report the case of a 7-year-old boy who was admitted to our hospital because of a depressed skull fracture. Soon after its initial evaluation, he had an episode of generalized tonic-clonic seizures; therefore, a detailed diagnostic work up was scheduled, which raised the diagnostic dilemma of ischemic stroke versus imaging alterations related to status epilepticus. He underwent surgical exploration, and a few days later the repeat MRI verified that the initial signal changes should be attributed to the ictus. CONCLUSIONS Brain edema, most commonly affecting a cerebral hemisphere in its entirety, is a rare post-ictal imaging finding that is causally related to focal-onset status epilepticus. The aforementioned perfusion changes can aid in the differentiation of ictal-related brain abnormalities from acute ischemic stroke, if regional or more diffuse areas of increased perfusion are shown on MRI. Consequently, MRI should be considered the preferred imaging modality when we are confronted with cases of post-ictal signal changes that could masquerade as acute ischemic stroke.
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http://dx.doi.org/10.12659/AJCR.922679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213816PMC
May 2020

Ruptured Arteriovenous Malformation Anterior to the Brainstem to a Child with Subsequent Spontaneous Thrombosis: Case Report and Literature Review.

Am J Case Rep 2020 May 1;21:e923289. Epub 2020 May 1.

Department of Neurosurgery, Pediatric Hospital of Athens, Agia Sophia, Athens, Greece.

BACKGROUND Cerebral arteriovenous malformations (AVMs) are considered to be abnormalities of congenital origin, presumably arising due to a disorder in the process of embryogenesis, in the phase of differentiation of premature vascular domes into mature arteries, capillaries, and veins. The end result of that process is the formation of direct arteriovenous communications, without intervening capillary beds. CASE REPORT We report the case of a 6-year-old female who suffered an abrupt deterioration of her level of consciousness due to a subarachnoid hemorrhage located in the basal cisterns. Radiological investigation with magnetic resonance arteriography-magnetic resonance venography (MRA-MRV) was negative, but digital subtraction angiography (DSA) revealed a micro-AVM in the vicinity of the brainstem. The patient subsequently developed communicating hydrocephalus and the repeat DSA, performed 1 month later, failed to re-imagine the lesion. Further workup with DSA 1 year after the ictus was negative for pathological findings. CONCLUSIONS There are a lot of controversies regarding the optimal imaging modality for surveillance of pediatric AVMs, the time period needed to follow-up a given lesion, even if it is considered treated, and the underlying mechanism of spontaneous thrombosis of untreated, yet ruptured, AVMs. All these issues, along with the unusual mode of evolution of the clinical picture of this lesion are discussed in detail, along with a review of the available literature.
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http://dx.doi.org/10.12659/AJCR.923289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213815PMC
May 2020

Antithrombotics in intracerebral hemorrhage in the era of novel agents and antidotes: A review.

J Popul Ther Clin Pharmacol 2020 04 3;27(2):e1-e18. Epub 2020 Apr 3.

Department of Neurosurgery, Agia Sofia Children's Hospital, Athens, Greece.

Background: Intracerebral hemorrhage (ICH)1 is characterized by the pathological accumulation of blood within the brain parenchyma, most commonly associated with hypertension, arteriovenous malformations, or trauma. However, it can also present in patients receiving antithrombotic drugs, either anticoagulants such as acenocoumarol/warfarin-novel oral anticoagulants or antiplatelets, for the prevention and treatment of thromboembolic disease.

Objective: The purpose of this review is to present current bibliographic data regarding ICH irrespective of the cause, as well as post-hemorrhage use of antithrombotic agents. Moreover, this review attempts to provide guidelines concerning the termination, inversion, and of course resumption of antithrombotic therapy.

Methods And Materials: We reviewed the most recently presented available data for patients who dealt with intracerebral hemorrhagic events while on antithrombotic agents (due to atrial fibrillation, prosthetic mechanical valves or recent/recurrent deep vein thrombosis). Furthermore, we examined and compared the thromboembolic risk, the bleeding risk, as well as the re-bleeding risk in two groups: patients receiving antithrombotic therapy versus patients not on antithrombotic therapy.

Conclusion: Antithrombotic therapy is of great importance when indicated, though it does not come without crucial side-effects, such as ICH. Optimal timing of withdrawal, reversal, and resumption of antithrombotic treatment should be determined by a multidisciplinary team consisting of a stroke specialist, a cardiologist, and a neurosurgeon, who will individually approach the needs and risks of each patient.
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http://dx.doi.org/10.15586/jptcp.v27i2.660DOI Listing
April 2020

Postoperative Tetraplegia to a Child after Cerebellar Pilocytic Astrocytoma Excision at Prone Position: Case Report and Literature Review.

Am J Case Rep 2020 Mar 12;21:e920213. Epub 2020 Mar 12.

Department of Neurosurgery, Agia Sophia, Pediatric Hospital, Athens, Greece.

BACKGROUND Various factors have been implicated in the pathogenesis of infarction after posterior fossa surgery such as venous air embolism, patient's position (seated or prone), hyperflexion of the neck, excessive spinal cord traction, cervical canal stenosis, and systemic arterial hypotension. The main aim of this case report was to elucidate a case in which hydrogen peroxide was implicated in a major and systemic complication after a neurosurgical procedure. CASE REPORT We describe the case of a 5-year-old female patient who was admitted to our hospital because of a cerebellar hemispheric astrocytoma associated with obstructive hydrocephalus and accompanied by 2 syringomyelic cavities in the cervicothoracic portion of the spinal cord. Immediately after gross total resection of the lesion, impaired mobility of the upper and lower extremities was observed, a finding that was not consistent with intraoperative neurophysiologic monitoring data. Hydrogen peroxide had been judiciously used to irrigate the resection tumor cavity. In the next few postoperative days, the patient suffered from transient diabetes insipidus and hyperpyrexia, indicative of hypothalamic injury. CONCLUSIONS Neurological evaluation of the patient, after stabilization of her medical condition, revealed residual spasticity of upper and lower extremities, rendering her able to mobilize via the aid of wheelchair only. The most possible pathophysiologic explanation of her neurological deterioration, including hypothalamic dysfunction, was analyzed. The role of hydrogen peroxide as a source of free radical formation, and its co-responsibility for vascular platelet aggregation and vasoconstriction was considered, upon case review, the main responsible etiologic factor.
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http://dx.doi.org/10.12659/AJCR.920213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081953PMC
March 2020

The 100 Most Cited Papers About Brain Metastases.

World Neurosurg 2020 06 5;138:98-114. Epub 2020 Mar 5.

Department of Neurosurgery, Pediatric Hospital of Athens, Goudi, Athens, Attica, Greece.

Background: A vast amount of articles centered on brain metastases have been published.

Objective: To present the 100 most-cited articles dedicated to brain metastasis and to accomplish a broad literature review.

Methods: In December 2019, we performed a title-focused search using the Thomson Reuters Web of Science database to identify the most cited articles centered on brain metastatic disease. Our search query term was based on using the following algorithm: "brain metastases" OR "brain metastasis" OR "brain metastatic disease" OR "cerebral metastases" OR "cerebral metastasis" OR "cerebral metastatic disease." Afterward, we reviewed the results to certify that they were relevant to the purposes of our research protocol. The 100 most cited papers were chosen and further analyzed.

Results: Our search resulted in 11,579 articles, published from 1975 until the completion of our survey. The most cited article, by Patchell et al., was published in 1990, with 1862 citations, and an average of 62.07 citations per year, whereas the last in our list, by Gaspar et al., was published in 2010, with 195 total citations, and an average of 19.50 citations per year. Countries with the highest-cited articles included the United States (75 records), followed by Canada (16 records).

Conclusions: We discovered the top 100 most-cited articles centered on brain metastasis, all of which show a potentially increased level of interest, because they are meaningful scientific reports. In addition, we reviewed the historical development and advances in brain metastasis research and relevant points of interest, alongside the relevant contributions of different authors, fields of special interest, and countries. Many of the most cited articles were written by authors whose specialty was not neurosurgery or by neurosurgeons who were supported by colleagues from other medical fields. As a consequence, many of these articles were not published in neurosurgery-dedicated journals.
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http://dx.doi.org/10.1016/j.wneu.2020.02.156DOI Listing
June 2020

Edema of the Floor of the Fourth Ventricle Accompanying Shunt Malfunction and Disappearance of It After Shunt Repair: Case Report and Literature Review.

Am J Case Rep 2019 Dec 25;20:1936-1941. Epub 2019 Dec 25.

Department of Neurosurgery, Agia Sophia Pediatric Hospital, Athens, Greece.

BACKGROUND The ventriculoperitoneal shunt remains, despite recent advances, the mainstay of treatment for hydrocephalus. Although it is used as a routine practice, and besides its recorded and documented safety, it often malfunctions due to a variety of reasons, most commonly referred to as obstruction, breakage, migration and infection. A usual finding of those children suspected to magnetic resonance imaging is the detection of a rim of hyperintensity in the periventricular white matter (halo). CASE REPORT We describe the case of a 7-year-old male patient, treated 4 years ago for an infratentorial ependymoma, who developed hydrocephalus at the time of clinical presentation. During his previous follow-up, he was disease-free but developed clinically evident acute shunt malfunction, accompanied by imaging findings on magnetic resonance imaging (MRI) consisting of interstitial edema surrounding the supratentorial ventricular system, with additional involvement of the floor of the fourth ventricle. This peculiar and novel imaging finding subsided after successful management of hydrocephalus. CONCLUSIONS At present, contemporary computed tomography and MRI modalities constitute the gold standard in order to assess and follow-up patients with established hydrocephalus. Periventricular interstitial edema is a well-established imaging feature of acute hydrocephalus and, in cases of ventriculoperitoneal shunt, of shunt malfunction. Besides that, a newly described, to the best of our knowledge, imaging feature could be the distinction of that signal alteration at the floor of the fourth ventricle. It seems to have prognostic significance regarding the adequacy of management of hydrocephalus, as it disappeared after its successful treatment.
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http://dx.doi.org/10.12659/AJCR.919893DOI Listing
December 2019

Recurrent arterial ischemic strokes in a patient with patent foramen ovale and ductus arteriosus: Presentation of our management and review of the literature.

Glob Cardiol Sci Pract 2019 Sep 20;2019(2):e201913. Epub 2019 Sep 20.

Cardiology Department of Pediatric Hospital of Athens, 'Agia Sophia', Thivon & Papadiamantopoulou St, Goudi, 11527 Athens, Greece.

Ischemic stroke in children is a relatively rare entity, relative to the adult population. The most common potential risk factors include cardiac embolism, prothrombotic states and vasculopathies. The diagnosis is concerning for the need to identify the underlying cause. Treatment of the proximate source of ischemia can often protect against future events. We present the case of a 7-year-old patient who initially presented with an ischemic brain insult which was repeated, despite the initiation of anticoagulation therapy. The investigation revealed patent foramen ovale and patent ductus arteriosus and because of the recurrent ischemic ictuses, transcatheter closure of both defects was decided. A brief description of the literature is also presented.
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http://dx.doi.org/10.21542/gcsp.2019.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865199PMC
September 2019

Severe Neuromuscular Scoliosis Implicated by Dysfunction of Intrathecal Baclofen Pump: Case Report and Review of the Literature.

World Neurosurg 2020 Feb 13;134:390-395. Epub 2019 Nov 13.

Neurosurgical Department, Pediatric Hospital of Athens, Agia Sophia, Athens, Greece.

Background: Complex spinal deformities are a common issue in pediatric patients with an underlying neurologic diagnosis or syndrome. Management of neuromuscular scoliosis is an awesome responsibility, because these patients present with the most challenging pathologies of the deformed spine. Along with surgical correction of the underlying deformity, an intrathecal baclofen (ITB) pump is considered effective in managing the associated spasticity.

Case Description: We present the case of an 11-year-old female who sustained an episode of severe ischemic encephalopathy accompanied by hydrocephalus and severe spastic quadriplegia. An ITB pump was inserted to manage spasticity. Two years later, a very severe decompensated spinal curvature developed. In addition, malfunction of the pump was noted, and the decision was made to perform revision along with open hemilaminectomy at the L3-4 level. The inability of cerebrospinal fluid (CSF) to access the pump was verified intraoperatively, with the absence of CSF glow through the intrathecal space demonstrating blockage of CSF flow.

Conclusions: The association of cerebral palsy and relevant disorders with the relentless progression of scoliosis is analyzed, along with the possible offending mechanisms. The efficacy of an ITB pump in controlling intractable spasticity associated with neuromuscular scoliosis is reviewed, as well as its potential to accentuate the clinical progression of neuromuscular scoliosis. Although this is an extremely infrequent situation, we must always bear in mind the possibility that malfunction of an ITB pump could be related to obstruction of CSF flow, owing to the extreme severity of the curves established during the course of, most likely untreated, neuromuscular scoliosis.
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http://dx.doi.org/10.1016/j.wneu.2019.11.027DOI Listing
February 2020

Central nervous system manifestation of lupus erythematosus resembling brain abscess.

Int J Pediatr Adolesc Med 2019 Mar 26;6(1):29-37. Epub 2018 Nov 26.

Neurosurgical Department of Pediatric Hospital of Athens, 'Agia Sophia', Thivon & Papadiamantopoulou St, Goudi, Athens, Attica, 11527, Greece.

Manifestations of central nervous system involvement are one of the leading causes of morbidity and mortality in patients suffering from systemic lupus erythematosus. It frequently involves the central nervous system and sometimes need to be differentiated from lesions of infectious etiology, thus representing a major diagnostic dilemma. We present the case of a male adolescent with a known history of idiopathic thrombocytopenic purpura who presented with a seizure ictus and a space-occupying lesion, which posed significant diagnostic challenges to specify its characteristics.
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http://dx.doi.org/10.1016/j.ijpam.2018.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603070PMC
March 2019

Herpes Simplex Encephalitis Initially Erroneously Diagnosed as Glioma of the Cerebellum: Case Report and Literature Review.

World Neurosurg 2019 Sep 26;129:421-427. Epub 2019 Jun 26.

Neurosurgical Department, Pediatric Hospital of Athens, 'Agia Sophia', Athens, Greece.

Background: Herpes simplex encephalitis caused by herpes simplex has an estimated annual prevalence in the order of 1 in 250,000 to 500,000 patients and is considered to be the most usually encountered nonendemic pathogenic cause of lethal encephalitis in well-developed countries. There are a few cases reported in the literature in which a diagnostic dilemma between was raised between herpes simplex encephalitis and brain glioma and a definitive diagnosis was difficult to obtain.

Case Description: We report the case of a 5-year-old girl with a previous medical history of premature thelarche. As a part of her investigation, magnetic resonance imaging of the brain was performed, which revealed a space-occupying lesion of the posterior fossa. Magnetic resonance spectroscopy was performed, which advocated for the diagnosis of glioma. She was operated on, but the histopathologic analysis failed to verify the imaging findings. Herpes simplex virus (HSV) 1 was detected in cerebrospinal fluid (CSF) samples. Follow-up magnetic resonance imaging scans illustrated the progression of the disease.

Conclusions: The accumulation of data regarding CSF sample analysis, electroencephalography, brain biopsy, and imaging findings, along with the progression of the clinical picture of our patient, verified the diagnosis of HSV encephalitis. When confronted with confounding data that can pose a diagnostic dilemma between HSV encephalitis and glioma, brain biopsy and polymerase chain reaction of CSF samples could be able to verify the definitive diagnosis. When interpreting our results, we always have to consider the evolution of the clinical picture.
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http://dx.doi.org/10.1016/j.wneu.2019.06.158DOI Listing
September 2019

Primary, Dural-Based, Ewing Sarcoma Manifesting with Seizure Activity: Presentation of a Rare Tumor Entity with Literature Review.

World Neurosurg 2019 Sep 14;129:216-220. Epub 2019 Jun 14.

Neurosurgical Department of Pediatric Hospital of Athens, Agia Sophia, Attica, Greece.

Background: Primary Ewing sarcoma arising from the calvarial bone and/or underlying dura matter are relatively rarely reported in the literature. Even rarer are considered to be those that originate from the dura and proliferate in both directions, toward the brain parenchyma and through the dura invading the overlying bone.

Case Description: We report the case of a girl aged 11 years who presented with an ictus of generalized tonic-clonic seizures, without known focal neurologic deficit. Neuroradiologic work-up verified the existence of a tumor in the right fronto-parietal area of the brain, invading both the bone and brain parenchyma and emanating from the dura. No other tumor location was discovered after radiologic work-up, and gross total resection was undertaken followed by adjuvant radiation therapy and chemotherapy.

Conclusions: The patient had an uneventful neurologic recovery without persistent neurologic deficit. One year after the operation, with the patient under close clinical and radiologic surveillance, no recurrence of the disease was detected. This case illustrates an extremely uncommon location of primary Ewing sarcoma, along with a constellation of clinical signs and symptoms that are fairly uncommon for this location of this rare disease entity.
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http://dx.doi.org/10.1016/j.wneu.2019.06.036DOI Listing
September 2019

Intraparenchymal Pericatheter Cyst after Cerebrospinal Fluid Shunt: A Rare Complication with Challenging Diagnosis - Case Presentation and Review of the Literature.

Asian J Neurosurg 2019 Apr-Jun;14(2):581-584

Department of Neurosurgery, Children Hospital "Aghia Sophia", Athens, Greece.

An intraparenchymal pericatheter cyst is a rare complication of ventriculoperitoneal shunt, which is not well described yet. Due to its rarity, lack of characteristic symptoms and radiological features that often mimic brain tumors or abscesses, especially in head computed tomography without contrast can be easily misdiagnosed. We report the case of a 9-year-old girl who was admitted to a peripheral hospital due to severe headaches and vomiting. The child had a history of craniotomy and ventriculoperitoneal shunt for posterior fossa tumor, performed in our department, 4 years earlier. The patient underwent a brain magnetic resonance imaging (MRI) scan and transmitted to our hospital with the diagnosis of brain tumor. However, a closer look at the MRI established the diagnosis of intraparenchymal pericatheter cerebrospinal fluid cyst; hence, the patient underwent shunt revision and cyst drainage. We researched the literature and described 20 reported cases, discussing the pathophysiological mechanisms, the radiological features, and the optimal treatment of this interesting, yet a challenging complication.
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http://dx.doi.org/10.4103/ajns.AJNS_288_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515991PMC
May 2019

Repair of a Transclival Meningocele Through a Transoral Approach: Case Report and Literature Review.

World Neurosurg 2019 Mar 19;123:259-264. Epub 2018 Dec 19.

Neurosurgical Department, "Agia Sophia" Children's Hospital, Athens, Greece.

Background: Transclival meningoceles and related primary spontaneous cerebrospinal fluid leaks at the clivus are extremely rare lesions, with only a few cases reported in the literature.

Case Description: An infant presented with nasal airway obstruction and meningitis secondary to cerebrospinal fluid leak from a transclival meningocele. The radiologic investigation and surgical repair of the lesion are reported, along with intraoperative findings. Basic anatomy, embryology, and development of the clivus are reviewed to clarify the relationship of anatomic variants with the formation of transclival meningoceles.

Conclusions: Transclival meningocele should be considered in patients with spontaneous cerebrospinal fluid rhinorrhea. The existing classification of meningoencephaloceles based on the location of the defect in the cranium should probably be reconsidered, taking into consideration the described entity.
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http://dx.doi.org/10.1016/j.wneu.2018.12.025DOI Listing
March 2019

Torkildsen shunt as a salvage procedure for an infant with post-hemorrhagic hydrocephalus.

Int J Surg Case Rep 2019 27;54:1-6. Epub 2018 Nov 27.

Thivon & Papadiamantopoulou St, Goudi, 11527, Athens, Attica, Greece. Electronic address:

Introduction: Torkildsen operation is a ventriculo-cisternal shunt that diverts the cerebrospinal fluid flow from one of the lateral ventricles, via a ventricular catheter, to the cisterna magna of the posterior fossa. It is the first described operation of CSF diversion for the treatment of hydrocephalus [1] (Scarff, 1963).

Presentation Of Case: We present the case of a premature infant who presented with post hemorrhagic hydrocephalus who underwent several failed CSF diversion surgeries before Torkildsen shunt procedure. The patient overcame the irregularities of CSF circulation that were observed before the operation and his post-operative course was uneventful, in terms of CSF -related complications.

Discussion: We summarize the historical data and the technical aspects of the procedure, and we present a brief literature review of the indications and limitations associated with it.

Conclusion: Torkildsen shunt can be effective in selected patients with hydrocephalus even in the modern era of computed tomography and magnetic resonance imaging. the procedure enables one to avoid a standard ventriculoperitoneal shunt, especially in cases it is not technically feasible.
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http://dx.doi.org/10.1016/j.ijscr.2018.11.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277217PMC
November 2018

A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas.

J Cardiovasc Electrophysiol 2018 12 5;29(12):1624-1634. Epub 2018 Oct 5.

Myocardial Function Section, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, UK.

Introduction: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation.

Methods And Results: High frequency stimulation was delivered through a Smart-Touch catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. Three dimensional locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia, or no effect. CARTO maps were exported, registered, and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated (AVD-GP) effects. There were 10 AVD-GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD-GPs (>20%) was identified in: inferoseptal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%).

Conclusion: It is feasible to map the entire left atrium for AVD-GPs before AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterize the autonomic network.
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http://dx.doi.org/10.1111/jce.13723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369684PMC
December 2018

The use of an esophageal catheter to check the results of left atrial posterior wall isolation in the treatment of atrial fibrillation.

Pacing Clin Electrophysiol 2018 10 3;41(10):1345-1355. Epub 2018 Sep 3.

South-West Cardiothoracic Centre, Plymouth Hospitals NHS Trust, Derriford Hospital, Plymouth, PL68DH, UK.

Background: Left atrial posterior wall isolation (LAPWI) via catheter, surgical, and hybrid techniques is a promising treatment for persistent atrial fibrillation (PersAF). We investigated whether confirmation of LAPWI can be achieved using an esophageal pacing and recording electrode.

Methods: Patients undergoing PersAF ablation with the intention to achieve LAPWI were enrolled. Two approaches to LAPWI were tested: (1) ablation using endocardial catheter ablation only, and (2) "Staged Hybrid" ablation with thoracoscopic epicardial ablation, followed by endocardial left atrial electrophysiological study and catheter ablation where necessary. Patients enrolled in the study all required further catheter ablation to achieve LAPWI in this group. In both the groups, esophageal recording and esophageal pacing was performed at the start of mapping and electrophysiological study and compared with endocardial electrophysiological findings. This was repeated at the end of the procedure.

Results: Twenty patients (16 M, four F) were studied. Endocardial electrophysiological study showed that in none of the cases was the posterior left atrial wall electrically isolated at the start of the study. One patient with Barrett's esophagus failed to sense or pace from the esophagus at any point in the study. In the remaining 19/19, esophageal pacing captured the atrial rhythm at the start of the procedure. LAPWI was then achieved in 17/19 using endocardial catheter ablation; retesting at this point showed sensing and capture of the atrium from the esophagus was abolished. In the remainder sensing and capture persisted.

Conclusions: Esophageal pacing can be used to confirm or refute electrical isolation of the left atrial posterior wall.
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http://dx.doi.org/10.1111/pace.13471DOI Listing
October 2018

Cerebral hemorrhagic infarction as the initial manifestation of deep venous thrombosis in a child with patent foramen ovale.

Glob Cardiol Sci Pract 2018 Jun 30;2018(2):17. Epub 2018 Jun 30.

Hemodynamic Cardiology Department, Pediatric hospital "Agia Sophia", Athens, Greece.

Arterial ischemic stroke (AIS), with an estimated incidence of 1.1-4.3 per 100,000, is an important cause of morbidity and mortality in children and the risk of recurrence is high. We present the case of an 11-year-old child who presented with a symptomatology of acute ischemic stroke of unknown etiology. The radiological investigation did not reveal any underlying brain abnormality that could cause the event. The diagnostic work up included an echocardiogram, which revealed a thrombus in the right atrium, in conjunction with a patent foramen ovale. The patient was initiated immediately on anticoagulation therapy with low molecular weight heparin and warfarin, but two days later she suffered pulmonary emboli, diagnosed with spiral thorax computed tomography (CT) scan. An ultrasound study of the vessels of the lower extremitiesgcsp201817-main-client.xml revealed deep venous thrombosis (DVT), which was considered to be the underlying causative mechanism.
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http://dx.doi.org/10.21542/gcsp.2018.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062758PMC
June 2018

Thrombo-embolic events in left ventricular endocardial pacing: long-term outcomes from a multicentre UK registry.

Europace 2018 12;20(12):1997-2002

Cardiac Arrhythmia Research, Barts Heart Centre, West Smithfields, London, UK.

Aims: Endocardial left ventricular (LV) pacing is a viable alternative in patients with failed coronary sinus (CS) lead implantation. However, long-term thrombo-embolic risk remains unknown. Much of the data have come from a small number of centres. We examined the safety and efficacy of endocardial LV pacing to determine the long-term thrombo-embolic risk.

Methods And Results: Registries from four UK centres were combined to include 68 patients with endocardial leads with a mean follow-up of 20 months. These were compared to a matched 1:2 control group with conventional CS leads. Medical records were reviewed, and patients contacted for follow-up. Ischaemic stroke occurred in four patients (6%) in the endocardial arm providing an annual event rate (AER) of 3.6% over a 20 month follow-up; compared to 9 patients (6.6%) amongst controls with an AER of 3.4% over a 23-month follow-up. Regression analyses showed a significant association between sub-therapeutic international normalized ratio and stroke (P = 0.0001) in the endocardial arm. There was no association between lead material and mode of delivery (transatrial/transventricular) and stroke. Mortality rate was 12 and 15 per 100 patient years in the endocardial and control arm respectively with end-stage heart failure being the commonest cause.

Conclusion: Endocardial LV lead in heart failure patients has a good success rate at 1.6 year follow-up. However, it is associated with a thrombo-embolic risk (which is not different from conventional CS leads) attributable to sub-therapeutic anticoagulation. Randomized control trials and studies on non-vitamin K antagonist oral anticoagulants are required to ascertain the potential of widespread clinical application of this therapeutic modality.
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http://dx.doi.org/10.1093/europace/euy107DOI Listing
December 2018

The Effect of Atrial Fibrillation Ablation Techniques on P Wave Duration and P Wave Dispersion.

Heart Lung Circ 2019 Mar 14;28(3):389-396. Epub 2018 Feb 14.

Southwest Cardiothoracic Centre, Derriford Hospital, Plymouth, UK.

Background: A reduction in surface electrocardiogram (ECG) P wave duration and dispersion is associated with improved outcomes in atrial fibrillation ablation. We investigated the effects of different ablation strategies on P wave duration and dispersion, hypothesising that extensive left atrial (LA) ablation with left atrial posterior wall isolation would give a greater reduction in P wave duration than more limited ablation techniques.

Methods: A retrospective analysis of ECGs from patients who have undergone atrial fibrillation (AF) ablation was performed and pre-procedural sinus rhythm ECGs were compared with the post procedure ECGs. Maximal P wave duration was measured in leads I or II, minimum P wave duration in any lead and values were calculated for P wave duration and dispersion. Left atrial dimensions and medications at the time of ECG were documented. Ablation strategies compared were; pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) and the persistent AF (PsAF) ablation strategies of pulmonary vein isolation plus additional linear lesions (Lines), left atrial posterior wall isolation via catheter (PWI) and left atrial posterior wall isolation via staged surgical and catheter ablation (Hybrid).

Results: Sixty-nine patients' ECGs were analysed: 19 PVI, 21 Lines, 14 PWI, 15 Hybrid. Little correlation was seen between pre-procedure left atrial size and P wave duration (r=0.24) but LA size and P wave duration was larger in PsAF patients. A significant difference was seen in P wave reduction driven by Hybrid AF ablation (p<0.005) and Lines (<0.02). There was no difference amongst P wave dispersion between groups but the largest reduction was seen in the Hybrid ablation group.

Conclusions: P wave duration increased with duration of continuous atrial fibrillation. Hybrid AF ablation significantly reduced P wave duration and dispersion compared to other ablation strategies including posterior wall isolation via catheter despite this being the same lesion set.
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http://dx.doi.org/10.1016/j.hlc.2018.02.003DOI Listing
March 2019

Intradural-Extramedullary Cervical Cord Lipoma: Case Report and Literature Review.

World Neurosurg 2018 02 14;110:162-168. Epub 2017 Nov 14.

Department of Neurosurgical Department, Aglaia Kyriakou Pediatric Hospital of Athens, Athens, Attica, Greece.

Background: Spinal lipomas are generally thought to occur as a result of failed primary neurulation. Failed primary neurulation allows invasion of mesenchymal tissue of mesodermic origin into the neural structure, leading to the formation of a spinal lipoma. Despite most spinal lipomas being regarded as the result of failed primary neurulation, some confusion in terms of the embryogenesis of spinal lipomas remains. Recently, a novel classification of spinal lipomas based on embryonic changes seen during primary and secondary neurulation was has been proposed.

Case Description: We present a case of an intradural-extramedullary spinal cord lipoma, associated with a subjacent subcutaneous lipoma at the cervicothoracic region. The patient presented with worsening neurologic symptoms, indicating ongoing cervical myelopathy. A subtotal resection along with posterior cervical stabilization was achieved, with mild improvement of neurologic symptoms. Clinical, pathologic, and radiologic records are reviewed.

Conclusions: To the best of our knowledge, this is the first described case of a spinal cord lipoma with at such a location, one that cannot be fully categorized within the newly proposed classification system.
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http://dx.doi.org/10.1016/j.wneu.2017.11.029DOI Listing
February 2018

Triazole double-headed ribonucleosides as inhibitors of eosinophil derived neurotoxin.

Bioorg Chem 2015 Dec 31;63:152-65. Epub 2015 Oct 31.

Department of Biochemistry and Biotechnology, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece. Electronic address:

Eosinophil derived neurotoxin (EDN) is an eosinophil secretion protein and a member of the Ribonuclease A (RNase A) superfamily involved in the immune response system and inflammatory disorders. The pathological actions of EDN are strongly dependent on the enzymatic activity and therefore, it is of significant interest to discover potent and specific inhibitors of EDN. In this framework we have assessed the inhibitory potency of triazole double-headed ribonucleosides. We present here an efficient method for the heterologous production and purification of EDN together with the synthesis of nucleosides and their biochemical evaluation in RNase A and EDN. Two groups of double-headed nucleosides were synthesized by the attachment of a purine or a pyrimidine base, through a triazole group at the 3'-C position of a pyrimidine or a purine ribonucleoside, respectively. Based on previous data with mononucleosides these compounds were expected to improve the inhibitory potency for RNase A and specificity for EDN. Kinetics data revealed that despite the rational, all but one, double-headed ribonucleosides were less potent than the respective mononucleosides while they were also more specific for ribonuclease A than for EDN. Compound 11c (9-[3'-[4-[(cytosine-1-yl)methyl]-1,2,3-triazol-1-yl]-β-d-ribofuranosyl]adenine) displayed a stronger preference for EDN than for ribonuclease A and a Ki value of 58μM. This is the first time that an inhibitor is reported to have a better potency for EDN than for RNase A. The crystal structure of EDN-11c complex reveals the structural basis of its potency and selectivity providing important guidelines for future structure-based inhibitor design efforts.
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http://dx.doi.org/10.1016/j.bioorg.2015.10.007DOI Listing
December 2015

Iodonium metathesis reactions.

Angew Chem Int Ed Engl 2014 Sep 14;53(36):9637-9. Epub 2014 Jul 14.

Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1 (Canada).

A metathesis reaction occurs when a diaryliodonium triflate is heated with an aryl iodide, resulting in the formation of a new diaryliodonium triflate.
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http://dx.doi.org/10.1002/anie.201405594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590373PMC
September 2014

Aggregatibacter aphrophilus brain abscess secondary to primary tooth extraction: Case report and literature review.

J Microbiol Immunol Infect 2016 Feb 12;49(1):119-22. Epub 2014 Feb 12.

Department of Neurosurgery, University Hospital of Heraklion, Heraklion, Crete, Greece.

We report on a rare case of Aggregatibacter aphrophilus brain abscess of odontogenic origin in a 6-year-old previously healthy boy, who had close contact with a pet dog. The poodle was the most likely source of the infecting organism, which subsequently colonized the patient's oral cavity. The abscess was surgically removed and he recovered completely after prolonged antibiotic treatment with meropenem. We also review the relevant medical literature on A. aphrophilus pediatric brain abscesses.
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http://dx.doi.org/10.1016/j.jmii.2013.12.007DOI Listing
February 2016