Incidence of Type 1 Diabetes Mellitus and Characteristics of Diabetic Ketoacidosis in Children and Adolescents during the First Two Years of the COVID-19 Pandemic in Vojvodina.

Background and Objectives: The COVID-19 pandemic has led to significant changes globally, which has also affected patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the incidence of T1DM and the characteristics of diabetic ketoacidosis (DKA) during the pandemic comparing it to pre-pandemic period. Materials and Methods: Data from patients <19 years with newly diagnosed T1DM between 1st January 2017 and 31st December 2021 from four regional centers in Vojvodina were retrospectively collected and analyzed. Results: In 2021, the highest incidence of T1DM in the last five years was recorded, 17.3/100,000. During the pandemic period (2020−2021), there were 99 new-onset T1DM, of which 42.4% presented in DKA, which is significantly higher than in the pre-pandemic period (34.1%). During the pandemic, symptom duration of T1DM lasted significantly longer than before the COVID-19 period. At the age of 10−14 years, the highest incidence of T1DM and COVID-19, the highest frequency rate of DKA, and severe DKA were observed. Conclusions: The pandemic is associated with a high incidence rate of T1DM, longer duration of symptoms of T1DM, a high frequency of DKA, and a severe DKA at diagnosis. Patients aged 10−14 years are a risk group for the occurrence of T1DM with severe clinical presentation. Additional studies are needed with a longer study period and in a wider geographical area, with data on exposure to COVID-19 infection, the permanence of new-onset T1DM, and the psychosocial impact of the pandemic.

Evolution of acute "black hole" lesions in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: Gadolinium-enhanced T1-weighted lesions are a well-established marker of areas with acute inflammatory activity. A majority of these gadolinium-enhanced T1 lesions are isointense relative to the surrounding white matter, but 20-40% of such active lesions will evolve during one year into areas of low signal ("black hole"). This study sought to characterize evolution of "black hole" lesions in patients with relapsing-remitting multiple sclerosis (MS) using the magnetic resonance imaging (MRI), which measures active lesions via the count of new or enlarged T2 and gadolinium-enhanced T1-weighted lesions. MATERIALS AND METHODS: This was a prospective, observational case-series study which utilized pre- and post-gadolinium contrast T1-weighted and Proton density MRI scans. Twenty-nine patients (8 males and 21 females) with average age of 38.86 ± 6.58 years and disease duration of 5.75 ± 7.00 years were used to analyze 196 acute demyelinating plaques detected on MRI images during the 24-month follow-up of post-gadolinium signal intensity enhancement of MS plaques. RESULTS: Significant difference in black hole development was found between the shapes of acute and chronic "black holes". Ring-shaped and patchy plaques were 4.09 (1.87-8.91) times more likely and 1.49 (0.71-3.12) times less likely to develop an acute "black holes" than homogeneous plaques, respectively. Acute plaques with higher lesion-to-CSF SI ratio and larger surface area showed a greater tendency to develop into acute and chronic "black holes". CONCLUSIONS: The value of lesion-to-CSF SI ratio and surface area were found as the predictors of the "black hole" formation.

Partial rhombencephalosynapsis: prenatal MR imaging diagnosis and postnatal follow up.

We present a case of partial rhombencephalosynapsis, diagnosed by magnetic resonance imaging (MRI), in fetus aged 27 gestational weeks, in a dizygotic twin pregnancy. The distinctive MRI features of this cerebellar malformation (segmental hypogenesis of the cerebellar vermis, partial fusion of the cerebellar hemispheres and dentate nuclei) without associated cerebral abnormalities were confirmed by 32-weeks prenatal and 3-months postnatal MRI studies. At the age of 12 months the affected twin had a slight delay in psychomotor development, mild hypotonia with normal cognitive development. To the authors' best knowledge, this is the first report of a fetal case with isolated partial rhombencephalosynapsis. Its MRI features enlarges the narrow spectrum of uncommon variants of rhombencephalosynapsis, and allow an accurate differentiation from other vermian and cerebellar anomalies with less favorable postnatal outcome.

Kawasaki Disease Complicated with Cerebral Vasculitis and Severe Encephalitis.

We report a case of a 7-year-old boy with Kawasaki disease (KD) complicated with cerebral vasculitis and encephalitis. The patient was admitted with signs of encephalopathy, seizures, and coma. The diagnosis of KD was made on the 2nd day of hospitalization based on the clinical features (fever >5 days, maculopapular rash, nonpurulent conjunctivitis, fissured lips, and cervical adenopathy). Brain magnetic resonance imaging findings suggested cerebral vasculitis. Treatment with intravenous immunoglobulin was followed by mild improvement. After a single dose of immunoglobulin, pulse methylprednisolone therapy was started resulting in gradual improvement of consciousness and eventual complete motor and cognitive function recovery with regression of brain magnetic resonance lesions. KD can present with marked neurological symptomatology. Therefore, it should be considered in the differential diagnosis of encephalitis and encephalopathy etiologies in children.

Transient cortical blindness following vertebral angiography in a young adult with cerebellar haemangioblastoma.

Transient cortical blindness is reported to occur in 0.3% to 1% of cerebral angiography procedures. It develops within minutes of contrast medium injection and lasts for up to several days. We report a long episode of transient cortical blindness in a 17-year-old boy with cerebellar haemangioblastoma, which started during the preoperative vertebral angiography and lasted for 5 days. CT performed 2 days after the sudden onset of bilateral visual loss showed multiple asymmetrical lesions within the brain parenchyma in the distribution of the posterior cerebral circulation. Even though the patient's vision was completely restored 5 days after angiography, repeat MRI performed 2 months after angiography showed improvement but with residual lesions in the thalami, cerebellum and occipital lobe.

Brain white matter 1 H MRS in Leber optic neuropathy mutation carriers.

OBJECTIVE: This study was conducted in order to test the hypothesis that proton MR spectroscopic (1H MRS) profile of Leber's hereditary optic neuropathy (LHON) mutation carriers group (including both symptomatic and asymptomatic) differs from group of healthy individuals and to determine metabolite or ratio that contributes most to differentiation. PATIENTS AND METHODS: We performed single voxel 1H MRS in normal appearing white matter of eighteen LHON mtDNA mutation carriers bearing one of three LHON mtDNA point mutations and in fifty control subjects. RESULTS: ANOVA showed significant difference for absolute concentration of creatine (Cr) (p < 0.01) and N-acetylaspartate to creatine ratio (NAA/Cr) (p < 0.01). Discriminant analysis revealed that decreased absolute Cr followed by decreased absolute NAA concentration have the most significant contribution in discriminating LHON mutation carriers from healthy controls. CONCLUSION: Abnormal metabolic profile in normal appearing white matter on MR imaging seems to be significantly present in LHON mutation carriers.

Intrauterine treatment of large fetal neck lymphangioma with OK-432.

Lymphangiomas are benign vascular malformations of the lymphatic system and most commonly present in the neck area. Large lymphangiomas may compress and/or displace the larynx, trachea and esophagus and cause serious respiratory and feeding problems in neonates. Prenatal therapy could eliminate the risks of the mentioned complications. Prenatal therapy may include the EXIT (ex utero intrapartum treatment) procedure. As this procedure has certain risks for both the neonate and mother, the introduction of a safer method is justified. The use of OK-432, as a sclerosing agent, has shown positive results in several published cases of cystic hygroma, but there is no study about the prenatal use of this agent in the treatment of lymphangioma. The aim of this study was to present our experience with intrauterine intralesional injection of OK-432 in the treatment of neck lymphangiomas. Two cases of large multicystic neck lymphangiomas that were closely situated to the fetal airway were treated by single intralesional injection of OK-432. We noticed a progressive decrease in tumor volume throughout gestation. We did not experience any complications and there were no respiratory or feeding problems in the neonates. The esthetical appearance was satisfactory and both children were normal at the age of 2 years and 6 months, respectively. This report suggests that prenatal intralesional injection of OK-432 might be a safe and effective treatment in selected cases with large fetal neck lymphangiomas.

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

BACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

DYKE-DAVIDOFF-MASSON SYNDROME - TYPICAL IMAGING FEATURES.

INTRODUCTION: Dyke-Davidoff-Masson syndrome is an uncommon neurological disorder clinically presented with seizures, various degrees of mental retardation, motor weakness and sometimes body asymmetry. Typical neuroimaging features include cerebral hemiatrophy with ipsilateral hyper pneumatization of paranasal sinuses. The purpose of this report was to present a rare cause of seizures revealed by Magnetic resonance imaging. CASE REPORT: We report a case of a 17-year-old boy admitted to hospital due to a severe headache. He had been treated because of partial epileptic seizures for six years. Neuropsychological examination revealed mild mental retardation, mild speech and reading difficulties and discrete right-sided hemiparesis. Typical magnetic resonance imaging features confirmed clinical suspicion of Dyke-Davidoff-Masson syndrome. revealing left frontal lobe atrophy, with consecutive widening of the left lateral ventricle frontal horn, thickening of the nearby frontal squama and hypertrophy of left frontal sinus. CONCLUSION: Magnetic resonance imaging is the key imaging modality that confirms clinical suspicion of Dyke-Davidoff-Masson syndrome based on a proper physical and neurological examination.

Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation.

Case studies of unusual traits can provide unique snapshots of the effects of modified systems. In this study, we report on an individual from a Serbian family with the ability to rapidly, accurately and voluntarily speak backwards. We consider psychological, neural and genetic correlates of this trait to identify specific relevant neural mechanisms and new molecular pathways for working memory and speech-related tasks. EEG data suggest that the effect of word reversal precedes semantic integration of visually presented backward-words, and that event-related potentials above the frontal lobe are affected by both word reversal and the maintenance of backward-words in working memory. fMRI revealed that the left fusiform gyrus may facilitate the production of backward-speech. Exome sequencing identified three novel coding variants of potential significance in the RIC3, RIPK1 and ZBED5 genes. Taken together, our data suggest that, in this individual, the ability to speak backwards is afforded by an extraordinary working memory capacity. We hypothesise that this is served by cholinergic projections from the basal forebrain to the frontal cortex and supported by visual semantic loops within the left fusiform gyrus and that these neural processes may be mediated by a genetic mutation in RIC3; a chaperone for nicotinic acetylcholine receptors.

Emery-Dreiffus muscular dystrophy: MR imaging and spectroscopy in the brain and skeletal muscle.

Emery-Dreifuss muscular dystrophy is a rare disorder characterized by childhood onset of contractures, humeroperoneal muscle atrophy, and cardiac conduction abnormalities. This report presents the cases of two brothers with this dystrophy in whom bilateral hypomyelination of the deep periatrial white matter was noted. In the hypomyelinated regions, a prominent peak centered at 1.5 parts per million was present on short-TE MR spectra likely representing prominence of proteolipids in the macromolecular region. Major peaks (N-acetyl-aspartate, creatine, choline, and myoinositol) were normal. With respect to muscle changes, atrophy of the medial head of the gastrocnemius muscle was noted at MR imaging, and phosphorus spectroscopy of this muscle revealed decreased phosphocreatine and inorganic phosphate peaks.

The functional neuroimaging evidence of cerebellar involvement in the simple cognitive task.

Cerebellar involvement in cognitive functions has been revealed in numerous anatomical, clinical and neuroimaging studies and several hypotheses about potential the role of the cerebellum in higher level brain function have been established. The aim of this study was to show involvement of the cerebellum in simple cognitive tasks. For this matter, we contrasted two tasks from the same semantic domain with specific cognitive content and level of practice: counting forward and counting backward. Twelve volunteers participated in this fMRI study and they were asked to perform both tasks within the same number range (1 to 30 and vice versa). Results showed greater activation in the right cerebellum for the task of counting forward than for counting backward, while for counting backward greater activation was found in prefrontal cortex, supplementary motor area, and anterior cingulate of both hemispheres. Our results correlate with already established hypotheses about cerebellar role in precise and smooth control, not only in well-trained motor but in well trained cognitive tasks as well.

L-2-Hydroxyglutaric aciduria: a case report.

INTRODUCTION: L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disease with a slowly progressive course and characterized by increased levels of hydroxyglutaric acid in urine, cerebrospinal fluid and plasma. In this condition clinical features mainly consist of mental deterioration, ataxia and motor deficits. CASE OUTLINE: The patient is a 16-year-old girl, the first and only child of healthy, non-consanguineous parents of Serbian origin. At the age of 4 years her walk became unsteady and ataxic. Other signs of cerebellar involvement were soon observed. Head circumference was above two standard deviations (55 cm). Mild mental retardation was revealed by formal intelligence testing (IQ 60). MR examination of the brain showed confluent subcortical white matter lesions spread centripetally, and atrophy of the cerebellar vermis with involvement of dentate nuclei, without deep white matter abnormalities. Laboratory investigation revealed increased amounts and a very large peak of HGA in urine and plasma. Enantiomeric analysis confirmed the L-configuration (> 90%) establishing the diagnosis of L-2-HGA. The first epileptic seizure, partial with secondary generalization, occurred at age of 8 years. Favorable seizure control was achieved. A slow progression of neurological impairment was noted. Therapeutic trials with oral coenzyme Q10 and with oral riboflavin showed no biochemical and clinical effects. Recently, the diagnosis was proven by the presence of a mutation in the L-2-HGA gene. CONCLUSION: To our knowledge, this is the first report of L-2-HGA in Serbia. L-2-HGA must be considered in the differential diagnosis based on specific findings in cranial MRI.

Dynamic magnetic resonance imaging of endoscopic third ventriculostomy patency with differently acquired fast imaging with steady-state precession sequences.

The aim of the study was to determine the possibilities of two differently acquired two-dimensional fast imaging with steady-state precession (FISP 2D) magnetic resonance sequences in estimation of the third ventricle floor fenestration patency after endoscopic third ventriculostomy (ETV) in the subjects with aqueductal stenosis/obstruction.Fifty eight subjects (37 males, 21 females, mean age 27 years) with previously successfully performed ETV underwent brain MRI on 1.5T MR imager 3-6 months after the procedure. Two different FISP 2D sequences (one included in the standard vendor provided software package, and the other, experimentally developed by our team) were performed respectively at two fixed slice positions: midsagittal and perpendicular to the ETV fenestration, and displayed in a closed-loop cinematographic format in order to estimate the patency. The ventricular volume reduction has been observed as well.Cerebrospinal fluid (CSF) flow through the ETV fenestration was observed in midsagittal plane with both FISP 2D sequences in 93.11% subjects, while in 6.89% subjects the dynamic CSF flow MRI was inconclusive. In the perpendicular plane CSF flow through the ETV fenestration was visible only by use of experimentally developed FISP 2D (TR30/FA70) sequence. Postoperative volume reduction of lateral and third ventricle was detected in 67.24% subjects.Though both FISP 2D sequences acquired in midsagittal plane may be used to estimate the effects of performed ETV, due to achieved higher CSF pulsatile flow sensitivity, only the use of FISP 2D (TR30/FA70) sequence enables the estimation of the treatment effect in perpendicular plane in the absence of phase-contrast sequences. 

[Ultrasonography and magnetic resonance imaging in prenatal diagnosis of tumour of the foetal head and neck].

INTRODUCTION: Foetal tumours are relatively rare; prenatal diagnosis enables additional diagnostics, and thus the decision on the continuation of pregnancy and planning of delivery. The paper presents prenatal ultrasound diagnostics of foetal head tumour with additionally analyzed magnetic resonance imaging (MRI). CASE OUTLINE: On ultrasound imaging, in a 27-year-old nullipara, a tumour of the foetal head was suspected at the 22nd gestational week. By consultative ultrasound, a 45 x 41 x 50 mm echogenic soft tissue tumour with hypoechogenic areas was confirmed, which originated from the left side of the skull spreading towards the neck on the left behind the ear. On colour Doppler no vascularisation was seen within the tumour but several vessels were seen along the border-line and on the surface. The scan showed no associated abnormalities. Karyotype was 46, XY. MRI scan using triplanar SSFSE and HASTE sequences was done at 26 weeks and confirmed a 84 x 45 x 71 mm tumour originating from the scalp, spreading along the endocranium over the entire surface of the fronto-temporal sqama and left parietal bone. The tumour did not disturb the integrity of the internal tabula, and did not spread intracranially. Based on these findings, the diagnosis of haemangioma was made. At 38 weeks gestation, a 3810 g male infant was delivered by Caesarean section. A bluish, well-defined, non-pulsatile tumour arising from the left frontoparietal region was seen, thus confirming the diagnosis of haemangioma. CONCLUSION: MRI improved delineation of the tumour facilitating better planning of postnatal management and mode of delivery, with the information on the postnatal course and prognosis. In the prenatal period, MRI following an ultrasound diagnosed foetal tumour, is an additional part of diagnostic examinations, and is not contraindicated during pregnancy.

[Functional magnetic resonance imaging of cortical changes in a low-grade glioma patient].

INTRODUCTION: New methods for studying brain functions have provided the new insights into human brain. It is really possible to study a cortical adaptation in adults who have sustained injury. We reported cortical changes in a left frontal low-grade glioma patient during disease progression and after reoperation by functional magnetic resonance imaging (fMRI). CASE REPORT: The use of fMRI exams for localisation of eloquent motor and language areas were performed three times in a period of 15 months: seven years after initial tumor resection, eleven months later and three months after the reoperation. The first fMRI demonstrated cortical activation for motor tasks in the expected location of primary motor area while later examinations showed activations of both primary motor areas for right hand movement. The first exam language evaluation showed the left hemisphere dominance for both language tasks, while the second fMRI demonstrated the right hemisphere dominance for complex word generation task, but the left hemisphere remained dominant in simple language task. After the reoperation, language mapping revealed the left hemisphere dominance for both language tasks. CONCLUSION: fMRI evaluation of cortical changes in low-grade glioma patients may additionally optimize and individualize neurosurgical treatment.

[Dynamic magnetic resonance imaging of the cerebrospinal fluid flow within the cerebral aqueduct by different FISP 2D sequences].

BACKGROUND/AIM: A vast majority of current radiogical techniques, such as computerized tomography (CT) and magnetic resonance imaging (MRI) have great potencial of vizualization and delineation of cerebrospinal fuid spaces morphology within cerebral aqueduct. The aim of this study was to determine the possibilities of two differently acquired FISP (Fast Imaging with Steady State Precession) 2D MR sequences in the estimation of the pulsatile cerebrospinal fluid (CSF) flow intensity through the normal cerebral aqueduct. METHODS: Sixty eight volunteers underwent brain MRI on 1.5T MR imager with additionally performed ECG retrospectively gated FISP 2D sequences (first one, as the part of the standard software package, with following technical parameters: TR 40, TE 12, FA 17, Matrix: 192 x 256, Acq 1, and the second one, experimentally developed by our investigation team: TR 30, TE 12, FA 70, Matrix: 192 x 256, Acq 1) respectively at two fixed slice positions--midsagittal and perpendicular to cerebral aqueduct, displayed and evaluated by multiplegated images in a closed-loop cinematographic (CINE) format. RESULTS: Normal brain morphology with preserved patency of the cerebral aqueduct in all of 68 healthy volunteers was demonstrated on MRI examination. Cerebrospinal fluid flow within the cerebral aqueduct was distinguishable on both CINE MRI studies in midsagittal plane, but the estimation of intraaqueductal CSF flow in perpendicular plane was possible on CINE MRI studies acquired with experimentally improved FISP 2D (TR 30, FA 70) sequence only. CONCLUSION: Due to the changes of technical parameters CINE MRI study acquired with FISP 2D (TR 30, FA 70) in perpendicular plane demonstrated significantly higher capability in the estimation of the CSF pulsation intensity within the cerebral aqueduct.