Comparative Targeted Metabolomics of Ischemic Stroke: Thrombi and Serum Profiling for the Identification of Stroke-Related Metabolites.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke. Metabolomics has been shown as a promising tool for biomarker discovery since many post-ischemic metabolites can be found in the plasma or serum of the patient. In this research, we performed a comparative targeted metabolomic analysis of stroke thrombi, stroke patient serums, and healthy control serums in order to determine the alteration in the patients' metabolomes, which might serve as biomarkers for early prediction or stroke prevention. The most statistically altered metabolites characterized in the patient serums compared with the control serums were glutamate and serotonin, followed by phospholipids and triacylglycerols. In stroke thrombi compared with the patients' serums, the most significantly altered metabolites were classified as lipids, with choline-containing phospholipids and sphingomyelins having the highest discriminatory score. The results of this preliminary study could help in understanding the roles of different metabolic changes that occur during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers for ischemic stroke.

Epistemic responsibilities in the COVID-19 pandemic: Is a digital infosphere a friend or a foe?

Digital technologies have a significant role in collecting, filtering and disseminating information, allowing for social, healthcare and economic activities even in the context of highly restrictive public health measures in the current COVID-19 pandemic. As personal contact is greatly reduced, they also create a shared informational landscape, allowing for a shared threat response. This is a difficult task, since truthfulness of content that leads to actionable knowledge is impossible to consistently validate. So, not only that curation of information is rarely congruent with pressing health issues, but digital spaces may also become fertile ground for misinformation and disinformation, contributing to the devastating effects of an infodemic. Digital intermediaries are useful exactly because their representation of reality is not a true construct, but a result of purposely curated information. However, they are active, dynamic epistemological agents with their own logic and aim. In dealing with a pandemic, we should reconsider the ways how our digital informational landscapes are created and sustained. This urges us to consider ethical governance of digital data curation and dissemination, alongside forms of control of the truthfulness and reach of its content. Some of the most fundamental issues in dealing with the COVID-19 pandemic, including the newly available vaccines are reliant on digital information and data sharing among experts, and the role of informing the general public. The need to create a reproducible, valid and truthful informational landscape is paramount, while allowing for free and rational, behavioral individual choices oriented toward preserving and promoting healthy behavior. These are issues at the heart of dealing with any pandemic, as well as a well-organized health care policy.

OPTIC NERVE SHEATH SONOGRAPHY IS A PROMISING TOOL FOR ASSESSMENT OF RAISED INTRACRANIAL PRESSURE IN PATIENTS ADMITTED TO NEUROLOGICAL INTENSIVE CARE UNIT.

Optic nerve sheath diameter (ONSD) enlargement is detectable in traumatic brain injury patients with raised intracranial pressure (ICP). The aim was to assess its value in neurological patients suspected to have increased ICP. Patient clinical imaging data and hospitalization outcome were analyzed. Patients were divided into groups according to brain pathology and level of consciousness with Glasgow Coma Score (GCS). Poor hospitalization outcome was assessed by modified Rankin scale (mRS) >3. Data obtained by ocular sonography performed in acute setting were compared with data of 100 control subjects. Data were expressed as mean ± SD. Intergroup comparison was performed by Student's t-test. Data of 34 patients (63+16 years) were suitable for analysis, including 8 primary intracerebral hemorrhage (PICH), 8 subarachnoid hemorrhage (SAH), 12 PICH or SAH and intraventricular hemorrhage (IVH), 4 tumors and 2 ischemic strokes. The mean ONSD was 5.86+0.69 mm in patients versus 4.38+0.41 mm in controls (p<0.01). ONSD was 6.28+0.61 mm in patients with GCS <8 and 5.77+0.55 mm in other patients (p<0.05). ONSD was 5.72+0.59 mm in PICH versus 6.20+0.65 mm in PICH/SAH with IVH (p=0.1). ONSD was 5.73+0.38 mm in SAH in comparison to PICH/SAH with IVH (p=0.05). There was no statistically significant difference in optic nerve diameter between patients and controls (2.48+0.28 mm vs. 2.39+0.33 mm; p>0.05). Pronounced enlargement of ONSD was observed in patients with ICH or SAH with IVH, and in patients with GCS <8. Enlarged ONSD was associated with poor neurological outcome (mRS >3).

Stroke Caused by Lung Cancer Invading the Left Atrium.

We describe a 59-year-old stroke patient presented with sudden onset left side weakness and a speech disorder due to a major acute cerebral infarction in the area of the right middle cerebral artery, right posterior cerebral artery, and small infarctions in the area of the left middle and left posterior cerebral artery. For the previous month, the patient had been feeling weak and had no appetite. The patient had not been previously seriously ill. A chest x-ray showed a large mass in the upper zone of the right lung. Chest computed tomography scan and echocardiography were performed and revealed advanced lung cancer invading the left atrium. Spontaneous tumor embolism is a rare cause of stroke and should be considered in the differential diagnosis of stroke in a cancer patient. Also, sometimes stroke can be the first manifestation of advanced cancer.

[CROATIAN GUIDELINES FOR DIAGNOSIS AND MANAGEMENT OF BENIGN PAROXYSMAL POSITIONAL VERTIGO (BPPV)]. / HRVATSKE SMJERNICE ZA DIJAGNOSTIKU I LIJECENJE BENIGNOGA PAROKSIZMALNOG POZICIJSKOG VERTIGA (BPPV-A).

BPPV is generally the most common cause of vertigo, caused by a pinch-off of tiny calcium carbonate crystals (called the otoconia or the otoliths) from the macula utriculi, most frequently due to the degenerative processes or a trauma, whereby the crystals, under the action of gravity in certain head positions coinciding with its direction, arrive to some of the semicircular canals, usually the posterior one, due to the existent anatomical circumstances and relationships, thus creating an inadequate stimulus of the cupular senses while floating through the endolymph and provoking symptoms of a strong and short-term dizziness. Two main clinical forms can be distinguished: canalolythiasis, with an accommodation of otolithic debris in the semicircular canal, and cupulolythiasis, with their location immediately next to the cupular sense. The diagnosis is established by a positive positioning test, Dix-Hallpike for the posterior and the supine roll for the lateral canal. Although one can expect a spontaneous recovery subsequent to few weeks or months, various methods of otolith repositioning to a less sensitive place lead to a prompt improvement while reducing or withdrawing the symptoms completely. These guidelines are intended for all who treat the BPPV in their work, with an intention to assist in the diagnosis and application of an appropriate therapeutic method.

General recommendations for the management of aneurysmal subarachnoid hemorrhage.

Subarachnoid hemorrhage is a neurologic emergency and a detrimental cerebrovascular event with a high rate of death and complications. Recommendations have been developed and based on literature search, evaluation of the results of large international clinical trials, collective experience of the authors, and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. The aim of these guidelines is to provide current and comprehensive recommendations and to assist physicians in making appropriate decisions in the management of subarachnoid hemorrhage. Evidence based information on the epidemiology, risk factors and prognosis, as well as recommendations on diagnostic work up, monitoring and management are provided, with regard to treatment possibilities in Croatia.

Recommendations for the management of medical complications in patients following aneurysmal subarachnoid hemorrhage.

These are evidence based guidelines for the management of medical complications in patients following aneurysmal subarachnoid hemorrhage, developed and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. They consist of recommendations for best monitoring, medical treatment and interventions based on the literature, evaluation of the results of large international clinical trials, and collective experience of the authors.

Acute polyradiculoneuritis syndrome: clinical observations and differential diagnosis.

Guillain-Barré syndrome (GBS) and neuroborreliosis may clinically manifest with symptoms related to acute polyradiculoneuritis. The aim and purpose of this study was analysis of clinical picture in patients with acute polyradiculoneuritis and their differential diagnosis into patients with GBS or meningoradiculoneuritis within the framework of neuroborreliosis. In this retrospective study, medical records of patients with acute polyradiculoneuritis hospitalized at University Department of Neurology, Sestre milosrdnice University Hospital Center during a 4-year period were analyzed. The study included data on 27 patients. Definitive diagnosis ofGBS was made in 23 patients and of neuroborreliosis in four (14.8%) patients. Acute inflammatory demyelinating polyneuropathy was recorded in 69% of GBS patients, Miller Fisher syndrome in four patients, and acute motor axonal neuropathy and/or acute motor and sensory axonal neuropathy in three patients. Clinically, patients with neuroborreliosis manifested flaccid tetraparesis, peripheral facial nerve paresis, bulbar paresis, ocular motility disorders, and sensory symptoms of radicular pain and paresthesias. Considering the relatively high prevalence of neuroborreliosis in north-west Croatia, it is important to exclude meningoradiculoneuritis caused by Borrelia burgdorferi on differential diagnosis of GBS in these patients.

Hemispheric asymmetry of visual cortical response by means of functional transcranial Doppler.

We assessed the visual evoked response and investigated side-to-side differences in mean blood flow velocities (MBFVs) by means of functional transcranial Doppler (fTCD) in 49 right-handed patients with severe internal carotid artery (ICA) stenosis and 30 healthy volunteers, simultaneously in both posterior cerebral arteries (PCAs) using 2 MHz probes, successively in the dark and during the white light stimulation. Statistically significant correlation (P = 0.001) was shown in healthy and in patients (P < 0.05) between MBFV in right PCA in physiological conditions and MBFV in right PCA during the white light stimulation and in the dark. The correlation between MBVF in right PCA and contralateral left PCA was not statistically significant (P > 0.05). The correlation between ipsilateral left PCA was significantly higher than the one with contralateral right PCA (P < 0.05). There is a clear trend towards the lateralisation of the visual evoked response in the right PCA.

Basilar impression as a possible cause of cerebellar stroke: case report.

A case is reported of a 72-year-old woman who presented with severe vertigo, vomit, and mild neck and occipital pain. She had a medical history of hypertension, angina pectoris, cholelithiasis, gastric ulcer, pyelonephritis and periodical mild dizziness. Neuroimaging revealed right vertebral artery occlusion, right cerebellar stroke and basilar impression. The therapeutic approach chosen in our patient was conservative, with non-steroid anti-inflammatory drugs and neck collar. Although our patient's prior risk factors for stroke supported a diagnosis of vertebrobasilar stroke, it is possible that the vertebral artery occlusion was the result of changes in the atlantoaxial anatomy and that cerebellar infarction was secondary to craniocervical anomaly. Although the presence of vertebral artery occlusion, cerebellar stroke and basilar impression in our patient may have been coincidental, we suggest that patients with basilar impression and craniocervical anomalies in general may be at an increased risk of vertebrobasilar vascular disease and vertebrobasilar stroke.

Cerebrovascular evoked response to repetitive visual stimulation in severe carotid disease--functional transcranial Doppler study.

Hemodynamic features of the posterior circulation were evaluated by assessing visual evoked response in posterior cerebral artery (PCA) by means of functional transcranial Doppler (fTCD) in 49 patients with high-grade (70%-99%) internal carotid artery (ICA) stenosis or occlusion and 30 healthy subjects. Mean blood flow velocities (MBFV) and mean reaction time (time to peak velocities) (MRT) in each PCA were measured in the dark (closed eyes) and during white light stimulation (opened eyes, looking at the electric bulb), during three consecutive repetitive periods of 1 minute each. In the group of severe carotid disease patients, there was no difference in MRT in PCA during the white light stimulation (P=0.1), whereas in the dark MRT values showed a statistically significantly prolonged visual evoked response (P=0.02), but with no clinical relevance. MBFV values did not differ significantly during white light stimulation (P=0.1), whereas in the dark the difference was also statistically significant (P=0.03), but with no clinical relevance. On the contrary, in the group of healthy subjects, MRT values differed significantly both during white light stimulation (P=0.0005) and in the dark (P=0.00054), showing a significantly prolonged visual evoked response. During white light stimulation, MBFV showed significant decrease and prolonged vasoreactive response (P=0.004). Prolonged vasoreactive response in PCA in healthy subjects during repetitive measurements may indicate exhaustion of the vasoreactive mechanisms. In carotid disease patients, stable vasoreactive response may indicate that the compensatory mechanisms of the posterior circulation are always maximally engaged to compensate for carotid insufficiency.

Visual evoked response in patients with severe carotid disease--functional transcranial doppler study of posterior circulation.

The goal of this study was to evaluate the visual evoked response in posterior cerebral artery (PCA) by means of functional transcranial doppler in patients with severe carotid disease and to determine the hemodynamic effect of severe carotid disease on posterior circulation. Measurements were performed successively in the dark and during the white light stimulation in 49 patients with high-grade (70-99%) internal carotid artery (ICA) stenosis or occlusion and compared with 30 healthy age and sex matched subjects. Mean blood flow velocities (MBFV) (cm/s +/- 2SD) and mean reaction time (MRT) (s +/- 2SD) during three consecutive repetitive periods of 1 minute each were analyzed. MBFV in PCA during the white light stimulation and in the dark between the two groups didn't differ. MRT in patients showed a significantly prolonged visual evoked response in both affected (light: patients 29.36 +/- 14.46, controls 19.67 +/- 11.25, respectively, p < 0.046; dark: patients 35.25 +/- 11.9 controls 21.89 +/- 10.31, respectively, p < 0.002 and unaffected side (dark: patients 33.13 +/- 11.12, controls 23.89 +/- 11.23, respectively, p < 0.032) of ICA. This data showed that MRT is the principal restrictive factor in the case of carotid stenosis suggesting the independence of cerebral vascular reserve capacity of the posterior part of Willis circle that is necessary to be considered separately.

Thrombolysis for acute ischemic stroke--our experiences as part of SITS-MOST.

Thrombolysis with intravenous recombinant tissue plasminogen activator (rtPA) is the first evidence based treatment for acute ischemic stroke, which aims to reduce the cerebrovascular lesion. At University Department of Neurology, Sestre milosrdnice University Hospital, Zagreb, thrombolytic therapy with intravenous rtPA (alteplase) (Actilyse) for acute ischemic stroke was introduced in 2004. We present our results referring to demographic, time logistics and clinical outcome data as part of SITS-MOST (Safe Implementation of Thrombolysis in Stroke - MOnitoring STudy) and compare them with the results from other centers in Croatia and all other participating centers. Up to now, 56 patients (61% of male and 39% of female, average age 67 years) have been treated at our department with intravenous rt-PA (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose given as a bolus followed by 60-minute infusion. Our experiences with thrombolytic therapy with intravenous rt-PA (alteplase) (Actilyse) for acute ischemic stroke confirm the safety and the efficacy of this therapy.

Stroke unit--where all stroke patients should be treated.

Acute stroke is one of the leading causes of morbidity and mortality worldwide, and as the most important cause of morbidity and long-term disability imposes an enormous economic burden. Stroke units (SU) are an effective option to fight stroke. According to the European Stroke Organization, SU should provide coordinated multidisciplinary care provided by medical personnel specialized in stroke care. Helsingborg declaration from 1995 urged for organized management of acute stroke in order to reduce mortality below 20% (SU for all stroke patients) and to achieve independency in more than 70% of 3-month stroke survivors. At the beginning of 2001, the first Croatian SU was established at Sestre milosrdnice University Hospital in Zagreb as a hospital ward with dedicated multidisciplinary stroke team consisting of neurologists specialized in the management of cerebrovascular disease, trained nurses and rehabilitation personnel, together with other professionals to enable treatment of stroke patients according to current guidelines.

The art: neuroscientific approach.

Scientists have for centuries tried to localize and define artistic talent. Modern diagnostic techniques that enable visualization and measurement of brain morphology and function are positron emission tomography (PET), magnetic resonance imaging (MRI), functional transcranial Doppler (fTCD) and some biochemical methods. In the majority of people, the left hemisphere is dominant, but the right hemisphere is considered to be creative, visual, imaginative and intuitive. Right hemisphere is associated with musical skills and good three-dimensional orientation. It is also associated with good coordination and athletic skills. Creative people have less marked hemispheric dominance. Using the functional (fMRI) technique, the activation of visual cortex while watching different kinds of compositions was visible; the specific pattern of cortical activation was identified for looking at the landscapes, portraits, abstract compositions or different combination of colors. For music perception, the interplay of activity on both sides of the brain is necessary. In the right side, the centers for perceiving pitch, certain aspects of melody, harmony, timbre and rhythm are placed, and in the left side the processes of rapid changes in frequency and intensity, both in music and words are taking place. Adaptation of the brain, i.e. brain plasticity can arise upon listening or performing music. It is possible to use music, painting and dancing as an aid in the treatment of somatic, neurologic or psychiatric disorders.

[Etiology and treatment of epilepsy in the elderly]. / Etiologija i lijecenje epilepsije osoba starije dobi.

UNLABELLED: Epilepsy currently affects 1.0%-1.5% of elderly population, and its prevalence and incidence rise as the number of old people increases worldwide. Antiepileptic drugs are the mainstay of treatment. Their phrarmacokinetics differ in old age and polypharmacotherapy often leads to drug interactions. Many of the affected have concomitant cardiovascular, metabolic, cerebrovascular, neurodegenerative or neoplastic diseases. Antiepileptic drugs add to the burden of medication and may produce neurotoxicity or cognitive impairment. PURPOSE: To give an overview of epidemiologic data and pharmacological management of epilepsy in the elderly. It is a common and important clinical problem. The increased awareness of this phenomenon has led to better understanding of the etiology of seizures and complexity of the pharmacokinetics in the elderly. METHOD: Data of 246 patients with epilepsy admitted to our Department during the year 2001 were retrospectively analyzed. RESULTS: Forty-three (17.4%) patients were older than 65. Thirty-two (74.4%) patients, 20 male and 12 female, had a newly diagnosed epilepsy. The etiology of seizures included cerebrovascular diseases in 22 (68.8%), trauma in 4 (12.5%), primary tumors in 3 (9.4%) and metastases in 3 patients (9.4%). The initial antiepileptic drug (AED) was phenytoin in 15 (46.9%), carbamazepine in 14 (43.8%), carbamazepine plus phenytoin in 2 (6.3%), valproic acid in 1 (3.1%), diazepam in 3 (9.4%) and oxazepam in 2 (6.3%) patients. Later, during follow-up, lamotrigine was introduced in 4 (12.5%) patients as a monotherapy and in 3 (9.4%) patients as add-on therapy. Topiramate was introduced in 1 patient as monotherapy and add-on therapy each. Gabapentin was introduced in one patient as add-on therapy. CONCLUSION: Cerebrovascular disease is the most common cause of new-onset seizures in the elderly. Pharmacological treatment is complicated by the age related changes of pharmacokinetics and pharmacodynamics and drug-drug interactions. Phenytoin and sodium valproate are the first choice agents for generalized tonic-clonic seizures, with carbamazepine preferred for partial seizures. The newer AEDs, such as gabapentin and lamotrigine, also warrant some consideration as the first-line agents because of their efficacy and favorable effect profile. The optimal management of epilepsy requires rapid investigation, accurate diagnosis, effective therapy, education and assured support.