ABSTRACT - Survival rate after operative treatment of malignant glioma combined with chemotherapy and radiotherapy significantly depends on the extensiveness of tumor resection. Therefore, any procedure that can assure better intraoperative tumor identification is useful. We present our experience with intraoperative usage of 5-aminolevulinic acid (5-ALA), a fluorescent porphyric substance that accumulates in tumor tissue and is visible under blue light incorporated in the operative microscope. Three hours after anesthesiology induction, the patient orally received a solution of 20 mg/kg 5-ALA in 50 mL of water. Intraoperatively, a red fluorescent porphyrin excitation was visible between tumor margins under violet-blue light. The fluorescent central part and also the marginal part of the tumor were histopathologically examined. Resection result was verified with early post enhancement computed tomography and magnetic resonance imaging. Porphyric fluorescence does not appear in normal brain tissue, whereas in malignant gliomas it stands out extremely red. Less intensive red color is seen at tumor margins. This was confirmed by biopsies obtained in many different parts of the operation field, depending on fluorescence intensity. There was no fluorescence bleaching during the surgery. In conclusion, the usage of 5-ALA during operative treatment of malignant gliomas leads to safer and more thorough tumor resection. Further improvement of contrast usage should enable lower stage glioma identification, which would certainly contribute to more successful treatment of this type of tumors.

ABSTRACT - Parkinson’s disease (PD) is a chronic neurodegenerative disorder which affects 1% of the population aged 60 and over. The etiology of PD has not yet been fully clarified, although it is known for years that the patients suffer from degeneration of dopaminergic, primarily nigrostriatal neurons. It is assumed that the disease results from interaction of genetic and environmental factors. An important role is attributed to the action of free radicals, mitochondrial dysfunction and oxidative stress mechanism. Therefore, previous research on the connection between the influence of different environmental factors and the development of PD is reviewed, with emphasis on the evaluation of current views and comparison of different results. While clear links to rural living, farming, well water consumption, metals, solvents, coffee and tea drinking, weight, physical activity, use of nonsteroidal anti-inflammatory drugs and narcotics have not been established, there is general agreement that exposure to pesticides and smoking increase the probability of developing PD. Insufficiency of accurate and relevant opinions on this problem indicates the need of further research with clearly defined criteria in terms of ‘evidence-based medicine’. Reliable data are essential in order to harmonize opinions, make major contribution and serve as a starting point to explore the possible neuroprotective mechanisms and more effective treatments of PD.

ABSTRACT - Various studies have attempted to determine the incidence and prevalence of seizures in multiple sclerosis (MS), although the exact prevalence of epileptic seizures is still controversial. The aim of this study was to assess the association between MS and epilepsy, to analyze clinical findings of epilepsy in MS patients, to estimate electroencephalography (EEG) and magnetic resonance imaging findings of the central nervous system (CNS), response to antiepileptic drug treatment and possible association of the prevalence of epileptic seizures with MS severity and duration. Medical records of 224 MS patients diagnosed at Pula General Hospital during a 25-year period (1985-2010) were reviewed. Seizures apparently occurred more commonly in MS patients than in the general population. Partial seizures with or without secondary generalization appeared to be more common. Primary generalized epilepsy has also been reported, although less frequently. The onset of epileptic seizures preceded the diagnosis of MS, occurred in parallel or within five years of MS onset. The occurrence of epileptiform EEG abnormalities in MS patients was rare. The lesions involved in the pathogenesis of epilepsy were plaques or demyelination affecting cortical or subcortical areas (predominantly frontal and temporal). Generally, seizure control with standard antiepileptic drugs was good.

ABSTRACT – Although palliative medicine has been advanced rapidly during the last few decades as an institutionalized response to the emergence of oncologic and other chronic diseases carrying the huge health burden, the Croatian medical system finds itself at the beginning after years of neglecting the palliative medicine problems. One of the goals of this short overview is to describe the basic principles of palliative medicine and the area of its practice. While assessing the various paradigms of palliative medicine, varying from hospice movement to palliative medicine integrated into the three levels of health care, the authors will try to clarify conceptual dilemmas in the area. Second goal arises in presenting the palliative care needs in the non-oncologic patients suffering from various chronic diseases and assessing the possible distinctions in these populations. Third goal is to bring an overview of palliative care in Croatia with the possible practical solutions for the implementation of palliative medicine in daily practice. From these particular goals, the ultimate goal of this overview arises, i.e. making the Croatian medical society familiar with the basic palliative medicine principles in order to additionally sensitize it for the overwhelming needs of palliative patients.

ABSTRACT – The main aim of this review is to give an overview of up-to-date tendencies in communication skills and theory with neurological patients. The authors characterized neurological disorders as the major public health problem and, therefore, present the results of various studies indicating insufficient communication skills with this group of patients. Also, we identified another vulnerable group, the caregivers of neurological patients suffering from various depressive and anxiety disorders associated with the burden of daily emotional and physical management of their significant others. Various factors possibly related to the inappropriate communication are stressed out from the physicians’ and patients’ point of view. In response to these needs, the authors present modern patient-oriented communication paradigms based on specific goals and various outcomes, applying the conceptual framework to Alzheimer disorder, focusing on the various dilemmas arising from the diagnosis disclosure to the disease progression. The need for personalized psychosocial intervention is stressed out in order to improve the quality of life of patients and their significant others.

ABSTRACT – Palliative care team is a multidisciplinary team that usually includes physician, clinical psychologist, nurses, social worker, occupational therapist, and number of other experts, offering support, help, counseling and advice designed to meet the individual needs of each patient and his family referred to the service. Clinical psychologist is an expert who is trained and professionally qualified to provide help to palliative patients with emotional and behavioral difficulties, as well as to members of palliative care team (to prevent burn out, to help them cope appropriately with daily stressful situations, etc.). Clinical psychologist working with palliative patients and with members of his family provides psychological assessment, counseling, psychotherapy, motivational interviewing to encourage intrinsic motivation to reach behavioral changes and better adaptation to the disease.

ABSTRACT – Today when efforts are made to diagnose dementia in the early course of disease, it is highly desirable to offer a high quality and continuous program of treatment and care to persons with dementia and their families. Although there is no cure for Alzheimer’s disease and dementia, the natural course of the disease can be slowed down and better quality of life offered to persons with dementia and their caregivers using standard (symptomatic) pharmacological treatment with anti-dementia drugs and other psychopharmaceuticals. In the management of dementia, non-pharmacological interventions should also be used because they may prove beneficial. Croatia as a country with one of the oldest population in Europe should develop an action plan to fight Alzheimer’s disease; in other words, we should be aware of the upcoming Alzheimer’s disease epidemic in the near future. Good quality palliative care is of great value in Alzheimer’s disease management, so all programs for palliative medicine in Croatia, such as those launched at the University but also in the field should be encouraged.

ABSTRACT – The methods of palliative care have long been defined exclusively in the frame of care for patients with malignant diseases. Recently, however, it has been realized that the group of patients requiring these methods of medical treatment is by far greater. In neurologic casuistics, the percentage of incurable diseases is very high. Curiously enough, palliative care has come into the focus of interest of this medical profession pretty late. Among neurologic diseases, cerebrovascular diseases definitely are of high medical and socioeconomic importance, as they still are the leading cause of disability and the third most common cause of mortality in the world, with palliative care being frequently necessary in their terminal stage. Statistical analysis of patients in the chronic stage of cerebrovascular diseases (post-stroke state with the grade of disability preventing independent mobility) revealed the patients and/or their families to complain mostly of the following: swallowing difficulties (dysphagia), speech disturbances (dysphasia/dysarthria), constipation, confusion, psychomotor agitation, incontinence and pain. One of four stroke patients is concerned for fear from pending death. A high proportion of patients with cerebrovascular diseases are also concerned about their disease impact on their close environment, while developing fear from disability, solitude and dependency. When talking about palliative care, special attention should be paid to patients in permanent vegetative state, which mostly develops following traumatic brain injury but may also be due to particular cerebrovascular diseases (e.g., subarachnoid hemorrhage). The management and palliative care for these patients should include therapy for pain, spasticity, muscle contractures, pathologic fractures, decubitus ulcers, or neuropathic pain.

AABSTRACT – Many neurologic diseases are progressive and incurable. The optimal care of such patients requires that neurologists understand and apply the principles of palliative medicine. Indeed, the principles of palliative care are relevant to the management of many patients because minimizing distress and controlling pain and other symptoms are important even for patients with curable disease. Palliative care is an approach that improves the quality of life of patients and their families facing the problems associated with a life-threatening disease. The aim of palliative care is prevention and relief of suffering by means of early identification, impeccable assessment and treatment of distressing symptoms and other problems, physical, psychosocial and spiritual. Although the term palliative care is often used to mean ‘end of life care’, palliative care is often very appropriate and applicable earlier in the course of disease, in conjunction with other therapies that are intended to prolong life. In this context, palliative care will enhance the patient’s quality of life and offer a support system that helps the patient live as actively as possible until death, thus affirming life while regarding dying as a normal process. Palliative care is a generic term which, in describing an approach to care, highlights the responsibility carried by all health care professionals to provide holistic care for their patients with progressive neurologic disease.

ABSTRACT – Palliative care is defined as an approach aimed at upgrading the quality of life of patients facing a lethal disease and of their families. The main principle and purpose of palliative care in a health care institution is providing due care for such patients through offering high-quality services on special wards or ward units. These services include prevention and alleviation of symptoms by early detection, assessment and management of pain, while alleviating other mental and psychosocial problems. It implies use of appropriate palliative interventions, which may include disease-modifying treatments, such as surgery, radiotherapy, chemotherapy, hormonal procedures, etc. Rehabilitation has been generally accepted as a major form of active palliative care. At this stage, the patient and his family are faced with numerous and complex issues that go beyond professional abilities of any individual profession; therefore, modern palliative care is inconceivable without the interdisciplinary team engagement, its members having the goal in common, i.e. to reduce suffering and to upgrade the quality of life of the patient and his family. The composition of the interdisciplinary team depends on the level of program development, program goals, and individual patient needs; however, the majority of programs include a physician, nurse, social worker, clerical person and volunteers. The patient and his family also are members of the team; it is of utmost importance that they feel acceptance and empathy from other team members, and to be free to speak out their feelings, with due respect for their informed consent. Currently, owing to the great advances in diagnostic and therapeutic options for patients with epilepsy, the role of palliative care is declining in this patient population. However, progressive myoclonus epilepsies make a special clinical entity in epileptology, which requires palliative care. The most important clinical entities of progressive myoclonus epilepsy for which palliative treatment is one of the major approaches included in therapeutic algorithm are presented in this report.

ABSTRACT – Palliative medicine is comprehensive care for patients and their family members, with the aim of improving their quality of life, according to the patients’ needs and desires. Although palliative medicine is traditionally associated with oncologic diseases, it is no less important in the care of patients suffering from chronic neurologic diseases such as multiple sclerosis. As there is no curative therapy for secondary progressive and primary progressive forms of multiple sclerosis, palliative medicine is crucial in the treatment of these forms of the disease and for relief of symptoms such as pain, spasticity, tremor, ataxia, sphincter and bowel disturbances, and mental disorders. Unfortunately, for the majority of symptom relieving drugs in multiple sclerosis, there is a lack of randomized studies to confirm their efficacy, thus their effectiveness has to be judged from the experiences of other medical branches. Good palliative care improves the quality of life of both the patients and their families.

ABSTRACT – Although new treatments for neuromuscular diseases are being developed, the palliative care approach to the care of neuromuscular patient is outlined and the role of the multidisciplinary team emphasized. Therefore, the palliative care approach to the care of neuromuscular patients and their families should be in the center of good clinical practice. Neuromuscular disease with the most demanding and challenging palliative care is probably a motor neuron disease. The term motor neuron disease covers a range of conditions in which the motor neuron cell bears the brunt of the disease process. The most severe complications of neuromuscular diseases are progressive muscle weakness, respiratory failure and dysphagia, but palliative care should be focused on speech and language therapy, and on emotional, spiritual and social aspects of the disease. Such a comprehensive palliative care should be focused on patient and all caregivers.

ABSTRACT – Palliative medicine implies care offered to patients in the advanced, terminal stage of oncologic and other chronic diseases. The goal of palliative care is symptom control and consequential improvement of the patient’s quality of life. Pain is one of the most common symptoms in the advanced stage of many chronic diseases including neurologic ones. Neuropathic pain caused by the lesion and disease of the nociceptive system, with a prevalence of 8% in the general population of Europe, requires specific treatment which is frequently missed or inadequately applied. Current principles in the clinical approach and therapy for neuropathic pain in the frame of palliative care are described.

ABSTRACT – Palliative care integrates holistic and multidisciplinary approach to patient, implying care offered to patient by a team of physicians, nurses, physical therapists, social workers, spiritual counsel and volunteers. From the aspect of social work, palliative care includes activities of all those involved in the team approach to care of patients whose disease has become unresponsive to treatment, all this in line with the patient’s needs and desires. Improving the quality of life of these patients and their families is the main goal of social workers’ activities.

ABSTRACT - Iron deficiency anemia (IDA) is the most common nutritional problem worldwide. Owing to the role of iron in brain energy metabolism, neurotransmitter function and myelin formation, IDA may lead to behavioral, developmental and cognitive dysfunctions. Iron is an essential element and has an important role in several metabolic and enzymatic processes including NADPH reductase activity and cytochrome oxidase system. Our aim was to investigate the electrophysiological effects of IDA on the peripheral nervous system, and to evaluate whether or not the possible electrophysiological abnormalities are reversible with appropriate doses of iron therapy. Electrophysiological evaluations were performed in 52 patients with newly diagnosed IDA and 30 age-matched healthy controls. Electrophysiological evaluations were repeated after 3 months of oral iron therapy. Normal electrophysiological findings were recorded in 38 (73.07%) patients, while 4 (7.69%) patients had polyneuropathy (PNP) and 10 (19.24%) had carpal tunnel syndrome (CTS) findings. Except for one patient with PNP and CTS findings each, the electrophysiological findings of all patients were found to have returned to normal ranges after 3 months of oral iron therapy. Detection of iron responsive neuropathic processes (PNP and CTS) in IDA patients suggested that IDA may cause peripheral nervous system involvement. It is important to emphasize the examinations for IDA as an etiologic factor on planning treatment for neuropathy patients. In cases where IDA is present, it would be beneficial to treat IDA with iron before applying other treatment options for neuropathy.

ABSTRACT – The aim was to determine prospectively the frequency and clinical characteristics of vertiginous syndromes in a neurology outpatient clinic of a community hospital during one-year period with 6- month follow up. The study was carried out at Department of Neurology, Varaždin General Hospital, in Varaždin County, Croatia, with a catchment population of 180,000. Data were prospectively collected from one neurologist’s practice during 12-month period with 6-month follow up (May 2007 – November 2008). During the study period, 1670 patients were examined and 173 (10.3%) of them complained of vertiginous symptoms (mean age 56, range 16-89 years; 113 (65.3%) females). Benign paroxysmal positional vertigo was most common, recorded in 52 (30.1%) cases, followed by vestibular neuritis in 29 (16.8%) and other etiology in 28 (16.2%) cases. Central forms of vertigo were present in 17 (9.8%) patients. The authors conclude that vertigo of peripheral origin, i.e. benign paroxysmal positional vertigo, is the most common type of vertiginous syndromes encountered in this secondary neurological practice. Since this diagnosis allows for rapid and effective relief of patient symptoms, it is crucial that the neurologist is trained in recognizing and treating this neuro-otologic entity.

ABSTRACT – Neurovascular diseases and stroke as their terminal stage currently are the third cause of mortality and morbidity in the population and the leading cause of disability and hospitalization. That is the reason for the great interest of thousands of experts in the research in all related fields, from medical and social to economic aspects of stroke. Recent studies show that besides common stroke risk factors there is strong association between stress, psychological stress in particular, and an increased stroke risk in terms of maladaptation to stressful situations. Exposure to permanent, chronic stressors and suspended or delayed physical reactions may break homeostatic mechanisms and power of adaptation and stress managing. After physiological, psychological and behavioral response of the body to prolonged and chronic stress, destructive power of stress reactions translates to the somatic level by changing the neurotransmitter, hormonal and immune responses, modifying and impairing organ functions. Eventually, this leads to a “degenerative cascade” and morphological changes, thus additionally elevating the risk of stroke.

ABSTRACT – Familial idiopathic basal ganglia calcification is a neurodegenerative autosomal dominant disorder of yet unknown gene locus. First manifestations of the disease start in the third to fifth decade. After good health during childhood and young adulthood, the disease occurs with progressive movement disorders, cognitive or behavior impairment and pyramidal failure. Neuroradiological visualization shows bilateral calcifications of the basal ganglia and subcortical calcifications of the brain and cerebellum. Metabolic course like hypo- and pseudohypoparathyroidism as well as neuroferritinosis was excluded. The disease is progressive and does not respond to usual therapy for extrapyramidal disorders.

ABSTRACT – Restless legs syndrome, primary or secondary, is one of the most common movement disorders. The most frequent causes of secondary restless legs syndrome are uremia, anemia, pregnancy, etc. A case is presented of a 77-year-old male with very pronounced restlessness in the legs at night and positive heredity for restless legs syndrome, resulting in continuous insomnia, poor quality of life and depression with suicidal impulses. Examinations ordered by a neurologist verified distinct sideropenic anemia. Upon consultation with a hematologist, substitution therapy with intravenous iron preparation was introduced along with clonazepam, which resulted in complete regression of restless legs syndrome, with significant improvement in sleep quality and thus in the patient’s quality of life. Although occurring at a high incidence, this syndrome often remains unrecognized and untreated. Continuous education about the features of this syndrome, its timely recognition, appropriate work-up algorithm and therapeutic guidelines are extremely important to improve the quality of life of patients with restless legs syndrome.

ABSTRACT - Aim of the study: To present a case of successful microsurgical clipping of the aneurysm within the fenestrated vertebrobasilar junction via far lateral transcondylar approach.
Background: Surgical treatment of low basilar aneurysm and vertebrobasilar (VB) junction remains one of the most challenging and most difficult procedures in neurosurgery. Saccular aneurysms of the VB junction are often associated with a fenestration of the basilar artery. Endovascular procedures are performed for the treatment of such aneurysms, but may be difficult in some cases.
Case description: A case is presented of a 53-year-old patient with VB junction aneurysm that was microsurgically clipped successfully via far lateral transcondylar approach. The patient was discharged from the hospital fully recovered 10 days after the surgery.
Conclusion: The far lateral approach adequately exposed the VB junction aneurysm for successful clipping of the aneurysm and was associated with no morbidity. It should be considered as a good alternative to endovascular treatment. In developing countries, the microsurgical procedure may be given preference because it is less expensive and does not require preoperative intra-arterial digital subtraction angiography or follow up.

ABSTRACT – Purpose: To assess whether retinal nerve fiber layer (RNFL) thickness value obtained with optical coherence tomography (OCT) in ocular hypertension patients can predict glaucomatous changes in visual field over a 2-year period.
Methods: This comparative analysis included 76 eyes: 36 ocular hypertension (OHT) and 40 healthy. The OCT parameter RNFL thickness and Octopus automated perimetry (SAP) were performed in ocular hypertension and healthy eyes at baseline and after 2 years.
Results: In ocular hypertension group, 6 (16.6%) eyes developed SAP glaucomatous abnormalities in 2-year period. Comparison of RNFL thickness between OHT eyes with and without glaucomatous changes and healthy eyes showed statistically significant thinning of RNFL in the inferior quadrant at baseline in OHT eyes with SAP glaucomatous changes.
Conclusion: Thinner OCT obtained inferior RNFL in OHT eyes is associated with future development of perimetric glaucoma changes.

ABSTRACT - Neuroprotection is a therapeutic procedure, which attempts to save brain tissue neurons from irreversible injury. In the last two decades, many pre-clinical (experimental) studies have been done on animal models, which have convincingly shown that different pharmacological and non-pharmacological interventions may reduce ischemic brain injury by acting on elements of ischemic cascade or preventing reperfusion injury. Even though we have been using the STAIR guidelines for pre-clinical and clinical testing of drugs in neuroprotection for nearly ten years, clinical studies of neuroprotective drugs (in humans) have not shown adequate neuroprotective effect in the treatment of acute ischemic stroke. Despite previous failures, clinical studies in the field of neuroprotection are continuing. At this moment, we are waiting for the results of ongoing studies. The most promising interventional or pharmacological agents are hypothermia, albumins, lovastatin, magnesium and citicoline. It is believed that the future of neuroprotection will be based on the usage of thrombolytic therapy along with new neuroprotective agents or procedures.

ABSTRACT - In September 2004, the Croatian Ministry of Health approved rt-PA for acute treatment of ischemic stroke. For the next almost 5 years, only three centers in Croatia started this mode of treatment. Since June 2008 started routine use of rt-PA in other neurological departments around Croatia. In our Neurological Intensive Care Unit since May 2006 till the end of May 2008, 66 patients have been thrombolysed. This kind of treatment is still applied to a relatively small group of patients due to at least: a quite narrow time window for treatment, strictly inclusion/exclusion criteria, low information level of general practitioner and emergency staff and fear od adverse effect. More frequent use of rt-PA begin since June 2008. thanks to continous informing on general and medical population, training of neurologists from hospitals around Croatia and finaly by expansion of the time window for tretament.

ABSTRACT – Wilson’s disease is a rare autosomal recessive disorder of copper transport resulting in copper accumulation in the liver, brain and cornea. The incidence is estimated to be 1:30000-80000 in most populations. The Wilson disease gene, now designated ATP7B, situated on 13th chromosome (13q14.3), was cloned in 1993. The clinical phenotypes include hepatic, neurologic and psychiatric diseases, or a combination of these. A combination of clinical features, various laboratory parameters and Kayser-Fleischer rings is necessary for making the diagnosis. Mutation analysis may provide definitive diagnosis and is becoming part of diagnostic algorithm, especially in patients with indeterminate clinical and biochemical features. Family screening of first-degree relatives should be undertaken. Recognition of the disease at an early stage is crucial because treatment prevents severe liver damage and/or lifelong neurologic disabilities. The aim of treatment is reduction of tissue copper concentration either by enhancing its urinary excretion or by decreasing its intestinal absorption. Treatment includes copper-chelators, such as penicillamine and trientine as well as zinc salts. Liver transplantation is treatment option in cases of acute liver failure or treatment-resistant and severe advanced liver disease. It is not indicated in patients with mainly neuropsychiatric presentation.

ABSTRACT – Vertebral artery dissection (VAD) has only recently been recognized as a rare cause of transient ischemic attack (TIA) or infarction in vertebrobasilar basin. Development of new diagnostic techniques associated with lower risk for the patient has resulted in a higher rate of this diagnosis. Early diagnosis is even more important knowing that cerebral infarction may ensue weeks after dissection. The symptoms of cerebellar or brain stem infarction can be prevented or alleviated by early diagnosis and timely treatment. Development of thrombi and potential thromboembolic events in vertebrobasilar basin can usually be prevented by timely anticoagulant therapy. Experiences acquired to date suggest that cerebral infarction or TIA due to VAD is generally found in younger persons, however, it does not mean that VAD cannot occur in individuals older than 50. Presentation is made of a female patient with VAD and recurrent TIAs in vertebrobasilar circulation. The aim is to remind the readers that VAD is by no means so very rare or harmless cause of TIA, and to present appropriate diagnostic work-up and treatment in case of suspect VAD.

ABSTRACT – Posttraumatic ischemic stroke after minor head injury is a rare and unexpected event. There are 65 cases of middle cerebral artery (MCA) occlusion described in the literature. Arterial dissection, cerebral vasospasm and thrombosis have been postulated as the possible pathogenetic mechanism. A case is presented of a 40-year-old man having sustained a minor head injury as a driver in a car accident. Twentyfour hours after the accident, he became soporous and was admitted to intensive care unit, where magnetic resonance imaging revealed mild brain edema on the left side with slight shift on the opposite side. He was transferred to our institution. Control computed tomography (CT) scan revealed edema and shift progression. Two days later, repeat CT scan showed further progression and the patient underwent decompression craniotomy; the patient died in two days. This case report points to the need of due attention be paid in any case of minor head injury where complications develop within 24 hours because a relatively mild head injury may be a cause and co-factor in the etiology of fatal stroke.

ABSTRACT – Neurinoma is a benign tumor originating from Schwann cells of the myelin sheath of peripheral nerves. The tumor is benign, encapsulated, not infiltrating the nerve, slowly growing, of homogeneous structure, and symptoms produced by neurinoma may be misdiagnosed. In this report, successful operative treatment of a large neurinoma of the superficial peroneal nerve as a very rare location in a 69-year-old female patient is described. Operative treatment is successful if performed before the irreversible nerve lesions have developed because the tumor itself does not infiltrate the nerve and can be extirpated in toto.

ABSTRACT – Due knowledge of the semiology of epileptic seizures and of the classification of the respective type of epilepsy or epileptic syndrome is necessary to reach an accurate diagnosis and to choose optimal antiepileptic drug. Following diagnostic guidelines, history, heterohistory and videopolygraphic data may occasionally suffice to delineate the clinical picture, which will then serve to define quite precisely the anatomic origin of epileptogenesis and localize the epileptic focus. A correctly made initial diagnosis will reduce the time needed for patient work-up and enable faster choice and introduction of the most potent antiepileptic or decision on a more radical mode of treatment, thus substantially decreasing the risk of developing a pharmacoresistant form of disease. At the same time, identification of the clinical phenotype and its anatomic correlate reduces the possibility of diagnostic error, which may result in extensive and unnecessary diagnostic procedures and specialist examinations.

ABSTRACT – Surgical techniques of treating patients with pharmacoresistant epilepsy have changed considerably in the last 25 years. Greatest success has been achieved in patients with magnetic resonance imaging (MRI) positive temporal lobe epilepsy (TLE), especially in patients with hippocampal sclerosis, and more recently in patients with extratemporal lesional epilepsy. This improvement is mostly due to large progress in imaging technology, but also in neurophysiological methods and microsurgical techniques. Very important is careful patient selection and preoperative evaluation via identification of the semiology of seizures, localization of epileptogenic lesion, and ictal onset zone. In preoperative evaluation of patients with pharmacoresistant epilepsy, modern diagnostic techniques can be divided into noninvasive and invasive. Noninvasive methods include: (a) video-electroencephalography (EEG) recording (interictal and ictal); (b) preoperative neuropsychological testing; (c) dedicated neuroradiological examination, i.e. 3T brain magnetic resonance imaging (MRI), with specialized MRI techniques including morphometric MR analysis, MR spectroscopy, functional MRI with MR tractography, and MR volumetry; (d) nuclear-medicine methods, i.e. single photon emission computed tomography (SPECT) and positron emission tomography (PET); and (e) magnetoencephalography (MEG). Invasive methods include: (a) Wada test (intracarotid amobarbital or etomidate testing); (b) semi-invasive video-EEG monitoring, using sphenoidal or foramen ovale electrodes; and (c) invasive video-EEG monitoring, using subdural strip and grid as well as depth electrodes. Invasive EEG monitoring, where selection of the type of intracranial electrodes and their placement depends on the localization of epileptogenic region, is used if MRI is nonlesional, if there is discrepancy between ictal or interictal EEG recordings and brain MRI, between the seizure semiology and the imaging findings, and between the seizure semiology and EEG recording. It is also used in case of dual pathology and polytope changes, when it is not known which pathomorphological lesion is epileptogenic, and in case of positive brain MRI, when pathomorphological lesion is localized near motor and eloquent cortex. The possible complications include intracranial hemorrhage, cortical lesions and infection.

ABSTRACT – Epilepsy is the most common neurologic disorder, which can be efficiently treated by pharmacotherapy in most patients. For full therapeutic success to achieve, the clinical phenotype or epileptic syndrome should be strictly defined; optimal dosage of appropriate antiepileptic therapy should be introduced as early as possible (or in the form of rational dual therapy as needed); and due care should be taken of the specific populations such as women of reproductive age and the elderly, considering their physiologic characteristics, comorbidities, altered mechanism of action of the antiepileptics used (pharmacokinetics and pharmacodynamics); adjuvant therapy and possible interactions with antiepileptics. According to literature data, there are 25%-40% of pharmacoresistant patients, in which a satisfactory control of seizures cannot be achieved by the antiepileptic therapy available. These patients are candidates for preoperative examination and neurosurgical treatment, i.e. classic neurosurgical resection or minimally invasive neurosurgical procedure (implantation of vagus nerve stimulator).

ABSTRACT – Lance-Adams syndrome, first described in 1963, is a condition characterized by development of chronic post-hypoxic action myoclonus due to a temporary lack of or inadequate brain oxygen supply. A coagulation disorder should be suspected when an unexplained hemorrhage occurs. Patients with Lance- Adams syndrome show favorable response to sodium valproate and clonazepam. A case is presented of a 22-year-old man admitted to University Department of Neurology, Zagreb University Hospital Center, in January 2008. Clinically, the patient presented with headache, nausea, vomiting, mild right hemiparesis and truncal ataxia. Brain magnetic resonance revealed spontaneous atypical subdural hematoma in the region of the right middle cerebellar peduncle, vermis and left cerebellar hemisphere. Laboratory findings revealed coagulation factor XIII deficiency. Two weeks of admission, the patient developed spontaneous subdural hematoma in the right frontoparietal region. In the meantime, clinically he also developed generalized action myoclonus that was, according to our belief, a part of chronic post-hypoxic action myoclonus, i.e. Lance- Adams syndrome (secondary to intracranial hemorrhage). Oral administration of sodium valproate and clonazepam, and replacement therapy for normalization of coagulation factor XIII concentration resulted in complete regression of myoclonus.

ABSTRACT – Ritscher-Schinzel syndrome or Cranio-Cerebello-Cardiac (3C) syndrome is a rare autosomal recessive disorder characterized by malformation of the posterior cranial fossa, congenital cardiac defect and craniofacial dysmorphism. The syndrome was first described in 1987 by the example of two sisters born to healthy parents. Criteria for the diagnosis of 3C syndrome were published in 2001 by Leonardi et al. Presentation is made of a 37-year-old patient that was operated on for cleft palate soon after birth, then also for ventricular septum defect. Since 1989, the patient has been treated for epilepsy with signs of psychomotor retardation. In 2008, computed tomography revealed Dandy-Walker malformation. In March 2009, the patient was hospitalized at University Department of Neurology, Zagreb University Hospital Center. Magnetic resonance of the brain verified the malformation described above, with enlargement of the posterior cranial fossa with a cystic growth and aplasia of the caudal part of the vermis, and expanded areas of gray matter heterotopy bilaterally subependymally. Clinical findings included craniofacial dysmorphism, syndactyly of the first and second right toes, flexion contractures of the second and third finger distal phalanges of both hands, and thoracic segment scoliosis. Radiologic examinations showed hypoplasia of the first rib on the right, and congenital block of the bodies and articular processes of C6-C7 vertebrae with sinistro-convex scoliosis of the thoracic spine. Based on clinical, radiological and neuroradiological examinations, we believe that our patient meets all the criteria for Ritscher-Schinzel syndrome. It is the first case described in Croatia and the oldest patient reported in the literature.

ABSTRACT – Neurosyphilis develops in 10%-33% of untreated persons with early syphilis about 15-30 years from the original infection with Treponema pallidum. The main signs of tertiary form of syphilis or general paresis are dementia, myoclonic jerks, seizures, psychosis, dysarthria, action tremor and quadriparesis. We reported on a 40-year-old patient that developed partial seizures with rare secondary generalization, while headache and slow progressive dementia occurred several months later. Except for cognitive decline, there were no other neurological signs of disease. Electroencephalography revealed slowing down of background frequency and paroxysmal delta activity with element of bi- and triphasic activity typical for encephalopathies, so extensive diagnostic evaluation was performed. Magnetic resonance imaging demonstrated cerebral atrophy and disseminated T2 and FLAIR hyperintense lesions, especially of frontal and temporal localization. Single photon emission computed tomography showed marked reduction of the cerebral blood flow. Blood and cerebrospinal serologic testing confirmed the diagnosis of neurosyphilis.

ABSTRACT – A 35-year-old female had been medically treated since age 8 for generalized seizures, and since age 19 for complex partial seizures, using carbamazepine (Tegretol®) ever since. After 4 years of carbamazepine administration, she developed systemic lupus erythematosus (SLE) symptoms such as rash, collapse, leukopenia, hypergammaglobulinemia and positive anti-nuclear factor (ANF). Clinical symptoms and leukopenia normalized upon carbamazepine discontinuation and administration of chloroquine.

ABSTRACT – One percent of the general population are affected with epilepsy, while 25%-30% of epilepsy patients are intractable to medications in spite of a recent increase in the number of new medications that are available, and need neurosurgical operation. Vagus nerve stimulation (VNS) is a relatively new tool that has been increasingly used in non-pharmacological management of pharmacoresistant epilepsies, reducing the rate of epileptic seizures by 60%-70%. Very rare adverse events related to VNS included bronchoconstriction in patients with a history of bronchial asthma associated with activation of the device. We present a patient with bronchial asthma and pharmacoresistant epilepsy, in whom a VNS implanted at a stimulation of 0.75 mA was associated with activation of the device, which was found to temporally correlate with bronchoconstriction as demonstrated by pulmonary function assessment.

Dana 23. travnja 2010. godine prvi puta u Hrvatskoj i u široj regiji izvedena je u KBC-u Zagreb na Rebru složena operacija 48-godišnje bolesnice s teškim, farmakorezistentnim oblikom epilepsije, koja se liječi od 7. godine života i u koje, usprkos cijelom nizu antiepileptika, nije postignuta zadovoljavajuća kontrola epileptičnih napadaja. Epileptični napadaji su joj onemogućavali normalno funkcioniranje u svim aspektima života. Bolesnica je prosječno imala 20-tak epileptičnih napadaja na dan, često u nizu; klinički fenotipski radilo se o kompleksnim parcijalnim napadajima frontalnog ishodišta (cingularna regija) obilježenim bizarnim grimasama i verbalnim automatizmima te perseveracijama, uz učestalu sekundarnu generalizaciju. Standardno EEG monitoriranje skalp elektrodama nije pokazivalo jasno područje mozga iz kojega započinje epileptični napadaj. U planiranju i izvedbi kirurškog zahvata, kao i u invazivnom elektroencefalografskom monitoriranju koji je izveden u kontinuitetu 4 dana ranije, a na inicijativu predstojnice Klinike za neurologiju doc. dr. sc. Sanje Hajnšek i predstojnika Klinike za neurokirurgiju prof. dr. sc. Josipa Paladina, te uz veliku potporu ravnatelja akademika Željka Reinera i pomoć prof. dr. sc. Jörga Wellmera, predstojnika Centra za epilepsiju Sveučilišne bolnice u Bochumu, sudjelovao je tim liječnika neurologa (doc. dr. sc. Sanja Hajnšek, doc. dr. sc. Željka Petelin, doc. dr. sc. Zdravka Poljaković, dr. Sibila Nanković, dr. Vlatko Šulentić), neurokirurga (prof. dr. sc. Josip Paladino, mr. sc. dr. Goran Mrak, dr. Andrej Desnica), biomedicinskih inženjera (doc. dr. sc. Velimir Išgum, dipl. ing. Magdalena Krbot, dipl. ing. Ana Branka Šefer, dipl. ing. Marija Mavar), neuroradiologa (doc. dr. sc. Marko Radoš, dr. sc. Goran Pavliša) te anesteziologa (mr. sc. dr. Tamara Murselović). U bolesnice je na visokorezolucijskom MR mozga (3T) otkriven poremećaj razvoja moždane kore, tzv. kortikalna displazija lokalizirana u desnom frontalnom režnju. Odluka za invazivno monitoriranje donešena je zbog planiranja opsežnosti neurokirurške resekcije, tj. operacije mozga. Budući da se u bolesnika u kojih se nađe promjena vidljiva na MR slikama ne može reći koji je dio mozga odgovoran za nastanak epileptičnog napadaja (tzv. epileptogena zona), jedini način njenog otkrivanja i potpunog uklanjanja je monitoriranje epileptične aktivnosti invazivnim elektrodama (strip i grid elektrode). O opsežnosti uklanjanja čitave epileptogene zone ovisi u kojoj je mjeri moguće smanjenje epileptičnih napadaja. U bolesnika u kojih nije uklonjena čitava epileptogena zona rezultati kirurškog liječenja pokazuju značajno slabiju kontrolu epilepsije nakon operacije nego u bolesnika u kojih je uklonjena čitava epileptogena zona. Bolesnici su u prvom aktu implantirane subduralne strip i grid elektrode u područje same kortikalne displazije i oko nje, frontalno desno. Dan nakon operacije pristupilo se, uz pomoć kortikalnog stimulatora Nicolet, kontinuiranom invazivnom elektroencefalografskom monitoriranju temeljem kojeg se s vrlo velikom preciznošću odredila zona početka epileptičnog napadaja, te je uz pomoć posebnog kompjutorskog programa napravljen plan neurokirurške resekcije. Kortikalni stimulator Nicolet sa 128-kanalnim pojačalom je uređaj koji je zadnja inovacija u funkcionalnom elektroencefalografskom monitoriranju. Uz Centar za epilepsiju KBC-a Zagreb na Rebru, uređaj takvog tipa posjeduju još samo dva epileptološka centra u Europi (u Londonu i u Oslu).Treba napomenuti da se invazivnim monitoriranjem može uz otkrivanje epileptogene zone obaviti i detaljan prikaz moždane kartografi je (kortikalnih centara za motoriku, govor, osjet). Uz pomoć navedene metode se u bolesnika koji su kandidati za resekciju tumora mozga ili kirurške zahvate kod epilepsija umanjuje mogućnost oštećenja kritičnih moždanih regija, što bi dovelo do neprihvatljivog neurološkog deficita, a što je od velike važnosti za poboljšanje kvalitete njihova života. Operacija uklanjanja patološke promjene, kortikalne displazije te elektrodama otkrivene epileptogene zone učinjena je nakon četiri dana intenzivnog monitoriranja, a nakon inicijalnog postavljanja subduralnih elektroda. U bolesnice je poslijeoperacijski tijek nakon postavljanja elektroda, tijekom četverodnevnog monitoriranja, kao i tijek nakon resekcije kortikalne displazije protekao uspješno, bez komplikacija. Poslijeoperacijski je bolesnica potpuno bez epileptičnih napadaja, značajnog kognitivnog poboljšanja, dobro se osjeća i nakon 40 godina upoznaje normalan život koji nikada prije nije imala. Učinjeni postupak invazivnog EEG monitoriranja uz resekciju epileptogene zone nadopuna je postojećem operacijskom programu epilepsija (lezionektomije, selektivne amigdalohipokampektomije, prednje temporalne resekcije, vagusne stimulacije i dr.) koji se već godinama kontinuirano primjenjuje suradnjom Referentnog centra Ministarstva zdravstva Republike Hrvatske za epilepsiju, Klinike za neurologiju, te Klinike za neurokirurgiju Kliničkog bolničkog centra Zagreb u liječenju farmakorezistentnih epilepsija. Za Centar za epilepsiju Klinike za neurologiju: Doc. dr. sc. Sanja Hajnšek Doc. dr. sc. Željka Petelin Dr. Sibila Nanković Za Kliniku za neurokirurgiju: Mr. sc. dr. Goran Mrak