[Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease]. / Smjernice za dijagnostiku, lijecenje i pracenje Anderson-Fabryjeve bolesti.

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the α-galactosidase A (α-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.

Cognitive performance in asymptomatic patients with advanced carotid disease.

OBJECTIVE: : In the absence of stroke or transient ischemic attack, patients with advanced carotid stenosis or occlusion (ICAs/o) are considered asymptomatic, yet they are prone to mostly subtle cognitive impairment. BACKGROUND: : The Mini-Mental State Examination (MMSE) often fails to detect mild cognitive impairment. The Montreal Cognitive Assessment (MoCA) is more sensitive in recognizing such changes. METHODS: : Scores on the MoCA and MMSE were compared in 70 asymptomatic patients with ICAs/o and 70 controls matched for demographic variables and vascular risk factors. RESULTS: : MMSE scores fell mostly within the normal range in both patients and controls. Differences were significant for total MoCA scores (P<0.001). Patients with ICAs/o performed worse on visuospatial and executive function (P=0.018), abstraction (P<0.001), and delayed recall (P<0.001). Lower MoCA scores were associated with diabetes (odds ratio=6.41; 95% confidence interval, 1.277-32.220; P=0.024) and older age (odds ratio=0.86; 95% confidence interval, 0.780-0.956; P=0.004). Patients with diabetes performed worse on delayed recall (P<0.001), and patients with hypertension were worse on the MoCA naming subtest (P=0.04). CONCLUSIONS: : The MoCA successfully identified reduced cognitive status in patients with ICAs/o. The MoCA subtest scores revealed a pattern of cognitive impairment similar to that documented in other studies using more extensive neuropsychological tests. MoCA could be used as part of the clinical evaluation of patients with ICAs/o.

Serum Brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression.

INTRODUCTION: The aim of this study was to compare the concentration of serum Brain-derived neurotrophic factor (BDNF) in patients suffering from major depressive disorder (MDD) considering the severity of MDD episode defined by the Hamilton rating scale for depression (HAMD-17). The other aim was to research the connection between serum BDNF and the symptomatic dimensions of MDD. SUBJECTS AND METHODS: The study includes 139 participants with major depressive disorder (MDD). Diagnosis of MDD was set by DSM-IV-TR criteria. The severity of MDD was estimated with HAM-D-17 in the manner that mild episode was diagnosed if the score on HAMD-17 was up to 18, moderately severe 18-25 and severe over 25. Concentration of BDNF was determined by the ELISA method. RESULTS: This research could not find a difference in BDNF concentration considering the severity of the depressive disorder in groups suffering from mild, moderately severe and severe episodes of MDD (F=1.816; p=0.169). Factor analysis of HAMD-17 extracted four dimensions of depressive symptoms. None of the symptomatic dimensions was significantly related to BDNF concentration. CONCLUSION: Results of this study indicate that serum BDNF levels are not related to the severity of depression and its specific symptomatic dimensions. These findings support the idea of a complex relationship between BDNF concentration at the periphery and in the CNS.

Mild cognitive impairment in symptomatic and asymptomatic cerebrovascular disease.

We tried to evaluate and to compare usefulness of two brief cognitive tests in early detection of cognitive decline in subjects with increased cerebrovascular (CV) risk. As CV risk factors are recognised as important in etiology of dementia, we also aimed to determine the possible associations of specific CV risk factors and cognitive results. Patients (PGs) with first-ever stroke or TIA (N=110) and CV symptoms-free controls (CGs) with CV risk factors present (N=45) matched for age, gender and education level were tested using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) on admission, at three- and six-month points. In all subjects, detailed CV risk factors profile was assessed. We observed the decrement in cognitive performance during the six-month study period in both groups, more evident if MoCA (p<0.001) than if MMSE was used (p=0.022). Six months after first stroke/TIA 83.6% PGs scored below normal range on MoCA. In PGs, positive associations for cognitive decrement and multiple CV risk factors (>2) were found (p=0.034 for MMSE; p=0.002 for MoCA). In CGs, positive associations were found for cognitive decrement and arterial hypertension with increased IMT values (p<0.001 for MMSE) and for multiple CV risk factors and arterial hypertension (p=0.003 for MoCA). The use of MoCA could aid to early recognition of cognitive deficits in persons with increased CV risk. Individuals with multiple CV risk factors seem to have increased risk of cognitive decline.

Impairment of proprioception after whiplash injury.

Whiplash injury usually occurs in traffic accidents. Persons experienced this injury might have an impairment of proprioception clinically expressed as inability to determine the exact position of their heads. The aim of this study was to examine the loss of proprioception in people who had a whiplash injury. The study included 60 subjects with cervical spine injury, aged 20 to 50 years and 60 healthy volunteers matched by sex and age. The instrument used for cervical spine mobility assessment was the Cervical Measurement System (CMS), which determines the ability of subjects to return their head in the exact position as it was before they turned it 30 degrees left or right. Patients with cervical spine injury showed significant impairment of proprioception in comparison with healthy subjects (P < 0.001). The results support the hypothesis that subject with recent cervical spine injury have incorrect perception of their head position. Therefore, their rehabilitation should include the correction of proprioception and head coordination.

The dissections of craniocervical arteries.

Dissection of craniocervical arteries internal carotid artery (ICA), or vertebral artery (VA) is an increasingly recognized entity and infrequent cause of stroke. We investigated 8 patients (4 women and 4 men) with dissections of the craniocervical arteries. Diagnostic procedures for detection of craniocervical dissection included: extracranial ultrasound-color Doppler flow imaging (CDFI) of carotid and vertebral arteries, transcranial Doppler sonography (TCD) and radiological computed tomography (CT) and digital subtractive angiography (DSA) examinations. Ultrasound findings (CDFI of carotid and vertebral arteries) were positive for vessel dissection in seven patients (or 87.5 per cent) and negative in one patient. DSA was consistent with dissection in five patients (or 62.5 per cent), negative in one, while in two patients the examination was not performed due to known allergy to contrast media. Five patients (62.5 per cent) were treated with anticoagulants, one with suppressors of platelet aggregation, and two patients were operated. Six patients (75 per cent) after the treatment showed partial recovery of neurological defects, and an improvement of ultrasound finding of dissected arteries. In one patient, following operation, stroke developed with deterioration of motor deficit, and one patient was readmitted three months later due to a newly developed stroke and soon died. The diagnosis should be suspected in any young or middle-age patient with new onset of otherwise unexplained unremitting headache or neck ache, especially in association with transient or permanent focal neurological deficits.

Ultrasound measurement of the volume of musculus quadriceps after knee joint injury.

The monitoring of the recovery of femoral muscles, after the knee-joint injury, is possible by the method of ultrasound measurement of the muscular volume. In a clearly defined longitudinal study, our object was to standardize the method of ultrasound measurement of muscular volume and to evaluate its adequacy in practical application in quadriceps muscle rehabilitation. The ultrasound measurements of m. rectus femoris and m. vastus intermedius were conducted in three intervals: in the first 24 hours after the injury; after 1 week, when immobilization was removed; and after 6 weeks, when rehabilitation was finished. The study comprised 30 patients with knee-joint injury, and 30 asymptomatic subjects, who formed the control group. The results showed significant decrease of muscular volume (mm3) after joint immobilization on injured leg and a significant increase of volume after rehabilitation. The same differences were observed on healthy legs, but without significance. Within the same intervals, there were no changes in the muscular mass in the control group. M. rectus femoris was completely recovered in greater number of patients (54.1%), comparing to m. vastus intermedius (25.4%). We conclude that the ultrasound is an appropriate method for monitoring the process of muscular atrophy during immobilization, as well as the course of muscular restitution during the physical therapy.

[Recommendations for care of patients with cerebral accident. Part One: Organization of care for patients with cerebral accidents, treatment of cerebral accident and neurorehabilitation]. / Preporuke za zbrinjavanje bolesnika s mozdanim udarom. Prvi Dio: Organizacija skrbi za bolesnike s mozdanim udarom, lijecenje mozdanog udara i neurorehabilitacija.

Stroke is the leading cause of disability in modern society. In developed countries stroke is the second or the third cause of death, and in Croatia it is the leading cause of death. Therefore, stroke is not only a great medical, but also economic burden. Figures show that the incidence of stroke in transitional countries is increasing, so the epidemic of stroke could be expected in the forthcoming years. The Croatian Society for Neurovascular Disorders of the Croatian Medical Association and the Croatian Stroke Society wrote the recommendations for stroke management. The first part presents the recommendations for organization of stroke care, stroke treatment and neurorehabilitation, and the second part will present the recommendations for prevention of stroke.

[Recommendations for management of patients with cerebral stroke. Part Two: Primary and secondary prevention of cerebral stroke]. / Preporuke za zbrinjavanje bolesnika s mozdanim udarom. Drugi Dio: Primarna i sekundarna prevencija mozdanog udara.

Despite the enormous progress done in the course of last years in diagnosis, treatment and rehabilitation of stroke patients, prevention is still main strategy in approaching the stroke. After the comprehensive review of the organization of stroke care, treatment and neurorehabilitation of stroke patients, this part shows the recommendations of the Croatian Society for Neurovascular Disorders of the Croatian Medical Association and the Croatian Stroke Society for primary and secondary prevention of stroke.

The association of inflammatory markers with cerebral vasoreactivity and carotid atherosclerosis in transient ischaemic attack.

OBJECTIVES: Inflammatory mediators have an important role in the pathogenesis of stroke. Increased activity of inflammatory mediators initiates the development of atherosclerosis independently of other risk factors, thus compromising brain microcirculation and causing transient ischaemic attack (TIA). The aim of our study was to evaluate the relationship between serum level of cellular adhesion molecules (ICAM-1), interleukin-6 (IL-6) and C-reactive protein (CRP) with carotid intima-media thickness (IMT) and breath-holding index (BHI) in subjects with transient ischaemic attack. We also aimed to assess the difference of those markers between TIA patients and disease-free control individuals. DESIGN AND METHODS: The study included 45 TIA patients and 36 disease-free controls matched for age, gender and vascular risk profile. The degree of carotid atherosclerosis was assessed by colour Doppler with measurements of carotid IMT. Transcranial Doppler (TCD) ultrasound was performed in order to assess BHI. IMT, TCD, BHI and serum concentrations of ICAM-1, IL-6, and CRP were measured for all study subjects. RESULTS: Inflammatory markers IL-6, ICAM-1 and CRP were significantly higher in TIA patients than in disease-free controls (P<0.001, P=0.026, P<0.001, respectively). TIA patients had significantly lower values of BHI and higher IMT relative to disease-free control individuals (P<0.001). CONCLUSIONS: TIA is associated with higher ICAM-1, IL-6 and CRP, pointing to the marked inflammatory response to cerebral ischaemia. Inflammatory markers are associated with higher IMT and lower BHI, indicating the insufficient cerebral perfusion due to the underlying atherosclerotic disease. Our findings highlight the key significance of inflammation in the early response to ischaemia during the transitory ischaemic episode.

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.

Diagnostic accuracy of serum brain derived neurotrophic factor concentration in antidepressant naïve patients with first major depression episode.

Diagnosing major depressive disorder (MDD) continues to be based on meeting phenomenological and descriptive criteria. As of yet, there is still no non-invasive, peripheral biomarker that would allow for a certain diagnosis of MDD. The objective of this paper is to use the receiver operating characteristic (ROC) analysis to test the diagnostic value of serum concentrations of brain derived neurotrophic factor (BDNF) in diagnosing the first episode of MDD. Among 1014 patients admitted for an initial psychiatric evaluation, antidepressant naïve patients diagnosed with first episode MDD were separated into the test group. Only patients signing an informed consent form were included in the study. Using DSM-IV-TR diagnostic criteria, those patients meeting the MDD criteria (N = 122) and patients not meeting MDD or other psychiatric disorder criteria (N = 142) were differentiated. Subjects with repeated episode MDD (N = 121) and other psychiatric comorbid illnesses (N = 138) in the MDD group were excluded from the study. In the group without MDD or other psychiatric illnesses, patients with physical comorbidities (N = 59) were excluded. The serum concentration of BDNF was determined in all patients using the ELISA assay. Subjects with first episode MDD showed differences in serum BDNF concentrations (ng/mL) in comparison to the control group of patients not meeting the criteria for first episode MDD (mean ± SD; 37.5 ± 13.3 vs. 56.8 ± 6.3; t = 1.372; df = 262; p < 0.01). The ROC analysis established a discriminant diagnostic value of serum BDNF in diagnosing MDD. The area under the curve (AUC) was 0.892 with a 95% confidence level (0.826-0.939), which was statistically significant at p < 0.01. The serum BDNF had a high diagnostic sensitivity of 83.9% and a specificity of 93%. Serum BDNF concentrations appear to be a promising tool in discriminating subjects with MDD from those without MDD.

Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease.

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the alpha-galactosidase A (alpha-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.

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.

Recommendations for diagnosis and management of multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating neurologic disorder that mainly affects young individuals (aged 20 to 50 years). Approximately 85% of patients experience an initial course with relapses and remissions (relapsing-remitting multiple sclerosis). Guidelines for the management of MS should be focused on three main areas: (a) the diagnosis of MS; (b) treatment of relapses; and (c) long-term preventive treatment including clinical follow up, dose adjustment, drug switch, control of therapeutic efficacy, and disease progression. Diagnosis should be established according to clinical and paraclinical criteria. Discussion on therapeutic recommendations is focused on the disease-modifying agents in acute phases and drugs for long-term treatment and symptomatic treatment. Differential diagnoses must be taken into account on making the diagnosis of MS. Therefore, diagnosis of MS should be established on clinical and radiological diagnostic criteria, cerebrospinal fluid analysis and evoked potentials.

Report of the Croatian Society for Neurovascular Disorders, Croatian Medical Association. Evidence based guidelines for treatment of primary headaches--2012 update.

These guidelines have been developed to assist the physician in making appropriate choices in work-up and treatment of patients with headaches. The specific aim of the Evidence Based Guidelines for Treatment of Primary Headaches--2012 Update is to provide recommendations for establishing an accurate diagnosis and choose the most appropriate therapy in the group of patients with primary headaches, based on a comprehensive review and meta-analysis of scientific evidence with regard to treatment possibilities in Croatia. These data are based on our previous Evidence Based Guidelines for Treatment of Primary Headaches published in 2005 and other recommendations and guidelines for headache treatment.

Diagnostic value of some less frequently considered blink reflex parameters in idiopathic trigeminal neuralgia.

AIM OF THE STUDY: We have done a study investigating the value of some less frequently considered Blink reflex parameters for establishing the diagnosis of idiopathic trigeminal neuralgia. PATIENTS: The study was done on 50 patients suffering from idiopathic trigeminal neuralgia, diagnosed according to the guidelines of the International Classification of Headache Disorders, with no other apparent illness. METHODS: We have stimulated the supraorbital nerve at the forehead (foramen n. supraorbitalis) and recorded the reflex response on both mm. orbiculares oculi. Incidence of following findings was determined: (1) occurrence of ipsilateral R3 component, (2) prolonged duration (>25 ms) of R2 when stimulating the affected side and (3) occurrence of R1 component during the stimulation of contralateral supraorbital nerve. We have compared these findings to those of 50 healthy subjects from the control group (Chi-square, p < 0.05). Sensitivity, specificity and diagnostic value for individual parameters were determined. RESULTS AND CONCLUSION: All three parameters tested proved to have a significantly higher incidence in the group of subjects. The occurrence of R3 component on the affected side showed the highest diagnostic value. SIGNIFICANCE: We believe these findings could electrophysiologically reinforce the clinically established diagnosis of idiopathic trigeminal neuralgia.

Breath holding index in detection of early cognitive decline.

The aim of the study was to evaluate role of breath holding index (BHI) as a functional parameter for intracranial subclinical atherosclerotic changes in recognizing patients who are at risk for developing cognitive impairment of the vascular type. We included 60 volunteers divided into 3 groups according to age and presence of cognitive impairment (healthy subjects 30-40 years old, controls 60-70 years old and subjects with mild cognitive impairment 60-70 years old). We excluded individuals with moderate and severe carotid stenosis. There was a decreasing trend in the mean blood flow velocities of the intracranial blood vessels due to age increase, but it was not statistically significant. BHI values were 1.66±0.20 in the first group, 1.35±0.31 in the second and 0.69±0.30 in the third group. There was a statistically significant difference between the first two groups and the group with a mild cognitive impairment (MCI) in Montreal cognitive assessment (MoCA) score (29±1, 27±1 and 19±1 respectively), no statistically significant difference was found in Mini mental state exam (MMSE) score (29±1, 28±1, and 28±1 respectively). After regressing out age and conventional vascular risk factors, we found a good correlation between the decreasing trend in BHI values and MoCA score, and no statistically significant correlation between the BHI values and MMSE score. Results of our study show that BHI test as a parameter of impaired cerebrovascular reactivity (intracranial small vessel wall dysfunction) might differentiate individuals with early cognitive decline from healthy subjects.

Is iron deficiency anemia related to menstrual migraine? Post hoc analysis of an observational study evaluating clinical characteristics of patients with menstrual migraine.

The aim of this study was to determine the relative prevalence and clinical characteristics of patients with pure menstrual migraine (PMM) and menstrually related migraine (MRM), and to compare them with the women free of it in an outpatient clinic-based population. Adult menstruating women with ICHD-2 migraine were included. Demographic data were obtained by verbal report. Study women were asked to keep a headache diary for 6 months, in which they recorded information on headache characteristics, medication use and presence of menses. Iron deficiency anemia was considered to be present if the patient had received therapy for iron deficiency anemia or laboratory tests indicated low iron and/or hemoglobin levels (within one year). A total of 289 women were included, 52 (18.0%) with PMM and 116 (40.1%) with MRM, whereas 121 (41.9%) women had not observed any relationship between migraine and their menstrual cycle (non-MM). Duration of migraine attacks was longer in PMM/MRM patients (P < 0.0001). No significant difference was observed according to other migraine-associated symptoms. Women with PMM/ MRM took significantly more tryptans (P < 0.0001) and iron deficiency anemia was significantly more common in women with PMM/MRM (P = 0.008). In conclusion, this study supported earlier findings that PMM/MRM has similar clinical characteristics as non-MM, except for longer duration. In addition, iron deficiency anemia is more common in women with PMM/MRM, which may be an underlying mechanism aggravating migraine attacks.