SPINAL SUBDURAL HEMATOMA ASSOCIATED WITH LUMBAR PUNCTURE - A CASE REPORT.

Spinal subdural hematoma caused by lumbar puncture is a rare state of acute blood clot in spinal subdural space, and in some cases, it can be the cause of local compression and consecutive neurological symptoms. We present a 36-year-old female patient who was hospitalized due to persistent headache despite pharmacological therapy. Therefore, we performed lumbar puncture in order to measure intracranial pressure and evaluate cerebrospinal fluid. After lumbar puncture, the patient was complaining of pain in the lumbar region. Emergency magnetic resonance imaging (MRI) of the lumbosacral (LS) region was performed to show acute subdural hematoma of up to 7.3 mm in the dorsal part of the spinal canal at the level of L1 vertebra to the inferior endplate of L4 vertebra. Repeat LS MRI after 3 hours showed unchanged finding. The patient reported gradual regression of pain in the LS region over the next few days, therefore conservative treatment was applied. Patients with a previously known blood clotting disorder and patients on anticoagulation therapy have worse outcome as compared with patients without such disorders. During treatment, it is necessary to monitor patient clinical state and consider the need of surgical treatment.

Treatment of relapsing multiple sclerosis - recommendations of the Croatian Neurological Society.

Untreated multiple sclerosis (MS) irretrievably leads to severe neurological impairment. In European health care systems, patient access to disease modifying therapies (DMT) is often confined to more advanced stages of the disease because of restrictions in reimbursement. A discrepancy in access to DMTs is evident between West and East European countries. In order to improve access to DMTs for people with MS (pwMS) living in Croatia, the Croatian Neurological Society issued new recommendations for the treatment of relapsing MS. The aim of this article is to present these recommendations. The recommendations for platform therapies are to start DMT as soon as the diagnosis is made. If poor prognostic criteria are present (≥9 T2 or FLAIR lesions on the initial brain and spinal cord magnetic resonance imaging [MRI] or ≥3 T1 lesions with postcontrast enhancement on the initial brain and spinal cord MRI or Expanded Disability Status Scale after treatment of the initial relapse ≥3), high-efficacy DMT should be initiated. If pwMS experience ≥1 relapse or ≥3 new T2 lesions while on platform therapies, they should be switched to high-efficacy DMT. Further efforts should be made to enable early and unrestricted access to high-efficacy DMT with a freedom of choice of an appropriate therapy for expert physicians and pwMS. The improvement of access to DMT achieved by the implementation of national treatment guidelines in Croatia can serve as an example to national neurological societies from other Eastern European countries to persuade payers to enable early and unrestricted treatment of pwMS.

The role of thyroid hormones in carotid arterial wall remodeling in women.

Introduction: Thyroid hormones affect the cardiovascular system, but the precise mechanisms of their effects on the development of atherosclerosis are not entirely clear. The relationship between subclinical hypothyroidism, dyslipidemia and carotid atherosclerosis has been widely investigated, but the findings were controversial. The aim of the present study was to determine whether female subjects with subclinical hypothyroidism (SHypo) have increased carotid intima-media thickness (IMT) compared with euthyroid subjects, as well as to examine the association of SHypo, carotid atherosclerosis and dyslipidemia.Methods: This research included 100 women aged 30 to 70 years who were divided into two groups: the SHypo group including subjects with signs of subclinical hypothyroidism and the control group of euthyroid subjects. Carotid IMT thickness using B mode ultrasound was determined and its correlation with serum concentrations of fT4, TSH, CRP, and lipid profile including small dense LDL (sdLDL) was analysed.Results: Subjects with SHypo had significantly increased carotid IMT (IMT ≥ 75th centile) in all three measured segments of the right (p <0.001) and the left (p = 0.001) carotid artery compared to the control group, with a significantly more frequent appearance of plaque (25% vs. 9%; p = 0.05). Significant positive correlations were found between higher TSH and higher IMT values. Increased age, LDL cholesterol, and TSH predicted thickening of the carotid artery IMT.Conclusions: It is important to screen people showing early, subclinical signs of thyroid gland dysfunction due to its impact on carotid atherosclerosis development.

Multiple sclerosis and Fabry disease - diagnostic "mixup".

A common disease like multiple sclerosis (MS) usually dominates the arena of demyelinating disorders; however, when a red flag such as a first relative family history of neurologic disease other than MS is present, the diagnostics may be more challenging. Recently, we have come across an intriguing clinical and diagnostic dilemma requiring extensive literature search and finally, decision making. Namely, initial presentation in our patient was that of a frequent condition such as optic neuritis and demyelinating CNS lesions, and then unexpected additional information during the usual diagnostic process, in the matter of first relative being diagnosed with a rare disease - Anderson-Fabry disease, oriented us in another direction. Almost paradoxically, the rare diagnosis being genetically confirmed, initiated treatment first. Furthermore, multitude of published data instigated clinical, radiological and laboratory uncertainty in our minds urging us to use a "wait and see" approach for the potential second diagnosis in order to prevent causing harm or labeling our patient wrongly by a potential misdiagnosis. However, further clinical course, a follow-up MRI, comparison with initial findings, and multi-disciplinary consultation safely directed us to a frequent diagnosis of multiple sclerosis. Our patient is currently treated for both conditions.

Attention modulates topology and dynamics of auditory sensory gating.

This work challenges the widely accepted model of sensory gating as a preattention inhibitory process by investigating whether attention directed at the second tone (S2) within a paired-click paradigm could affect gating at the cortical level. We utilized magnetoencephalography, magnetic resonance imaging and spatio-temporal source localization to compare the cortical dynamics underlying gating responses across two conditions (passive and attention) in 19 healthy subjects. Source localization results reaffirmed the existence of a fast processing pathway between the prefrontal cortex (PFC) and bilateral superior temporal gyri (STG) that underlies the auditory gating process. STG source dynamics comprised two gating sub-components, Mb1 and Mb2, both of which showed significant gating suppression (>51%). The attention directed to the S2 tone changed the gating network topology by switching the prefrontal generator from a dorsolateral location, which was active in the passive condition (18/19), to a medial location, active in the attention condition (19/19). Enhanced responses to the attended stimulus caused a significant reduction in gating suppression in both STG gating components (>50%). Our results demonstrate that attention not only modulates sensory gating dynamics, but also exerts topological rerouting of information processing within the PFC. The present data, suggesting that the cortical levels of early sensory processing are subject to top-down influences, change the current view of gating as a purely automatic bottom-up process.

RECURRENT ATYPICAL OPTIC NEURITIS AS THE LEADING SIGN OF FABRY DISEASE.

Acute optic neuritis has the age and sex adjusted incidence of 1-5/100,000 in general population. It is mostly a disorder affecting young Caucasian women (31-32 years). Patients present to a wide range of clinicians including general practitioner, emergency physician, ophthalmologist, neurologist, etc. There are two main clinical presentations of optic neuritis, typical and atypical. It is of great importance to distinguish these two types of optic neuritis in order to detect the underlying etiology and plan appropriate and timely treatment. We present a young female patient (36 years) admitted to Department of Ophthalmology due to visual loss on the left eye. Magnetic resonance imaging showed demyelinating lesions in frontal and parietal lobe, periventricularly, in mesencephalon and right cerebellar hemisphere, and left optic neuritis; magnetic resonance angiography was normal. The patient's history revealed renal dysfunction, hypothyroidism, and miscarriage in the 6th month of pregnancy due to eclampsia, and Fabry disease in family (mother and two sisters). She was transferred to the Department of Neurology for further evaluation of the demyelinating disorder of the central nervous system. The patient received corticosteroid therapy (methylprednisolone 1 g) for 5 days with regression of visual disturbances on the left eye. After this acute treatment, the question of definitive diagnosis remained, along with further treatment of the underlying cause. Considering renal dysfunction, miscarriage, arterial hypertension, positive genetic and biochemical testing for Fabry disease in close relatives (mother), we suspected that she also had Fabry disease. She was tested and the results were positive. We concluded that optic neuritis was the first sign of Fabry disease in this case, reflecting acute atypical neuroinflammatory disease.

MULTIPLE SCLEROSIS OR FABRY DISEASE - PROS AND CONS.

- Fabry disease is a rare X-linked inherited lysosomal storage disease affecting multiple organ systems, presenting in the central nervous system (CNS) as white matter lesions with underlying cerebral vasculopathy and autoinflammatory changes of the choroid plexus and leptomeninges. We present a young female patient (age 36 years) admitted to our department due to visual loss on the left eye. Magnetic resonance imaging (MRI) showed demyelinating lesions in the frontal and parietal lobe, periventricularly, in mesencephalon and right cerebellar hemisphere, and left optic neuritis; MR angiography was normal. Her medical history revealed renal dysfunction, hypothyroidism, and miscarriage in the 6th month of pregnancy due to eclampsia and Fabry disease in the family (mother). Cerebrospinal fluid analysis showed mild pleocytosis, normal blood brain barrier function and oligoclonal bands type 3. Visual evoked potentials showed prechiasmal dysfunction of the left optic nerve. Genetical testing for Fabry disease was positive (two heterozygous mutations), with decreased alpha galactosidase activity values and increased Lyso GB3 values. The patient received corticosteroid therapy (methylprednisolone) 1 g for 5 days, which led to regression of visual disturbances on the left eye. After this acute treatment, there was a question of definitive diagnosis and further treatment of the underlying cause. Considering renal dysfunction, miscarriage, arterial hypertension, positive genetic and biochemical testing for Fabry disease, as well as MRI findings showing lesions in posterior circulation, we concluded that the patient probably had Fabry disease with autoinflammatory changes in the CNS and should be treated with enzyme replacement therapy. Still, there was a question of optic neuritis on the left eye and positive oligoclonal bands favoring the diagnosis of multiple sclerosis. Therefore, further clinical and neuroradiological follow up was needed to distinguish multiple sclerosis and Fabry disease in this patient.

Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C).

BACKGROUND: Usually both hypothyroidism and hyperthyroidism are related to the cardiovascular and cerebrovascular disease development. The relationship between subclinical hypothyroidism has been widely investigated but the findings remain controversial. The aim of the present study was to evaluate the lipid profile in patients with subclinical hypothyroidism (SHypo) in comparison to controls and to determine the association of SHypo and dyslipidemia in attempt to find importance of small dense low-density lipoprotein cholesterol (sdLDL-C) in atherosclerosis. MATERIAL AND METHODS: In this study we included 100 women, aged 30 to 70 years that were divided into subgroups according to their age. According to the values of levels of thyroid hormones they were divided into euthyroid (control) group (n = 64) and (newly discovered) subclinical hypothyroidism (SHypo) group (n = 36). A high-sensitivity C-reactive protein (hs-CRP) and lipid profile, including small dense low-density lipoprotein cholesterol (sdLDL-C) were determined. Body weight and height were measured and BMI calculated. History of the current illness, medication, alcohol consumption and cigarettes smoking were noted. RESULTS: Changed lipid profile as well as elevated triglycerides and sdLDL-C were observed in the group with subclinical hypothyroidism compared to the control group. CONCLUSIONS: It is important to determine serum lipid levels, especially serum sdLDL-C levels at an early stage of subclinical hypothyroidism, since they represent atherogenic LDL particles and are better indicators for dyslipidaemia in subclinical hypothyroidism and the development of atherosclerosis with potential complications such as cardiovascular and cerebrovascular diseases.

AGE AND GENDER DIFFERENCES IN ACUTE STROKE HOSPITAL PATIENTS.

Stroke is the second leading cause of death and the most important cause of adult disability worldwide and in Croatia. In the past, stroke was almost exclusively considered to be a disease of the elderly; however, today the age limit has considerably lowered towards younger age. The aim of this study was to determine age and gender impact on stroke patients in a Croatian urban area during one-year survey. The study included all acute stroke patients admitted to our Department in 2004. A compiled stroke questionnaire was fulfilled during hospitalization by medical personnel on the following items: stroke risk factors including lifestyle habits (smoking and alcohol), pre-stroke physical ability evaluation, stroke evolution data, laboratory and computed tomography findings, outcome data and post-stroke disability assessment. Appropriate statistical analysis of numerical and categorical data was performed at the level of p < 0.05. Analysis was performed on 396 patients, 24 of them from the younger adult stroke group. Older stroke patients had worse disability at hospital discharge and women had worse disabilities at both stroke onset and hospital discharge, probably due to older age at stroke onset. Younger patients recovered better, while older patients had to seek secondary medical facilities more often, as expected. The most important in-hospital laboratory findings in young stroke patients were elevated lipid levels, while older patients had elevated serum glucose and C-reactive protein. Stroke onset in younger patients most often presented with sudden onset headache; additionally, onset seizure was observed more frequently than expected. Stroke risk factor analysis showed that women were more prone to hypertension, chronic heart failure and atrial fibrillation, whereas men had carotid disease more frequently, were more often smokers and had higher alcohol intake. Additionally, age analysis showed that heart conditions and smoking were more prevalent among older stroke patients. In conclusion, considerable differences were established between age and gender stroke patient groups, confirming the need of permanent national stroke registry and subsequent targeted action in secondary care, and prevention with education on risk factors, preferably personally tailored.

MIGRAINE, CAROTID STIFFNESS AND GENETIC POLYMORPHISM.

Recently migraine has been associated with increased arterial stiffness, procoagulant state, increased incidence of cerebral white matter lesions (WML) and stroke. Our aim was to compare the characteristics of migraineurs to headache free controls regarding their functional carotid ultrasound parameters. Sixty patients (45 women) with migraine (mean age 40.42 ± 10.61 years) were compared with 45 controls (30 women) with no prior history of repeating headache (mean age 38.94 ± 5.46 years) using E-tracking software on Alpha 10 ultrasound platform. Student's t-test was used on statistical analysis with alpha < 0.05. All tested carotid vascular parameters were worse in patients with migraine including increased intima-media thickness, greater carotid diameter and carotid diameter change, as well as several arterial stiffness indices. Additionally, patients with migraine had greater incidence of homozygous mutations for procoagulant genes (MTHFR (C677T), PAI-1 and ACE I/D) than expected. Computed tomography and magnetic resonance imaging of the brain showed WML in 11 patients, four of them migraine with aura patients. Since we established increased carotid stiffness and higher frequency of procoagulant gene mutations in migraineurs, we propose prospective ultrasound monitoring in such patients, especially those with detected WML, in order to timely commence more active and specific preventive stroke management strategies.

Vascular characteristics of patients with dementia.

Arterial beta stiffness index is a potential risk factor for increased stroke occurrence. Vascular component appears to be significant in both Alzheimer's disease (AD) and vascular dementia (VAD). We aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. There were 38 patients; 16 diagnosed with AD and 22 with VAD. Vascular risk factors were assessed and ultrasound measurements on common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with 13 MHz linear probe. Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima-media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients. Even though there was no significant difference found among two explored subgroups of patients with dementia, there was a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence.

Can beta stiffness index be proposed as risk factor for dementia.

BACKGROUND AND AIM: Changes of arterial stiffness indicate alteration in arterial mechanics predisposing to the evolution of stroke or vascular dementia. The aim of this pilot study was to investigate whether ultrasound parameters, particularly beta stiffness index (BSI), should be further explored as independent markers or risk factors for dementia. PATIENTS AND METHODS: There were 38 demented patients included in this study (72.53+/-7.87 yrs) and 33 clinically healthy controls (68.85+/-3.52 yrs). Risk factors were noted and ultrasound measurements performed on common carotid artery (CCA) using eTracking software on Aloka ProSound ALPHA 10 with 13 MHz linear probe. Level of significance was p<0.05. RESULTS: Arterial hypertension was present in 24 patients, atrial fibrillation in 9, diabetes in 3, and hypercholesterolemia in 18. Hypertension was present as a single risk factor in 15 controls with average diastolic blood pressure significantly lower in patients. Significantly higher in patients were mean intima-media thickness, systolic and diastolic CCA diameters (CD), and mean BSI in CCA bilaterally. Linear regression analysis for groups of Alzheimer's dementia and vascular dementia proved that MMSE of the two groups relates to CCA diameter change (CDc) and BSI change explaining up to 5% of variability. CONCLUSIONS: CD, CDc and BSI should be monitored in patients with cognitive decline and further explored as possible independent markers or risk factors; in future studies groups of demented and non-demented patients should be age, sex and risk factor matched.

Beta stiffness--setting age standards.

Beta stiffness index is one of the most commonly used measures of depicting mechanical arterial properties and development of preclinical atherosclerosis. Main influences on its value hold age and blood pressure levels. The goal of this study was to determine age standards of beta stiffness index on common carotid artery in our population using a formula modified by Kawasaki. The study was conducted in 150 healthy volunteers aged 25-75 on an Aloka 5500-SSD Pro-sound ultrasound platform using B and M modes. The data obtained were analyzed by appropriate statistical methods. Study results confirmed linear relationship of beta index and age. Calculation of beta index is applicable for assessment and monitoring of vascular physiology changes because it is simple for use, prompt in analysis and suitable for bed-side evaluation.

The association of obesity and cerebrovascular disease in young adults--a pilot study.

Obesity has been recognized as an isolated risk factor for stroke. In obese patients, other risk factors for stroke such as hypertension, hyperlipidemia, ischemic heart disease and obstructive sleep apnea are more frequently present. The aim of this study was to assess the presence of obesity among other risk factors for stroke in younger adult patients with ischemic stroke. It was a pilot study performed in ischemic stroke patients aged 18-55. In addition to the routine diagnostic work-up, body height, weight and waist circumference were measured in study patients. The study included 50 patients, 23 female and 27 male. The mean age of male patients was 39.8 +/- 10.5 and of female patients 41.6 +/- 7.7 years. In control group The mean waist circumference was 94.9 +/- 5.8 cm in the control group and 102.6 +/- 9.8 cm in the male stroke group. There was no significant difference in waist circumference between the control and patient female groups and in body mass index among all groups. In younger males, waist circumference could be considered as an important risk factor for stroke.

[Vascular age assessment in smokers]. / Vaskularna dob pusaca.

AIM: Smoking is the most harmful social habit and is the origin of many diseases including direct damaging of arterial walls. The aim of this study was to assess the possible differences in vascular age of smokers versus never smokers, measured in common carotid artery (CCA). METHODS: The study included healthy volunteers with age and sex risk factors for cerebrovascular disease development. Measurements in CCA were performed in M mode on an Aloka 5500 Prosound ultrasound platform bilaterally. Carotid intima-media thickness (IMT), carotid interadventitial diameter (CID) and carotid interadventitial diameter change (CIDc) were recorded, and carotid interadventitial strain (CIS) was calculated. Median age subanalysis was performed for IMT, CIDc and CIS. Mann-Whitney statistics was used to determine group differences. RESULTS: There were 121 subjects, 80 women and 41 men, mean age 47.43 +/- 14.15 years. There were 23 (19%) current smokers, 17 (14%) occasional smokers, 11 (9%) past smokers, and 70 (58%) non-smokers. A statistical increase in IMT was found in the group of previous smokers (the eldest) in the left CCA (P < 0.05). CIDc and CIS were statistically higher in the right CCA in the group of current smokers (P < 0.05 both). Older subjects had an increase in IMT values in both CCA and decrease in CIDc and CIS in the right CCA. CONCLUSIONS: The results indicated cigarette smoking to primarily cause an increase in CIDc, whereas CIS remained preserved. Smoking influences vascular age. Additional studies are necessary to address the issue in a greater number of smokers.

Music as an auditory stimulus in stroke patients.

Auditory stimulation increases mean blood flow velocity (MBFV) in the middle cerebral artery (MCA) in healthy individuals. Our aim was to monitor such changes in the affected MCA of patients with acute ischemic stroke (AIS). The study included 66 non-thrombolysed patients with AIS who were divided into groups according to National Institutes of Health Stroke Scale (NIHSS) score. Group I consisted of patients with NIHSS score 10 and group II with NIHSS score > or =11. Affected MCA was insonated with transcranial Doppler (TCD). MCA MBFVs were monitored during listening to music for 30 minutes. The first response of MBFV increase was measured as time (Tmax) and percentage of amplitude change (Amax). Pearson Chi-Square test was used. In 78.85% of patients there was a significant increase in MBFV compared to baseline values as a reaction to the music. There was no significant difference in Tmax or Amax between the two groups. However, a trend of longer Tmax was observed with every 2 NIHSS score increase. Music is an auditory stimulus in stroke patients and can be measured with TCD as MCA MBFV increase. Although our study showed no significant change of reaction time with the severity of stroke, a trend of prolonged Tmax was observed with NIHSS score increase.

How to monitor vascular aging with an ultrasound.

BACKGROUND: The discrimination between the terms "vascular disease" and "vascular aging-vascular disease interaction" can be used for active health patrolling and disease prevention. Our aim was to set age standards for vascular ultrasound parameters usable in epidemiological studies. METHODS: Investigation was conducted on healthy volunteers (age range 25-75 years). The evaluated parameters were: intima-media thickness (IMT), diameter change and circumferential arterial stiffness (CAS), resistance (RI), pulsatility (PI) and A/B indexes on common carotid artery (CCA). Measurements were performed on Aloka 5500-SSD Prosound ultrasound platform in B and M modes by standard protocols. ANOVA statistics was used for evaluation. RESULTS: There were 104 women and 46 men, 20% were hypertensive (all values still within the normal range under medication), 24% were overweight and 13% were active smokers. Investigated vascular parameters were within the normal age. IMT values bilaterally, RI on the right CCA and interadventitial diameters and CAS on the right CCA were found dependent to age (p<0.05). PI, A/B index, luminal diameters were not found age dependant (p>0.05). CONCLUSIONS: Ultrasound can be used to determine proper vascular age of individuals offering proposition of different strategies for reduction or retardation of clinical manifestation of cerebrovascular disease.