Cerebral venous thrombosis: a retrospective unicentric analysis of clinical and neuroimaging characteristics.

Thrombosis of dural sinuses and/or cerebral veins (CVT) is an uncommon form of stroke, usually affecting young individuals. It has a variable clinical presentation ranging from mild cases presenting only headaches, to severe cases featuring encephalopathy, coma or status epilepticus. A retrospective cross-sectional study of patients treated in the outpatient department and in-hospital during the period from 2014 to 2020 at the Neurology Clinic-University Clinical Centre of Serbia was conducted. Forty-nine patients (24 men; 25 women) were included in the study. Twenty-three patients (46.9%) suffered a subacute form of CVT (48 h-4 weeks), 19 (38.8%) presented with an acute form (< 48 h) and 7 (14.3%) with a chronic form (> 4 weeks). Around 75% of patients reported headaches during disease course. Focal neurological deficit (FND) was observed in 27 (55.1%) patients. Patients who did not report headaches (22.4%) presented with more severe symptoms (seizures and coma). More than 70% of patients had no radiologically evident brain parenchymal lesion. The most frequent locations of CVT were transverse sinus (79.6%), sigmoid sinus (44.9%) and superior sagittal sinus (36.7%). Thrombosis of more than one sinus/vein occurred in 33 (67.3%) patients. Hereditary thrombophilia was observed in 9 (18.4%) patients, 11 (22.4%) patients had some type of infection and 20% of women reported OCT usage. As much as 25% of cases remained without evident risk factors. The most common symptom in our cohort was acute unilateral throbbing headache of high intensity, while patients without headaches had more severe symptoms.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Transcranial Doppler Evaluation of the Cerebral Vasculature in Women Patients who Have Migraine with Aura.

BACKGROUND: Previous studies suggest that increased cerebrovascular reactivity might be a feature of patients who have migraine with aura (MwA). The correlation between the clinical presentation of migraine with aura and transcranial Doppler parameters remains unclear. OBJECTIVE: The main aim of this study was to explore cerebral blood flow, vascular resistance, and cerebrovascular reactivity in women MwA. Also, the relationships between hemodynamic conditions and aura characteristics are examined. DESIGN: Cross-sectional study. SETTING: Headache Center, Neurology Clinic, Clinical Center of Serbia. SUBJECTS: Fifty-four women MwA and 49 healthy controls (HCs). METHODS: Transcranial Doppler sonography examination was used to determine blood flow mean velocity (MV) and pulsatility index (PI), as well as breath-holding index (BHI), in 15 arterial segments comprising the circle of Willis. RESULTS: A total of 54 women MwA and 49 HCs were studied. The PIs of all segments of the left and right middle cerebral arteries and the left and right anterior cerebral arteries were significantly higher in MwA with regards to HCs. Also, both the left and right BHIs were significantly higher in MwA than HCs. In addition, MVs of the right vertebral artery and the first segment of the basilar artery were significantly lower in MwA than HCs. Longer duration of migraine aura showed a weak negative correlation with the PI of the left posterior cerebral artery. CONCLUSIONS: Our findings suggest increased vessel pulsatility, abnormal cerebrovascular reactivity, and decreased cerebral blood flow velocity in several arterial segments of the Willis circle in women MwA.

Dysphasia and Other Higher Cortical Dysfunctions During the Migraine Aura-a Systematic Review of Literature.

PURPOSE OF THE REVIEW: Although visual and somatosensory disturbances are the most common migraine aura (MA) symptoms, patients can also experience other symptoms during their MA. The aim of this review is to provide an overview of studies that report symptoms of dysphasia and other higher cortical dysfunctions (HCDs) during MA, as well as to determine the frequency of HCDs. RECENT FINDINGS: Five studies met the inclusion criteria, corresponding to 697 patients overall. The most frequently reported HCDs were those of the language group (range 10-53%). The occurrence of visual HCDs was noted in 12-40 patients, somatosensory HCDs in 12-20%, and memory disturbances in 10-22% of the patients during MAs. MA is associated with a wide range of neurological symptoms, including symptoms of HCD. A better strategy for investigation of the HCD symptoms is needed to correctly stratify patients thus allowing meaningful studies of aura pathophysiology.

Proposal for a Migraine Aura Complexity Score.

OBJECTIVES: Currently, there is no scoring system for assessing the complexity of migraine aura. Our goal was to develop a Migraine Aura Complexity Score that synthesizes the quantity and quality of aura symptoms and to test its applicability in neuroimaging studies. METHODS: Patients with migraine aura were interviewed in order to obtain characteristics of migraine aura. Explorative and confirmatory analyses were used to develop the Migraine Aura Complexity Score. Median values were derived from 10 consecutive migraine auras in each patient. The Migraine Aura Complexity Score was correlated with an average cortical thickness of different brain areas in studied patients. The Surface-based Morphometric Analysis approach was used to estimate cortical thickness. RESULTS: This study included 23 (16 females and seven males) migraineurs with aura. Confirmatory factor analysis suggested the second-order model with three-factor measurement for grading migraine aura. The first factor is linked to higher cortical dysfunction during migraine aura, while the second is associated with the degree of involvement of primary visual and somatosensory cortices; the third linked symptoms of somatosensory aura and hand and head involvement. Positive correlation of Migraine Aura Complexity Score and averaged cortical thickness were found in the left and right hemispheres overall (r = 0.568, p = 0.007; r = 0.617, p = 0.003) and in some of their regions. CONCLUSIONS: This study demonstrates that the Migraine Aura Complexity Score could be a valuable tool for assessing migraine aura. The score could be used in neuroradiological studies in order to achieve a stratification of patients with migraine aura.

Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: A prospective cohort study.

Objective To evaluate long-term predictors of remission in patients with medication-overuse headache (MOH) by prospective cohort study. Background Knowledge regarding long-term predictors of MOH outcome is limited. Methods Two hundred and forty MOH patients recruited from 2000 to 2005 were included in a one-year follow-up study and then subsequently followed until 31 December 2013. The median follow-up was three years (interquartile range, three years). Predictive values of selected variables were assessed by the Cox proportional hazard regression model. Results At the end of follow-up, 102 (42.5%) patients were in remission. The most important predictors of remission were lower number of headache days per month before the one-year follow-up (HR-hazard ratio = 0.936, 95% confidence interval (CI) 0.884-0.990, p = 0.021) and efficient initial drug withdrawal (HR = 0.136, 95% CI 0.042-0.444, p = 0.001). Refractory MOH was observed in seven (2.9%) and MOH relapse in 131 patients (54.6%). Conclusions Outcome at the one-year follow-up is a reliable predictor of MOH long-term remission.

The efficacy of fluoxetine in BMS-A cross-over study.

BACKGROUND: Burning mouth syndrome (BMS) is an intraoral burning or dysaesthetic sensation, recurring daily for more than two hours during the period longer than 3 months. The objective was to evaluate and analyse the efficacy of serotonin reuptake inhibitor fluoxetine on psychological factors, as well as on pain in participants with BMS. METHODS: In a 6-month study, 100 participants with primary and secondary BMS were divided into two groups-fluoxetine and control (placebo) and examined by the dentist and the neurologist. Depression and anxiety were estimated by Hamilton Scale for Depression (HAM-D) and Anxiety (HAM-A) and Beck Depression Inventory (BDI) and the pain intensity by visual analogue scale (VAS). RESULTS: Mean age of the participants was 60.33 in fluoxetine group and 67.4 in control group. Most of the participants were female-74% in the fluoxetine and 78% in the control group. Statistical difference between the fluoxetine and the control group was found in HAM-D results (P < .05). Values of other scales and VAS decreased significantly after the therapy in both groups (P < .05). CONCLUSIONS: Our trial results indicate that fluoxetine therapy not only improves the psychological status of participants with BMS but also fluoxetine decreases the intensity of pain in these patients.

Baseline characteristic of patients presenting with lacunar stroke and cerebral small vessel disease may predict future development of depression.

OBJECTIVE: Cerebral small vessel disease (SVD) is associated with late-onset depression and increases the risk for depression after stroke. We aimed to investigate baseline predictors of depression after long-term follow-up in patients with SVD, initially presenting with first-ever lacunar stroke, free of depression and cognitive impairment. METHODS: A total of 294 patients with SVD were evaluated 3-5 years after the qualifying event. We analyzed baseline demographic data, vascular risk factors, functional status expressed as a score on modified Rankin Scale (mRS), cognitive status, presence of depression, total number of lacunar infarcts and severity of white matter hyperintensities (WMH) on MRI with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. RESULTS: On follow-up, depression was registered in 117 (39.8%) SVD patients. At the baseline, patients with depression compared with non-depressed were older (64.4 vs 60.9 years; p = 0.007), had higher mRS score (2.8 ± 0.7 vs 1.5 ± 0.7; p < 0.0001) and had more severe lesions on MRI scales (p < 0.0001 for all parameters). On follow-up, depressed patients more frequently exhibited cognitive decline (75.2% depressed vs 56.5% non-depressed; p = 0.003). No difference was detected in risk factor frequency between groups. Multivariate Cox regression analysis adjusted by age and gender revealed independent predictors of depression: baseline mRS >2 (HR 2.17, 95%CI 1.74-2.72; p < 0.0001) and tARWMC (HR 1.05, 95%CI 1.02-1.09; p = 0.005), and cognitive decline on follow-up (HR 1.80, 95%CI 1.12-2.89; p = 0.015). CONCLUSIONS: Baseline functional status and severity of WMH and development of cognitive decline predict the occurence of late-onset depression in patients with SVD.

Headache service quality: evaluation of quality indicators in 14 specialist-care centres.

BACKGROUND: The study was a collaboration between Lifting The Burden (LTB) and the European Headache Federation (EHF). Its aim was to evaluate the implementation of quality indicators for headache care Europe-wide in specialist headache centres (level-3 according to the EHF/LTB standard). METHODS: Employing previously-developed instruments in 14 such centres, we made enquiries, in each, of health-care providers (doctors, nurses, psychologists, physiotherapists) and 50 patients, and analysed the medical records of 50 other patients. Enquiries were in 9 domains: diagnostic accuracy, individualized management, referral pathways, patient's education and reassurance, convenience and comfort, patient's satisfaction, equity and efficiency of the headache care, outcome assessment and safety. RESULTS: Our study showed that highly experienced headache centres treated their patients in general very well. The centres were content with their work and their patients were content with their treatment. Including disability and quality-of-life evaluations in clinical assessments, and protocols regarding safety, proved problematic: better standards for these are needed. Some centres had problems with follow-up: many specialised centres operated in one-touch systems, without possibility of controlling long-term management or the success of treatments dependent on this. CONCLUSIONS: This first Europe-wide quality study showed that the quality indicators were workable in specialist care. They demonstrated common trends, producing evidence of what is majority practice. They also uncovered deficits that might be remedied in order to improve quality. They offer the means of setting benchmarks against which service quality may be judged. The next step is to take the evaluation process into non-specialist care (EHF/LTB levels 1 and 2).

Dialysis headache in patients undergoing peritoneal dialysis and hemodialysis.

OBJECTIVES: Headache is among most frequently encountered neurological symptom during hemodialysis (HD), but still under investigated in peritoneal dialysis (PD) patients. The aim of this study was to assess the incidence and clinical characteristics of dialysis headache (DH) in HD and PD patients. MATERIAL AND METHODS: A total of 409 patients (91 on PD and 318 on HD) were interviewed using a structured questionnaire, designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. Patients with DH underwent a thorough neurological examination. RESULTS: DH was reported by 21 (6.6%) HD patients and 0 PD patients. PD patients had significantly lower serum sodium, potassium, calcium, phosphate, urea and creatinine, calcium-phosphate product, and diastolic blood pressure than HD patients. HD patients had significantly lower hemoglobin compared to PD patients. Primary renal disease was mostly parenchymal in HD patients, and vascular in PD patients. DH appeared more frequently in men, mostly during the third hour of HD. It lasted less than four hours, was bilateral, non-pulsating and without associated symptoms. CONCLUSION: Biochemical alterations may be implicated in the pathophysiology of DH. Specific features of DH might contribute to better understanding of this secondary headache disorder.

Cluster headache: Is age of onset important for clinical presentation?

BACKGROUND: The age of onset of cluster headache (CH) attacks most commonly is between 20 and 40 years old, although CH has been reported in all age groups. There is increasing evidence of CH with early or late onset and a different course of the disorder. The aim of the study was to analyze the influence of the age of onset on clinical features, disorder course, and therapy effectiveness in CH patients. METHODS: A retrospective and cross-sectional analysis was performed on 182 CH patients divided into three groups according to the age of onset. The first group consisted of patients with the first CH attack before 20 years of age, the second group was patients with age of onset between 20 and 40 years of age, and the third group was patients with age of onset after 40 years of age. Demographic data, features of CH periods and attacks, and the response to standardized treatment were compared among the groups. RESULTS: Patients with CH onset after 40 years of age reported a lower number of autonomic features and less frequently had conjunctival injection and nasal congestion/rhinorrhea phenomena during their attacks. Diagnostic delay was the longest in the patients with CH onset before 20 years of age. CONCLUSION: The influence of the age of onset of CH is intriguing for further studies and could possibly extend the knowledge about CH pathophysiology. From a clinical point of view, the differences in CH presentation are insufficient to preclude a correct diagnosis and treatment because the same criteria could be applied regardless of patient age.

Underestimated phenomena: higher cortical dysfunctions during migraine aura.

INTRODUCTION: Aura occurs in 20-30% of patients with migraine. Some descriptions of aura go far beyond the most frequent visual and sensory symptoms, suggesting the involvement of different cortical areas. The aim of this prospective study was to evaluate the frequency and types of disorders of higher cortical functions (HCF) that occur during visual and/or sensory aura. METHODS: We interviewed 60 patients with visual and/or sensory aura about HCF disorders of praxia, gnosia, memory, and speech, during aura. Patients were divided into two groups, with and without HCF disorders, and were compared in terms of demographic data and aura characteristics. RESULTS: From all 60 patients, 65% reported at least one HCF disorder during aura. The patients with HCF disorders had longer-lasting auras (28.51 ± 16.39 vs. 19.76 ± 11.23, P = 0.016). The most common HCF disorders were motor dysphasia (82.05%) and dysnomia (30.74%). Motor dysphasia was more often reported by patients with visual as well as sensory aura ( P = 0.002). The number of HCF disorders correlated with the aura duration ( P = 0.003). CONCLUSION: According to our results, HCF disorders during aura occur more often than previously thought. The aura duration has some influence on the HCF disorders.

Migraine-like accompanying features in patients with cluster headache. How important are they?

BACKGROUND: According to the International Classification of Headache Disorders diagnostic criteria, the differences between migraine and cluster headache (CH) are clear. In addition to headache attack duration and pain characteristics, the symptoms accompanying headache represent the key features in a differential diagnosis of these 2 primary headache disorders. Just a few studies of patients with CH exist examining the presence of nausea, vomiting, photophobia, phonophobia, and aura, the features commonly accompanying migraine headache. The aim of this study was to determine the presence of migraine-like features (MF) in patients with CH and establish the significance of these phenomena related to other clinical features and response to treatment. METHODS: One hundred and fifty-five patients with CH were studied, and 24.5% of them experienced at least one of MF during every CH attack. Nausea and vomiting were the most frequently reported MF. The clinical presentation between CH patients with and without MF was not significantly different with the exception of aggravation of pain by effort (20.6% vs 4.1%) and facial sweating (13.2% vs 0.85%), both more frequent in CH patients with MF. CONCLUSION: Inferred from the results of our study, the presence of MF in CH patients had no important influence on the diagnosis and treatment of CH patients. The major differences of these 2 primary headache disorders, attack duration, lateralization, and the nature of associated symptoms, as delineated in the International Classification of Headache Disorders, are still useful tools for effective diagnosis.

Skin and sural nerve biopsies: ultrastructural findings in the first genetically confirmed cases of CADASIL in Serbia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disorder caused by Notch3 gene mutations. The main histopathological hallmark is granular osmiophilic material (GOM) deposited in the close vicinity of vascular smooth muscle cells (VSMCs). The authors report the first 7 ultrastructurally and genetically confirmed cases of CADASIL in Serbia. Samples of skin and sural nerve were investigated by transmission electron microscopy. GOM deposits were observed around degenerated VSMCs in all the skin biopsies examined. Sural nerve biopsies revealed severe alterations of nerve fibers, endoneurial blood vessels with GOM deposits, endoneurial fibroblasts, and perineurial myofibroblasts. Total genomic DNA was extracted from peripheral blood leukocytes, and exons 2-6 of the Notch3 gene were amplified by PCR and subsequently sequenced. Four different mutations in exons 2 (Cys65Tyr), 3 (Gly89Cys and Arg90Cys), and 6 (Ala319Cys), which determine the CADASIL disease, were detected among all described patients. A novel missense mutation Gly89Cys involving exon 3 was detected. Due to the difficulties in the determination of the Notch3 mutations, these data suggest that electron microscopic analysis for GOMs in dermal vessel wall provides a rapid and reliable screening method for this disease.

Is the female sex associated with an increased risk for long-term cognitive decline after the first-ever lacunar stroke? Prospective study on small vessel disease cohort.

Background: Sex is a significant determinant of survival and functional outcome after stroke. Long-term cognitive outcome after acute lacunar stroke in the context of sex differences has been rarely reported. Methods: A cohort of small vessel disease (SVD) patients presenting with first-ever acute lacunar stroke and normal cognitive status has been evaluated 4 years after the qualifying event for the presence of cognitive impairment (CI) with a comprehensive neuropsychological battery. Differences in baseline clinical and neuroimaging characteristics were compared between sexes in relation to cognitive status. Results: A total of 124 female and 150 male patients were analyzed. No difference was detected between the groups regarding age (p = 0.932) or frequency of common vascular risk factors (p > 0.1 for all). At the baseline assessment, women had more disabilities compared to men with a mean modified Rankin scale (mRS) score of 2.5 (1.5 in men, p < 0.0001). Scores of white matter hyperintensities (WMH) of presumed vascular origin and a total number of lacunes of presumed vascular origin on brain MRI were higher in women compared to men (p < 0.0001 for all). As many as 64.6% of patients had CI of any severity on follow-up, women more frequently (77.4%) than men (54.0%; p < 0.0001). Univariate logistic regression analysis showed that female sex, higher NIHSS and mRS scores, presence of depression, and increasing WMH severity were associated with an increased risk for CI. Multivariate regression analysis indicated that only depression (OR 1.74, 95%CI 1.25-2.44; p = 0.001) and WMH severity (OR 1.10, 95%CI 1.03-1.17; p = 0.004) were independently associated with the CI. Conclusion: At the long-term follow-up, women lacunar stroke survivors, compared to men, more frequently had CI in the presence of more severe vascular brain lesions, but this association was dependent on the occurrence of depression and severity of WMH, and could not be explained by differences in common vascular risk factors.

Comorbidities in cluster headache and migraine.

The aim of this study was to investigate the most frequent comorbid diseases occurring in patients with cluster headache (CH) and, for comparison, in migraine patients. Over a period of eight years 130 patients with CH and 982 patients with migraine were diagnosed according to ICHD-II criteria. In all patients the presence and type of different diseases were assessed from medical records and coded by the ICD, X revision. Odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were calculated by logistic regression analyses. Comorbid disorders were present in 56.9% patients with CH and in 56.7% migraine patients. Chronic sinusitis (p = 0.001), malignancy (p = 0.012), diabetes mellitus (p = 0.021), glaucoma (p = 0.038), as well as another primary headache disorders were more frequently present in patients with cluster headache (p = 0.001), than in migraine patients. In the multivariate analysis, chronic sinusitis (OR = 7.6, p = 0.001) and diabetes mellitus (OR = 4.2, p = 0.035), adjusted by gender, age and duration of headache, are more frequently associated with CH than with migraine. Comorbid disorders in CH patients were frequent and similar to those noticed in migraine patients, except chronic sinusitis and diabetes mellitus.

Postdural puncture headache leads to clinical worsening of pre-existing chronic headache.

The incidence of postdural puncture headache (PDPH) in relation to pre-existing chronic headache (CH) was assessed, as was the clinical course of CH, at one, three, and six months after PDPH. The study was conducted as a single center cohort prospective study that included 252 patients (105 men and 147 women), average age of 47.3 ± 15.0 years, on whom lumbar puncture (LP) was performed. PDPH was reported in 133 (52.8%) patients; CH was reported in 82 (32.5%) patients. Patients with CH were more likely to have PDPH (p = 0.003). The individual clinical type of CH did not have an effect on the incidence of PDPH (p = 0.128). Patients with PDPH had a clinical deterioration of CH three and six months after LP (p = 0.047, p = 0.027, respectively) in terms of increased headache days per month and/or incomplete efficacy of performed therapy in relation to baseline values. Six months after LP, the worsening of CH was more common in women with PDPH (OR 5,687 [95% CI: 1526-21,200], p = 0.010) and patients with a longer history of CH (OR 1064 [95% CI: 1007-1124], p = 0.027). Multivariate analysis confirmed the direct association of female sex and duration of CH and its worsening six months after PDPH (OR 4478 [95% CI: 1149-17,452], p = 0.031; OR 1448 [95% CI: 1292-1808], p = 0.022). The presented results could be significant for the prediction/differential diagnosis of PDPH in patients with CH and for the prediction/prevention of CH clinical worsening after PDPH.

Calcitonin gene-related peptide levels in saliva of patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is an intraoral burning sensation for which no medical or dental cause can be found. Recent studies suggest that primary neuropathic dysfunction might be involved in the pathogenesis of BMS. Calcitonin gene-related peptide (CGRP) plays an important role in the development of pain and serves as a biological marker of trigeminovascular activation. The aim of this study was to determine the levels of CGRP in the saliva of BMS patients and estimate the trigeminovascular activation in BMS. CGRP levels were measured, by RIA method in 78 BMS patients and 16 healthy subjects. The levels of CGRP were non-significantly decreased in BMS patients in comparison to healthy subjects. These results suggest that trigeminal nerve degeneration may be the underlying cause of BMS.