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.

Comprehensive Ultrasound Assessment of the Craniocervical Circulation in Transient Global Amnesia.

OBJECTIVES: Structural changes and metabolic stress have been reported on diffusion-weighted magnetic resonance imaging in the cornu ammonis 1 area of the hippocampus in patients with transient global amnesia (TGA), but a consensus on pathogenesis is still lacking. The aim of our study was to perform a comprehensive ultrasound analysis of the cerebrovascular circulation in our population of patients with TGA. METHODS: One hundred patients with TGA and 50 age- and sex-matched control participants underwent ultrasound examinations of the cervicocranial circulation. RESULTS: The most significant risk factor for TGA was arterial hypertension (P < .01). There were no significant atherosclerotic lesions on the large arteries of the neck (mean internal carotid artery stenosis ± SD, 28.7% ± 11.7%) or on the large intracerebral arteries (good structural and hemodynamic status; P > .05). Rarely detected microembolic signals or a right-left cardiopulmonary shunt excluded an emboligenic mechanism of TGA (P > .05). The internal jugular vein valves were incompetent in 54% of patients with TGA, and this condition was associated with an increased risk of TGA (odds ratio, 4.16; 95% confidence interval, 1.91-9.04). The mean values of the breath holding index and pulsatility index, as parameters of small-vessel function, were within normal ranges and without differences between the TGA and control groups (P > .05). CONCLUSIONS: Our ultrasound examination did not detect significant structural atherosclerotic changes of cervicocranial arteries, and an emboligenic mechanism was excluded. Only a significant rise of blood pressure in TGA and significant valvular insufficiency of the internal jugular vein were established. New research should clarify whether these simultaneous functional circulatory changes have relevance for metabolic stress in the cornu ammonis of the hippocampus.

Drug treatment of vertigo in neurological disorders.

Vertigo is a common symptom in everyday clinical practice. The treatment depends on the specific etiology. Vertigo may be secondary to inner ear pathology, or any existing brainstem or cerebellar lesion but may also be psychogenic. Central vertigo is a consequence of a central nervous system lesion. It is often associated with a focal neurological deficit. Peripheral vertigo is secondary to dysfunction of the peripheral vestibular system and is usually characterized by an acute vertigo with loss of balance, sensation of spinning in the space or around self, and is exaggerated with changes of the head and body position; no other neurological deficit is present. Some medications may also cause vertigo. Depending on the cause of the vertigo, drugs with different mechanisms of action, physical therapy, psychotherapy, as well as surgery may be used to combat this disabling malady. Symptomatic treatment has a particularly important role, regardless of the etiology of vertigo. We reviewed the current medications recommended for patients with vertigo, their mechanisms of action and their most frequent side effects.

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.

Transcranial brain parenchymal sonography in neurodegenerative and psychiatric diseases.

Transcranial sonography is a highly sensitive noninvasive sonographic method for detection of early and specific echogenic changes in basal ganglia of patients with some neurodegenerative diseases. Transcranial sonography showed substantia nigra hyperechogenicity as a typical echo feature in idiopathic Parkinson disease and lenticular nucleus hyperechogenicity as a characteristic finding in atypical parkinsonian syndromes. Brain stem raphe hypoechogenicity or interruption has been shown to be highly prevalent in patients with unipolar depression as well as depression associated with certain neurodegenerative diseases. Transcranial sonography also revealed basal ganglia hyperechoic changes in movement disorders with trace metal accumulation such as Wilson disease, some entities of neurodegeneration with brain iron accumulation, as well as several forms of spinocerebellar ataxia. Transcranial sonography is a valuable neuro imaging method for early and differential diagnosis and follow-up of patients with neurodegenerative and psychiatric diseases.

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.

Is sonothrombolysis an effective stroke treatment?

New therapeutic strategies under development aim to improve recanalization rates and clinical outcomes after ischemic stroke. One such approach is ultrasound (US)-enhanced thrombolysis, or sonothrombolysis, which can improve thrombolytic drug actions and even intrinsic fibrinolysis. Although the mechanisms are not fully understood, it is postulated that thrombolysis enhancement is related to nonthermal mechanical effects of US. Recent results indicate that US with or without microbubbles may be effective in clot lysis of ischemic stroke even without additional thrombolytic drugs. Sonothrombolysis is a promising tool for treating acute ischemic stroke, but its efficacy, safety, and technical details have not been elucidated and proved yet in stroke treatment.

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.

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.

Multivoxel MRS: right frontal parafalcine cortex - area of neurobiochemical gender differentiation?

OBJECTIVE: To determine the presence of gender neurometabolic differences in healthy men and women by multivoxel magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: We performed multivoxel magnetic resonance imaging and spectroscopy in 50 healthy volunteers (27 women and 23 men) using 1.5T scanner. Spectra from 12 different voxels were obtained, covering frontal, paracentral, and parietal white and gray matter. Three dominant signals were analyzed: NAA, tCr and Cho, and expressed as ratios of Cho/tCr, NAA/tCr, NAA/Cho. RESULTS: There was statistically significant gender difference between Cho/Cr and NAA/Cr metabolites ratio in only one location - the right frontal parafalcine cortex. There was no statistically significant difference in NAA/Cho ratio between men and women. CONCLUSION: Our study suggests that right frontal parafalcine cortex is a sexually dysmorphic area and supports the value of multivoxel MRS as a method able to define spatial biochemical heterogeneity of the cerebral tissue.

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.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with severe factor XII deficiency.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited adult-onset microangiopathy caused by missense mutations in the Notch3gene on chromosome 19. However, common vascular risk factors may additionally modify clinical expression and progression of the disease. The role of various prothrombotic factors has also been implied. We report a case of a middle-aged man with typical clinical, neuroimaging and histological features of CADASIL, but with notably prolonged activated partial thromboplastin time. Hematological investigations revealed severe clotting Factor XII deficiency. This case illustrates that the occurrence of vascular risk factors should not be overlooked in patients with CADASIL.

Bilateral SUNCT-like headache in a patient with prolactinoma responsive to lamotrigine.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome is a rare trigeminal autonomic cephalalgia. The cases of SUNCT with attacks that affected both sides simultaneously have only rarely been reported and some of them had underlying pathology. We have reported a case of bilateral SUNCT-like headache secondary to a prolactinoma and responsive to lamotrigine treatment.

Role of prediabetes in stroke.

Stroke is one of the leading causes of death and probably the greatest cause of adult disability worldwide. Diabetes mellitus (DM) is a state of accelerated aging of blood vessels. Patients with diabetes have increased risk of stroke. Hyperglycemia represents a risk factor for poor outcome following stroke, and probably is just a marker of poor outcome rather than a cause. Lowering of blood glucose levels has not been shown to improve prognosis. Also, prevention of stroke risk among patients with DM is not improved with therapy for reduction of glucose levels. On the other hand, prediabetes, a metabolic state between normal glucose metabolism and diabetes, is a risk factor for the development of DM type 2 and subsequently for stroke. Several methods are known to identify prediabetes patients, including fasting plasma glucose levels, 2-hour post load glucose levels, and glycosylated hemoglobin levels. In this text, we tried to summarize known data about diagnosis, epidemiology, risk factors, pathophysiology, and prevention of prediabetes in relation to DM and stroke.

Is there a difference in risk factors for single and multiple symptomatic lesions in small vessel disease? What is the difference between one and plenty--experience from 201 Serbian patients.

OBJECTIVES/PURPOSES: Small vessel disease (SVD) is associated with traditional vascular risk factors (RF). The aim of our study was to determine whether different SVD types, single lacunar infarction (LI) and multiple LI (MLI) with or without white matter lesions (WML), have different RF profiles. PATIENTS AND METHODS: Forty RF parameters were analysed in 201 consecutive patients with magnetic resonance imaging finding of SVD. RESULTS: History of arterial hypertension, higher systolic and mean blood pressure (BP) but also hypotension, and higher plasma homocysteine levels were more frequent in MLI compared to single LI patients (p<0.05). Patients with one LI were younger, more frequently had clinically evident stroke and family history of cardiovascular disease (CVD) (p<0.05). Significant difference between groups was found only in these RF, indicating that similar pathological processes led to both types of SVD. CONCLUSION: Positive correlation with age and family history of CVD necessitates further analyses of other factors, predominantly genetic, as the key to the answer why patients develop different lesions in SVD.

Leptomeningeal carcinomatosis can be presenting manifestation of breast carcinoma.

INTRODUCTION: Leptomeningeal carcinomatosis (LC) is a serious complication occuring in solid cancer patients with rather poor prognosis. CASE REPORT: We presented a 47-year-old woman with the 6-month history of diffuse headache, nausea and visual obscuration. Initially, clinical status and brain magnetic resonance imaging (MRI) indicated syndrome of idiopathic intracranial hypertension. Due to clinical progression and high papillary stasis, cerebrospinal fluid (CSF) examination was performed only after ventriculoperitoneal shunt was implanted. This led to a significant although transient clinical improvement. Futher investigations led to the diagnosis of invasive lobular breast carcinoma and repeated CSF analysis revealed malignant breast carcinoma cells. In this case LC was an initial presentation of a malignant-disease. CONCLUSION: In the presence of a high clinical suspicion of LC, in spite of initially negative findings, a clinician should persist in repeating relevant tests, such are MRI with larger amounts of gadolinium and high-volume cytological CSF analyses in order to make the diagnosis.

Carotid artery wall stiffness is increased in patients with small vessel disease: A case-control study.

INTRODUCTION: Cerebral ischemic small-vessel disease (SVD), causing lacunar infarcts and white matter hyperintensities on brain magnetic resonance imaging (MRI), is a progressive disease associated with an increased risk of stroke, dementia and death. Increased arterial stiffness has been associated with ischemic stroke and cerebral SVD independently of common vascular risk factors. OBJECTIVE: The aim of the study was to analyze arterial stiffness in our patients with symptomatic SVD. METHODS: In a cross-sectional study design we included 30 patients with clinical and MRI evidence of cerebral SVD and 30 age-, gender- and risk factor-matched control subjects with no neurological diseases. Patients were evaluated at the Ultrasound Laboratory at the Neurology Clinic, Clinical Center of Serbia in Belgrade, during a three-month period (from September 1st to December 1st 2012). Baseline demographic and vascular risk factors were recorded. All patients underwent standard carotid ultrasound scans with measuring of intima-media thickness (IMT) and analysis of atheromatous plaques. Internal carotid artery stiffness was evaluated with the use of e-tracking option as beta stiffness index (BSI) value. RESULTS: There were no differences between study groups in regard to degree of carotid stenosis and type of carotid plaques (p > 0.05). Patients in SVD group had significantly higher mean IMT (p = 0.0093) and mean BSI (p < 0.0001) than subjects in the control group. No significant correlation was detected between IMT and BSI in SVD group (r = 0.168; p = 0.376). Brain lesions severity correlated with BSI (r = 0.733; p < 0.0001). CONCLUSION: Arterial stiffness is increased in symptomatic patients with SVD, independently of vascular risk factors and IMT.