The 7-year follow-up of the Hungarian BICAMS validation cohort implies that cognitive performance may improve in multiple sclerosis patients.

BACKGROUND: Cognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS) and has a great impact on the patients' quality of life, so screening is essential. The brief international cognitive assessment for multiple sclerosis (BICAMS) was developed for this purpose. However, longitudinal data is lacking with the use of the battery. OBJECTIVE: This study is to assess the performance of patients after 5 and 7 years of the original BICAMS validation study and to identify any influencing factors. METHODS: BICAMS was used to measure cognitive function of 52 relapsing-remitting MS patients (RRMS) from the original validation study after 5 years (n = 43) and again, after 7 years (n = 42). Patients filled out the fatigue impact scale (FIS) and multiple sclerosis quality of life-54 (MSQoL-54) questionnaire, and we evaluated expanded disability status scale (EDSS). RESULTS: There was an improvement in the BVMT-R and the CVLT-II assessments at both the 5-year (p<0.001 and p=0.025) and the 7-year retest (p<0.001 and p=0.002). The prevalence of CI significantly decreased at the 5-year mark (p=0.021) but remained stable after that. There was no deterioration in MSQoL scores during the study. The basic cognitive performance is the most important influencing factor, but the duration of the disease, the EDSS score, and the escalation of the therapy also affect the cognitive scores. CONCLUSION: This is the longest longitudinal study utilizing the BICAMS battery, reinforcing its feasibility as a clinical screening tool. It seems that cognitive performance may improve in the long term and early initiation of effective therapy may influence this outcome.

Examining the Prevalence of Left Atrial Appendage Thrombus in a Cohort of Acute Stroke Patients with an Extended Computed Tomography Angiographic Protocol.

INTRODUCTION: Current guidelines recommend transthoracic echocardiography (TTE) for routine screening of cardiac emboli; however, the visualization of the left atrial appendage (LAA) where the thrombi are commonly found is poor. Transesophageal echocardiography (TEE) would provide better detectability of LAA thrombus, but it is a time-consuming and semi-invasive method. Extending non-gated carotid computed tomography angiography (CTA) examination to the LAA could reliably detect thrombi and could also aid treatment and secondary prevention of stroke. METHODS: We extended the CTA scan range of acute stroke patients 4 cm below the carina to include the left atrium and appendage. During the review, we evaluated LAA thrombi based on contrast relations. We then used gradient boosting to identify the most important predictors of LAA thrombi from a variety of different clinical parameters. RESULTS: We examined 240 acute stroke patients' extended CTA scans. We detected LAA thrombi in eleven cases (4.58%), eight of them had atrial fibrillation. 23.75% of all patients (57 cases) had recently discovered or previously known atrial fibrillation. Windsack morphology was the most commonly associated morphology with filling defects on CTA. According to the gradient-boosting analysis, LAA morphology showed the most predictive value for thrombi. CONCLUSION: Our extended CTA scans reliably detected LAA thrombi even in cases where TTE did not and showed that 2 patients' LAA thrombus would have been untreated based on electrocardiogram monitoring and TTE. We also showed that the benefits of CTA outweigh the disadvantages arising from the slight amount of excess radiation.

Functional Connectivity Lateralisation Shift of Resting State Networks is Linked to Visuospatial Memory and White Matter Microstructure in Relapsing-Remitting Multiple Sclerosis.

Laterality patterns of resting state networks (RSN) change in various neuropsychiatric conditions. Multiple sclerosis (MS) causes neuro-cognitive symptoms involving dysfunctional large-scale brain networks. Yet, whether healthy laterality patterns of RSNs are maintained in MS and whether altered laterality patterns explain disease symptoms has not been explicitly investigated. We analysed functional MRI and diffusion tensor imaging data from 24 relapsing-remitting MS patients and 25 healthy participants. We performed group-level independent component analysis and used dual regression to estimate individual versions of well-established RSNs. Voxelwise laterality indices were calculated for each RSN. Group differences were assessed via a general linear model-based approach. The relationship between functional laterality and white matter microstructural asymmetry was assessed using Tract-Based Spatial Statistics. Spearman's correlation was calculated between laterality indices and Brief International Cognitive Assessment for Multiple Sclerosis scores. Functional laterality of the dorsal attention network showed a significant leftward shift in the MS group in the posterior intraparietal sulcus (p < 0.033). Default-mode network laterality showed a significant leftward shift in the MS group in the angular gyrus (p < 0.005). Diminished dorsal attention network laterality was associated with increased fractional anisotropy asymmetry in the superior longitudinal fasciculus (p < 0.02). In the default-mode network, leftward laterality of the angular gyrus was associated with higher BVMT-R scores (R = - 0.52, p < 0.023). Our results confirm previous descriptions of RSN dysfunction in relapsing-remitting MS and show that altered functional connectivity lateralisation patterns of RSNs might contibute to cognitive performance and structural remodellation even in patients with mild clinical symptoms.

Multicenter Study on COVID-19 Lung Computed Tomography Segmentation with varying Glass Ground Opacities using Unseen Deep Learning Artificial Intelligence Paradigms: COVLIAS 1.0 Validation.

Variations in COVID-19 lesions such as glass ground opacities (GGO), consolidations, and crazy paving can compromise the ability of solo-deep learning (SDL) or hybrid-deep learning (HDL) artificial intelligence (AI) models in predicting automated COVID-19 lung segmentation in Computed Tomography (CT) from unseen data leading to poor clinical manifestations. As the first study of its kind, "COVLIAS 1.0-Unseen" proves two hypotheses, (i) contrast adjustment is vital for AI, and (ii) HDL is superior to SDL. In a multicenter study, 10,000 CT slices were collected from 72 Italian (ITA) patients with low-GGO, and 80 Croatian (CRO) patients with high-GGO. Hounsfield Units (HU) were automatically adjusted to train the AI models and predict from test data, leading to four combinations-two Unseen sets: (i) train-CRO:test-ITA, (ii) train-ITA:test-CRO, and two Seen sets: (iii) train-CRO:test-CRO, (iv) train-ITA:test-ITA. COVILAS used three SDL models: PSPNet, SegNet, UNet and six HDL models: VGG-PSPNet, VGG-SegNet, VGG-UNet, ResNet-PSPNet, ResNet-SegNet, and ResNet-UNet. Two trained, blinded senior radiologists conducted ground truth annotations. Five types of performance metrics were used to validate COVLIAS 1.0-Unseen which was further benchmarked against MedSeg, an open-source web-based system. After HU adjustment for DS and JI, HDL (Unseen AI) > SDL (Unseen AI) by 4% and 5%, respectively. For CC, HDL (Unseen AI) > SDL (Unseen AI) by 6%. The COVLIAS-MedSeg difference was < 5%, meeting regulatory guidelines.Unseen AI was successfully demonstrated using automated HU adjustment. HDL was found to be superior to SDL.

Altered brain network function during attention-modulated visual processing in multiple sclerosis.

BACKGROUND: Multiple sclerosis may damage cognitive performance in several domains, including attention. Although attention network deficits were described during rest, studies that investigate their function during task performance are scarce. OBJECTIVE: To investigate connectivity within and between task-related networks in multiple sclerosis during a visual attention task as a function of cognitive performance. METHODS: A total of 23 relapsing-remitting multiple sclerosis (RRMS) patients and 29 healthy controls underwent task-functional magnetic resonance imaging (fMRI) scans using a visual attention paradigm on a 3T scanner. Scans were analysed using tensor-independent component analysis (TICA). Functional connectivity was calculated within and between components. We assessed cognitive function with the Brief International Cognitive Assessment for MS (BICAMS) battery. RESULTS: TICA extracted components related to visual processing, attention, executive function and the default-mode network. Subject scores of visual/attention-related and executive components were greater in healthy controls (p < 0.032, p < 0.023). Connectivity between visual/attention-related and default-mode components was higher in patients (p < 0.043), correlating with Brief Visuospatial Memory Test-Revised (BVMT-R) scores (R = -0.48, p < 0.036). Patients showed reduced connectivity between the right intraparietal sulcus (rIPS) and frontal eye field (rFEF), and bilateral frontal eye fields (p < 0.012, p < 0.003). Reduced rIPS-rFEF connectivity came with lower Symbol Digit Modalities Test (SDMT)/BVMT-R scores in patients (R = 0.53, p < 0.02, R = 0.46, p < 0.049). CONCLUSION: Attention-related networks show altered connectivity during task performance in RRMS patients, scaling with cognitive disability.

The sensitivity and specificity of chest CT in the diagnosis of COVID-19.

PURPOSE: The identification of patients infected by SARS-CoV-2 is highly important to control the disease; however, the clinical presentation is often unspecific and a large portion of the patients develop mild or no symptoms at all. For this reason, there is an emphasis on evaluating diagnostic tools for screening. Chest CT scans are emerging as a useful tool in the diagnostic process of viral pneumonia cases associated with COVID-19. This review examines the sensitivity, specificity, and feasibility of chest CT in detecting COVID-19 compared with real-time polymerase chain reaction (RT-PCR). METHODS: Sensitivity and specificity of chest CT in detecting COVID-19 in its various phases was compared using RT-PCR as a gold standard. A "reverse calculation approach" was applied and treated chest CT as a hypothetical gold standard and compared RT-PCR to it point out the flaw of the standard approach. RESULTS: High sensitivity (67-100%) and relatively low specificity (25-80%) was reported for the CT scans. However, the sensitivity of RT-PCR was reported to be modest (53-88%), hence cannot serve as an appropriate ground truth. The "reverse calculation approach" showed that CT could have a higher specificity (83-100%) if we consider the modest sensitivity of the RT-PCR. CONCLUSIONS: The sensitivity and specificity of the chest CT in diagnosing COVID-19 and the radiation exposure have to be judged together. Arguments are presented that chest CT scans have added value in diagnosing COVID-19 especially in patients, who exhibit typical clinical symptoms and have negative RT-PCR results in highly infected regions. KEY POINTS: • CT scans have higher specificity if we take into account the low sensitivity of the RT-PCR. • Avoid chest CT as a sole diagnostic approach for COVID-19 infection. • Patients who had negative RT-PCR result with typical clinical symptoms in highly infected regions or with close contact of COVID-19-infected patients; the use of chest CT is warranted.

Macro- and microstructural alterations of the subcortical structures in episodic cluster headache.

Background Previous functional and structural imaging studies have revealed that subcortical structures play a key a role in pain processing. The recurring painful episodes might trigger maladaptive plasticity or alternatively degenerative processes that might be detected by MRI as changes in size or microstructure. In the current investigation, we aimed to identify the macro- and microstructural alterations of the subcortical structures in episodic cluster headache. Methods High-resolution T1-weighted and diffusion-weighted MRI images with 60 gradient directions were acquired from 22 patients with cluster headache and 94 healthy controls. Surface-based segmentation analysis was used to measure the volume of the subcortical nuclei, and mean diffusion parameters (fractional anisotropy, mean, radial and axial diffusivity) were determined for these structures. In order to understand whether the size and diffusion parameters could be investigated in a headache lateralised manner, first the asymmetry of the size and diffusion parameters of the subcortical structures was analysed. Volumes and diffusion parameters were compared between groups and correlated with the cumulative number of headache days. To account for the different size of the patient and control group, a bootstrap approach was used to investigate the stability of the findings. Results A significant lateralisation of the size (caudate, putamen and thalamus) and the diffusion parameters of the subcortical structures were found in normal controls. In cluster headache patients, the mean fractional anisotropy of the right amygdalae, the mean axial and mean diffusivity of the right caudate nucleus and the radial diffusivity of the right pallidum were higher. The mean anisotropy of the right pallidum was lower in patients. Conclusion The analysis of the pathology in the subcortical structures in episodic cluster headache reveals important features of the disease, which might allow a deeper insight into the pathomechanism of the pain processing in this headache condition.

[The role of MRI in measuring the effectivity of disease modifying treatments I]. / Az MRI helye a sclerosis multiplex kezelés hatékonyságának megítélésében I.: mérési markerek.

MRI has a significant role in the diagnosis of multiple sclerosis. The newer and newer treatment options of the disease make it necessary to monitor the effectiveness of the therapy. Besides the clinical signs (clinical relapses and progression), the different MRI parameters can also reflect the disease activity. In our current article we summarize those MRI markers, which best predict the long-term disability, based on the international standards.

Ipsilateral Alteration of Resting State Activity Suggests That Cortical Dysfunction Contributes to the Pathogenesis of Cluster Headache.

The pathomechanism of cluster headache (CH) is not entirely understood, but central and peripheral components were suggested. A recent report showed that transcranial magnetic stimulation measured cortical excitability was increased in the hemisphere ipsilalteral to the pain. In the current study we set out to investigate the amplitude of resting brain fMRI activity to find signatures of the increased excitability. High resolution T1 weighted and resting state functional MRI images were acquired from seventeen patients with CH in pain free period and from twenty-six healthy volunteers. Patients' data were normalized (e.g. inverted along the midsagittal axis) according to the headache side. Independent component analysis and a modified dual regression approach were used to reveal the differences between the resting state networks. Furthermore, the timecourses were decomposed into five frequency bands by discrete wavelet decomposition and were also re-regressed to the original data to reveal frequency specific resting activity maps. Two of the identified resting state networks showed alterations in CH. When the data were inverted to have patients' headaches on the left, the ipsilateral attention network showed increased connectivity in 0.08-0.04 Hz frequency band in the in CH group. In the same dataset, cerebellar network showed higher functional connectivity in 0.02-0.01 Hz range in the ipsilateral cerebellum. When the data of patients having headache on the left were inverted to the right, similar increased signal was found in the ipsilateral attention network in 0.08-0.04 Hz band. The cerebellar network showed increased connectivity in the cerebellum in 0.02-0.01 Hz band in patients. The Fourier analysis of these area revealed increased power in CH at all cases. Our results showed alterations of brain functional networks in CH. The alterations of resting state activity were found in the hemisphere ipsilateral to the pain, signifying the altered cortical processing in the pathomechanism of CH.

Interictal brain activity differs in migraine with and without aura: resting state fMRI study.

BACKGROUND: Migraine is one of the most severe primary headache disorders. The nature of the headache and the associated symptoms during the attack suggest underlying functional alterations in the brain. In this study, we examined amplitude, the resting state fMRI fluctuation in migraineurs with and without aura (MWA, MWoA respectively) and healthy controls. METHODS: Resting state functional MRI images and T1 high-resolution images were acquired from all participants. For data analysis we compared the groups (MWA-Control, MWA-MWoA, MWoA-Control). The resting state networks were identified by MELODIC. The mean time courses of the networks were identified for each participant for all networks. The time-courses were decomposed into five frequency bands by discrete wavelet decomposition. The amplitude of the frequency-specific activity was compared between groups. Furthermore, the preprocessed resting state images were decomposed by wavelet analysis into five specific frequency bands voxel-wise. The voxel-wise amplitudes were compared between groups by non-parametric permutation test. RESULTS: In the MWA-Control comparison the discrete wavelet decomposition found alterations in the lateral visual network. Higher activity was measured in the MWA group in the highest frequency band (0.16-0.08 Hz). In case of the MWA-MWoA comparison all networks showed higher activity in the 0.08-0.04 Hz frequency range in MWA, and the lateral visual network in in higher frequencies. In MWoA-Control comparison only the default mode network revealed decreased activity in MWoA group in the 0.08-0.04 Hz band. The voxel-wise frequency specific analysis of the amplitudes found higher amplitudes in MWA as compared to MWoA in the in fronto-parietal regions, anterior cingulate cortex and cerebellum. DISCUSSION: The amplitude of the resting state fMRI activity fluctuation is higher in MWA than in MWoA. These results are in concordance with former studies, which found cortical hyperexcitability in MWA.

[Magnetic resonance imaging in the course of alemtuzumab and teriflunomide therapy]. / Mágnesesrezonancia-képalkotás alemtuzumabés teriflunomidkezelés során.

Our work aimed to review the published results of magnetic resonance imaging (MRI) obtained in the course of alemtuzumab and teriflunomide therapy in multiplex sclerosis. In multiplex sclerosis MRI sensitively detects subclinical pathological processes, which do not manifest clinically in the early course of the disease, however have substantial significance from the viewpoint of the long-term disease prognosis. MRI has an increasingly important role in the early monitoring of the therapeutic efficacy. In the last 15 years several clinical trials have been conducted with alemtuzumab and teriflunomide in multiple sclerosis providing evidence about the favourable clinical effect of these drugs. MRI images were acquired in these trials as well, and the results published recently in the scientific literature. These MRI results denote the suppression of the disease activity and the neurodegenerative processes, which may imply a favourable effect on the long-term prognosis of the disease.

[Change of therapeutic algorithm in sclerosis multiplex based on two case reports]. / Terápiás algoritmus változása sclerosis multiplexben két esettanulmány alapján.

The aim of our case reports is to demonstrate the therapeutic use and possibilities one has with alemtuzumab, should it be used either as a first or second line therapy. Our first patient's disease in the beginning seemed to be benign. It was not the case however, over several years the diesase showed high activity both radiologically and clinically, she was treated with alemtuzumab as part of an esclationbased therapeutic strategy. The second patient's disease on the other hand showed formidable activity since the very beginning both radiologically and clinically. Therefore we were facing a very disastrous prognosis on the long run, accordingly he received alemtuzumab treatment very early into his illness.

Release of PACAP-38 in episodic cluster headache patients - an exploratory study.

BACKGROUND: Activation of the trigeminal-autonomic reflex, involving the trigeminal ganglion, the superior salivatory nucleus and the sphenopalatine ganglion (SPG) is crucial in the pathophysiology of cluster headache (CH). Since pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is present both in the SPG and the trigeminal ganglion (TG) and its role in migraine has been described, our aim was to determine the plasma PACAP-38 levels in different phases of episodic CH (ECH). Peripheral cubital fossa blood samples were taken during the ictal and inter-bout periods of male ECH patients and from age-matched healthy controls (n = 9). Plasma PACAP-38-like immunoreactivity (LI) was measured with specific and sensitive radioimmunoassay. FINDINGS: Significantly lower plasma PACAP-38-LI was detected in the inter-bout period of ECH patients than in healthy controls. However, PACAP-38 was significantly elevated in the plasma during CH attacks as compared to the inter-bout phase in the same subjects (n = 5). CONCLUSIONS: This exploratory study suggests that PACAP-38 may be released during the attacks of ECH. Further patients and long-term follow-up are necessary to reveal its function.

[THE THERAPUETIC USE OF TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION]. / TRANSCRANIALIS MÁGNESES STIMULÁCIÓ TERÁPIÁS ALKALMAZÁSA MAJOR DEPRESSZIÓBAN.

The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention.

Gray matter atrophy in presymptomatic Huntington's patients.

BACKGROUND AND PURPOSE: Background - Huntington's disease is a progressive disease in which neurodegeneration is on-going from the early presymptomatic phase. Development of sensitive biomarkers in this presymptomatic stage that are able to monitor the disease progression and test the efficacy of putative neuroprotective treatments are essential. METHODS: Methods - Seven presymptomatic Huntington mutation carriers and ten age-matched healthy controls were recruited. Six of the patients participated in a 24 months longitudinal study having MRI scans 12 and 24 months after the baseline measurements. High resolution T1 weighted images were carried out and voxel based morphometry was used to analyse the data. Apart of group differences, correlation of CAG repeat number with focal cortical thickness and with global gray matter volume was calculated. RESULTS: Results - Focal cortical atrophy was found bilaterally in the superior temporal sulcus and in the left middle frontal gyrus in presymptomatic Huntington patients in whom no sign of cognitive or motor deterioration was detected. Global gray matter atrophy (p<0.048) and decreased total brain volume was found. The number of CAG triplets showed no correlation with the focal gray matter atrophy and total brain volume. Strong correlation between the CAG repeat number and global gray matter volume was found (p<0.016). CONCLUSION: Conclusion - Cortical atrophy is apparent in the early, presymptomatic stage of the disease. With further validation in large patient sample atrophy measure could be biomarker of disease progression and putatively of neurodegeneration.

HYPERGLYCAEMIC HEMIBALLISMUS: IMPLICATIONS FROM CONNECTIVITY ANALYSIS FOR COGNITIVE IMPAIRMENTS.

Hyperglycaemia induced movement disorders, such as hemiballism are rare disorders. The syndrome is characterised by the triad of hemiballism, contralateral T1-hyperintense striatal lesion and non-ketotic hyperglycaemia. Here we report a patient with untreated diabetes presenting with acute onset of hemiballism. MRI revealed T1 hyperintensity of the head of the caudate nucleus and the anterior putamen. The patient also had acantocytosis. Based on the detailed examination of the neuroradiological results and earlier findings we will discuss the pathomechanism. Based on previous findings microhemorrhages, extensive mineralisation, gemistocytic astrocytosis might play a role in the development of the imaging signs. The connectivity pattern of the striatal lesion showed extensive connections to the frontal cortex. In coexistence with that the most severe impairment was found on the phonemic verbal fluency task measuring frontal executive functions.

Grey matter atrophy in patients suffering from multiple sclerosis.

White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

D-dimer levels to exclude pulmonary embolism and reduce the need for CT angiography in COVID-19 in an outpatient population.

OBJECTIVES: Emerging results indicate that, in COVID-19, thromboembolic complications contribute to the high mortality and morbidity. Previous research showed that the prevalence of pulmonary embolism (PE) is between 25-50% in COVID-19 patients, however, most of these reports are based on data from patients with severe pneumonia, treated in intensive care units. MATERIALS AND METHODS: We conducted a retrospective, single-center, observational study to estimate the prevalence of PE in COVID-19 patients who underwent CT angiography and to identify the most important predictors. Adult outpatients with COVID-19, who presented at our COVID Outpatient Clinic between 1st and 31st of March in 2021 and underwent CTA examination were included in this study. Multiple linear regression analysis was used to identify predictors of PE in COVID-19 patients. The predictors were: age, gender, disease duration, CT severity index and log-transformed quantitative D-dimer (logQDDIM) value. RESULTS: 843 COVID-19 patients were included into the study. 82.56% (693 patients) of the infected patients had a pulmonary CTA examination and D-dimer levels (mean age: 59.82 years ± 15.66). 7.61% (53 patients) of the patients had PE. 2.02% (14 patients) of the patients had main branch or lobar PE. The multiple regression analysis found that only logQDDIM was a significant predictor. A logQDDIM cut-off value of 0.0169 (1.0171 ug/ml serum D-dimer) predicted PE with 99% sensitivity (p<0.0001, degree-of-freedom = 570, AUC = 0.72). CONCLUSIONS: We demonstrated in a large cohort of COVID-19 patients that a cut-off value of QDDIM of 1ug/ml can exclude pulmonary embolism in an outpatient setting, implicating that QDDIM might potentially supersede CTA as a screening approach in COVID-19 outpatient clinics.

Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients.

BACKGROUND: Recent studies on migraineurs and our own animal experiments have revealed that pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) has an important role in activation of the trigeminovascular system. The aim of this study was to determine the PACAP-38-like immunoreactivity (LI) in the plasma of healthy subjects, and parallel with the calcitonin gene-related peptide (CGRP)-LI in migraine patients in the ictal and interictal periods. METHODS: A total of 87 migraineurs and 40 healthy control volunteers were enrolled in the examination. Blood samples were collected from the cubital veins in both periods in 21 patients, and in either the ictal or the interictal period in the remaining 66 patients, and were analysed by radioimmunoassay. RESULTS: A significantly lower PACAP-38-LI was measured in the interictal plasma of the migraineurs as compared with the healthy control group ( P < 0.011). In contrast, elevated peptide levels were detected in the ictal period relative to the attack-free period in the 21 migraineurs ( P PACAP-38 < 0.001; P CGRP < 0.035) and PACAP-38-LI in the overall population of migraineurs ( P < 0.009). A negative correlation was observed between the interictal PACAP-38-LI and the disease duration. CONCLUSION: This is the first study that has provided evidence of a clear association between migraine phases (ictal and interictal) and plasma PACAP-38-LI alterations.

White matter disintegration in cluster headache.

BACKGROUND: Previous studies in primary headache disorders showed microstructural alterations in the white matter as measured by diffusion imaging. However these investigations are not in full agreement and some of those, especially in cluster headache, restricted the analysis to only a limited number of diffusion parameters. Therefore, in the current study we examined white matter microstructure in cluster headache patients. METHODS: Diffusion weighted MRI images with 60 directions were acquired from thirteen patients with cluster headache and sixteen age-matched healthy controls. Tract based spatial statistics were used to compare white matter integrity in the core of the fibre bundles. Correlation of the diffusion parameters with cumulative number of headache days was examined. RESULTS: There was a significant increment of the mean, axial and perpendicular diffusivity in widespread white matter regions in the frontal, parietal, temporal and occipital lobes. Reduced fractional anisotropy was found in the corpus callosum and some frontal and parietal white matter tracts mainly in the contralateral side of the pain. Axial diffusivity showed negative correlation to the number of the headache attacks. CONCLUSIONS: The in vivo analysis of microstructural alterations in cluster headache provides important features of the disease, which might offer a deeper insight into the pathomechanism of the disease.