Interictal Period Research Articles

Investigation of serum vaspin, visfatin, chemerin and IL-18 levels in migraine patients.

Migraines are headaches caused by changes in the trigeminovascular metabolic pathway. Migraine headache attacks are associated with neurovascular inflammation, but their pathophysiological mechanisms have not been fully explained. To investigate the relationship between serum vaspin, visfatin, chemerin and interleukin-18 (IL-18) levels and the frequency of attacks in migraine headache. Three groups were established: migraine with aura (n = 50), migraine without aura (n = 50) and control group (n = 50). The migraine diagnosis was made in accordance with the International Classification of Headache Disorders-III beta diagnostic criteria. The analyses on serum vaspin, visfatin, chemerin and IL-18 levels were performed using the enzyme-linked immunosorbent assay method. The serum vaspin, visfatin, chemerin and IL-18 levels were found to be significantly higher in the migraine patients than in the control group (p < 0.01). No statistically significant differences in serum vaspin, visfatin, chemerin and IL-18 levels were found among the migraine patients during attacks or in the interictal period (p>0.05). The serum visfatin and chemerin levels of the migraine patients were positively correlated with their serum IL-18 levels (p < 0.01), while their serum chemerin and visfatin levels were positively correlated with their serum vaspin levels (p < 0.05). This study showed that these biomarkers may be related to migraine pathogenesis. Nonetheless, we believe that more comprehensive studies are needed in order to further understand the role of vaspin, visfatin, chemerin and IL-18 levels in the pathophysiology of migraine headaches.

Interictal Cognitive Deficits in Migraine Sufferers: A Meta-Analysis.

While a significant proportion of the population suffer from migraine, the existing research literature does not provide a clear indication as to whether migraineurs experience objective cognitive deficits outside of acute migraine attacks. This meta-analysis was conducted to investigate which cognitive domains if any were affected by migraine, by synthesising the existing research quantitatively. The meta-analysis was prospectively registered with the PROSPERO International prospective register of systematic reviews (registration no.: CRD42019134138). A search of the electronic databases PubMed, Ovid MEDLINE, and PsycINFO was conducted for journal articles published between January 1980 and January 2020. Seventeen studies met the inclusion criteria, allowing for the calculation of pooled effect sizes between migraineurs (with and without aura) and healthy controls in the several cognitive domains. During the interictal period, migraineurs demonstrated a moderate, negative effect on complex attention immediate and delayed memory, spatial cognition, and executive functioning. This effect was not attributable to migraine history, attack frequency, or participant age. However, the lack of performance validity testing, and limited data on mood symptomatology and migraine medication use in the included studies may be confounds potentially overestimating the magnitude of effect. Comparison with a clinical control group, which may have accounted for some these extraneous variables, was unable to be conducted. Recommendations for comprehensive future neuropsychological research are provided.

Effect of gap junction blockers on hippocampal ripple energy expression in rats with status epilepticus.

To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE). A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX (n=6 each). A rat model of SE induced by lithium-pilocarpine (PILO) was prepared. The QUIN, VPA, and CBX groups were given intraperitoneal injection of QUIN (50 mg/kg), VPA by gavage (200 mg/kg), and intraperitoneal injection of CBX (50 mg/kg) respectively, at 3 days before PILO injection. Electroencephalography was used to analyze the change in hippocampal ripple energy before and after modeling, as well as before and after chloral hydrate injection to control seizures. Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups (P<0.05). The QUIN group had the highest expression level of mean ripple energy 60 minutes after PILO injection. The mean ripple energy returned to normal levels in the three intervention groups immediately after chloral hydrate injection, while in the model group, the mean ripple energy returned to normal levels 1 hour after chloral hydrate injection. The mean ripple energy remained normal till to day 3 after SE in the four groups. The changing trend of maximum ripple energy was similar to that of mean ripple energy. The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.

Altered thalamo-cortical functional connectivity in patients with vestibular migraine: a resting-state fMRI study.

To explore the functional connectivity (FC) between the bilateral thalamus and the other brain regions in patients with vestibular migraine (VM). Resting-state fMRI and 3D-T1 data were collected from 37 patients with VM during the interictal period and 44 age-, gender-, and years of education-matched healthy controls (HC). The FC of the bilateral thalamus was analyzed using a standard seed-based whole-brain correlation method. Furthermore, the correlations between thalamus FC and clinical characteristics of patients were investigated using Pearson's partial correlation. Compared with HC, VM patients showed decreased FC between the left thalamus and the left anterior cingulate cortex (ACC), bilateral insular and right supplementary motor cortex. We also observed decreased FC between the right thalamus and the left insular and ACC in VM patients. Furthermore, patients with VM also exhibited increased FC between the left thalamus and the right precuneus and middle frontal gyrus, between the right thalamus and superior parietal lobule. FC between the right thalamus and the left insular was negatively correlated with disease duration (p = 0.019, r = - 0.399), FC between the left thalamus and the left ACC was negatively correlated with HIT-6 score (p = 0.004, r = - 0.484). VM patients showed altered FC between thalamus and brain regions involved in pain, vestibular and visual processing, which are associated with specific clinical features. Specifically, VM patients showed reduced thalamo-pain and thallamo-vestibular pathways, while exhibited enhanced thalamo-visual pathway, which provided first insight into the underlying functional brain connectivity in VM patients.

Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms.

We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period. Scalp ripples were detected and compared during the interictal periods before and after 2weeks of treatment. After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure-free group than in the non-seizure-free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non-relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling

BackgroundMigraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine.MethodsThis study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated.ResultsIn comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R.ConclusionsOur results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

O-AD006. Heart rate variability as a tool for predicting epileptic seizures

Introduction . Epilepsy is a neurological disorder that affects the patient’s quality of life and health care budget. Autonomic involvement, particularly respiratory and cardiac involvement is extremely dangerous. A particularly life-threatening complication is SUDEP. HRV represents ANS activity. We aim to compare the HRV in preictal, interictal and postictal period in patient with various types of epilepsy. Methods . Patients admitted for presurgical evaluation for epilepsy surgery and patients with epilepsy admitted for prolonged EEG monitoring (>8 hours) having various types of seizures were selected. Amongst these 49 patients, 142 seizures with various semiologies were recorded and were sent for processing. ECG signal was extracted from EEG data. Signal processing and HRV extraction was performed using EDF browser based on MATLAB. Time domain measurements like mean HR, RRI, RMSSD, SDNN and pNN50 were analyzed at different times – 20 min before the seizure, 1 minute before the seizure, during the seizure and 20 min after the seizure for each individual event. Results . Mean age was 27.14 ± 12.15 years with a minimum age of 5 years and maximum age of 58 years. Out of a total of 142 events recorded, 23 events were focal seizures with preserved consciousness, 73 events were focal seizures with impaired consciousness, 45 events were generalized seizures and 1 was a psychogenic seizure. There was significant rise in the mean HR and a drop in RRI, RMSSD, SDNN and pNN50 in the immediate preictal and interictal period. A comparison of various time intervals compared with respect to type of event showed that generalized event had a more autonomic dysregulation compared to focal seizures. Conclusion . HRV analysis is a valid method for quantifying central influences on autonomic nervous system and its cardiac control, and can give important information when used as an adjunct during clinical seizures.

Brain state-dependent high-frequency activity as a biomarker for abnormal neocortical networks in an epileptic spasms animal model.

Epileptic spasms are a hallmark of a severe epileptic state. A previous study showed neocortical up and down states defined by unit activity play a role in the generation of spasms. However, recording unit activity is challenging in clinical settings, and more accessible neurophysiological signals are needed for the analysis of these brain states. In the tetrodotoxin model, we used 16-channel microarrays to record electrophysiological activity in the neocortex during interictal periods and spasms. High-frequency activity (HFA) in the frequency range of fast ripples (200-500Hz) was analyzed, as were slow wave oscillations (1-8Hz), and correlated with the neocortical up and down states defined by multiunit activity (MUA). HFA and MUA had high temporal correlation during interictal and ictal periods. Both increased strikingly during interictal up states and ictal events but were silenced during interictal down states and preictal pauses, and their distributions were clustered at the peak of slow oscillations in local field potential recordings. In addition, both HFA power and MUA firing rates were increased to a greater extent during spasms than interictal up states. During non-rapid eye movement sleep, the HFA rhythmicity faithfully followed the MUA up and down states, but during rapid eye movement sleep when MUA up and down states disappeared the HFA rhythmicity was largely absent. We also observed an increase in the number of HFA down state minutes prior to ictal onset, consistent with the results from analyses of MUA down states. This study provides evidence that HFA may serve as a biomarker for the pathological up states of epileptic spasms. The availability of HFA recordings makes this a clinically practical technique. These findings will likely provide a novel approach for localizing and studying epileptogenic neocortical networks not only in spasms patients but also in other types of epilepsy.

Functional reorganization of brain regions into a network in childhood absence epilepsy: A magnetoencephalography study

ObjectiveEpilepsy is considered as a network disorder. However, it is unknown how normal brain activity develops into the highly synchronized discharging activity seen in disordered networks. This study aimed to explore the epilepsy brain network and the significant re-combined brain areas in childhood absence epilepsy (CAE). MethodsTwenty-two children with CAE were recruited to study the neural source activity during ictal-onset and interictal periods at frequency bands of 1–30 Hz and 30–80 Hz with magnetoencephalography (MEG) scanning. Accumulated source imaging (ASI) was used to analyze the locations of neural source activity and peak source strength. ResultsMost of the participants had more active source activity locations in the ictal-onset period rather than in the interictal period, both at 1–30 Hz and 30–80 Hz. The frontal lobe (FL), the temporo-parietal junction (T-P), and the parietal lobe (PL) became the main active areas of source activity during the ictal period, while the precuneus (PC), cuneus, and thalamus were relatively inactive. ConclusionsSome brain areas become more excited and have increased source activity during seizures. These significant brain regions might be re-combined to form an epilepsy network that regulates the process of absence seizures. SignificanceThe study confirmed that important brain regions are reorganized in an epilepsy network, which provides a basis for exploring the network mechanism of CAE development. Imaging findings may provide a reference for clinical characteristics.

Cerebrovascular Function in Hormonal Migraine: An Exploratory Study.

Background: Migraineurs, particularly young premenopausal women, are at increased risk of cerebrovascular disease; however, there is currently limited evidence as to whether hormonal migraine is associated with poor cerebrovascular function.Objectives: The objectives of this study were to: (1) investigate the potential association of cerebrovascular function with hormonal migraine and (2) determine whether abnormalities of cerebrovascular function in hormonal migraineurs are associated with migraine-related disability and/or quality of life.Method: A cross-sectional study was undertaken in 50 hormonal migraineurs (mean age: 38.7 ± 1.2 years) and 29 controls (mean age: 35.6 ± 1.8 years). Data were collected at a single point in time from all participants during the inter-ictal period when they were free from migraine and not menstruating. Transcranial Doppler ultrasound was used to measure resting blood flow velocity and cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimulation (neurovascular coupling) in the left and right middle cerebral artery (MCA). Additionally, hormonal migraineurs completed three questionnaires to assess migraine-related disability and quality of life as well as migraine frequency and intensity: Headache Impact Test-6™, Migraine-Specific Quality of Life and Migraine Disability Assessment.Results: Hormonal migraineurs had lower resting mean blood flow velocity (MBFV) (P = 0.009) and neurovascular coupling during cognitive stimulation (P = 0.010) in the left MCA than controls. No such differences were found in the right MCA. Additionally, heart rate (P = 0.004) was higher in hormonal migraineurs than controls. However, no differences in CVR to hypercapnia were found between hormonal migraineurs and controls. Multi-variate analysis revealed age to be a significant (P = 0.012) predictor of MBFV in the left MCA. Negative correlations between headache frequency and CVR to hypercapnia in the left (P = 0.026) and right MCA (P = 0.044) were found. Additionally, negative correlations between neurovascular coupling during the 2-Back 1.5 s task in the right MCA and the MSQoL emotional (P = 0.013) and role-function restrictive (P = 0.039) domains were found.Conclusions: This is the first study to show that hormonal migraineurs have poorer cerebrovascular function, as represented by lower resting MBFV and impaired neurovascular coupling in the left MCA. Future studies should investigate whether improving cerebrovascular function can prevent hormonal migraine and improve quality of life.Clinical Trial Registration: ACTRN12618001230246.

Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period

BackgroundAltered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous glutamatergic antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, a neuropeptide with known migraine-inducing properties. Hence, our aim was to reveal the role of the peripheral kynurenine pathway (KP) in episodic migraineurs. We focused on the complete tryptophan (Trp) catabolism, which comprises the serotonin and melatonin routes in addition to kynurenine metabolites. We investigated the relationship between metabolic alterations and clinical characteristics of migraine patients.MethodsFemale migraine patients aged between 25 and 50 years (n = 50) and healthy control subjects (n = 34) participated in this study. Blood samples were collected from the cubital veins of subjects (during both the interictal/ictal periods in migraineurs, n = 47/12, respectively). 12 metabolites of Trp pathway were determined by neurochemical measurements (UHPLC-MS/MS).ResultsPlasma concentrations of the most Trp metabolites were remarkably decreased in the interictal period of migraineurs compared to healthy control subjects, especially in the migraine without aura (MWoA) subgroup: Trp (p < 0.025), L-kynurenine (p < 0.001), kynurenic acid (p < 0.016), anthranilic acid (p < 0.007), picolinic acid (p < 0.03), 5-hydroxy-indoleaceticacid (p < 0.025) and melatonin (p < 0.023). Several metabolites showed a tendency to elevate during the ictal phase, but this was significant only in the cases of anthranilic acid, 5-hydroxy-indoleaceticacid and melatonin in MWoA patients. In the same subgroup, higher interictal kynurenic acid levels were identified in patients whose headache was severe and not related to their menstruation cycle. Negative linear correlation was detected between the interictal levels of xanthurenic acid/melatonin and attack frequency. Positive associations were found between the ictal 3-hydroxykynurenine levels and the beginning of attacks, just as between ictal picolinic acid levels and last attack before ictal sampling.ConclusionsOur results suggest that there is a widespread metabolic imbalance in migraineurs, which manifests in a completely depressed peripheral Trp catabolism during the interictal period. It might act as trigger for the migraine attack, contributing to glutamate excess induced neurotoxicity and generalised hyperexcitability. This data can draw attention to the clinical relevance of KP in migraine.

Ictal Occurrence of High-Frequency Oscillations Correlates With Seizure Severity in a Rat Model of Temporal Lobe Epilepsy.

High-frequency oscillations (HFOs, ripples 80–250 Hz, fast ripples 250–500 Hz) are biomarkers of epileptic tissue. They are most commonly observed over areas generating seizures and increase in occurrence during the ictal compared to the interictal period. It has been hypothesized that their rate correlates with the severity of epilepsy and seizure in affected individuals. In the present study, it was aimed to investigate whether the HFO count mirrors the observed behavioral seizure severity using a kainate rat model for temporal lobe epilepsy. Seizures were selected during the chronic epilepsy phase of this model and classified by behavioral severity according to the Racine scale. Seizures with Racine scale 5&6 were considered generalized and severe. HFOs were marked in 24 seizures during a preictal, ictal, and postictal EEG segment. The duration covered by the HFO during these different segments was analyzed and compared between mild and severe seizures. HFOs were significantly increased during ictal periods (p < 0.001) and significantly decreased during postictal periods (p < 0.03) compared to the ictal segment. Ictal ripples (p = 0.04) as well as fast ripples (p = 0.02) were significantly higher in severe seizures compared to mild seizures. The present study demonstrates that ictal HFO occurrence mirrors seizure severity in a chronic focal epilepsy model in rats. This is similar to recent observations in patients with refractory mesio-temporal lobe epilepsy. Moreover, postictal HFO decrease might reflect postictal inhibition of epileptic activity. Overall results provide additional evidence that HFOs can be used as biomarkers for measuring seizure severity in epilepsy.

Post-traumatic stress disorder (PTSD) in patients with epilepsy

Anxiety and depression in epilepsy are strongly documented but post-traumatic stress disorder (PTSD) is underestimated and poorly known. We studied the links between psycho-traumagenic events (TE), onset of epilepsy, and severity of PTSD symptoms in patients with epilepsy. The study included 54 patients with epilepsy and 61 controls. We used validated questionnaires to screen for anxiety, depression, and PTSD symptoms and we conducted an interview to measure the prevalence of TE. We developed an original exploratory questionnaire to assess the presence of PTSD during interictal and peri-ictal periods. The results show that patients reported more exposure to a TE and presented significantly more severe PTSD symptoms than controls. Seventy-eight percent of patients (vs. 52% of controls) had been exposed to a TE, and 26% (vs. 7%) had a score above the diagnostic threshold of the PTSD scale. In addition, 18.6% of patients reported that their epilepsy began at the same time as they began to experience PTSD symptoms following a TE. Patients with high PTSD scores (above the threshold, n = 14) reported significantly more depression symptoms than patients without PTSD and reported PTSD symptoms both during the ictal and peri-ictal periods. Within the whole group of patients, anxiety (72%) and depression (33%) symptoms significantly correlated with PTSD symptoms reported by the scale. This study shows that patients with epilepsy have increased prevalence of self-reported PTSD symptoms. We describe the clinical picture specific to patients with epilepsy, which may include classical PTSD symptoms but also specific peri-ictal symptoms.

Influence of Migraine on Axon Reflex-Mediated and Endothelial-Dependent Vasodilatation in the Skin

Abstract The aim of the study was to evaluate the changes in skin blood flow as a result of local heating tests in migraine patients during the interictal period, measured by laser Doppler perfusion imaging (LDI). The aim of the study was also to estimate the correlations between the results of these tests and interleukin (IL)-8 levels. Twelve migraine patients during their interictal period were compared with twelve healthy control subjects. Only women were included in the study. Both groups were matched with regard of their age, body mass index and blood pressure. For the purpose of measuring cutaneous microvascular blood flow, heating (+44 °C) of the dorsal side of the palm as a response to the local LDI was used. IL-8 was measured in serum by ELISA method. The findings suggested that migraine patients have a cutaneous vasomotor dysfunction during the interictal period. The results showed a significant decrease in the initial peak of vasodilation and the second peak of vasodilation (plateau phase). Also there were significant changes observed in the length of the time interval required to reach the first and second vasodilation peak. It is known that migraine patients have a shorter time interval to reach the first perfusion peak (axonal reflex-mediated) and longer time interval to reach the second peak (endothelium-dependent). The results confirmed the correlation between proinflammatory chemokine IL-8 levels, and the time interval till the second peak of blood flow in all study subjects.

Brain function state in different phases and its relationship with clinical symptoms of migraine: an fMRI study based on regional homogeneity (ReHo).

BackgroundUsing fMRI to analysis of brain function state in migraineurs at different phases, and combined with the clinical symptoms to explore the mechanisms and outcomes of migraine.MethodsIt’s a case-control study. We analyzed the resting-state brain functional magnetic resonance imaging in 19 patients with episodes, 22 patients with interictal phase, and 22 healthy controls. The ReHo method was used for post-processing. All subjects were evaluated using the Montreal cognitive assessment (MoCA) scale, simple mental state examination (MMSE), Hamilton anxiety (HAMA) scale, and Hamilton depression (HAMD) scale. The subjects’ clinical indicators (such as frequency of attack, course of disease, duration of each headache, and severity of headache) were correlated with the ReHo values of brain regions. This study was approved by the ethics committee of Yangtze River Shipping General Hospital.ResultsCompared with the interictal, patients in the episode group had lower activation in bilateral anterior cingulate cortex (ACC), with Montreal Neurological Institute (MNI) (−9, 42, 15); and had stronger activation in bilateral paracentral lobule (PCL), with MNI (−3, −24, 66). Compared with the control group, patients in interictal phase had lower activation in the bilateral cuneus and bilateral lingual gyrus, with MNI scores of (9, −84, 36) and (0, −72, 6), respectively. No significant difference in brain area was found between the episodes group and the control group. In the episodes group, a significant correlation was observed between attack frequency and ReHo value of the bilateral PCL (r=0.492; P=0.038).ConclusionsWe need to observe the course of migraine as a whole. In the interictal period, the cuneus and lingual gyrus may affect the development of the disease. The ACC regulates different states of migraine by inducing anti-injury sensation regulation function. The paracentric lobule is not only associated with migraine attacks, but also with the frequency. This may have an effect on the outcome of subsequent migraines, as well as whether the condition becomes chronic, and the remodeling of the brain.

Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period.

Background: Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.Methods: Six patients (one man and five women, mean age: 39 ± 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 ± 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 ± 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.Results: The MWoA-DA patients had lower glutathione/total creatine ratio (GSH/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline/total creatine ratio (tCho/tCr) than those in the other two groups. The GSH/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.Conclusion: The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.

Single-pulse stimulation of cerebellar nuclei stops epileptic thalamic activity

BackgroundEpileptic (absence) seizures in the cerebral cortex can be stopped by pharmacological and optogenetic stimulation of the cerebellar nuclei (CN) neurons that innervate the thalamus. However, it is unclear how such stimulation can modify underlying thalamo-cortical oscillations. HypothesisHere we tested whether rhythmic synchronized thalamo-cortical activity during absence seizures can be desynchronized by single-pulse optogenetic stimulation of CN neurons to stop seizure activity. MethodsWe performed simultaneous thalamic single-cell and electrocorticographical recordings in awake tottering mice, a genetic model of absence epilepsy, to investigate the rhythmicity and synchronicity. Furthermore, we tested interictally the impact of single-pulse optogenetic CN stimulation on thalamic and cortical recordings. ResultsWe show that thalamic firing is highly rhythmic and synchronized with cortical spike-and-wave discharges during absence seizures and that this phase-locked activity can be desynchronized upon single-pulse optogenetic stimulation of CN neurons. Notably, this stimulation of CN neurons was more effective in stopping seizures than direct, focal stimulation of groups of afferents innervating the thalamus. During interictal periods, CN stimulation evoked reliable but heterogeneous responses in thalamic cells in that they could show an increase or decrease in firing rate at various latencies, bi-phasic responses with an initial excitatory and subsequent inhibitory response, or no response at all. ConclusionOur data indicate that stimulation of CN neurons and their fibers in thalamus evokes differential effects in its downstream pathways and desynchronizes phase-locked thalamic neuronal firing during seizures, revealing a neurobiological mechanism that may explain how cerebellar stimulation can stop seizures.

In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish

SummarySTXBP1 mutations are associated with encephalopathy, developmental delay, intellectual disability, and epilepsy. While neural networks are known to operate at a critical state in the healthy brain, network behavior during pathological epileptic states remains unclear. Examining activity during periods between well-characterized ictal-like events (i.e., interictal period) could provide a valuable step toward understanding epileptic networks. To study these networks in the context of STXBP1 mutations, we combine a larval zebrafish model with in vivo fast confocal calcium imaging and extracellular local field potential recordings. Stxbp1b mutants display transient periods of elevated activity among local clusters of interacting neurons. These network “cascade” events were significantly larger in size and duration in mutants. At mesoscale resolution, cascades exhibit neurodevelopmental abnormalities. At single-cell scale, we describe spontaneous hyper-synchronized neuronal ensembles. That calcium imaging reveals uniquely disordered brain states during periods between pathological ictal-like seizure events is striking and represents a potential interictal biomarker.

Ictal hypoperfusion and iron deposition in the symptomatogenic zone of epilepsia partialis continua – A case report

Ictal hypoperfusion and iron deposition in the symptomatogenic zone of epilepsia partialis continua – A case report

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy.

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.