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Abstract Background To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem–cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine. Methods This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models. Results The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing. Conclusion Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians.

Abstract Objective Quantitative sensory testing is widely used in clinical and research settings to assess the sensory functions of healthy subjects and patients. It is of importance to establish normative values in a healthy population to provide reference for studies involving patients. Given the absence of normative values for pain thresholds in Taiwan, the aim of this study was to report the normative values for future reference in the Taiwanese population and compare the differences between male and female participants. Methods Healthy adults without any chronic or acute pain condition were recruited. The pain thresholds were assessed over the cephalic (supraorbital area and masseter muscle) and extracephalic (medio‐volar forearm and thenar eminence) areas. The heat, cold, mechanical punctate, and pressure pain thresholds were measured with a standardized protocol. Comparisons between male and female participants were performed. Results One hundred and thirty healthy participants (55 males: 30.4 ± 7.4 years; 75 females: 30.5 ± 8.1 years) finished the assessments. Male participants were less sensitive to mechanical stimuli, including pressure over masseter muscle (male vs. female: 178.5 ± 56.7 vs. 156.6 ± 58.4 kPa, p = .034) and punctate over medio‐volar forearm (male vs. female: 116.4 ± 45.2 vs. 98.7 ± 65.4 g, p = .011), compared to female participants. However, female participants were less sensitive to cold stimuli, indicated by lower cold pain thresholds over the supraorbital area (male vs. female: 18.6 ± 8.4 vs. 13.6 ± 9.3°C, p = .004), compared to male participants. No significant differences were found between sexes in other pain threshold parameters. Conclusions We provided the normative values of healthy male and female adults in Taiwan. This information is crucial for comparison in future pain‐related studies to identify potential hypoalgesia or hyperalgesia of tested subjects.

Abstract Objective The present study aimed to compare sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache (MOH). Methods Consecutive patients with newly diagnosed chronic migraine (CM) with and without MOH based on the Third Edition of International Classification of Headache Disorders (ICHD-3) were enrolled prospectively from the headache clinic of a tertiary medical center. Demographics and clinical profiles were collected by using a questionnaire, which included current use of tobacco, alcohol, and caffeinated beverages, the Leeds Dependence Questionnaire (LDQ), the Severity of Dependence Scale (SDS), the Headache Impact Test-6 (HIT-6), and the Pittsburgh Sleep Quality Index (PSQI). Results In total, 1419 CM patients (1135F/284 M, mean age 41.7 ± 13.9 years) were recruited, including 799 with MOH (640F/159 M, mean age 42.5 ± 13.2 years) (56.3%). Smoking was associated with an increased risk for MOH in men (odds ratio [OR] = 3.60 [95% confidence interval = 1.73–7.50], p = 0.001), but not in women (OR = 1.34 [0.88–2.04], p = 0.171) (p = 0.021 for interaction). Hypnotic use ≥ 3 days/week was a risk factor for MOH (OR = 2.55 [95% confidence interval = 2.00–3.24], p

Abstract To determine specific resting-state network patterns underlying alterations in chronic migraine, we employed oscillatory connectivity and machine learning techniques to distinguish patients with chronic migraine from healthy controls and patients with other pain disorders. This cross-sectional study included 350 participants (70 healthy controls, 100 patients with chronic migraine, 40 patients with chronic migraine with comorbid fibromyalgia, 35 patients with fibromyalgia, 30 patients with chronic tension-type headache, and 75 patients with episodic migraine). We collected resting-state magnetoencephalographic data for analysis. Source-based oscillatory connectivity within each network, including the pain-related network, default mode network, sensorimotor network, visual network, and insula to default mode network, was examined to determine intrinsic connectivity across a frequency range of 1–40 Hz. Features were extracted to establish and validate classification models constructed using machine learning algorithms. The findings indicated that oscillatory connectivity revealed brain network abnormalities in patients with chronic migraine compared with healthy controls, and that oscillatory connectivity exhibited distinct patterns between various pain disorders. After the incorporation of network features, the best classification model demonstrated excellent performance in distinguishing patients with chronic migraine from healthy controls, achieving high accuracy on both training and testing datasets (accuracy > 92.6% and area under the curve > 0.93). Moreover, in validation tests, classification models exhibited high accuracy in discriminating patients with chronic migraine from all other groups of patients (accuracy > 75.7% and area under the curve > 0.8). In conclusion, oscillatory synchrony within the pain-related network and default mode network corresponded to altered neurophysiological processes in patients with chronic migraine. Thus, these networks can serve as pivotal signatures in the model for identifying patients with chronic migraine, providing reliable and generalisable results. This approach may facilitate the objective and individualised diagnosis of migraine.

Abstract Background Sphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles. Methods We prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0–5) were recorded to analyze their association with SPG volume. Results The inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84–0.90, p

Abstract To identify and validate the neural signatures of resting-state oscillatory connectivity for chronic migraine (CM), we used machine learning techniques to classify patients with CM from healthy controls (HC) and patients with other pain disorders. The cross-sectional study obtained resting-state magnetoencephalographic data from 240 participants (70 HC, 100 CM, 35 episodic migraine [EM], and 35 fibromyalgia [FM]). Source-based oscillatory connectivity of relevant cortical regions was calculated to determine intrinsic connectivity at 1–40 Hz. A classification model that employed a support vector machine was developed using the magnetoencephalographic data to assess the reliability and generalizability of CM identification. In the findings, the discriminative features that differentiate CM from HC were principally observed from the functional interactions between salience, sensorimotor, and part of the default mode networks. The classification model with these features exhibited excellent performance in distinguishing patients with CM from HC (accuracy ≥ 86.8%, area under the curve (AUC) ≥ 0.9) and from those with EM (accuracy: 94.5%, AUC: 0.96). The model also achieved high performance (accuracy: 89.1%, AUC: 0.91) in classifying CM from other pain disorders (FM in this study). These resting-state magnetoencephalographic electrophysiological features yield oscillatory connectivity to identify patients with CM from those with a different type of migraine and pain disorder, with adequate reliability and generalizability.

Recently, immune checkpoint inhibitors (ICIs) have become the standard treatment option for patients with lung cancer, including small cell lung cancer (SCLC). ICI-induced neurological immune-related adverse events are rare and exhibit diverse clinical manifestations, often leading to missed or delayed diagnosis. Herein, we report the case of a patient with extensive-stage SCLC who received atezolizumab with etoposide/platinum and gradually developed neurological symptoms after three cycles of chemoimmunotherapy. Subsequently, the patient received a diagnosis of subacute immune-related cerebellar ataxia and was treated successfully with pulse steroid therapy. The patient exhibited almost complete remission of neurological symptoms and had progression-free survival for >24 months.

Abstract Background Migraine has complex pathophysiological characteristics and episodic attacks. To decipher the cyclic neurophysiological features of migraine attacks, in this study, we compared neuronal excitability in the brainstem and primary somatosensory (S1) region between migraine phases for 30 consecutive days in two patients with episodic migraine. Methods Both patients underwent EEG recording of event-related potentials with the somatosensory and paired-pulse paradigms for 30 consecutive days. The migraine cycle was divided into the following phases: 24–48 h before headache onset (Pre2), within 24 h before headache onset (Pre1), during the migraine attack (Ictal), within 24 h after headache offset (Post1), and the interval of ˃48 h between the last and next headache phase (Interictal). The normalised current intensity in the brainstem and S1 and gating ratio in the S1 were recorded and examined. Results Six migraine cycles (three for each patient) were analysed. In both patients, the somatosensory excitability in the brainstem (peaking at 12–14 ms after stimulation) and S1 (peaking at 18–19 ms after stimulation) peaked in the Pre1 phase. The S1 inhibitory capability was higher in the Ictal phase than in the Pre1 phase. Conclusion This study demonstrates that migraine is a cyclic excitatory disorder and that the neural substrates involved include the somatosensory system, starting in the brainstem and spanning subsequently to the S1 before the migraine occurs. Further investigations with larger sample sizes are warranted.

Introduction: The development of quantitative, objective signatures or predictors to evaluate pain sensitivity is crucial in the clinical management of pain and in precision medicine. This study combined multimodal (neurophysiology and psychometrics) signatures to classify the training dataset and predict the testing dataset on individual heat pain sensitivity. Methods: Healthy individuals were recruited in this study. Individual heat pain sensitivity and psychometric scores, as well as the resting-state electroencephalography (EEG) data, were obtained from each participant. Participants were divided into low-sensitivity and high-sensitivity subgroups according to their heat pain sensitivity. Psychometric data obtained from psychometric measurements and power spectral density (PSD) and functional connectivity (FC) derived from resting-state EEG analysis were subjected to feature selection with an independent t test and were then trained and predicted using machine learning models, including support vector machine (SVM) and k-nearest neighbor. Results: In total, 85 participants were recruited in this study, and their data were divided into training (n = 65) and testing (n = 20) datasets. We identified the resting-state PSD and FC, which can serve as brain signatures to classify heat pain as high-sensitive or low-sensitive. Using machine learning algorithms of SVM with different kernels, we obtained an accuracy of 86.2%–93.8% in classifying the participants into thermal pain high-sensitivity and low-sensitivity groups; moreover, using the trained model of cubic SVM, an accuracy of 80% was achieved in predicting the pain sensitivity of an independent dataset of combined PSD and FC features of resting-state EEG data. Conclusion: Acceptable accuracy in classification and prediction by using the SVM model indicated that pain sensitivity could be achieved, leading to considerable possibilities of the use of objective evaluation of pain perception in clinical practice. However, the predictive model presented in this study requires further validation by studies with a larger dataset.

Abstract Objective Mutations in the colony‐stimulating factor 1 receptor gene (CSF1R) were identified as a cause of adult‐onset inherited leukoencephalopathy. The present study aims at investigating the frequency, clinical characteristics, and functional effects of CSF1R mutations in Taiwanese patients with adult‐onset leukoencephalopathy. Methods Mutational analysis of CSF1R was performed in 149 unrelated individuals with leukoencephalopathy by a targeted resequencing panel covering the entire coding regions of CSF1R. In vitro analysis of the CSF1‐induced autophosphorylation activities of mutant CSF1R proteins was conducted to assess the pathogenicity of the CSF1R mutations. Results Among the eight CSF1R variants identified in this study, five mutations led to a loss of CSF1‐induced autophosphorylation of CSF1R proteins. Four mutations (p.K586*, p.G589R, p.R777Q, and p.R782C) located within the tyrosine kinase domain of CSF1R, whereas the p.T79M mutation resided in the immunoglobulin‐like domain. The five patients carrying the CSF1R mutations developed cognitive decline at age 41, 43, 50, 79, and 86 years, respectively. Psychiatric symptoms and behavior changes were observed in four of the five patients. The executive function and processing speed were severely impaired at an early stage, and their cognitive function deteriorated rapidly within 3–4 years. Diffusion‐restricted lesions at the subcortical regions and bilateral corticospinal tracts were found in three patients. Interpretation CSF1R mutations account for 3.5% (5/149) of the adult‐onset leukoencephalopathy in Taiwan. CSF1R mutations outside the tyrosine kinase domain may also disturb the CSF1R function and lead to the clinical phenotype. Molecular functional validation is important to determine the pathogenicity of novel CSF1R variants.

Abstract Background Pain sensitivity may determine the risk, severity, prognosis, and efficacy of treatment of clinical pain. Magnetic resonance imaging studies have linked thermal pain sensitivity to changes in brain structure. However, the neural correlates of mechanical pain sensitivity remain to be clarified through investigation of direct neural activities on the resting-state cortical oscillation and synchrony. Methods We recorded the resting-state magnetoencephalographic (MEG) activities of 27 healthy individuals and 30 patients with episodic migraine (EM) and analyzed the source-based oscillatory powers and functional connectivity at 2 to 59 Hz in pain-related cortical regions, which are the bilateral anterior cingulate cortex (ACC), medial orbitofrontal (MOF) cortex, lateral orbitofrontal (LOF) cortex, insula cortex, primary somatosensory cortex (SI), primary motor cortex (MI), and posterior cingulate cortex (PCC). The mechanical punctate pain threshold (MPPT) was obtained at the supraorbital area (the first branch of the trigeminal nerve dermatome, V1) and the forearm (the first thoracic nerve dermatome, T1) and further correlated with MEG measures. Results The MPPT is inversely correlated with the resting-state relative powers of gamma oscillation in healthy individuals (all corrected P

Abstract Introduction Fibromyalgia (FM) is a chronic pain condition characterized by impaired emotional regulation. This study explored the brain response to pain-related fear as a potential brain signature of FM. Methods We used a conditioned fear task and magnetoencephalography to record pain-related fear responses in patients with FM. Two blocks of 30 fear responses were collected to compute the response strength in the first block and the strength difference between the first and second blocks (fear habituation). These measurements were investigated for their clinical relevance and compared with measurements obtained from healthy controls and patients with chronic migraine (CM), a different chronic pain condition often comorbid with FM. Results Pain-related fear clearly activated the bilateral amygdala and anterior insula in patients with FM (n = 52), patients with CM (n = 50), and the controls (n = 30); the response strength in the first block was consistent across groups. However, fear habituation in the right amygdala decreased in the FM group (vs. CM and control groups, both p ≤ 0.001, no difference between CM and control groups). At the 3-month follow-up, the patients with FM reporting 0.7). Conclusions Amygdala activation to pain-related fear is maladaptive and linked to treatment outcomes in patients with FM. Because the aberrant amygdala response was not observed in the CM group, this response is a potential brain signature of FM. Trial Registration ClinicalTrials.gov Identifier, NCT02747940.

Abstract Background The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month). Methods We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction

ObjectivesTo identify the neuroimaging predictors for the responsiveness of patients to sumatriptan and use an independent cohort for external validation.MethodsStructuralized headache questionnaire and 3-Tesla brain magnetic resonance imaging were performed in migraine patients. Regional brain volumes were automatically calculated using FreeSurfer version 6.0, including bilateral amygdala, anterior cingulated cortex, caudate, putamen, precuneus, orbitofrontal cortex, superior frontal gyri, middle frontal gyri, hippocampus, and parahippocampus. A sumatriptan-responder was defined as headache relief within 2 h after the intake of sumatriptan in at least two out of three treated attacks. We constructed a prediction model for sumatriptan response using the regional brain volume and validated it with an independent cohort of migraine patients.ResultsA total of 105 migraine patients were recruited, including 73 sumatriptan responders (69.5%) and 32 (30.5%) non-responders. We divided the migraine patients into derivation (n = 73) and validation cohorts (n = 32). In the derivation cohort, left hippocampal volume was larger in sumatriptan responders (responders vs. non-responders: 3,929.5 ± 403.1 vs. 3,611.0 ± 389.9 mm3, p = 0.002), and patients with a larger left hippocampal volume had a higher response rate to sumatriptan (>4,036.2 vs. ≤4,036.2 mm3: 92.0 vs. 56.3%, p = 0.001). Based on the findings, we constructed a prediction model using the cutoff value of 4,036.2 mm3, and we found that patients with a left hippocampal volume >4,032.6 mm3 had a higher response rate to sumatriptan than those with a left hippocampal volume ≤4,032.6 mm3 (84.6 vs. 42.1%, odds ratio [OR] = 7.6 [95% confidence interval = 1.3–44.0], p = 0.013) in the validation cohort.ConclusionOur study showed that left hippocampal volume is helpful to identify sumatriptan non-responders. This proof-of-concept study shows that left hippocampal volume could be used to predict the treatment response to sumatriptan in migraine patients.

Dependence behaviors are common in patients with medication-overuse headache (MOH). This prospective study aimed to characterize dependence behaviors in MOH by using Leeds dependence questionnaire (LDQ), and to determine the clinical utility of LDQ in the diagnosis of MOH. In total, 563 consecutive chronic migraine (CM) patients (451F/112M, mean age 41.7 ± 12.0 years) were recruited, including 320 with MOH (56.8%) (254F/66M, mean age 42.3 ± 11.6 years). LDQ scores were positively correlated with the monthly frequency of acute medication use (Spearman’s rho = 0.680, p < 0.001). When compared with patients without, those with MOH scored higher on LDQ (13.0 ± 7.6 vs. 3.9 ± 5.1, p < 0.001). By using a receiver operating characteristics curve, the cutoff value of LDQ was determined at 7 (sensitivity = 77.5%, specificity = 77.4%, area under curve = 0.85) for a diagnosis of MOH. An LDQ score of ≥7 was predictive of MOH (odds ratio = 11.80, 95% confidence interval = 7.87–17.67, p < 0.001). In conclusion, the presence of MOH in patients with CM is associated with more severe dependence behaviors. An LDQ score of ≥7 is useful in the detection of MOH in CM patients.

Abstract Background Despite evidently distinct symptoms, tension-type headache (TTH) and migraine are highly comorbid and exhibit many similarities in clinical practice. The purpose of this study was to investigate whether both types of headaches are similar in brain morphology. Methods Consecutive patients with TTH and age- and sex-matched patients with migraine and healthy controls were enrolled for brain magnetic resonance imaging examination. Patients with TTH were excluded if they reported any headache features or associated symptoms of migraine. Changes in gray matter (GM) volume associated with headache diagnosis (TTH vs. migraine) and frequency (episodic vs. chronic) were examined using voxel-based morphometry. The correlation with headache profile and the discriminative ability between TTH and migraine were also investigated for these GM changes. Results In comparison with controls (n = 43), the patients with TTH (25 episodic and 24 chronic) exhibited a GM volume increase in the anterior cingulate cortex, supramarginal gyrus, temporal pole, lateral occipital cortex, and caudate. The patients with migraine (31 episodic and 25 chronic) conversely exhibited a GM volume decrease in the orbitofrontal cortex. These GM changes did not correlate with any headache profile. A voxel-wise 2 × 2 factorial analysis further revealed the substantial effects of headache types and frequency in the comparison of GM volume between TTH and migraine. Specifically, the migraine group (vs. TTH) had a GM decrease in the superior and middle frontal gyri, cerebellum, dorsal striatum, and precuneus. The chronic group (vs. episodic group) otherwise demonstrated a GM decrease in the bilateral insula and anterior cingulate cortex. In receiver operating characteristic analysis, the GM volumes of the left superior frontal gyrus and right cerebellum V combined had good discriminative ability for distinguishing TTH and migraine (area under the curve = 0.806). Conclusions TTH and migraine are separate headache disorders with different characteristics in relation to GM changes. The major morphological difference between the two types of headaches is the relative GM decrease of the prefrontal and cerebellar regions in migraine, which may reflect a higher allostatic load associated with this disabling headache.

Sensory gating, a habituation-related but more basic protective mechanism against brain sensory overload, is altered in patients with migraine and linked to headache severity. This study investigated whether somatosensory (SI) gating responses determined 3-months treatment outcomes in patients with episodic migraine (EM) and chronic migraine (CM). A 306-channel magnetoencephalography (MEG) with paired-pulse stimulation paradigm was used to record their neuromagnetic responses. To calculate the peak amplitude and latency and compute the gating ratios (second vs. first amplitude), the first and second responses to the paired stimuli from the primary somatosensory cortex were obtained. All patients were assigned to subgroups labeled good or poor according to their headache frequency at baseline compared with at the third month of treatment. The gating ratio in the CM group (n = 37) was significantly different between those identified as good and poor (p = 0.009). In the EM group (n = 30), the latency in the second response differed by treatment outcomes (p = 0.007). In the receiver operating characteristic analysis, the areas under the curve for the CM and EM groups were 0.737 and 0.761, respectively. Somatosensory gating responses were associated with treatment outcomes in patients with migraine; future studies with large patient samples are warranted.

The palmomental reflex (PMR) is a brief contraction of the mentalis muscles caused by a scratch over the thenar eminence, i.e. a brainstem reflex to afferents of upper limb. Using electrophysio-logic methods, we studied the characteristics of brainstem excitability in PMR subjects. Methods: Ten healthy PMR subjects were included in the study. Brainstem excitability was assessed with electrical stimulation at the trigeminal nerve, median nerve, ulnar nerve, and sural nerve with recordings at the mentalis muscles. A comparison was made by the probability between the mechanical scratch and the electrical stimulation to evoke the visible muscle contraction of mentalis. Results: An electrical stimulus was able to elicit mentalis muscle responses (MMRelectrical) in all the subjects if the stimulus was of sufficient strength. Using electrical stimulation, the median nerve at the wrist was the best site to evoke MMRelectrical. However, in PMR subjects, the probability of MMRelectrical to median nerve stimulation was less than that of MMRscratch, i.e. the clinical findings of PMR. Significantly lower thresholds and higher amplitudes were noted in PMR subjects only when the median nerve was stimulated. The onset latency did not show any difference between the two groups despite the stimulation sites. Conclusion: The facial motor neurons to median nerve stimulation are more sensitive in PMR subjects. In healthy PMR subjects, this indicates that the excitability increases only in the specific neuronal circuits between the lower cervical spinal cord and the facial motor nucleus in the rostral medulla. MMRelectrical is a physiologic phenomenon, and PMR is a sign of increased brainstem excitability.

Background: The visual cortex is involved in the generation of migraine aura. Voxel-based multivariate analyses applied to this region may provide complementary information about aura mechanisms relative to the commonly used massunivariate analyses. Methods: Structural images constrained within the functional resting-state visual networks were obtained in migraine patients with (n = 50) and without (n = 50) visual aura and healthy controls (n = 50). The masked images entered a multivariate analysis in which Gaussian process classification was used to generate pairwise models. Generalizability was assessed by five-fold cross-validation and non-parametric permutation tests were used to estimate significance levels. A univariate voxel-based morphometry analysis was also performed. Results: A multivariate pattern of grey matter voxels within the ventral medial visual network contained significant information related to the diagnosis of migraine with visual aura (aura vs. healthy controls: classification accuracy = 78%, p < 0.001; area under the curve = 0.84, p < 0.001; migraine with aura vs. without aura: classification accuracy = 71%, p < 0.001; area under the curve = 0.73, p < 0.003). Furthermore, patients with visual aura exhibited increased grey matter volume in the medial occipital cortex compared to the two other groups. Conclusions: Migraine with visual aura is characterized by multivariate and univariate patterns of grey matter changes within the medial occipital cortex that have discriminative power and may reflect pathological mechanisms. [ABSTRACT FROM AUTHOR]

Background: To investigate the characteristics and clinical correlates of transient visual disturbances (TVDs) in patients with migraine without aura (MO). Patients with MO frequently report TVDs, which differ from typical visual aura, but the clinical significance of these TVDs has not been determined. Methods: Patients with MO who attended our headache clinics were enrolled. Structured questionnaires were used to acquire data on participants' headache profiles, disability, comorbidities, and lifetime suicidal ideation and suicide attempts. A semistructured visual phenomenon questionnaire was used to characterize TVDs. Headache specialists interviewed the participants for diagnosis and the verification of questionnaire responses. Results: Patients with MO (n = 7200; female/male ratio = 3.56, mean age 40.1 ± 13.4 years) were divided into two groups based on the presence (n = 2488) or absence (n = 4712) of TVDs. Patients with TVDs had more headache-related disability, psychiatric comorbidities, and photophobia than did those without TVDs. Suicidal ideation and suicide attempts were more common among patients with than among those without TVDs [ideation: odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.71-2.15, p < 0.001; suicide attempt: OR = 2.23, 95% CI 1.80-2.75, p < 0.001]. Conclusion: The presence of TVDs may imply greater migraine-related disability, photophobia, and suicidal ideation/suicide attempt risk in patients with MO. [ABSTRACT FROM AUTHOR]

Background: Expanded HTT alleles with 40 or more CAG repeats were recently found to be a rare cause of frontotemporal dementia and amyotrophic lateral sclerosis (ALS) spectrum diseases. The aim of this study was to investigate the role of HTT repeat expansions in a Taiwanese cohort with ALS. Methods: We analyzed the numbers of CAG repeats in exon 1 of HTT in a cohort of 410 Taiwanese patients with ALS and 1514 control individuals by utilizing polymerase chain reaction and amplicon fragment length analysis. Results: Only one of the 410 ALS patients carried a reduced-penetrance HD-causing allele with 39 CAG repeats, and none had an expanded HTT CAG repeats =40. The patient presented with rapidly progressive bulbar-onset ALS with disease onset at the age of 64 years. He had neither chorea nor cognitive impairment. He had a family history of chorea, but no other family member manifested with ALS. None of the 1514 control individuals carried an HTT expanded allele with CAG repeats larger than 37 repeats. Conclusion: The HTT allele with 39 CAG repeats could be a genetic factor linked to ALS susceptibility. [ABSTRACT FROM AUTHOR]

Backgrounds: Conditioned responses of paired nociceptive blink reflex (nBR) can reflect the excitability of trigeminofacial circuit. In the present study, we studied paired homotopic nBR with different inter-stimulus intervals (ISI). By monitoring different ISIs and consequential conditioned R2 of nBR, we aimed to investigate the impact of ISIs on the recovery cycle of nBR in normal individuals. Methods: Twelve healthy volunteers (mean age: 29.9 ± 7.0 years; M/F: 7/5) were enrolled in this study. After individuals' reflex threshold was determined, triple pulses were given in pairs with ISIs 125 to 10000 milliseconds randomly. We calculated the ratio of conditioned and unconditioned nBR area-under-curve (AUC) (defined as recovery index), and amplitude of each ISI. Results: The average latency of unconditioned nR2 is 42.6 ± 5.5 ms, with amplitude of 53.4 ± 43.9 μV and the AUC of 563.5 ± 480.6 ms·μV. The conditioned nBR/unconditioned nBR response ratio was less than 100% while the ISI is shorter than 1667 ms, suggesting an inhibited conditioned response. The recovery index and the amplitude of conditioned nBR gradually increased with increasing ISI. The recovery index was greater than 100% at ISI of 10 s (p = 0.005), implying full recovery and facilitation of conditioned nBR. Conclusion: Our study established the time-dependent dynamic recovery curve of paired nBR. The facilitated nBR at ISI longer than 10 s might be associated with temporal summation to the facial motor neurons after repeated stimuli. Our study results provided potential applications for patients with pain disorders involving trigeminofacial region. [ABSTRACT FROM AUTHOR]

Migraine chronification is associated with a dysfunctional thalamocortical pathway. The present study addressed whether abnormal concentrations of neurochemicals exist in key brain regions of this pathway in chronic migraine. Magnetic resonance spectroscopic imaging of the bilateral medial walls of the brain was used to measure choline, creatine, glutamate and glutamine, myo-inositol, and N-acetyl-aspartate in chronic migraine patients and in matched groups of episodic migraine patients and healthy controls. A region of interest analysis was conducted to examine whether N-acetyl-aspartate, a marker of neuronal integrity, was reduced in the thalamus, occipital cortex and anterior cingulate cortex in chronic migraine. Interregional N-acetyl-aspartate correlations among these regions of interest were also examined. Additionally, statistical mapping was performed for all the metabolites throughout the medial walls. Chronic migraine was associated with N-acetyl-aspartate reductions in the bilateral thalami and in the right anterior cingulate. The N-acetyl-aspartate reduction in the right thalamus correlated with disease duration. Compared with healthy controls, patients with chronic migraine had altered interregional N-acetyl-aspartate correlations between the right thalamus-anterior cingulate and thalamus-occipital cortex, and between the left and right anterior cingulate. N-acetyl-aspartate concentrations and interregional correlations in patients with episodic migraine were between those of healthy controls and chronic migraine patients. The unconstrained analyses revealed a reduction of myo-inositol in the left anterior and posterior cingulate in both patient groups as well as a negative association with depression scores for the anterior cingulate in the combined patient group. In addition, migraine patients with headache on the scan day (irrespective of diagnosis) had reduced N-acetyl-aspartate and total creatine concentrations in the right dorsal anterior cingulate. Reduced N-acetyl-aspartate metabolism and altered interregional N-acetyl-aspartate correlations lend support to the role of thalamocortical dysfunction in migraine chronification. It remains to be established if the pattern of changes within the N-acetyl-aspartate network is specific to chronic migraine or can be found in other chronic pain conditions. [ABSTRACT FROM AUTHOR]

Background: Medication overuse headache shares several characteristics with substance use disorders. However, key features of substance use disorders such as increased impulsivity and alterations in reward processing remain little explored in medication overuse headache. Methods: Temporal discounting and impulsive decision making behavior and the associated brain mechanisms were assessed in 26 chronic migraine patients with medication overuse headache and in 28 healthy controls. Regions-of-interest analyses were first performed for task-related regions, namely the ventral striatum and the ventromedial and dorsomedial prefrontal cortices. Resting-state functional connectivity between these regions were then explored. An additional 27 chronic migraine patients without medication overuse headache were included for comparison in the latter analysis. Results: Patients with medication overuse headache showed steeper temporal discounting behavior than healthy controls. They also showed weaker subjective value representations in the dorsomedial prefrontal cortex, when accepting larger delayed rewards, and in ventral striatum and ventromedial prefrontal cortex, when accepting the smaller immediate reward. Resting-state functional connectivity was reduced among the valuation regions when comparing patients with medication overuse headache to the other two control groups. Conclusions: Patients with medication overuse headache were characterized by altered processing and dysconnectivity in the reward system during intertemporal choices and in the resting-state. [ABSTRACT FROM AUTHOR]

A 48-year-old woman suddenly lost consciousness as a result of a right rostral pontine tegmentum haemorrhage. The patient presented with decerebrate rigidity (DR) and regained full consciousness 5 days after the initial onset. The patient was given gabapentin 1200 mg/day nasogastrically and her DR significantly improved, although other antiepileptic drugs such as phenytoin and carbamazepine were given in larger dosages to decrease muscle hypertonicity. The patients’ preserved consciousness and motor-evoked potentials to transcranial magnetic stimulation indicated a derangement of the extrapyramidal tracts with preservation of the pyramidal tracts. This case report discusses the possible mechanisms of action of gabapentin in DR. [ABSTRACT FROM AUTHOR]