Existence and Significance of Internal Border Zone Infarcts with Accessory Lesions Located in the Anteromedial Temporal Lobe.

OBJECTIVES: To examine the existence and significance of internal border zone (IBZ) infarcts with accessory lesions in the anteromedial temporal lobe (ATL). MATERIALS AND METHODS: IBZ infarcts located at the corona radiata were selected based on diffusion-weighted imaging of 2535 consecutive patients with ischemic stroke and the presence of lesions in the ATL was identified. The Mann-Whitney U test, Student t-test, Pearson χ2 test, or Fisher exact test was used to analyze differences between the IBZ infarct groups with and without accessory lesions in the ATL. RESULTS: Thirty-six of 2535 patients (1.4%) had IBZ infarcts. The IBZ group with accessory lesions in the ATL (17 cases, 47.2%) showed a higher portion of occluded middle cerebral arteries than the IBZ group without accessory lesions in the ATL (p = 0.02). The initial National Institutes of Health Stroke Scale score (odds ratio, 2.03; 95% confidence interval, 1.04-3.99;   = 0.039) and progression after admission (odds ratio, 25.43; 95% confidence interval, 2.47-261.99; p = 0.007) were independently associated with poor prognosis in patients with IBZ infarcts. There were no differences in the progression rate and clinical outcomes, regardless of the presence of lesions in the ATL. CONCLUSIONS: Our study suggests the existence of a distinct type of IBZ infarct characterized by accessory lesions in the ATL, which is associated with different arterial features but has a similar clinical course to IBZ infarcts without accessory lesions in the ATL.

Characteristics of Perfusion Computed Tomography Imaging in Patients with Seizures Mimicking Acute Stroke.

INTRODUCTION: Seizures as acute stroke mimics are a diagnostic challenge. OBJECTIVE: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke. METHODS: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group. RESULTS: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan). CONCLUSIONS: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.

Orthostatic dizziness in Parkinson's disease is attributed to cerebral hypoperfusion: A transcranial doppler study.

OBJECTIVES: Orthostatic hypotension (OH) is controversially regarded as the cause of orthostatic dizziness in Parkinson's disease (PD). We sought to evaluate whether cerebral autoregulation is an alternative cause for orthostatic dizziness in PD patients, using transcranial Doppler monitoring during head-up tilting. METHODS: Forty-five PD patients with dizziness, 13 PD patients without dizziness, and 10 age-matched healthy controls were enrolled. Participants were divided into the following four groups: patients with dizziness and OH (group 1, n = 22), patients with dizziness but no OH (n = 23, group 2), patients without dizziness (n = 11, group 3), and age-matched healthy controls (n = 10, group 4). All participants underwent transcranial Doppler and blood pressure monitoring for 10 minutes during the head-up tilt test. Changes in the cerebral blood flow velocity (CBFV) in the middle cerebral artery and the mean blood pressure (mBP) within 3 minutes after head-up tilting were compared between groups. RESULTS: Group 1 showed a significantly higher change in mBP (-16.3 ± 10.8 mmHg) than groups 2 (-2.6 ± 4.9), 3 (-2.2 ± 3.6), or 4 (1.8 ± 6.0) (p < 0.001). However, groups 3 (4.6 ± 3.0 cm/s) and 4 (-4.2 ± 2.5) showed a significantly smaller change in CBFV than groups 1 (-9.0 ± 4.2) and 2 (-8.1 ± 5.1) (p < 0.01). CONCLUSIONS: Our results suggest that cerebral hypoperfusion contributes to dizziness in PD patients despite a lack of OH. Transcranial Doppler monitoring during head-up tilting may be a useful tool for evaluating dizziness in PD patients with or without OH. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:337-342, 2017.

Clinical Significance of Fluid-Attenuated Inversion Recovery Vascular Hyperintensities in Borderzone Infarcts.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensities (FVHs) are seen in some cases with cerebral hemodynamic impairment and collateral flow. Because the worst outcomes of patients with borderzone infarcts were mainly correlated with impaired hemodynamics, the presence of FVH might provide another clue for predicting the prognosis of patients with borderzone infarcts. METHODS: We reviewed 1377 consecutive patients with ischemic stroke. Cortical borderzone (CBZ) and internal borderzone infarcts were selected based on diffusion-weighted imaging. FVHs were defined as tubular- or serpentine-shaped hyperintensities in the subarachnoid space. We investigated the clinical significance of FVHs in borderzone-infarcted patients. RESULTS: Among 87 patients with borderzone infarcts, the presence of FVH was observed in 30 (34.5%). We identified 62 patients with CBZ infarcts and 25 patients with internal borderzone infarcts. In the cases with CBZ infarcts, the initial National Institutes of Health Stroke Scale scores and the portions of nonfavorable outcome at 3 months in the FVH(+) group were significantly higher than in the FVH(-) group (P<0.05 and P<0.001, respectively). Unlike the cases with CBZ infarcts, there were no significant differences of these clinical features between the FVH(+) group and the FVH(-) group in the patients with internal borderzone infarcts. CONCLUSIONS: The findings of FVH are associated with relatively severe clinical presentation and nonfavorable prognosis in patients with CBZ infarcts, but not in patients with internal borderzone infarcts. The presence of FVH may help to identify CBZ-infarcted patients who require close observation and hemodynamic control.

25-hydroxyvitamin D status is associated with chronic cerebral small vessel disease.

BACKGROUND AND PURPOSE: The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease. METHODS: We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses. RESULTS: Mean age was 68 (±13) years. Mean level of 25(OH)D was 34.1±17.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02-0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41-3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01-1.63). Also, 25(OH)D deficiency (≤25 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04-0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31-6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03-2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients. CONCLUSIONS: 25(OH)D is inversely associated with lacunes, white matter hyperintensity, and deep CMB. Our findings suggest that 25(OH)D is linked to small vessel disease, and in future trials it should be tested whether 25(OH)D supplementation can prevent small vessel disease.

Cortical Morphology in Patients with Orthostatic Intolerance.

BACKGROUND: We evaluated the cortical morphology in patients with orthostatic intolerance. METHODS: Thirty patients with orthostatic intolerance, as well as age- and sex-matched normal controls, were enrolled in this study. We divided the patients into orthostatic hypotension (n = 22) and postural tachycardia syndrome (n = 8) groups based on their response to a head-up tilt table test. We analyzed whole-brain T1-weighted MRI images using FreeSurfer 5.1. The measures of cortical morphology were compared between the groups. RESULTS: The cortical thickness in the right hemisphere, including the medial orbitofrontal, peri-calcarine, post-central, inferior temporal, and lateral occipital cortex, and in the peri-calcarine cortex of the left hemisphere was thinned in patients with orthostatic hypotension compared to normal controls. The other measures of cortical morphology, including the surface area, volume, and curvatures, did not differ between patients with orthostatic hypotension and normal controls. However, none of the measures of cortical morphology differed between patients with postural tachycardia syndrome and normal controls. CONCLUSIONS: We demonstrated that the cortical morphology significantly changed in patients with orthostatic hypotension but not in patients with postural tachycardia syndrome compared to normal controls. These findings support the hypothesis that orthostatic intolerance is a heterogeneous syndrome.

Carotid artery calcification is associated with deep cerebral microbleeds.

BACKGROUND/AIMS: The aim of the present study was to determine the association between arterial calcification and cerebral microbleeds (CMB) relative to their distribution. METHODS: We identified 834 consecutive patients with acute ischemic stroke or transient ischemic attack who underwent CT angiography and susceptibility-weighted imaging. RESULTS: Internal carotid artery (ICA) calcification and CMB were found in 660 patients (79.1%) and 335 patients (40.2%), respectively. ICA calcification was independently associated with CMB of any location (odds ratio, OR, 2.86, 95% CI 2.01-4.08, p < 0.0001). The association between calcification and deep CMB was stronger (OR 3.51, 95% CI 2.39-5.14, p < 0.0001). However, ICA calcification was not associated with CMB in a strictly lobar area. CONCLUSION: ICA calcification is an independent risk factor for deep CMB but not for a strictly lobar CMB. Our findings might contribute to the elucidation of the pathogenesis of cerebral small vessel disease.

Isolated rotational vertigo due to internal capsular infarction.

Isolated rotational vertigo is most often associated with disorders of the semicircular canals, vestibular nerve, brainstem, or cerebellum but rarely observed following a supratentorial stroke. A 64-year-old man developed sudden onset of vertigo and horizontal right-beating nystagmus with a torsional component in primary and eccentric gazes, unsteady gait, and axial lateropulsion to the right side. Magnetic resonance imaging demonstrated an infarction in the posterior limb of left internal capsule, an unusual cause of the patient's signs and symptoms.

A Case of Acute Vestibular Neuritis Visualized by Three-Dimensional FLAIR-VISTA Magnetic Resonance Imaging.

A 72-year-old man presented with vertigo and unsteady gait. The three-dimensional fluid-attenuated inversion recovery-volume isotopic turbo spin echo acquisition (3D-FLAIR-VISTA) magnetic resonance imaging (MRI) showed high signal intensity in the cisternal segment of the right vestibular nerve. The video-based oculography with caloric test revealed spontaneous left-beating nystagmus and canal paresis in the right ear. This case suggests that 3D-FLAIR-VISTA images are useful for the visualisation of acute vestibular neuritis.

Cavernous malformations associated with dural arteriovenous shunts in the central nervous system.

INTRODUCTION: Some cerebral cavernous malformations (CCMs) may be associated with vascular malformations that occur on the capillary-venous side of the cerebral circulation. The association between CCMs and dural arteriovenous shunts (DAVSs) is not well known. The purpose of this study is to investigate the relationship between CCMs and DAVSs. METHODS: We retrospectively analyzed 179 patients diagnosed as intracranial DAVSs and performed with digital subtraction angiography (DSA). The DSA images were investigated for the location, cortical venous reflux (CVR), multiplicity, and treatment method/result of DAVS. MR images were investigated for the location, number, and size of CCMs and correlated with the DSA images. RESULTS: Six of the 179 patients with DAVSs presented with coexistent CCMs (3.4 %; M/F = 3:3; mean age, 38 ± 22 years). Five of the six DAVS patients with CCMs were associated with CVR (83 %). The total number of CCMs associated with DAVS was 20. Multiple CCMs (range, 2-7) were seen in four (66 %) of six patients. Eighteen (90 %) of the 20 CCMs were located on the ipsilateral hemisphere of the CVR (n = 10) or adjacent to the deep venous reflux (n = 8). Five de novo CCMs were detected in two patients. All de novo CCMs were located on the ipsilateral hemisphere of the DAVS with CVR or juxtapositioned to abnormally dilated deep vein. CONCLUSION: CCMs may develop in association to DAVSs. The relationship between CCMs and DAVSs suggests the venous pathogenic origin of CCMs and the role of venous hypertension in the de novo development of CCMs.

Venous angioarchitectural features of intracranial dural arteriovenous shunt and its relation to the clinical course.

INTRODUCTION: The aim of this study is to assess the relationship between the venous angioarchitectural features and the clinical course of intracranial dural arteriovenous shunt (DAVS) with cortical venous reflux (CVR). METHODS: With institutional review board approval, 41 patients (M:F = 24:17; median age, 52 years (range, 1-72 years), median follow-up; 1.5 years; partial treatment, n = 36) with persistent CVR were included. We evaluated the initial presentation and the incidence of annual morbidity (hemorrhage or new/worsened nonhemorrhagic neurological deficit (NHND)) according to the venous angiographic patterns-isolated venous sinus, occlusion of the draining sinus, direct pial venous drainage, pseudophlebitic pattern, venous ectasia, brisk venous drainage, and length of pial vein reflux-on digital subtraction angiography. Cox regression was performed to identify independent factors for clinical course. RESULTS: During 111.9 patient-years of follow-up, the overall annual morbidity rate was 11.6 % (mortality; n = 3, rate; 2.6 %/year). Hemorrhage occurred in five patients (12.2 %, rate; 4.5 %/year) and new/worsened NHND occurred in eight patients (19.5 %, rate; 7.2 %/year). Patients with isolated venous sinus, direct pial venous drainage, and pseudophlebitic pattern were associated with initial aggressive presentation. Venous ectasia was associated with initial hemorrhagic presentation. Brisk venous drainage was associated with initial benign presentation. Patients with isolated venous sinus showed a poor clinical course with a higher annual incidence of hemorrhage or new/worsened NHND (91.2 %/year vs 9.2 %/year; hazard ratio, 6.681; p = 0.027). CONCLUSIONS: Venous angioarchitectural features may be predictive of the clinical course of DAVSs. DAVS patients with isolated venous sinus may be especially at high risk for future aggressive clinical course.

Assessment of thrombus using susceptibility-weighted filtered-phase images in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Recognizing the location and length of the thrombus responsible for large vessel occlusion in patients with acute ischemic stroke can facilitate effective endovascular recanalization therapy (ERT). We hypothesized that the aliasing or dipole effect produced by filtered-phase susceptibility-weighted imaging (SWI) would facilitate thrombus delineation. METHODS: Of the patients with middle cerebral artery occlusion who underwent ERT, we screened those who underwent noncontrast CT (NCCT), multiphase CT angiography (mCTA), and SWI before the endovascular procedure. We used an arbitrary index termed measurement of equivalence in thrombus assessed by digital subtraction angiography (METAD) defined as having the same location as the thrombus observed in the digital subtraction angiography (DSA) and length differing by less than 5 mm. For NCCT, mCTA, SWI_m (magnitude), and SWI_p (phase), the length of the thrombus and METAD were assessed. RESULTS: The mean lengths of the thrombi determined using NCCT, mCTA, SWI_m, SWI_p, and DSA were 14.03, 13.47, 13.89, 9.93, and 8.96 mm, respectively. The absolute agreement for thrombus length was excellent for SWI_p and DSA (intraclass correlation coefficient [ICC] = .96), moderate for SWI_m and DSA (ICC = .53), and poor for mCTA and DSA (ICC = .14). The METADs were 26.7%, 40.0%, 33.3%, and 73.3% for NCCT, mCTA, SWI_m, and SWI_p, respectively. The METADs for NCCT and SWI_p were significantly different (p = .045) and those for mCTA and SWI_m were not (p = .537 and .093, respectively). CONCLUSIONS: The SWI_p was best matched with the DSA for the measurement of the lengths and locations of thrombi. The use of pre-thrombectomy SWI_p imaging for acute ischemic stroke may facilitate a successful ERT strategy.

Sulcal effacement on fluid attenuation inversion recovery magnetic resonance imaging in hyperacute stroke: association with collateral flow and clinical outcomes.

BACKGROUND AND PURPOSE: The clinical significance of sulcal effacement has been widely investigated in CT studies, but the results are controversial. In this study, we evaluated the presence of perisylvian sulcal effacement (PSE) on fluid attenuation inversion recovery MRI and hypothesized that PSE may be related to collateral flow status together with hyperintense vessels on fluid attenuation inversion recovery in hyperacute stroke. In addition, we investigated whether an association between PSE and clinical outcome could be found in these patients. METHODS: Consecutive patients with acute middle cerebral artery infarcts within 6 hours of symptom onset were included. All patients had internal carotid artery or middle cerebral artery occlusion and underwent MRI including FLAIR. The presence of PSE and hyperintense vessels on fluid attenuation inversion recovery and the collateral status and occurrence of early recanalization (ER) on conventional angiography were evaluated. RESULTS: Of 139 patients, 79 (56.8%) had PSE. Multivariate testing revealed PSE was independently associated with collateral status. The association between hyperintense vessels and collaterals was different depending on PSE. Compared to PSE-positive and ER-negative patients, PSE-negative and ER-negative patients (odds ratio, 4.11; 95% confidence interval, 1.12-15.17) and PSE-negative and ER-positive patients (odds ratio, 34.62; 95% confidence interval, 5.75-208.60), but not PSE-positive and ER-positive patients, were more likely to experience favorable clinical outcomes (modified Rankin Scale score ≤ 2 at 3 months). CONCLUSIONS: PSE is independently associated with collateral status in patients with acute middle cerebral artery stroke. Moreover, PSE in conjunction with recanalization status can predict clinical outcomes in these patients.

Subsequent Subarachnoid Hemorrhage from Clinically Unrelated Vertebral Artery Dissection after Thrombolytic Therapy.

Thrombolysis administration poses certain safety issues in ischemic stroke patients with cerebrovascular changes that are vulnerable to hemorrhage. Furthermore, the lack of related studies has resulted in an unclear understanding of thrombolysis safety in ischemic stroke patients with intracranial dissection, including those involving the vertebral artery. This study describes a case of a 59-year-old female who developed subarachnoid hemorrhage from clinically unrelated vertebral artery dissection after thrombolysis. Histories of severe headache with posterior fossa involvement in patients receiving thrombolytic therapy may indicate careful assessment for intracranial vertebral artery dissection, even if the clinical picture of the patient suggests another arterial syndrome.

Intracranial Flow Velocity Quantification Using Non-Contrast Four-Dimensional Flow MRI: A Prospective Comparative Study with Transcranial Doppler Ultrasound.

Four-dimensional (4D) flow magnetic resonance imaging (MRI) allows three-dimensional velocity encoding to measure blood flow in a single scan, regardless of the intracranial artery direction. We compared blood flow velocity quantification by non-contrast 4D flow MRI and by transcranial Doppler ultrasound (TCD), the most widely used modality for measuring velocity. Twenty-two patients underwent both TCD and non-contrast 4D flow MRI. The mean time interval between TCD and non-contrast 4D flow MRI was 0.7 days. Subsegmental velocities were measured bilaterally in the middle cerebral and basilar arteries using TCD and non-contrast 4D flow MRI. Intracranial velocity measurements using TCD and non-contrast 4D flow MRI demonstrated a strong correlation in the bilateral M1, especially at the proximal segment (right r = 0.74, left r = 0.78; all p < 0.001). Mean velocities acquired with 4D flow MRI were approximately 8 to 10% lower than those acquired with TCD according to the location of M1. Intracranial arterial flow measurements estimated using non-contrast 4D flow MRI and TCD showed strong correlation. 4D flow MRI enables simultaneous assessment of vascular morphology and quantitative hemodynamic measurement, providing three-dimensional blood flow visualization. 4D flow MRI is a clinically useful sequence with a promising role in cerebrovascular disease.

Quantitative gait and postural analyses in patients with diabetic polyneuropathy.

BACKGROUND: Although gait disturbances are relatively common symptoms in diabetic polyneuropathy (DPN), few studies have quantitatively analyzed gait and posture in DPN patients. This study aimed to analyze gait and posture quantitatively in DPN patients and to determine the association between clinical and electrophysiological parameters and gait and posture parameters. METHODS: Sixty-four DPN patients were enrolled in this study. DPN was clinically assessed using the Toronto clinical neuropathy score (TCNS). All participants underwent nerve conduction study (NCS), three-dimensional motion analysis, and static posturography. We evaluate the correlation of gait and posture parameters with electrophysiological and clinical parameters. RESULTS: Foot height, step length, and stride length among gait parameters were inversely correlated with the TCNS. Anteroposterior range during eyes-closed and mediolateral distance and range during eyes-open and eyes-closed were inversely correlated with the sensory nerve action potential amplitude in the sural nerve. Mediolateral distance during eyes-open and eyes-closed was correlated with the compound muscle action potential amplitude in the peroneal nerve. CONCLUSIONS: Gait parameters are associated with clinical parameters, and postural parameters are associated with electrophysiological parameters, particularly sensory NCS. Gait and postural analysis can be a useful tool for assessing the neurological status in DPN patients.

Development of a predictive scale for cardioembolic stroke using extracted thrombi and angiographic findings.

We analyzed the histopathological findings of the clots obtained from patients with acute ischemic stroke by mechanical thrombectomy. We then developed a clinical scoring system for predicting pathogenic causes in patients with undetermined ischemic stroke using these histopathological and the angiographic findings during endovascular treatment. Only cases with the occlusion of the intracranial internal carotid artery or the proximal part of the middle cerebral artery were included in this study. Histopathologic findings of clots were compared and analyzed using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST; large artery atherosclerosis, cardioembolic, and undetermined groups) and angiographic occlusion type (AOT; branching-site occlusion and truncal-type occlusion groups) classification systems. Fifty-two patients had enough clots extracted by mechanical thrombectomy for full histopathologic examination. There was no significant within-group difference in the fraction of components in the thrombi for either the TOAST or AOT system; however, the platelet distribution patterns were different. The large artery atherosclerotic group and truncal-type occlusion group had mostly peripheral patterns, whereas the cardioembolic group, undetermined group and branching-site occlusion group had mostly clustering patterns (p = 0.02 in TOAST classification; p = 0.007 in AOT classification). Patients with scores of 3 or 4 on our new scale had a sensitivity of 93.5% and a specificity of 100% for cardioembolic stroke. The BOCS2 scale, developed using a combination of the TOAST and AOT classification systems, may be helpful as an adjunctive diagnostic tool for identifying cases caused by cardiogenic embolism in patients with undetermined ischemic stroke.

Alterations of structural connectivity in episodic cluster headache: A graph theoretical analysis.

We evaluated structural volumes and connectivity using graph theoretical analysis in patients with cluster headache. Ten patients with episodic cluster headache were recruited, who had a normal brain MRI on visual inspection. We also enrolled a control group of 20 healthy volunteers. All of the participants underwent 3-D volumetric T1-weighted imaging. We obtained the structural volumes using FreeSurfer image analysis and performed structural global and local connectivity analysis using BRAPH. The volumes of the left caudal anterior cingulate and postcentral gyrus were decreased in the patients with cluster headache compared to healthy individuals. In addition, in the measures of local structural connectivity, there was significant hub re-organization in the patients with cluster headache; the strength of the right frontopolar, left pericalcarine, and left posterior cingulate gyrus, the betweenness centrality of the right precentral and left pericalcarine gyrus, and the closeness centrality of the left pericalcarine and left posterior cingulate gyrus were decreased. Whereas the betweenness centrality of the right rostral middle frontal and left inferior temporal gyrus were increased in the patients with cluster headache. However, the measures of global structural connectivity were not different between the patients with cluster headache and healthy individuals. We demonstrate that the structural volumes and connectivity in patients with cluster headache are significantly different from those in healthy controls, especially revealing hub re-organization. These alterations are implicated in the pathogenesis of cluster headache and suggest that cluster headache is a network disease.

Efficacy, tolerability, and blood concentration of zonisamide in daily clinical practice.

We aimed to evaluate the efficacy, tolerability, and blood concentration of zonisamide (ZNS) used in daily clinical practice. This was a retrospective study performed at a single epilepsy center and included 149 patients with epilepsy. The efficacy and retention of ZNS for 52 weeks, percentage of patients who were seizure free for 26 weeks, and the 5-year retention rate were analyzed. The tolerability was assessed based on treatment-emergent adverse effects (AEs) and the adverse effect profile (AEP). More than 70% (105/149) of patients were on ZNS polytherapy. The mean dose of ZNS was 300 ±â€¯170.6 mg/day, and the antiepileptic drug (AED) load was 2.0 ±â€¯1.1 (median 1.8, range 0.2-5.3). The retention rate for 52 weeks and the percentage of patients who were seizure-free for 26 weeks were 73% and 42%, respectively. The retention rate decreased with time and reached 43% in 5 years. Younger age of onset was a significant variable affecting retention rate for 52 weeks (p = 0.044), whereas fewer concomitant AEDs were significantly associated with being seizure free for 26 weeks (p = 0.0006). AEs were reported in 24% (36/147) of patients. The number, mechanism of action, or drug load of the AEDs did not predict the development of AEs; however, blood concentration of ZNS was significantly higher in patients with AEs (p = 0.0011) than in those without AEs. ZNS is a well-tolerated and effective AED in daily clinical practice, and several clinical factors may predict the efficacy and tolerability of ZNS.