Anti-CV2/Collapsin Response Mediator Protein 5 (CRMP5) Paraneoplastic Encephalitis Induced by Small Cell Lung Cancer.

Paraneoplastic neurological syndrome (PNS) associated with anti-CV2/CRMP5 antibodies is a rare entity that can present in various clinical manifestations, from encephalitis to chorea, depending on the brain region involved. We report a case of an elderly person with small cell lung cancer who presented with PNS encephalitis associated with anti-CV2/CRMP5 antibodies which were confirmed on immunological analysis.

MRI evaluation of the relationship between carotid artery endothelial shear stress and brain white matter lesions in migraine.

Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients (n = 29 females, 75 years [SD 3]) and 219 controls (n = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; P = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group (P for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (ß-0.421; P = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume.

Microstructural white matter changes preceding white matter hyperintensities in migraine.

OBJECTIVE: We used magnetization transfer imaging to assess white matter tissue integrity in migraine, to explore whether white matter microstructure was more diffusely affected beyond visible white matter hyperintensities (WMHs), and to explore whether focal invisible microstructural changes precede visible focal WMHs in migraineurs. METHODS: We included 137 migraineurs (79 with aura, 58 without aura) and 74 controls from the Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA) study, a longitudinal population-based study on structural brain lesions in migraine patients, who were scanned at baseline and at a 9-year follow-up. To assess microstructural brain tissue integrity, baseline magnetization transfer ratio (MTR) values were calculated for whole brain white matter. Baseline MTR values were determined for areas of normal-appearing white matter (NAWM) that had progressed into MRI-detectable WMHs at follow-up and compared to MTR values of contralateral NAWM. RESULTS: MTR values for whole brain white matter did not differ between migraineurs and controls. In migraineurs, but not in controls, NAWM that later progressed to WMHs at follow-up had lower mean MTR (mean [SD] 0.354 [0.009] vs 0.356 [0.008], p = 0.047) at baseline as compared to contralateral white matter. CONCLUSIONS: We did not find evidence for widespread microstructural white matter changes in migraineurs compared to controls. However, our findings suggest that a gradual or stepwise process might be responsible for evolution of focal invisible microstructural changes into focal migraine-related visible WMHs.

Volumetric brain changes in migraineurs from the general population.

OBJECTIVE: To assess volumetric brain changes in migraineurs from the general population compared with controls. METHODS: Structural brain changes in migraineurs from the general population-based MRI Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis (CAMERA)-2 observational cohort study were assessed by state-of-the-art voxel-based morphometry. T1-weighted MRIs of 84 migraineurs (52 with aura, 32 without aura) and 35 headache-free controls were evaluated. Regional volumes were compared voxelwise, corrected for age, sex, and total intracranial volume, with region-of-interest and whole-brain analyses. RESULTS: In region-of-interest analyses, migraineurs showed decreased gray matter volume in the visual areas V3 and V5 of the right occipital cortex compared to controls (p < 0.05, familywise error correction). Post hoc analyses revealed that similar changes were present regardless of migraine aura status, disease activity (>1 year attack-free [inactive] vs ≥1 attack within the last year [active] and attack frequency [≤1 (low) vs ≥1 attack per month [high]). In exploratory whole-brain analyses (p < 0.001, uncorrected for multiple comparisons), we identified additional structural differences in migraineurs in other cortical and subcortical areas, including white matter tracts, that are particularly involved in visual processing. CONCLUSIONS: Migraineurs from the general population showed small volumetric brain changes, mainly in cortical areas involved in visual motion processing, compared to controls. The presence of morphologic changes regardless of the presence of migraine aura or disease activity suggests that migraines with and without aura share common pathophysiologic pathways and suggests that these changes are (partially) irreversible or might have been present throughout life.

Bilateral trampoline fracture of the proximal tibia in a child.

Trampoline fractures are transversely oriented impaction fractures of the proximal tibia sustained by young children jumping on a trampoline. Unaware of the mechanism of this specific nontraumatic fracture, physicians may fail to detect these fractures on plain radiographs, as radiological findings may be very subtle. In this case report, we present a rare case of bilateral trampoline fractures with an explanation of the trauma mechanism.

The cavernous sinus in cluster headache - a quantitative structural magnetic resonance imaging study.

Background It has been hypothesized that a constitutionally narrow cavernous sinus might predispose individuals to cluster headache. Cavernous sinus dimensions, however, have never been assessed. Methods In this case-control study, we measured the dimensions of the cavernous sinus, skull base, internal carotid and pituitary gland with high-resolution T2-weighted magnetic resonance imaging in 25 episodic, 24 chronic and 13 probable cluster headache patients, 8 chronic paroxysmal hemicrania patients and 22 headache-free controls. Dimensions were compared between groups, correcting for age, sex and transcranial diameter. Results On qualitative inspection, no relevant pathology or anatomic variants that were previously associated with cluster headache or chronic paroxysmal hemicranias were observed in the cavernous sinus or paracavernous structures. The left-to-right transcranial diameter at the temporal fossa level (mean ± SD) was larger in the headache groups (episodic cluster headache: 147.5 ± 7.3 mm, p = 0.044; chronic cluster headache: 150.2 ± 7.3 mm, p < 0.001; probable cluster headache: 146.0 ± 5.3 mm, p = 0.012; and chronic paroxysmal hemicrania: 145.2 ± 9.4 mm, p = 0.044) compared with controls (140.2 ± 8.0 mm). After adjusting for transcranial diameter and correcting for multiple comparisons, there were no differences in the dimensions of the cavernous sinus and surrounding structures between headache patients and controls. Conclusion Patients with cluster headache or chronic paroxysmal hemicrania had wider skulls than headache-free controls, but the proportional dimensions of the cavernous sinus were similar.

The anterior hypothalamus in cluster headache.

Objective To evaluate the presence, localization, and specificity of structural hypothalamic and whole brain changes in cluster headache and chronic paroxysmal hemicrania (CPH). Methods We compared T1-weighted magnetic resonance images of subjects with cluster headache (episodic n = 24; chronic n = 23; probable n = 14), CPH ( n = 9), migraine (with aura n = 14; without aura n = 19), and no headache ( n = 48). We applied whole brain voxel-based morphometry (VBM) using two complementary methods to analyze structural changes in the hypothalamus: region-of-interest analyses in whole brain VBM, and manual segmentation of the hypothalamus to calculate volumes. We used both conservative VBM thresholds, correcting for multiple comparisons, and less conservative thresholds for exploratory purposes. Results Using region-of-interest VBM analyses mirrored to the headache side, we found enlargement ( p < 0.05, small volume correction) in the anterior hypothalamic gray matter in subjects with chronic cluster headache compared to controls, and in all participants with episodic or chronic cluster headache taken together compared to migraineurs. After manual segmentation, hypothalamic volume (mean±SD) was larger ( p < 0.05) both in subjects with episodic (1.89 ± 0.18 ml) and chronic (1.87 ± 0.21 ml) cluster headache compared to controls (1.72 ± 0.15 ml) and migraineurs (1.68 ± 0.19 ml). Similar but non-significant trends were observed for participants with probable cluster headache (1.82 ± 0.19 ml; p = 0.07) and CPH (1.79 ± 0.20 ml; p = 0.15). Increased hypothalamic volume was primarily explained by bilateral enlargement of the anterior hypothalamus. Exploratory whole brain VBM analyses showed widespread changes in pain-modulating areas in all subjects with headache. Interpretation The anterior hypothalamus is enlarged in episodic and chronic cluster headache and possibly also in probable cluster headache or CPH, but not in migraine.

Cerebral volumetric abnormalities in Neurofibromatosis type 1: associations with parent ratings of social and attention problems, executive dysfunction, and autistic mannerisms.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a single-gene neurodevelopmental disorder, in which social and cognitive problems are highly prevalent. Several commonly observed central nervous system (CNS) abnormalities in NF1 might underlie these social and cognitive problems. Cerebral volumetric abnormalities are among the most consistently observed CNS abnormalities in NF1. This study investigated whether differences were present between NF1 patients and healthy controls (HC) in volumetric measures of cortical and subcortical brain regions and whether differential associations existed for NF1 patients and HC between the volumetric measures and parent ratings of social skills, attention problems, social problems, autistic mannerisms, and executive dysfunction. METHODS: Fifteen NF1 patients (mean age 12.9 years, SD 2.6) and 18 healthy controls (HC, mean age 13.8 years, SD 3.6) underwent 3 T MRI scanning. Segmentation of cortical gray and white matter, as well as volumetry of subcortical nuclei, was carried out. Voxel-based morphometry was performed to assess cortical gray matter density. Correlations were calculated, for NF1-patients and HC separately, between MRI parameters and scores on selected dimensions of the following behavior rating scales: the Social Skills Rating System, the Child Behavior Checklist, the Social Responsiveness Scale, the Behavior Rating Inventory of Executive Functioning, and the Dysexecutive Questionnaire. RESULTS: After correction for age, sex, and intracranial volume, larger volumes of all subcortical regions were found in NF1 patients compared to controls. Patients further showed decreased gray matter density in midline regions of the frontal and parietal lobes and larger total white matter volume. Significantly more social and attention problems, more autistic mannerisms, and poorer executive functioning were reported for NF1 patients compared to HC. In NF1 patients, larger left putamen volume and larger total white matter volume were associated with more social problems and poorer executive functioning, larger right amygdala volume with poorer executive functioning and autistic mannerisms, and smaller precentral gyrus gray matter density was associated with more social problems. In controls, only significant negative correlations were observed: larger volumes (and greater gray matter density) were associated with better outcomes. CONCLUSIONS: Widespread volumetric differences between patients and controls were found in cortical and subcortical brain regions. In NF1 patients but not HC, larger volumes were associated with poorer behavior ratings.

Infratentorial Microbleeds: Another Sign of Microangiopathy in Migraine.

BACKGROUND AND PURPOSE: Migraine is a risk factor for clinical stroke and for subclinical white matter hyperintensities and infratentorial infarcts. These subclinical lesions are linked to small-vessel pathology. Cerebral microbleeds (CMBs) are another biomarker of small-vessel disease but have not yet been studied in migraine. METHODS: Identification of CMBs in 63 migraineurs (25 with aura/35 without aura/3 unknown aura status) and 359 controls (aged, 73-85 years) from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) magnetic resonance imaging study. We assessed the modifying role of migraine in the co-occurrence of CMBs, infarcts, and white matter hyperintensity-load. RESULTS: Infratentorial microbleeds were more prevalent in migraine without aura patients than controls (14% versus 4%). Prevalence of other CMBs, infarcts, and white matter hyperintensities did not differ between groups. Migraineurs with CMBs had more often infarcts than controls with CMBs (65% versus 43%). In comparison with controls with infarcts, migraineurs with infarcts had more commonly CMBs (55% versus 30%). CONCLUSIONS: Migraine, notably without aura, is associated with infratentorial CMBs at older age. CMBs and infarcts co-occur more often in migraine than in controls. This supports the hypothesis of small-vessel involvement in migraine pathophysiology.

Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements.

INTRODUCTION: The increased risk of cerebro- and cardiovascular disease in migraineurs may be the consequence of a systemic condition affecting whole body vasculature. At cerebrovascular level, this may be reflected by interictal global or regional cerebral perfusion abnormalities. Whether focal perfusion changes occur during interictal migraine has not been convincingly demonstrated. METHODS: We measured brain perfusion with dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in 29 interictal female migraineurs (12 migraine with aura (MA), 17 migraine without aura (MO)), and 16 female controls. Perfusion maps were compared between these groups with a voxelwise (p < 0.001, uncorrected, minimum cluster size 20 voxels) and a region-of-interest approach. RESULTS: In whole brain voxelwise analyses interictal hyperperfusion was observed in the left medial frontal gyrus in migraineurs and in the inferior and middle temporal gyrus in MO patients, in comparison with controls. Hypoperfusion was seen in the postcentral gyrus and in the inferior temporal gyrus in MA patients and in the inferior frontal gyrus in MO patients. Additional focal sites of hyperperfusion were noted in subgroups based on attack frequency and disease history. Region-of-interest analyses of the pons, hypothalamus, occipital lobe, and cerebellum did not show interictal perfusion differences between migraineurs and controls. CONCLUSIONS: We conclude that interictal migraine is characterized by discrete areas of hyper- and hypoperfusion unspecific for migraine pathophysiology and not explaining the increased vulnerability of particular brain regions for cerebrovascular damage.

Frontal lobe structure and executive function in migraine patients.

Neuroimaging studies have identified frontal lobe brain abnormalities in migraineurs. Neuropsychological investigations highlighted frontal lobe related cognitive impairments in migraineurs, including working memory and executive function deficits. The relationship between brain anatomy and cognitive function in migraine, however, is unclear. The aim of this study was to simultaneously investigated cortex structure and executive function (EF) in patients with migraine and control subjects. Thus, we assessed grey matter (GM) density in 25 adult patients with migraine, compared to age and sex-matched control subjects, using magnetic resonance imaging (MRI) and voxel-based-morphometry (VBM), and we measured EF in the same population, employing three EF tasks of the Maudsley attention and response suppression (MARS) battery. Migraineurs, compared to control subjects, showed decreased frontal and parietal lobe GM density and slower response time to task set-shifting and, the delayed response time correlated significantly with reduced GM density of the frontal lobes in migraineurs. Frontal and parietal lobe abnormalities in migraineurs could be an underlying cause of significantly slower response time during cognitive set-shifting.

Attack frequency and disease duration as indicators for brain damage in migraine.

OBJECTIVE: The aim of this study was to pinpoint predilection sites of brain damage in migraine by quantitatively identifying morphometric and diffusion differences in migraineurs, compared with control subjects, and to assess whether migraine attack frequency and attack history are indicators for brain abnormalities in migraineurs. BACKGROUND: Previous clinical neuroimaging investigations introduced the concept of migraine as a progressive brain disease. They reported an increased risk of white matter hyperintensities (WMH) with increasing attack frequency in migraineurs. METHODS: We investigated 28 patients with migraine, using high-resolution T1- and diffusion-weighted magnetic resonance imaging and optimized voxel-based morphometry to localize gray and WM density, and fractional anisotropy and apparent diffusion coefficient differences. RESULTS: We identified predilection sites of brain abnormalities in migraineurs in the frontal lobes, brainstem, and the cerebellum, and we show that both attack frequency and disease duration are indicators for brain damage in migraine. CONCLUSION: Our findings report an unbiased quantitative whole brain assessment of morphological abnormalities in migraine. This might help to identify indicators for migraine as a possibly progressive brain disease. In order to reveal the causes and consequences of brain damage in migraine, further neuroimaging studies have to investigate quantitative brain changes in a longitudinal design.