Association of LTA and SOD Gene Polymorphisms with Cerebral White Matter Hyperintensities in Migraine Patients.

White matter hyperintensities (WMHs) in migraine could be related to inflammatory and antioxidant events. The aim of this study is to verify whether migraine patients with WMHs carry a genetic pro-inflammatory/pro-oxidative status. To test this hypothesis, we analyzed lymphotoxin alpha (LTA; rs2071590T and rs2844482G) and superoxide dismutase 1 (SOD1; rs2234694C) and 2 (SOD2; rs4880T) gene polymorphisms (SNPs) in 370 consecutive patients affected by episodic (EM; n = 251) and chronic (CM; n = 119) migraine and in unrelated healthy controls (n = 100). Brain magnetic resonance was available in 183/370 patients. The results obtained show that genotypes and allele frequencies for all tested SNPs did not differ between patients and controls. No association was found between single SNPs or haplotypes and sex, migraine type, cardiovascular risk factors or disorders. Conversely, the LTA rs2071590T (OR = 2.2) and the SOD1 rs2234694C (OR = 4.9) alleles were both associated with WMHs. A four-loci haplotype (TGCT haplotype: rs2071590T/rs2844482G/rs2234694C/rs4880T) was significantly more frequent in migraineurs with WMHs (7 of 38) compared to those without WMHs (4 of 134; OR = 8.7). We may, therefore, conclude by suggesting that that an imbalance between pro-inflammatory/pro-oxidative and antioxidant events in genetically predisposed individuals may influence the development of WMHs.

Diffusion MRI Findings in Encephalopathy Induced by Immunosuppressive Therapy after Liver Transplantation.

Neurological complications are common after liver transplantation, as they affect up to one-third of the transplanted patients and are associated with significant morbidity. The introduction of calcineurin inhibitors, cyclosporine A and tacrolimus, in immunosuppressive regimens significantly improved the outcome of solid-organ transplantation even though immunosuppression-associated neurotoxicity remains a significant complication, particularly occurring in about 25% of cases after liver transplantation. The immunosuppressant cyclosporine A and tacrolimus have been associated with the occurrence of major neurological complications, diffuse encephalopathy being the most common. The biochemical and pathogenetic basis of calcineurin inhibitors-induced neurotoxicity are still unclear although several mechanisms have been suggested. Early recognition of symptoms could help reduce neurotoxic event. The aim of the study was to evaluate cerebral changes through MRI, in particular with diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps, in two patients undergoing liver transplantation after immunosuppressive therapy. We describe two patients in which clinical pictures, presenting as a severe neurological condition, early after orthotopic liver transplantation during immunosuppression therapy, showed a different evolution in keeping with evidence of focal-multifocal lesions at DWI and ADC maps. At clinical onset, DWI showed hyperintensity of the temporo-parieto-occipital cortex with normal ADC values in the patient with following good clinical recovery and decreased values in the other one; in the latter case, MRI abnormalities were still present after ten days, until the patient's exitus. The changes in DWI with normal ADC may be linked to brain edema with a predominant vasogenic component and therefore reversible, while the reduction in ADC is due to cytotoxic edema and linked to more severe, nonreversible, clinical picture. Brain MRI and particularly DWI and ADC maps provide not only a good and early representation of neurological complications during immunosuppressant therapy but can also provide a useful prognostic tool on clinical outcome of the patient.

White matter involvement in young non-demented Down's syndrome subjects: a tract-based spatial statistic analysis.

PURPOSE: Cognitive decline in Down syndrome generally shows neurodegenerative aspects similar to what is observed in Alzheimer's disease. Few studies reported information on white matter integrity. The aim of this study was to evaluate white matter alterations in a cohort of young Down subjects, without dementia, by means of DTI technique, compared to a normal control group. METHODS: The study group consisted of 17 right-handed subjects with DS and many control subjects. All individuals participating in this study were examined by MR exam including DTI acquisition (32 non-coplanar directions); image processing and analysis were performed using FMRIB Software Library (FSL version 4.1.9, http://www.fmrib.ox.ac.uk/fsl )) software package. Finally, the diffusion tensor was estimated voxel by voxel and the FA map derived from the tensor. A two-sample t test was performed to assess differences between DS and control subjects. RESULTS: The FA is decreased in DS subjects, compared to control subjects, in the region of the anterior thalamic radiation, the inferior fronto-occipital fasciculum, the inferior longitudinal fasciculum, and the cortico-spinal tract, bilaterally. CONCLUSIONS: The early white matter damage visible in our DS subjects could have great impact in the therapeutic management, in particular in better adapting the timing of therapies to counteract the toxic effect of the deposition of amyloid that leads to oxidative stress.

Age-Related Cortical Thickness Reduction in Non-Demented Down's Syndrome Subjects.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the characteristic pattern of age-related cortical thinning in patients with Down Syndrome (DS), as assessed by MRI and automatic cortical thickness measurements. METHODS: Ninety-one non-demented subjects with DS (range 11-53 years) were examined using a 1.5 T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package., The Pearson product-moment correlation coefficient between age and mean cortical thickness was evaluated for all subjects participating in the study. RESULTS: A significant negative correlation between cortical thickness and age was found bilaterally in the frontal, temporal, parietal and cingulate gyrus. Specific investigation of cerebral lobes showed a more evident involvement of the frontal one, compared to others. Moreover, the age related reduction of cortical thickness appeared to be more significant and rapid in patients between 20 and 30 years of age. CONCLUSIONS: Our findings showed that Down Syndrome subjects are affected by a diffuse cortical thinning. The involvement of cortical structures can be observed at an earlier age than previous studies have reported.

Age effects on cortical thickness in young Down's syndrome subjects: a cross-sectional gender study.

INTRODUCTION: The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down's syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects. METHODS: Eighty-four subjects with DS, 30 females (11-35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11-35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated. RESULTS: A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects. CONCLUSIONS: Females with Down's syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects.

Role of multidetector CT in the recognition of hyperdense middle cerebral artery sign (HMCAS) in patients with acute cerebral ischaemia: correlation with DWI-MRI sequences and clinical data.

PURPOSE: The aim of this study was to verify the sensitivity and specificity of the hyperdense middle cerebral artery sign (HMCAS) obtained by multidetector computed tomography (CT) in predicting acute stroke, using diffusion-weighted (DW) magnetic resonance imaging (MRI) as a reference. The location of the HMCAS, the extension of the ischaemic lesion and its prognostic value were also assessed. MATERIALS AND METHODS: The CT examinations of 654 patients with symptoms related to acute cerebral stroke were retrospectively reviewed. DW-MRI confirmed recent stroke in 175 patients. Two expert neuroradiologists analysed the CT examinations of these patients in four phases. Sensitivity, specificity and interobserver reliability was evaluated. Patients were divided into three groups according to the HMCAS site (M1-M2-M3) and the Alberta Stroke Program Early CT Score (ASPECTS) on DW-MRI was calculated. The ASPECTS average score was correlated with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at 3 months. RESULTS: In 41 patients, the presence of HMCAS was confirmed (71 % sensitivity; 100 % specificity; Interobserver reliability k, 84 %). An inverse correlation was found by comparing the ASPECTS and NIHSS scores (Rsq = -0.206). After logistic regression analysis, HMCAS was found to be independently associated with a poor outcome (mRS >2) at 3 months after adjusting for age, NIHSS on admission, risk factors and aetiology of stroke. CONCLUSIONS: Our study demonstrated that HMCAS obtained with multidetector CT can be detected in more than 70 % of patients with large acute ischaemic lesion and it is an unfavourable prognostic sign.

A cervical flexion-extension MRI study in Down syndrome.

OBJECTIVE: To assess what kind of information MR examination in flexed and extended positions provides in Down syndrome subjects with suspected cranio-cervical instability. METHODS: Between 2005 and 2008, 35 subjects with DS were recruited in the study. Ethics committee approval was granted and a signed informed consent was obtained from the parents. All the subjects were affected by hypotonic status and ligament laxity established by clinical evaluation, but were asymptomatic about focal neurological symptoms due to medullar damage caused by cranio-cervical instability. Each patient underwent lateral supine radiographs and MR imaging in the neutral, active flexed and extended positions. For evaluating the atlanto-axial and atlanto-occipital joint stability, multiple measurements were calculated. RESULTS: A significant reduction of anterior subarachnoid space in flexed position was evident in DS subjects compared to healthy controls in neutral and flexed positions. Both, space available for cord and ligamentous thickness showed significant differences between DS subjects and healthy controls. In DS subjects with occipito-cervical instability, the anterior subarachnoidal space reduction was significantly reduced in flexed position. CONCLUSIONS: In DS subjects with asymptomatic cranio-cervical instability, anterior subarachnoidal evaluation and ligamentous status could add new information about the risk of spinal cord damage.

Diffuse axonal injury with selective involvement of the corticospinal tract. A diffusion tensor imaging case study.

The identification of diffuse axonal injury (DAI) can be difficult, especially using conventional imaging (CT or MRI), which usually appears normal. Diffusion tensor imaging (DTI) is useful in identifying white matter abnormalities in patients with DAI. We describe the case of a 17-year-old female with severe closed head injury and right-side hemiparesis, studied with DTI and MR-tractography. In this case, DTI was useful to detect focal and diffuse signs of DAI.

Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome.

In order to investigate alterations in brain morphology and a possible temporal pattern of neuroanatomical abnormalities in the gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of young patients with Down syndrome (DS), high-resolution magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was performed on 21 children and adolescents with this chromosomal aberration and 27 age-matched participants as controls. In comparison with control subjects, children and adolescents with DS showed not only an overall smaller whole-brain volume, but also volume reductions of the GM in the cerebellum, frontal lobes, frontal region of the limbic lobe, parahippocampal gyri and hippocampi and of the WM in the cerebellum, frontal and parietal lobes, sub-lobar regions and brainstem. By contrast, volume preservation was observed in the GM of the parietal lobes, temporal lobe and sub-lobar regions and in the WM of the temporal lobe and temporal regions of the limbic lobe. A lower volume of CSF was also detected in the frontal lobes. This study is the first to use the high-resolution MRI VBM method to describe a whole-brain pattern of abnormalities in young DS patients falling within such a narrow age range and it provides new information on the neuroanatomically specific regional changes that occur during development in these patients.

Cerebral transverse sinus morphology as detected by MR venography in patients with chronic migraine.

OBJECTIVE: To clarify the frequency and characteristics of altered transverse sinus morphology in a series of consecutive patients with chronic migraine. BACKGROUND: As terminology, neuroradiological techniques and patient selection differ widely across various studies, reliable, reproducible information is lacking on the frequency of cerebral transverse sinus asymmetry as measured by cerebral magnetic resonance venography in patients with chronic migraine. METHODS: We assessed the frequency and characteristics of transverse sinus asymmetries and their correlation with the chronic migraine phenotype in a blind, cross-sectional magnetic resonance venographic study in a series of 83 consecutive patients with chronic migraine. RESULTS: After excluding mild (≤ 10%) physiological differences in transverse sinus diameter, we found magnetic resonance venographic evidence of altered transverse sinus morphology in 50.6% of the patients: 16.9% had moderate transverse sinus asymmetry (≤ 50%), 24.1% severe asymmetry (>50%), and 9.6% aplasia. Among the tested risk factors for migraine chronification, analgesic consumption, anxiety, and high systolic blood pressure were more frequent in patients with transverse sinus aplasia than in those without. CONCLUSIONS: Advanced magnetic resonance venographic techniques used in strictly selected subjects disclose transverse sinus asymmetries in as many as 50.6% of patients with chronic migraine, even when mild differences in physiological caliber are excluded. The unexpected correlation between transverse sinus aplasia and some risk factors for migraine chronification requires confirmation in larger studies.

Pre- and intraoperative tractographic evaluation of corticospinal tract shift.

BACKGROUND: Magnetic resonance with diffusion tensor image (DTI) may be able to estimate trajectories compatible with subcortical tracts close to brain lesions. A limit of DTI is brain shifting (movement of the brain after dural opening and tumor resection). OBJECTIVE: To calculate the brain shift of trajectories compatible with the corticospinal tract (CST) in patients undergoing glioma resection and predict the shift directions of CST. METHODS: DTI was acquired in 20 patients and carried out through 12 noncollinear directions. Dedicated software "merged" all sequences acquired with tractographic processing and the whole dataset was sent to the neuronavigation system. Preoperative, after dural opening (in 11) and tumor resection (in all) DTI acquisitions were performed to evaluate CST shifting. The extent of shifting was considered as the maximum distance between the preoperative and intraoperative contours of the trajectories. RESULTS: An outward shift of CST was observed in 8 patients and an inward shift in 10 patients during surgery. In the remaining 2 patients, no intraoperative displacement was detected. Only peritumoral edema showed a statistically significant correlation with the amount of shift. In those patients in which DTI was acquired after dural opening as well (11 patients), an outward shifting of CST was evident in that phase. CONCLUSION: The use of intraoperative DTI demonstrated brain shifting of the CST. DTI evaluation of white matter tracts can be used during surgical procedures only if updated with intraoperative acquisitions.

Contrast echocardiography and migraine in divers with patent foramen ovale.

BACKGROUND: It has been proposed that the patent foramen ovale (PFO) may be associated with migraine, in particular migraine with aura. However, it is not clear whether paradoxical embolism triggers crises of headache. Cerebral embolization is provoked in subjects with PFO through contrast echocardiography, a safe method to diagnose the presence of foramen ovale pervium. METHODS: Twenty-four men practicing diving, an activity characterized by increased prevalence of PFO and migraine, underwent trans-thoracic echocardiography with contrast solution, composed of saline and air mixture and checked for the occurrence of migraine in the following 24 hours. RESULTS: A PFO (five of minimal size, i.e. visible only during Valsalva, one of small and two of medium size) was detected in 8/24 divers (33%). No one reported headache over the 24 hours after the procedure. DISCUSSION: Our preliminary data suggest that cerebral micro-embolism, provoked by contrast echocardiography, does not systematically trigger migraine crises when a minimal-to-medium sized patent foramen ovale is present.

Spastic paraplegia with thinning of the corpus callosum and white matter abnormalities: further mutations and relative frequency in ZFYVE26/SPG15 in the Italian population.

Spastic paraplegia with thinning of the corpus callosum (ARHSP-TCC) is a relatively frequent form of complicated hereditary spastic paraplegia in which mental retardation and muscle stiffness at onset are followed by slowly progressive paraparesis and cognitive deterioration. Although genetically heterogeneous, ARHSP-TCC is frequently associated with mutations in the SPG11 gene, on chromosome 15q. However, it is becoming evident that ARHSP-TCC can also be the clinical presentation of mutations in ZFYVE26 (SPG15), as shown by the recent identification of eight families with a variable phenotype. Here, we present an additional Italian ARHSP-TCC patient harboring two new, probably loss-of-function mutations in ZFYVE26. This finding, together with the report of a mutation in another Italian family, provides confirmation that ZFYVE26 is the second gene responsible for ARHSP-TCC in the Italian population.

Relationship between supratentorial arachnoid cyst and chronic subdural hematoma: neuroradiological evidence and surgical treatment.

OBJECT: Arachnoid cysts are relatively common congenital intracranial mass lesions that arise during the development of the meninges. They can be complicated by the formation of an ipsilateral chronic subdural hematoma (CSDH) after minor cranial trauma. Treatment of these coexisting conditions remains controversial. In this study the authors describe the anatomical, clinical, and neuroradiological features and outcome in a series of patients whose CSDH associated with arachnoid cysts were managed surgically by draining the hematoma alone and leaving the cyst intact. The authors based this surgical management on histological and neuroradiological observations concerning these associated medical conditions. METHODS: A series of 8 patients with CSDHs associated with arachnoid cysts underwent surgery to drain the hematoma though a bur hole. The arachnoid cyst was left intact. Postoperative follow-up included CT scanning and T1- and T2-weighted MR imaging. RESULTS: Clinical, anatomical, and radiological observations suggest that because separate membranes cover arachnoid cysts and the related hematoma, arachnoid cysts remain unaffected by the subdural bleeding. In the present study, these observations received support from the neuroimaging appearances, suggesting that arachnoid cysts related to hematoma contained only blood breakdown products from the hematoma that had filtered through the reciprocal dividing membranes. CONCLUSIONS: Arachnoid cysts associated with SDH are anatomically separate conditions whose neurological symptoms respond to surgical drainage of the CSDH alone.

Status epilepticus in a patient with fragile X syndrome: electro-clinical features and peri-ictal neuroimaging.

Fragile X syndrome (Fra-X) is a common cause of mental retardation that can be associated with partial epilepsy characterized by a variety of electro-clinical features. A wide spectrum of interictal activities are reported, although no data regarding ictal EEG activity have as yet been published. Drug-resistant seizures are uncommon, and the occurrence of clustering seizures or status epilepticus has only been reported anecdotally. We describe a Fra-X patient with refractory partial epilepsy related to a malformation of cortical development who experienced a partial status epilepticus that was well documented by video-EEG and MRI. We report the electro-clinical features and peri-ictal neuroimaging data.

Pituitary macroadenomas: preoperative evaluation of consistency with diffusion-weighted MR imaging--initial experience.

PURPOSE: To prospectively evaluate use of diffusion-weighted (DW) magnetic resonance (MR) images and apparent diffusion coefficient (ADC) maps for determination of the consistency of macroadenomas. MATERIALS AND METHODS: The study protocol was approved by the institutional ethics committee, and informed consent was obtained from all patients. Twenty-two patients with pituitary macroadenoma (10 men, 12 women; mean age, 54 years +/- 17.09 [standard deviation]; range, 21-75 years) were examined. All patients underwent MR examination, which included T1-weighted spin-echo and T2-weighted turbo spin-echo DW imaging with ADC mapping and contrast material-enhanced T1-weighted spin-echo imaging. Regions of interest (ROIs) were drawn in the macroadenomas and in normal white matter on DW images, ADC maps, and conventional MR images. Consistency of macroadenomas was evaluated at surgery and was classified as soft, intermediate, or hard. Histologic examination was performed on surgical specimens of macroadenomas. Mean ADC values, signal intensity (SI) ratios of tumor to white matter within ROIs on conventional and DW MR images, and degree of enhancement were compared with tumor consistency and with percentage of collagen content at histologic examination by using analysis of variance for linear trend. RESULTS: The mean value of ADC in the soft group was (0.663 +/- 0.109) x 10(-3) mm(2)/sec; in the intermediate group, (0.842 +/- 0.081) x 10(-3) mm(2)/sec; and in the hard group, (1.363 +/- 0.259) x 10(-3) mm(2)/sec. Statistical analysis revealed a significant correlation between tumor consistency and ADC values, DW image SI ratios, T2-weighted image SI ratios, and percentage of collagen content (P < .001, analysis of variance). No other statistically significant correlations were found. CONCLUSION: Findings in this study suggest that DW MR images with ADC maps can provide information about the consistency of macroadenomas.

Tolosa-Hunt syndrome in a patient with systemic lupus erythematosus.

We report a case of Tolosa-Hunt syndrome (THS) in a patient with systemic lupus erythematosus studied with MRI. Magnetic resonance showed enlargement of the cavernous sinus and compression of the carotid syphon by enhancing tissue. In particular, fat-suppressed T1-weighted images before and after contrast agent injection and MR angiography showed extension of the abnormal tissue to the apex of the orbit and narrowing of the internal carotid artery. A presumptive diagnosis of THS was made and steroid treatment was started with rapid relief of symptoms. Follow-up MR study after steroid therapy demonstrated sub-total resolution of the neuroradiological findings. Neuroradiological findings in THS are quite typical but they may be subtle; furthermore, the presence of a systemic disease may suggest secondary involvement of the cavernous sinus. Utilization of the appropriate MR techniques and follow-up exams may contribute to the diagnosis of THS even in the presence of other systemic diseases.