External Ophthalmoplegia and Brainstem White Matter Lesions: Presentation of Myotonic Dystrophy Type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is an autosomal dominant condition which phenotype can be extremely variable considering its multisystem involvement, including the central nervous system. Neuromuscular findings are facial and distal extremities muscle weakness, muscle atrophy and myotonia. Standard diagnosis is obtained with molecular testing to detect CTG expansions in the myotonic dystrophy protein of the kinase gene. Brain magnetic resonance imaging typically shows characteristic subcortical white matter (WM) abnormalities located within anterior temporal lobes. CASE REPORT: We present a 39-year-old male patient with a progressive external ophthalmoplegia, facial and limb muscle weakness, percussion myotonia and atypical brain magnetic resonance imaging findings, showing confluent brainstem WM lesions, affecting the pons, a rare radiologic feature in this disorder. Genetic testing confirmed the diagnosis for DM1. CONCLUSION: This presentation with external ophthalmoplegia and brainstem WM loss in DM1 can show an important correlation with clinical findings and have an important diagnostic and prognostic value.

Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach.

Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.

Differential activation of the default mode network in jet lagged individuals.

Long-term exposure to transmeridian flights has been shown to impact cognitive functioning. Nevertheless, the immediate effects of jet lag in the activation of specific brain networks have not been investigated. We analyzed the impact of short-term jet lag on the activation of the default mode network (DMN). A group of individuals who were on a transmeridian flight and a control group went through a functional magnetic resonance imaging acquisition. Statistical analysis was performed to test for differences in the DMN activation between groups. Participants from the jet lag group presented decreased activation in the anterior nodes of the DMN, specifically in bilateral medial prefrontal and anterior cingulate cortex. No areas of increased activation were observed for the jet lag group. These results may be suggestive of a negative impact of jet lag on important cognitive functions such as introspection, emotional regulation and decision making in a few days after individuals arrive at their destination.

Cerebral and cerebellar MRI volumes in Williams syndrome.

Individuals with Williams syndrome (WS) present a set of cognitive, affective and motor symptoms that resemble those of patients with lesions to the cerebellum. Although there is some evidence for overall structural alterations in this brain region in WS, explorations on cerebellar white matter and cerebellar cortex volumes remain rather neglected. We aimed to compare absolute and relative cerebellar volumes, as well as patterns of white matter to cortex volumes in this brain region, between a group of individuals with WS and a group of healthy controls. T1-weighted magnetic resonance images were acquired in 17 individuals with WS and in 15 typically developing individuals. Our results showed that even though individuals from the clinical group had significantly smaller cerebrums (and cerebellums), cerebellar volumes relative to intracranial volumes were significantly enlarged. In addition, while gray matter was relatively spared and white matter disproportionately reduced in the cerebrum in WS, relative cerebellar cortex and white matter volumes were preserved. These findings support the hypothesis that volume alterations in the cerebellum are associated with the cognitive, affective and motor profiles in WS.

Morphometry of corpus callosum in Williams syndrome: shape as an index of neural development.

Brain abnormalities in Williams syndrome (WS) have been consistently reported, despite few studies have devoted attention to connectivity between different brain regions in WS. In this study, we evaluated corpus callosum (CC) morphometry: bending angle, length, thickness and curvature of CC using a new shape analysis method in a group of 17 individuals with WS matched with a typically developing group. We used this multimethod approach because we hypothesized that neurodevelopmental abnormalities might result in both volume changes and structure deformation. Overall, we found reduced absolute CC cross-sectional area and volume in WS (mean CC and subsections). In parallel, we observed group differences regarding CC shape and thickness. Specifically, CC of WS is morphologically different, characterized by a larger bending angle and being more curved in the posterior part. Moreover, although CC in WS is shorter, a larger relative thickness of CC was found in all callosal sections. Finally, groups differed regarding the association between CC measures, age, white matter volume and cognitive performance. In conclusions, abnormal patterns of CC morphology and shape may be implicated in WS cognitive and behavioural phenotype.

MRI amygdala volume in Williams Syndrome.

One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched controls. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices and were used to measure whole gray matter, white matter and cerebrospinal fluid volumes, as well as amygdala volume (right and left). Results revealed significantly reduced intracranial volume in individuals with WS, compared with controls. There were no differences between groups in absolute amygdalae volume, although there was a relative increase in amygdalae volumes, when adjusted for total intracranial content. There were no inter-hemispheric differences in amygdalae volumes in both groups. These results suggest a relative increase in amygdala volume in WS compared with healthy controls that likely reflects abnormal neurodevelopmental processes of midline brain structures.

Williams syndrome and memory: a neuroanatomic and cognitive approach.

Williams Syndrome (WS) is described as displaying a dissociation within memory systems. As the integrity of hippocampal formation (HF) is determinant for memory performance, we examined HF volumes and its association with memory measures in a group of WS and in a typically development group. A significantly reduced intracranial content was found in WS, despite no differences were observed for HF absolute volumes between groups. When volumes were normalized, left HF was increased in WS. Moreover, a lack of the normal right > left HF asymmetry was observed in WS. No positive correlations were found between volumetric and neurocognitive data in WS. In sum, a relative enlargement of HF and atypical patterns of asymmetry suggest abnormal brain development in WS.

MRI assessment of superior temporal gyrus in Williams syndrome.

OBJECTIVE: To evaluate volumes and asymmetry of superior temporal gyrus (STG) and correlate these measures with a neurocognitive evaluation of verbal performance in Williams syndrome (WS) and in a typically developing age-matched and sex-matched group. BACKGROUND: Despite initial claims of language strength in WS, recent studies suggest delayed language milestones. The STG is implicated in linguistic processing and is a highly lateralized brain region. METHOD: Here, we examined STG volumes and asymmetry of STG in WS patients and in age-matched controls. We also correlated volume of STG with a subset of verbal measures. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices, and were used to measure whole gray matter, white matter, and cerebrospinal fluid volumes, and also STG volume. RESULTS: Results revealed significantly reduced intracranial volume in WS patients, compared with controls. Right and left STG were also significantly smaller in WS patients. In addition, compared with normal controls, a lack of normal left >right STG asymmetry was evident in WS. Also of note was the finding that, in contrast to controls, WS patients did not reveal a positive correlation between verbal intelligence quotient and left STG volume, which further suggests a disruption in this region of the brain. CONCLUSIONS: In conclusion, atypical patterns of asymmetry and reduced STG volume in WS were observed, which may, in part, contribute to some of the linguistic impairments found in this cohort of WS patients.

Lobar brain hemorrhages and white matter changes: Clinical, radiological and laboratorial profiles.

BACKGROUND: White matter changes have several histopathologic correlates including cerebral amyloid angiopathy (CAA). The aim of this study was to characterize the clinical, laboratorial and neuroradiological profile of a CAA-related lobar hemorrhages case series. METHODS: A cohort of 50 consecutive patients with cerebral lobar hemorrhages was studied and clinical, radiological data and ApoE polymorphisms were analyzed. White matter changes were graded and microbleeds were characterized according to number and location using T2* MRI. RESULTS: A statistically significant association was found between the prestroke cognitive performance and poststroke dementia and between hemorrhage volume and mortality. More severe white matter changes were found in probable CAA when comparing to possible CAA. The most prominent white matter lesions are associated with the presence and the number of microbleeds. The frequency of APOE epsilon 2 and epsilon 4 alleles was higher in this cohort when compared to a Northern Portuguese population. CONCLUSION: White matter changes are frequent in lobar hemorrhage patients and are associated with cortical microbleeds, the radiological hallmark of CAA. Therefore, white matter changes may be the sole phenotype of CAA and, potentially, involved in the pre-stroke cognitive impairment presented by the patients, which are genetically distinct from the population in general.

[Aneurysmal malformation of the vein of Galen in adults]. / Malformação aneurismática da veia de galeno no adulto.

We present an adult male harbouring a vascular malformation, manifested by haemorrhage, which localization, arterial feeders and venous drainage, match the pattern of choroidal type vein of Galen aneurysmal malformations seen in babies, excepting the absence of anterior choroidal arteries participation. A few cases of vein of Galen aneurysmal malformations were already reported in adults, but haemorrhage was never well documented. This haemorrhage may have a pathogenesis similar to those of pial arteriovenous malformations.

[Phenotypic evolution in adrenoleukodystrophy]. / Evolução fenotípica na adrenoleucodistrofia.

The X-linked adrenoleukodystrophy (ALD) is a genetic disease, caused by a defect mapped to Xq28. It is characterised by progressive demyelination of the cerebral white matter and adrenal insufficiency. The most important change that occurs is the accumulation of very long chain fatty acids (VLCFAs). The authors describe a patient whom the initial phenotype was Addison disease only (AO). With 21 years old he developed neurological complaints and the electrophysiological and neuroradiological studies performed, confirmed the phenotypic change from AO to pure Adrenomyeloneuropathy. Less than 2 years later, the clinical condition worsened and the magnetic resonance performed confirmed cerebral involvement by the disease. The authors point out the need to determine the levels of VLCFAs in all men with adrenal insufficiency. They also put much emphasis on the endocrinology and neurology following of any patient with ALD because of the possibility of a phenotypic change to occur.

Is percutaneous vertebroplasty without pretreatment venography safe? Evaluation of 205 consecutives procedures.

BACKGROUND AND PURPOSE: Vertebral venography has been advocated before bone cement injection when performing percutaneous vertebroplasty (PV) for benign or malignant lesions of the spine. Although venography can document sites of potential leakage during subsequent cement application, stagnant contrast agent renders the cement injection more difficult to monitor, and an allergic reaction to contrast agent remains a potential risk. We evaluated our experience with PV without prior venographic evaluation. METHODS: Two hundred five consecutive PV procedures performed in 137 patients without pretreatment venography were evaluated for complications linked to bone cement injection. Treated lesions were 172 benign compression fractures, 27 metastases, two hemangiomas, and four multiple myelomas. PV was performed with a single-pedicle technique in 146 cases and a two-pedicle technique in 59 cases. RESULTS: No major complication occurred in our series. Three minor complications (1.5%) were documented: One patient had a transient episode of arterial hypotension during cement injection, without cement leak; one patient had a spontaneously resolving patch of cutaneous hypoesthesia at the puncture site; and one patient had a radiculopathy four levels above the treated level, not caused by cement deposition, and successfully treated with a nerve block. None of these three minor complications were related to cement leakage. CONCLUSION: PV can, in our experience, be performed safely without prior angiographic evaluation of the vertebral venous system.