Extra-hippocampal grey matter density abnormalities in paediatric mesial temporal sclerosis

The aim of this study was to identify grey matter density abnormalities in children with temporal lobe epilepsy and mesial temporal sclerosis. Magnetic resonance T1 weighted 3D datasets were obtained in children with temporal lobe epilepsy (20 left and 10 right sided, mean age 11.9 years, range 6.6-17.5) and compared to scans obtained from age-matched controls (n = 22, mean age 12.8 years, range 7.1-17.5) using voxel-based morphometry. This method detected reduced grey matter ipsilateral to the seizure focus not only in the hippocampus, but also in the lateral temporal lobe and in extra-temporal regions including the thalamus, posterior cingulate cortex and cerebellum. Bilateral differences were present in the frontal and parietal opercular cortices and lateral temporal regions. These grey matter density reductions broadly reflect the pattern of hippocampal connections and may be caused by the disruption of cortical development by the recurrent seizures, as well as by loss of functional input from the sclerotic hippocampus.     

UK guidelines for the management of pituitary apoplexy

Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone maybe life saving. It is a clinical syndrome characterized by the sudden onset of headache, vomiting, visual impairment and decreased consciousness caused by haemorrhage and/or infarction of the pituitary gland. It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. If diagnosed patients should be referred to a multidisciplinary team comprising, amongst others, a neurosurgeon and an endocrinologist. Apart from patients with worsening neurological symptoms in whom surgery is indicated, it is unclear currently for the majority of patients whether conservative or surgical management carries the best outcome. Post apoplexy, there needs to be careful monitoring for recurrence of tumour growth. It is suggested that further trials be carried out into the management of pituitary apoplexy to optimize treatment.     

A patient-reported outcome measure for patients with pituitary adenoma undergoing transsphenoidal surgery

Pituitary - Pituitary adenomas affect patients’ quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While...     

Neuroanatomy in adolescents and young adults with 22q11 deletion syndrome: comparison to an IQ-matched group

22q11 deletion syndrome (22q11DS) is a common genetic condition associated with learning disability and high risk for psychiatric illness, in particular schizophrenia. Previous neuroimaging studies in children and adults with 22q11DS have uncovered a number of abnormalities, but have not differentiated between features relating to cognitive impairment and features relating to risk for schizophrenia. This structural MRI study compares adolescents with 22q11DS (n=14) to adolescents with idiopathic learning disability (n=13) and to typically-developing controls (n=14). Voxel-based morphometry and region-of-interest volumetric analyses were employed to test specific hypotheses based on prior studies of 22q11DS. Features that differentiated 22q11DS participants from both matched-IQ and higher-IQ controls were total white matter volume reduction, occipito-parietal and anterior temporal grey matter reduction, frontal and insula grey matter enlargement, and corpus callosum enlargement. On the other hand, hippocampal volume and cerebellar hemisphere reductions differed between 22q11DS and higher-IQ controls only. The neuroanatomical substrates for cognitive impairment and psychiatric illness in 22q11DS are at least partially separable. Correlations between regional volumetric abnormalities and age suggest that exaggerated processes of normal adolescent brain maturation contribute to psychosis-risk in 22q11DS, consistent with previous findings in childhood-onset schizophrenia.     

Neocortical and hippocampal volume loss in a human ciliopathy: A quantitative MRI study in Bardet-Biedl syndrome

Cilia are ubiquitous cell surface organelles with diverse roles from embryogenesis to adult life. The neurodevelopmental functions of the cilium are currently under investigation in animal systems, but relevance to human brain development remains uncertain. We present the first systematic investigation of structural neuroanatomy in a ciliopathy-Bardet-Biedl syndrome (BBS). Qualitative and quantitative aspects of brain structure were evaluated via magnetic resonance imaging in 10 patients with BBS (ages 14-28 years). In comparison to age and gender-matched healthy controls, BBS patients had significantly reduced total gray matter (GM) volume but no total white matter (WM) or cerebrospinal fluid volume changes. Voxel-based morphometric analysis indicated regional GM volume loss bilaterally in the anterior temporal lobes and in the medial orbitofrontal cortex, and WM volume loss in the right inferior longitudinal fasciculus. Region-of-interest measurements revealed reduced volume of the hippocampus. Two patients were found to have ventriculomegaly. Global GM reduction and regional volume reductions in the temporal lobe may underlie the learning disabilities and behavioral problems experienced by some patients with BBS. These findings are consistent with previous observations in mouse models of BBS, and further implicate the cilium in neurodevelopmental processes relevant to human cognitive function.     

Language fMRI abnormalities associated with FOXP2 gene mutation

Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.     

Detecting seizure origin using basic, multiscale population dynamic measures: preliminary findings

Many types of electrographic seizures are readily identifiable by direct visual examination of electroencephalographic or electrocorticographic recordings. This process can, however, be painstakingly slow, and much effort has been expended to automate the process using various dynamic properties of epileptiform waveforms. As methods have become more subtle and powerful they have been used for seizure subclassification, seizure prediction, and seizure onset identification and localization. Here we concentrate on the last, with reference to seizures of neocortical origin. We briefly review some of the methods used and introduce preliminary results from a very simple dynamic model based on key electrophysiological properties found in some seizure types: occurrence of very fast oscillations (sometimes called ripples), excess gamma frequency oscillations, electroencephalographic/electrocorticographic flattening, and changes in global synchrony. We show how this multiscale analysis may reveal features unique to seizure onset and speculate on the underlying cellular and network phenomena responsible.     

Detecting white matter injury in sickle cell disease using voxel-based morphometry

OBJECTIVE: Sickle cell disease (SCD) is associated with cerebrovascular disease, cerebral infarction, and cognitive dysfunction. This study aimed to detect the presence and extent of white matter abnormalities in individuals with SCD using voxel-based morphometry (VBM). METHODS: Thirty-six children and adolescents with SCD (age range, 9-24 years) and 31 controls (8-25 years) underwent magnetic resonance investigations using T1- and T2-weighted protocols. White and gray matter density maps were obtained from three-dimensional magnetic resonance imaging (MRI) data sets. Using VBM, we compared the maps between controls and SCD individuals with silent white matter infarct lesions (SCD+L; n = 16), and those without visible abnormality (SCD-L; n = 20). RESULTS: In comparison with controls, intelligence quotients (IQs) were lower in both SCD groups irrespective of presence of visible lesions. VBM showed widespread bilateral white matter abnormalities in the SCD+L group, extending beyond the regions of focal infarction in the deep anterior and posterior white matter borderzones. Bilateral white matter abnormalities were also observed in the SCD-L group, in locations similar to those in the SCD+L group. INTERPRETATION: VBM is sensitive to detection of widespread white matter injury in SCD patients in borderzones between arterial territories even in the absence of evidence of infarction. Those changes may contribute to cognitive deficits in this population.     

Mismatch negativity in schizophrenia: a family study

BACKGROUND: Mismatch negativity (MMN) is a measure of cortical activity that occurs in response to a change in auditory stimuli. We investigated whether MMN is a potential marker of genetic vulnerability to schizophrenia by comparing MMN in a group of patients with schizophrenia, their unaffected relatives, and controls. METHOD: There are 25 schizophrenic patients, 37 of their unaffected first-degree relatives, and 20 unrelated controls that performed the MMN task. Linear regression with robust standard errors, and accounting for correlations within families, was employed to test for differences in MMN amplitude between the groups. RESULTS: Patients had significantly smaller MMN amplitudes compared to both their unaffected relatives and controls at FZ (P<0.01) and at F3 (P=0.01), whereas relatives and controls did not differ at FZ or at F3. No differences were found between any of the groups at F4. Furthermore, we found no strong evidence that the MMN amplitude is a familial trait. CONCLUSIONS: Our results confirm that the MMN amplitude is reduced in schizophrenia. However, the MMN does not show a significant familial influence and is normal among the unaffected relatives. We conclude that while the MMN is abnormal in patients with schizophrenia, it is a weak or unreliable marker of vulnerability when applied to subclinical populations, and therefore is unlikely to be an endophenotype for the disorder.