Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder

Järnum H, Eskildsen SF, Steffensen EG, Lundbye‐Christensen S, Simonsen CW, Thomsen IS, Fründ E‐T, Théberge J, Larsson E‐M. Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder. Objective: To determine whether patients with major depressive disorder (MDD) display morphologic, functional, and metabolic brain abnormalities in limbic‐cortical regions at a baseline magnetic resonance (MR) scan and whether these changes are normalized in MDD patients in remission at a follow‐up scan. Method: A longitudinal 3.0‐Tesla (T) magnetic resonance imaging (MRI) study was carried out with cortical thickness measurements with a surface‐based approach, perfusion measurements with three‐dimensional (3D) pseudo‐continuous arterial spin labeling (pCASL), and spectroscopy (1H‐MRS) measurements in the anterior cingulate cortex (ACC) with water as an internal reference adjusted for cerebrospinal fluid content. We examined 23 MDD patients and 26 healthy controls. MDD patients underwent a baseline MRI at inclusion and were invited to a follow‐up scan when they were in remission or after a 6‐month follow‐up period. Results: Major findings were a significantly thinner posterior cingulate cortex in non‐remitters than in remitters, a significant decrease in perfusion in the frontal lobes and the ACC in non‐remitters compared with healthy controls at baseline and significantly reduced N‐acetylaspartate, myo‐inositol, and glutamate levels in MDD patients compared with healthy controls at baseline. Conclusion: Using novel MRI techniques, we have found abnormalities in cerebral regions related to cortical‐limbic pathways in MDD patients.     

Resting state cortical electroencephalographic rhythms and white matter vascular lesions in subjects with Alzheimer's disease: an Italian multicenter study

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.     

Patients with epilepsy and patients with psychogenic non-epileptic seizures: Video-EEG, clinical and neuropsychological evaluation

Purpose

The incidence of psychogenic non-epileptic seizures (PNES) is 4.9/100,000/year and it is estimated that about 20–30% of patients referred to tertiary care epilepsy centers for refractory seizures have both epilepsy and PNES.The purpose of our study is to evaluate psychiatric disorders and neuropsychological functions among patients with PNES, patients with epilepsy associated with PNES and patients with epilepsy.

Methods

We evaluated 66 consecutive in-patients with video-EEG recordings: 21 patients with epilepsy, 22 patients with PNES and 10 patients with epilepsy associated with PNES; 13 patients were excluded (8 because of mental retardation and 5 because they did not present seizures or PNES during the recording period).

Results

All patients with PNES had a psychiatric diagnosis (100%) vs. 52% of patients with epilepsy. Cluster B personality disorders were more common in patients with PNES.We observed fewer mood and anxiety disorders in patients with PNES compared with those with epilepsy.We did not find statistically significant differences in neuropsychological profiles among the 3 patient groups.

Conclusion

This study can help to contribute to a better understanding of the impact of PNES manifestations, in addition to the occurrence of seizures, in order to provide patients with more appropriate clinical, psychological and social care.     

Brief Report: Delayed Diagnosis of Treatable Inborn Errors of Metabolism in Children with Autism and Other Neurodevelopmental Disorders

Journal of Autism and Developmental Disorders - The objective of our study was to evaluate the frequency of treatable inborn errors of metabolism (IEM) in a clinical sample of Mexican children and...     

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.     

Importancia de la arteriografía cerebral y la monitorización neurofisiológica intraoperatoria en la endarterectomía carotídea

It is an increasingly common practice to indicate a carotid endarterectomy procedure based on the information provided by non-invasive tests like Duplex ultrasound, MR angiography or CT angiography, thereby obviating the performance of a conventional cerebral angiography. We present a case of symptomatic left carotid artery 80% stenosis in which cerebral angiography showed absence of the right A1 segment and bilateral anterior cerebral artery territories that filled only from a left injection. Just 90 seconds after carotid artery clamping at the neck, brain oximetry and somatosensory evoked potentials significantly dropped, that recovered after immediate clamp removal. Endarterectomy was dismissed and a carotid stent was successfully placed. This case highlights the importance of knowing the dynamics of cerebral blood circulation distal to the stenosis. If endarterectomy had been attempted, unawareness of the information provided by the cerebral angiography would have likely result in severe bi-hemispheric ischemia.     

Advanced glycation end products, oxidative stress and metalloproteinases are altered in the cerebral microvasculature during aging

Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.     

Epileptic spikes in Rasmussen’s encephalitis: Migratory pattern and short-term evolution. A MEG study

Objective

We aimed this study at identifying cortical areas involved in the generation of interictal spikes in Rasmussen’s Encephalitis (RE) patients using magnetoencephalography (MEG), at comparing spike localization with the degree of cortical atrophy detected by MRI, and at identifying short-term changes during the follow-up.

Pilot randomized controlled trial to assess a physical therapy program on upper extremity function to counteract inactivity in chronic stroke

Background: In chronic stroke, feasible physical therapy (PT) programs are needed to promote function throughout life.

Objective: This randomized controlled pilot trial investigated the feasibility and effect of a PT program composed of strengthening exercises with elastic bands and bimanual functional training, with clearly defined doses based on the rate of perceived exertion (Borg scale), to counteract inactivity in chronic stroke.

Methods: Fifteen subjects > 6 month post-stroke were randomized to three-month of UE function training (UE group), or to lower extremity function training (LE group). At baseline (T0), post-intervention (T1) and three-month follow-up (T2) assessment included the Fugl-Meyer Assessment scale (FMA), Wolf Motor Function test (WMFT), grip strength, and muscle tone. Feasibility was also evaluated.

Results: The mixed-model ANOVAs revealed a significant interaction between the time and group factors for FMA (p < .001) and WMFT (p = .009). The UE group improved upper extremity function and motor recovery significantly more than the LE group. There was no significant interaction between treatment group and change in grip strength over time (p = .217). No between-group differences (p > .05) were found in muscle tone. In the UE group, the attendance rate was ≥85% for 71.4% of subjects and 85.7% showed high satisfaction. No adverse events were recorded. After treatment, adherence to the program was higher in the UE group.

Conclusions: The suggested PT program may be useful to improve the paretic UE function and motor recovery in chronic stroke. Moreover, it may be helpful to facilitate lifelong active involvement of stroke subjects in exercise.