Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage
; ; et al
in Brain : A Journal of Neurology (2015), 138Detailed reference viewed: 76 (7 ULg)
Inositol trisphosphate 3-kinase B is increased in human Alzheimer brain and exacerbates mouse Alzheimer pathology
; ; et al
in Brain : A Journal of Neurology (2014), 137
S. Schurmans and J.-P. Brion contributed equally to this work Corresponding author: S. Schurmans, Laboratoire de Génétique Fonctionnelle, GIGA-Research Centre, Building 34, Université de Liège, rue de ... [more ▼]
S. Schurmans and J.-P. Brion contributed equally to this work Corresponding author: S. Schurmans, Laboratoire de Génétique Fonctionnelle, GIGA-Research Centre, Building 34, Université de Liège, rue de l’Hôpital 1, 4000-Liège, Belgium. Abstract: Inositol (1,4,5) trisphosphate 3-kinase B phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate and controls signal transduction in various hematopoietic cells. Surprisingly, it has been reported that Inositol (1,4,5) trisphosphate 3-kinase B mRNA level is significantly increased in the cerebral cortex of Alzheimer patients, compared to control subjects. Since Extracellular signal-regulated kinases 1/2 activation is increased in Alzheimer brain and since Inositol (1,4,5) trisphosphate 3-kinase B is a regulator of Extracellular signal-regulated kinases 1/2 activation in some hematopoietic cells, we tested whether this increased activation in Alzheimer’s disease might be related to an increased activity of Inositol (1,4,5) trisphosphate 3-kinase B. We show here that Inositol (1,4,5) trisphosphate 3-kinase B protein level was 3 fold increased in the cerebral cortex of most Alzheimer patients, compared to control subjects, and accumulated in dystrophic neurites associated to amyloid plaques. In mouse Neuro-2a neuroblastoma cells, Inositol (1,4,5) trisphosphate 3-kinase B overexpression was associated with increased cell apoptosis and increased β-secretase 1 activity leading to amyloid-β peptides overproduction. In this cellular model, an inhibitor of Mitogen-activated kinase kinases 1/2 completely prevented amyloid-β peptides overproduction. Transgenic overexpression of Inositol (1,4,5) trisphosphate 3-kinase B in mouse forebrain neurons was not sufficient to induce amyloid plaques formation or TAU hyperphosphorylation. However, in the 5X Familial Alzheimer’s Disease mouse model, neuronal Inositol (1,4,5) trisphosphate 3-kinase B overexpression significantly increased Extracellular signal-regulated kinases 1/2 activation and β-secretase 1 activity, resulting in exacerbated Alzheimer pathology as shown by increased astrogliosis, amyloid-β40 peptide production and TAU hyperphosphorylation. No impact on pathology was observed in the 5X Familial Alzheimer’s Disease mouse model when a catalytically inactive Inositol (1,4,5) trisphosphate 3-kinase B protein was overexpressed. Together, our results point to the Inositol (1,4,5) trisphosphate 3-kinase B /Inositol 1,3,4,5-tetrakisphosphate/Extracellular signal-regulated kinases 1/2 signaling pathway as an important regulator of neuronal cell apoptosis, Amyloid precursor protein processing and TAU phosphorylation in Alzheimer’s disease, and suggest that Inositol (1,4,5) trisphosphate 3-kinase B could represent a new target for reducing pathology in human AD patients with increased cortical Inositol (1,4,5) trisphosphate 3-kinase B expression. [less ▲]Detailed reference viewed: 39 (15 ULg)
Impact of blindness onset on the functional organization and the connectivity of the occipital cortex
; ; et al
in Brain : A Journal of Neurology (2013)Detailed reference viewed: 22 (1 ULg)
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.
; ; et al
in Brain : a journal of neurology (2013), 136(Pt 10), 3140-50
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are ... [more ▼]
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 x 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures. [less ▲]Detailed reference viewed: 11 (3 ULg)
Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.
; Gosseries, Olivia ; et al
in Brain : A Journal of Neurology (2012), 135(Pt 4), 1308-20
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing ... [more ▼]
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment. [less ▲]Detailed reference viewed: 107 (2 ULg)
Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state.
; Bruno, Marie-Aurélie ; Noirhomme, Quentin et al
in Brain : A Journal of Neurology (2011), 134(Pt 8), 2222-32
The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate ... [more ▼]
The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate patients in a vegetative state from patients in a minimally conscious state. Using high-density electroencephalographic sleep recordings, 11 patients with disorders of consciousness (six in a minimally conscious state, five in a vegetative state) were studied to correlate the electrophysiological changes associated with sleep to behavioural changes in vigilance (sustained eye closure and muscle inactivity). All minimally conscious patients showed clear electroencephalographic changes associated with decreases in behavioural vigilance. In the five minimally conscious patients showing sustained behavioural sleep periods, we identified several electrophysiological characteristics typical of normal sleep. In particular, all minimally conscious patients showed an alternating non-rapid eye movement/rapid eye movement sleep pattern and a homoeostatic decline of electroencephalographic slow wave activity through the night. In contrast, for most patients in a vegetative state, while preserved behavioural sleep was observed, the electroencephalographic patterns remained virtually unchanged during periods with the eyes closed compared to periods of behavioural wakefulness (eyes open and muscle activity). No slow wave sleep or rapid eye movement sleep stages could be identified and no homoeostatic regulation of sleep-related slow wave activity was observed over the night-time period. In conclusion, we observed behavioural, but no electrophysiological, sleep wake patterns in patients in a vegetative state, while there were near-to-normal patterns of sleep in patients in a minimally conscious state. These results shed light on the relationship between sleep electrophysiology and the level of consciousness in severely brain-damaged patients. We suggest that the study of sleep and homoeostatic regulation of slow wave activity may provide a complementary tool for the assessment of brain function in minimally conscious state and vegetative state patients. [less ▲]Detailed reference viewed: 32 (2 ULg)
Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.
Vanhaudenhuyse, Audrey ; Noirhomme, Quentin ; Tshibanda, Luaba et al
in Brain : A Journal of Neurology (2010), 133(Pt 1), 161-71
The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than ... [more ▼]
The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. [less ▲]Detailed reference viewed: 96 (22 ULg)
The neural correlates of verbal short-term memory in Alzheimer's disease: an fMRI study.
; Collette, Fabienne ; Degueldre, Christian et al
in Brain : A Journal of Neurology (2009), 132(7), 1833-1846
Although many studies have shown diminished performance in verbal short-term memory tasks in Alzheimer's disease, few studies have explored the neural correlates of impaired verbal short-term memory in ... [more ▼]
Although many studies have shown diminished performance in verbal short-term memory tasks in Alzheimer's disease, few studies have explored the neural correlates of impaired verbal short-term memory in Alzheimer's disease patients. In this fMRI study, we examined alterations in brain activation patterns during a verbal short-term memory recognition task, by differentiating encoding and retrieval phases. Sixteen mild Alzheimer's disease patients and 16 elderly controls were presented with lists of four words followed, after a few seconds, by a probe word. Participants had to judge whether the probe matched one of the items of the memory list. In both groups, the short-term memory task elicited a distributed fronto-parieto-temporal activation that encompassed bilateral inferior frontal, insular, supplementary motor, precentral and postcentral areas, consistent with previous studies of verbal short-term memory in young subjects. Most notably, Alzheimer's disease patients showed reduced activation in several regions during the encoding phase, including the bilateral middle frontal and the left inferior frontal gyri (associated with executive control processes) as well as the transverse temporal gyri (associated with phonological processing). During the recognition phase, we found decreased activation in the left supramarginal gyrus and the right middle frontal gyrus in Alzheimer's disease patients compared with healthy seniors, possibly related to deficits in manipulation and decision processes for phonological information. At the same time, Alzheimer's disease patients showed increased activation in several brain areas, including the left parahippocampus and hippocampus, suggesting that Alzheimer's disease patients may recruit alternative recognition mechanisms when performing a short-term memory task. Overall, our results indicate that Alzheimer's disease patients show differences in the functional networks underlying memory over short delays, mostly in brain areas known to support phonological processing or executive functioning. [less ▲]Detailed reference viewed: 49 (14 ULg)
Chromosomal profiles of gene expression in Huntington's disease.
; ; et al
in Brain : A Journal of Neurology (2008), 131(Pt 2), 381-8
Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread ... [more ▼]
Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread transcriptional dysregulation. Mutant huntingtin also interacts with histone acetyltransferases, consequently interfering with the acetylation and deacetylation states of histones. Because histone modifications and chromatin structure coordinate the expression of gene clusters, we have applied a novel mathematical approach, Chromowave, to analyse microarray datasets of brain tissue and whole blood to understand how genomic regions are altered by the effects of mutated huntingtin on chromatin structure. Results show that, in samples of caudate and whole blood from Huntington's disease patients, transcription is indeed deregulated in large genomic regions in coordinated fashion, that transcription in these regions is associated with disease progression and that altered chromosomal clusters in the two tissues are remarkably similar. These findings support the notion of a common genome-wide mechanism of disruption of RNA transcription in the brain and periphery of Huntington's disease patients. [less ▲]Detailed reference viewed: 37 (2 ULg)
Interictal habituation deficit of the nociceptive blink reflex: an endophenotypic marker for presymptomatic migraine?
; ; Magis, Delphine et al
in Brain : A Journal of Neurology (2007), 130(Pt 3), 765-770
Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible ... [more ▼]
Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible abnormality in migraine which has a familial character, or to central trigeminal sensitization due to repeated attacks. We compared nBR habituation in healthy volunteers devoid of personal or family history of migraine (HV), in migraine without aura patients (MO) and in healthy volunteers with a family history of migraine in first degree relatives (HV-F). We elicited the nBR by stimulating the right supraorbital region with a custom-built electrode in 16 MO between attacks, 15 HV and 14 HV-F. Habituation was measured as the percentage area-under-the-curve decrease in 10 consecutive blocks of five averaged rectified responses. nBR habituation was clearly reduced in MO and HV-F compared to HV. Percentage area under the curve decreased between the 1st and the 10th block by 55.01% in HV, 25.71% in MO (P = 0.001) and 26.73% in HV-F (P = 0.043). HV-F had the most pronounced abnormality with potentiation instead of habituation in the second block. We found a positive intraindividual correlation between attack frequency and habituation in MO (r = 0.621; P = 0.010). Migraine patients have interictally a deficient habituation of the nBR which is inversely related to attack frequency, suggesting that it is not due to trigeminal sensitization. Surprisingly, the most pronounced habituation deficit is found in asymptomatic individuals with a family history of migraine. Deficient nBR habituation could thus be a trait marker for the genetic predisposition to migraine. [less ▲]Detailed reference viewed: 40 (2 ULg)
Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study.
; ; et al
in Brain : A Journal of Neurology (2006), 129(Pt 8), 2029-37
Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related ... [more ▼]
Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching. [less ▲]Detailed reference viewed: 40 (0 ULg)
Sequential loss of myelin proteins during Wallerian degeneration in the human spinal cord
; ; et al
in Brain : A Journal of Neurology (2005), 128(Part 2), 356-364
Axons undergo Wallerian degeneration (WD) distal to a point of injury. In the lesioned PNS, WD may be followed by successful axonal regeneration and functional recovery. However, in the lesioned mammalian ... [more ▼]
Axons undergo Wallerian degeneration (WD) distal to a point of injury. In the lesioned PNS, WD may be followed by successful axonal regeneration and functional recovery. However, in the lesioned mammalian CNS, there is no significant axonal regeneration. Myelin-associated proteins (MAPs) have been shown to play significant roles in preventing axonal regeneration in the CNS. Since relatively little is known about such events in human CNS pathologies, we performed an immunohistochemical investigation on the temporal changes of four MAPs during WD in post-mortem spinal cords of 22 patients who died 2 days to 30 years after either cerebral infarction or traumatic spinal cord injury. In contrast to experimental studies in rats, the loss of myelin sheaths is greatly delayed in humans and continues slowly over a number of years. However, in agreement with animal data, a sequential loss of myelin proteins was found which was dependent on their location within the myelin sheath. Myelin proteins situated on the peri-axonal membrane were the first to be lost, the time course correlating with the loss of axonal markers. Proteins located within compact myelin or on the outer myelin membrane were still detectable 3 years after injury in degenerating fibre tracts, long after the disappearance of the corresponding axons. The persistence of axon growth-inhibitory proteins such as NOGO-A in degenerating nerve fibre tracts may contribute to the maintenance of an environment that is hostile to axon regeneration, long after the initial injury. The present data highlight the importance of correlating the well documented, lesion-induced changes that take place in controlled laboratory investigations with those that take place in the clinical domain. [less ▲]Detailed reference viewed: 18 (2 ULg)
Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord
; ; et al
in Brain : A Journal of Neurology (2004), 127(Part 1), 34-44
Axons undergo Wallerian degeneration distal to a point of injury. Experimental investigations have documented many of the cellular and molecular events that underlie this behaviour. Since relatively ... [more ▼]
Axons undergo Wallerian degeneration distal to a point of injury. Experimental investigations have documented many of the cellular and molecular events that underlie this behaviour. Since relatively little is known about such events in human CNS pathologies and current experimental intervention strategies indicate the possibility of significant axon regeneration along the original degenerated fibre tract, we performed an immunohistochemical investigation of the dynamics of Wallerian degeneration in post mortem spinal cords of patients who died 2 days to 30 years after either cerebral infarction or traumatic spinal cord injury. Neurofilament (NF) staining demonstrated a spatio-temporal pattern of axonal loss within degenerating descending nerve fibre tracts that could be detected close to the lesion as early as 12 days after injury and progressed to an almost complete loss of NF immunoreactivity at survival times of 1 year and longer. Immunohistochemistry for glial fibrillary acidic protein revealed a late astrocytic reaction starting at 4 months after injury in the degenerating tracts, leading to the long-term deposition of a dense astrocytic scar. These events were accompanied by the gradual reduction of myelin basic protein in affected nerve fibre tracts, leading to almost complete loss by 3 years after injury. Since the extracellular matrix molecule chondroitin sulphate proteoglycan (CSPG) is known to be strongly inhibitory for axonal regeneration and to be a major component of gliotic scar tissues, we investigated the possible deposition of CSPG within the degenerating nerve fibre tracts. Apart from a local up-regulation close to the lesion site, our results show no enhanced CSPG expression within degenerated tracts at any survival time. This suggests that despite the apparent lack of CSPG in Wallerian degeneration, the slow reduction of CNS myelin and the long-term deposition of a dense astrocytic scar may present an environment that is non-supportive for axon regrowth. [less ▲]Detailed reference viewed: 24 (3 ULg)
KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum.
; ; Charlier, Carole et al
in Brain : A Journal of Neurology (2003), 126(Pt 12), 2726-37
Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant generalized epilepsy of the newborn infant. Seizures occur repeatedly in the first days of life and remit by approximately 4 months ... [more ▼]
Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant generalized epilepsy of the newborn infant. Seizures occur repeatedly in the first days of life and remit by approximately 4 months of age. Previously our laboratory cloned two novel potassium channel genes, KCNQ2 and KCNQ3, and showed that they are mutated in patients with BFNC. In this report, we characterize the breakpoints of a previously reported interstitial deletion in the KCNQ2 gene and show that only KCNQ2 is deleted. We identify 11 novel mutations in KCNQ2 and one novel mutation in the KCNQ3 potassium channel genes. In one family, the phenotype extends beyond neonatal seizures and includes rolandic seizures, and a subset of families has onset of seizures in infancy. In the Xenopus oocyte expression system, we characterize five KCNQ2 and one KCNQ3 disease-causing mutations. These mutations cause a variable loss of function, and selective effects on the biophysical properties of KCNQ2/KCNQ3 heteromultimeric channels. We report here the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment. [less ▲]Detailed reference viewed: 64 (0 ULg)
Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine.
; Fumal, Arnaud ; et al
in Brain : A Journal of Neurology (2002), 125(Pt 4), 912-22
Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical ... [more ▼]
Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical excitability. We have studied the changes in visual cortex excitability by recording pattern-reversal visual evoked potentials (PR-VEP) after low- and high-frequency repetitive transcranial magnetic stimulation (rTMS), known respectively for their inhibitory and excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was set to the phosphene threshold or to 110% of the motor threshold if no phosphenes were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy volunteers, PR-VEP amplitude was significantly decreased in the first block after 1 Hz rTMS and the habituation normally found in successive blocks after sustained stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was followed by a significant increase of first block PR-VEP amplitude and by a reversal to normal habituation of the potentiation (or dishabituation) characteristic of the disorder. This effect was similar in both forms of migraine and lasted for at least 9 min. There were no significant changes of PR-VEP amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy volunteers, nor after sham stimulation. The recovery of a normal PR-VEP habituation pattern after high-frequency rTMS is probably due to activation of the visual cortex and the dishabituation in healthy volunteers to cortical inhibition. We conclude, therefore, that the deficient interictal PR-VEP habituation in migraine is due to a reduced, and not to an increased, pre-activation excitability level of the visual cortex. [less ▲]Detailed reference viewed: 33 (8 ULg)
Auditory processing in the vegetative state.
Laureys, Steven ; Faymonville, Marie ; Degueldre, Christian et al
in Brain : A Journal of Neurology (2000), 123 ( Pt 8)
H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin ... [more ▼]
H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness. [less ▲]Detailed reference viewed: 43 (7 ULg)
Ergotamine in the acute treatment of migraine: a review and European consensus.
; ; et al
in Brain : A Journal of Neurology (2000), 123 ( Pt 1)
Ergotamine has been used in clinical practice for the acute treatment of migraine for over 50 years, but there has been little agreement on its place in clinical practice. An expert group from Europe ... [more ▼]
Ergotamine has been used in clinical practice for the acute treatment of migraine for over 50 years, but there has been little agreement on its place in clinical practice. An expert group from Europe reviewed the pre-clinical and clinical data on ergotamine as it relates to the treatment of migraine. From this review, specific suggestions for the patient groups and appropriate use of ergotamine have been agreed. In essence, ergotamine, from a medical perspective, is the drug of choice in a limited number of migraine sufferers who have infrequent or long duration headaches and are likely to comply with dosing restrictions. For most migraine sufferers requiring a specific anti-migraine treatment, a triptan is generally a better option from both an efficacy and side-effect perspective. [less ▲]Detailed reference viewed: 28 (2 ULg)
Corticomotoneuronal synaptic connections in normal man. An electrophysiological study.
Maertens de Noordhout, Alain
in Brain : A Journal of Neurology (1999), 122
In order to determine the mono- or oligosynaptic character of connections between pyramidal axons and individual spinal motor neurons, we constructed peri-stimulus time histograms (PSTHs) of the firing ... [more ▼]
In order to determine the mono- or oligosynaptic character of connections between pyramidal axons and individual spinal motor neurons, we constructed peri-stimulus time histograms (PSTHs) of the firing probability of voluntarily activated single motor units (SMUs) of various upper and lower limb muscles upon slightly suprathreshold transcranial anodal electrical stimulations of the motor cortex in normal subjects. Weak anodal cortical stimuli are known to activate preferentially fast-conducting pyramidal axons directly, bypassing cell bodies and cortical interneurons. A narrow bin width (0.1 ms) was chosen to measure precisely the duration of the PSTH excitatory peak, which corresponds to the rise time of the underlying compound excitatory post-synaptic potentials (EPSP). A short duration PSTH peak indicates sharp-rising EPSPs, most commonly encountered in the case of monosynaptic connections. In flexor carpi radialis and soleus SMUs, the PSTHs of built-in responses to anodal cortical stimuli were compared with those produced by 1A afferent stimulation able to elicit a Hoffmann reflex, which is known to be largely monosynaptic. In all upper and lower limb muscles, excitable SMUs responded to anodal cortical stimuli with a highly synchronized peak of increased firing probability. In flexor carpi radialis and soleus SMUs, the mean duration of this peak was significantly narrower than that evoked by 1A afferent stimulation, indicating that monosynaptic corticomotor neuronal transmission dominates low-threshold motor units, even in proximal arm and leg muscles. In the various muscles studied, and particularly in forearm SMUs, we did not observe broad PSTH peaks against the activation of non-monosynaptic corticomotor neuronal pathways, even with near-threshold stimuli. In some triceps and forearm flexor SMUs, subthreshold anodal pulses caused significant inhibition of their voluntary firing, with a latency consistent with activation of 1A inhibitory interneurons by the descending volleys. Measurements of the maximal number of counts in the excitatory PSTH peak upon anodal cortical stimuli provide comparisons of the strength of monosynaptic inputs to various muscles which seems to be maximal for hand and finger extensor muscles, and also for deltoid. [less ▲]Detailed reference viewed: 15 (3 ULg)
Visual evoked potentials during long periods of pattern-reversal stimulation in migraine.
; ; DE PASQUA, Victor et al
in Brain : A Journal of Neurology (1998), 121(2), 233-41
We have previously shown that during repetitive pattern-reversal stimulation, lasting 2 min, the amplitude of the visual evoked potential (PR-VEP) increases in migraineurs when tested interictally whereas ... [more ▼]
We have previously shown that during repetitive pattern-reversal stimulation, lasting 2 min, the amplitude of the visual evoked potential (PR-VEP) increases in migraineurs when tested interictally whereas it decreases in healthy control subjects. According to Sappey-Marinier et al. (J Cereb Blood Flow Metab 1992; 12: 584-92) habituation of the PR-VEP in normal subjects is maxima after 12 min, at a time when there is a decrease of stimulation-enhanced lactate levels in the occipital cortex. We have therefore compared PR-VEP during long periods of repetitive stimulation in healthy control subjects (n = 25) and in patients suffering from migraine without (n = 25) and with aura (n = 15) between attacks. During uninterrupted stimulation at 3.1 Hz VEPs were sequentially averaged in blocks of 100 responses for a total duration of 15 min and analysed in terms of latencies and peak-to-peak amplitudes of N1-P1 and P1-N2 peaks. Amplitude changes from the baseline were calculated for each block, by comparison with the first block, and analysed statistically using Zerbe's method. The N1-P1 and P1-N2 amplitudes in the first block tended to be lower in migraineurs than in healthy control subjects. During the 15 min of stimulation, amplitudes of both components progressively decreased in control subjects, but remained stable in both groups of patients. The difference between patients and control subjects proved to be significant (P < 0.05). The neurophysiological data were not correlated with clinical features such as attack frequency or duration of illness. These results are yet another demonstration in migraine of an interictal habituation deficit in cortical information processing, which might favour lactate accumulation in sensory cortices during sustained activation. [less ▲]Detailed reference viewed: 25 (2 ULg)
Genetic disorders and cerebellar structural abnormalities in childhood
RAMAEKERS, Vincent ; ; et al
in Brain : a journal of neurology (1997), 120 ( Pt 10)
Amongst 78 patients with either unilateral or bilateral (ponto-) cerebellar hypoplasia, atrophy or lesions on neuro-imaging (CT and/or MRI), 16 showed unilateral hypoplasia or lesions, 15 vermis defects ... [more ▼]
Amongst 78 patients with either unilateral or bilateral (ponto-) cerebellar hypoplasia, atrophy or lesions on neuro-imaging (CT and/or MRI), 16 showed unilateral hypoplasia or lesions, 15 vermis defects, nine pontocerebellar hypoplasia, 10 non-progressive conditions with bilateral cerebellar hemisphere hypoplasia or lesions and 28 progressive cerebellar atrophy. Known genetic conditions did not occur with unilateral cerebellar involvement, whereas a high incidence of mostly autosomal recessively inherited diseases could be diagnosed in more than half of the patients with either pontocerebellar hypoplasia or progressive bilateral cerebellar atrophy. A minority of patients with vermis defects or non-progressive cerebellar hypoplasia suffered from genetic conditions. An overview of the literature is presented describing genetic and non-genetic syndromes, or metabolic disorders associated with cerebellar structural abnormalities. From these data, new proposals for improved diagnostic investigations will be presented. [less ▲]Detailed reference viewed: 7 (0 ULg)