Phenotypical characterization of alpha-galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young.

in Clinical Neurology & Neurosurgery (2012)

OBJECTIVE: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar ... [more ▼]

OBJECTIVE: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with alpha-galactosidase A (alpha-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population. METHODS: Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed. RESULTS: Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot alpha-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation. CONCLUSIONS: We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants. [less ▲]

La vignette diagnostique de l'étudiant. La paralysie faciale ... pas toujours si facile que cela !

in Revue Médicale de Liège (2011), 66(11)

We report the case of a 45 years old woman who experienced two episodes of facial palsy, first on the left side, then on the other. this particular case allows us to discuss the diagnostic process and ... [more ▼]

We report the case of a 45 years old woman who experienced two episodes of facial palsy, first on the left side, then on the other. this particular case allows us to discuss the diagnostic process and clinical reasoning to follow in front of this symptomatology -using a didactic questioning- and to briefly review the anatomy of the seventh cranial nerve. treatment and possible complications are also discussed [less ▲]

Comment prédire l'évolution du coma post-anoxique?

in Revue Médicale de Liège (2008), 63(5-6), 263-268

Des statines pour le cerveau. Le point en 2008.

in Revue Médicale de Liège (2008), 63(5-6), 287-92

Statins are essential drugs for the prevention of coronary artery disease. There is now evidence that they can also prevent ischemic stroke. The protective effect is related to the reduction in total and ... [more ▼]

Statins are essential drugs for the prevention of coronary artery disease. There is now evidence that they can also prevent ischemic stroke. The protective effect is related to the reduction in total and LDL cholesterol levels and the clinical benefit is especially high in secondary prevention patients with previous stroke and/or transient ischemic accident. The favourable role of statins is less well documented during an acute stroke than during an acute coronary syndrome, and certainly deserves further studies. Besides their specific cholesterol-lowering effect, statins exert various pleiotropic effects, which probably contribute to vascular protection. Furthermore, statins are able to reduce the formation of beta-amyloid peptide, which plays a key-role in the pathogenesis of Alzheimer disease. However, currently available results are heterogeneous and could not firmly support a protective effect of statins in dementia in general, neither in Alzheimer disease more specifically, nor in the reduction of cognitive function in the elderly. Several ongoing trials should confirm or not confirm this new potential indication of statins in a near future. [less ▲]

Quelles indications pour les statines hormis le traitement de l'hypercholesterolemie?

in Revue Médicale Suisse (2005), 1(30), 19541956-9

Statins are essential drugs for the prevention of coronary and cerebral vascular complications. Besides their specific cholesterol-lowering effect, these agents exert various pleiotropic effects, which ... [more ▼]

Statins are essential drugs for the prevention of coronary and cerebral vascular complications. Besides their specific cholesterol-lowering effect, these agents exert various pleiotropic effects, which probably contribute to the cardiovascular protection, but may also play a favourable effect in various other pathologies. Some recent data suggested that statins may play a positive effect in the prevention of Alzheimer disease and colorectal cancer. In contrast, after some initial hope, recent observations in the field of osteoporosis prevention provided discordant and finally rather disappointing results. New prospective studies are mandatory before accepting such new potential indications of statins. [less ▲]

Sodium bromide encephalopathy with decreased serum Cl- level and increased anion gap: report of one case.

in European Neurology (2004), 51(4), 246-7

Brain function in the vegetative state

in Acta Neurologica Belgica (2002), 102(4), 177-185

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates ... [more ▼]

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction. [less ▲]

Forme scapulo-peroniere a revelation tardive d'une dystrophie musculaire facio-scapulo-humerale, liee a une deletion chromosomique 4q35.

in Revue Neurologique (2002), 158(12), 1210-3

L'image du mois. Une thrombose veineuse cerebrale

in Revue Médicale de Liège (2001), 56(2), 61-2

Exploration neuropsychologique et par imagerie fonctionnelle cérébrale d'une apraxie visuo-imitative

in Revue Neurologique (2000), 156(5), 459-472

We describe the case of a 58-years-old right-handed women suffering from an occipital-parietal lesion. The administration of a cognitively based assessment tool for limb praxis (Batterie d'Evaluation des ... [more ▼]

We describe the case of a 58-years-old right-handed women suffering from an occipital-parietal lesion. The administration of a cognitively based assessment tool for limb praxis (Batterie d'Evaluation des Praxies, B.E.P., Peigneux and Van der Linden, 1998) demonstrated bilateral visuo-imitative apraxia. Gesture production was mainly characterised by spatial, errors, and imitation of meaningful gestures was worse than their pantomime on verbal command. Moreover, the imitation of meaningless gestures and their reproduction on a manikin were worse than imitation of their matched meaningful gestures. In a cognitive perspective, adapted from the Rothi et al. (1997) and Goldenberg (1995) contributions to our understanding of limb praxis, this configuration of performance suggests deficits occurring at multiple levels. On one hand, it suggests either access difficulties or alteration of the output praxicon, i.e., the lexicon for visuo-kinesthetic engrams of meaningful gestures. On the other hand, the simultaneous deficit for meaningless gesture reproduction on the subject's own body and on a manikin favors an alteration of the structural descriptions of the human body (i.e., human body knowledge), underlying the mental transposition processes occurring between the visual analysis of a meaningless gestural configuration and its effective reproduction on oneself or on a manikin, thus contradicting the classic view of a direct pathway linking visual analysis and motor planning in meaningless gesture imitation. Finally, due to the output praxicon deficit, imitation of meaningful gestures is partly processed in the same way as meaningless gestures (also impaired in this case), leading to an interference effect between both degraded memory-based and visually-transposed traces, which account for imitation of meaningful gestures being worse than their pantomime on verbal command. We also assess regional cerebral metabolism using positron emission tomography (PET). Comparison with 41 healthy subjects (SPM96) demonstrated a statistically significant hypometabolism in the left intraparietal sulcus and superior parietal lobule, and in the right dorsal prestriate cortex. These results, together with a review of the other studies of visuo-imitative apraxia, suggest that the left intraparietal sulcus may be associated with access or integration of information from the output praxicon. The left superior parietal and the right dorsal prestriate deficits functionally impaired a bilateral dorsal network implied in the mental transformations of the body, thus suggesting that these mental transformations are underlined by knowledge of the human body, which may subsequently explain the deficit for the reproduction of meaningless and meaningful configurations. [less ▲]