Gustave Moonen

Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS− (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [18F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46xa0±xa018xa0years) and 27 MCS patients of whom 13 were MCS− (aged 49xa0±xa019xa0years; 4 traumatic; 21xa0±xa023xa0months post injury) and 14 MCS+ (aged 43xa0±xa019xa0years; 5 traumatic; 19xa0±xa026xa0months post injury). Results were thresholded for significance at false discovery rate corrected pxa0<xa00.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS−, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca’s region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS− as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS− is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression.

MRI preclinical detection and asymptomatic course of a progressive multifocal leucoencephalopathy (PML) under natalizumab therapy.

Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role of MR scanning has not been investigated but holds promise since MR detection is highly sensitive for PML lesions. The authors report a case of presymptomatic PML of the posterior fossa detected by MR scans. Immediate suspension of natalizumab and plasma exchanges resulted in a rapid decline of natalizumab serum concentration. Intravenous steroids started together with plasma exchanges followed by an oral tapering course were used to minimise the immune reconstitution inflammatory syndrome. No symptoms (beyond mild headache) developed, and the repeat PCR for JC Virus (JCV) DNA detection performed 10u2005weeks later was negative. This case suggests that: (1) periodic brain MR scans may detect signs of presymptomatic PML in MS patients treated with natalizumab, (2) corticosteroid management of inflammatory reaction may contribute to optimal control of the immune reconstitution inflammatory syndrome routinely seen with natalizumab-associated PML and (3) early radiological detection of PML can have an excellent outcome even in a clinically critical region and despite prior immunosuppressant exposure. The potential benefit of regular MR scanning just using the T2/FLAIR modalities could be further investigated in order to detect early natalizumab-associated PML, leading to benign outcomes.

MicroRNAs tune cerebral cortical neurogenesis

MicroRNAs (miRNAs) are non-coding RNAs that promote post-transcriptional silencing of genes involved in a wide range of developmental and pathological processes. It is estimated that most protein-coding genes harbor miRNA recognition sequences in their 3′ untranslated region and are thus putative targets. While functions of miRNAs have been extensively characterized in various tissues, their multiple contributions to cerebral cortical development are just beginning to be unveiled. This review aims to outline the evidence collected to date demonstrating a role for miRNAs in cerebral corticogenesis with a particular emphasis on pathways that control the birth and maturation of functional excitatory projection neurons.

Cycling or not cycling: cell cycle regulatory molecules and adult neurogenesis

The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs) residing both in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles continuously generate neurons that populate the dentate gyrus and the olfactory bulb, respectively. The regulation of NPC proliferation in the adult brain has been widely investigated in the past few years. Yet, the intrinsic cell cycle machinery underlying NPC proliferation remains largely unexplored. In this review, we discuss the cell cycle components that are involved in the regulation of NPC proliferation in both neurogenic areas of the adult brain.

A corrected version of the Timed-25 Foot Walk Test with a dynamic start to capture the maximum ambulation speed in multiple sclerosis patients

BACKGROUNDnNo clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace.nnnOBJECTIVESnIn order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW(+)allowing a dynamic start after a 3 meters run-up.nnnMETHODSnSixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW(+).nnnRESULTSnThe T25FW(+)was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW(+) was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW.nnnCONCLUSIONnThe T25FW(+)allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs.

Partial Trisomy 4q Associated With Young-Onset Dopa-Responsive Parkinsonism

OBJECTIVEnTo describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q.nnnDESIGNnCase report.nnnSETTINGnMovement Disorder Outpatient Clinic at the University Hospital Centre, Liège, Belgium.nnnPATIENTnA 31-year-old woman.nnnMAIN OUTCOME MEASURESnClinical, neuroimaging, and genetic data.nnnRESULTSnThe duplicated region contains 150 known genes, including the α-synuclein (SNCA) gene locus. Motor and 6-[(18)F]fluoro-L-dopa positron emission tomography features are similar to those previously reported in heterozygote SNCA duplication carriers. Altered expression of other genes contained in the duplicated region may contribute to clinical features that are uncommon in the phenotypic spectrum of SNCA multiplications such as delayed developmental psychomotor milestones during infancy and musculoskeletal abnormalities.nnnCONCLUSIONnThis case report provides new insights on the genetic basis of parkinsonism.