Determinant of the cerebellar cognitive affective syndrome in Friedreich's ataxia.

BACKGROUND: Individuals with Friedreich's ataxia (FRDA) display significantly lower performances in many cognitive domains with a pattern of impairment that falls within the cerebellar cognitive affective syndrome (CCAS). OBJECTIVE: To assess in a large cohort of individuals with FRDA, the main determinant of the CCAS using multiple variable regression models. METHODS: This is a monocentric observational study that included 39 individuals with FRDA. Ataxic motor symptoms were evaluated with the SARA and cognitive functions with the CCAS-Scale (CCAS-S). Age, SARA, GAA1, Age of symptoms onset (ASO), Age and disease duration (DD) were chosen as covariates in a linear regression model to predict CCAS-S failed items and covariates in a logistic regression model to predict definite CCAS. RESULTS: Patients mean age, SARA score, ASO, DD and GAA1 were respectively of 29 ± 14, 22 ± 10, 14 ± 11, 15 ± 9 and 712 ± 238 (4 point-mutations). Mean CCAS-S raw score was of 86 ± 16, mean number of failed items was 2.9 ± 1.6. Twenty-three individuals had definite CCAS. The multiple linear regression model with age, SARA, ASO, DD & GAA1 as covariates was statistically significant to predict CCAS-S failed items. The SARA was the only significant coefficient in regression models for predicting CCAS-S failed items number and the definite CCAS occurrence. CONCLUSIONS: CCAS is highly prevalent in adult individuals with FRDA. CCAS is predicted by ataxic motor symptoms severity. This finding supports common core cerebellar pathophysiology in both cognitive and motor symptoms in FRDA and warrants screening for CCAS, especially in patients with SARA > 20.

Insights in the pathophysiology of haemorrhagic strokes in a sub-Sahara African country, an epidemiological and MRI study.

OBJECTIVE: Intra-cerebral Haemorrhage (ICH) seems more prevalent in sub-Saharan Africa (SSA) than in High-Income Countries (HIC) with poorer clinical outcome. Higher impact of hypertension and/or amyloid angiopathy could account for this disproportion. Here, we sought to (i) retrospectively compare ICH clinical and imaging patterns in Belgium and Guinea and in a subsequent cohort (ii) prospectively compare brain MRI characteristics to seek evidence for a different proportion of amyloid angiopathy patterns. METHODS: Ninety one consecutive patients admitted for spontaneous ICH at Brussels Erasme-ULB Hospital and at Conakry Ignace Deen-UGANC were retrospectively compared in terms of ICH volume estimated with the ABC/2 method, clinical characteristics and modified ranking (mRS) score at 30 days. mRS was dichotomised as good outcomes (≤3) and poor outcomes (>3). A prospective cohort of 30 consecutive patients with ICH admitted at CHU Conakry Ignace Deen-UGANC was prospectively included to undergo brain MRI. Results of the Guinean MRI were compared to 30 patients randomly selected from Brussels' initial cohort. Paired Student's t-test and Mann-Whitney u-test were used for group comparisons. RESULTS: Age of ICH onset was higher in Belgium (68 ± 17 years vs. 56 ± 14 years, P < 0.01) while ICH volume and 30-day mortality rate were higher in Guinea (20 ml vs. 11 ml, P < 0.01 and mortality 33% vs. 10 %, P < 0.01). ICH burden in survivors in Conakry and Brussels showed respectively good outcomes in 56.7% and 60.4% (P = 0.09) and poor outcomes in 10.3% vs. 29.6% (P < 0.001). MRI analysis of the prospective cohort failed to disclose significant differences regarding brain MRI characteristics. CONCLUSIONS: Intra-cerebral Haemorrhage affected patients 15 years younger in Guinea with larger haematoma volumes and higher mortality than in Belgium. MRI findings did not show more prevalent amyloid angiopathy pathology suggesting that better primary prevention of hypertension could positively impact ICH epidemiology in Guinea.

OBJECTIF: L'hémorragie intracérébrale (HIC) semble plus répandue en Afrique subsaharienne (ASS) que dans les pays à revenu élevé (PRE), avec des résultats cliniques moins bons. Un impact plus élevé de l'hypertension et/ou de l'angiopathie amyloïde pourrait expliquer cette disproportion. Ici, nous avons cherché à (i) comparer rétrospectivement les schémas cliniques et d'imagerie de l'HIC en Belgique et en Guinée et dans une cohorte subséquente (ii) comparer de manière prospective les caractéristiques de l'IRM cérébrale pour rechercher des preuves d'une proportion différente des profils d'angiopathie amyloïde. MÉTHODES: 91 patients consécutifs admis pour HIC spontanée à l'hôpital Erasme-ULB de Bruxelles et à Ignace Deen-UGANC de Conakry ont été rétrospectivement comparés en termes de volume d'HIC estimé avec la méthode ABC/2, les caractéristiques cliniques et le score de classement modifié (mRS) à 30 jours. Le mRS a été dichotomisé en bons résultats (≤3) et mauvais résultats (>3). Une cohorte prospective de 30 patients consécutifs atteints d'HIC admis au CHU Ignace Deen-UGANC de Conakry a été incluse de manière prospective pour subir une IRM cérébrale. Les résultats de l'IRM guinéenne ont été comparés à ceux de 30 patients sélectionnés aléatoirement dans la cohorte initiale de Bruxelles. Le test t de Student apparié et le test u de Mann-Whitney ont été utilisés pour les comparaisons de groupe. RÉSULTATS: L'âge d'apparition de l'HIC était plus élevé en Belgique (68 ± 17 ans vs 56 ± 14 ans, P < 0,01) tandis que le volume de l'HIC et le taux de mortalité à 30 jours étaient plus élevés en Guinée (20 ml vs 11 ml, P < 0,01 et mortalité 33% vs 10%, P <0,01). La charge de l'HIC chez les survivants à Conakry et à Bruxelles a montré respectivement de bons résultats dans 56,7% et 60,4% (P = 0,09) et de mauvais résultats dans 10,3% vs 29,6% (P < 0,001). L'analyse IRM de la cohorte prospective n'a pas permis de révéler de différences significatives concernant les caractéristiques de l'IRM cérébrale. CONCLUSIONS: L'HIC a touché des patients 15 ans plus jeunes en Guinée avec des volumes d'hématomes plus importants et une mortalité plus élevée qu'en Belgique. Les résultats de l'IRM n'ont pas montré de pathologie angiopathique amyloïde plus répandue, ce qui suggère qu'une meilleure prévention primaire de l'hypertension pourrait avoir un impact positif sur l'épidémiologie de l'HIC en Guinée.

Stroke burden in Guinea: Results from the Conakry Ignace Deen Hospital stroke registry.

Sub-Saharan Africa has extremely high stroke prevalence and case fatality. Most Sub-Saharan African regions are uncharted in terms of stroke characteristics, epidemiology, and burden. We report here the results from the first stroke registry in Guinea.

Epileptic activity in neurological deterioration after ischemic stroke, a continuous EEG study.

OBJECTIVE: Despite improvement in acute stroke care, almost 40% of patients with ischemic stroke present neurological deterioration. Neurological deterioration is associated with higher death and dependency rates. Neurological deterioration mechanisms are unknown, and half of neurological deterioration remains unexplained. We postulate that a substantial proportion of neurological deterioration in ischemic stroke is associated with periodic discharges/non-convulsive seizures that negatively impact the recovery of ischemic stroke and worsen symptoms. METHODS: Retrospective review of 24 h continuous EEG monitoring (cEEG) performed for neurological deterioration in the stroke unit of a tertiary academic centre. RESULTS: Eighty-one patients were included. cEEG detected epileptic activities in 44% of cases (Non-convulsive seizures/non-convulsive status epilepticus: 10/81 (12%), periodic discharges: 17/81 (21%) and sporadic epileptiform discharges in 14/81 (17%)). The proportion of patients who did not receive recanalization therapy was significantly higher in the NCSE/NCSz/PDs group than in the group devoid of NCSE/NCSz/PDs: 17/22 (77%) vs 13/59 (22%); p < 0,001. Treatment of Non-convulsive seizures /non-convulsive status epilepticus and periodic discharges was followed by EEG improvement in respectively 7/8 and 10/16 of treated patients. CONCLUSIONS: Non-convulsive seizures /non-convulsive status epilepticus /periodic discharges are associated to neurological deterioration after ischemic stroke. SIGNIFICANCE: Treatment of Non-convulsive seizures /non-convulsive status epilepticus and periodic discharges, if such patterns are detected, could help prevent adverse metabolic consequences of epileptic activities on ischemic brain tissue.

Neuromagnetic Cerebellar Activity Entrains to the Kinematics of Executed Finger Movements.

This magnetoencephalography (MEG) study aims at characterizing the coupling between cerebellar activity and the kinematics of repetitive self-paced finger movements. Neuromagnetic signals were recorded in 11 right-handed healthy adults while they performed repetitive flexion-extensions of right-hand fingers at three different movement rates: slow (~ 1 Hz), medium (~ 2 Hz), and fast (~ 3 Hz). Right index finger acceleration was monitored with an accelerometer. Coherence analysis was used to index the coupling between right index finger acceleration and neuromagnetic signals. Dynamic imaging of coherent sources was used to locate coherent sources. Coupling directionality between primary sensorimotor (SM1), cerebellar, and accelerometer signals was assessed with renormalized partial directed coherence. Permutation-based statistics coupled with maximum statistic over the entire brain volume or restricted to the cerebellum were used. At all movement rates, maximum coherence peaked at SM1 cortex contralateral to finger movements at movement frequency (F0) and its first harmonic (F1). Significant (statistics restricted to the cerebellum) coherence consistently peaked at the right posterior lobe of the cerebellum at F0 with no influence of movement rate. Coupling between Acc and cerebellar signals was significantly stronger in the afferent than in the efferent direction with no effective contribution of cortico-cerebellar or cerebello-cortical pathways. This study demonstrates the existence of significant coupling between finger movement kinematics and neuromagnetic activity at the posterior cerebellar lobe ipsilateral to finger movement at F0. This coupling is mainly driven by spinocerebellar, presumably proprioceptive, afferences.

Neural Basis of Early Somatosensory Change Detection: A Magnetoencephalography Study.

The mismatch negativity (MMN) reflects the early detection of changes in sensory stimuli at the cortical level. The mechanisms underlying its genesis remain debated. This magnetoencephalography study investigates the spatio-temporal dynamics and the neural mechanisms of the magnetic somatosensory MMN. Somatosensory evoked magnetic fields elicited by tactile stimulation of the right fingertip (Single), tactile stimulation of the right middle phalanx and fingertip (Double) or omissions (Omitted) of tactile stimuli were studied in different paradigms: in oddballs where Double/Omitted followed a sequence of four Single, in sequences of two stimuli where Double occurred after one Single, and in random presentation of Double only. The predictability of Double occurrence in oddballs was also manipulated. Cortical sources of evoked responses were identified using equivalent current dipole modeling. Evoked responses elicited by Double were significantly different from those elicited by Single at the contralateral secondary somatosensory (cSII) cortex. Double elicited higher cSII cortex responses than Single when preceded by a sequence of four Single, compared to when they were preceded by one Single. Double elicited higher cSII cortex response when presented alone compared to when Double were preceded by one or a sequence of Single. Omitted elicited similar cSII cortex response than Single. Double in oddballs led to higher cSII cortex responses when less predictable. These data suggest that early tactile change detection involves mainly cSII cortex. The predictive coding framework probably accounts for the SII cortex response features observed in the different tactile paradigms.

[Endovascular treatment of ischemic strokes : outcomes and practical issues]. / Intégration de la thrombectomie mécanique dans le traitement de l'AVC ischémique en phase aiguë : rôle et mise en oeuvre.

INTRODUCTION: Ischemic stroke is a leading cause of disability and death due to brain arterial occlusion and subsequent ischemia. Acute treatment aims to recanalize the occluded artery as soon as possible. Treatment to achieve recanalization of the occluded artery has evolved during the last couple of years. First therapeutic improvement : intra-veinous thrombolysis (IV rt-PA) was the first validated treatment to achieve reduction in ischemic stroke morbi-mortality. However, rt-PA is efficient in the first hours of stroke onset and for small calibers occluded vessels. Second therapeutic improvement : since 2015, mechanic thrombectomy in combination with IV rt-PA or alone, extended acute ischemic stroke treatment to large vessel occlusions that are responsible for most death and disability in stroke patients, and this, in a time window less restrictive than the 4,5hours after which the rt-PA is no longer effective. Discussion and practical issues : the aim of acute ischemic stroke treatment is to recanalize as soon as possible the occluded vessel to preserve as much viable brain tissue as possible. Here, we propose to base stroke work-up on injected brain computed tomography : before the contrast is injected, brain CT is sufficient for rt-PA infusion decision, then contrast injection can be made within another vein while rt-PA is injected to select patients with proximal occlusion in need of thrombectomy.

INTRODUCTION: L'accident vasculaire cérébral ischémique (AVCi) est une cause majeure de handicap et de mortalité dû à l'occlusion d'une artère cérébrale et à l'ischémie du territoire d'aval. Pendant la phase aiguë, le principe du traitement vise à recanaliser le plus rapidement possible l'artère occluse. Ces traitements ont considérablement évolué ces dernières années. Première révolution thérapeutique : l'injection IV d'un traitement thrombolytique (rt-PA) a permis, en phase aiguë, de diminuer le handicap et la mortalité liés à l'AVCi. Cependant, le rt-PA n'est efficace que dans les heures qui suivent le début des symptômes et pour des vaisseaux occlus de petit calibre. Seconde révolution thérapeutique : depuis 2015, la thrombectomie mécanique, combinée ou non au rt-PA IV, a permis d'étendre les possibilités de recanalisation aux vaisseaux de gros calibre dont les occlusions sont responsables de la majorité des décès et des handicaps sévères, et ce, dans un intervalle de temps moins restrictif que les 4h30 au-delà de laquelle la rt-PA n'est plus efficace. Discussion et mise en oeuvre pratique : l'objectif du traitement de l'AVCi en phase aiguë est de recanaliser le plus rapidement l'artère occluse pour préserver un maximum de tissu cérébral viable. Nous utilisons le CT-scan cérébral comme méthode diagnostique : à blanc, il permet de décider l'administration de rt-PA IV ; après injection de produit de contraste, l'angioscanner et le scanner de perfusion permettent de sélectionner les patients éligibles pour une thrombectomie sans retarder l'injection du rt-PA.

Yield of training exchanges between Europe and Sub-Saharan Africa.

Opportunities that allow neurologists-in-training from Western Europe and Sub-Saharan Africa to benefit from exchanges between their respective neurological departments are rare. In a pilot exchange program, we compare the patterns of neurological diseases encountered in neurological wards of public hospitals in Brussels and Yaoundé to underline educational benefits. For 5 months the age, sex, mortality, HIV cases and clinical characteristics of admitted patients were prospectively analyzed. Eighty Cameroonian and 105 Belgian patients were classified into the following neurological entities: infectious, vascular, immune-related, epileptic, degenerative, neoplastic, psychogenic and movement disorders. Means and proportions were compared using Student's test and Fisher's exact test, respectively. Patients were younger in Yaoundé (mean age 45.3 vs. 54.0 years, p = 0.002), but died four times more (23.75 vs. 4.75 % of admissions, p < 0.001). HIV proportion was 43.75 % in Yaoundé and nil in Brussels. Infectious complications were responsible for 100 % of deaths in HIV-positive patients against 44 % in HIV-negative patients (p = 0.0108). The proportions of vascular, neoplastic and movement disorders were comparable. Neurological complications of infections occurred ten times more in Yaoundé (69 vs. 6.7 %, p < 0.0001). Multiple sclerosis accounted for 11.4 % of admissions in Brussels but other immune-related diseases were more frequent in Yaoundé (8.75 vs. 2 %, p = 0.04). Epileptic, degenerative and psychogenic diseases were more frequent in Brussels: 38.1 versus 12.5 % (p < 0.001), 16.2 versus 5 % (p < 0.0194) and 3.75 versus 14.3 % (p < 0.0224), respectively. Exchanges between Western Europe and Sub-Saharan neurological wards could offer neurologists-in-training firsthand experience with diseases seldom met; otherwise, an understanding of different healthcare systems and a better understanding of the concept of neurology as a public health challenge.

Acute behavioural change in a young woman evolving towards cerebellar syndrome.

Symptomatic paraneoplastic neurological syndromes are rare manifestations of cancers. Recently, a new type of encephalitis associated with antibodies against NMDA-glutamate receptors (A-NMDAR) was defined. The patients, usually young women, present with acute onset of psychiatric symptoms and decreased consciousness. We describe the case of a patient who presented with acute onset of delirium alternating with sub-comatose state. Blood analyses were within normal range. Lumbar puncture showed lymphocytic pleiocytosis. Brain gadolinium injected MRI, brain and full body PET scans were normal. Investigations led to suspect a paraneoplastic syndrome and a right ovarian teratoma and A-NMDAR were found and the teratoma removed. The remaining sequellae included a cerebellar syndrome seldom described before. As cerebellar and cortical neurons share the same excitatory pathway through NMDA-glutamate receptors, the cerebellar function impairment observed in our patient could be explained by a disabling action on glutamate NMDAR by the A-NMDAR.

[Misdiagnosis of sinus thrombosis with reversible posterior leucoencephalopathy]. / Thrombose ou hypoplasie veineuse cérébrale avec leucoencéphalopathie postérieure réversible.

Reversible posterior leucoencephalopathy and cerebral venous thrombosis share many symptoms. Both of them may lead to coma, and cause epilepsy or focal neurological signs. Moreover, diffuse leucoencephalopathy can be observed in both cases. Cerebral venous thrombosis needs anticoagulation which is not a riskless treatment. We describe a case of reversible posterior leucoencephalopathy in an hypertensed, seventy-year old man, presenting with a left lateral sinus hypoplasia whose clinical history and paramedical results first suggested a cerebral veinous thrombosis. Our case shows the misleadings a congenital vascular asymmetry can induce when confronted with a subacute coma.

B-cell lymphoma presenting with renal failure associated to spontaneous tumor lysis syndrome and urinary tract obstruction.

The acute tumor lysis syndrome (ATLS) may be a dramatic complication of anticancer treatment. It occurs mostly in haematological malignancies and less commonly in solid tumors. Spontaneous tumor lysis syndrome (STLS) has been reported more frequently in Burkitt's lymphomas than in other haematological tumors, and exceptionally in solid tumors like small-cell lung carcinoma and germ-cell tumors. We report on the case of a patient with a diffuse large B-cell lymphoma (DLBCL) of the urinary tract involved by acute renal failure due to STLS and complicated by obstructive uropathy subsequent to neoplastic infiltration of the bladder. Hyperhydration, urine alkalinization, urate oxidase administration and continuous veno-venous haemodiafiltration (CVVHDF) permitted to control the initial renal failure and to administer chemotherapy. The patient then developed chemotherapy-induced tumor lysis syndrome (TLS) controlled by urate oxidase administration, hyperhydration and urine alkalinization. The treatment of TLS and the differences between ATLS and STLS are discussed.