Jean Christophe Bier

Is the Addenbrooke's cognitive examination effective to detect frontotemporal dementia?

Abstract.We evaluated the Addenbrooke’s cognitive examination (ACE), a simple instrument to differentiate frontotemporal dementia (FTD) from Alzheimer’s disease (AD), in our dementia patients clinic population. The Verbal-Language/Orientation-Memory (VLOM) ratio, which compares its language and memory scores, determines whether FTD or AD is more likely. The ACE was translated into French with adaptation maintaining the number of words in the name and address learning and delayed recall test, and with cultural adaptation for the semantic memory. The 85 included subjects had no evidence of two or more organic pathologies, after at least six months of follow-up, and an MMSE score ≥ 20/30. Patients with cognitive impairment due to alcohol intake were excluded. The diagnosis of a specific dementing illness was based on the consensus of the neurologist and neuropsychologists in the team. Thereafter, another neurologist expert in dementia, blinded to the ACE result and to the diagnosis and treatment, reviewed all cases files and proposed a diagnosis. A diagnostic agreement was reached for 79 cases (92.9%) with 40 (50.6%) dementia: 25 AD (62.5 %), 9 FTD (22.5 %).We estimated that the sensitivity for detecting dementia of an ACE score ≤ 83/100 was 90% with a specificity of 64.1%. When the ACE score was ≤ 88/100, the sensitivity for diagnosing FTD of a VLOM ratio < 2.2 was 11.1% with a specificity of 88 % and the sensitivity for diagnosing AD of a VLOM ratio > 3.2 was 72%,with a specificity of 69.4%. We conclude that, when used as originally proposed, ACE is very accurate for the detection of dementia, but much less effective in discriminating the most common frontal variant of FTD.

The French Addenbrooke’s Cognitive Examination Is Effective in Detecting Dementia in a French-Speaking Population

We evaluated the sensitivity and specificity of our French version of Addenbrooke’s cognitive examination (ACE) to detect dementia in our patient population. One hundred and fifty-eight cases were included in the study. In our patient series, the sensitivity for diagnosing dementia with a Mini-Mental State Examination (MMSE) score of ≤24/30 was 48.5%, the sensitivity of an MMSE score of ≤27/30 was 82.5% with a specificity of 72.1%, the sensitivity of an ACE score of ≤83/100 was 86.6% with a specificity of 70.5% and the sensitivity of an ACE score of ≤88/100 was 97.9% with a specificity of 59%. We conclude that the French version of the ACE is a very accurate test for the detection of dementia, and should be widely used in clinical practice.

Effects of the oral form of ondansetron on cerebellar dysfunction: a multi-center double-blind study

Abstract. The aim of this study was to assess the efficacy and the safety of ondansetron administered orally in patients with a cerebellar disorder. The study was a randomised, multi-center, double-blind trial. The patients were randomised either to oral ondansetron 8 mg or to placebo twice daily for seven days. Cerebellar dysfunction was quantified before and after treatment using the International Cooperative Ataxia Rating Scale (ICARS). We performed a global analysis (total scores), we analysed by subscores (4 subscores: oculomotor, speech, kinetic, postural) and subgroups (4 subgroups: Cerebellar Cortical Atrophy (CCA), Multiple Systemic Atrophy (MSA), Familial Cerebellar Degeneration (FCD) and miscellaneous cerebellar disorders), and we also performed an analysis by individual test items. We investigated whether ondansetron and placebo had different effects upon ICARS total scores and subscores in the 4 subgroups considered together or separately. For p values < 0.05, we subsequently applied the Mann-Whitney test to compare ondansetron and placebo effect for each individual item. We evaluated 45 of the 46 patients included. No effect was found in global analysis. We found no difference in the analysis of the ICARS subscores. Concerning the individual test items, there was a significant difference between the placebo and ondansetron for the finger-to-nose test (p = 0.049), the Heel-to-Knee test (HK); (p = 0.03), the Body Sway Eyes Closed (p = 0.017) and the Body Sway Eyes Open (BSEO); (p = 0.014). There was no significant difference for tremor in upper limbs (p = 0.32) or for gait (p = 0.49). The Mann-Whitney test showed a greater effect of ondansetron than placebo for BSEO in miscellaneous disorders (p = 0.013) and for HK in FCD (p = 0.036), but ondansetron was deleterious for HK in CCA (p = 0.019). Our study showed no effect of oral ondansetron on global cerebellar dysfunction. The analysis by subgroups showed that the oral form of ondansetron (a) is deleterious for coordination in patients with CCA, (b) has no effect upon tremor in upper limbs, and (c) has a mild effect upon posture and coordination in lower limbs in some subgroups of ataxic diseases.

Case report: cerebral vein thrombosis after subarachnoid analgesia for labour.

PurposeWe report a case of sagittal sinus thrombosis occurring after spinal analgesia for labour to highlight the difficulty of such diagnosis in the presence of postpartum atypical headache following regional anesthesia/analgesia.Clinical featuresA previously healthy 21 -yr-old, primiparous, preeclamptic parturient was admitted to the hospital at 37 weeks gestation for uterine contractions. Before pregnancy she was taking no medication other than oral contraceptives and was a non-smoker. Spinal analgesia was established on the first attempt at 8 cm of cervical dilation, in the setting of rapid progression of labour. Following an uneventful delivery, on the third day postpartum, the patient experienced gradual onset of an atypical headache with unclear postural character, followed by focal neurological signs five days later. Emergency neuroimaging revealed direct evidence of thrombosis in the posterior sagittal venous sinus. Anticoagulation was initiated with iv heparin (500 UI·kg-1·day-1). The patient’s headache decreased progressively and full motor recovery was noted by day 14 postpartum. After 24 days, the patient was discharged without any neurological disability. Common inherited thrombophilic dispositions were absent, with the exception of a decrease in protein S level.ConclusionCentral venous thrombosis, while rare, is a recognized cause of puerperium stroke. The present case highlights the importance of considering the diagnosis in the presence of postpartum atypical headache following spinal anesthesia/analgesia. Early intervention with systemic heparinization is critical when the diagnosis is confirmed.RésuméObjectifPrésenter un cas de thrombose du sinus longitudinal, survenue après une rachianalgésie de fin de travail obstétrical, pour illustrer la difficulté d’établir ce diagnostic en présence de céphalées atypiques du postpartum.Éléments cliniquesUne parturiente primipare de 21 ans, prééclamptique, antérieurement en bonne santé, est admise à l’hôpital à 37 semaines de grossesse pour contractions utérines. Avant la grossesse, elle prenait des contraceptifs oraux et ne fumait pas. La rachianalgésie est réalisée sans difficulté au premier essai, au moment où la dilatation cervicale est de 8 cm et le travail en progression rapide. Après un accouchement sans incident, au troisième jour du postpartum, la patiente présente des céphalées atypiques d’apparition graduelle à caractère postural mal défini, suivies de signes neurologiques focaux cinq jours plus tard. Un scanner cérébral et une résonance magnétique en urgence révèlent une thrombose du sinus veineux longitudinal postérieur. L’anticoagulation par héparine iv (500 UI·kg-1·jour-1) est instaurée. Les céphalées diminuent progressivement et la récupération motrice complète est établie au 14e jour du postpartum. La patiente quitte l’hôpital après 24 jours sans séquelles neurologiques. Le bilan de thrombophilie héréditaire s’est avéré négatif, à l’exception d’une baisse du niveau de protéine S.ConclusionLa thrombose veineuse centrale, bien que rare, est une cause connue d’accident vasculaire puerpéral. Il est important de tenir compte du diagnostic en présence de céphalées atypiques du postpartum après une anesthésie/analgésie rachidi-enne. L’intervention précoce par une héparinisation complète est cruciale pour la confirmation du diagnostic.

Acyclovir-resistant herpes simplex encephalitis in a patient treated with anti-tumor necrosis factor-α monoclonal antibodies

Herpes simplex virus is the most common cause of severe sporadic encephalitis. We report a case of herpes simplex type 1-encephalitis in a 50-year-old woman receiving anti-tumor necrosis factor-α monoclonal antibodies adalimumab. Although she was an acyclovir naïve patient, a mixed viral population (wild-type and acyclovir-resistant bearing a thymidine-kinase mutation) was identified in the cerebrospinal fluid. The virus in cerebrospinal fluid evolved and a second thymidine-kinase mutant virus emerged. Combined foscavir and acyclovir treatment resolved the herpes simplex encephalitis. To our knowledge, this is the first report of acyclovir-resistant herpes simplex encephalitis in a patient treated with adalimumab.

The Addenbrooke’s Cognitive Examination Revised Is as Effective as the Original to Detect Dementia in a French-Speaking Population

Introduction: This paper presents the validation of the French version of the Addenbrooke’s Cognitive Examination Revised (ACE-R). Methods: The variability of the 3 versions of the ACE-R (A, B and C), performed by the same observer, hence mainly 2 or 3 times on 119 patients showing no progression, was first calculated by Cronbach’s alpha coefficient, t test and linear regression. The alpha coefficients of the 3 versions were obtained showing that the ACE-R versions can be considered as one, and an analysis of the interobserver variability was performed by Cohen’s kappa coefficient, t test and linear regression on 12 patients. Eventually, we performed a receiver operating characteristic (ROC) analysis to compare the sensitivities and specificities to detect dementia of the ACE, the ACE-R and Mini Mental State Examination on 319 consecutive patients. Results: The ROC areas of sensitivities and specificities of the ACE and ACE-R were very similar. Two cutoffs were identified at 83/100 and 89/100 with a specificity to normality of 98.6% if the ACE-R score was ≥83 and a sensitivity to dementia of 98.4% if the ACE-R score was ≤89. Conclusion: ACE-R in French is as reliable and valid as the original version to detect dementia.

Striatal lesions: an underestimated complication of cerebral malaria?

Sirs, Cerebral malaria (CM) is characterized by altered consciousness, acute confusional state, seizures, anaemia, hypoglycaemia, brainstem involvement and retinal haemorrhage with confirmation of Plasmodium parasitaemia, when other causes of encephalopathy have been excluded. (Nguyen et al., 1996; Newton andWarrell, 1998) Brain imaging in CM typically shows an increase in brain volumewith or without cerebral oedema whereas focal cerebral lesions are usually not present (Newtonand Warrell, 1998). We here report the first description of CM complicated by bilateral striatal lesions and propose a possible physiopathological mechanism. A37-year-old right-handedBelgianman presented with fever (40 C), diarrhoea, hypotension (71/43 mmHg) and anuric renal failure 5 days after his return from Kenya where he had not taken any antimalarial prophylactic therapy. His medical history was unremarkable. Peripheral blood smear was positive for Plasmodium falciparum (40% parasitaemia). Plasma lactate was >8 mEq/l with a pH of 7, 18. Treatment by quinine 1.5 g/day was initiated. He then presented generalized tonic-clonic seizures. Brain magnetic resonance imaging showed bilateral lesions affecting globus pallidus, subthalamic nucleus and substantia nigra (Fig. 1). When he was admitted in our rehabilitation unit 2 months later, he suffered from tetraparesis and parkinsonism. Neurological examination revealed saccadic pursuit and several extrapyramidal signs including bilateral upper limbs rigidity, postural tremor and bradykinesia, a tetraparesis predominantly affecting the lower limbs with bilateral lower limb hyporeflexia. There were no pyramidal or cerebellar signs. Electrophysiological investigations disclosed an ongoing axonal sensorimotor polyneuropathy suggesting intensive care unit polyneuropathy. Striatal lesions have never been described as a complication of CM. The identified causes of bilateral striatal necrosis are severe metabolic acidosis, methanol intoxication, carbon monoxide intoxication, hypoxic encephalopathy, cyanide poisoning, venous infarction, osmotic demyelination, Wilson’s disease, Leigh’s syndrome, mitochondrial encephalopathy, haemolytic-uraemic syndrome, sickle-cell disease acidosis, metformin-induced lactic acidosis,Mycoplasma pneumoniae infection, Arthrinium-produced mycotoxin, glutaric acidemia and rare cases of familial striatal necrosis (Goodman and Norenberg, 1983; He et al., 1995; Kamei et al., 1996; Mewborne et al., 1998; Faris et al., 2000; Zambrino et al., 2000). In most of these cases, the implicated pathogenic mechanism is thought to be a preferential sensibility of striatal neurons to lactic acidosis induced by disturbance of the mitochondrial metabolism (Kamei et al., 1996). Compared with these cases, our patient presented bilateral lesions of the striatum and parkinsonism almost disappeared after 1 year of follow-up. Interestingly, there are only few descriptions of extrapyramidal syndrome associated with CM (Arya et al., 1989; Chaudhary et al., 1992) or following chloroquine therapy (Singhiet al., 1979). In these cases, neither focal brain lesion were reported nor physiopathological mechanism proposed (Singhi et al., 1979; Arya et al., 1989; Chaudhary et al., 1992). However, mild parkinsonism because of striatal lesions may have been underestimated in developing countries where CM is more frequent. In our case the co-occurrence of CM, lactic acidosis and systemic hypotensionmay explain the severity of the clinicalradiological picture (Kamei et al., 1996). In conclusion, clinicians should be aware that CMmay cause striatal lesions and should systematically search for extrapyramidal signs in patients with CM and lactic acidosis, especially when systemic hypoxia or hypotension are present.

Clinical utility and applicability of biomarker-based diagnostic criteria for Alzheimer’s disease: a BeDeCo survey

We conducted a survey regarding the medical care of patients with dementia in expert settings in Belgium. Open, unrestricted and motivated answers were centralized, blindly interpreted and structured into categories. The report of the results was then submitted to the participants in subsequent plenary meetings and through email. Fourteen experts responded to the questionnaire, confirming that recent propositions to modify Alzheimer’s disease (AD) diagnostic criteria and options have stirred up debate among well-informed and dedicated experts in the field. The opinions were not unanimous and illustrate how difficult it is to find a standardized method of diagnosing this disease. The responses to the survey suggest that application of a step-by-step pragmatic method is used in practice. Only when the combination of clinical findings and classical structural neuro-imaging is insufficient for a diagnosis or suggests an atypical presentation, additional biomarkers are considered. Interestingly, few differences, if any, were observed between the use of biomarkers in MCI and in AD. In conclusion, the Belgian experts consulted in this survey were generally in agreement with the new diagnostic criteria for AD, although some concern was expressed about them being too “amyloidocentric”. Although the clinical examination, including a full neuropsychological evaluation, is still considered as the basis for diagnosis, most experts also stated that they use biomarkers to help with diagnosis.

Hemispatial neglect and serial order in verbal working memory

Working memory refers to our ability to actively maintain and process a limited amount of information during a brief period of time. Often, not only the information itself but also its serial order is crucial for good task performance. It was recently proposed that serial order is grounded in spatial cognition. Here, we compared performance of a group of right hemisphere-damaged patients with hemispatial neglect to healthy controls in verbal working memory tasks. Participants memorized sequences of consonants at span level and had to judge whether a target consonant belonged to the memorized sequence (item task) or whether a pair of consonants were presented in the same order as in the memorized sequence (order task). In line with this idea that serial order is grounded in spatial cognition, we found that neglect patients made significantly more errors in the order task than in the item task compared to healthy controls. Furthermore, this deficit seemed functionally related to neglect severity and was more frequently observed following right posterior brain damage. Interestingly, this specific impairment for serial order in verbal working memory was not lateralized. We advance the hypotheses of a potential contribution to the deficit of serial order in neglect patients of either or both (1) reduced spatial working memory capacity that enables to keep track of the spatial codes that provide memorized items with a positional context, (2) a spatial compression of these codes in the intact representational space.

Alzheimer's disease and driving: review of the literature and consensus guideline from Belgian dementia experts and the Belgian road safety institute endorsed by the Belgian Medical Association.

Alzheimer’s disease (AD) is a highly prevalent condition and its prevalence is expected to further increase due to the aging of the general population. It is obvious that the diagnosis of AD has implications for driving. Finally, driving discussions are also emotionally charged because driving is associated with independence and personal identity. However, it is not clear how to implement this in clinical practice and the Belgian law on driving is rather vague in its referral to neurodegenerative brain diseases in general nor does it provide clear-cut instructions for dementia or AD compared to for example driving for patients with epilepsy and as such does not prove to be very helpful. The present article reviews what is known from both literature and existing guidelines and proposes a consensus recommendation tailored to the Belgian situation agreed by both AD experts and the Belgian Road Safety Institute endorsed by the Belgian Medical Association. It is concluded that the decision about driving fitness should be considered as a dynamic process where the driving fitness is assessed and discussed early after diagnosis and closely monitored by the treating physician. The diagnosis of AD on itself definitely does not imply the immediate and full revocation of a driving license nor does it implicate a necessary referral for a formal on-road driving assessment. There is no evidence to recommend a reduced exposure or a mandatory co-pilot. A MMSE-based framework to trichotomise AD patients as safe, indeterminate or unsafe is presented. The final decision on driving fitness can only be made after careful history taking and clinical examination, neuropsychological, functional and behavioral evaluation and, only for selected cases, a formal assessment of driving performance.