Igor Sibon

[123I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5–Ch6)

We evaluated in vivo the integrity of brain cholinergic pathways in Multiple System Atrophy (MSA) and the relationship between cholinergic dysfunction and motor disturbances, by measuring the vesicular acetylcholine transporter (VAChT) expression using Single Photon Emission Computed Tomography (SPECT) and [123I]-iodobenzovesamicol ([123I]-IBVM). Methods Nine patients with probable MSA and 12 healthy volunteers underwent a dynamic [123I]-IBVM SPECT–CT scan and a magnetic resonance imaging (MRI) scan. All patients were examined with the Unified MSA Rating Scale (UMSARS; subscale I = activities of daily living (ADL), II = motor and IV = disability). CT and MRI images were used to register the dynamic SPECT image to the Montreal Neurological Institute brain template, which includes the regions of interest (ROI) of striatum and Ch1 (medial septum nucleus-hippocampus), Ch4 (nucleus basalis of Meynert-cortex) and Ch5–Ch6 (pedunculopontine and laterodorsal tegmental nuclei-thalamus) cholinergic pathways. For each ROI, pharmacokinetic modeling of regional time activity curves led to the calculation of [123I]-IBVM to VAChT binding potential (BPND) value, proportional to VAChT expression. Results When compared to controls, BPND values for MSA in Ch5–Ch6 were significantly decreased in both the pedunculopontine–laterodorsal nuclei and the thalamus (p = 0.004 and p = 0.006, respectively). Additionally, thalamus BPND values were correlated with UMSARS ADL (p = 0.006), motor (p = 0.002) and disability (p = 0.02) sub-scores. UMSARS motor subscale items 13 (postural instability) and 14 (gait) were also correlated with thalamus BPND values (p = 0.04). Conclusion Ch5–Ch6 are the most affected cholinergic pathways in MSA at both cell bodies and thalamic cholinergic terminals. These results underscore the relevant role of [123I]-IBVM SPECT for improving our understanding of the pathophysiology in MSA.

Limbic encephalitis as a relapse of Whipple’s disease with digestive involvement and spondylodiscitis

IntroductionMany clinical manifestations can be related to Tropheryma whipplei infection.Case reportWe report a Tropheryma whipplei limbic encephalitis developed as a relapse of classical Whipple’s disease.DiscussionThis case is to the best of our knowledge the first proof of the effective brain–blood barrier crossing of both doxycycline and hydroxychloroquine as demonstrated by direct concentration monitoring on brain biopsy.

Gait Change Is Associated with Cognitive Outcome after an Acute Ischemic Stroke

Background: Cognition and gait have often been studied separately after stroke whereas it has been suggested that these two domains could interact through a cognitive-motor interference. Objective: To evaluate the influence of gait changes on cognitive outcome after an ischemic stroke (IS). Methods: We conducted a prospective and monocentric study including patients admitted for an acute supratentorial IS with a National Institute of Health Stroke Score ≤ 15. Cognition, gait and motor disability were evaluated at baseline, 3 months and 1 year post-stroke, using the Montreal Cognitive Assessment (MoCA), the 10-m walking test (10-MWT) and the Fugl-Meyer motor assessment (FMMA). The effect of changes in 10-MWT over the year of follow-up on MoCA changes was estimated using a generalized linear mixed model with FMMA, age and gender as covariates. Results: Two hundred and Twelve patients were included (71% male, age 64 ± 13 years old). 10-MWT improved from baseline to 1 year (p < 0.001), as did MoCA (p < 0.001) and FMMA (p < 0.001) scores. Ninety-nine patients (47%) had a MoCA <26 at 1 year. Changes in 10-MWT were independently associated with changes in MoCA (β = −0.2, 95% CI −0.24 to −0.07, Bonferroni-corrected p-value = 0.002). Analyses of MoCA sub-scores suggested that changes in gait performance was associated with changes in executive functions and recall. Conclusion: Gait performance is associated with cognitive outcome after a mild to moderate IS, suggesting that they should be managed together to improve post-stroke independence.

Impulsive aggressive obsessions following cerebellar strokes: a case study.

Out of the total ischemic stroke events, about 4 % of them affect the cerebellum [1]. Traditionally, studies on cerebellar function have focused on the motor functions. It is clear now that the cerebellum underlies numerous nonmotor networks [2] and has a role not only in higher cognitive functions [3], but also in emotional and behavioral processing [4]. ‘‘Mr. M’’ is a 56-year-old left-handed man with 11 years of educational level and was professionally active (baker). His medical history reveals neither significant previous medical history nor any mental disorder. He was admitted for a sudden vertigo and dysarthria and left paresthesia. Brain MRI showed a right cerebellar punctiform infarction (lobule VI). A stroke recurrence occurred few days later, with similar minor symptoms. Brain MRI demonstrated a new ischemic lesion in the left superior cerebellar artery territory (lobule VI), and in a right perforating branch of the pons (pyramidal tract) (Fig. 1). In the acute phase of stroke, Mr. M presented a moderate level of anxiety, but he had no apathy, depression or cognitive disorders when assessed by reliable scales (data available on request). Five months after stroke, the patient started to experience invasive obsessive thoughts leading to an important distress. The content of these obsessions focus on an unacceptable theme: stabbing a relative. The intensity of these obsessions was associated with daily life alteration, avoidance behavior and anxiety. In the distress to an immediate hetero-aggressive gesture by cold steel on his daughter, he committed impulsive suicide attempts by drowning. In this context, he was hospitalized in a psychiatric hospital with the final diagnosis of obsessive– compulsive disorder (OCD) complicated by a major depressive disorder (MDD). Following the recent guidelines for pharmacotherapy in OCD [5], first-line selective serotonin reuptake inhibitor (SSRI) (escitalopram, sertraline, paroxetine) then second-line antidepressant (venlafaxine) until the dosage of 225 mg/day with antipsychotic as adjunctive therapy (risperidone 2 mg/day) were tried but they failed. At last, the combination of diazepam (20 mg/day), paroxetine (40 mg/day) and quetiapine (100 mg/day) was efficient for MDD but failed to significantly improve the impulsive aggressive obsessions leading to recurrent hospitalizations. Cognitive behavioral therapy (CBT) was tried but was unfortunately poorly efficient on obsessions. A meta-analysis in 2008 reported that lobule VI is involved in emotional processing by a cerebellar-limbic circuit [6]. Chronology and infarct localization suggest that the second cerebellar stroke, involving lobules VI and Crus I, was preferentially responsible of the onset of psychiatric disorder and fully supports our hypothesis. However, we cannot exclude the potential influence of the first stroke’s stress, or the influence of bilateral lesions. The cerebellum seems to be less activated in patients with OCD [7, 8], but there is a lack of studies exploring the clinical implications of this phenomenon. Several studies & Arnaud Tessier atessier@ch-perrens.fr