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Cerebrotendineous xanthomatosis (CTX) is an autosomal recessive disorder of bile acids synthesis. Patients may present with a variety of clinical manifestations: bilateral cataract and chronic diarrhea during childhood, then occurrence of neurological debilitating symptoms in adulthood (cognitive decline, motor disorders). Plasma cholestanol is used as a diagnostic marker of CTX, and to monitor the response to the treatment. Current treatment for CTX is chenodeoxycholic acid (CDCA), which was reported to improve and/or stabilize clinical status and decrease levels of plasma cholestanol. Rare published reports have also suggested a potential efficacy of cholic acid (CA) in patients with CTX. In this retrospective Franco-Belgian multicentric study, we collected data from 12 patients treated with CA, evaluating their clinical status, cholestanol levels and adverse effects during the treatment period. The population was divided in two subgroups: treatment-naive (who never had CDCA prior to CA) and non-treatment-naive patients (who had CDCA prior to CA introduction). We found that treatment with CA significantly and strongly reduced cholestanol levels in all patients. Additionally, 10 out of 12 patients clinically improved or stabilized with CA treatment. Worsening was noted in one treatment-naive patient and one non-treatment-naive patient, but both patients experienced similar outcomes with CDCA treatment as well. No adverse effects were reported from patients with CA treatment, whereas elevated transaminases were observed in some patients while they were treated with CDCA. In conclusion, these findings suggest that CA may be a suitable alternative treatment for CTX, especially in patients with side effects related to CDCA.

According to the modified Boston criteria, cerebral amyloid angiopathy (CAA) can present with lobar hematoma (LH) or superficial siderosis (SS). Recently, decreased CSF β-amyloid peptide 40 and 42 (Aβ40; Aβ42) and increased total and phosphorylated tau (t-tau; p-tau) concentrations have been described in CAA presenting with LH. Our aim was to analyze CSF biomarkers as a diagnostic tool for CAA according to the modified Boston criteria. We prospectively included patients with possible or probable CAA according to the modified Boston criteria. CSF was analyzed for t-tau, p-tau, Aβ42, and Aβ40. Data were compared with AD patients (n = 42) and controls (n = 14). Thirteen CAA patients were included, nine presenting with LH and four with SS. T-tau and p-tau levels in CAA were higher than controls, but lower than in AD. Differences in t-tau and p-tau levels between CAA versus controls and AD were all significant apart of the CAA p-tau levels comparison with controls. Aβ42 levels in CAA were significantly lower than in controls, and slightly higher than in AD, though non-significantly. Aβ40 levels in CAA were non-significantly lower than in controls, and significantly lower than in AD. Combining the findings of our study and the earlier report, we confirm that patients with suspected CAA have significantly different values for t-tau, Aβ42, Aβ42/t-tau, and Aβ40. Especially Aβ40 levels seem to be of clinical interest to differentiate CAA from AD. CSF biomarkers have to be analyzed in a larger number of CAA patients, and compared to patients with other disorders causing LH or SS.

We present a 48-year-old mother [with history of seizures, migraine, diabetes mellitus, neurosensory hearing loss, short stature, cognitive deficit, and ataxia, and onset of stroke-like episodes 3 years after initial magnetic resonance imaging (MRI)] and her 20-year-old son (with history of one strokelike episode at the moment of the initial MRI, and another stroke-like episode 3 months later, in absence of other signs) with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS, m.3243A [G tRNALeu[UUR] mutation), both showing on computed tomography (CT) bipallidal microcalcifications and on initial 3-T T2*-weighted MRI (TE = 13 ms, TR = 475 ms) large bilateral hypointensities in the pallidum and the substantia nigra (Fig. 1). Basal ganglia showed normal intensities on T1-weighted and fluid-attenuated inversion recovery (FLAIR) imaging, and very slight hypointense (i.e., nearnormal) signal on T2-weighted imaging (Fig. 1). One strokelike lesion (accompanying stroke-like symptoms) was seen on initial MRI in the son, and another stroke-like lesion occurred 3 months later, and the mother presented strokelike lesions 3 years after the initial MRI (Fig. 2). Both patients also showed cerebral and cerebellar atrophy, and slight bilateral posterior leukoencephalopathy on MRI (Fig. 2). MRI follow-up (3 years in the mother, and 3 months in the son) did not show evolution of the T2*-weighted hypointensities in the pallidum and the substantia nigra. Radiological abnormalities (sometimes absent or discrete, especially in the early stage of the disease) encountered in MELAS include cerebral and cerebellar atrophy, basal ganglia signal changes, stroke-like lesions, and leukodystrophy. Extensive calcifications are the most frequently encountered basal ganglia abnormalities in MELAS, most frequently described on CT and only rarely on MRI in the literature [1]. Basal ganglia calcifications in our two patients were discrete on CT. The extent of the MRI abnormalities, when compared with CT, may be explained by the magnetic susceptibility effect of T2*weighted imaging (potentially exaggerated by the highfield 3-T MRI used in our patients) and/or the presence of microscopic calcium and iron deposition [2, 3]. Both calcium and iron deposition in the globus pallidus have been demonstrated earlier on autopsy in MELAS [2]. T2and diffusion-weighted MRI changes and necrotizing lesions on autopsy have been reported in the substantia nigra in another mitochondrial syndrome, i.e., Leigh syndrome [4, 5]. In a general population, incidence of basal ganglia calcifications on CT scan varies between 0.6 and 0.8 % [6, 7]. Incidence increases with increasing age [7, 8]. In the elderly, basal ganglia calcifications are encountered in 38.7 % of patients on CT scan, with the globus pallidus as the most frequently involved structure [9]. The precise agematched incidence, the MRI-based incidence of age-related basal ganglia calcifications, and the pathophysiology explaining the predominant involvement of certain substructures (e.g., the pallidum in our MELAS patients and in the elderly) are unknown. When MELAS is suspected clinically, T2*-weighted MRI imaging (and thus not only CT scan) may be an interesting additional radiological tool to detect discrete calcium and/or iron deposition, especially in young patients (in whom age-related basal ganglia calcifications are less D. Renard (&) C. Campello A. Le Floch G. Castelnovo G. Taieb Department of Neurology, CHU Nimes, Hopital Caremeau, Place du Pr Debre, 30029 Nimes Cedex 4, France e-mail: dimitrirenard@hotmail.com

An 87-year-old right-handed man with untreated hypertension and hypercholesterolaemia presented with acute flinging and throwing movements of the left upper and lower limb. Clinical examination confirmed involuntary, irregular, wide amplitude movements of the left limbs consistent with left hemiballism in the absence of other neurological deficit. Blood count, CRP, glucose level, calcium, renal and liver function tests, ANF, lupus anticoagulant, anticardiolipin antibodies, thyroid function, serology of HIV, and arterial blood gas analysis were all normal. Brain MRI showed an acute infarction in the left (i.e. ipsilateral to the hemiballistic movements) subthalamic nucleus (STN) zone (Fig. 1), together with signs of chronic ischaemic microangiopathy in the brainstem and the periventricular areas (Fig. 2). [F] FDG PET performed 1 week after symptom onset revealed hypometabolism in the left hemispheric cortex (preserving only the anteromedial part of the frontal lobe) and the left caudate nucleus and the putamen (Fig. 1), probably due to deafferentation via connections between the STN and the ipsilateral basal ganglia system and the cortex, respectively. Carotid duplex sonography showed bilateral nonstenotic carotid atheroma. Electrocardiography and transthoracic echocardiography were normal. Recent infarction was probably due to occlusion of a small artery related to untreated cardiovascular risk factors. Secondary prevention treatment for ischaemic stroke was started. Neuropsychological testing 1 week after symptom onset showed a mild to moderate amnestic syndrome with preserved executive functions. Hemiballism disappeared progressively over the following months. [F] FDG PET 5 months after hemiballism onset showed near complete recovery of hypometabolism (Fig. 1), and neuropsychological testing normalized. Historically, acute hemiballism was thought to be related almost exclusively to contralateral (ischaemic or haemorrhagic) STN lesions. However, recently the era of modern neuroimaging has allowed identification of lesions often outside the STN (e.g. thalamus, globus pallidum, putamen, caudate nucleus, white matter, and cortex) [1]. The vast majority of lesions are contralateral to the hemiballism. Only a few cases with ipsilateral STN lesions have been described [2, 3]. The pathophysiology of ipsilateral hemiballism is poorly understood. The possibility that the STN exerts a bilateral control of motor function may explain this. This is supported by the observation that unilateral stereotaxic neurosurgery in Parkinson’s disease frequently results in bilateral improvement of abnormal movements. Anatomic pathways related to this bilateral control are unknown. [F] FDG PET in our patient nicely showed the connections between the STN and the other ipsilateral brain structures. DimitriRenard (&) A. Le Floch G. Castelnovo P. Labauge Department of Neurology, CHU Nimes, Hopital Caremeau, Place du Pr Debre, 30029 Nimes Cedex 4, France e-mail: dimitrirenard@hotmail.com