BACKGROUND AND PURPOSE:Stroke-related restless legs syndrome (sRLS) secondary to ischemic lesions is an emerging entity and an interesting condition, but there are limited available data to help us further understand its underlying pathways. In this study, we characterized sRLS clinically, neuroanatomically and functionally.METHODS:Consecutive patients hospitalized in the Stroke Unit of the University Hospital of Strasbourg were assessed clinically and electrophysiologically for sRLS characteristics. They underwent brain magnetic resonance imaging for the neuroanatomical study of involved structures, and received functional evaluations with 18 F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography (PET) for glucose consumption, 123 I-FP-CIT ([123]I-2beta-carbometoxy-3beta-[4-iodophenyl]-N-[3-fluoropropyl]nortropane) single-photon emission computed tomography for dopamine reuptake and PET with 18 F-FDOPA ((3,4-dihydroxy-6-[18]F-fluoro-l-phenylalanine) for presynaptic dopaminergic synthesis.RESULTS:Sixteen patients with sRLS, eight women and eight men, aged 41-81 years, were included. The clinical characteristics of sRLS and idiopathic RLS were similar. Most patients presented with bilateral and symmetric de novo RLS. Eight patients had infarction in the lenticulostriate area (middle cerebral artery and internal carotid arteria). The body of the caudate nucleus was most commonly affected. Seven patients had sRLS secondary to ventral brainstem infarction (perforating branches of the basilar arteria) affecting the pons in six patients and the medulla oblongata in one patient. Both the corticospinal tract and the cortico-pontocerebellar fibres were lesioned in all patients with brainstem stroke. One patient had infarction in the left posterior cerebellar vermis and occipital area (posterior cerebral artery and superior cerebellar artery). Isotopic explorations showed a significantly increased dopaminergic tone in the striatum ipsilateral to lenticulostriate infarction. Dopamine fixation was normal in patients with stroke outside of the lenticulostriate area.CONCLUSIONS:Clinicians should be aware of the characteristics of sRLS for the appropriate diagnosis and treatment of this condition.

Les rythmes circadiens sont altérés dans la maladie de Parkinson idiopathique (MPI). Ils impactent la qualité de vie des patients via leur retentissements multiples (sommeil, vigilance, humeur, cognition, ….). Évaluation de différents rythmes circadiens réalisée chez 16 patients avec MPI via actimétrie, dosages salivaires de la mélatonine et échelle de chronotype (MEQ). Corrélations effectuées entre les différentes caractéristiques cliniques, les symptômes moteurs et symptômes non-moteurs. Les patients sont principalement « du matin » (MEQ 62,45 ± 7,48). Leurs 5 heures les moins actives débutent en moyenne à 0h28 et les 10 les plus actives à 08h14. Le début de la sécrétion de mélatonine moyen en lumière faible a été estimé à 20h11. L’amplitude relative (RA) est plutôt basse (0,84 ± 0,11), la variabilité intra jour ou fragmentation du cycle plutôt élevée (0,88 ± 0,21) et la stabilité inter-jours faible (0,52 ± 0,14) signifiant une atteinte de leurs rythmes veille/sommeil. Ces derniers paramètres sont corrélés de manière significative à l’apathie (LARS). Par ailleurs, les patients somnolents sécrètent moins de mélatonine salivaire (TILE, Epworth) et ont une RA moindre (PDSS). Corrélations statistiquement significatives. Renforcer les rythmes circadiens (lutter contre l’apathie et la somnolence, exposition lumineuse et activité motrice en journée, …) doit faire partie de la stratégie thérapeutique dans la MPI. Il reste incertain si les troubles du rythme circadien sont davantage une cause ou une conséquence de la neurodégénérescence.

L’altération du sommeil et la somnolence diurne excessive (SDE) font partie des symptômes non moteurs de la maladie de Parkinson idiopathique (MPI) et dégradent la qualité de vie. Évaluations du sommeil et de la somnolence réalisées chez 16 patients avec MPI via polysomnographie, TILE, actimétrie et échelles d’auto-évaluation (PSQI, PDSS, Epworth). Corrélations effectuées entre les différentes caractéristiques cliniques, symptômes moteurs et symptômes non-moteurs. 75 % des patients sont considérés comme mauvais dormeurs selon l’auto-questionnaire PSQI. Leur sommeil lent léger (SLL) était de 73,33 % du temps total de sommeil (TTS) et le sommeil lent profond (SLP) de 9,26 % (« normes » 60 % et 23 %). 40,1 % des patients présentaient une SDE objective et 45 % une SDE subjective. Selon le score d’Epworth, les hommes étaient davantage somnolents et les patients ayant une pression artérielle systolique plus élevée avaient moins de somnolence. 45,45 % de nos patients avaient un SAOS modéré ou sévère avec des TILE davantage pathologiques. Une atteinte des fonctions exécutives (diminution du score à la BREF) était corrélée à l’augmentation du SLL et la diminution du SLP. Une évolution de la maladie depuis au moins 8 ans impactait la fragmentation du sommeil et le TTS. Corrélations statistiquement significatives. En plus de la nécessité d’optimiser le traitement dans la MPI, il est primordial de mieux appréhender l’altération du sommeil qui pourrait participer à la pathogenèse de cette maladie neurodégénérative, possiblement via le rôle primordial du SLP dans le système glymphatique.

CONTEXT:Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the lower limbs often accompanied by unpleasant sensations in the legs, worsened at rest and in the evening. Symptoms are improved by movement. Its pathophysiology remains poorly understood. Lesion-related RLS has been reported, mainly in cases of stroke-related RLS involving the brainstem and lenticulostriate nuclei. Only few data of RLS in a context of spinal cord injury have been reported.FINDINGS:We report the case of a woman with secondary RLS due to hemorrhage of a spinal cord cavernoma located at T9-T10. Following recovery from the acute phase of the hemorrhage, the patient began to complain about restlessness in her legs causing impaired sleep and daytime somnolence. Polysomnographic investigations found a high index of periodic leg movements during sleep (71/hour), but no sleep disordered breathing. Iron stores were normal. Relief of symptom's severity was obtained with gabapentin 600mg in the evening.CONCLUSION/CLINICAL RELEVANCE:We hypothesize a possible involvement of the diencephalospinal pathway in the patient's RLS pathophysiology. A systematic study of focal lesions associated with RLS may contribute to improving our understanding of the pathophysiological mechanisms underlying this condition. The frequency of RLS associated with lesions of the spinal cord might be underestimated. Clinicians should be aware of spinal cord lesion-related RLS, especially as efficient treatments are available.

Le période de notre horloge biologique endogène est un peu plus longue que 24 heures. Chaque jour, le rythme endogène est réaligné sur 24 heures, notamment par sa synchronisation par l’alternance entre lumière et obscurité. Nous rapportons le cas d’un patient de 35 ans qui nous est adressé en raison d’un décalage entre le cycle lumière/obscurité de 24 heures et son rythme circadien endogène de la propension veille-sommeil qui n’est plus entraîné. Les symptômes sont apparus, sans facteur déclencheur, vers l’âge de 27 ans. Initialement il développe un syndrome de retard de phase au départ bien toléré. Ce trouble s’aggrave progressivement avec un endormissement qui devient de plus en plus tardif, un lever matinal compliqué suite à une ivresse du sommeil et devient incompatible avec des activités socioprofessionnelles régulières. À partir de l’âge de 32 ans, ce décalage de phase prend une allure de rythme hypernyctéméral (encore appelé rythme différent de 24 heures ou rythme en libre cours). Différentes approches thérapeutiques pour entraîner son rythme endogène par luminothérapie, mélatonine et modafinil avaient échoué chez un patient qui présente par ailleurs un retrait social. La mesure de différents rythmes circadiens avec agenda du sommeil et actimétries sur de longues périodes, bilans polysomnographiques et dosages itératifs de mélatonine et cortisol confirme le rythme en libre cours avec une période endogène à 25 h 37 min. Notre patient présente un profil en libre cours dans un contexte d’horloge trop longue apparu sans trouble visuel, ni trouble neurologique. Différentes stratégies de resynchronisation ont échoué, sa période circadienne endogène se situe au-delà de la gamme d’entraînement sur 24 heures. Ce trouble rare est sûrement sous-diagnostiqué dans un contexte actuel d’importantes modifications sociétales (lumière artificielle, travail posté). Une meilleure compréhension de la physiopathologie d’une période circadienne endogène allongée au-delà de la gamme d’entraînement sur 24 heures est nécessaire pour mieux soigner les sujets non-malvoyants atteints de ce trouble.

Les lésions médullaires entraînant un syndrome des jambes sans repos (SJSR) permettent d’avancer des hypothèses physiopathologiques sur la genèse du SJSR, une de celles-ci est la voie diencéphalospinale. Nous rapportons le cas d’une patiente de 47 ans présentant un SJSR secondaire à un saignement d’un angiome caverneux médullaire de niveau T9. Ce dernier se manifesta par un déficit sensitivomoteur des membres inférieurs et des troubles sphinctériens, régressifs. Sa plainte était une somnolence importante, son score d’Epworth était à 21/24, mais non objectivée au test itératif des latences d’endormissement avec une latence moyenne d’endormissement à 13,2 minutes. Elle présentait un SJSR, selon les critères de l’International Study Group for Diagnosis of Restless Legs Syndrome (IRLS), d’une sévérité modérée à 17/40 selon l’IRLS Severity Scale. La polysomnographie ne retrouva pas de troubles respiratoires du sommeil, avec un index apnée-hypopnée à 3,4 par heure. Il fut mis en évidence un syndrome des mouvements périodiques du sommeil particulièrement sévère avec un index à 71 mouvements par heure et une importante fragmentation du sommeil avec un index d’éveil et micro-éveil à 58,2 par heure. Du fait des mouvements éveillant, la rotigotine fut essayée mais mal tolérée. La gabapentine 300 mg 3 heures avant le coucher, permit une amélioration des symptômes. Ce cas illustre un SJSR secondaire à une lésion médullaire pouvant possiblement impliquer une voie dopaminergique peu connue : la voie diencéphalospinale, comprenant le noyau A11 de l’hypothalamus qui fait synapse avec diverses structures cérébrales et médullaires. D’autres cas de SJSR secondaires ont été décrits dans la littérature, mais la plupart sont secondaires à un infarctus cérébral. Même si cette présentation est inhabituelle, il est important pour les neurologues de ne pas méconnaître un SJSR secondaire à une lésion sur la voie diencéphalospinale, bien que cette voie nécessite plus d’investigations.

Le rôle de la dopamine dans le SJSR reste peu compris. Les agonistes dopaminergiques sont un traitement efficace du SJSR, mais ils peuvent également causer un syndrome d’augmentation. Par ailleurs, l’apparition d’un SJSR dans les suites d’un AVC a été décrite en cas d’infarctus des noyaux gris centraux et de la corona radiata, de la partie paramédiane du pont, du thalamus et de la capsule interne. Les patients adressés pour SJSR apparu dans les suites d’un AVC impliquant les noyaux gris centraux ont été inclus sur une période d’un an. L’IRM cérébrale a permis une évaluation structurelle de la lésion et le métabolisme neuronal a été étudié via une TEP au 18F-FDG. Le fonctionnement dopaminergique a été exploré en utilisant une TEP au 18F-F-DOPA et un DATScan. Quatre patients ont été inclus. Morphologiquement, le corps du noyau caudé était la seule structure atteinte chez tous les patients. Les données métaboliques mettaient en évidence chez les 4 patients un hypométabolisme dans le territoire de l’infarctus, dans le thalamus homolatéral et dans le cervelet controlatéral. Tous les patients avaient une augmentation de la 18F-FDOPA et une diminution de la fixation du transporteur de la dopamine en regard du putamen homolatéral. Ces données suggèrent qu’un tonus hyperdopaminergique dans le striatum puisse participer à la physiopathologie du SJSR. Par ailleurs, ces observations encouragent à étudier davantage les petites lésions bien définies en cas de SJSR symptomatique afin de mieux appréhender leur physiopathologie.

Background: Since the use of tissue plasminogen activator for acute ischemic stroke (IS), stroke care pathways have been developed for patients with suspicion of acute stroke. The aim of this prospective observational study was to analyze the stroke mimic (SM) characteristics in patients who were part of our stroke care pathway. Methods: All consecutive patients admitted in the code stroke within a 1-year period were prospectively enrolled in this study. Patients with a sudden onset of neurological focal deficit in a time window less than 4H30 as indicated for intravenous thrombolysis, had been accepted in the pathway by a neurologist who was directly contactable by the prehospital emergency medical service 24 h per day. Patients arrived directly on the MRI site without passing by the emergency department. A clinical neurological evaluation and a brain MRI with tri-dimensional time-of-flight magnetic resonance angiography were performed. The FAST score was calculated a posteriori. The final discharge diagnosis was concluded either immediately after both neurological examination and cerebrovascular neuroimaging or after other relevant investigations. We classified the discharge diagnosis into neurovascular diseases (NVDs) and into SM. Results: There were 1,361 consecutive patients admitted for suspicion of acute stroke. Sixty-two percent (n = 840) had an NVD including IS (n = 529), transient ischemic attacks (n = 236), intracranial hemorrhages (n = 68), cerebral venous thrombosis (n = 3) and neurovascular medullar pathologies (n = 4). SM represented 38% of cases (n = 521) and the most frequent discharge diagnosis was defined as headaches (18.6%), psychological disorders (16.7%), peripheral vertigo (11.9%) and epilepsy (10.6%). The comparison between the characteristics of the NVD and those of the SM groups showed some significant differences: in the SM group, women were more represented, patients were younger and the NIHSS was lower than in the NVD group. All cardiovascular risk factors were more represented in the NVD group. Concerning the symptoms, motor deficit, speech disturbances, homonymous lateral hemianopia and head and gaze deviation were more represented in the NVD group, whereas vertigo, non-systematized visual trouble, headache, confusion, weakness, neuropsychological symptoms, seizure and chest pain were significantly more frequent in the SM group. The negative predictive value of the FAST score was 64% and the positive predictive value was 76%. Conclusions: A rate of SM up to 38% of the code stroke system confirms the difficulty to distinguish clinically a stroke from another diagnosis. In this study, using cerebral MRI in first intention was of special interest in patients with acute neurological symptoms to differentiate an NVD from an SM.

Objective: The pathophysiology of restless legs syndrome (RLS) involves a dopaminergic dysregulation that remains poorly understood, with controversial data from the literature. Stroke-related RLS is a rare condition that involves primarily the basal ganglia, the paramedian pons, and the thalamus. Given these elements, we studied dopaminergic metabolism in patients with RLS secondary to lenticulostriate infarction using structural and nuclear imaging in the striatum ipsilateral to the infarction area, as compared to the contralateral side. We hypothesized that dopaminergic metabolism would be impaired in the striatum ipsilateral to stroke.Methods: In this observational case-control study, we aimed to prospectively include patients with RLS secondary to lenticulo-striate infarction, for analyses of dopamine dysfunction ipsilateral to stroke as compared to the contralateral striatum and to a control population. Four patients fulfilled inclusion criteria with either de novo RLS or major exacerbation of RLS existing prior to stroke, and all four patients were included. Structural imaging was performed using brain magnetic resonance imaging, and the stroke-induced metabolic modifications were assessed by F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET). Dopamine reuptake via DAT was explored using I-123-FP-CIT SPECT. PET with 18F-FDOPA was used to evaluate the functional integrity of the presynaptic dopaminergic synthesis.Results: The only structure damaged in all patients was the body of the caudate nucleus, right-sided for three and left-sided for one, as illustrated by magnetic resonance imaging. 18F-FDG PET showed a hypometabolism in the infarcted area, the ipsilateral thalamus, and the contralateral cerebellum. All patients displayed, in the ipsilateral putamen, increased dopaminergic tone.Conclusion: The present findings suggest that increased dopaminergic tone in the striatum may participate in the pathogenesis of RLS. These observations should encourage further research on RLS symptomatic with well-defined lesions as a promising way to further improve our understanding of its pathophysiology. (C) 2016 Elsevier B.V. All rights reserved.

Objectif Le SJSR est une affection neurologique frequente et invalidante avec des consequences pouvant etre multiples. Les difficultes rencontrees pour traiter ces patients soulignent la necessite de trouver des traitements adjuvants efficaces. L’objectif de notre etude est d’analyser l’effet de trois semaines de LT sur la severite du SJSR (score IRLS, test d’immobilisation suggere) et des mouvements periodiques du sommeil (polysomnoraphie), la qualite du sommeil (Pittsburh sleep quality index, agenda du sommeil, actimetrie, polysomnographie), le rythme circadien (agenda et actimetrie), la vigilance (Epworth, Karolinska) et l’humeur (echelle de Beck BDI-II, Spielberer questionnaire, PANAS). Methodes Etude pilote controlee avec une LT active versus une condition placebo aupres de 24 patients. Les patients sont apparies par paire selon l’âge, le sexe et la severite du SJSR en l’absence de traitement en cours. L’horaire d’exposition a la LT est adapte au prealable au rythme de chaque patient. Resultats La LT n’a pas permis d’ameliorer significativement la severite du SJSR. Toutefois, le temps de sommeil a ete significativement ameliore sous LT. Un impact favorable a egalement ete observe sur les symptomes depressifs. Conclusion L’effectif de cette etude pilote etait trop faible pour montrer des effets statistiquement significatifs et elle necessite d’etre repetee aupres d’une population plus large. Meme si la LT n’impacte pas directement la severite du SJSR, elle semble avoir un effet benefique sur la qualite du sommeil et sur l’humeur, des symptomes frequemment associes avec le SJSR. La prise en charge de la depression est particulierement delicate chez ces patients, la plupart des antidepresseurs etant connus pour aggraver le SJSR. En conclusion la LT semble constituer une approche therapeutique interessante et innovante dans le SJSR. Les effets evalues correspondent a des effets directs de la lumiere, c. a d. des effets independants de ceux qui impliquent le rythme circadien. D’autres etudes a plus large echelle sont necessaires pour confirmer ces resultats et comprendre les mecanismes sous-jacents afin de mieux definir la place de la LT.

A 73-year-old man complained at bedtime of electric shock sensations, corresponding to myoclonic-like jerks, observed solely in both arms, causing severe insomnia. These involuntary movements appeared at rest and were accompanied by an urge to move that relieved symptoms (video on the Neurology (R) Web site at Neurology.org). To date, few observations have been reported on arm restlessness and periodic movements of the upper limbs.(1,2) This variant shares common features with restless legs syndrome and periodic limb movement disorder, such as therapeutic response to dopaminergic agonists. Clinicians should be aware of restlessness of the upper limbs, which likely remains underdiagnosed and requires appropriate therapeutic management.

OBJECTIVE: To explore dopaminergic metabolism in lenticulostriate stroke-related restless legs syndrome (RLS) using MRI and isotopic explorations of both glucose and dopamine. BACKGROUND: The role of dopamine in the pathophysiology of RLS remains poorly understood. Dopaminergic agonists are an efficient treatment of RLS, but they might also cause augmentation syndrome. Further, secondary RLS related to stroke has been previously reported in the case of infarction of basal ganglia and adjacent corona radiate, paramedian pons and thalamus with contiguous internal capsule. We explored the dopaminergic metabolism in patients presenting with lenticulostriate stroke-related RLS. DESIGN/METHODS: All patients referred to our sleep disorder center and presenting with stroke-related RLS following infarction of the basal ganglia were prospectively included over a period of one year. Structural imaging was performed using cerebral MRI, whereas the neural metabolism was analysed using PET with 18F-FDG and brain dopamine was explored using both PET with 18F-F-DOPA and SPECT with 123I-FP-CIT. RESULTS: Four patients were included. For MRI study the body of the caudate nucleus was the only structure that was affected in all patients. Metabolic findings showed in all four patients a hypometabolism in the infarction area, in the ipsilateral thalamus and in the contralateral cerebellum. Three patients displayed decreased dopamine transporter binding in the ipsilateral striatum, whereas higher levels of dopamine precursor were observed in the ipsilateral putamen of all four patients. CONCLUSIONS: A systematic study of small lesions associated with RLS may contribute to understanding the pathophysiological mechanisms underlying this condition. In this regard, the body of the caudate nucleus might be an important structure. The isotopic results reinforce the hypothesis of an increased dopaminergic tone in the striatum as part of RLS pathophysiology. Thus, the efficacy with low doses of dopaminergic agonists in RLS could be explained by stimulation of inhibitory D2-like autoreceptors.

Objective. To describe a new phenotype of Pompe disease. Background. Pompe disease is a rare metabolic affection caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase encoded by the GAA gene and responsible for the degradation of lysosomal glycogen. Children with early-onset Pompe disease usually present with severe myopathy, cardiomyopathy and respiratory failure. In adults, late-onset Pompe disease (LOPD) is generally restricted to skeletal muscles. Cerebral and aortic dilative arteriopathy has been described in a few patients with LOPD, always in association with myopathy. Methods. A 52-year-old male caucasian presented with 2 acute renal infarcts in a 3-year interval. Abdominal magnetic resonance imaging (MRI) demonstrated bilateral dilative renal and iliac arteriopathy without aortic involvement. At age 53, he presented with left middle cerebral artery stroke, and brain MRI demonstrated bilateral dilative carotid and vertebral arteriopathy. The patient did not fulfill the diagnostic criteria for Marfan syndrome, and Fabry disease was not found. Pompe disease was then considered despite the patient presenting with normal motor examination and normal creatine kinase levels, echocardiography, pulmonary function tests and muscle biopsy. Results. Acid alpha-glucosidase deficiency was found in blood lymphocytes, skin fibroblasts and skeletal muscle, and the patient was compound heterozygous for 2 GAA gene pathogenic variants. Temporal artery biopsy was normal, with no glycogen accumulation. The patient was treated with oral anticoagulation, and he presented with no additional brain and kidney infarct at 1 year follow-up. As he presented with no myopathy, cardiomyopathy and respiratory insufficiency, acid alpha-glucosidase replacement therapy was not considered. Conclusion. This case demonstrates that LOPD may present as an isolated generalized dilative arteriopathy with repeated kidney and brain infarcts, and no myopathy. Pompe disease should be systematically screened in patients with generalized dilative arteriopathy. Disclosure: Dr. Echaniz-Laguna has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. Dr. Bataillard has nothing to disclose. Dr. Quenardelle has nothing to disclose.

The onset of restless legs syndrome (RLS) is usually progressive and the neural substrates underlying its pathophysiology remain to be identified. Here we report on a patient presenting with acute-onset RLS that was symptomatic of a right anteromedial pontine infarction. This case is exceptional because RLS appeared several hours before the occurrence of a regressive dysarthria clumsy-hand syndrome. Additionally, millimetric MRI sections showed that the structures possibly involved in RLS pathogenesis were the corticospinal tract, the pontine nuclei, and the pontocerebellar fibers. Although this is uncommon, clinicians should be aware that RLS characterized by a sudden onset can be a clinical manifestation related to stroke.

Background: Given the discordant results of studies that have reported cases of RLS associated with brainstem stroke and the absence of RLS in large series describing the clinical spectrum of brainstem infarctions, we decided to assess RLS in all patients admitted for brainstem stroke. Methods: All patients who were consecutively referred to the Strasbourg stroke unit for brainstem infarction were prospectively evaluated for RLS. The different parameters analyzed were the topography of the ischemic lesions (magnetic resonance imaging), the different symptoms (sensory, motor, cerebellar, cranial nerves and dysarthria) and the NIH stroke scale. Statistical analyses used the Bayesian paradigm. Results: Thirty patients have been included, and RLS was observed in three patients (10%). Two patients suffered from an exacerbation of symptoms anterior to the stroke, and the other patient a de novo, but transient, RLS. Patients with stroke-induced sensory symptoms have a higher risk to develop brainstem stroke-related RLS as compared to patients without sensory symptoms. Conclusion: The results suggest that RLS should be systematically screened in patients affected with brainstem stroke, especially in the case of stroke-induced sensory symptoms. Clinicians should be aware of this association, especially as efficient treatments are available and allow improving the management of patients affected with stroke. i 2014 S. Karger AG, Basel

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.

OBJECTIVE: To determine relative frequencies of different leukodystrophies in a cohort of patients with adult-onset and the rentability of a systematic diagnostic approach.