A clinical and neurophysiological motor signature of Unverricht-Lundborg disease.

OBJECTIVES: Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time, contributing along with myoclonus to motor disability. The purpose of the present work was to clarify the motor and neurophysiological characteristics of ULD patients. METHODS: Nine patients with genetically proven ULD were evaluated clinically (medical history collected from patient charts, the Scale for the Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale). Neurophysiological investigations included EEG, surface polymyography, long-loop C-reflexes, somatosensory evoked potentials, EEG jerk-locked back-averaging (JLBA) and oculomotor recordings. All patients underwent brain MRI. Non-parametric Mann-Whitney tests were used to compare ULD patients' oculomotor parameters with those of a matched group of healthy volunteers (HV). RESULTS: Myoclonus was activated by action but was virtually absent at rest and poorly induced by stimuli. Positive myoclonus was multifocal, often rhythmic and of brief duration, with top-down pyramidal temporospatial propagation. Cortical neurophysiology revealed a transient wave preceding myoclonus on EEG JLBA (n=8), enlarged somatosensory evoked potentials (n=7) and positive long-loop C-reflexes at rest (n=5). Compared with HV, ULD patients demonstrated decreased saccadic gain, increased gain dispersion and a higher frequency of hypermetric saccades associated with decreased peak velocity. CONCLUSION: A homogeneous motor pattern was delineated that may represent a ULD clinical and neurophysiological signature. Clinical and neurophysiological findings confirmed the pure cortical origin of the permanent myoclonus. Also, oculomotor findings shed new light on ULD pathophysiology by evidencing combined midbrain and cerebellar dysfunction.

Comparing ataxias with oculomotor apraxia: a multimodal study of AOA1, AOA2 and AT focusing on video-oculography and alpha-fetoprotein.

Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 µg/L), AOA2 (15-65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.

Switching between two targets with non-constant velocity profiles reveals shared internal model of target motion.

Several experiments have shown that smooth pursuit and saccades interact while tracking an object moving across the visual scene. It was proposed two decades ago that the amplitude of saccades triggered during smooth pursuit ('catch-up saccades') were corrected by a delayed sensory signal to account for the ongoing target displacement during catch-up saccades. However, recent studies used targets with non-constant velocity profiles and suggested that the correction of catch-up saccade amplitude must be done through an internal model of target motion. It is widely accepted that an internal model of target motion is also used by the central nervous system (CNS) to cancel inherent delays between visual input and smooth pursuit motor output, ensuring accurate tracking of moving targets. Our study proposes a new paradigm in which the target switches unexpectedly from one target with a non-constant periodic velocity profile to another with a non-constant aperiodic velocity profile. Our results confirm the hypothesis that the CNS uses an internal model of target motion to correct catch-up saccade amplitude. In addition, we reconcile the sensory delayed and the internal model of target motion hypotheses and show that a common internal model of target motion is shared within the CNS to control smooth pursuit and to correct catch-up saccade amplitude.

[Severe dysautonomia revealing Wernicke's encephalopathy]. / Dysautonomie sévère révélatrice d'une encéphalopathie de Gayet-Wernicke.

INTRODUCTION: Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated. CASE REPORT: We report the case of a 42-year-old HIV-positive women who, four days after recurrent episodes of vomiting, developed severe dysautonomia and symptoms suggestive of Wernicke's encephalopathy. Treatment with parenteral thiamine induced dramatic improvement within a few days. CONCLUSION: This case report highlights an unusual presentation of symptomatic thiamin deficiency associating severe dysautonomia with the classical manifestations of Wernicke's encephalopathy. As dysautonomia is frequently the earliest sign of beriberi, this case illustrates the continuum between these two diseases whose cause, symptomatic thiamin deficiency, is the same. It also draws attention to the multiple risk factors that may be associated, leading to symptomatic thiamin deficiency. This deficiency, while often overlooked, is frequent in HIV-infected patients. Finally, this case contributes to the discussion on the possible genetic polymorphism that may make a limited deficiency symptomatic.