French validation of the Quality of life in Essential Tremor Questionnaire (QUEST) and the Essential Tremor Embarrassment Assessment (ETEA).

Two scales have been developed and validated in English to evaluate the impact of tremor on daily life, namely Quality of life in Essential Tremor Questionnaire (QUEST) and Essential Tremor Embarrassment Assessment (ETEA). The psychometric properties of the French version of these two scales were assessed for 117 patients with head tremor. Both scales showed excellent acceptability, very good internal consistency (Cronbach's alpha coefficient>0.8) and reproducibility (Lin concordance coefficient>0.8), satisfactory external validity and satisfactory sensitivity to change. In conclusion, the French versions of QUEST and ETEA are comprehensive, valid and reliable instruments for assessing patients with head tremor.

Functional Neurological Disorders in the medical education: An urgent need to fill the gaps.

BACKGROUND: FND is a disabling disease that accounts for 5 to 10% of the reason for consultation in neurology. However, young physicians often say they have little or no training in their management. AIM: The aim of the present study was to assess whether French junior neurologists, psychiatrists and physical and rehabilitation medicine (PRM) specialists received teaching on FND during their medical studies, including the residency, and to evaluate their knowledge and perception of the disorder. METHODS: The survey was distributed by the means of a Google form questionnaire to specialist registrars and young specialists with the help of resident's organizations. RESULTS: 568 respondents from the 3 specialties were included in the study. Most respondents (72.4%) were specialists registrars. Almost half of the respondents (45.5%) answered they never received any teaching on FND, and only 20.5% of them knew the Hoover's sign, a positive sign specific of functional weakness. A large majority of respondents felt they were not sufficiently trained in FND (87.9%), and they did not have sufficient knowledge of these disorders (85.3%). DISCUSSION: Better training would allow clinicians to make a diagnosis earlier, to better explain it to patients, and to limit the costs associated with diagnosis delays. A better training of clinicians about FND would also improve the prognosis of patients, as early diagnosis and good explanation is associated with a better prognosis. CONCLUSION: This survey shows that there is a gap about FND in the training programs in the medical studies and during the specialization training of young doctors in France.

Botulinum toxin therapy improves masseter spasticity in Amyotrophic Lateral Sclerosis.

Fifteen ALS patients, with troublesome symptoms linked to masseter spasticity, benefited from BoNT-A injections in each masseter. Based on the medical records of patients, the effect of the first injection was assessed one month later. We retrospectively collected information for 12 patients. Eight of them reported a beneficial effect after the injection for the following symptoms: trismus, tongue, lip and cheek biting, and jaw clonus. Five patients indicated that dental care was easier after injection. Our study showed that injections of BoNT-A unequivocally reduced masseter spasticity in ALS patients who subsequently enjoyed greater comfort in their daily living.

The "Neurological Hat Game": A fun way to learn the neurological semiology.

INTRODUCTION: In-class courses are deserted by medical students who tend to find it more beneficial to study in books and through online material. New interactive teaching methods, such as serious games increase both performance and motivation. We developed and assessed a new teaching method for neurological semiology using the "Hat Game" as a basis. METHODS: In this game, two teams of second-year medical students are playing against one another. The game is played with a deck of cards. A neurological symptom or sign is written on each card. Each team gets a predefined period of time to guess as many words as possible. One member is the clue-giver and the others are the guessers. There are three rounds: during the first round, the clue-giver uses any descriptive term he wants and as many as he wants to make his team guess the maximum number of words within the allocated time. During the second round, the clue-giver can only choose one clue-word and, during the third round, he mimes the symptom or sign. The team that has guessed the most cards wins the game. To assess the efficacy of this learning procedure, multiple choices questions (MCQs) were asked before and after the game. Exam results of second-year students on their final university Neurology exam were analyzed. A satisfaction survey was proposed to all participating students. RESULTS: Among 373 students, 121 volunteers (32.4%) were enrolled in the "Neurology Hat Game" and 112 attended the game. One hundred and seven of the 112 students completed the MCQs with a significant improvement in their responses after the game (P<0.001). The 112 students who completed the satisfaction self-administered questionnaire were very satisfied with this funny new teaching method. CONCLUSIONS: Teaching neurological semiology via the "Hat Game" is an interesting method because it is student-centered, playful and complementary to the lecturer-centered courses. A randomized controlled study would be necessary to confirm these preliminary results.

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.

"De-novo" consultation: Evaluation of an outpatient's clinic dedicated to early diagnosis of parkinsonian syndromes.

INTRODUCTION: In the absence of specific clinical signs, imaging or biomarkers, the differential diagnosis of degenerative parkinsonian syndromes may be difficult at early stages of the disease. To reduce the risk of misdiagnosis or delayed diagnosis and referral to multiple medical centers at disease onset, easier access to expert centers should be available. To improve the initial care of parkinsonian patients, the Parkinson's disease Expert Center (PEC) at Pitié-Salpêtrière Academic Hospital has set up a specific outpatients clinic with short waiting times dedicated to the diagnosis of early Parkinson's disease and related disorders. METHODS: The PEC setup first identifies requests for diagnostic confirmation of parkinsonian syndromes, then specific outpatients clinic visits are scheduled weekly, with examinations carried out by neurologists at the PEC on a rotating schedule. Data from the first year of the new procedure were analyzed retrospectively through self-administered questionnaires sent to patients seen during this period. The main outcomes were to confirm the ability to keep to short delays for patients' examinations and to assess patients' satisfaction with the setup. RESULTS: Both study outcomes were achieved. The creation of an outpatients clinic dedicated to the early diagnosis of parkinsonian syndromes allowed shorter delays before the first examination of 5 weeks instead of several months. Keeping to the weekly schedule and limited time taken for each visit was also achieved. Following this initial outpatients visit, diagnosis of a parkinsonian syndrome was clinically confirmed or further specified in 80% of cases. A survey of patients' satisfaction showed a rate of over 91% in terms of the timing and course of clinical examinations at our PEC. DISCUSSION/CONCLUSION: This study of our quality-improvement program for Parkinson's disease management has shown that specific consultations with shorter waiting times aiming to allow early specialized assessment of parkinsonian syndromes is beneficial for patients and reduces the risk of delayed diagnoses.

Preservation of the hyperdirect pathway of basal ganglia in a rodent brain slice.

Basal ganglia are a network of interconnected nuclei, involved in motor control, goal-directed behaviors and procedural learning. Basal ganglia process information from the cerebral cortex through three main pathways. The striatum is the input nucleus of the direct (cortico-striato-nigral) and indirect (cortico-striato-pallido-subthalamo-nigral) pathways while the subthalamic nucleus (STN) is the input structure of the hyperdirect (cortico-subthalamo-nigral) pathway. Despite the fact that the hyperdirect pathway constitutes a central part of most of basal ganglia models, experimental studies concerning its synaptic transmission and plasticity are still lacking. This is mainly because in vitro brain slices do not preserve the hyperdirect pathway. Here, we address this by developing a hyperdirect pathway brain slice where cortico-subthalamo-nigral connections were preserved. We characterized the transmission properties and its monosynaptic features between the frontal cortex and the STN, and between the STN and the substantia nigra pars reticulata (SNr), the output nucleus of the hyperdirect pathway. Cortical stimulation evoked monosynaptic glutamatergic events in STN neurons with a mean latency of 11.3 ms and a mean amplitude of 21 pA. STN stimulations evoked monosynaptic glutamatergic events in SNr neurons with a mean latency of 2.5 ms and a mean amplitude of 116 pA. This brain slice also preserved a part of the direct and indirect pathways such as the cortico-striatal connection. This novel slice configuration containing the hyperdirect pathway is a useful tool to better understand the transmission and plasticity in this pathway and hence the physiology and the pathophysiology of basal ganglia.

C2orf37 mutational spectrum in Woodhouse-Sakati syndrome patients.

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder that encompasses hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. The syndrome is caused by mutation of the C2orf37 gene. Here we studied a cohort of seven new cases from three ethnic backgrounds, presenting with the hallmarks of WSS, in an effort to extend the mutational spectrum of this disorder. Genetic analysis revealed a novel mutation in each of the four families investigated, of which three were nonsense mutations and the fourth was a splice site ablation. We also examined a separate collection of 11 cases presenting with deafness and dystonia, two constituents of WSS, but found no pathogenic changes. This study doubles the number of known mutations for this disorder, confirms that truncating mutations in C2orf37 are the only known cause of WSS, and suggests that mutations in this gene do not contribute significantly to cases presenting with isolated elements of WSS such as deafness and dystonia. The lack of correlation between clinically expressivity of WSS and the site of the eight truncating mutations strongly supports that they are equally null, while the intrafamilial variability argues for an important role of modifiers in this disease.

[Ataxia associated with gluten sensitivity, myth or reality?]. / Ataxie avec sensibilité au gluten, mythe ou réalité?

INTRODUCTION: Gluten ataxia refers to the association of idiopathic ataxia despite exhaustive investigations with gluten sensitivity defined by anti-gliadin antibodies (AGA) presence in blood. This is a controversial concept. PATIENTS AND METHODS: We screened 33 patients, who were hospitalized in 2003 and had subacute or chronic ataxia for presence of circulating AGA. Twelve patients were positive and their clinical and biological features were studied. RESULTS: Among the twelve patients, we concluded that gluten ataxia was present in only eight, including one case of celiac disease. Among these eight patients, five had the usual features of gluten ataxia (progressive cerebellar ataxia affecting mainly lower limbs), but one patient presented unusual left cerebellar hemisyndrome and the two others displayed polyneuropathy with proprioceptive ataxia. Cerebellar atrophy was confirmed with magnetic resonance imaging in five cases and association with other antibodies was found in six cases. Among the four other patients positive for AGA, investigations revealed one case of multiple sclerosis, one case of late-onset Friedreich ataxia, one case of basilar tuberculous meningitis and one case of type 2 diabetes. CONCLUSION: Screening for AGA presence should be systematically performed at presentation of patients with unknown etiology ataxia; in the event AGA are present without any other etiology, treatment with gluten-free diet must be discussed. However, the responsibility of AGA in the pathogenesis of neurological signs is highly debatable and further experimental work is required. Two pathophysiological hypotheses are suggested: (1) overexpression of cerebellar epitopes, in case of primary cerebellar pathology, leading to excessive immune response directed against these epitopes; and (2) molecular mimicry with cross-reactivity of antigens usually directed against gliadin, but also recognizing Purkinje cells epitopes.

[Hereditary neuropathy with liability to pressure palsy presenting with an acute inflammatory demyelinating polyneuropathy]. / Polyradiculonévrite aiguë inflammatoire révélant une neuropathie héréditaire avec hypersensibilité à la pression.

INTRODUCTION: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant peripheral neuropathy characterized by compressive focal neuropathies and an underlying sensorimotor demyelinative polyneuropathy. It is usually caused by a 1.5 Mb deletion of the PMP22 gene (17p11.2). CASE REPORT: We describe the case of a 31 year-old woman who presented with acute demyelinative peripheral polyneuropathy affecting the four limbs and elevated cerebrospinal fluid protein content a few days after a viral illness. Acute inflammatory demyelinating polyneuropathy (AIDP, Guillain-Barré syndrome) was suspected. However, electrophysiologic examination suggested HNPP and subsequent genetic testing was confirmatory. CONCLUSION: This case demonstrates that HNPP can present in an acute manner, mimicking AIDP.