[Hiccups, not always unremarkable]. / Les hoquets : pas toujours banals.

Hiccups are most often benign and of short duration. However, they may also be persistent (superior to 48h) or even refractory (superior to 1 month). In such cases, they markedly alter the quality of life and can lead to severe impairment of health. We here review hiccups pathophysiology, etiologies, work up and treatment. We suggest that hiccups should be considered as a non-epileptic myoclonic movement disorder.

Le hoquet est le plus souvent bénin et de courte durée, mais il peut aussi être persistant (sup�rieur a 48h), voire réfractaire (sup�rieur a 1 mois). Dans ces cas, il altère la qualité de vie et peut avoir des conséquences graves sur la santé. Nous en revoyons ici la physiopathologie, les étiologies, la mise au point diagnostique et les traitements. Nous concluons par une réflexion sur la nature du hoquet que nous considérons comme un mouvement anormal appartenant au groupe des myoclonies non épileptiques.

[Paraneoplastic neurological syndromes]. / Les syndromes neurologiques paranéoplasiques.

Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.

Les syndromes neurologiques paranéoplasiques sont des complications neurologiques non métastatiques de cancers systémiques résultant, le plus souvent, d'une réaction immunitaire croisée dirigée contre des antigènes neuronaux membranaires ou intracellulaires. Certains de ces syndromes paranéoplasiques sont classiques comme les ataxies cérébelleuses, les neuronopathies sensitives ou ganglionopathies, l'encéphalite limbique, les encéphalomyélites ou le syndrome de Lambert-Eaton. Devant de tels tableaux cliniques, une étiologie paranéoplasique doit, surtout chez les patients présentant des facteurs de risque, être systématiquement recherchée. Bien que cette règle souffre de nombreuses exceptions, il y a souvent concordance entre un syndrome clinique spécifique, un type d'anticorps et une tumeur associée. Le diagnostic d'un syndrome neurologique paranéoplasique est essentiel puisqu'il révèle souvent le cancer sous-jacent. Le traitement comporte deux axes principaux : celui du cancer responsable et le contrôle de la réponse immunitaire.

[Erdheim-Chester disease : a case report]. / Cas clinique. Maladie d'Erdheim-Chester.

We report the case of a 47-year-old woman with unexplained inflammatory syndrome and asthenia. Imaging findings show bilateral abnormalities of femurs and tibias, suggesting an Erdheim-Chester disease, which is confirmed by a bone marrow biopsy of the left femur. The BRAF V600E mutation is detected, allowing the administration of targeted therapies such as BRAF and MEK inhibitors that lead to the improvement of symptoms.

Nous rapportons le cas d'une patiente de 47 ans explorée pour un syndrome inflammatoire inexpliqué et une asthénie chronique. Les examens en imagerie démontrent la présence d'importants remaniements osseux au niveau du périoste des deux fémurs et tibias, évoquant une maladie d'Erdheim-Chester. Celle-ci est confirmée par l'analyse d'une biopsie ostéomédullaire réalisée au niveau du fémur gauche. La détection de la mutation V600E du gène BRAF permet à la patiente de bénéficier d'un traitement ciblé anti-BRAF et anti-MEK, améliorant sa symptomatologie.

[Progressive ataxia and falls in a 62 year old woman]. / La vignette diagnostique de l'étudiant. Ataxie subaiguë et chutes chez une patiente de 62 ans.

We discuss the diagnostic workup of a 62 year old woman without any significant past medical history. We take this opportunity to point out three aspects : 1. The necessary contextualization of the whole process allowing to avoid unrealistic differentials; 2. The requirement to prioritize the diagnostic tests as a function of their expected contribution to the diagnosis, their invasive characteristic and their availability, including their cost and 3. The evolving character of the diagnostic process that, if needed, has to be reconsidered to integrate the information obtained from the first diagnostic tests and the evolution of the patient.

Nous discutons la démarche sémiologique et diagnostique d'un cas d'ataxie chez une patiente de 62 ans, indemne de tout antécédent médical significatif. A l'occasion de cette vignette diagnostique, nous insistons sur trois aspects : 1. La nécessité de contextualiser la démarche pour éviter d'évoquer des diagnostics différentiels irréalistes; 2. La nécessité de choisir les examens complémentaires pertinents en les hiérarchisant en fonction de la probabilité de contribuer au diagnostic, de leur invasivité et de leur disponibilité, y compris de leur coût et 3. Le caractère évolutif de la démarche diagnostique qu'il faut pouvoir remettre en question au fil des informations que fournissent l'évolution du patient et les résultats des investigations.

[Loss of balance, gait disturbance and falls in an elderly woman]. / LA VIGNETTE DIAGNOSTIQUE DE L'ÉTUDIANT. Troubles de l'équilibre, de la marche et chutes chez une patiente âgée.

We report the diagnostic workup of a 75-year old woman seen in the outpatient clinic and complaining of a very common symptom that is walking difficulty and falls. We stress the complexity of the clinical examination and of the pathophysiology of equilibrium and gait disorders. They are numerous aetiologies that are very often associated in elderly patients. The therapeutic approach is necessarily multidisciplinary, both medical and paramedical. In the particular case of the patient illustrated in this vignette, the diagnosis was myofibrillar myopathy, a rare and recently described muscle disease. This is the occasion to stress that for many rare disorders, it is the disease, but not the signs or symptoms, which is rare.

Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis.

AIMS: Synaptic vesicle proteins 2 (SV2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV2 isoforms in the hippocampus of patients with temporal lobe epilepsy (TLE). METHODS: SV2A, SV2B and SV2C immunostaining and QuantiGene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis (MTS) and compared with 10 autopsy controls. SV2 expression was further compared with Timm's staining, and synaptophysin, Zinc transporter 3 (ZnT3), dynorphin, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) expression. RESULTS: In TLE patients, SV2A and SV2B expression was decreased in areas of synaptic loss. SV2C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1A and mossy fibre sprouting but not in cases with other types of MTS. SV2C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT3 and VGLUT1, suggesting selective expression in presynaptic glutamatergic Zn(2+) -rich terminals of abnormal sprouting fibres. SV2 expression patterns correlated with histological subtypes of MTS, but not with clinical features or therapeutic regimens in this patient cohort. CONCLUSION: In classical MTS1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A and SV2B paralleling synaptic loss and a selective increase of SV2C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2C-specific strategies.

[Recurring vertigo]. / Vertiges récidivants.

We report the case of a young patient who was seen at the outpatient clinic for recurring vertigo. The diagnosis was vestibular migraine. Considering the long delay between the onset of symptoms and the definite diagnosis, we found it appropriate to review the diagnostic workup in such cases which is multidisciplinary, implying otologists, ophtalmologists and neurologists.We take also the opportunity to review the diagnosis and treatment of less known, more recently described disorders such as vestibular migraine, perilymph fistula, vestibular paroxysmia and bilateral vestibulopathy.

[Cerebrotendinous xanthomatosis, a rare, severe, but treatable metabolic disorder]. / La xanthomatose cérébro-tendineuse, une maladie métabolique rare, grave mais curable.

Cerebrotendinous xanthomatosis (CTX) is a rare and treatable autosomal recessive disease. The diagnosis should be suspected in the presence of a suggestive clinical triad characterized by early-onset cataract, tendinous xanthomata and neurological symptoms and signs, notably cerebellar ataxia, mental retardation and pyramidal syndrome.The diagnosis is confirmed by demonstrating an increased blood level of cholestanol, or/and by molecular genetic analysis.In typical cases, brain MRI shows bilateral hyperintensity of the cerebellar nucleus dentatus together with cerebral atrophy and leukoencephalopathy. The treatment is based on the administration of chenodeoxycholic acid. The aim is to restore the negative feedback on the enzymatic cascade altered by mutation in the gene CYP27 which induces a 27-hydroxylase deficiency

MicroRNAs tune cerebral cortical neurogenesis.

MicroRNAs (miRNAs) are non-coding RNAs that promote post-transcriptional silencing of genes involved in a wide range of developmental and pathological processes. It is estimated that most protein-coding genes harbor miRNA recognition sequences in their 3' untranslated region and are thus putative targets. While functions of miRNAs have been extensively characterized in various tissues, their multiple contributions to cerebral cortical development are just beginning to be unveiled. This review aims to outline the evidence collected to date demonstrating a role for miRNAs in cerebral corticogenesis with a particular emphasis on pathways that control the birth and maturation of functional excitatory projection neurons.

[Vitamin D tweets light to genes in multiple sclerosis]. / La vitamine D connecte la lumière aux gènes dans la sclérose en plaques.

The relationship between sunlight exposure and the incidence of multiple sclerosis and the understanding of immunomodulatory effects of vitamin D triggered, in recent years, a broad range of investigations. Immunological studies performed in vitro and in vivo have demonstrated how tolerogenic vitamin D can be. Epidemiological studies confirmed an increased incidence of multiple sclerosis in vitamin D deficient subjects and signs of increased disease activity in such MS patients. Although small-scale observational studies have suggested a beneficial impact of vitamin D supplementation on the incidence and severity of multiple sclerosis, large scale clinical trials remain warranted to confirm these preliminary results.

Sudden sensorineural hearing loss: when ophthalmology meets otolaryngology.

OBJECTIVES: Sudden sensorineural hearing loss is a perplexing entity in otology. Susac's syndrome (also called retinocochleocerebral vasculopathy) is a rare disorder that consists of microangiopathy of the brain, retina, and inner ear, and usually affects women in young adulthood. We describe the clinical aspects, radiographic findings, and management of one such case. CASE REPORT: A 30-year-old woman was admitted to the hospital because of sudden onset of bilateral deafness and headache. During her hospitalization, she developed discrete right hemiparesis and hypoesthesia. RESULTS: Magnetic resonance imaging revealed multiple signal hyperintensities and atrophy of the corpus callosum. The differential diagnosis was a myelinating condition, such as multiple sclerosis or acute demyelinating encephalomyelitis. CONCLUSION: Retinal fluorescein angiography helped the diagnosis of Susac's syndrome.

[Clinical vignette for the medical school student: jugular foramen syndrome]. / La vignette diagnostique de l'etudiant. Syndrome du trou déchiré postérieur (foramen jugulaire).

Cranial neuropathies are frequent and their semiological analysis is the basis of the diagnostic workup. This is even more true in the case of multiple cranial neuropathies. We here propose a diagnostic exercise in the case of a simultaneous cranial nerves IX (glossopharyngeal), X (vagus) and XI (spinal) deficit. This case exemplifies that knowledge of nervous anatomy and physiology is the basis of the semiology of the nervous system.

A corrected version of the Timed-25 Foot Walk Test with a dynamic start to capture the maximum ambulation speed in multiple sclerosis patients.

BACKGROUND: No clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace. OBJECTIVES: In order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW(+)allowing a dynamic start after a 3 meters run-up. METHODS: Sixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW(+). RESULTS: The T25FW(+)was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW(+) was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW. CONCLUSION: The T25FW(+)allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs.

[Structured differential diagnosis of a transient impairment of consciousness]. / La vignette diagnostique de l'étudiant. Diagnostic différentiel structuré d'une perte brève de conscience.

Transient impairment of consciousness frequently prompts the patient to consult a neurologist or a cardiologist. Detailed medical history and physical examination allow to distinguish fainting from epileptic seizure, metabolic or psychogenic events. We report the history of an 83-year-old woman who presented a transient loss of consciousness.The vascular, investigation demonstrated a subocclusive stenosis of one of the internal carotid arteries. We shall consider the differential diagnosis of transient impairment of consciousness and discuss the relationship between fainting and carotid artery disease.

Attitudes towards end-of-life issues in disorders of consciousness: a European survey.

Previous European surveys showed the support of healthcare professionals for treatment withdrawal [i.e., artificial nutrition and hydration (ANH) in chronic vegetative state (VS) patients]. The recent definition of minimally conscious state (MCS), and possibly research advances (e.g., functional neuroimaging), may have lead to uncertainty regarding potential residual perception and may have influenced opinions of healthcare professionals. The aim of the study was to update the end-of-life attitudes towards VS and to determine the end-of-life attitudes towards MCS. A 16-item questionnaire related to consciousness, pain and end-of-life issues in chronic (i.e., >1 year) VS and MCS and locked-in syndrome was distributed among attendants of medical and scientific conferences around Europe (n = 59). During a lecture, the items were explained orally to the attendants who needed to provide written yes/no responses. Chi-square tests and logistic regression analyses identified differences and associations for age, European region, religiosity, profession, and gender. We here report data on items concerning end-of-life issues on chronic VS and MCS. Responses were collected from 2,475 participants. For chronic VS (>1 year), 66% of healthcare professionals agreed to withdraw treatment and 82% wished not to be kept alive (P < 0.001). For chronic MCS (>1 year), less attendants agreed to withdraw treatment (28%, P < 0.001) and wished not to be kept alive (67%, P < 0.001). MCS was considered worse than VS for the patients in 54% and for their families in 42% of the sample. Respondents' opinions were associated with geographic region and religiosity. Our data show that end-of-life opinions differ for VS as compared to MCS. The introduction of the diagnostic criteria for MCS has not substantially changed the opinions on end-of-life issues on permanent VS. Additionally, the existing legal ambiguity around MCS may have influenced the audience to draw a line between expressing preferences for self versus others, by implicitly recognizing that the latter could be a step on the slippery slope to legalize euthanasia. Given the observed individual variability, we stress the importance of advance directives and identification of proxies when discussing end-of-life issues in patients with disorders of consciousness.

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.

BACKGROUND: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs). METHODS: A retrospective, observational study was carried out. All patients (n=45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. RESULTS: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. CONCLUSIONS: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs.