[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

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.

[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.

[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.

[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.

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.

Primary diffuse leptomeningeal gliomatosis: an autopsy case and review of the literature.

We report a case of primary diffuse leptomeningeal gliomatosis (PDLG) in a 76-year-old male presenting with confusion, dysarthria, diplopia, lumbal pain and headaches of recent onset. Neurological examination revealed nuchal rigidity and bilateral sixth cranial nerve palsy. The cerebrospinal fluid showed a marked hyperproteinorachia (4711 mg/L) and mild cytorachia (5-10 leucocytes/mm3) with a few atypical lymphoid cells. On admission, brain CT scan and MRI demonstrated diffuse and nodular leptomeningeal contrast enhancement predominant at the skull base and several osteolytic lesions in the right parietal bone. Extensive serological studies for infectious, autoimmune or neoplastic diseases were negative. The work-up diagnosis was neurosarcoidosis or multiple meningeal and osseous metastases of an unknown primary cancer. Surgical biopsy of the right parietal bone lesion showed only fibrous tissue with no evidence of tumour or inflammation. The patient was treated with high dose corticosteroids but its neurological status progressively worsened and he died of aspiration pneumonia 35 days after admission. Post-mortem examination revealed a PDLG, a rare fatal tumour with about 60 cases reported. PDGL is characterized by the diffusion of neoplastic glial cells throughout the leptomeninges without evidence of a primary intra-parenchymal lesion. Recognition of this rare brain tumour is important as recent reports suggest that radiotherapy and chemotherapy can improve patient survival.

[Diagnostic exercise for the medical school student: how to analyze an abnormality of eye movements?]. / La vignette diagnostique de l'étudiant. Comment raisonner une anomalie des mouvements oculaires?

Eye movements abnormalities are common symptoms in neurology. We report a clinical observation of ischemic unilateral internuclear ophtalmoplegia to illustrate how much anatomical diagnosis is based on 1) a detailed neurological examination and 2) a deep knowledge and understanding of the anatomy and physiology of ocular movements. We also take this opportunity to review ocular symptoms and signs encountered in neurological practice.

Pain and non-pain processing during hypnosis: a thulium-YAG event-related fMRI study.

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation.

Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient.

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico-thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico-cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio-respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age-matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task-positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long-distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population.

Retinoic acid stimulates regeneration of mammalian auditory hair cells.

Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage.

Bispectral index correlates with regional cerebral blood flow during sleep in distinct cortical and subcortical structures in humans.

The relationship between the Bispectral Index (BIS), an EEG-based monitor of anesthesia, and brain activity is still unclear. This study aimed at investigating the relationship between changes in BIS values during natural sleep and regional cerebral blood flow (rCBF) variations, as measured by Positron Emission Tomography (PET). Data were obtained from six young, healthy, right-handed, male volunteers (20-30 years old) using the H2(15)O infusion method. PET scans were performed both during waking and various stages of sleep. BIS values were monitored continuously and recorded during each PET scan. Positive correlations were detected between BIS and rCBF values in dorsolateral prefontal, parietal, anterior and posterior cingulate, precuneal, mesiofrontal, mesiotemporal and insular cortices. These areas belong to a frontoparietal network known to be related to awareness of self conscious sensory perception, attention and memory. BIS values also positively correlated with activity in brainstem and thalami, both structures known to be involved in arousal and wakefulness. These results show that BIS changes associated with physiological sleep depth co-vary with the activity of specific cortical and subcortical areas. The latter are known to modulate arousal, which in turn allows sustained thalamo-cortical enhancement of activity in a specific frontoparietal network known to be related to the content of consciousness. Thus, although mainly derived from frontal EEG, BIS could represent a wider index of cerebral activity.