RESUMEN
Kleine-Levin syndrome (KLS) is characterized by recurrent episodes of hypersomnia, compulsive hyperphagia, disinhibition, hypersexuality and self modifications. To investigate the Self, we used afunctional magnetic resonance imaging paradigm evaluating Self-reference processing (SRP) and Self-reference effect (SRE) in a17-year-old male adolescent at the end of an episode. We observed enhanced activations in right hemisphere and posterior areas- associated with physical Self representations- during the SRP condition, while during the SRE condition, enhanced activations in bilateral but prevailing left frontal areas- associated with the conceptual Self. These results suggest amodified Self during aKLS episode being more physically grounded.
Asunto(s)
Síndrome de Kleine-Levin , Adolescente , Humanos , Síndrome de Kleine-Levin/diagnóstico por imagen , Imagen por Resonancia Magnética , MasculinoRESUMEN
PURPOSE: We aimed to analyze the tears of patients with Benin Essential Blepharospasm (BEB) to explore possible corneo-conjunctival mechanisms for photophobia, tear deficiency and ocular pain. METHODS: Using an observational cohort of 42 patients diagnosed with BEB, we performed Schirmer's testing, measurement of tear film pH, tear film protein electrophoresis and conjunctival impression cytology. RESULTS: Schirmer's testing showed dry eye (8.4±9.7mm) with 71.3% eyes having a Schirmer's score<10mm. Surprisingly, the pH was basic (8.4±0.4) and was improved in patients receiving the standard treatment of quarterly botulinum toxin injections (8.32±0.36 for treated patients vs. 8.74±0.53 for untreated patients; P=0.045). Together, tear protein electrophoresis and conjunctival impression cytology showed conjunctival inflammation associated with BEB. CONCLUSION: For the first time, this study emphasizes corneo-conjunctival mechanisms to explain the photophobia, dry eye and pain in Benign Essential Blepharospasm. While encouraging, complementary studies remain necessary to evaluate the effect of correcting tear film pH and inflammation on the quality of life of blepharospasm patients.
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Blefaroespasmo , Síndromes de Ojo Seco , Blefaroespasmo/complicaciones , Blefaroespasmo/diagnóstico , Blefaroespasmo/tratamiento farmacológico , Síndromes de Ojo Seco/complicaciones , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/tratamiento farmacológico , Humanos , Calidad de Vida , Lágrimas/metabolismoRESUMEN
PURPOSE: To assess the severity of dry eye disease in patients with blepharospasm (BEB) before (control) and after injection of botulinum neurotoxin A (BoNT/A). DESIGN: Cross-sectional study. METHODS: Patients with clinically diagnosed BEB and no known history of dry eye syndrome prior to the onset of the disease, before (controls) or after injection with one of the three available types of BoNT/A: onabotulinumtoxinA (Botox®; Allergan, Irvine, CA, USA), abobotulinumtoxinA (Dysport®; Beaufour Ipsen Pharma SAS, Paris, France) or incobotulinumtoxinA (Xeomin®; Merz Pharma GmbH, Frankfurt, Germany) every 3 months. Tear osmolarity and Schirmer's I-test were measured at the first visit for non-treated BEB patients as controls and 3 months after BoNT/A injection. RESULTS: The study consisted of 101 BEB patients (86 females, 15 males) with a mean age of 67 years (range 30-86 years). Seventeen patients were untreated, 26 treated with onabotulinumtoxinA, 23 treated with abobotulinumtoxinA and 35 treated with incobotulinumtoxinA. Post-injection mean tear osmolarity was not significantly higher among patients treated with onabotulinumtoxinA, abobotulinumtoxinA, or incobotulinumtoxinA (P=0.65, P=0.92, and P=0.15, respectively), compared to controls, remaining less than 308 mosm/mL. Mean Schirmer's I-test results remained under 5mm and did not vary between the four groups. CONCLUSIONS: The results clearly demonstrate that reduced tear secretion appears to be present in BEB patients even prior to treatment. This decreased lacrimal secretion was not correlated with hyperosmolarity. Clinicians should proactively treat dry eye syndrome in conjunction with management of the blepharospasm.
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Blefaroespasmo , Toxinas Botulínicas Tipo A , Síndromes de Ojo Seco , Adulto , Anciano , Anciano de 80 o más Años , Blefaroespasmo/diagnóstico , Blefaroespasmo/tratamiento farmacológico , Estudios Transversales , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Concentración Osmolar , LágrimasRESUMEN
PURPOSE: To localize the brain structures involved in blepharospasm. MATERIALS AND METHODS: This is a retrospective consecutive series of brain MRI's of patients with secondary blepharospasm whose immediate past medical history included cerebrovascular accident or head trauma. RESULTS: Six patients, including 4 with CVA with ischemic or hemorrhagic lesions of the thalamus and caudate nuclei and 2 with head trauma with contusive sequellae to the tectal plate and frontal cortical and cerebellar atrophy. CONCLUSION: According to the literature, brain lesions associated with blepharospasm involve mainly the thalamus, head of the caudate nucleus, corpus striatum, globus pallidus, internal capsule, cerebral cortex and cerebellum. This study demonstrates that blepharospasm is associated with a lesion of a complex neural network - cortex-thalamus-globus pallidus-cortex - and does not correspond to a single, unique lesion. This network is connected with ascending and descending sensory-motor pathways and motor nuclei.
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Blefaroespasmo , Blefaroespasmo/diagnóstico , Encéfalo , Humanos , Imagen por Resonancia Magnética , Estudios Retrospectivos , TálamoRESUMEN
PURPOSE: To localize the brain structures involved in blepharospasm. MATERIALS AND METHODS: This is a retrospective consecutive series of brain MRI's of patients with secondary blepharospasm whose immediate past medical history included cerebrovascular accident or head trauma. RESULTS: Six patients, including 4 with CVA with ischemic or hemorrhagic lesions of the thalamus and caudate nuclei and 2 with head trauma with contusive sequellae to the tectal plate and frontal cortical and cerebellar atrophy. CONCLUSION: According to the literature, brain lesions associated with blepharospasm involve mainly the thalamus, head of the caudate nucleus, corpus striatum, globus pallidus, internal capsule, cerebral cortex and cerebellum. This study demonstrates that blepharospasm is associated with a lesion of a complex neural network - cortex-thalamus-globus pallidus-cortex - and does not correspond to a single, unique lesion. This network is connected with ascending and descending sensory-motor pathways and motor nuclei.
Asunto(s)
Blefaroespasmo , Blefaroespasmo/complicaciones , Blefaroespasmo/diagnóstico , Encéfalo , Humanos , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
INTRODUCTION: Hemifacial spasm (HFS) is an involuntary contracture of the facial muscles innervated by the ipsilateral facial nerve. We studied the etiology of these HFS. MATERIALS AND METHODS: This retrospective study included 233 patients with HFS who came to the ophthalmologist for quarterly botulinum neurotoxin A injection. Of these, we analyzed the 198 patients for whom MRI scans were performed. We recorded patient clinical data and clarified the etiology of their HFS. RESULTS: The 198 patients (62.6% women) had a mean age of 55.7±14years. An etiology was found in 52.5% of cases. In 34.5% of HFS, MRI revealed vascular compression where the facial nerve emerged from the brainstem. We specify the arteries involved. Brain tumors accounted for 1.5% of cases. MRI was normal in 64.5% of cases. In these secondary cases of HFS, we found 8.5% peripheral facial palsy, 4% post-traumatic HFS and 4% secondary to an eye injury. Stress was found in 17% of patients. DISCUSSION AND CONCLUSION: This study illustrates the need for MRI with attention to the posterior fossa in the work-up of HFS in order to identify primary HFS associated with vascular compression of the facial nerve and to rule out a rare but serious posterior fossa tumor. The treatment of HFS is based on quarterly injections of botulinum neurotoxin/A (NTBo/A), the three brands of which have market approval. The injection pattern and frequency is customized according to the results. In cases of insufficient response to injections of NTBo/A, neurosurgical microvascular decompression may be considered for cases of primary HFS.
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Toxinas Botulínicas Tipo A , Espasmo Hemifacial , Adulto , Anciano , Músculos Faciales , Nervio Facial , Femenino , Espasmo Hemifacial/diagnóstico , Espasmo Hemifacial/epidemiología , Espasmo Hemifacial/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The purpose of this report is to describe the experience of a specialized medico-surgical ENT team sent to hospital centers in Atalaha and Tulear, Madagascar by a nonprofit organization called "Terre rouge" from the Reunion Island. In three separate short-term missions, a total of 93 patients received care. Discussion focuses on the particular pathological, cultural, and pedagogical features of the Island and on the resources that were deployed during the missions. Providing ENT care in district hospitals in Madagascar requires adaptation to the difficult climatic conditions, poor hospital facilities (infrastructure, equip ment, and personnel), and advanced stage of diseases. To ensure continuous access to ENT care, it will be necessary to provide practical and didactic training for healthcare personnel in the country.
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Misiones Médicas , Enfermedades Otorrinolaringológicas/terapia , Grupo de Atención al Paciente , Femenino , Hospitales de Distrito , Humanos , Madagascar , Masculino , Organizaciones sin Fines de Lucro , Estudios RetrospectivosRESUMEN
PURPOSE: To study whether there is an association between benign essential blepharospasm and Sjögren's syndrome by analyzing the presence of antibodies to extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We excluded patients with hemifacial spasm or blepharospasm secondary to known corneal pathology. We recorded results of Schirmer I testing as well as levels of anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Our study included 72 patients (144 eyes), of which 62 (86.1%) were women. The mean age was 74.3±10.73 years. The mean Schirmer I test result was 3.14±4.00mm. Five women (8% of this female population) were found to have positive anti-SSA/Ro and anti-SSB/La antibodies. Their mean age was 65.66±13.24 years, while the mean age of the antibody-negative patients was 75.42±9.27 years. There was no statistically significant difference between the Schirmer I tests of the antibody positive and negative patients. CONCLUSION: This study demonstrates a possible association between Sjögren's syndrome and benign essential blepharospasm, justifying anti-SSA/Ro and anti-SSB/La testing in these patients.
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Anticuerpos Antinucleares/sangre , Blefaroespasmo/sangre , Blefaroespasmo/epidemiología , Síndromes de Ojo Seco/sangre , Síndromes de Ojo Seco/epidemiología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antinucleares/análisis , Antígenos Nucleares/inmunología , Blefaroespasmo/complicaciones , Blefaroespasmo/diagnóstico , Comorbilidad , Síndromes de Ojo Seco/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnósticoRESUMEN
PURPOSE: The goal of this study is to determine a link between benign essential blepharospasm and Sjogren's syndrome by analyzing the presence of extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We eliminated patients with hemifacial spasm or blepharospasm secondary to corneal pathology. We collected the values of the Schirmer I test and the results of the anti-SSA and anti-SSB antibodies. RESULTS: Our study included 72 patients (144 eyes) whose 62 women (86.1%). Mean age was 74.3 years±10.73. Average Schirmer I test was 3.14mm±4.00mm. Five women (8% of this female population) had positive anti-SSA and SSB antibodies. Their mean age was 65.66 years±13.24 whereas the negative antibody patients had an average age of 75.42±9.27. There was no significant difference between their Schimer I test and the Schirmer I of negative antibody population. CONCLUSION: This study illustrates the possible association between the presence of Sjögren's syndrome and the occurrence of a BEB justifying the search for anti-SSA and anti SSB in blepharospasm patients.
Asunto(s)
Anticuerpos Antinucleares/sangre , Antígenos Nucleares/inmunología , Blefaroespasmo/sangre , Blefaroespasmo/epidemiología , Síndromes de Ojo Seco/sangre , Síndromes de Ojo Seco/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Blefaroespasmo/complicaciones , Síndromes de Ojo Seco/complicaciones , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Síndrome de Sjögren/sangre , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/epidemiologíaRESUMEN
OBJECTIVE: To analyze the impact of the first month of lockdown related to the 2020 SARS-Cov-2 epidemic on the consulting activity of private ENT physicians in Réunion Island. MATERIAL AND METHODS: A multicenter prospective study analyzed the consulting activity of 12 ENT physicians in full-time private practice. The main endpoints were the number, characteristics and conditions of consultations. Secondary endpoints comprised presenting symptoms, diagnosis, prescriptions, adverse effects, and progression of monthly consulting turnover. RESULTS: Six hundred and ninety three consultations were performed during the study period (Appendix 1), with 50% emergency consultations. In 57.9% were face-to-face, 28.4% by phone and 13.7% video. In face-to-face consultation, the physician wore gloves in 53.8% of cases and a mask in 92.2%: surgical mask in 71.6% of cases and FFP2 in 28.4%. The three most frequent symptoms (48.5% of cases) were otalgia, hearing impairment, and vertigo. The three most frequent diagnoses (60.6% of cases) were otitis, intra-auricular foreign body (including wax), and pharyngeal infection. The three most frequently prescribed complementary exams (74.3% of cases) were imaging, hearing work-up, and specialist opinion. The three most frequently prescribed treatments (52.7% of cases) were intra-auricular drops, oral antibiotics, and nasal spray. The incidence of adverse effects was 0.001%. None of the physicians or patients seemed to have been infected by Covid-19 during the study period. There was a 47.3-91% (median, 75.6%) drop in monthly consultation turnover. CONCLUSION: The present study underscored the availability and adaptability of ENT physicians in the Réunion Island in an epidemic context, although economic impact was detrimental.
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Infecciones por Coronavirus/epidemiología , Otolaringología , Enfermedades Otorrinolaringológicas , Neumonía Viral/epidemiología , Práctica Privada/estadística & datos numéricos , Cuarentena/estadística & datos numéricos , COVID-19 , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Enfermedades Otorrinolaringológicas/diagnóstico , Enfermedades Otorrinolaringológicas/terapia , Pandemias , Estudios Prospectivos , Reunión , Factores de TiempoRESUMEN
Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.
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Encefalopatías Metabólicas Innatas/enzimología , Encefalopatías Metabólicas Innatas/genética , Núcleo Celular/enzimología , Mutación Missense , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Secuencia de Bases , Encefalopatías Metabólicas Innatas/patología , Encefalopatías Metabólicas Innatas/fisiopatología , Células COS , Preescolar , Chlorocebus aethiops , Análisis Mutacional de ADN , Electroencefalografía , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Fenotipo , Plásmidos/genética , ARN Mensajero/genética , Homología de Secuencia de Aminoácido , Transfección , Inactivación del Cromosoma XRESUMEN
PURPOSE: To determine the significance of dry eye syndrome in benign essential blepharospasm. DESIGN: Retrospective consecutive case series. PARTICIPANTS: One hundred and forty-four patients (288 eyes) with benign essential blepharospasm. METHODS: All subjects had Schirmer I tear tests. Those scores were analysed as a function of patient age, sex, and blepharospasm severity. MAIN OUTCOME MEASURES: Individual Schirmer-test scores in both eyes of all patients. RESULTS: A total of 144 eligible subjects (mean age±SD: 68.3±11.5 years; 76% females) were evaluated. Benign essential blepharospasm was significantly associated with female sex (P=0.0044). The mean Schirmer-test value was 5.9±7.5 (median: 2.5) mm; it was <15mm for 86.8% of the patients and <10mm for 75%, with no difference observed between men and women (P=0.27). Dry-eye syndrome severity was not correlated with age at diagnosis, for men (r=-0.22, P=0.22) or women (r=-0.067, P=0.49), or benign essential blepharospasm severity (P=0.15), but was strongly associated with benign essential blepharospasm independently of age, sex or blepharospasm intensity. CONCLUSION: Dry-eye syndrome and benign essential blepharospasm are strongly linked, independently of age, sex or BEB severity, and should be considered for the diagnosis of benign essential blepharospasm. The useful symptomatic treatment of dry eye will not cure the blepharospasm or the ocular pain, and specific treatment for blepharospasm is required, i.e., quarterly injections of botulinum toxin A into the orbicularis oculi muscle.
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Blefaroespasmo/epidemiología , Síndromes de Ojo Seco/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Blefaroespasmo/complicaciones , Blefaroespasmo/patología , Síndromes de Ojo Seco/complicaciones , Síndromes de Ojo Seco/patología , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , LágrimasRESUMEN
Action selection, the problem of choosing what to do next, is central to any autonomous agent architecture. We use here a multi-disciplinary approach at the convergence of neuroscience, dynamical system theory and autonomous robotics, in order to propose an efficient action selection mechanism based on a new model of the basal ganglia. We first describe new developments of contraction theory regarding locally projected dynamical systems. We exploit these results to design a stable computational model of the cortico-baso-thalamo-cortical loops. Based on recent anatomical data, we include usually neglected neural projections, which participate in performing accurate selection. Finally, the efficiency of this model as an autonomous robot action selection mechanism is assessed in a standard survival task. The model exhibits valuable dithering avoidance and energy-saving properties, when compared with a simple if-then-else decision rule.
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Ganglios Basales/fisiología , Toma de Decisiones/fisiología , Movimiento/fisiología , Neurociencias/métodos , Robótica/métodos , Algoritmos , Animales , Inteligencia Artificial , Humanos , Redes Neurales de la Computación , Vías Nerviosas/fisiología , Neurociencias/tendencias , Dinámicas no Lineales , Robótica/tendenciasRESUMEN
The organization of episodic and semantic memory is currently debated, and especially the rule of the hippocampus in the functioning of these two systems. Since theories derived from the observation of the famous patient HM, that highlighted the involvement of this structure in these two systems, numerous studies questioned the implication of the hippocampus in learning a new semantic knowledge. Among these studies, we found Vargha-Kadem's cases of developmental amnesia. In spite of their clear hippocampal atrophy and a massive impairment of episodic memory, these children were able to acquire de novo new semantic knowledge. In the present paper, we describe a new case of developmental amnesia characteristic of this syndrome. In conclusion, the whole published data question the implication of the hippocampus in every semantic learning and suggest the existence of a neocortical network, slower and that needs more exposures to semantic stimuli than the hippocampal one, which can supply a massive hippocampal impairment.
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Envejecimiento/psicología , Amnesia/fisiopatología , Amnesia/psicología , Memoria/fisiología , Animales , Hipocampo/fisiopatología , Humanos , Neocórtex/fisiología , Neocórtex/fisiopatología , Red Nerviosa/fisiología , Red Nerviosa/fisiopatologíaRESUMEN
HEADINGS: Retrospective longitudinal study to evaluate the efficacy of botulinum neurotoxin A (BoNT/A) therapy for epiphora with patent lacrimal ducts. BACKGROUND/PURPOSE: BoNT/A has been used since 2000 in axillary hyperhidrosis to reduce sweat secretion. Some isolated cases of hyperlacrimation or crocodile tear syndrome have been treated with BoNT/A on this basis. We report our experience in the treatment of tearing despite patent lacrimal ducts by BoNT/A injection into the lacrimal gland. METHODS: We reviewed qualitative and quantitative criteria to evaluate the degree of improvement of epiphora after BoNT/A injections in the palpebral lobe of the lacrimal gland in patients referred for epiphora despite patent lacrimal ducts between 2009 and 2016. Epiphora was graded using a functional questionnaire, Munk score and Schirmer test performed before and after the injections. Side effects were recorded. RESULTS: Sixty-five palpebral lacrimal glands of forty-two patients with epiphora despite patent lacrimal ducts, of mean age 65 years, sex ratio 0.8, were treated with BoNT/A (IncobotulinumtoxinA, XEOMIN®, MERZ Pharma France) from April 2009 to April 2016. The etiology of the epiphora was represented by 56 paroxysmal lacrimal hypersecretion, 2 crocodile tear syndrome and 7 facial palsies. No conventional medical or surgical treatment had been effective in these cases. The technique of injection, dilution and dosage of BoNT/A were specific. We re-injected 33/65 cases a second time upon patient request due to recurrence of epiphora, 16/65 cases three times, 8/65 cases four times, 6/65 cases five times and 3/65 six times. The Schirmer's test measured a decrease of lacrimal secretion in 51/65 glands (78%) after the first botulinum neurotoxin injection. Side effects were limited to ptosis in 2 cases (3%) and six patients (9%) with rapidly regressing diplopia. Two patients experienced immediate lacrimal gland hematoma (3%) with no sequelae. The authors describe the injection techniques, the dosage, the volume and concentration of BoNT/A. CONCLUSION: Patients with intractable epiphora despite patent lacrimal ducts can be effectively treated with BoNT/A (IncobotulinumtoxinA) injection into the palpebral lobe of the lacrimal gland. Most of the patients (80%) were very satisfied with few side effects (hematoma, ptosis or mild diplopia lasting from 3 days to 3 weeks). More studies are needed to delineate which types of epiphora can be treated with BoNT A.
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Toxinas Botulínicas Tipo A/uso terapéutico , Enfermedades del Aparato Lagrimal/tratamiento farmacológico , Anciano , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/farmacología , Evaluación de Medicamentos , Ingestión de Alimentos , Parálisis Facial/complicaciones , Femenino , Hematoma/etiología , Humanos , Inyecciones Intraoculares/efectos adversos , Aparato Lagrimal , Enfermedades del Aparato Lagrimal/etiología , Masculino , Persona de Mediana Edad , Regeneración Nerviosa , Estudios Retrospectivos , Glándulas Salivales/inervación , Tasa de Secreción/efectos de los fármacos , Lágrimas/metabolismoRESUMEN
The trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) increases in many different neuron types following injury; a response postulated to support cell survival and regeneration. In acutely isolated cardiac ganglia, approximately 1% of the cardiac neurons exhibited PACAP immunoreactivity whereas after 72 h in culture, approximately 25% of the neurons were PACAP immunoreactive. In contrast, there was no increase in vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) cells. Using a combination of immunocytochemical and molecular techniques, we have quantified PACAP expression, during explant culture of guinea-pig cardiac ganglia. Using real time polymerase chain reaction, PACAP transcript levels increased progressively up to 48 h in culture with no further increase after 72 h. PACAP transcript levels were reduced by neurturin at 48 h in culture but not after 24 or 72 h in culture. In addition, neurturin partially suppressed the percentage of PACAP-IR neurons after 72 h in culture, an effect mediated by activation of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. The addition of different known regulatory molecules, including ciliary neurotrophic factor (CNTF), interleukin-1 beta (Il-1beta), tumor necrosis factor-alpha (TNFalpha), fibroblast growth factor basic (bFGF), transforming growth factor-beta (TGF-beta) and nerve growth factor (NGF) did not increase the percentage of PACAP-IR neurons after 24 h in culture; a result indicating that the generation and secretion of these factors did not stimulate PACAP expression. The presence of 20 nM PACAP or 10 muM forskolin increased the percentage of PACAP-IR cardiac neurons in 24 h cultures, but not in 72 h cultures. Neither treatment enhanced the number of VIP-IR neurons. The addition of the PACAP selective receptor (PAC(1)) receptor antagonist, M65 (100 nM) suppressed the 20 nM PACAP-induced increase in percentage of PACAP-IR cells in 24 h cultures indicating the effect of PACAP was mediated through the PAC(1) receptor. However, 100 nM M65 had no effect on the percentage of PACAP-IR cells in either 24 or 48 h cultures not treated with exogenous PACAP, suggesting that endogenous release of PACAP likely did not contribute to the enhanced peptide expression. We postulate that the enhanced PACAP expression, which occurs in response to injury is facilitated in the explant cultured cardiac ganglia by the loss of a target-derived inhibitory factor, very likely neurturin. In intact tissues the presence of neurturin would normally suppress PACAP expression. Lastly, our results indicate that many common trophic factors do not enhance PACAP expression in the cultured cardiac neurons. However, the stimulatory role of an, as yet, unidentified factor cannot be excluded.
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Ganglios Parasimpáticos/citología , Regulación de la Expresión Génica/fisiología , Neuronas/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Análisis de Varianza , Animales , Recuento de Células/métodos , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Cobayas , Interleucina-1beta/farmacología , Factores de Crecimiento Nervioso/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , ARN Mensajero , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The brain circuitry of saccadic eye movements, from brainstem to cortex, has been extensively studied during the last 30 years. The wealth of data gathered allowed the conception of numerous computational models. These models proposed descriptions of the putative mechanisms generating this data, and, in turn, made predictions and helped to plan new experiments. In this article, we review the computational models of the five main brain regions involved in saccade generation: reticular formation saccadic burst generators, superior colliculus, cerebellum, basal ganglia and premotor cortical areas. We present the various topics these models are concerned with: location of the feedback loop, multimodal saccades, long-term adaptation, on the fly trajectory correction, strategy and metrics selection, short-term spatial memory, transformations between retinocentric and craniocentric reference frames, sequence learning, to name the principle ones. Our objective is to provide a global view of the whole system. Indeed, narrowing too much the modelled areas while trying to explain too much data is a recurrent problem that should be avoided. Moreover, beyond the multiple research topics remaining to be solved locally, questions regarding the operation of the whole structure can now be addressed by building on the existing models.
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Tronco Encefálico/fisiología , Corteza Cerebral/fisiología , Modelos Neurológicos , Redes Neurales de la Computación , Movimientos Sacádicos/fisiología , Animales , Tronco Encefálico/anatomía & histología , Corteza Cerebral/anatomía & histología , Humanos , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiologíaRESUMEN
OBJECTIVE: Cataract surgery for 50 Alzheimer patients (55 eyes). METHODS: Cinquante Alzheimer's patients with 0≤MMS≤25, with bilateral disabling cataracts were included for surgery. The surgical technique is analyzed. RESULTS AND CONCLUSION: The preoperative examination of Alzheimer's patients is time consuming and requires experience in this area, which is important to integrate into the practice of ophthalmology. The type of cataract is unusual, with a predilection for pseudoexfoliation syndrome and zonular fragility that has to be managed during surgery. The procedure may be performed under local anesthesia. Three months after surgery, Alzheimer's patients demonstrated improved visual acuity (P<0.001) with no worsening of their dementia.
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Enfermedad de Alzheimer/cirugía , Extracción de Catarata , Catarata/complicaciones , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Extracción de Catarata/rehabilitación , Síndrome de Exfoliación/cirugía , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Estilo de Vida , Masculino , Complicaciones Posoperatorias/etiología , Agudeza VisualRESUMEN
PURPOSE: Retrospective long-term study to evaluate the efficacy of botulinum neurotoxin A (BoNT/A) therapy for epiphora due to non-surgical nasolacrimal duct obstruction. INTRODUCTION: BoNT/A has been used successfully since 2000 in axillary hyperhidrosis to reduce secretory disorders. Some isolated cases of hyperlacrimation or crocodile tear syndrome have been treated on this basis. We used BoNT/A to decrease lacrimal secretion in cases of epiphora. METHODS: We reviewed the qualitative and quantitative degree of improvement of epiphora after botulinum neurotoxin injections in the palpebral lobe of the lacrimal gland, carried out in an ophthalmic centre between 2009 and 2016. Epiphora was graded using a questionnaire, Munk scores and Schirmer tests before and after injections. Severity of side effects was recorded. RESULTS: Twenty-seven palpebral lacrimal glands of twenty patients with epiphora, mean age 65±13, were treated with BoNT/A (Botox® or Xeomin®) from April 2009 to April 2016. The epiphora was induced by persistent nasolacrimal duct stenosis after surgical treatment. No conventional medical nor surgical treatment was effective at this time. The technique of injection, dilution and dosage were specific. We re-injected 14/27 cases on an as-needed basis, 7/27 cases three times, 3/27 cases four times, and 2/27 cases (same patient both glands) five times. The Schirmer test measured a decrease of lacrimal secretion in 24/27 (89%) lacrimal glands after neurotoxin injection. Side effects were ptosis in 4 cases and transient esotropia in 2 cases. The authors describe the injection techniques, the dosage, the volume and concentration of BoNT/A. CONCLUSION: Patients with epiphora can be treated effectively with BoNT/A to reduce lacrimal secretion of the principal lacrimal gland in its palpebral portion. Ninety percent of the patients were very satisfied, with few side effects (ptosis or mild diplopia lasting from 3 days to 3 weeks). More studies are needed to delineate which types of epiphora can be treated with BoNT/A.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Enfermedades del Aparato Lagrimal/tratamiento farmacológico , Obstrucción del Conducto Lagrimal/tratamiento farmacológico , Anciano , Blefaroptosis/tratamiento farmacológico , Blefaroptosis/etiología , Toxinas Botulínicas Tipo A/efectos adversos , Femenino , Humanos , Inyecciones Intraoculares/efectos adversos , Enfermedades del Aparato Lagrimal/complicaciones , Obstrucción del Conducto Lagrimal/complicaciones , Masculino , Persona de Mediana Edad , Conducto Nasolagrimal/efectos de los fármacos , Conducto Nasolagrimal/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the point of view of young physicians training in pediatrics in France on their theoretical courses during residency. METHODS: A free-access electronic anonymous survey was sent three times by e-mail to the 1215 residents in pediatrics, from July to October 2015. RESULTS: Fifty-seven percent of French residents in pediatrics responded to the survey. It was established that they took part in six (range, 3-10) half-days of specific theoretical teaching in pediatrics from November 2014 to mid-April 2015. Only 54% participated in more than 75% of regional theoretical training. The main self-declared reason for their absence was that they could not leave their clinical activities. Fifty-three per cent of the residents took part in additional training, 45% of them because they found the primary theoretical training insufficient. The overall quality of the theoretical teaching was rated 5 (range, 3-7) out of 10. Eighty-five percent of residents expected to be evaluated on their knowledge during their residency. CONCLUSION: In pediatrics, additional training is individually undertaken because they deemed their initial training insufficient during their residency. An evaluation of knowledge is requested by residents. The reform of the national residency program must take into account these results in redesigning the theoretical training in pediatrics, integrating innovative teaching techniques to daily practice, for example.