Aproximaciones a la epidemiología de la neuropatía óptica hereditaria de Leber en la comunidad autónoma de Madrid a través de una encuesta a los neuroftalmólogos / Approaches to the epidemiology of NOHL in the region of Madrid: Survey of neuro-ophthalmologists

Objective To estimate the epidemiology of Leber's optic neuropathy (NOHL) in the Region of Madrid. Material and methodsThe neuro-ophthalmologists who work at public hospitals of the CAM were interviewed by telephone. They were asked about the number of patients with NOHL that they had diagnosed during the time that they had been responsible for the neuro-ophthalmology department of that public hospital. The time worked and the population attended by the hospital were used to calculate the number of patient-years in follow-up by each center during the corresponding period. The basic information of each case (date of birth, mutation, and date of visual loss) was registered to avoid duplications. Results Our work estimates a global incidence of 2.34 cases for 10,000,000 inhabitants-year and a prevalence estimated from incidence of one case for each 106,682 inhabitants. This prevalence was very similar in all the studied areas and considerably lower than that reported by other studies. Conclusion This work constitutes the first approach to the epidemiology of this disease in Spain. The prevalence of NOHL in the region of Madrid is probably lower than that reported in the literature in other regions. The prevalence and the incidence were homogeneously low in the 26 studied areas. (AU)

Objetivo Estimar la epidemiología (incidencia y prevalencia) de la neuropatía óptica de Leber (NOHL) en la comunidad autónoma de Madrid (CM). Material y métodosLos neuroftalmólogos que trabajan en los hospitales públicos de la CAM fueron entrevistados telefónicamente. Se les preguntó por el número de pacientes con NOHL que habían diagnosticados durante el tiempo que han sido responsables de la consulta de neuroftalmología de ese hospital público. El tiempo trabajado y la población atendida por el hospital se utilizaron para calcular el número de habitantes-años en seguimiento por cada centro durante el periodo correspondiente y estimar la incidencia en cada área. La prevalencia estimada a partir de la incidencia (PEI) se calculó considerando que un paciente con NOHL vive unos 40 años con la enfermedad. Se registró la información básica de cada caso cuando estaba disponible (sexo, fecha de nacimiento, mutación, fecha de la pérdida visual) para evitar duplicaciones. Resultados Nuestro trabajo estima una incidencia global de 2,34 casos por cada 10.000.000 habitantes-año y una PEI de 1 caso por cada 106.682 habitantes. Esta prevalencia es inferior a la referida por otros estudios. Conclusión Este trabajo constituye la primera aproximación a la epidemiología de esta enfermedad en España. La prevalencia estimada de la NOHL en la CM es probablemente inferior a la reportada en la literatura en otras regiones. La prevalencia y la incidencia fueron homogéneamente bajas en las 26 áreas estudiadas. (AU)

Approaches to the epidemiology of NOHL in the region of Madrid: Survey of neuro-ophthalmologists.

OBJECTIVE: To estimate the epidemiology of Leber's optic neuropathy (NOHL) in the Region of Madrid. MATERIAL AND METHODS: The neuro-ophthalmologists who work at public hospitals of the CAM were interviewed by telephone. They were asked about the number of patients with NOHL that they had diagnosed during the time that they had been responsible for the neuro-ophthalmology department of that public hospital. The time worked and the population attended by the hospital were used to calculate the number of inhabitant-years in follow-up by each center during the corresponding period. The basic information of each case (date of birth, mutation, date of visual loss) was registered to avoid duplications. RESULTS: Our work estimates a global incidence of 2.34 cases for 10,000,000 inhabitants-year and a prevalence estimated from incidence of one case for each 106.682 inhabitants. This prevalence was very similar in all the studied areas and considerably lower than that reported by other studies. CONCLUSION: This work constitutes the first approach to the epidemiology of this disease in Spain. The prevalence of LHON in the region of Madrid, is probably lower than that reported in the literature in other regions. The prevalence and the incidence were homogeneously low in the 26 studied areas.

Principais achados em um paciente com diagnóstico de Amaurose Congênita de Leber / Main findings in a patient diagnosed with Leber's Congenital Amaurosis

RESUMO A amaurose congênita de Leber, também conhecida como neuropatia óptica hereditária de Leber, é caracterizada por uma das formas mais graves de distrofia da retina com início na infância. Os achados clássicos são deficiência visual grave e precoce, nistagmo e eletrorretinograma (ERG) anormal ou não detectável. O objetivo deste estudo é relatar um caso de um paciente com amaurose congênita de Leber com comprometimento visual desde os 6 meses de vida e acentuado declínio visual a partir dos 15 anos de idade. A realização de exames específicos para confirmar o diagnóstico é importante para o manejo e o seguimento adequado do paciente e para proporcionar melhor qualidade de vida para o mesmo.

ABSTRACT Leber Congenital Amaurosis, also known as Leber hereditary optic neuropathy, is characterized by one of the most severe forms of childhood-onset retinal dystrophy. Classic findings are severe and early visual impairment, nystagmus, and abnormal or undetectable electroretinogram. The aim of this study is to report a case of a patient with Leber Congenital Amaurosis with visual impairment since the first six months of age and marked visual decline from fifteen years of age. Performing specific tests to confirm the diagnosis is important for the proper management and follow-up of the patient and to provide them with a better quality of life.

Terapia genética de injeção intravítrea de rAAV2-ND4 para neuropatia óptica hereditária de Leber: uma revisão sistemática / rAAV2-ND4 intravitreal injection gene therapy for Leber's hereditary optic neuropathy: a systematic review

RESUMO A neuropatia óptica hereditária de Leber é uma doença mitocondrial hereditária neurodegenerativa. A taxa potencial de recuperação espontânea é controversa na literatura. A terapia genética tem sido estudada como suporte aos pacientes. O objetivo desta revisão foi avaliar qualitativamente a segurança, os efeitos adversos e a eficácia da terapia gênica disponível. Trata-se de uma revisão sistemática de artigos indexados nas bases de dados PubMed®, Biblioteca Virtual em Saúde, SciELO, Cochrane, ScienceDirect, Scopus e Lilacs no primeiro semestre de 2021. Os critérios de inclusão e filtros foram: artigos relacionados ao tema, estudos randomizados, ensaios clínicos, trabalhos em humanos, últimos 5 anos, nas línguas portuguesa, inglesa e espanhola e texto completo disponível gratuitamente. Os parâmetros de exclusão foram: artigos duplicados, fuga ao tema, artigos de revisão, trabalhos não disponíveis e que fugiam aos critérios de inclusão. O coeficiente de kappa foi 0,812. A terapia não apresentou efeitos adversos sérios em nenhum dos artigos selecionados, e os efeitos menores sofreram 100% de remissão espontânea após o tratamento. Apesar de NAbs terem sido encontrados no soro de alguns pacientes, não houve associação entre a resposta imune adaptativa e a injeção do vetor viral. O tratamento foi eficaz na melhora da acuidade e campo visual. Vários estudos confirmaram a eficácia da terapia gênica, em doses baixas e médias, na melhora da acuidade visual e também sobre os efeitos adversos comuns relacionados à altas doses. A resposta imune humoral e a variação dos NAbs no soro foi citada em mais de um artigo. A terapia foi eficaz na melhora da acuidade visual e os efeitos adversos que surgiram foram tratados facilmente. No entanto, a resposta imune humoral ainda precisa ser estudada.

ABSTRACT Leber's Hereditary Optic Neuropathy (LHON) is an inherited neurodegenerative mitochondrial disease. The potential rate of spontaneous recovery is controversial in the literature. Gene therapy has been studied to support patients. The objective of this review was to qualitatively assess the safety, adverse effects, and efficacy of available gene therapy. This is a systematic review of articles indexed in PubMed®, VHL, SciELO, Cochrane, ScienceDirect, Scopus, and Lilacs databases, in the first half of 2021. Inclusion criteria and filters were: articles related to the topic, randomized studies, clinical trials, work in humans, last 5 years, in Portuguese, English, and Spanish and full text available for free. The exclusion parameters were: duplicate articles, not related to the topic, review articles, not available works, and works that did not meet the inclusion criteria. The kappa coefficient was 0.812. The therapy had no serious adverse effects in any of the selected articles, and minor effects experienced 100% spontaneous remission after treatment. Although NAbs were found in the serum of some patients, there was no association between the adaptive immune response and the injection of the viral vector. The treatment was effective in improving acuity and visual field. Several studies have confirmed the effectiveness of gene therapy, at low and medium doses, in improving visual acuity and also on common adverse effects related to high doses. The humoral immune response and the variation in serum NAbs was cited in more than one article. The therapy was effective in improving visual acuity and the adverse effects that arose were easily treated. However, the humoral immune response still needs to be studied.

Visual acuity loss and sixth nerve palsy as the only manifestations of slit ventricle syndrome.

The case is presented of a girl diagnosed with obstructive hydrocephalus due to pilomyxoid astrocytoma, which required a ventriculoperitoneal shunt (VPS) at the age of 5 years and 10 months. Two months later, magnetic resonance imaging of the brain did not show ventriculomegaly or other signs of increased intracranial pressure. At the age of 6 years and 2 months, a rapid onset of bilateral visual acuity loss developed and she was diagnosed with slit ventricle syndrome. Despite valve revisions of the VPS, she developed an abrupt decline of visual acuity to hand motion at 10 cm. Fundus examination revealed bilateral optic atrophy. She did not report any other systemic symptoms suggesting increased intracranial pressure, such as headache, nausea, vomiting, lethargy, irritability, or altered levels of consciousness.

Pérdida de agudeza visual y parálisis de VI nervio craneal como únicas manifestaciones de un síndrome de colapso ventricular / Visual acuity loss and sixth nerve palsy as the only manifestations of slit ventricle syndrome

Se describe una niña con hidrocefalia obstructiva por un astrocitoma pilomixoide, que requirió implantar una derivación ventrículo-peritoneal (DVP) a los 5 años y 10 meses de edad. Dos meses después, la resonancia magnética cerebral no mostró ventriculomegalia ni otros signos de aumento de la presión intracraneal. A la edad de 6 años y 2 meses desarrolló una rápida disminución de la agudeza visual bilateral siendo diagnosticada de síndrome de colapso ventricular. A pesar de las revisiones valvulares de la DVP, se produjo una disminución abrupta de la agudeza visual a movimientos de mano a 10cm. El examen del fondo de ojo reveló atrofia óptica bilateral. No refirió otros síntomas sistémicos que sugirieran un aumento de la presión intracraneal, como dolor de cabeza, náuseas, vómitos, letargia, irritabilidad o niveles alterados de conciencia.

The case is presented of a girl diagnosed with obstructive hydrocephalus due to pilomyxoid astrocytoma, which required a ventriculoperitoneal shunt (VPS) at the age of 5 years and 10 months. Two months later, magnetic resonance imaging of the brain did not show ventriculomegaly or other signs of increased intracranial pressure. At the age of 6 years and 2 months, a rapid onset of bilateral visual acuity loss developed and she was diagnosed with slit ventricle syndrome. Despite valve revisions of the VPS, she developed an abrupt decline of visual acuity to hand motion at 10cm. Fundus examination revealed bilateral optic atrophy. She did not report any other systemic symptoms suggesting increased intracranial pressure, such as headache, nausea, vomiting, lethargy, irritability, or altered levels of consciousness.

Tumor de hipófise em paciente com hidrocefalia: um desafio diagnóstico / Pituitary tumor in a patient with hydrocephalus: a diagnostic challenge

RESUMO A hidrocefalia é definida como a dilatação ventricular pelo aumento da pressão intraventricular e intracraniana quando não tratada ou por insucesso do tratamento. Muitas vezes, leva ao dano das vias ópticas, podendo causar atrofia óptica, devido à proximidade dessas vias com o ventrículo lateral quando ocorre a dilatação. Assim como a hidrocefalia pode levar à atrofia óptica, outras patologias também podem. Tumores hipofisários compartilham desse mesmo sinal, além de causar hemianospsia bitemporal quando o tumor comprime quiasma óptico. Ademais, a hemianopsia bitemporal é o distúrbio visual mais comum encontrado em pacientes com tumor de hipófise. Os tumores de hipófise, por exemplo, geram manifestações clínicas que podem estar relacionadas à disfunção da glândula ou aos efeitos mecânicos da expansão tumoral. Sinais e sintomas visuais estão mais ligados ao efeito mecânico do tumor. Assim, muitas vezes, o paciente procura o oftalmologista antes do endocrinologista. Neste caso, analisaremos uma paciente portadora de hidrocefalia que apresentava, concomitantemente, um tumor hipofisário, e a investigação oftalmológica fez toda a diferença no tratamento da paciente.

ABSTRACT Hydrocephalus is defined as ventricular dilation caused by increased intraventricular and intracranial pressure when untreated or due to treatment failure. Optical pathways can often cause optic atrophy due to the proximity to the lateral hazard when dilation occurs. Hydrocephalus can lead to optic atrophy, as well as other pathologies. Pituitary tumors share this same sign, in addition to causing bitemporal hemianopia when it compresses the optic chiasm. In addition, bitemporal hemianopia is the visual disturbance most commonly found in patients with pituitary tumors. Pituitary tumors, for example, have clinical manifestations that may be related to gland dysfunction, or to mechanisms of tumor expansion. Visual signs and symptoms are more linked to the mechanical effect of the tumor. Therefore, the patient usually seeks the ophthalmologist before the endocrinologist. In this case, we analyzed a patient with hydrocephalus who presented, at the same time, a pituitary tumor, and the ophthalmological investigation made all the difference in the treatment of the patient.

Deficiencia visual y neurológica posterior a la disfunción del sistema de derivación ventrículoperitoneal: reporte de caso / Visual and neurological impairment post-dysfunction in the ventricle-peritoneal shunt system: A case report

Resumen | Las alteraciones visuales de origen neurológico en los niños tienen diversas causas, algunas reversibles y otras no. La hidrocefalia es una de las más comunes e importantes, ya que puede producir deficiencias permanentes. Las causas de la hidrocefalia son variadas; entre las principales está la hemorragia intraventricular, generalmente debida al sangrado de la matriz germinal, el cual es muy común en recién nacidos prematuros. Se presenta el caso clínico de una paciente prematura con parálisis cerebral infantil, hemorragia intraventricular e hidrocefalia, producto de un embarazo múltiple, que presentó atrofia óptica en la infancia secundaria a la disfunción del sistema de derivación ventrículo-peritoneal. Durante su rehabilitación y tratamiento, ha recibido sesiones de neurorrehabilitación que le han permitido mejorar su agudeza y capacidad visual. Se comparó el caso de la paciente con algunos similares para establecer las semejanzas y las diferencias entre los cuadros clínicos presentados y la importancia del tipo de tratamiento médico utilizado en el curso de recuperación de la capacidad visual.

Abstract | Neurological visual impairments in children have multiple causes, some of them reversible while others are not. Hydrocephalus is one of the most important and common ones as it can result in permanent impairment. There are multiple causes of hydrocephalus, intraventricular hemorrhage being the main one. This generally occurs when the germinal matrix bleeds and is very common in preterm newborns. We present the clinical case of a patient with cerebral palsy, intraventricular hemorrhage, and hydrocephalus as a result of a preterm multiple pregnancy who developed optic atrophy during childhood secondary to ventricle-peritoneal shunt dysfunction. During the rehabilitation and treatment period, she received neurorehabilitation sessions, which improved her visual acuity and capacity. We found similarities and differences with other cases and we confirmed the importance of the treatment chosen for the recovery of visual capacity.

Visual acuity loss and sixth nerve palsy as the only manifestations of slit ventricle syndrome. / Pérdida de agudeza visual y parálisis de VI nervio craneal como únicas manifestaciones de un síndrome de colapso ventricular.

The case is presented of a girl diagnosed with obstructive hydrocephalus due to pilomyxoid astrocytoma, which required a ventriculoperitoneal shunt (VPS) at the age of 5 years and 10 months. Two months later, magnetic resonance imaging of the brain did not show ventriculomegaly or other signs of increased intracranial pressure. At the age of 6 years and 2 months, a rapid onset of bilateral visual acuity loss developed and she was diagnosed with slit ventricle syndrome. Despite valve revisions of the VPS, she developed an abrupt decline of visual acuity to hand motion at 10cm. Fundus examination revealed bilateral optic atrophy. She did not report any other systemic symptoms suggesting increased intracranial pressure, such as headache, nausea, vomiting, lethargy, irritability, or altered levels of consciousness.

Síndrome de Wolfram - Diagnóstico clínico de condição rara multissistêmica / Wolfram syndrome - Clinical diagnosis of rare multisystemic condition

Resumo A Síndrome de Wolfram consiste em uma patologia neurodegenerativa de caráter genético, também conhecida pela sigla DIDMOAD que traduz os principais achados dessa doença, Diabetes Insipidus, Diabetes Mellitus, Atrofia Óptica e Surdez. O artigo visa relatar ocaso de um paciente diagnosticado clinicamente com essa síndrome em um ambulatório geral de oftalmologia. Tendo em vistaque os pacientes portadores dessa alteração genética apresentam mais de um par craniano afetado e quadro clínico sem históricode meningite ou outras alterações neurológicas, tem-se que pensar em alterações raras, como é o caso dessa síndrome. A partir dodiagnóstico, aplicou-se o questionário WRUS em consulta, o qual permitiu a comparação do paciente abordado com dados obtidosinternacionalmente disponíveis na literatura.

Abstract Wolfram Syndrome consists of a neurodegenerative pathology of genetic character, also known by the acronym DIDMOAD that translates the main findings of this disease, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness. The article report the case of a patient diagnosed clinically with this syndrome in a general ophthalmology out patient clinic. Considering that patients with this genetic alteration have more than one cranial nerve affected by the disease and clinical history without meningitis or other neurological alterations, one has to think about rare alterations, as is the case with this syndrome. From the diagnosis, the WRUS questionnaire was applied in consultation, which all owed the comparation of the patient with concepts obtained internationally available in the literature.

Síndrome GAPO, a propósito de un caso / GAPO syndrome: case report

El síndrome GAPO es una rara enfermedad autosómica recesiva caracterizada por retraso en el crecimiento, alopecia, pseudoanodoncia y atrofia óptica. Se han descrito mutaciones en el gen ANTXR1 como origen etiológico. Presenta afectación de múltiples aparatos, por lo que requiere un manejo multidisciplinar para lograr su adecuado tratamiento.

GAPO syndrome is a rare autosomal recessive disease characterized by growth retardation, alopecia, pseudoanodontia and optic atrophy. Gene alterations in the ANTXR1 gene have been reported to be causative of this disorder. Abnormalities of diverse organs and systems have been described. A multidisciplinary management to achieve an adequate treatment is required.

Presentación de dos hermanos con síndrome de Wolfram / Presentation of Two Brothers with Wolfram Syndrome

El síndrome de Wolfram es una enfermedad neurodegenerativa progresiva con transmisión autosómica recesiva, caracterizada por la presencia de diabetes mellitus y atrofia óptica, también pueden estar presentes la diabetes insípida y la disacusia neurosensorial explicando el acrónimo DIDMOAD (diabetes insípida, diabetes mellitus, atrofia óptica y sordera). Cursa con diversas manifestaciones clínicas, además, como la dilatación de las vías urinarias, alteraciones neurológicas, alteraciones psiquiátricas y alteraciones gonadales. La diabetes mellitus, de aparición precoz y con poca prevalencia de cetoacidosis y la atrofia óptica se consideran criterios diagnósticos fundamentales en este síndrome. Se presenta en la infancia, lo que da lugar a una mayor dificultad diagnóstica y terapéutica, con una elevada morbimortalidad y deterioro de la calidad de vida por las afectaciones neurológicas y urológicas. Se presentaron dos pacientes, hermanos, con síndrome de Wolfram y sus manifestaciones oftalmológicas, cuyo diagnóstico se realizó por la presencia de diabetes mellitus en la primera década de la vida y atrofia óptica bilateral, ahora con 18 y 11 años de edad, respectivamente.

Wolfram syndrome is a progressive neurodegenerative disease with an autosomal recessive inheritance, characterized by the presence of diabetes mellitus and optic atrophy, diabetes insipidus and neurosensorial deafness can also be present, explaining the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness).The syndrome shows some various clinical manifestations such as urinary tract dilation and, neurological, psychiatric and gonadal disorders.The early onset diabetes mellitus, a low prevalence of ketoacidosis and an optic atrophy are considered key diagnostic criteria in this syndrome. It occurs during childhood what leads to a bigger diagnostic and therapeutic difficulty, with an elevated morbi-mortality and deterioration of the quality of life due to the neurological and urological affectations. Two brother patients with Wolfram syndrome and his ophthalmological manifestations were reported, whose diagnosis was made by the presence of diabetes mellitus in the first decade of life and bilateral optic atrophy, now they are 18 and 11 years old.

Presentación de dos hermanos con síndrome de Wolfram / Presentation of Two Brothers with Wolfram Syndrome

El síndrome de Wolfram es una enfermedad neurodegenerativa progresiva con transmisión autosómica recesiva, caracterizada por la presencia de diabetes mellitus y atrofia óptica, también pueden estar presentes la diabetes insípida y la disacusia neurosensorial explicando el acrónimo DIDMOAD (diabetes insípida, diabetes mellitus, atrofia óptica y sordera). Cursa con diversas manifestaciones clínicas, además, como la dilatación de las vías urinarias, alteraciones neurológicas, alteraciones psiquiátricas y alteraciones gonadales. La diabetes mellitus, de aparición precoz y con poca prevalencia de cetoacidosis y la atrofia óptica se consideran criterios diagnósticos fundamentales en este síndrome. Se presenta en la infancia, lo que da lugar a una mayor dificultad diagnóstica y terapéutica, con una elevada morbimortalidad y deterioro de la calidad de vida por las afectaciones neurológicas y urológicas. Se presentaron dos pacientes, hermanos, con síndrome de Wolfram y sus manifestaciones oftalmológicas, cuyo diagnóstico se realizó por la presencia de diabetes mellitus en la primera década de la vida y atrofia óptica bilateral, ahora con 18 y 11 años de edad, respectivamente.(AU)

Wolfram syndrome is a progressive neurodegenerative disease with an autosomal recessive inheritance, characterized by the presence of diabetes mellitus and optic atrophy, diabetes insipidus and neurosensorial deafness can also be present, explaining the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness).The syndrome shows some various clinical manifestations such as urinary tract dilation and, neurological, psychiatric and gonadal disorders.The early onset diabetes mellitus, a low prevalence of ketoacidosis and an optic atrophy are considered key diagnostic criteria in this syndrome. It occurs during childhood what leads to a bigger diagnostic and therapeutic difficulty, with an elevated morbi-mortality and deterioration of the quality of life due to the neurological and urological affectations. Two brother patients with Wolfram syndrome and his ophthalmological manifestations were reported, whose diagnosis was made by the presence of diabetes mellitus in the first decade of life and bilateral optic atrophy, now they are 18 and 11 years old.

[Optic neuropathy in a case of recurrent idiopathic hypertrophic pachymeningitis unresponsive to steroids and immunosuppressants]. / Neuropatía óptica en un caso de paquimeningitis hipertrófica idiopática recurrente sin respuesta a esteroides e inmunosupresores.

CASE REPORT: A 38-year-old female patient with bilateral papilledema who presented with loss of vision in her left eye. The Magnetic Resonance Imagining (MRI) showed thickening of the dura mater, and the intracranial pressure was elevated. A cancer, infectious, and autoimmune origin was ruled out. DISCUSSION: The initial response to high doses of corticoids was satisfactory, with disappearance of the optic disc enema, with visual acuity and an improvement in the MRI. However, after one year without treatment she had a new outbreak of the disease. Despite renewed treatment with corticoids and azathioprine, the patient developed a left optic neuropathy and irreversible visual loss.

Síndrome de Wolfram: informe de dos casos / Wolfram syndrome: report two cases

El síndrome de Wolfram o DIDMOAD es un trastorno neuroendocrino degenerativo hereditario, caracterizado por la asociación de diabetes insípida, diabetes mellitus de inicio en la juventud, atrofia óptica, sordera neurosensorial y otros trastornos. Se presentan dos hermanos con el síndrome de Wolfram atendidos en el Hospital Oftalmológico Amistad Argelia-Cuba, El Oued, Argelia, en agosto de 2015. Resulta importante su detección temprana debido a las devastadoras consecuencias físicas y emocionales en los pacientes que la padecen(AU)

The Wolfram´s syndrome is an inherited degenerative DIDMOAD neuroendocrine disorder characterized by the association of diabetes insipidus, diabetes mellitus onset youth, optic atrophy, sensorineural hearing loss and other disorders. Two brothers are presented with Wolfram syndrome treated at the Hospital-Cuba Friendship with Algeria, El Oued, Algeria, in August 2015. It is important to early detection due to the devastating physical and emotional consequences in patients who have it(AU)

Neuropatia óptica dominante associada à hipoacusia e apresentação tardia / Kjer's disease associated with hypoacusis and late clinical manifestation

A neuropatia óptica de Kjer, ou atrofia óptica dominante, é a mais frequente das neuropatias ópticas familiares. Trata-se de uma atrofia óptica de caráter autossômico dominante que se dá por uma alteração no gene OPA1, no cromossomo 3q28, com penetrância de 98% Apenas 15% dos casos possuem acuidade visual de 0,1 ou pior, apresentando ainda diferentes graus de atrofia do disco. Este relato objetiva descrever as características genéticas e clínicas da doença, bem como apresentar medidas de aconselhamento familiar. Para isso, será relatado um caso clínico de atrofia óptica dominante no qual se constata perda acentuada da acuidade visual, início de manifestações atipicamente tardias e hipoacusia bilateral.

The optic neuropathy of Kjer, or dominant optic atrophy, is the most common among optic neuropathies. iI is an optical atrophy of dominant autosomal character that is caused by an alteration in the gene on chromosome 3q28 with OPA1 penetration of 98% Only 15% of cases have visual acuity of 0.1 or worse, while demonstrating different grades of atrophy of the disc. This report aims to describe the genetic and clinical characteristics, and methods of family counseling through the presentation of a case of dominant optic atrophy with severe loss of visual acuity, together with the onset of unusually late and bilateral hearing loss.

Síndrome de Charles Bonnet en cuatro casos con atrofia óptica / Charles Bonnet syndrome in four cases with optical atrophy

El síndrome de Charles Bonnet constituye un trastorno muy poco reportado. En Cuba, que se conozca, no hay referencia de casos publicados hasta este momento. Se caracteriza por la presencia de alucinaciones visuales complejas en individuos con pérdida visual, mentalmente sanos y con conciencia crítica de la naturaleza irreal de sus alucinaciones. Se presentan cuatro casos con este síndrome relacionados con déficit visual secundario a atrofia óptica...

Charles Bonnet syndrome is an underreported disorder. As far as we know, there are no publicized references in Cuba up to the present time. This syndrome involves complex visual hallucinations in visually impaired individuals, who are mentally healthy and have intact cognition of the unreal nature of their hallucinations...

Síndrome de Charles Bonnet en cuatro casos con atrofia óptica / Charles Bonnet syndrome in four cases with optical atrophy

El síndrome de Charles Bonnet constituye un trastorno muy poco reportado. En Cuba, que se conozca, no hay referencia de casos publicados hasta este momento. Se caracteriza por la presencia de alucinaciones visuales complejas en individuos con pérdida visual, mentalmente sanos y con conciencia crítica de la naturaleza irreal de sus alucinaciones. Se presentan cuatro casos con este síndrome relacionados con déficit visual secundario a atrofia óptica...

Charles Bonnet syndrome is an underreported disorder. As far as we know, there are no publicized references in Cuba up to the present time. This syndrome involves complex visual hallucinations in visually impaired individuals, who are mentally healthy and have intact cognition of the unreal nature of their hallucinations...

Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report / Anticorpo da neuromielite óptica em neuropatia óptica hereditária de Leber: relato de caso

Neuromyelitis optica antibody (or aquaporin-4 antibody) is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

Anticorpo da neuromielite óptica (ou anticorpo aquaporina-4) é um marcador sorológico bem estabelecido associado à síndrome de alto risco para neuromielite óptica, doença inflamatória desmielinizante, caracterizada por ocorrência bilateral, simultânea de neurite óptica ou por episódio isolado de mielite transversa com achado de lesões espinais longitudinais extensas. Por outro lado, a neuropatia óptica hereditária de Leber é uma doença primariamente hereditária que afeta todos os tecidos do corpo e sua apresentação clínica envolve o nervo óptico e, eventualmente, a medula espinal. Aspectos clínicos comuns sugerem que neuromielite óptica e neuropatia óptica hereditária de Leber possam atingir os mesmos órgãos. O caso descrito enfatiza a coexistência de marcadores sorológicos das duas doenças e sugere a necessidade de investigação futura desta apresentação clínica atípica para confirmar ou não esta associação.

Consanguinidade e síndrome de Wolfram: relato de caso / Consanguinity and Wolfram syndrome: case report

JUSTIFICATIVA E OBJETIVOS: A síndrome de Wolfram (SW) é uma condição neurodegenerativa rara, progressiva e de herança autossômica recessiva, envolvendo o sistema nervoso central, nervos periféricos e tecidos neuroendócrinos. Este estudo teve por objetivo relatar um caso de SW. RELATO DO CASO: Paciente do sexo masculino, 17 anos, admitido com quadro de retenção urinária, parestesias e fortes dores nos membros inferiores. Era portador de diabetes mellitus (DM) tipo 1 mal controlado negativo para anticorpos anti-GAD e anti-insulina e apresentava história familiar de consanguinidade, além de dois irmãos com DM. Durante sua avaliação, constataram-se presença de amaurose com atrofia óptica, redução da acuidade auditiva, baixa estatura, atraso puberal, distúrbios psiquiátricos e diabetes insipidus. Foi tratado de infecção urinária, porém apresentou piora súbita aos 35 dias de internação com quadro de crises convulsivas, hipotensão, insuficiência respiratória e óbito. CONCLUSÃO: O diagnóstico de SW deve ser considerado em pacientes com DM associado à atrofia do nervo óptico.

BACKGROUND AND OBJECTIVES: Wolfram syndrome (WS) is a rare, progressive, autosomal recessive neurodegenerative disorder, involving the central nervous system, peripheral nerves and neuroendocrine tissues. This study aimed to reporta case of WS. CASE REPORT: A male patient, aged 17, was admitted with signs of urinary retention, paresthesias and severe pain in the lower limbs. He also had poorly controlled type 1 diabetes mellitus (DM) negative for anti-GAD and anti-insulin and had a family history of consanguinity, and two brothers with DM. During his assessment, he was found to have amaurosis with optic atrophy, decreased hearing acuity, short stature, delayed puberty, psychiatric disorders and diabetes insipidus. He was treated for urinary infection, but suddenly worsened at 35 days of hospital admission, with seizures, hypotension, respiratory failure and death. CONCLUSION: The diagnosis of WS should be considered in patients with DM associated with atrophy of the optic nerve.