Distrofia miotónica tipo 1: 13 años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo / Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation

Introducción: Se desconoce la incidencia de la distrofia miotónica tipo 1 (DM1), enfermedad con gran variedad fenotípica, en nuestra región. El objetivo de nuestro trabajo es estimar la incidencia de DM1 en nuestro centro (referencia en Aragón) e identificar las características propias de nuestra población (correlación genotipo-fenotipo). Métodos: Estudio descriptivo retrospectivo de 459 pacientes clasificados según número de repeticiones CTG en: normal (5-35), premutado (36-50), protomutado (51-80), pequeñas expansiones (81-150), intermedias (151-1.000) y grandes (> 1.000). Además, según el fenotipo mostrado, se categorizaron como: no afectos (5-50 CTG), forma leve o asintomática (51-150 CTG), clásica (151-1.000 CTG) y severa (> 1.000 CTG). Resultados: La incidencia de DM1 fue de 20,61 (IC 95%: 19,59-21,63) casos por millón de individuos-año. Se evidenció una correlación inversa entre el número de CTG y la edad al diagnóstico genético (ρ = −0,547; IC 95%: −0,610 a −0,375; p < 0,001). El CTG5 fue el alelo polimórfico más frecuente en sanos. Del total de afectos, el 28,3% presentaron la forma leve o asintomática, el 59,1% la forma clásica y el 12,6% la forma severa. El 35,1% presentaron herencia materna, el 59,4% herencia paterna y el 5,5% herencia incierta. En las formas leves la calvicie frontal en varones fue el rasgo fenotípico más prevalente, junto con miotonía y cataratas, mientras que en la clásica predominó la ptosis palpebral, la debilidad facial, las alteraciones en la voz y la pronunciación, la miotonía y la sensación de cansancio/somnolencia. Conclusiones: La incidencia de DM1 es relevante en Aragón. La revisión multidisciplinar del fenotipo de pacientes con DM1 es clave para un diagnóstico precoz y medicina personalizada.(AU)

Introduction: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). Methods: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). Results: The incidence of DM1 was 20.61 cases per million person-years (95% CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = −0.547; 95% CI: −0.610 to −0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. Conclusions: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.(AU)

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation.

INTRODUCTION: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = -0.547; 95% CI, -0.610 to -0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Myotonic dystrophy type1: 13years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation. / Distrofia miotónica tipo1: 13años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo.

INTRODUCTION: The incidence of myotonic dystrophy type1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (>1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (>1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95%CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ=-0.547; 95%CI: -0.610 to -0.375; P<.001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

[Bethlem myopathy: when the phenotype is misleading]. / Miopatía de Bethlem: cuando el fenotipo confunde.

TITLE: Miopatía de Bethlem: cuando el fenotipo confunde.

[Relationship between homocysteinaemia and sympathetic skin response in Parkinson's disease]. / Relacion entre homocisteinemia y respuesta simpaticocutanea en la enfermedad de Parkinson.

INTRODUCTION: High levels of homocysteine linked to treatment with levodopa have been observed in patients with Parkinsons disease (PD). Our aim was to assess the influence of serum homocysteine levels and other PD-related on the sympathetic skin response. PATIENTS AND METHODS: An observational, cross-sectional study was conducted that consecutively included patients with PD. We unilaterally assessed the sympathetic skin response in the upper limbs. We measured the influence of PD severity (measured by the Hoehn and Yahr and the Schwab and England scales, and the Unified Parkinson Disease Rating Scale) and blood homocysteine, vitamin B12 and folic acid levels on the latency and amplitude of the sympathetic skin response. RESULTS: A total of 78 patients were enrolled, and all achieved a sympathetic skin response. In the bivariate analysis, latency was significantly correlated with age, age at PD onset and homocysteinaemia levels. The presence of hyper-homocysteinemia was associated with a longer latency. The amplitude was only correlated with the score on the Schwab and England scale. In the multivariate analysis, age was the only variable that showed a significant association with the latency duration and homocysteine levels. CONCLUSION: A direct association could not be established between the increase in homocysteinaemia levels and sympathetic skin response dysfunction in PD. The results of the multivariate analysis suggest that latency prolongation in elderly patients could be due to the fact that these patients have higher blood levels of homocysteinaemia.

TITLE: Relacion entre homocisteinemia y respuesta simpaticocutanea en la enfermedad de Parkinson.Introduccion. En la enfermedad de Parkinson (EP) se han observado niveles elevados de homocisteina en relacion con el tratamiento con levodopa. Nuestro objetivo ha sido valorar su influencia y la de otras variables relacionadas con la propia EP sobre la respuesta simpaticocutanea. Pacientes y metodos. Estudio observacional, transversal, en el que se incluyo de forma consecutiva a pacientes con EP. Se valoro la respuesta simpaticocutanea de forma unilateral en los miembros superiores, y se determino la influencia de la gravedad de la EP segun la Unified Parkinson Disease Rating Scale, y las escalas de Hoehn y Yahr y de Schwab y England, y de los niveles sanguineos de homocisteina, vitamina B12 y acido folico sobre la latencia y amplitud de la respuesta simpaticocutanea. Resultados. Se incluyo a 78 pacientes. La respuesta simpaticocutanea se obtuvo en todos ellos. En el analisis bivariante, la latencia se correlaciono significativamente con la edad, con la edad de inicio de la EP y con los niveles de homocisteina. La presencia de hiperhomocisteinemia se relaciono con una latencia mas prolongada. La amplitud solo se correlaciono con la puntuacion en la escala de Schwab y England. En el analisis multivariante, la edad fue la unica variable que demostro una asociacion significativa tanto con la duracion de la latencia como con los niveles de homocisteina. Conclusion. No pudo establecerse una asociacion directa entre el aumento de homocisteinemia y la disfuncion de la respuesta simpaticocutanea. Los resultados del analisis multivariante sugieren que la prolongacion de la latencia en los pacientes de una mayor edad podria deberse a que estos presentan unos mayores niveles sanguineos de homocisteina.

[Association between myasthenia gravis and systemic lupus erythematosus: is it safe to use hydroxychloroquine?] / Asociacion entre miastenia grave y lupus eritematoso sistemico: es seguro el uso de hidroxicloroquina?

TITLE: Asociacion entre miastenia grave y lupus eritematoso sistemico: es seguro el uso de hidroxicloroquina?

Angioedema orolingual secundario al tratamiento con alteplasa en el ictus / Orolingual angiooedema secondary to alteplase treatment in cases of stroke

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Congenital endplate acetylcholinesterase deficiency responsive to ephedrine.

The authors describe two patients with congenital myasthenic syndrome (CMS) with end plate acetylcholinesterase (AChE) deficiency caused by mutations in the collagenic tail (ColQ) of AChE: a homozygous C-terminal Y230S mutation in Patient 1 and Y430S and a C-terminal splice-site mutation in Patient 2. In Patient 1, a Prostigmin (neostigmine bromide) test failed to distinguish between AChE deficiency and a slow-channel CMS. Both patients responded dramatically to ephedrine therapy.

[Hereditary neuromuscular diseases in paediatrics. Our experience over the last 14 years]. / Enfermedades neuromusculares hereditarias en pediatría. Nuestra experiencia de 14 años.

INTRODUCTION: Hereditary neuromuscular diseases are disorders which can vary largely in their age of onset, symptoms and severity. Many are severe, disabling and have an important personal, familial and social impact and can restrict the prognosis for survival. The constant progress being made in diagnostics makes it necessary to continually update knowledge and information. PATIENTS AND METHODS: We carried out a review of the hereditary neuromuscular diseases contained in the Neuropaediatrics database at the Hospital Miguel Servet in Zaragoza from May 1990 to October 2004. RESULTS: Of the 7,805 patients in the database, 123 (1.5% of the total) were patients with hereditary neuromuscular diseases, of whom 71 were males and 52 females. These included: 35 sensory-motor hereditary neuropathies, 17 dystrophinopathies, 10 myotonic dystrophies, 10 spinal muscular atrophies, four merosin-deficient congenital dystrophies, four other muscular dystrophies, three mitochondrial myopathies, three myasthenias, two familial neuropathies with insensitivity to pain, two Friedreich's ataxias, one familial neuropathy with liability to pressure palsies, one case of Walker-Warburg syndrome, five polyneuropathies associated to leukodystrophy and another 25 cases that could not be classified. Genetic studies provided a diagnosis in 36 cases (29.2%): nine myotonic dystrophies, eight dystrophinopathies, eight cases of spinal muscular atrophy, four demyelinating sensory-motor hereditary neuropathies, two instances of Friedreich's ataxia, two limb-girdle muscular dystrophies, one congenital myasthenia, one McArdle's disease and one case of Kearns-Sayre syndrome. CONCLUSIONS: Genetic studies enable us to establish diagnoses that were previously limited to the realm of assumption, and allow us to avoid the need for muscle tissue biopsies, which is a welcome development, especially when dealing with children. Immunohistochemical studies need to be updated and biological samples should be systematically saved in cases where no diagnosis is reached.

Actualización farmacológica de un caso de encefalomielitis progresiva con rigidez, con respuesta favorable a gabapentina / Progressive encephalomyelitis with rigidity responsive to gabapentin: a pharmacological update

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[Progressive encephalomyelitis with rigidity. Clinical and electrophysiological aspects]. / Encefalomielitis progresiva con rigidez. Aspectos clínicos, electrofisiológicos y tratamiento con gabapentina.

A 72-year-old man presented with a chronic illness constituted by muscle rigidity affecting his lower limbs, trunk and neck, either spontaneous or triggered by stimuli, together with a spastic paraparesis, manual amyotrophy and pseudobulbar syndrome. The electrophysiologic study showed continuous motor unit activity integrated by normal motor unit potentials. Biochemical and imaging results were normal. These data suggest the diagnosis of idiopathic progressive encephalomyelitis with rigidity. Following administration of gabapentin (2000 mg daily), muscle rigidity and electromyographic continuous motor unit activity were suppressed. Transient drowsiness was the only side effect. The authors have tried to relate these findings to those found in the literature.

Encefalomielitis progresiva con rigidez. Aspectos clínicos, electrofisiológicos y tratamiento con gabapentina / Progressive encephalomyelitis with rigidity. Clinical and electrophysiologic aspects, and treatment with gabapentin

Se describe el caso de un paciente de 72 años de edad que presentó un proceso de evolución crónica constituido, esencialmente, por rigidez muscular de tronco, cuello y extremidades inferiores, exacerbada por estímulos tanto exógenos como endógenos, junto con paraparesia espástica, amiotrofia de las manos y síndrome seudobulbar. El estudio electrofisiológico evidenció una actividad muscular continua en forma de potenciales de unidad motora normales. Las pruebas complementarias bioquímicas y de imagen fueron normales. Estos datos apuntan al diagnóstico de encefalomielitis progresiva con rigidez, sin asociación con otra enfermedad. La administración de gabapentina a dosis de 2.000 mg/día suprimió la rigidez muscular y la actividad muscular continua en el estudio electromiográfico, con somnolencia transitoria como único efecto secundario. Se ha realizado una revisión bibliográfica sobre esa entidad, con la que se intentan relacionar los principales aspectos clínicos, neurofisiológicos y terapéuticos de nuestros hallazgos (AU)

[Thromboangiitis obliterans with cerebral involvement]. / Tromboangeítis obliterante con isquemia cerebral.

We report the case of a male with Buerger's disease and neurologic involvement. Cerebral arteriography showed multiple distal arterial obliterans with left-sided Moya-moya phenomena. Thromboangiitis obliterans is a chronic segmental occlusive disease affecting medium-sized and small arteries and veins throughout the body. Neurologic signs are rare, occurring in fewer than 2 % of cases, and most often found on the cortical surface and adjacent territories. We review the most common signs of this entity and its main diagnostic difficulties.

[Myasthenia gravis and non-Hodgkin's lymphoma]. / Miastenia grave y linfoma no hodgkiniano.

We describe 2 patients with myasthenia gravis and non-Hodgkin's lymphoma outside the thymus gland, in whom the two diseases progressed at different rates. Diagnosis of myasthenia gravis was based on clinical signs and compatible neurophysiologic studies, specifically by high acetylcholine antireceptor titers in the first patient and a positive Tensilon test in the second. In the first patient the clinical and serological signs of the two diseases progressed similarly. The association of these two diseases may have been the result of an underlying immunological disorder favoring their appearance, or of an immune response, caused by the lymphoma involving postsynaptic nicotinic acetylcholine receptors.