Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy.

BACKGROUND: Between 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI) favouring predominant expression of the DMD mutant allele. However the prognostic use of XCI analysis is controversial. We aimed to evaluate the correlation between X-chromosome inactivation and development of clinical symptoms in a series of symptomatic female carriers of dystrophinopathy. METHODS: We reviewed the clinical, pathological and genetic features of twenty-four symptomatic carriers covering a wide spectrum of clinical phenotypes. DMD gene analysis was performed using MLPA and whole gene sequencing in blood DNA and muscle cDNA. Blood and muscle DNA was used for X-chromosome inactivation (XCI) analysis thought the AR methylation assay in symptomatic carriers and their female relatives, asymptomatic carriers as well as non-carrier females. RESULTS: Symptomatic carriers exhibited 49.2% more skewed XCI profiles than asymptomatic carriers. The extent of XCI skewing in blood tended to increase in line with the severity of muscle symptoms. Skewed XCI patterns were found in at least one first-degree female relative in 78.6% of symptomatic carrier families. No mutations altering XCI in the XIST gene promoter were found. CONCLUSIONS: Skewed XCI is in many cases familial inherited. The extent of XCI skewing is related to phenotype severity. However, the assessment of XCI by means of the AR methylation assay has a poor prognostic value, probably because the methylation status of the AR gene in muscle may not reflect in all cases the methylation status of the DMD gene.

Ictus embólico de circulación anterior secundario a una oclusión trombótica del tronco braquiocefálico: utilidad del estudio neurosonológico / Anterior circulation embolic stroke secondary to thrombotic occlusion of the brachiocephalic trunk: the usefulness of neurosonological studies

Introducción. La oclusión ateroesclerótica del tronco braquiocefálico (TBC) es una patología infrecuente y su presentación en forma de embolismo arterioarterial resulta poco común, pero su identificación precoz es importante debido a sus implicaciones terapéuticas. Caso clínico. Varón de 49 años de edad que presentaba un cuadro deficitario brusco en el territorio de la arteria cerebralmedia derecha. El estudio Doppler transcraneal urgente mostraba un patrón de oclusión proximal de la porción M1 de dicha arteria. Tras la administración de activador del plasminógeno tisular recombinante intravenoso se constató la recanalización parcial del vaso. El cuadro clínico evolucionó favorablemente. El estudio dúplex cervical y transcraneal demostró una oclusión del TBC que se confirmó mediante angiotomografía y cateterismo aórtico. Tras un bypass aorto-TBC distal, el estudio anatomopatológico confirmó el origen aterotrombótico de la obstrucción. Conclusiones. La presentación clínica más habitual de la oclusión del TBC cursa con síntomas transitorios debidos a fenómenos de robo en el territorio vertebrobasilar. Los síntomas cerebrales relacionados con alteración del territorio carotídeo responden en mayor medida a un mecanismo de embolización arterioarterial, y su identificación precoz es importante por sus implicaciones terapéuticas. Está indicado el tratamiento trombolítico. El estudio neurosonológico permite un diagnóstico rápido y preciso que aporta datos sobre la situación hemodinámica y la presencia de fenómenos embólicos distales (AU)

Introduction. Atherosclerotic occlusion of the brachiocephalic trunk (CBT) is a rare clinical entity and its presentation in the form of arterio-arterial embolism is uncommon. Early identification of patients with CBT occlusion may have important therapeutic implications. Case report. A man aged 49 presents with sudden onset symptoms involving the territory of the right middle cerebral artery. Emergent transcranial doppler evaluation showed a flow pattern of proximal right M1 occlusion. After intravenous recombinant tissue plasminogen activator administration, partial recanalization of the vessel was found and the patient improved clinically. Cervical and transcranial duplex sonography demonstrated an occlusion in CBT, which was later confirmed on CT angiography and digital angiography of supraaortic vessels. After aorto-innominate bypass, pathological analysis confirmed the atherosclerotic origin. Conclusions. The most common clinical presentation of CBT occlusion are transient ischemic symptoms related to steal phenomenon in the vertebro-basilar territory. Symptoms of carotid circulation stroke usually result from arterio-arterial embolic mechanism. Early recognition is important for its therapeutic implications, therefore thrombolytic therapy should be indicated. Neurosonologic study allows rapid and reliable examination on hemodynamic status and the presence of distal embolic phenomena (AU)

Mononeuritis múltiple en un paciente con síndrome de Churg-Strauss. Pseudobloqueos como expresión electroclínica temprana / Multiple mononeuritis in a patient with Churg-Strauss syndrome. Pseudo conduction block as an early electroclinical expression

Introducción. La mononeuritis múltiple es una de las manifestaciones más frecuentes del síndrome de Churg-Strauss. Caso clínico. En un varón de 53 años con síndrome de Churg-Strauss, se describe una mononeuritis múltiple aguda sensitivomotora de las cuatro extremidades. Mediante electrodiagnóstico en los primeros siete días se demostraron bloqueos de conducción en varios nervios. Los estudios posteriores objetivaron una polineuropatía axonal sensitivomotora difusa y bilateral con asimetrías, pero sin bloqueos. La electrofisiología y la histología, así como los estudios experimentales, indicaban que se trataba de una axonopatía secundaria a isquemia aguda. Conclusiones. Sólo en pocos casos, como en éste, y en estudios muy incipientes se han descrito bloqueos de conducción que, por su relación habitual con desmielinización, provocan confusión diagnóstica y pronóstica. La evolución suele demostrar una axonopatía por degeneración walleriana. Por tanto, en estos casos parece recomendable extremar la cautela y realizar estudios neurofisiológicos en las siguientes semanas para evitar inadecuados juicios diagnósticos y pronósticos (AU)

Introduction. Multiple mononeuritis is one of the most frequent manifestations of Churg-Strauss syndrome. Case report. We describe a case of acute sensory-motor multiple mononeuritis in all four limbs of a 53-year-old male with Churg-Strauss syndrome. Electrodiagnosis performed within the first seven days revealed conduction blocks in several nerves. Follow-up studies showed diffuse bilateral sensory-motor axonal polyneuropathy with symmetries, but without blocks. Electrophysiological and histological analyses, together with experimental studies, showed it to be an axonopathy secondary to acute ischaemia. Conclusions. In only a few cases, such as this one and in a small number of incipient studies, have there been reports of conduction blocks that, owing to the fact that they are commonly related with demyelination, give rise to confusion when it comes to diagnoses and prognoses. The condition usually displays axonopathy due to Wallerian degeneration. It therefore seems recommendable in these cases to proceed with caution and to perform neurophysiological studies in the following weeks in order to prevent inappropriate diagnostic and prognostic judgements from being formed (AU)

[Multiple mononeuritis in a patient with Churg-Strauss syndrome. Pseudo conduction block as an early electroclinical expression]. / Mononeuritis múltiple en un paciente con síndrome de Churg-Strauss. Pseudobloqueos como expresión electroclínica temprana.

INTRODUCTION: Multiple mononeuritis is one of the most frequent manifestations of Churg-Strauss syndrome. CASE REPORT: We describe a case of acute sensory-motor multiple mononeuritis in all four limbs of a 53-year-old male with Churg-Strauss syndrome. Electrodiagnosis performed within the first seven days revealed conduction blocks in several nerves. Follow-up studies showed diffuse bilateral sensory-motor axonal polyneuropathy with symmetries, but without blocks. Electrophysiological and histological analyses, together with experimental studies, showed it to be an axonopathy secondary to acute ischaemia. CONCLUSIONS: In only a few cases, such as this one and in a small number of incipient studies, have there been reports of conduction blocks that, owing to the fact that they are commonly related with demyelination, give rise to confusion when it comes to diagnoses and prognoses. The condition usually displays axonopathy due to Wallerian degeneration. It therefore seems recommendable in these cases to proceed with caution and to perform neurophysiological studies in the following weeks in order to prevent inappropriate diagnostic and prognostic judgements from being formed.

Usefulness of multimodal MR imaging in the differential diagnosis of HaNDL and acute ischemic stroke.

BACKGROUND: Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) is a rare disease which can present with focal neurological deficits and mimic stroke. A neurologist-on-duty faced with a HaNDL patient in the first hours might erroneously decide to use thrombolytic drugs, a non-innocuous treatment which has no therapeutic effect on this syndrome. CASE PRESENTATION: We present a case where neuroimaging, together with the clinical picture, led to a presumed diagnosis of HaNDL avoiding intravenous thrombolysis. CONCLUSIONS: This report shows the usefulness of multimodal MR imaging in achieving early diagnosis during an acute neurological attack of HaNDL. Our experience, along with that of others, demonstrates that neuroimaging tests reveal the presence of cerebral hypoperfusion in HaNDL syndrome.