Stroke treatment outcomes in hospitals with and without Stroke Units. / Resultados en el tratamiento del ictus en hospitales con y sin Unidad de Ictus.

INTRODUCTION: Organisational capacity in terms of resources and care circuits to shorten response times in new stroke cases is key to obtaining positive outcomes. This study compares therapeutic approaches and treatment outcomes between traditional care centres (with stroke teams and no stroke unit) and centres with stroke units. METHODS: We conducted a prospective, quasi-experimental study (without randomisation of the units analysed) to draw comparisons between 2 centres with stroke units and 4 centres providing traditional care through the neurology department, analysing a selection of agreed indicators for monitoring quality of stroke care. A total of 225 patients participated in the study. In addition, self-administered questionnaires were used to collect patients' evaluations of the service and healthcare received. RESULTS: Centres with stroke units showed shorter response times after symptom onset, both in the time taken to arrive at the centre and in the time elapsed from patient's arrival at the hospital to diagnostic imaging. Hospitals with stroke units had greater capacity to respond through the application of intravenous thrombolysis than centres delivering traditional neurological care. CONCLUSION: Centres with stroke units showed a better fit to the reference standards for stroke response time, as calculated in the Quick study, than centres providing traditional care through the neurology department.

Molecular characterization of congenital myasthenic syndromes in Spain.

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations. Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A > C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management.

[Auditing as a tool for ongoing improvement in the Stroke Care Plan of the Region of Aragon]. / El audit como herramienta de mejora continua en el Plan de Atencion al Ictus de Aragon.

INTRODUCTION: The Aragon Stroke Care Plan (PAIA) was created in 2008 within the framework of the Spanish National Health System. Monitoring hospital care of strokes by means of periodic audits was defined as one of its lines of work. AIM: To determine the quality of the hospital care process for stroke patients in Aragon by using quality indicators. MATERIALS AND METHODS: Three audits were carried out (in the years 2008, 2010 and 2012) following the same methodology, based on the retrospective review of a representative sample of admissions due to stroke in each of the general hospitals belonging to the Aragonese Health Service. Information was collected on 48 indicators selected according to their scientific evidence or clinical relevance. RESULTS: Altogether 1011 cases were studied (331 in the first audit, and 340 in the second and the third). Thirty-one indicators showed a significant improvement (some of the most notable being the indicators of quality of the medical record, neurological assessment, initial preventive measures and, especially relevant, performing the swallowing test), two underwent a decline in their condition (related with rehabilitation treatment) and 15 did not register any significant variation. CONCLUSIONS: The implementation of the PAIA has given rise to a notable improvement in most of the quality indicators evaluated, which reflects an ongoing improvement in hospital stroke care. The progressive generalisation of specialised care and the creation of stroke units are some of the determining factors.

TITLE: El audit como herramienta de mejora continua en el Plan de Atencion al Ictus de Aragon.Introduccion. El Plan de Atencion al Ictus de Aragon (PAIA) se creo en 2008 en el marco de la Estrategia Nacional en Ictus del Sistema Nacional de Salud. La monitorizacion de la atencion hospitalaria al ictus mediante auditorias periodicas se definio como una de sus lineas de trabajo. Objetivo. Determinar la calidad del proceso asistencial hospitalario prestado al paciente con ictus en Aragon mediante el uso de indicadores de calidad. Materiales y metodos. Se realizaron tres audits (en los años 2008, 2010 y 2012) siguiendo la misma metodologia, basada en la revision retrospectiva de una muestra representativa de ingresos por ictus en cada uno de los hospitales generales del Servicio Aragones de Salud. Se recogio informacion sobre 48 indicadores seleccionados segun su evidencia cientifica o relevancia clinica. Resultados. Se estudiaron 1.011 casos (331 en el primer audit, y 340 en el segundo y en el tercero). Treinta y un indicadores presentaron una mejoria significativa (entre ellos destacan los indicadores de calidad de la historia clinica, de evaluacion neurologica, las medidas preventivas iniciales y, con especial relevancia, la realizacion de test de deglucion), dos sufrieron empeoramiento (relacionados con el tratamiento rehabilitador) y 15 no registraron variaciones significativas. Conclusiones. La implantacion del PAIA ha supuesto una mejoria notable en la mayoria de los indicadores de calidad evaluados, reflejo de una mejora continua en la atencion hospitalaria del ictus. La generalizacion progresiva de la atencion especializada y la creacion de las areas de ictus son algunos de los factores determinantes.

Long-term follow-up in patients with congenital myasthenic syndrome due to RAPSN mutations.

Rapsyn (RAPSN) mutations are a common cause of postsynaptic congenital myasthenic syndromes. We present a comprehensive description of the clinical and molecular findings of ten patients with CMS due to mutations in RAPSN, mostly with a long-term follow-up. Two patients were homozygous and eight were heterozygous for the common p.Asn88Lys mutation. In three of the heterozygous patients we have identified three novel mutations (c.869T > C; p.Leu290Pro, c.1185delG; p.Thr396Profs*12, and c.358delC; p.Gln120Serfs*8). In our cohort, the RAPSN mutations lead to a relatively homogeneous phenotype, characterized by fluctuating ptosis, occasional bulbar symptoms, neck muscle weakness, and mild proximal muscle weakness with exacerbations precipitated by minor infections. Interestingly, episodic exacerbations continue to occur during adulthood. These were characterized by proximal limb girdle weakness and ptosis, and not so much by respiratory insufficiency after age 6. All patients presented during neonatal period and responded to cholinergic agonists. In most of the affected patients, additional use of 3,4-diaminopyridine resulted in significant clinical benefit. The disease course is stable except for intermittent worsening.

[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.

[Reasons for requesting neuroimaging studies in the evaluation of primary headache]. / Motivos de solicitud de neuroimagen en las cefaleas primarias.

INTRODUCTION: There is some controversy concerning the need to perform neuroimaging studies in patient complaining of headache. 90% of the people had a complaint of headache during their life, and it is impossible to perform neuroimaging studies in all of them. OBJECTIVE: The aim of this study is knowing the reasons for indications neuroimaging studies in the evaluation of primary headaches and the effectiveness at the diagnosis. PATIENTS AND METHODS: The clinical records of patients who a neuroimaging study was performed for headache during 1998 were retrospectively studied. We analysed in all patients: the age, sex, diagnosis of headache, suspicion of diagnosis, reason and time for indication the neuroimaging study, and if the study modified the diagnosis. RESULTS: During 1998, were performed 107 neuroimaging studies in 96 patients. The mean age were 38 years. 60% were females. The suspicion of diagnosis was primary headache in 71% patients. Only one patient had an abnormality. The reasons for applying a neuroimaging study were: in 20 of the patients the migraine was more frequent and they didn t relieve with abortive drugs, in 20 there was a migraine aura, in 11 because the migraine turned to daily headache, in 17 the family asked for a neuroimaging study, there was a 17 of patients seemed to have an organic disease, in 2 the headache appeared daily, and in 7 of the cases weren't any reasons. CONCLUSIONS: Headache is the most frequent reason for asking a neuroimaging study. Primary headache is the type of headache that justifies most of indications. The most frequent reasons for performing a study were common changes in characteristics of migraine.

[Early presentation of crises and the development of epilepsy in cerebral intra-parenchymatous hemorrhage]. / Presentación precoz de crisis y evolución de la epilepsia en la hemorragia intraparenquimatosa cerebral.

PATIENTS AND METHODS: Of a total of 283 patients with spontaneous or hypertensive cerebral intraparenchymatous hemorrhage, 18 (6.3%), with no previous epilepsy, had crises whilst being followed-up for a period of between 2 and 7 years. In 14 cases the hematoma was lobar and 4 involved the basal ganglia or thalamus. In 8 cases (2.8% of all hemorrhage), these crises occurred during the first 24 hours, or as a first symptom of intraparenchymatous hemorrhage. One patient presented with status epilepticus with generalized crises and two had subentrant secondarily generalized partial crises at the time of the ictus. Treatment with anti-epileptic drugs was started in 13 patients. Twelve patients (4.2% of the hemorrhages) developed symptomatic epilepsy with partial crises with or without secondary generalization. RESULTS AND CONCLUSIONS: The maximum rate of recurrence was four crises per year. However, in one patient, reduction of the dose of medication led to the appearance of status epilepticus. Patients with crises of late onset developed epilepsy more often than those who had early crises. In those with crises there was a predominance of bilobular involvement with participation of the parietal lobe and extension of the hematoma or oedema to the cerebral cortex.

[Determining factors in decisions regarding cardio-pulmonary resuscitation in patients with cerebral hemorrhage]. / Factores determinantes de las decisiones de reanimación cardiopulmonar en pacientes con hemorragia cerebral.

INTRODUCTION AND OBJECTIVE: Some medical factors related with cardiopulmonary resuscitation (CPR) outcome are known. Moreover, there are other factors, not strictly medical ones, as age, gender, race and socioeconomic status, that influence on decisions of CPR. The aim of this study was to analyse the influence of all this factors on in-hospital CPR of the patients with intracerebral hemorrhage. MATERIAL AND METHODS: This retrospective study comprised all the consecutive patients hospitalized with spontaneous intracerebral hemorrhage who died within 30 days of hospital admission in a public hospital during the period 1987-1994. We used stepwise logistic regression to identify variables that had a significant independent relation with decision of CPR. RESULTS: We identified 73 patients, 50 men and 23 women. Their mean age was 61 years. RCP was performed in 25 patients (34%). A logistic regression revealed that age (OR 0.8), Glasgow score on admission (OR 0.67) and time of death (OR 1.2) were significantly associated with CPR decision. CONCLUSIONS: CPR was less probable in aged even though they had better level of consciousness on admission. Moreover, CPR was less probable early in the morning.

[Neurocutaneous melanosis]. / Melanosis neurocutánea.

INTRODUCTION: Neurocutaneous melanosis is an infrequent condition characterized by the presence of numerous gigantic cutaneous naevi and melanocytic infiltration of the central nervous system and/or the leptomeningeal layers. Different clinical features may be seen: endocranial hypertension due to hydrocephalus, cranial nerve paralysis, myelopathy, convulsive seizures, etc. The prognosis is considered to be malignant. Only positive CNS histological findings confirm the diagnosis. CLINICAL CASE: We present the case of a man with cutaneous lesions compatible with the diagnosis of neurocutaneous melanosis since birth, with benign self-limiting epilepsy in early childhood. Cerebral CT and MR scans were normal until the age of 17, when hipper-signal lesions appeared on MR, infiltrating the leptomeninges of the deep temporal pole and anterior aspect of the cerebral peduncles, which suggested the presence of melanocytes in the CNS. CONCLUSIONS: There are cases of neurocutaneous melanosis with a good medium-term prognosis and benign manifestations until infiltration of the CNS occurs. Then they start to show the classical behavior of cases with a malignant prognosis. MR should be included as part of the diagnostic criteria for neurocutaneous melanosis. MR should be done periodically in patients with cutaneous lesions suggestive of this condition.

[Spontaneous intracranial hypotension: findings of cerebral NMR]. / Hipotensión intracraneal espontánea: hallazgos en RMN cerebral.

INTRODUCTION: The intracranial hypotension syndrome is characterized by a cerebrospinal fluid (CSF) pressure of less than 60 mmH2O and presents as postural hypotension which is often accompanied by nausea, vomiting, cervicalgia and some degree of neck rigidity. It is considered to be spontaneous when there is no known precipitating factor. It is believed that there is a CSF leak across the subarachnoid space, although it is not always possible to detect this. In recent years several authors have described different pathological findings on magnetic resonance (MR) studies. CLINICAL CASE: We present the radiological studies of a patient with clinical evidence of headache which was worse on standing and improved when lying down. The outflow pressure of CSF was 6 mmH2O when lying down. On isotopic cisternography using Tc DTPA-99m there was no detectable CSF leak. On cerebral MR there was diffuse pachymeningeal thickening with increased signals in T1 sequences. This was more pronounced in T2 with lineal dural uptake of contrast at infra and supratentorial levels. The brain stem meninges were intact. In parallel with a favorable clinical course, following clinical resolution the radiological images were seen to have returned to normal. CONCLUSIONS: Radiological findings, together with a compatible clinical condition, help to establish the diagnosis of spontaneous intracranial hypotension and avoids the use of unnecessary clinical investigations.

[Etiology in complex partial epilepsy. I. Neuroimaging studies]. / Etiología en epilepsia parcial compleja. I. Estudios de neuroimagen.

With the appearance of MR, a great advance has been made in the study of the aetiology of epilepsy. This technique can show anomalies not detected in CT scans, obtain images of multiple planes, improve the differentiation of cerebral tissues and allow improved visualization of the temporal lobe, making it very useful in the study of patients with complex partial crises (CPC). We studied 151 epileptics with CPC by means of CT scan and MR in all cases; the anomolous topography was the same in all cases, but the diagnosis was not. In patients with a previously normal CT scan, on MR anomalies were detected in 24 cases. We found a statistical differences on evaluation of the MR anomaly depending on whether the CT scan was normal or abnormal. Statistical differences were also found when there were a greater number of anomalies on MR depending on the frequency of crises at the onset of the disorder.

[Aspects of neuropathy in mitochondrial diseases]. / Caracterización de la neuropatía en las enfermedades mitocondriales.

INTRODUCTION: The existence of neuropathy has been described in mitochondrial disorders such as MELAS, MERRF, Leigh's syndrome, the Kearns-Saye syndrome, myoneurogastro-intestinal encephalopathy and progressive external ophthalmoplegia and constitutes a basic component of the NARP (neuropathy, ataxia and retinosis pigmentosa). However, the general prevalence of the neuropathy and its characteristics within the mitochondrial encephalopathies is not well understood. OBJECTIVES: To characterize the neuropathy and try to establish a genotype-phenotype correlation. PATIENTS AND METHODS: Within study guidelines, we made a retrospective study of 27 patients, diagnosed as having mitochondrial disease, who had had neurophysiological studies (EMG-ENG). In those in whom neuropathy had been found we analysed the clinical, neurophysiological and genetic characteristics. RESULTS: Neuropathy was present in 37% of the patients who had an average age of 13 years, ranging from 1 to 25 years. Syndromic diagnoses were: 7 encephalomyopathies, one MELAS, one MERRF and one NARP. Four of the patients were classified genetically. In all but two of the patients the neuropathy was asymptomatic. The biochemical alterations seen were: deficit of Complex 1 in 3 patients, of complex III in 3 patients, of complex IV in 2 and of pyruvate dehydrogenase in one patient. The type of neuropathy found was varied, with predominance of axonal-type motor neuropathy but no correlation with either biochemical defects or genetic diagnosis. CONCLUSIONS: Neuropathy is a common finding in mitochondrial disorders and probably is under-diagnosed. The axonal form predominates. We have not been able to establish correlations between phenotypes and genotypes.