Factors de confusió en el diagnòstic de narcolepsia

[cat] La narcolèpsia és una malaltia crònica causada per un dèficit d’hipocretina de probable etiologia autoimmune. El diagnòstic es basa en la clínica, els estudis electrofisiològics i les proves biològiques. Hi ha altres malalties que comparteixen símptomes amb la narcolèpsia, com pot ser la somnolència diürna excessiva, que també podem observar en pacient amb síndrome d’apnea/hipopnea del son (SAHS), o les al·lucinacions, que també es poden observar en pacients amb esquizofrènia. En quant a les proves electrofisiològiques, el diagnòstic s’estableix objectivant inicis de son en REM (SOREMP) en el test de latències múltiples del son (TLMS). Es sap que la possibilitat de presentar son REM no és igual durant tot el dia, però això no es contempla a l’hora de realitzar un TLMS. Hem estudiat una població de 153 pacients amb narcolèpsia atesos a l’Hospital Clínic de Barcelona. S’ha analitzat la coexistència de SAHS analitzant pacients amb un índex d’apnea/hipopnea (AHI) ≥ 10 i s’ha mirat la resposta d’aquests pacients al tractament amb CPAP i també si la presència d’aquestes apnees havia retardat el diagnòstic de narcolèpsia. Hem vist que el SAHS es presenta en el 24,8% de pacients amb narcolèpsia, que retarda significativament el diagnòstic de narcolèpsia i que la resposta al tractament amb CPAP és escassa. En aquesta mateixa població s’ha mirat la distribució de SOREMP durant el TLMS i si aquesta és homogènia o no, veient que hi ha un descens signiticatiu del nombre de SOREMP en la quarta becaina, i pensem que això hauria de tenir-se en compte a l’hora de realitzar l’exploració, especialment si se n’usen versions escurçades. D’altra banda s’ha estudiat la prevalença de narcolèpsia en una sèrie de 378 pacients amb esquizofrènia o trastorn esquizoafectiu de l’Hospital Parc Taulí. Aquest estudi s’ha realitzat en diverses etapes. En primer lloc s’ha passat un breu qüestionari per a detectar la presència de símptomes narcoleptiformes. Aquells en els que s’ha sospitat la presència d’aquests símptomes (n 24) s’ha realitzat una anamnesi més completa i s’ha obtingut una mostra de sèrum per a determinació d’HLA. En aquells amb HLA positiu per narcolèpsia (n 5) s’ha ofert realitzar una determinació d’hipocretina-1 en líquid cefaloraquidi, en els que ha estat normal. El nostre estudi no recolza la hipòtesi que aquestes dues entitats estiguin relacionades. També hem vist que la prevalença d’hipersòmnia és molt baixa en la nostra mostra de pacients, i, en la major part dels casos, està clarament relacionat amb l’inici de la malaltia psiquiàtrica o la possible coexistència d’un trastorn respiratori del son.[eng] Narcolepsy is a chronic disease caused by a deficiency in orexin. The diagnosis is based on symptoms, electrophysiological studies and biological tests. There are other diseases that share symptoms with narcolepsy, such as excessive daytime sleepiness, which can also be observed in patients with sleep apnea / hypopnea syndrome (OSA), or the hallucinations, which can also be seen in patients with schizophrenia. Regarding the electrophysiological tests, the diagnosis is established by detection of sleep onset periods in REM sleep (SOREMP) in the multiple sleep latency test (MSLT). We studied a population of 153 patients with narcolepsy evaluated at the Hospital Clinic of Barcelona. We analyzed the coexistence of SAHS patients, the response of patients to treatment with CPAP and if the presence of apnea was delayed diagnosis of narcolepsy. We saw that OSA occurs in 24.8% of patients with narcolepsy, which significantly delays the diagnosis of narcolepsy and the response to treatment with CPAP is scarce. In the same population we analyzed the distribution of SOREMP during TLMS and we found that there is a significant decrease in the number of SOREMP in the fourth nap, and we think that this should be taken into account when performing the test, especially if shortened versions are used. Finally we studied the prevalence of narcolepsy in a series of 378 patients with schizophrenia or schizoaffective disorder of Hospital Parc Taulí. This study was conducted in several stages. First we screened patients with a brief questionnaire to detect narcoleptiform symptoms. Those who presented narcoleptiform symptoms (n 24) were reevaluated obtaining complete medical sleep history and a serum sample for determination of HLA. Those with positive HLA narcolepsy (n 5) were offered to make a determination orexin-1 in cerebrospinal fluid, which was normal in all of them. Our study does not support the hypothesis that these two entities are related. We have also seen that the prevalence of hypersomnia is very low in our sample of patients, and in most cases, it’s clearly related to the onset of psychiatric illness and the possible coexistence of a respiratory disorder

Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: A multicentric observational study.

Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin being the most common first line treatment. Intravenous levetiracetam (ivLEV) is a new antiepileptic drug with interesting properties for SE. MATERIAL AND METHODS: Efficacy and effectiveness of ivLEV in SE were assessed in an observational, multicentric and retrospective study. Efficacy was defined as cessation of seizures in the 24h subsequent to starting ivLEV, with no need of any further antiepileptic drug. All patients were treated following the standard protocol (benzodiazepines plus phenytoin or valproate). ivLEV was used as add-on therapy, except in those cases with contraindication for the standard protocol, when it was administered earlier. RESULTS: 40 patients were included, 57% men, with a mean age of 63 years. The most common type of SE was partial convulsive (90%). ivLEV was effective in approximately half of the patients (57.5%), in a mean time of 14.4h. ivLEV was used as add-on treatment in 26 patients (after benzodiazepines plus phenytoin, valproate or both) with an efficacy of 46.1%, and as early treatment (pretreatment with benzodiazepines or nothing) in 14 patients with an efficacy of 78.5% (p 0.048). Adverse events were observed in 15% of patients. CONCLUSIONS: ivLEV was an effective antiepileptic drug for SE, but its efficacy depends on the timing of its administration, being more effective when used as early treatment, and less effective as add-on treatment

Additional file 1: of Exploring the presence of narcolepsy in patients with schizophrenia

Screening questionnaires: This questionnaire was developed as a screening tool for the main symptoms of narcolepsy. (DOCX 13 kb

Impairments in sleep and brain molecular clearance in people with cognitive deterioration and biological evidence of AD: a report of four cases

Abstract Background Recent evidence suggests that the failure of the glymphatic system – the brain’s waste clearance system, which is active during sleep – plays a key role in the pathophysiology of Alzheimer’s Disease (AD). Glymphatic function can be investigated using serial MRIs after intrathecal gadobutrol injection. This technique can reveal the health of the glymphatic system, but has not yet been used in participants with cognitive impairment due to AD. Case report This report describes the sleep and gadobutrol tracer clearance patterns of four participants diagnosed with mild to moderate cognitive impairment with evidence of AD pathology (pathological levels of Ab and p-tau in cerebrospinal fluid). We performed polysomnography and MRI studies before tracer injection and MRI scans at 1.5-2 h, 5–6 h, and 48 h after injection. Despite participants reporting no sleep problems, polysomnography revealed that all participants had moderate to severe sleep disturbances, including reduced sleep efficiency during the study and obstructive sleep apnea. Severe side-effects related to tracer administration were observed, impeding the completion of the protocol in two participants. Participants who finished the protocol displayed delayed and persistent tracer enrichment in the cortex and white matter, even 48 h after injection. These outcomes have not been observed in previous studies in participants without AD. Conclusion The findings suggest that brains with sleep impairment and AD pathology have poor glymphatic function, and therefore cannot clear the contrast tracer efficiently. This is likely to have caused the severe side effects in our participants, that have not been reported in healthy individuals. Our results may therefore represent the only available data acquired with this technique in participants with AD pathology

EEG extreme delta brush: An ictal pattern in patients with anti-NMDA receptor encephalitis.

INTRODUCTION: The anti-NMDA receptor (NMDAr) encephalitis-associated syndrome includes neuropsychiatric symptoms, impaired consciousness, seizures, autonomic instability, and hypoventilation. The electroencephalographic (EEG) activity throughout the course of the disease has still not been well documented. We reviewed electroclinical data of patients with NMDAr encephalitis to characterize their EEG and its clinical correlation. MATERIAL AND METHODS: We retrospectively identified 16 patients with NMDAr encephalitis from 8 Spanish medical centers, 15 of whom underwent video-EEG in the acute phase. RESULTS: In 15 patients (11 females, median age: 37.4, range: 14-87 years), seizures occurred in 9 (60%) and status epilepticus (SE) in 5 (33.3%). Magnetic resonance imaging (MRI) was abnormal in 10 (66.6%), and CSF (cerebrospinal fluid) was normal in 3 and abnormal in 12, with positive PCR (polymerase chain reaction) for Mycoplasma pneumoniae (1/15) and herpes simple virus (1/15). An ovarian teratoma was found in 1 patient and other malignancies (small cell lung carcinoma) in 1 patient. The EEG was abnormal in the acute phase in 14/15 (93.3%). Extreme delta brush (EDB) was observed in 5 (33.3%), and the presence of EDB was associated with SE in all cases. Rhythmic delta activity without EDB was observed in 5 (33.3%), while excessive beta activity was present in 4 (26.6%). Extreme delta brush can follow a pattern of well-characterized electroclinical seizures. CONCLUSIONS: Almost invariably, patients with NMDAr encephalitis had abnormal EEG. The presence of EDB, which can follow a pattern of well-characterized electroclinical seizures, in our patients was associated with seizures and SE. These findings suggest that EDB could be an evolutive pattern of an SE in NMDAr encephalitis. This article is part of a Special Issue entitled "Status Epilepticus"

Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (