1,720,993 research outputs found
Distrofia miotonica tipo 1 (Malattia di Steinert) e disturbi del sonno: prevalenza e severità dei disturbi respiratori durante il sonno al momento della diagnosi e scarsa consapevolezza da parte del paziente
No full textIntroduzione ed obiettivi dello studio: La distrofia miotonica (DM), la distrofia più comune nell'adulto, è una malattia autosomica dominante caratterizzata da una ampia varietà di manifestazioni multisistemiche. La distrofia miotonica di tipo 1 (DM1) è causata da espansione della tripletta CTG all’estremità 3’ del gene della DM proteina chinasi. Tra le caratteristiche cliniche multisistemiche della DM1 vi è la compromissione respiratoria. Gli obiettivi di questo studio consistevano nel valutare la prevalenza e la gravità dei disturbi respiratori nei pazienti con DM1 al momento della diagnosi e nell'indagare sulla consapevolezza di malattia e di compromissione respiratoria da parte dei pazienti.
Pazienti e Metodi: Tra i pazienti ricoverati presso la Clinica Neurologica di Ancona tra settembre 2007 e ottobre 2010 sono stati arruolati tutti i soggetti a cui veniva formulata la diagnosi genetica di DM1 confermata geneticamente. I pazienti sono stati sottoposti ad esame obiettivo generale e neurologico, visita oculistica, radiografia del torace e elettromiografia (EMG). Abbiamo analizzato le caratteristiche cliniche dei pazienti, il motivo che ha portato alla diagnosi, la presenza di sintomi suggestivi di un disturbo respiratorio (come affaticamento, dispnea, cefalea mattutina, ecc.). Tutti i pazienti venivano sottoposti a monitoraggio cardiorespiratorio notturno, spirometria ed emogasanalisi. Miotonia ed ipostenia sono state valutate utilizzando la scala per la disabilità (MDRS) e l'eccessiva sonnolenza diurna è stata determinata mediante la scala di sonnolenza di Epworth (ESS). Sono stati considerati come affetti da alterata funzione polmonare, i pazienti che avevano almeno uno dei seguenti reperti: PaCO2 diurna ≥ 45 mm Hg, capacità vitale forzata (FVC) 10 eventi per ora di sonno, SaO2 <90% per ≥ 5% della notte. L'indicazione alla ventilazione a pressione positiva non invasiva (NIV) veniva posta in presenza di uno tra PaCO2 ≥ 45 mm Hg, saturazione di ossigeno notturna ≤ 88% per 5 minuti consecutivi, FVC <50% del predetto.
Risultati: I dati sono stati raccolti su 21 pazienti (11 femmine/10 maschi), età media 39,7 anni (range 19-61 anni). L'EMG mostrava un quadro di distrofia miotonica in tutti i pazienti. Nessuno dei pazienti aveva deformità della gabbia toracica. Il motivo che ha portato alla diagnosi di DM1 è stata la presenza di un parente affetto in 7 casi (33,35%), il fenomeno miotonico in tre (14,3%), il rilievo di iperCKemia agli esami ematici in 2 (9, 5%), ipostenia in 7 (33,35%) e altri motivi (mal di testa e vertigini) in 2 (9,5%). Il 33% dei pazienti risultava avere emogasanalisi, spirometria e monitoraggio cardiorespiratorio notturno nella norma mentre il restante 67% presentava un’alterazione di almeno uno di tali esami. L’indagine che evidenziava compromissione della funzionalità respiratoria era il solo esame notturno in un paziente (5%), la sola spirometria in due pazienti (10%), emogasanalisi ed esame notturno in un paziente (5%), emogasanalisi e spirometria in tre pazienti (15%), spirometria ed esame notturno in tre pazienti (15%), tutti e tre gli esami in 4 pazienti (20%). Dei 14 soggetti con compromissione della funzione respiratoria 9 avevano una situazione così severa da soddisfare i criteri per NIV. Soltanto quattro dei 21 pazienti esaminati, adeguatamente interrogati, riportavano sintomi indicativi di alterazione della funzionalità respiratoria.Uno di questi pazienti non aveva compromissione della funzione respiratoria.
Conclusioni: In tre anni, sono stati arruolati 21 pazienti con DM1. E' probabile che l'incidenza di DM1 nella nostra regione sia significativamente più elevata rispetto a quanto ci si possa aspettare in relazione ai dati epidemiologici della letteratura. La maggior parte dei pazienti arruolati aveva prove di funzionalità respiratoria alterate. Non è stata trovata nessuna relazione significativa tra sintomi soggettivi, caratteristiche clinico-demografiche dei pazienti e compromissione respiratoria (p> 0,005). Un tempestivo riconoscimento di una compromissione respiratoria può portare ad un miglioramento della sopravvivenza e della qualità della vita mediante l'applicazione di NIV. L'importanza del monitoraggio della funzione respiratoria nei pazienti affetti da DM1 ha lo scopo di evitare procedure d’urgenza come l’intubazione. In relazione alla disomogeneità del quadro strumentale respiratorio, i tre esami che indagano la funzionalità respiratoria nei pazienti con DM1 andrebbero eseguiti tutti sin dal momento della diagnosi. Le linee guida relative alla indicazione alla NIV non tengono inoltre conto delle differenze che esistono tra le diverse patologie neuromuscolari, sarebbe pertanto necessaria la stesura di linee guida specifiche per ciascuna patologia neuromuscolare ed in particolare per la DM1.Background and purpose: Myotonic dystrophy (DM) is the most common dystrophy in adults. It is an autosomal dominant disease characterized by a variety of multisystemic features. Myotonic dystrophy type 1 (DM1) is caused by trinucleotide expansion of CTG in the myotonic dystrophy protein kinase gene. Clinical manifestations of DM1 include respiratory disorders. The goals of this study were to evaluate the prevalence and the severity of respiratory disorders in DM1 patients at diagnosis and to assess the awareness of the patients about the disease and the respiratory condition.
Patients and Methods: Consecutive patients with a genetically confirmed diagnosis of DM1 admitted in Clinica Neurologica of Ancona from September 2007 to October 2010 were enrolled at diagnosis. Patients underwent general and neurological physical examination, ophthalomological assessment, chest X-ray and electromyography (EMG). We analysed the clinical features of patients, the reason that led to diagnosis, the presence of symptoms suggestive of a respiratory disorder (such as fatigue, dyspnea, morning headache, etc). Nocturnal cardiorespiratory monitoring as well as spirometry and blood gases were performed in all DM1 patients. Myotonia and muscle weakness were rated using the five point muscular disability rating scale (MDRS) and excessive daytime sleepness was assessed by the Epworth Sleepiness Scale (ESS). Were regarded as suffering from impaired lung function, patients who had at least one of the following: daytime PaCO2 ≥ 45 mm Hg, forced vital capacity (FVC) 10 events per hour of sleep, SaO2 <90% for ≥ 5% of the night. Indication for Noninvasive Positive Pressure Ventilation (NIV) was one of PaCO2 ≥ 45 mm Hg, nocturnal oxygen saturation ≤ 88% for 5 consecutive minutes, FVC< 50% predicted.
Results: Data were collected on 21 patients (11 female/10 male), mean age 39,7 years (range 19-61 years). EMG revealed typical myotonic changes in all patients. None of the patients had chest deformity. The reason that led to diagnosis of DM1 was the presence of a sick relative in 7 cases (33.35%), the myotonic phenomenon in 3 (14.3%), detection of iperCKemia to blood tests in 2 (9, 5%), weakness in 7 (33.35%) and other reasons (headache and dizziness) in 2 (9.5%). One third of patients appeared to have normal blood gases, spirometry and nocturnal parameters while the remaining 66,7% had impaired lung function. The impaired lung function test was just the nocturnal cardiorespiratory monitoring in one patient (5%), just the spirometry in two patients (10%), blood gases and nocturnal cardiorespiratory monitoring in one patient (5%), blood gases and spirometry in three patients (15%), spirometry and nocturnal cardiorespiratory monitoring in three patients (15%), all three tests in 4 patients (20%). Of the 14 subjects with impaired respiratory function 9 had a so severe situation to met the criteria for NIV. Only four of the 21 patients properly interrogated reported symptoms suggestive of impaired lung function. One of these patients had no impairment of lung function.
Conclusions: We enrolled 21 DM1 patients in three years. Probably the incidence of DM1 in our region is significantly higher than expected according to the literature. The majority of the patients enrolled had evidence of impaired lung function. No significant relationships were found between subjective complaints, clinical-demographic features and respiratory compromission (p>0.005). Timely recognition of a respiratory compromission may lead to improved survival and quality of life by the application of non-invasive ventilatory support. Importance of monitoring respiratory function in patients with DM1 is designed to avoid emergency procedures such as intubation. In relation to the heterogeneity of respiratory involvement features, all the three pneumological tests should be performed in all DM1 patients from the time of diagnosis. The guidelines regarding the indication for NIV don't take into account the differences that exist between the various neuromuscular diseases, is therefore necessary to draw up specific guidelines for each neuromuscular disease and in particular for DM1
Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis.
No full textBACKGROUND
Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.
OBJECTIVE
The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.
METHODS
Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).
RESULTS
Four trials involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1-31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8-28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55-8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28-7.41; p = 0.657) and 4.20 (95% CI 1.82-9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87-16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22-12.86; p = 0.626) and 6.89 (95% CI 2.28-20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11-1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.
CONCLUSIONS
Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo
Brivaracetam add-on for refractory focal epilepsy
No full textOBJECTIVE:
To evaluate the efficacy and safety of the new antiepileptic drug brivaracetam (BRV) as add-on treatment for drug-resistant partial epilepsy using meta-analytical techniques.
METHODS:
Randomized, placebo-controlled, single- or double-blind, add-on trials of BRV in adult patients with drug-resistant partial epilepsy were identified through a systematic literature search. The following outcomes were assessed: 50% or greater reduction in seizure frequency, seizure freedom, incidence of treatment-emergent adverse events (TEAEs), and treatment withdrawal. Risk ratio (RR) with 95% confidence interval was estimated for each outcome.
RESULTS:
Six trials were included involving 2,399 participants according to the intent-to-treat, 1,715 for BRV, and 684 for placebo groups, respectively. The pooled RRs for the 50% responders and seizure freedom were 1.79 (1.51-2.12) and 4.74 (2.00-11.25), respectively. The subanalysis by levetiracetam (LEV) status did not show a statistically significant difference in the 50% responder rate when comparing BRV with placebo in patients with concomitant assumption of LEV. The TEAEs significantly associated with BRV were irritability (2.99 [1.28-6.97]), fatigue (2.19 [1.44-3.33]), somnolence (1.97 [1.45-2.68]), and dizziness (1.66 [1.19-2.31]). The overall RRs for treatment withdrawal due to TEAEs or any reason were 1.58 (1.04-2.40) and 1.27 (0.93-1.73), respectively.
CONCLUSIONS:
In adults with drug-refractory focal epilepsy, add-on BRV was effective to reduce seizure frequency and fairly well-tolerated. Further studies are needed to draw definitive conclusions about its efficacy in non-LEV-naive participants and evaluate its long-term safety profile
Efficacy and safety of adjunctive cannabidiol in patients with Lennox-Gastaut Syndrome: a systematic review and meta-analysis
No full textBACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs). OBJECTIVE: The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques. METHODS: Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the ≥ 50% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method. RESULTS: Two trials were included involving 396 participants. Patients presenting ≥ 50% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48-3.03); p < 0.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09-2.43); p = 0.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50-16.22; p = 0.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11-1.38; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases. CONCLUSIONS: Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs
Blood pressure variability and clinical outcome in patients with acute intracerebral hemorrhage
Full text linkBACKGROUND:
The aim of this study was to evaluate whether fluctuations of blood pressure (BP) levels occurring in the acute stage of spontaneous intracerebral hemorrhage (ICH) affect the 3-month clinical outcome.
METHODS:
We retrospectively identified consecutive patients hospitalized for acute spontaneous ICH. BP measurements over the first 72 hours from the onset of symptoms were recorded, and standard deviation (SD), coefficient of variation (CV), and maximum-minimum difference (max-min) were determined to characterize both systolic and diastolic BP variability (BPV). The measure of outcome was the 3-month functional status assessed by the modified Rankin Scale following a baseline severity-adjusted analysis.
RESULTS:
Among the 138 enrolled patients with ICH, 67 (48.6%) were classified as having a poor 3-month functional recovery. A dose-response relationship with poor outcome was found for each measure of systolic BPV--adjusted odds ratios (ORs) for the highest thirds of SD 7.95 (95% confidence interval [CI], 2.88-21.90), CV 7.74 (95% CI, 2.88-20.80), and max-min 8.36 (95% CI, 2.72-25.62; P < .001). The strength of association with diastolic BPV turned out to be weaker and significant only for the higher values (adjusted ORs for the highest thirds of SD 6.74 [95% CI, 2.52-18.04], CV 4.57 [95% CI, 1.77-11.81], and max-min 4.34 [95% CI, 1.72-10.93]).
CONCLUSIONS:
In patients with acute ICH, BPV was a strong predictor of the 3-month clinical outcome and may represent a still neglected potential therapeutic target
Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage
No full textBACKGROUND AND PURPOSE:
Increasing evidence suggests that inflammatory mechanisms are involved in the intracerebral hemorrhage-induced brain injury. We evaluated the prognostic role of the peripheral leukocyte counts and neutrophil-to-lymphocyte ratio (NLR) in patients with intracerebral hemorrhage.
METHODS:
Patients with acute spontaneous intracerebral hemorrhage were retrospectively identified. Total white blood cells, absolute neutrophil count, and absolute lymphocyte count were obtained and the NLR computed from the admission blood work. The study end point was the occurrence of death or major disability at 3 months.
RESULTS:
One hundred seventy-seven subjects were enrolled. Ninety-four (53.1%) had unfavorable outcome. The absolute neutrophil count, absolute lymphocyte count, and NLR were independently associated with the 3-month status. The NLR resulted the best discriminating variable and the best predictive cut-off value was 4.58.
CONCLUSIONS:
In patients with acute intracerebral hemorrhage, higher neutrophils, lower lymphocytes, and higher NLRs predicted worse 3-month outcome
Neutrophil-to-lymphocyte ratio and neurological deterioration following acute cerebral hemorrhage
No full textImmunity plays key roles in pathophysiology of intracerebral hemorrhage (ICH). The aim of the study was to determine whether the peripheral leukocyte count and neutrophil-to-lymphocyte ratio (NLR) predicted neurological deterioration (ND) after ICH. We identified consecutive patients with ICH who had blood sampling performed within 24 hours from symptom's onset. Total white blood cells (WBC), absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were retrieved, and the NLR computed as the ratio of the ANC to ALC values. The study endpoint was the occurrence of neurological deterioration (ND) within 7 days after ICH. One hundred ninety-two subjects were enrolled, whose 54 (28.1%) presented ND. At multivariate analysis, the WBC (adjusted odd ratio [adjOR] for 1,000 leukocytes increase 1.29, 95% confidence interval [CI] 1.11-1.50), ANC (adjOR for 1,000 neutrophils increase 1.61, 95% CI 1.30-1.99), ALC (adjOR for 1,000 lymphocytes increase 0.21, 95% CI 0.09-0.49) and NLR (adjOR for 1-point increase 1.65, 95% CI 1.36-2.00) were independently associated with ND (p≤0.001). The NLR resulted the best discriminating variable for the occurrence of the adverse outcome (area under the curve 0.888, 95% CI 0.832-0.945; p < 0.001). The NLR predicted ND after acute ICH and can aid in the risk stratification of patients
How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis
Full text linkSUMMARY:
The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels
- …
