RESUMO
OBJECTIVE: To obtain insight in the spectrum of narcolepsy symptoms and associated burden in a large cohort of patients. METHODS: We used the Narcolepsy Monitor, a mobile app, to easily rate the presence and burden of 20 narcolepsy symptoms. Baseline measures were obtained and analyzed from 746 users aged between 18 and 75 years with a reported diagnosis of narcolepsy. RESULTS: Median age was 33.0 years (IQR 25.0-43.0), median Ullanlinna Narcolepsy Scale 19 (IQR 14.0-26.0), 78% reported using narcolepsy pharmacotherapy. Excessive daytime sleepiness (97.2%) and lack of energy were most often present (95.0%) and most often caused a high burden (79.7% and 76.1% respectively). Cognitive symptoms (concentration 93.0%, memory 91.4%) and psychiatric symptoms (mood 76.8%, anxiety/panic 76.4%) were relatively often reported to be present and burdensome. Conversely, sleep paralysis and cataplexy were least often reported as highly bothersome. Females experienced a higher burden for anxiety/panic, memory, and lack of energy. CONCLUSIONS: This study supports the notion of an elaborate narcolepsy symptom spectrum. Each symptom's contribution to the experienced burden varied, but lesser-known symptoms did significantly add to this as well. This emphasizes the need to not only focus treatment on the classical core symptoms of narcolepsy.
Assuntos
Cataplexia , Distúrbios do Sono por Sonolência Excessiva , Narcolepsia , Adulto , Feminino , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Estudos de Amostragem , Narcolepsia/diagnóstico , Cataplexia/diagnóstico , Cataplexia/epidemiologia , AnsiedadeRESUMO
Background It has been suggested that migraine attacks strike according to circadian patterns and that this might be related to individual chronotype. Here we evaluated and correlated individual chronotypes, stability of the circadian rhythm, and circadian attack timing in a large and well-characterised migraine population. Methods In 2875 migraine patients and 200 non-headache controls we assessed differences in: (i) distribution of chronotypes (Münich Chronotype Questionnaire); (ii) the circadian rhythm's amplitude and stability (Circadian Type Inventory); and (iii) circadian timing of migraine attacks. Data were analysed using multinomial and linear regression models adjusted for age, gender, sleep quality and depression. Results Migraineurs more often showed an early chronotype compared with controls (48.9% versus 38.6%; adjusted odds ratio [OR] = 2.42; 95% confidence interval [CI] = 1.58-3.69; p < 0.001); as well as a late chronotypes (37.7% versus 38.1%; adjusted OR = 1.69; 95% CI = 1.10-2.61; p = 0.016). Migraineurs, particularly those with high attack frequency, were more tired after changes in circadian rhythm (i.e. more languid; p < 0.001) and coped less well with being active at unusual hours (i.e. more rigid; p < 0.001) than controls. Of 2389 migraineurs, 961 (40.2%) reported early morning attack onset. Conclusion Migraine patients are less prone to be of a normal chronotype than controls. They are more languid and more rigid when changes in circadian rhythm occur. Most migraine attacks begin in the early morning. These data suggest that chronobiological mechanisms play a role in migraine pathophysiology.
Assuntos
Ritmo Circadiano/fisiologia , Transtornos de Enxaqueca/fisiopatologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Our aim was to study not only the prevalence but more importantly the severity and the correlation between sleep quality and restless legs syndrome (RLS) in a large population of well-defined migraine patients as poor sleep presumably triggers migraine attacks. METHODS: In a large cross-sectional and observational study, data on migraine and RLS were collected from 2385 migraine patients (according to the International Classification of Headache Disorders ICHD-IIIb) and 332 non-headache controls. RLS severity (International RLS Study Group severity scale) and sleep quality (Pittsburgh Sleep Quality Index) were assessed. Risk factors for RLS and RLS severity were calculated using multivariable-adjusted regression models. RESULTS: Restless legs syndrome prevalence in migraine was higher than in controls (16.9% vs. 8.7%; multivariable-adjusted odds ratio 1.83; 95% confidence interval 1.18-2.86; P = 0.008) and more severe (adjusted severity score 14.5 ± 0.5 vs. 12.0 ± 1.1; P = 0.036). Poor sleepers were overrepresented amongst migraineurs (50.1% vs. 25.6%; P < 0.001). Poorer sleep quality was independently associated with RLS occurrence (odds ratio 1.08; P < 0.001) and RLS severity (P < 0.001) in migraine patients. CONCLUSION: Restless legs syndrome is not only twice as prevalent but also more severe in migraine patients, and associated with decreased sleep quality.
Assuntos
Transtornos de Enxaqueca/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Síndrome das Pernas Inquietas/diagnóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.
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Pesquisa Biomédica/tendências , Neurologia/tendências , Psiquiatria/tendências , Transtornos do Sono-Vigília/fisiopatologia , Sono/fisiologia , HumanosRESUMO
PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.
Assuntos
Tumor do Corpo Carotídeo/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Tumor do Corpo Carotídeo/diagnóstico , Tumor do Corpo Carotídeo/fisiopatologia , Tumor do Corpo Carotídeo/cirurgia , Células Quimiorreceptoras/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/fisiopatologia , Neoplasias Primárias Múltiplas/cirurgia , Oxigênio/sangue , Polissonografia , Reflexo/fisiologia , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
AIMS/HYPOTHESIS: Decreased sleep duration and/or impaired sleep quality negatively influence glucoregulation. The aim of this study was to assess subjective sleep characteristics in patients with type 1 diabetes, to relate sleep characteristics to long-term glycaemic control and to assess possible risk factors for impaired sleep. METHODS: We studied 99 adult patients with type 1 diabetes (55 men, 44 women, duration of diabetes 26.9 ± 1.2 years) and 99 age-, sex- and BMI-matched non-diabetic controls. Subjective sleep characteristics were assessed by validated questionnaires, i.e. Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and the Berlin Questionnaire. Glucoregulation was assessed by HbA(1c) values. Clinical variables were obtained from medical charts. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS). Peripheral polyneuropathy was assessed by neurological examination and quantitative sensory testing. RESULTS: Of the patients with type 1 diabetes, 35% had subjective poor sleep quality compared with 20% of the control participants (p = 0.021). A higher proportion of the patients with type 1 diabetes were at increased risk for obstructive sleep apnoea (OSA) (17.2% vs 5.1%, p = 0.012). There was no significant association between individual sleep characteristics and HbA(1c) values. On logistic regression analysis, the HADS depression score, presence of peripheral polyneuropathy, habitual snoring and other sleep disturbances (e.g. hypoglycaemia) were independently associated with poor sleep quality. CONCLUSIONS/INTERPRETATION: Adult patients with long-standing type 1 diabetes mellitus have disturbed subjective sleep quality and a higher risk for OSA compared with control participants. Subjective sleep disturbances are part of the complex syndrome of long-standing type 1 diabetes.
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Diabetes Mellitus Tipo 1/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/fisiopatologia , Transtornos do Sono-Vigília/psicologiaRESUMO
We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.
Assuntos
Química Encefálica/genética , Proteínas de Transporte , Peptídeos e Proteínas de Sinalização Intracelular , Mutação , Narcolepsia/genética , Neuropeptídeos/genética , Receptores de Neuropeptídeos/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/química , Feminino , Testes Genéticos , Humanos , Hipotálamo/química , Hipotálamo/citologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neuropeptídeos/análise , Neurotransmissores/genética , Receptores de Orexina , Orexinas , Ponte/química , Processamento de Proteína Pós-Traducional , Receptores Acoplados a Proteínas G , Distribuição Tecidual , População BrancaRESUMO
INTRODUCTION: Excessive Daytime Sleepiness is a core symptom of narcolepsy and idiopathic hypersomnia, which impairs driving performance. Adequate treatment improves daytime alertness, but it is unclear whether driving performance completely normalizes. This study compares driving performance of patients with narcolepsy and idiopathic hypersomnia receiving treatment to that of healthy controls. METHODS: Patients diagnosed with narcolepsy type 1 (NT1, n = 33), narcolepsy type 2 (NT2, n = 7), or idiopathic hypersomnia (IH, n = 6) performed a standardized one-hour on-the-road driving test, measuring standard deviation of lateral position (SDLP). RESULTS: Results showed that mean SDLP in patients did not differ significantly from controls, but the 95%CI of the mean difference (+1.02 cm) was wide (-0.72 to +2.76 cm). Analysis of subgroups, however, showed that mean SDLP in NT1 patients was significantly increased by 1.90 cm as compared to controls, indicating impairment. Moreover, four NT1 patients requested to stop the test prematurely due to self-reported somnolence, and two NT1 patients were stopped by the driving instructor for similar complaints. CONCLUSION: Driving performance of NT1 patients may still be impaired, despite receiving treatment. No conclusions can be drawn for NT2 and IH patients due to the low sample sizes of these subgroups. In clinical practice, determination of fitness to drive for these patients should be based on an individual assessment in which also coping strategies are taken into account.
Assuntos
Atenção/fisiologia , Condução de Veículo/psicologia , Distúrbios do Sono por Sonolência Excessiva/complicações , Hipersonia Idiopática/complicações , Narcolepsia/complicações , Acidentes de Trânsito/prevenção & controle , Adulto , Estudos de Casos e Controles , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/dietoterapia , Humanos , Hipersonia Idiopática/diagnóstico , Hipersonia Idiopática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Narcolepsia/dietoterapia , VigíliaRESUMO
STUDY OBJECTIVES: Sleep state misperception is common in various sleep disorders, especially in chronic insomnia with a prevalence ranging between 9-50%. Most prior studies used nocturnal polysomnography (PSG) for the identification of sleep state misperception during nighttime. Our objective was to assess sleep state misperception during daytime in people with sleep disorders with excessive daytime sleepiness (EDS). METHODS: In this prospective observational study, we assessed the occurrence of, and factors influencing sleep state misperception in consecutive patients undergoing a routine multiple sleep latency test (MSLT) in a tertiary sleep-wake centre included between 2014 and 2017. Mixed models were applied to assess the influence of patients' clinical data on sleep state perception. RESULTS: People with narcolepsy type 1 (NT1, n = 33) and type 2 (NT2, n = 14), idiopathic hypersomnia (IH, n = 56), obstructive sleep apnea (OSA, n = 31) and insufficient sleep syndrome (ISS, n = 31) were included. The prevalence of both classical and reverse sleep state misperception did not differ between the sleep disorders (mean 25%, range 8-37%) after correction for sleep stage, sleep onset latency and age. Longer sleep onset latency and reaching only non-rapid eye movement (REM) sleep stage 1 were significant predictors for classical sleep state misperception. CONCLUSIONS: Sleep state misperception is common in people with NT1 and NT2, IH, OSA, and ISS. Classical sleep state misperception is more frequent in patients with longer sleep onset latencies who only reach non-REM sleep stage 1 during a nap.
Assuntos
Hipersonia Idiopática , Narcolepsia , Apneia Obstrutiva do Sono , Transtornos Intrínsecos do Sono/epidemiologia , Latência do Sono , Adulto , Fatores Etários , Distúrbios do Sono por Sonolência Excessiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Prevalência , Estudos ProspectivosRESUMO
Following the 2009 H1N1 influenza pandemic, an increased risk of narcolepsy type 1 was observed. Homology between an H1N1 hemagglutinin and two hypocretin sequences has been reported. T cell reactivity to these peptides was assessed in 81 narcolepsy type 1 patients and 19 HLA-DQ6-matched healthy controls. HLA-DQ6-restricted H1N1 hemagglutinin-specific T cell responses were detected in 28.4% of patients and 15.8% of controls. Despite structural homology between HLA-DQ6-hypocretin and -H1N1 peptide complexes, T cell cross-reactivity was not detected. These results indicate that it is unlikely that cross-reactivity between H1N1 hemagglutinin and hypocretin peptides presented by HLA-DQ6 is involved in the development of narcolepsy.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígenos HLA-DQ/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Narcolepsia/imunologia , Orexinas/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Proteínas do Líquido Cefalorraquidiano/análise , Criança , Cristalografia por Raios X , Feminino , Antígenos HLA-DQ/química , Cadeias alfa de HLA-DQ/análise , Cadeias beta de HLA-DQ/análise , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Humanos , Vírus da Influenza A Subtipo H1N1 , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Mimetismo Molecular , Narcolepsia/etiologia , Orexinas/líquido cefalorraquidiano , Orexinas/química , Pandemias , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Conformação Proteica , Adulto JovemRESUMO
OBJECTIVE: Besides excessive daytime sleepiness, disturbed nocturnal sleep is a major complaint of patients with narcolepsy. Previously, alterations in skin temperature regulation in narcoleptic patients have been shown to be related to increased sleepiness. This study tests the hypothesis that direct control of nocturnal skin temperature might be applied to improve the disturbed sleep of narcoleptic patients. METHODS: Participants were eight patients (five males) diagnosed as having narcolepsy with cataplexy according to the ICSD-2 criteria, mean (SD) age 28.6 (6.4) years, range 18-35 years. During two nights, sleep was recorded polysomnographically while proximal and distal skin temperature were manipulated using a comfortable thermosuit that induced skin temperature to cycle slowly with an amplitude of only 0.4 degrees C within the comfortable range normally observed during sleep. Logistic regression was used to evaluate the effect of skin temperature manipulation on the probability of occurrence of different sleep stages and nocturnal wakefulness. RESULTS: Proximal skin warming significantly suppressed wakefulness and enhanced slow wave sleep (SWS). In contrast, distal skin warming enhanced wakefulness and stage 1 sleep at the cost of SWS and REM sleep. The optimal combination of proximal skin warming and distal skin cooling led to a 160% increase in SWS, a 50% increase in REM sleep and a 68% decrease in wakefulness, compared with the least beneficial combination of proximal skin cooling and distal skin warming. INTERPRETATION: Subtle skin temperature manipulations under controlled conditions significantly improved the typical nocturnal sleep problems in narcolepsy.
Assuntos
Regulação da Temperatura Corporal/fisiologia , Fadiga/diagnóstico , Narcolepsia/diagnóstico , Temperatura Cutânea , Adolescente , Adulto , Feminino , Humanos , Masculino , Narcolepsia/terapia , Polissonografia/métodos , Sono , Transtornos do Sono-Vigília/diagnóstico , Temperatura , Resultado do Tratamento , Vigília/fisiologiaRESUMO
Sleep disturbances occur in 70% of the patients with multiple system atrophy (MSA). Disturbances of the hypothalamic hypocretin neurotransmission have been suggested as a possible cause. Since a systematic study of CSF hypocretin-1 levels in MSA has not yet been performed, we analysed CSF hypocretin-1 concentrations in 6 MSA-P and 6 MSA-C patients and 11 age-matched controls. We did not observe any differences from control values.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Atrofia de Múltiplos Sistemas/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/classificação , OrexinasRESUMO
We performed a double-blind placebo-controlled crossover study in 13 patients with myotonic dystrophy to address the question whether modafinil, known to improve hypersomnolence in myotonic dystrophy, may improve levels of activity as well. We used the Epworth Sleepiness Scale as a measure of hypersomnolence and a structured interview of the patient and the partner or housemate as a measure of activity. We additionally used a restricted form of the RAND-36 to relate a possible improvement of activity to perceived general health. We confirmed earlier positive findings of modafinil regarding reduced somnolence (p=0.015), but no significant effects were seen regarding activity levels (p=0.2 for patients' self-reports and 0.5 for partners' reports).
Assuntos
Atividades Cotidianas , Compostos Benzidrílicos/uso terapêutico , Atividade Motora/efeitos dos fármacos , Distrofia Miotônica , Fármacos Neuroprotetores/uso terapêutico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Entrevistas como Assunto/métodos , Masculino , Pessoa de Meia-Idade , Modafinila , Distrofia Miotônica/tratamento farmacológico , Distrofia Miotônica/fisiopatologia , Distrofia Miotônica/psicologia , Inquéritos e QuestionáriosRESUMO
The 5 classic symptoms of narcolepsy are excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. The presence of cataplexy is strongly associated with a deficiency of the neuropeptide hypocretin. This discovery has led to new diagnostic subclassifications: narcolepsy without cataplexy, which can be demonstrated by a multiple sleep latency test, and narcolepsy with cataplexy, which can be confirmed with a multiple sleep latency test or a cerebrospinal fluid deficiency of hypocretin I. Various treatment options are available, including psychostimulants and gamma hydroxybuterate.
Assuntos
Cataplexia/diagnóstico , Cataplexia/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Narcolepsia/diagnóstico , Narcolepsia/tratamento farmacológico , Cataplexia/complicações , Diagnóstico Diferencial , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Narcolepsia/complicações , Neuropeptídeos/deficiência , Orexinas , Sono REM/efeitos dos fármacos , Oxibato de Sódio/uso terapêuticoRESUMO
An 80-year-old man was admitted because of head trauma following a fall down a staircase. Initial CT-imaging of the brain showed only global atrophy, but repeated CT-imaging 4 days later revealed a subdural hygroma. Because of the discrepancy between the radiological deterioration and the unchanged neurological condition, we refrained from neurosurgical evacuation. Two months after the trauma, the subdural hygroma had been spontaneously resorbed, but neurological examination revealed severe residual neurological abnormalities. Subdural hygroma is a little known complication in the acute stage ofhead trauma, which is seen mainly in elderly patients. The pathophysiology is not well known. Differentiating subdural hygroma (cerebrospinal fluid (CSF) accumulation in the subdural space) from external hydrocephalus (excessive CSF accumulation in the subarachnoid space) is important in view of the therapeutic consequences. Because CT-imaging usually cannot differentiate between these 2 conditions, we recommend the use of MRI.
Assuntos
Acidentes por Quedas , Doenças do Sistema Nervoso/etiologia , Derrame Subdural/diagnóstico , Derrame Subdural/etiologia , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças do Sistema Nervoso/epidemiologia , Derrame Subdural/complicações , Tomografia Computadorizada por Raios XRESUMO
Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.
Assuntos
Comitês Consultivos/normas , Narcolepsia/tratamento farmacológico , Antidepressivos/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Catalepsia/tratamento farmacológico , Catalepsia/fisiopatologia , Catalepsia/psicologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Gerenciamento Clínico , Europa (Continente) , Humanos , Modafinila , Narcolepsia/fisiopatologia , Narcolepsia/psicologia , Oxibato de Sódio/uso terapêuticoRESUMO
BACKGROUND: Kleine Levin Syndrome (KLS) is a rare disease with periodic hypersomnia as its main feature. Hyperphagia and hypersexuality are also described as classical symptoms, although quite recently it has become clear that the full triad is absent in the majority of patients. CASE DESCRIPTION: A 14-year-old boy developed KLS after a period of flu-like symptoms. Over the course of three years he suffered from seven one-week episodes of extreme hypersomnia (sleeping 18 hours a day), depersonalisation, apathy, anxiety, paranoia, confusion, hallucinations and uninhibited sexual behaviour. He ate little. Ancillary investigations did not reveal any abnormalities. In between these episodes he had no symptoms. CONCLUSION: From this case description and a summary of the symptoms of twelve other patients with KLS, it appears that neuropsychiatric symptoms are much more prominent than hyperphagia and hypersexuality. It is important that the typical KLS phenotype be reappraised, so that the condition can be recognised early and patients managed appropriately.
Assuntos
Síndrome de Kleine-Levin/complicações , Síndrome de Kleine-Levin/diagnóstico , Adolescente , Ansiedade , Alucinações , Humanos , Síndrome de Kleine-Levin/psicologia , Masculino , Fenótipo , Doenças Raras , Comportamento SexualRESUMO
BACKGROUND: The suprachiasmatic nucleus (SCN) may play an important role in central autonomic control, since its projections connect to (para)sympathetic relay stations in the brainstem and spinal cord. The cardiac autonomic modifications during nighttime may therefore not only result from direct effects of the sleep-related changes in the central autonomic network, but also from endogenous circadian factors as directed by the SCN. To explore the influence of the SCN on autonomic fluctuations during nighttime, we studied heart rate and its variability (HRV) in a clinical model of SCN damage. METHODS: Fifteen patients in follow-up after surgical treatment for nonfunctioning pituitary macroadenoma (NFMA) compressing the optic chiasm (8 females, 26-65 years old) and fifteen age-matched healthy controls (5 females, 30-63 years) underwent overnight ambulatory polysomnography. Eleven patients had hypopituitarism and received adequate replacement therapy. HRV was calculated for each 30-second epoch and corrected for sleep stage, arousals, and gender using mixed effect regression models. RESULTS: Compared to controls, patients spent more time awake after sleep onset and in NREM1-sleep, and less in REM-sleep. Heart rate, low (LF) and high frequency (HF) power components and the LF/HF ratio across sleep stages were not significantly different between groups. CONCLUSIONS: These findings suggest that the SCN does not play a dominant role in cardiac autonomic control during sleep.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Coração/fisiologia , Sono/fisiologia , Núcleo Supraquiasmático/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The opsoclonus-myoclonus syndrome (OMS) was diagnosed in nine patients, two men and seven women, varying in age from 34 to 65 years. In two cases the findings indicated a post-infectious form, in three cases there was a malignancy, in one case there was a connection with the use of medication and in three cases the cause was unknown. OMS is a rare neurological disorder with symptoms of rapid, involuntary saccadic eye movements (opsoclonus) and sudden involuntary muscle contractions (myoclonus). It has been associated with infections, malignancies, intoxications and metabolic disorders. In 50% of the cases no cause can be identified. There is evidence for dysfunction ofbrainstem and cerebellar pathways and in many cases an (auto-)immune process is implied. Once the diagnosis has been established, screening for occult malignancy is indicated. The prognosis of idiopathic and post-infectious OMS is generally good and the treatment is mainly supportive.
Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Infecções/complicações , Infecções/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Prognóstico , Resultado do TratamentoRESUMO
Recent observations have implicated hypocretin deficiency in the pathogenesis of narcolepsy. Hypocretin neurotransmission also affects energy balance, and narcoleptic patients tend to become obese. Because hypocretins appear to have important neuroendocrine effects, we hypothesized that the neuroendocrine systems that regulate energy balance might be distinctly set in narcolepsy. As leptin is a pivotal part of these systems, we explored the 24-h plasma leptin (20-min sampling interval) concentration profile in six narcoleptic males and six normal controls, matched for age, sex, body mass index, waist/hip ratio, and fat mass. We thus demonstrated a reduction of the mean 24-h leptin concentration in narcoleptics to 52% of that in controls (5.9 microg/liter in narcolepsy vs. 11.4 microg/liter in controls; P < 0.05). Further, a nocturnal acrophase (clock time of the highest concentration), which is typical of normal leptin secretion, was observed in controls (mean, 2335 h; 95% confidence interval, 2105-0205 h), but not in narcoleptic patients. The mechanisms that potentially disturb the circadian rhythm of leptin levels in hypocretin-deficient narcoleptic humans include anomalies of the sleep-wake cycle and/or disruption of the circadian distribution of autonomic activity. As leptin deficiency clearly leads to morbid obesity in experimental animals and humans, we infer that the observed reduction of plasma leptin levels may predispose narcoleptic humans to weight gain.