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Huntington's disease (HD) is a rare neurodegenerative disorder with a distinct phenotype, including involuntary movements, cognitive decline, and behavioral disturbances. Sleep disorder include insomnia, increased sleep onset latency, decrease in total sleep time with frequent nocturnal awakenings and excessive daytime sleepiness. Increased sleep motor activities and abnormal nocturnal agitation have been increasingly recognized as an important component affecting negatively the sleep quality. Here, we report a case of an intensification of diurnal choreic movement during the night, notably during REM-sleep in a patient with manifest HD. This case highlights the diversity of nocturnal sleep motor disorders encountered in HD.
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Enfermedad de Huntington , Humanos , Enfermedad de Huntington/complicaciones , Enfermedad de Huntington/fisiopatología , Masculino , Persona de Mediana Edad , Femenino , Trastornos del Sueño-Vigilia/fisiopatología , Trastornos del Sueño-Vigilia/etiología , Sueño REM/fisiología , Polisomnografía , Sueño/fisiologíaRESUMEN
BACKGROUND: Iron dysmetabolism has long been identified as a primary key factor involved in Restless Legs Syndrome (RLS) pathophysiology and may account for the high prevalence of RLS observed in chronic liver diseases (CLD). Prevalence of RLS was also reported to be high in genetic hemochromatosis (GH) but whether this is due to the unique iron metabolism disorder and to treatment procedure in GH remains unknown. If this assumption is true, then one would hypothesize that RLS prevalence is higher in GH than in another CLD such as chronic hepatitis B (CHB). MATERIALS AND METHODS: We conducted a prospective questionnaire-based survey to assess the prevalence of RLS symptoms in consecutive patients with either GH or CHB. Patients who were screened positive for RLS based on the criteria of the International RLS Study Group were further interviewed by telephone and if needed by face to face assessment to confirm RLS diagnosis. RESULTS: Symptoms of confirmed RLS were confirmed in 8.9% of the 101 participants with CHB and in 10% of the 105 patients with GH. Low ferritin levels were not associated with the presence of RLS in both groups nor were the severity of the liver disease. CONCLUSION: GH is not a risk factor for RLS occurrence as any other cause of CLD, as RLS prevalence in both GH and CHB is within the range of RLS prevalence in the general Caucasian population.
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Hemocromatosis , Síndrome de las Piernas Inquietas , Humanos , Hemocromatosis/complicaciones , Hemocromatosis/epidemiología , Síndrome de las Piernas Inquietas/diagnóstico , Estudios Prospectivos , Factores de Riesgo , Hierro , PrevalenciaRESUMEN
Restless legs syndrome (RLS) is a sensorimotor disorder that severely affects sleep. It is characterized by an urge to move the legs, which is often accompanied by periodic limb movements during sleep. RLS has a high prevalence in the population and is usually a life-long condition. While its origins remain unclear, RLS is initially highly responsive to treatment with dopaminergic agonists that target D2-like receptors, in particular D2 and D3, but the long-term response is often unsatisfactory. Over the years, several putative animal models for RLS have been developed, mainly based on the epidemiological and neurochemical link with iron deficiency, treatment efficacy of D2-like dopaminergic agonists, or genome-wide association studies that identified risk factors in the patient population. Here, we present the first systematic review of putative animal models of RLS, provide information about their face and construct validity, and report their role in deciphering the underlying pathophysiological mechanisms that may cause or contribute to RLS. We propose that identifying the causal links between genetic risk factors, altered organ functions, and changes to molecular pathways in neural circuitry will eventually lead to more effective new treatment options that bypass the side effects of the currently used therapeutics in RLS, especially for long-term therapy.
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Agonistas de Dopamina , Síndrome de las Piernas Inquietas , Animales , Humanos , Agonistas de Dopamina/uso terapéutico , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Síndrome de las Piernas Inquietas/genética , Estudio de Asociación del Genoma Completo , Modelos Animales , Resultado del TratamientoRESUMEN
STUDY OBJECTIVES: Although sympathetic hyperactivity with preserved parasympathetic activity has been extensively recognized in fatal familial insomnia (FFI), the symptoms of parasympathetic nervous system failure observed in some patients are difficult to explain. Using heart rate variability (HRV), this study aimed to discover evidence of parasympathetic dysfunction in patients with FFI and the difference of parasympathetic activity between patients with FFI and Creutzfeldt-Jakob disease (CJD). METHODS: This study enrolled nine patients with FFI, eight patients with CJD and 18 healthy controls (HCs) from May 2013 to August 2020. All participants underwent a nocturnal video-polysomnography with lead II electrocardiography, and the data were analyzed using linear and nonlinear indices of HRV during both wake and sleep states. RESULTS: Compared to the HC and CJD groups, the FFI group had a continuously higher heart rate with a lower amplitude of oscillations. The low frequency (LF)/high frequency (HF) ratio and ratio of SD1 to SD2 and correlation dimension D2 (CD2) were significantly different in the FFI group compared to the HC group. The root mean square of successive differences (RMSSD), HF and SD1 in the FFI group were significantly lower than in the HC group. RMSSD, SD1, and CD2 in the FFI group were all significantly lower than in the CJD group. CONCLUSIONS: Cardiovascular dysautonomia in FFI may be partly attributable to parasympathetic abnormalities, not just sympathetic activation. HRV may be helpful as a noninvasive, quantitative, and effective autonomic function test for FFI diagnosis.
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Insomnio Familiar Fatal , Humanos , Frecuencia Cardíaca/fisiología , Corazón , Sistema Nervioso Autónomo/fisiologíaRESUMEN
Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS.
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Síndrome de las Piernas Inquietas , Comités Consultivos , Animales , Hierro , Reproducibilidad de los Resultados , Síndrome de las Piernas Inquietas/diagnóstico , Síndrome de las Piernas Inquietas/tratamiento farmacológico , RoedoresRESUMEN
BACKGROUND: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. MATERIALS AND METHODS: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. RESULTS: The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. CONCLUSIONS: Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.
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Insomnio Familiar Fatal , Tálamo , Estudios de Casos y Controles , Humanos , Insomnio Familiar Fatal/diagnóstico por imagen , Insomnio Familiar Fatal/patología , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Tálamo/diagnóstico por imagen , Tálamo/patologíaRESUMEN
BACKGROUND: The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio. METHODS: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with two-round expert consultation: (1) Validation of the 2018 FFI criteria. (2) Diagnostic item selection according to statistical analysis and expert consensus. (3) Validation of the new criteria. RESULTS: The 2018 criteria for possible FFI had a sensitivity of 90.6%, a specificity of 83.3%, with a positive likelihood ratio (PLR) of 5.43, and a negative likelihood ratio (NLR) of 0.11; and the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, with a PLR of 11.77, and a NLR of 0.18. The new criteria included more specific and/or common clinical features, two exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had therefore reached a better sensitivity and specificity (92.2% and 96.1%, respectively), a PLR of 23.64 and a NLR of 0.08, whereas the probable FFI criteria showed a sensitivity of 90.6%, a specificity of 98.2%, with a PLR of 50.33 and a NLR of 0.095. CONCLUSIONS: We propose new clinical diagnostic criteria for FFI, for a better refining of the clinical hallmarks of the disease that ultimately would help an early recognition of FFI and a better differentiation from other prion diseases.
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Insomnio Familiar Fatal , Enfermedades por Prión , Humanos , Insomnio Familiar Fatal/diagnóstico , Insomnio Familiar Fatal/genética , Enfermedades por Prión/diagnóstico , Sensibilidad y EspecificidadRESUMEN
Comorbidity between Restless Legs Syndrome and Attention-Deficit/Hyperactivity Disorder remains a matter of debate. This putative association, possibly reflecting a shared brain iron homeostasis and dopaminergic dysfunction, supports the hypothesis of a neurodevelopmental component in Restless Legs Syndrome pathogenesis. The aim of this study was to investigate Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms prevalence in adult patients with primary Restless Legs Syndrome compared to another ill group of patients with obstructive sleep apnea syndrome to control for the disease specific effects on psychiatric symptoms and a healthy individuals control group. Clinical data were obtained through standardized and validated self-administrated questionnaires evaluating Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms frequencies in 139 outpatients with idiopathic Restless Legs Syndrome, 111 patients with treated obstructive sleep apnea syndrome and 136 healthy subjects. Our findings demonstrate a higher prevalence of Attention-Deficit/Hyperactivity Disorder symptoms among both male and female patients with Restless Legs Syndrome, compared to obstructive sleep apnea syndrome patients and healthy subjects (33.3 and 43.5%, respectively, p < 0.001). Only women presented a strong relationship between Attention-Deficit/Hyperactivity Disorder and Restless Legs Syndrome severity (p < 0.001). Male and female in the three groups showed similar Obsessive-Compulsive Disorder symptom prevalence. These findings indicate that Attention-Deficit/Hyperactivity Disorder symptoms among adult patients with Restless Legs Syndrome populations are a robust phenomenon. These data provide arguments in favor of an enlargement of the clinical neuropsychological presentation of Restless Legs Syndrome and question the role of decreased brain iron of these psychiatric symptoms.
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Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified.
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Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Atrofia de Múltiples Sistemas/complicaciones , HumanosRESUMEN
Focusing on a specific population when studying dream characteristics can shed light on underlying mechanisms and correlates of dreaming. The aim of this study is to establish a clearer description of specific dream aspects and beliefs in a large cohort of students using a validated questionnaire, and to further investigate the role of sociodemographic variables such as age, gender and field of study. Participants were 1137 students aged from 18 to 34 (mean age: 22.2) who responded to an online version of the questionnaire. Our results showed a difference between humanities and science students, and a differential effect of gender on dream variables. Our results are discussed in light of previous investigations using the same questionnaire or focusing on the same population.
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Cultura , Sueños/psicología , Estudiantes/psicología , Encuestas y Cuestionarios , Adolescente , Adulto , Estudios de Cohortes , Emociones/fisiología , Femenino , Francia , Humanos , Masculino , Recuerdo Mental/fisiología , Análisis de Regresión , Estudiantes/estadística & datos numéricos , Adulto JovenRESUMEN
Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by an urge to move the legs. This urge is often accompanied by pain or other uncomfortable and unpleasant sensations, it either occurs or worsens during rest, particularly in the evening and/or at night, and temporarily improves with activity. Affecting nearly 3% of the North American and European populations in its moderate-to-severe form, RLS has a considerable negative impact on the quality of life, and sleep and is associated with significant morbidity. Although new developments have deepened our understanding of the disorder, yet, the corresponding pathophysiologic features that underlie the sensorimotor presentation are still not fully understood. Usually, symptoms respond well to dopamine agonists (DA), anticonvulsants, or opiates, used either alone or in any combination, but still, a subset of patients remains refractory to medical therapy and serious side effects such as augmentation and impulse control disorder may occur in patients with RLS under DA. Convincing treatment alternative are lacking but recently patients' spontaneous reports of a remarkable and total remission of RLS symptoms following cannabis use has been reported. The antinociceptive effect of marijuana has been documented in many painful neurological conditions and the potential benefit of cannabis use in patients with refractory RLS should, therefore, be questioned by robust clinical trials. Here, we review basic knowledge of RLS and the putative mechanisms by which cannabis may exert its analgesic effects.
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Cannabis , Síndrome de las Piernas Inquietas , Analgésicos Opioides/uso terapéutico , Agonistas de Dopamina/efectos adversos , Humanos , Calidad de Vida , Síndrome de las Piernas Inquietas/tratamiento farmacológicoRESUMEN
Restless legs syndrome (RLS) is a chronic sensorimotor disorder diagnosed by clinical symptoms. It is challenging to translate the diagnostic self-reported features of RLS to animals. To help researchers design their experiments, a task force was convened to develop consensus guidelines for experimental readouts in RLS animal models. The RLS clinical diagnostic criteria were used as a starting point. After soliciting additional important clinical features of RLS, a consensus set of methods and outcome measures intent on capturing these features-in the absence of a face-to-face interview-was generated and subsequently prioritized by the task force. These were, in turn, translated into corresponding methods and outcome measures for research on laboratory rats and mice and used to generate the final recommendations. The task force recommended activity monitoring and polysomnography as principal tools in assessing RLS-like behavior in rodents. Data derived from these methods were determined to be the preferred surrogate measures for the urge to move, the principal defining feature of RLS. The same tools may be used to objectively demonstrate sleep-state features highly associated with RLS, such as sleep disturbance and number and periodicity of limb movements. Pharmacological challenges and dietary or other manipulations that affect iron availability are desirable to aggravate or improve RLS-like behavior and lend greater confidence that the animal model being proffered replicates key clinical features of RLS. These guidelines provide the first consensus experimental framework for researchers to use when developing new rodent models of RLS. © 2020 International Parkinson and Movement Disorder Society.
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Síndrome de las Piernas Inquietas , Trastornos del Sueño-Vigilia , Animales , Consenso , Ratones , Polisomnografía , Síndrome de las Piernas Inquietas/diagnóstico , RoedoresAsunto(s)
Trastornos del Movimiento , Síndrome de las Piernas Inquietas , Humanos , Pierna , Dedos del PieRESUMEN
Restless legs syndrome (RLS) is one of the most disabling and sometimes painful sensorimotor ailment of the nervous system that has only in recent years become more widely accepted as a clinical disorder with its own distinct features. Usually, symptoms respond well to dopamine agonists, anticonvulsants, or opiates, but still a subset of patients remains refractory to medical therapy and/or reports serious side effects. Recently, patients' statement of a remarkable and total remission of RLS symptoms following cannabis use has been reported. Here, we confirm and extend these findings to more patients with RLS. The antinociceptive effect of marijuana has been documented in many painful neurological conditions, and the potential benefit of cannabis use in patients with refractory RLS should therefore be questioned by robust clinical trials.
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Marihuana Medicinal/uso terapéutico , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Humanos , Síndrome de las Piernas Inquietas/diagnóstico , Resultado del TratamientoRESUMEN
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor is an additional feature for MSA diagnosis, showing a high diagnostic positive predictive value, and its early occurrence might contribute to shorten survival. A consensus definition of stridor in MSA is lacking, and disagreement persists about its diagnosis, prognosis, and treatment. An International Consensus Conference among experts with methodological support was convened in Bologna in 2017 to define stridor in MSA and to reach consensus statements for the diagnosis, prognosis, and treatment. Stridor was defined as a strained, high-pitched, harsh respiratory sound, mainly inspiratory, occurring only during sleep or during both sleep and wakefulness, and caused by laryngeal dysfunction leading to narrowing of the rima glottidis. According to the consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording. Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful. The impact of stridor on survival and quality of life remains uncertain. Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain. Several research gaps emerged involving diagnosis, prognosis, and treatment. Unmet needs for research were identified.
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Conferencias de Consenso como Asunto , Atrofia de Múltiples Sistemas/diagnóstico , Atrofia de Múltiples Sistemas/fisiopatología , Ruidos Respiratorios/fisiopatología , Humanos , Atrofia de Múltiples Sistemas/terapia , Pronóstico , Resultado del TratamientoRESUMEN
The pathophysiology of Restless Legs Syndrome (RLS) remains uncertain. Although the dopaminergic and/or the iron breakdown homeostasis hypotheses are still considered to be the mainstay of the RLS underlying mechanism, therapeutic intervention aiming to alleviate RLS syndrome through dopamine agonists use and iron stores recovery failed so far to show short-term remarkable efficacy, and controlled trials to establish sustained long-term efficacy, tolerability and safety are lacking. Here we review available literature dealing with pharmacological treatment of RLS and consider some rational aspects of RLS pathophysiology that may support the use of available drug classes in treating this condition.
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Síndrome de las Piernas Inquietas/tratamiento farmacológico , Adenosina/metabolismo , Ensayos Clínicos como Asunto , Agonistas de Dopamina/uso terapéutico , Humanos , Hierro/metabolismo , LigandosRESUMEN
Dopaminergic treatments targeting the D3 receptor subtype to reduce the symptoms of RLS show substantial initial clinical benefits but fail to maintain their efficacy over time. Sensorimotor circuits in the spinal cord are the gateway for the sensory processing of the symptoms and critical for the associated leg movements that relieve the symptoms and the periodic limb movements that often develop during sleep. There is a high preponderance of the inhibitory D3 receptor in the sensory-processing areas of the spinal cord (dorsal horn), whereas the motor areas in the ventral horn more strongly express the excitatory D1 receptor subtype. D3 and D1 receptors can form functional heteromeric ensembles that influence each other. In the spinal cord, long-term treatment with D3 receptor agonists is associated with the upregulation of the D1 receptor subtype and block of D1 receptor function at this stage can restore the D3 receptor effect. Alternate scenarios for a role of dopamine involve a role for the D5 receptor in regulating motor excitability and for the D4 receptor subtype in controlling D3-like effects. A model emerges that proposes that the behavioral changes in RLS, while responsive to D3 receptor agonists, may be ultimately be the result of unmasked increased D1-like receptor activities.