RESUMO
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.
Assuntos
Síndrome das Pernas Inquietas , Transtornos do Sono-Vigília , Animais , Consenso , Camundongos , Polissonografia , Síndrome das Pernas Inquietas/diagnóstico , RoedoresRESUMO
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.
Assuntos
Cannabis , Síndrome das Pernas Inquietas , Analgésicos Opioides/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Humanos , Qualidade de Vida , Síndrome das Pernas Inquietas/tratamento farmacológicoRESUMO
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.
Assuntos
Maconha Medicinal/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Humanos , Síndrome das Pernas Inquietas/diagnóstico , Resultado do TratamentoRESUMO
PURPOSE: The Self-Efficacy Measure for Sleep Apnea (SEMSA) is a 26-item self-questionnaire composed of three factors: risk perception of obstructive sleep apnea syndrome (OSAS), benefit of continuous positive airway pressure (CPAP), and self-efficacy (the confidence to engage in CPAP use). It is used to evaluate health beliefs about OSAS and CPAP in order to optimize CPAP use. The purpose of this study was to design and validate a French version of the SEMSA. METHODS: A forward-backward translation of the SEMSA was performed. Subjects with OSAS treated by CPAP and followed by our sleep clinic were invited to complete the questionnaire. The psychometric properties of the French SEMSA version were analyzed in terms of its construct validity (with confirmatory factor analysis, CFA), internal structural validity (Cronbach's alpha coefficient), and external validity (Pearson's correlation between SEMSA score and duration of CPAP use). RESULTS: Two hundred eighty-eight subjects filled in the questionnaire. The mean age was 63.16 ± 12.73 years. The number of years since the beginning of CPAP treatment was 6.58 ± 6.03 years. The mean CPAP use duration was 6.19 ± 2.03 h/night. CFA was unsatisfactory (RMSEA = 0.066 and CFI = 0.88). The exploratory factor analysis revealed a fourth factor named "cardiovascular risk" factor. Cronbach's alpha coefficient was 0.886. The correlation between the "self-efficacy" factor and the duration of CPAP use was significant (r = 0.26, p ≤ 0.001). CONCLUSIONS: The French version of the SEMSA is a psychometrically acceptable self-report questionnaire for measuring health beliefs and behavior in French patients with OSAS treated with CPAP. Such translation and validation should lead to the adoption of validated psychosocial methods for improving CPAP use.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/psicologia , Autoeficácia , Apneia Obstrutiva do Sono/psicologia , Apneia Obstrutiva do Sono/terapia , Inquéritos e Questionários/estatística & dados numéricos , Idoso , Atitude Frente a Saúde , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Correlação de Dados , Comparação Transcultural , Cultura , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Psicometria/estatística & dados numéricos , Medição de RiscoRESUMO
OBJECTIVES: To investigate the prevalence of attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) symptoms in adult patients with primary restless legs syndrome (RLS) and to determine the iron biological correlates of these comorbidities. PARTICIPANTS AND METHODS: We obtained demographic and clinical data from consecutive 105 outpatients with idiopathic RLS who answered validated questionnaires designed to assess the presence of ADHD and OCD symptoms. In these patients, iron blood parameters were routinely checked. RESULTS: Of the total sample, 42.86% of the patients with RLS showed symptoms reminiscent either of ADHD or OCD. Prevalence of ADHD and OCD symptoms was 27.62% and 7.62%, respectively. Compared to other groups, a significantly higher percentage of RLS patients with ADHD symptoms was on antidepressant (p = 0.012); and women with ADHD symptoms, either alone or combined with OCD symptoms, showed significant reduced ferritin concentrations compared to men with either isolated ADHD symptoms or with combined ADHD and OCD symptoms (p = 0.028 and p = 0.025, respectively). CONCLUSIONS: Our findings highlight the high prevalence of ADHD and OCD symptoms in adult patients with primary RLS and independently of serum iron stores decrease, except for women with ADHD symptoms either alone or in combination with OCD symptoms. This may suggest an overlapping neurobiological dopaminergic and serotoninergic dysfunction in ADHD, OCD, and RLS, and question the expression of different RLS phenotypes. The efficacy of dopamine agonists in these groups of patients should be questioned in future studies.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno Obsessivo-Compulsivo/etiologia , Síndrome das Pernas Inquietas/complicações , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Síndrome das Pernas Inquietas/patologia , Inquéritos e QuestionáriosRESUMO
Bruxism is an abnormal repetitive movement disorder characterized by jaw clenching and tooth gnashing or grinding. It is classified into two overlapping types: awake bruxism (AB) and sleep bruxism (SB). Theories on factors causing bruxism are a matter of controversy, but a line of evidence suggests that it may to some extent be linked to basal ganglia dysfunction although so far, this topic has received little attention. The purpose of this article was to review cases of bruxism reported in various movement disorders. The biomedical literature was searched for publications reporting the association of bruxism with various types of movement disorders. As a whole, very few series were found, and most papers corresponded to clinical reports. In Parkinsonian syndromes, AB was rarely reported, but seems to be exacerbated by medical treatment, whereas SB is mainly observed during non-REM sleep, as in restless leg syndrome. AB is occasionally reported in Huntington's disease, primary dystonia, and secondary dystonia; however, its highest incidence and severity is reported in syndromes combining stereotypies and cognitive impairment, such as Rett's syndrome (97%), Down syndrome (42%), and autistic spectrum disorders (32%). Taken as a whole, AB seems to be more frequent in hyperkinetic movement disorders, notably those with stereotypies, and is influenced by anxiety, suggesting an involvement of the limbic part of the basal ganglia in its pathophysiology.
Assuntos
Bruxismo/etiologia , Transtornos dos Movimentos/complicações , Bruxismo/fisiopatologia , Coreia/complicações , Humanos , Transtornos dos Movimentos/fisiopatologia , Transtornos Parkinsonianos/complicações , Transtornos Psicomotores/complicações , Bruxismo do Sono/etiologia , Bruxismo do Sono/fisiopatologiaRESUMO
Endogenous acetylcholine (ACh) is a well-known modulator of nociceptive transmission in the spinal cord of rodents. It arises mainly from a sparse population of cholinergic interneurons located in the dorsal horn of the spinal cord. This population was thought to be absent from the spinal cord of monkey, what might suggest that spinal ACh would not be a relevant clinical target for pain therapy. In humans, however, pain responses can be modulated by spinal ACh, as evidenced by the increasingly used analgesic procedure (for postoperative and labor patients) consisting of the epidural injection of the acetylcholinesterase inhibitor neostigmine. The source and target of this ACh remain yet to be elucidated. In this study, we used an immunolabeling for choline acetyltransferase to demonstrate, for the first time, the presence of a plexus of cholinergic fibers in laminae II-III of the dorsal horn of the macaque monkey. Moreover, we show the presence of numerous cholinergic cell bodies within the same laminae and compared their density and morphological properties with those previously described in rodents. An electron microscopy analysis demonstrates that cholinergic boutons are presynaptic to dorsal horn neurons as well as to the terminals of sensory primary afferents, suggesting that they are likely to modulate incoming somatosensory information. Our data suggest that this newly identified dorsal horn cholinergic system in monkeys is the source of the ACh involved in the analgesic effects of epidural neostigmine and could be more specifically targeted for novel therapeutic strategies for pain management in humans.
Assuntos
Neurônios Colinérgicos/fisiologia , Células do Corno Posterior/fisiologia , Medula Espinal/citologia , Animais , Contagem de Células , Colina O-Acetiltransferase/metabolismo , Neurônios Colinérgicos/ultraestrutura , Feminino , Imageamento Tridimensional , Macaca fascicularis , Masculino , Camundongos , Microscopia Imunoeletrônica , Proteínas do Tecido Nervoso/metabolismo , Células do Corno Posterior/ultraestrutura , Proteína Quinase C/metabolismo , Especificidade da Espécie , Medula Espinal/ultraestrutura , Sinapses/metabolismo , Sinapses/ultraestrutura , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Both excessive daytime sleepiness (EDS) and rapid eye movement (REM) sleep deregulation are part of Parkinson's disease (PD) non-motor symptoms and may complicate dopamine replacement therapy. We report here that dopamine agonists act differentially on sleep architecture in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine macaque monkey. Continuous sleep and wake electroencephalographic monitoring revealed no effect of the selective dopamine D2 receptor agonist quinpirole on EDS, whereas the selective dopamine D1 receptor agonist SKF38393 efficiently alleviated EDS and restored REM sleep to baseline values. The present results question the relevance of abandoning D1 receptor agonist treatment in PD as it might actually improve sleep-related disorders.
Assuntos
Agonistas de Dopamina/uso terapêutico , Transtornos Parkinsonianos/complicações , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico , Transtornos do Sono do Ritmo Circadiano/etiologia , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/uso terapêutico , Análise de Variância , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrocardiografia , Eletroencefalografia , Eletromiografia , Feminino , Levodopa/uso terapêutico , Macaca fascicularis , Macaca mulatta , Transtornos Parkinsonianos/tratamento farmacológico , Quimpirol/uso terapêutico , Sono/efeitos dos fármacos , Telemetria , Fatores de Tempo , Vigília/efeitos dos fármacosRESUMO
The purpose of the study was to evaluate the frequency of restless legs syndrome in 30 patients with multiple system atrophy. Eight patients complained from restless legs syndrome, their severity score was 19.4 ± 4.1. Pittsburgh Sleep Quality Index scores were significantly higher in patients with restless legs syndrome than those without (9.3 ± 3.7 vs. 4.8 ± 2.9, p = 0.00165). Periodic limb movements were found in 75% of patients with restless legs syndrome. Restless legs syndrome is more prevalent in multiple system atrophy as compared to the acknowledged prevalence in the general population.
Assuntos
Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/epidemiologia , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
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.
Assuntos
Doença de Huntington , Humanos , Doença de Huntington/complicações , Doença de Huntington/fisiopatologia , Masculino , Pessoa de Meia-Idade , Feminino , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/etiologia , Sono REM/fisiologia , Polissonografia , Sono/fisiologiaRESUMO
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.
Assuntos
Hemocromatose , Síndrome das Pernas Inquietas , Humanos , Hemocromatose/complicações , Hemocromatose/epidemiologia , Síndrome das Pernas Inquietas/diagnóstico , Estudos Prospectivos , Fatores de Risco , Ferro , PrevalênciaRESUMO
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.
Assuntos
Agonistas de Dopamina , Síndrome das Pernas Inquietas , Animais , Humanos , Agonistas de Dopamina/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/genética , Estudo de Associação Genômica Ampla , Modelos Animais , Resultado do TratamentoRESUMO
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.
Assuntos
Insônia Familiar Fatal , Humanos , Frequência Cardíaca/fisiologia , Coração , Sistema Nervoso Autônomo/fisiologiaRESUMO
BACKGROUND: The Unified Multiple System Atrophy Rating Scale (UMSARS) was developed to provide a surrogate measure of disease progression in multiple system atrophy. In the present study, the intrarater agreement of the motor examination part of the UMSARS was determined. METHODS: All patients were first examined face to face, while being video-recorded, by two senior and two junior investigators. The patients' videotaped examinations were reevaluated after 3 months. Intrarater reliability for each item was analyzed by kappa statistics. RESULTS: Overall weighted kappa (κ) values were at least substantial or excellent for all UMSARS motor examination items, except for ocular motor dysfunction, which showed only moderate intrarater agreement. Intrarater reliability was comparable between senior and junior raters, with all κ differences being ≤ 0.22. CONCLUSIONS: The motor examination part of the UMSARS was found to have satisfactory intrarater reliability in the present cohort.
Assuntos
Avaliação da Deficiência , Atrofia de Múltiplos Sistemas/diagnóstico , Exame Neurológico , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Gravação em VídeoRESUMO
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.
RESUMO
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.
Assuntos
Síndrome das Pernas Inquietas , Comitês Consultivos , Animais , Ferro , Reprodutibilidade dos Testes , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/tratamento farmacológico , RoedoresRESUMO
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.
Assuntos
Insônia Familiar Fatal , Tálamo , Estudos de Casos e Controles , Humanos , Insônia Familiar Fatal/diagnóstico por imagem , Insônia Familiar Fatal/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tálamo/diagnóstico por imagem , Tálamo/patologiaRESUMO
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.
Assuntos
Insônia Familiar Fatal , Doenças Priônicas , Humanos , Insônia Familiar Fatal/diagnóstico , Insônia Familiar Fatal/genética , Doenças Priônicas/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Several models of dystonia have emerged from clinical studies providing a comprehensive explanation for the pathophysiology of this movement disorder. However, several points remain unclear notably concerning the specific role of brainstem, basal ganglia nuclei and premotor cortex. We review data collected in sub-human primate to see whether they might provide new insights into the pathophysiology of dystonia. As in human patients, lesions of the putamen induce dystonia, as well as pharmacological manipulations of the dopaminergic system. In addition, primate studies revealed that lesions in brain stem areas involved in the control of muscular tone and GABAergic manipulations in various basal ganglia nuclei or thalamus also lead to dystonia. Moreover, there is a dramatic disruption in the processing of proprioceptive information with abnormal large receptive fields in the basal ganglia, thalamus, primary somesthetic cortex and premotor cortex of dystonic monkeys. These data highlight the idea that dystonia is associated with aberrant sensory representations interfering with motor control. Considering that the supplementary motor area (SMAp) is the target of basal ganglia projections within the motor loop, we propose a model of dystonia in which abnormal excitability, associated with alteration in sensory receptive fields within the SMAp, leads to an abnormal synchronization between primary motor cortex columns. Such a phenomenon might account for the co-contractions of antagonist muscles favored by action and the abnormal postures observed in dystonia.