RESUMO
Dominant optic atrophy (DOA) is genetically heterogeneous and pathogenic mutations have been identified in the OPA1 and OPA3 genes, both encoding for mitochondrial proteins. We characterized clinical and laboratory features in a large OPA1-negative family with complicated DOA. Search for mitochondrial dysfunction was performed by studying muscle biopsies, fibroblasts, platelets and magnetic resonance (MR) spectroscopy. Genetic investigations included mitochondrial DNA (mtDNA) analysis, linkage analysis, copy number variation (CNV) analysis and candidate gene screening. Optic neuropathy was undistinguishable from that in OPA1-DOA and frequently associated with late-onset sensorineural hearing loss, increases of central conduction times at somato-sensory evoked potentials and various cardiac abnormalities. Serum lactic acid after exercise, platelet respiratory complex activities, adenosine triphosphate (ATP) content in fibroblasts and muscle phosphorus MR spectroscopy all failed to reveal a mitochondrial dysfunction. However, muscle biopsies and their mtDNA analysis showed increased mitochondrial biogenesis. Furthermore, patient's fibroblasts grown in the galactose medium were unable to increase ATP content compared with controls, and exhibited abnormally high rate of fusion activity. Genome-wide linkage revealed a locus on chromosome 16q21-q22 with a maximum two-point LOD score of 8.84 for the marker D16S752 and a non-recombinant interval of â¼ 6.96 cM. Genomic screening of 45 genes in this interval including several likely candidate genes (CALB2, CYB5B, TK2, DHODH, PLEKHG4) revealed no mutation. Moreover, we excluded the presence of CNVs using array-based comparative genome hybridization. The identification of a new OPA locus (OPA8) in this pedigree demonstrates further genetic heterogeneity in DOA, and our results indicate that the pathogenesis may still involve mitochondria.
Assuntos
Cromossomos Humanos Par 16/genética , Atrofia Óptica Autossômica Dominante/genética , Adolescente , Adulto , Criança , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Feminino , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Linhagem , Polimorfismo Genético/genética , Vasos Retinianos/patologia , Adulto JovemRESUMO
Pathophysiology of restless legs syndrome is poorly understood. A role of the thalamus, specifically of its medial portion which is a part of the limbic system, was suggested by functional magnetic resonance imaging and positron emission tomography studies. The aim of this study was to evaluate medial thalamus metabolism and structural integrity in patients with idiopathic restless legs syndrome using a multimodal magnetic resonance approach, including proton magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis. Twenty-three patients and 19 healthy controls were studied in a 1.5 T system. Single voxel proton magnetic resonance spectra were acquired in the medial region of the thalamus. In diffusion tensor examination, mean diffusivity and fractional anisotropy were determined at the level of medial thalamus using regions of interest delineated to outline the same parenchyma studied by spectroscopy. Voxel-based morphometry was performed focusing the analysis on the thalamus. Thalamic volumes were obtained using FMRIB's Integrated Registration and Segmentation Tool software, and shape analysis was performed using the FMRIB Software Library tools. Proton magnetic resonance spectroscopy study disclosed a significantly reduced N-acetylaspartate:creatine ratio and N-acetylaspartate concentrations in the medial thalamus of patients with restless legs syndrome compared with healthy controls (P < 0.01 for both variable). Lower N-acetylaspartate concentrations were significantly associated with a family history of restless legs syndrome (ß = -0.49; P = 0.018). On the contrary, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis of the thalami did not show differences between the two groups. Proton magnetic resonance spectroscopic findings in patients with restless legs syndrome indicate an involvement of medial thalamic nuclei of a functional nature; however, the other structural techniques of the same region did not show any changes. These findings support the hypothesis that dysfunction of the limbic system plays a role in the pathophysiology of idiopathic restless legs syndrome.
Assuntos
Mapeamento Encefálico , Síndrome das Pernas Inquietas/metabolismo , Síndrome das Pernas Inquietas/patologia , Tálamo/metabolismo , Adulto , Análise de Variância , Anisotropia , Ácido Aspártico/análogos & derivados , Creatina , Estudos Transversais , Imagem de Tensor de Difusão , Processamento Eletrônico de Dados , Humanos , Inositol , Espectroscopia de Ressonância Magnética , Pessoa de Meia-Idade , PrótonsRESUMO
The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case-control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group.
Assuntos
Epilepsia do Lobo Frontal/epidemiologia , Epilepsia do Lobo Frontal/psicologia , Hábitos , Tabagismo/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Eletroencefalografia , Epilepsia do Lobo Frontal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polissonografia , Receptores Nicotínicos/genética , Estudos Retrospectivos , Tabagismo/psicologia , Gravação em Vídeo , Adulto JovemRESUMO
BACKGROUND: Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field. Furthermore, the management of RLS is now a part of routine neurological practice in Europe. New drugs have also become available, and further randomized controlled trials have been undertaken. These guidelines were undertaken by the EFNS in collaboration with the European Neurological Society and the European Sleep Research Society. OBJECTIVES: To provide an evidence-based update of new treatments published since 2005 for the management of RLS. METHODS: First, we determined what the objectives of management of primary and secondary RLS should be. We developed the search strategy and conducted a review of the scientific literature up to 31 December 2011 (print and electronic publications) for the drug classes and interventions employed in RLS treatment. Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations made according to the 2004 EFNS criteria for rating. RECOMMENDATIONS: Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS. However, for the long-term treatment for RLS, rotigotine is considered effective, gabapentin enacarbil is probably effective, and ropinirole, pramipexole and gabapentin are considered possibly effective. Cabergoline has according to our criteria a level A recommendation, but the taskforce cannot recommend this drug because of its serious adverse events.
Assuntos
Síndrome das Pernas Inquietas/terapia , Medicina Baseada em Evidências , HumanosRESUMO
BACKGROUND: Hypocretins (orexins) are hypothalamic neuropeptides which are involved in a wide range of physiological processes in mammals including central pain processing. Genetic studies in humans evidenced a role for the hypocretinergic system in cluster headache (CH). PATIENTS AND METHODS: We tested cerebrospinal fluid (CSF) hypocretin-1 (orexin-A) levels in 10 CH patients during an active cluster period. CSF hypocretin-1 levels were measured by radioimmunoassay. RESULTS: CSF hypocretin-1 levels were within the normal range (mean 457.3±104.98 pg/ml, range 304-639) in our 10 patients, with a slight reduction in one case (304 pg/ml). There were no associations between CSF hypocretin-1 levels and the clinical features of CH. A trend towards higher hypocretin-1 levels was disclosed in patients with chronic CH compared to episodic CH. CONCLUSIONS: CSF hypocretin-1 levels seem not to influence the clinical course of CH, but our results cannot completely exclude a functional involvement of the hypothalamic hypocretinergic system in the pathogenesis of CH.
Assuntos
Cefaleia Histamínica/líquido cefalorraquidiano , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orexinas , RadioimunoensaioRESUMO
BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis. METHODS: One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality. RESULTS: RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality. CONCLUSIONS: This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.
Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/mortalidade , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Falência Renal Crônica/mortalidade , Masculino , Estudos Prospectivos , Diálise Renal/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idiopathic hypersomnia (IH) without long sleep time] and REM sleep [narcolepsy without cataplexy (NwoC) and narcolepsy with cataplexy (NC)]-related hypersomnias of central origin. We analysed sleep onset characteristics at the multiple sleep latency test (MSLT) applying simultaneously two sleep onset criteria in 44 NC, seven NwoC and 16 IH consecutive patients referred for subjective EDS complaint. Sleep latency (SL) at MSLT was assessed both as the time elapsed to the occurrence of a single epoch of sleep Stage 1 NREM (SL) and of unequivocal sleep [three sleep Stage 1 NREM epochs or any other sleep stage epoch, sustained SL (SusSL)]. Idiopathic hypersomnia patients showed significantly (P<0.0001) longer SusSL than SL (7.7±2.5 versus 5.6±1.3 min, respectively) compared to NwoC (5.8±2.5 versus 5.3±2.2 min) and NC patients (4.1±3 versus 3.9±3 min). A mean difference threshold between SusSL and SL ≥27 s reached a diagnostic value to discriminate IH versus NC and NwoC sufferers (sensitivity 88%; specificity 82%). Moreover, NC patients showed better subjective sleepiness perception than NwoC and IH cases in the comparison between naps with or without sleep occurrence. Simultaneous application of the two widely used sleep onset criteria differentiates IH further from NC and NwoC patients: IH fluctuate through a wake-Stage 1 NREM sleep state before the onset of sustained sleep, while NC and NwoC shift abruptly into a sustained sleep. The combination of SusSL and SL determination at MSLT should be tested as an additional objective differential criterion for EDS disorders.
Assuntos
Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Adulto , Biomarcadores , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Polissonografia , Estudos Prospectivos , Sono/fisiologia , Sono REM/fisiologia , Fatores de TempoRESUMO
Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells are more concentrated around the fovea and are lost with ageing. The current results provide a plausible explanation for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells.
Assuntos
Degeneração Neural/fisiopatologia , Atrofia Óptica Autossômica Dominante/fisiopatologia , Atrofia Óptica Hereditária de Leber/fisiopatologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Vias Visuais/fisiopatologia , Adulto , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Envelhecimento/fisiologia , Estudos de Casos e Controles , Feminino , Humanos , Hipotálamo/patologia , Hipotálamo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/patologia , Doenças Mitocondriais/fisiopatologia , Degeneração Neural/patologia , Atrofia Óptica Autossômica Dominante/patologia , Atrofia Óptica Hereditária de Leber/patologia , Retina/patologia , Retina/fisiopatologia , Células Ganglionares da Retina/patologia , Vias Visuais/patologiaRESUMO
While dreaming amputees often experience a normal body image and the phantom limb may not be present. However, dreaming experiences in amputees have mainly been collected by questionnaires. We analysed the dream reports of amputated patients with phantom limb collected after awakening from REM sleep during overnight videopolysomnography (VPSG). Six amputated patients underwent overnight VPSG study. Patients were awakened during REM sleep and asked to report their dreams. Three patients were able to deliver an account of a dream. In all dreaming recalls, patients reported that the amputated limbs were intact and completely functional and they no longer experienced phantom limb sensations. Phantom limb experiences, that during wake result from a conflict between a pre-existing body scheme and the sensory information on the missing limb, were suppressed during sleep in our patients in favour of the image of an intact body accessed during dream.
Assuntos
Amputados/psicologia , Sonhos/psicologia , Membro Fantasma/psicologia , Adulto , Idoso , Sonhos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Membro Fantasma/fisiopatologia , Polissonografia , Sono REM/fisiologia , Inquéritos e QuestionáriosRESUMO
The purpose of this study was to evaluate the distribution of the polymorphisms of the SCN1A gene in a series of children and adolescents with primary headache and idiopathic or cryptogenic epilepsy compared to controls. Five non-synonymous exonic polymorphisms (1748A > T, 2656T > C, 3199A > G, 5771G > A, 5864T > C) of the SCN1A gene were selected and their genotyping was performed, by high resolution melting (HRM), in 49 cases and 100 controls. We found that among the five polymorphisms, only 3199A > G was a true polymorphism. We did not find a statistically significant difference between distribution of 3199A > G genotypes between cases and controls. We excluded the role of the SCN1A gene in the pathogenesis of comorbidity between headache (especially migraine) and epilepsy. The SCN1A gene is a major gene in different epilepsies and epilepsy syndromes; the HRM could be the new methodology, more rapid and efficacious, for molecular analysis of the SCN1A gene.
Assuntos
Epilepsia/epidemiologia , Epilepsia/genética , Predisposição Genética para Doença/genética , Transtornos da Cefaleia Primários/epidemiologia , Transtornos da Cefaleia Primários/genética , Proteínas do Tecido Nervoso/genética , Canais de Sódio/genética , Adolescente , Estudos de Casos e Controles , Criança , Comorbidade , Epilepsia/complicações , Feminino , Genótipo , Transtornos da Cefaleia Primários/complicações , Humanos , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1 , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodosRESUMO
STUDY OBJECTIVES: To investigate the occurrence of restless legs syndrome (RLS) in narcolepsy with cataplexy (NC). DESIGN: A case-control study assessing the frequency of comorbidity of RLS and NC in three European sleep disorder centers. PATIENTS: Three sleep research centers recruited 184 NC patients and 235 age-matched controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: NC patients and controls underwent a face-to-face interview investigating demographics, medical and drug history, sleep habits, and sleep disorders, in particular RLS based on the 4 international criteria and on a frequency > or =2 times/week, with a detailed description of RLS symptoms when present. RLS was significantly more prevalent among NC patients (14.7%) than in controls (3.0%). The age at onset of RLS in NC patients fits with the age at onset in idiopathic RLS, and RLS appeared more than 10 years after NC onset. Unlike idiopathic RLS, RLS in NC subjects was not more prevalent in women and was less familial (15.4% of cases). Lastly, NC patients with RLS showed a moderate disease severity and an almost daily occurrence of symptoms, which were also diurnal in 35% of cases. Older age, higher blood ferritin levels, and sleep paralysis seem to have a predictive value for RLS in NC. The higher ferritin levels indicate that different pathophysiological mechanisms underlie secondary RLS associated with NC. CONCLUSIONS: This study highlights the association between RLS and NC. The nature of this association is still investigational, but it does indicate that RLS must be addressed in the evaluation and management of nocturnal sleep impairment in NC patients.
Assuntos
Narcolepsia/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Distribuição por Idade , Idade de Início , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Feminino , Ferritinas/sangue , França/epidemiologia , Humanos , Entrevistas como Assunto , Itália/epidemiologia , Masculino , Narcolepsia/sangue , Valor Preditivo dos Testes , Prevalência , Síndrome das Pernas Inquietas/sangue , Índice de Gravidade de Doença , Distribuição por Sexo , Paralisia do Sono/sangue , Paralisia do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
The combination of recessive early-onset parkinsonism and pyramidal tract signs caused by pallidopyramidal degeneration is known as pallidopyramidal disease or syndrome (PPD/S). We investigated whether patients diagnosed as Davison's PPD/S showed any definite proof of pyramidal and pallidal involvement, without findings suggestive of other nosological entities. Since Davison's original description, 15 other PPD/S cases have been reported, yet all lack proof of pyramidal or pallidal degeneration. Because of the dopa-responsiveness in all patients subsequent to Davison's report, we argue that these patients probably suffered from early-onset nigral parkinsonism or dopa-responsive dsystonia, rather than pallidal parkinsonism; in such cases, the presumed pyramidal Babinski could be a pseudobabinski ("striatal toe"). Secondary pallidopyramidal syndromes do occur, for example, in multiple system atrophy or Wilson's disease, but in these patients additional findings indicate diseases other than Davison's PPD/S. We conclude that the existence of PPD/S as a distinct clinico-pathological nosological entity, as proposed by Davison, is doubtful. In cases reported as Davison's PPD/S, the description "pallidopyramidal" seems to be a misnomer.
Assuntos
Globo Pálido/patologia , Doenças Neurodegenerativas/patologia , Tratos Piramidais/patologia , Feminino , História do Século XIX , História do Século XX , Humanos , Masculino , Doenças Neurodegenerativas/história , Doenças Neurodegenerativas/fisiopatologia , Doença de Parkinson/patologiaRESUMO
PURPOSE: Retrospective observations disclosed an overlap between parasomnias and nocturnal frontal lobe epilepsy (NFLE) not only in patients but also in their relatives, suggesting a possible common pathogenetic mechanism. This study aimed to verify whether relatives of patients with NFLE have a higher frequency of parasomnias, namely arousal disorders, and thereby shed light on the still unknown pathophysiologic mechanisms underlying NFLE. METHODS: We undertook a case-control family study in which we recruited NFLE probands and healthy controls, matched for age, sex, education, and geographic origin. At least four relatives were included for each proband and control. Each subject underwent a standardized interview, with application of the International Classification of Sleep Disorders-Revised (ICSD-R 2001) minimal criteria to diagnose the lifetime prevalence of the main parasomnias. RESULTS: Four hundred fifty-eight individuals were recruited: 33 NFLE probands, 200 relatives of probands, 31 controls, and 194 control relatives. All NFLE probands but one have sporadic NFLE. The lifetime prevalence of the following parasomnias differed in proband relatives versus control relatives: arousal disorders [odds ratio (OR) 4.7, 95% confidence interval (CI) 2.0-11.6; p < 0.001] and nightmares (OR 2.6, 95% CI 1.6-4.2; p < 0.001) were more frequent among NFLE proband relatives. In the secondary analysis comparing NFLE probands to controls, arousal disorders (OR 6.3, 95% CI 1.3-31.7; p = 0.023) and bruxism (OR 5.4, 95% CI 1.3-21.7; p = 0.017) were more frequent among NFLE probands. DISCUSSION: The higher frequency of arousal disorders in NFLE families suggests an intrinsic link between parasomnias and NFLE and an abnormal (possibly cholinergic) arousal system as a common pathophysiologic mechanism.
Assuntos
Epilepsia do Lobo Frontal/epidemiologia , Família/psicologia , Lobo Frontal/fisiopatologia , Parassonias/epidemiologia , Transtornos do Despertar do Sono/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Comorbidade , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Frontal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parassonias/diagnóstico , Parassonias/fisiopatologia , Sistema Nervoso Parassimpático/fisiopatologia , Prevalência , Estudos Retrospectivos , Transtornos do Despertar do Sono/diagnóstico , Transtornos do Despertar do Sono/epidemiologiaRESUMO
Recent studies suggest that heterozygous female Fabry disease (FD) patients develop peripheral neuropathy. We used skin biopsy to define somatic and autonomic peripheral nerve characteristics in 21 females with FD who were mainly asymptomatic and had normal renal function. Somatic epidermal and dermal autonomic nerve fiber reductions were found, prevalently in the leg, and no differences were found between symptomatic and asymptomatic individuals. Our findings suggest that females with FD, although asymptomatic, may have somatic and autonomic small fiber neuropathy.
Assuntos
Sistema Nervoso Autônomo/patologia , Doença de Fabry/patologia , Fibras Nervosas Amielínicas/patologia , Doenças do Sistema Nervoso Periférico/patologia , Pele/inervação , Adulto , Eletrodiagnóstico , Doença de Fabry/complicações , Feminino , Humanos , Microscopia Confocal , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Medição da Dor , Limiar da Dor , Doenças do Sistema Nervoso Periférico/etiologia , Pele/patologiaRESUMO
Migraine is associated with stroke-like episodes in mitochondrial encephalomyopathy, lactic acidosis, stroke-like syndrome (MELAS). Moreover, abnormalities of oxidative phosphorylation are also reported in migraine. We studied two maternal lineages with MELAS and chronic progressive external ophthalmoplegia (CPEO) affected probands carrying the 3243 A>G tRNA(Leu) (MELAS) mutation, remarkable for a high frequency of subjects suffering only migraine. Thus, migraine could be a monosymptomatic expression of the MELAS mutation. We assessed the 3243 A>G tRNA(Leu) mutational load in skeletal muscle and other somatic tissues from the migraine-only subjects, as well as lactic acid levels after exercise. All migraine-only subjects did not carry the MELAS mutation. Muscle biopsy showed mild mitochondrial abnormalities in the non-mutant, migraine-only subjects and, occasionally, abnormal lactic acid. Clear features of mitochondrial myopathy and pathological lactic acid characterised the subjects carrying the MELAS mutation. Our study demonstrates that migraine-only subjects lacked the MELAS mutation, but still had a possible mtDNA-associated genetic predisposition, being maternally related and having some evidence of impaired mitochondrial oxidative phosphorylation.
Assuntos
DNA Mitocondrial/genética , Síndrome MELAS/complicações , Síndrome MELAS/genética , Transtornos de Enxaqueca/genética , Mutação , Adolescente , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , RNA de Transferência de Leucina/genéticaRESUMO
OBJECTIVE: The objective of this study is to present a view of the primary headaches as genetically determined behavioral responses consistent with sickness behavior and defense reaction, respectively. BACKGROUND AND DESIGN: A review of the literature bearing on the behavioral, humoral, and functional imaging aspects of the primary headaches shows that migraine and cluster headache (CH) are pain conditions characterized by different behaviors during the attacks. Here it is postulated that the behavioral responses to migraine and CH are evolutionary conserved reactions consistent with sickness behavior and defense reaction. RESULTS: The sickness behavior observed during migraine attacks is a pan-mammalian adaptive response to internal and external stressors, characterized by withdrawal and motor quiescence, sympatho-inhibition and lethargy, in which visceral pain signals a homeostatic imbalance of the body and/or brain. In contrast, the defense reaction in CH consists of a fight-or-flight reaction, with motor restlessness and agitation, in which pain is exteroceptive in kind. CONCLUSION: These different behavioral responses are thus specific to different kinds of pain, distinguished by the behavioral significance of the pain (visceral pain in migraine vs exteroceptive pain in CH), and imply brain matrices involving different networks in the brainstem, hypothalamus, and forebrain regions that engender evolutionarily conserved adaptive genetic responses. Cytokines play an important role in their development. Predictions and limitations of the hypothesis are discussed together with implications for genetic studies on headaches.
Assuntos
Adaptação Fisiológica/genética , Evolução Biológica , Predisposição Genética para Doença/genética , Transtornos da Cefaleia Primários/genética , Transtornos da Cefaleia Primários/fisiopatologia , Comportamento de Doença/fisiologia , Animais , Sistema Nervoso Autônomo/fisiopatologia , Citocinas/fisiologia , Homeostase/fisiologia , Humanos , Rede Nervosa/fisiopatologia , Fibras Aferentes Viscerais/fisiopatologiaRESUMO
OBJECTIVES: The aim of our study was to investigate the prevalence of sleep disorders in chronic headache patients and to evaluate the role of psychiatric comorbidity in the association between chronic headache and sleep complaints. BACKGROUND: The prevalence of sleep disorders in chronic headache has been seldom investigated, although from the earliest description chronic headache has been associated with sleep disturbances. On the contrary, mood disorders are commonly associated with both sleep disturbances and chronic headache--each of which are, in turn, core features of mood disorders. Therefore, it may be important to discriminate between sleep problems that can be attributed to a comorbid psychiatric disorder, and those specifically associated with headache. Only a few studies investigating the association of chronic headache with sleep difficulties have also taken into account to consider the possible role of anxiety and depression. PATIENTS AND METHODS: A total of 105 consecutive patients with daily or nearly daily headache and 102 patients with episodic headache, matched by age, sex, and type of headache at onset, underwent a structured direct interview about their sleep habits and psychiatric diseases. RESULTS: In total, 80 out of 105 patients with chronic headache received a diagnosis of medication overuse headache, 21 patients were classified as chronic migraine and 4 as chronic tension-type headache without drug overuse. PATIENTS: Patients with chronic headache showed a high prevalence of insomnia, daytime sleepiness, and snoring with respect to controls (67.7% vs 39.2%, 36.2% vs 23.5%, and 48.6% vs 37.2%, respectively). Forty-five patients with chronic headache (42.9%) had psychiatric comorbidity (anxiety and/or depressive disorders), vs 27 episodic headache patients (26.5%). Multivariate analysis disclosed that low educational level, lower mean age at headache onset, and insomnia are independently associated with chronic headache. CONCLUSIONS: Patients with chronic headache had a high prevalence of sleep complaints. Insomnia may thus represent an independent risk factor for headache chronification. Recognition of sleep disorders, alone or in association with depression or anxiety, may be useful in episodic headache patients to prevent chronification.
Assuntos
Transtornos da Cefaleia/complicações , Transtornos da Cefaleia/epidemiologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Adulto , Estudos de Casos e Controles , Criança , Maus-Tratos Infantis/diagnóstico , Maus-Tratos Infantis/psicologia , Comorbidade , Feminino , Transtornos da Cefaleia/psicologia , Humanos , Masculino , Prevalência , Fatores de Risco , Transtornos do Sono-Vigília/psicologiaRESUMO
The intra vitam diagnosis of prion disease is challenging and a definite diagnosis still requires neuropathological examination in non-familial cases. Magnetic resonance imaging has gained increasing importance in the diagnosis of prion disease. The aim of this study was to compare the usefulness of different magnetic resonance imaging sequences and proton magnetic resonance spectroscopy in the differential diagnosis of patients with rapidly progressive neurological signs compatible with the clinical diagnosis of sporadic prion disease. Twenty-nine consecutive patients with an initial diagnosis of possible or probable sporadic prion disease, on the basis of clinical and electroencephalography features, were recruited. The magnetic resonance protocol included axial fluid-attenuated inversion recovery-T2- and diffusion-weighted images, and proton magnetic resonance spectroscopy of the thalamus, striatum, cerebellum and occipital cortex. Based on the clinical follow-up, genetic studies and neuropathology, the final diagnosis was of prion disease in 14 patients out of 29. The percentage of correctly diagnosed cases was 86% for diffusion-weighted imaging (hyperintensity in the striatum/cerebral cortex), 86% for thalamic N-acetyl-aspartate to creatine ratio (cutoff =1.21), 90% for thalamic N-acetyl-aspartate to myo-inositol (mI) ratio (cutoff =1.05) and 86% for cerebral spinal fluid 14-3-3 protein. All the prion disease patients had N-acetyl-aspartate to creatine ratios =1.21 (100% sensitivity and 100% negative predictive value) and all the non-prion patients had N-acetyl-aspartate to myo-inositol ratios >1.05 (100% specificity and 100% positive predictive value). Univariate logistic regression analysis showed that the combination of thalamic N-acetyl-aspartate to creatine ratio and diffusion-weighted imaging correctly classified 93% of the patients. The combination of thalamic proton magnetic resonance spectroscopy (10 min acquisition duration) and brain diffusion-weighted imaging (2 min acquisition duration) may increase the diagnostic accuracy of the magnetic resonance scan. Both sequences should be routinely included in the clinical work-up of patients with suspected prion disease.
Assuntos
Química Encefálica/fisiologia , Encéfalo/patologia , Doenças Priônicas/patologia , Proteínas 14-3-3/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Logísticos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Priônicas/diagnóstico , Proteínas Priônicas , Príons/químicaRESUMO
The purpose of this study was to analyse the comorbidity between headache and epilepsy in a large series of children with headache (1,795). Fifty-six cases (3.1%) suffered from idiopathic headache and idiopathic or cryptogenic epilepsy or unprovoked seizures. There was a strong association between migraine and epilepsy: in migraineurs (46/56) the risk of epilepsy was 3.2 times higher when compared with tension-type headache, without significant difference between migraine with and without aura (P = 0.89); children with epilepsy had a 4.5-fold increased risk of developing migraine than tension-type headache. In cases with comorbidity, focal epilepsies prevailed (43/56, 76.8%). Migraineurs affected by focal epilepsies (36/56) had a three times higher risk of having a cryptogenic epilepsy (27/36, 75%) than an idiopathic epilepsy (9/36, 25%) (P = 0.003). In migraine with aura, epilepsy preceded migraine in 71% of cases. Photosensitivity (7/56, 12.5%) and positive family history for epilepsy (22/56, 39%) were frequent in cases with comorbidity.
Assuntos
Epilepsia/epidemiologia , Transtornos da Cefaleia/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Cefaleia do Tipo Tensional/epidemiologia , Adolescente , Fatores Etários , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Epilepsia/classificação , Epilepsia/diagnóstico , Epilepsia Reflexa/epidemiologia , Epilepsia Reflexa/fisiopatologia , Feminino , Predisposição Genética para Doença/epidemiologia , Transtornos da Cefaleia/genética , Transtornos da Cefaleia/fisiopatologia , Inquéritos Epidemiológicos , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Itália/epidemiologia , Masculino , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/fisiopatologia , Prevalência , Estudos Retrospectivos , Cefaleia do Tipo Tensional/genética , Cefaleia do Tipo Tensional/fisiopatologia , Adulto JovemRESUMO
Serotonin is involved in several central nervous system functions including pain threshold, mood regulation and drug reward. Overuse of acute medications is commonly identified as a causative factor for medication overuse headache (MOH). Apparently, MOH shares with other kinds of drug addiction some common neurobiological pathways. The objective of this study is to assess the role of serotonin metabolism genes in the genetic liability to MOH. We performed a genetic association study using polymorphisms of five serotonin metabolism-related genes: serotonin transporter (5HTT), serotonin receptor 1A(5-HT1A), serotonin receptor 1B (5-HT1B), serotonin receptor 2A (5-HT2A) and serotonin receptor 6 (5HT6)genes. We compared 138 patients with MOH with a control sample of 117 individuals without headache and without drug overuse, and with 101 patients with migraine without aura but without drug overuse (MO). The genotypic and allelic distributions of all polymorphisms investigated didnot differ among the three groups. In conclusion, our studydoes not provide evidence that the 5HTT, 5-HT1A, 5HT1B,5HT2A and 5HT6 gene polymorphisms play a role in the genetic predisposition to MOH.