RESUMO
Functional neurological disorders have a broad phenotypic spectrum and include different clinical syndromes, which are sometimes associated to each other or appear consecutively over the course of the disease. This clinical anthology provides details on the specific and sensitive positive signs that are to be sought in the context of a suspected functional neurological disorder. Beside these positive elements leading to the diagnosis of functional neurological disorder, we should keep in mind the possibility of an associated organic disorder as the combination of both organic and functional disorders is a relatively frequent situation in clinical practice. Here we describe the clinical characteristics of different functional neurological syndromes: motor deficits, abnormal hyperkinetic and hypokinetic movements, voice or speech disorders, sensory disorders, and functional dissociative seizures. The clinical examination and the identification of positive signs play a critical role in the diagnosis of functional neurological disorder. Knowledge of the specific signs associated with each phenotype render possible to make an early diagnosis. For that matter, it contributes to the improvement of patient care management. It allows to a better engagement in an appropriate care pathway, which influence their prognosis. Highlighting and discussing positive signs with patients can also be an interesting step in the process of explaining the disease and its management.
Assuntos
Transtorno Conversivo , Humanos , Síndrome , Transtorno Conversivo/complicaçõesRESUMO
Movement disorders are extremely common and diverse in autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS). They can sometimes represent the main neurological disorder of a given patient, or just be part of a larger neurological syndrome. Early diagnosis of AE or PNS is essential, as the associated abnormal movements can be effectively treated with immunomodulators. Nevertheless, the diagnosis is often delayed because of the large number of differential diagnoses (infections, metabolic disorders, genetic and degenerative diseases) and because the semiology of abnormal movements arising during AE and PNS is often not well known. However, there are highly specific clinical features, depending on the associated autoantibodies, age and gender of the patient, and associated cancers. Such features are likely to rely on specific mechanisms, the knowledge of which could lead to new therapeutic proposals. Also, the growing body of work on AE and PNS provides a better understanding of the links between immunity and neuronal degeneration, and immunity and genetic specificities. Thus, the purpose of this article is to present the current knowledge and different subtypes of movement disorders associated with AE and PNS, as well as the mechanisms that can lead to neuronal dysfunction.
Assuntos
Doenças Autoimunes/complicações , Encefalite/complicações , Transtornos dos Movimentos/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Doenças Autoimunes/terapia , Encefalite/terapia , Humanos , Transtornos dos Movimentos/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/terapiaRESUMO
Movement disorders (tremor, chorea, dystonia, tics, and myoclonus) are related to basal ganglia and/or interconnected brain areas dysfunction. Clinical examination is a key point in order to characterize the abnormal movement and identify associated signs that can guide etiological approach. Iatrogenic diseases will be systematically ruled out before conducting additional investigations (brain MRI, electrophysiological studies). Wilson disease, but also other treatable metabolic and/or genetic diseases, and auto-immune diseases will be systematically considered. Therapeutic management is symptomatic and based on specific oral drugs appropriate to each movement disorders. In some cases, radiosurgery and deep brain stimulation should be helpful, especially for tremor and generalized dystonia.
Assuntos
Transtornos dos Movimentos , Administração Oral , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Diagnóstico Diferencial , Eletrofisiologia , Humanos , Imageamento por Ressonância Magnética , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/terapiaRESUMO
CEREBROVASCULAR DISEASES: The benefit of the thrombectomy using stents retrievers in the acute stroke phase is now demonstrated when there is a proximal occlusion of an intracranial artery, whatever its mechanism. The place of the anticoagulants in the management of cervical artery dissections remains uncertain, while the benefit of the blood pressure control in the secondary prevention of deep and lobar intracerebral hemorrhages is critical. The development of cardiac MRI, prolonged cardiac monitoring and transcranial doppler seems to improve the diagnosis of cardio-embolic sources of stroke. EPILEPSY: A specialized urgent-access single seizure clinic represents a model which reduces wait-times and improves patient access after a first fit. Co-locating a psychiatrist within outpatient epilepsy center leads to a reduction in psychiatric symptoms and people with psychogenic non-epileptic seizures. When neurologists around the world assess identical case scenarios for the diagnosis of epilepsy, concordance is between moderate and poor, showing that epilepsy diagnosis remains difficult. More than one third of elderly with new-onset epilepsy of unknown etiology exhibit temporal lobe atrophy on brain imaging. MOVEMENT DISORDERS: There is no major progress in the therapeutic approach of Parkinson's disease but the discovery of new genetic markers such as glucocerebrosidase mutations may greatly change our knowledge of the disease process and may induce new therapeutic strategies in the future. The natural history of the disease is also better understood from the prodromal phase to the post-mortem analysis of the brain and the classification of the processes based on abnormal protein deposits. DEMENTIA: The respective value of biomarkers (amyloid imaging versus CSF biomarkers) for in vivo diagnosis of Alzheimer's disease (AD) has been detailed. Therapeutic expectations mainly rely on anti-Aß immunization trials performed in preclinical (and no longer prodromal) stages of AD, with the aim of slowing the evolution of neuronal loss. Besides a lot of communications on dementia genetics or physiopathogeny, fascinating and promising results were presented on deep brain stimulation for depression resistant to medical treatment. PERIPHERAL NEUROPATHY: Ibudilast, administered with riluzole, is safe and tolerable in patients with amyotrophic lateral sclerosis (ALS), improves ALS function and delays progression. Patients with painful small fiber neuropathy have a high rate of mutations in the SCN9A gene, coding for Nav1.7 voltage-gated sodium-channels. Peripheral nerve lymphoma (NL) is a multifocal painful neuropathy that causes endoneurial inflammatory demyelination: primary NL is less severe than secondary NL, which occurs after remission, suggesting that nerve may be considered a "safe lymphoma haven". MULTIPLE SCLEROSIS (MS): Biotin in progressive forms of MS and daclizumab in relapsing-remitting forms appear to be promising treatments. In case of failure of current first-line and/or second-line therapeutics, alemtuzumab may be an interesting alternative treatment. Teriflunomide, dimethyl fumarate and fingolimod are oral treatments with confirmed efficacy and acceptable safety. Besides vitamin D insufficiency and smoking, which are confirmed risk factors for the disease, testosterone insufficiency (in males) and obesity are emerging risk factors, which could also be corrected.
Assuntos
Neurologia/tendências , Transtornos Cerebrovasculares/genética , Humanos , Transtornos dos Movimentos/genética , Esclerose Múltipla/genética , Doenças do Sistema Nervoso Periférico/genéticaRESUMO
Tremor and myoclonus are very common manifestations of psychogenic movement disorders (PMD). In this context, recording of movement disorders aims to provide objective criteria for a positive diagnosis of PMD, independently of the psychological situation. Neurophysiological observations are therefore considered to have a huge impact both on diagnosis and on therapeutic approaches. A specific recording strategy should be employed whenever the medical history or clinical clues raise the eventuality of a PMD. Polymyography coupled to accelerometry is used to demonstrate the major electrophysiological criteria of psychogenic tremor, namely spontaneous variability of tremor frequency and frequency entrainment induced by contralateral rhythmic tasks. Other features, such as paradoxical increase of tremor amplitude with mass loading, co-activation preceding tremor onset and alteration of voluntary contralateral motor performances when tremor is present, are also of interest. The clinical presentation of psychogenic myoclonus is extremely rich and polymorphous and can mimic virtually all forms of cortical, subcortical or spinal myoclonus. Focal, multifocal, axial or generalized jerks can occur. Psychogenic jerks can be sporadic or repetitive, rhythmic or arrhythmic, spontaneous or stimulus-induced. All of these parameters are crucial to determine an individualized neurophysiological strategy. Polymyography is critical to identify a ballistic pattern or a discordant or non-reproducible temporo-spatial organisation of the jerks, but has usually to be completed by other potentially decisive approaches. Reflex psychogenic myoclonus for example displays stimulus-response delays that are too long and variable. Spontaneous psychogenic jerks may be also preceded by a pre-movement potential, detectable by jerk-locked-back-averaging methods.
Assuntos
Mioclonia/diagnóstico , Mioclonia/psicologia , Tremor/diagnóstico , Tremor/psicologia , Eletromiografia , Humanos , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/fisiopatologia , Transtornos dos Movimentos/psicologia , Mioclonia/fisiopatologia , Tremor/fisiopatologiaRESUMO
Mitochondrial disorders have a broad clinical spectrum and are genetically heterogeneous, involving two genomes. These disorders may be develop at any age, with isolated or multiple system involvement, and any pattern of inheritance. Neurological involvement is the most frequent, and concerns muscular, peripheral and central nervous system. Among these diverse signs, some are suggestive of mitochondrial disease, such as progressive external ophthalmoplegia, exercise intolerance, psychomotor regression, stroke-like episodes, refractory epilepsy and Epilepsia Partialis Continua. Others are less specific and mitochondrial hypothesis may be evocated because of either association of different neuromuscular signs or a multisystemic involvement. This review describes the wealth of this neurological and neuromuscular symptomatology through different syndromes reported in the literature, according to preponderant signs and to modes of inheritance, as key elements to guide genetics testing.
Assuntos
Doenças Mitocondriais/complicações , Doenças do Sistema Nervoso/etiologia , Doenças Neuromusculares/etiologia , DNA Mitocondrial/genética , Predisposição Genética para Doença , Humanos , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Doenças do Sistema Nervoso/diagnóstico , Doenças Neuromusculares/diagnóstico , SíndromeRESUMO
INTRODUCTION: Glucose transporter type 1 deficiency syndrome is caused by heterozygous, mostly de novo, mutations in the SLC2A1 gene encoding the glucose transporter GLUT1. Mutations in this gene limit brain glucose availability and lead to cerebral energy deficiency. STATE OF THE ART: The phenotype is characterized by the variable association of mental retardation, acquired microcephaly, complex motor disorders, and paroxysmal manifestations including seizures and non-epileptic paroxysmal episodes. Clinical severity varies from mild motor dysfunction to severe neurological disability. In patients with mild phenotypes, paroxysmal manifestations may be the sole manifestations of the disease. In particular, the diagnosis should be considered in patients with paroxysmal exercise-induced dyskinesia or with early-onset generalized epilepsy. Low CSF level of glucose, relative to blood level, is the best biochemical clue to the diagnosis although not constantly found. Molecular analysis of the SLC2A1 gene confirms the diagnosis. Ketogenic diet is the cornerstone of the treatment and implicates a close monitoring by a multidisciplinary team including trained dieticians. Non-specific drugs may be used as add-on symptomatic treatments but their effects are often disappointing. CONCLUSION: Glucose transporter type 1 deficiency syndrome is likely under diagnosed due to its complex and pleiotropic phenotype. Proper identification of the affected patients is important for clinical practice since the disease is treatable.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos , Proteínas de Transporte de Monossacarídeos/deficiência , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/terapia , Dieta Cetogênica/métodos , Transportador de Glucose Tipo 1/genética , Humanos , Proteínas de Transporte de Monossacarídeos/genética , Fenótipo , Ácido Tióctico/uso terapêutico , Triglicerídeos/uso terapêuticoRESUMO
This historical article describes the life and work of the British physician Samuel Alexander Kinnier Wilson (1878-1937), who was one of the world's greatest neurologists of the first half of the 20th century. Early in his career, Wilson spent one year in Paris in 1903 where he learned from Pierre-Marie at Bicêtre Hospital. He subsequently retained uninterrupted links with French neurology. He also visited in Leipzig the German anatomist Paul Flechsig. In 1904, Wilson returned to London, where he worked for the rest of his life at the National Hospital for the Paralysed and Epileptic (later the National Hospital for Nervous Diseases, and today the National Hospital for Neurology and Neurosurgery) in Queen Square, and also at Kings' College Hospital. He wrote on 'the old motor system and the new', on disorders of motility and muscle tone, on the epilepsies, on aphasia, apraxia, tics, and pathologic laughing and crying, and most importantly on Wilson's disease. The other objective of our paper is to commemorate the centenary of Wilson's most important work published in 1912 in Brain, and also in Revue Neurologique, on an illness newly recognized and characterized by him entitled "Progressive lenticular degeneration, a familial nervous disease associated with liver cirrhosis". He analyzed 12 clinical cases, four of whom he followed himself, but also four cases previously published by others and a further two that he considered in retrospect had the same disease as he was describing. The pathological profile combined necrotic damage in the lenticular nuclei of the brain and hepatic cirrhosis. This major original work is summarized and discussed in the present paper. Wilson not only delineated what was later called hepato-lenticular degeneration and Wilson's disease, but also introduced for the first time the terms extrapyramidal syndrome and extrapyramidal system, stressing the role of the basal ganglia in motility. The present historical work emphasizes the special contributions made by Wilson to the study of movement disorders, including akinesia and bradykinesia in Parkinson's disease, and their relation to basal ganglia pathology.
Assuntos
Degeneração Hepatolenticular/história , Neurologia/história , Inglaterra , Degeneração Hepatolenticular/complicações , História do Século XX , Humanos , Cirrose Hepática/etiologia , Transtornos dos Movimentos/história , Transtornos dos Movimentos/terapiaRESUMO
Texts published, in 1912, 100 years ago, by Sir K. Wilson on his eponymous disease in Brain, The Lancet and La Revue Neurologique highlight the relevance of his descriptions in the light of the current knowledge. Wilson's invocation of an "unknown toxin" appears today as a prophetic intuition as the presence of excess copper in the liver was mentioned for the first time a year later whereas the role of copper in this disease was not described until 1929. Progress has been made to better understand the physiology of Wilson's disease (WD). The ATP7B gene implicated in WD is located on chromosome 13 and more than 500 mutations and 100 polymorphisms have been to date identified. The phenotypic expression is highly variable, even within a family. This can partly be explained by environmental factors as nutrition. Modulator genes are also involved in the phenotypic expression of the disease. Most of symptoms observed in WD have already been described in detail by Wilson in 1912, but subsequent progress was made over the following 100 years, helping the physician diagnose WD. Hepatic and neurological symptoms are the most frequent expressions of the disease. Other extrahepatic features include renal manifestations, osteoarticular disorders, myocardial abnormalities, endocrine disturbances, realizing a multisystemic disease. The diagnosis of the disease is based on a combination of clinical symptoms, biological, radiological and genetic data and new tools (Brain MRI, relative exchangeable copper ) allow reducing delay to diagnosis. Therapeutic findings have also changed the disease prognosis. Treatment is based on the use of copper chelators to promote copper excretion from the body (D-penicillamine and Triethylenetetramine) and zinc salts to reduce copper absorption. Tetratiomolybdate appears to be a promising treatment. While significant progress has been made during this century, many physiological aspects of this disease remain unknown and require further research to find answers in the next 100 years.