RESUMO
Cerebellar ataxia is a heterogeneous group of neural disorders clinically characterized by cerebellar dysfunction. The diagnosis of patients with progressive cerebellar ataxia is complex due to the direct correlation with other neuron diseases. Although there is still no cure for this pathological condition, some metabolic, hereditary, inflammatory, and immunological factors affecting cerebellar ataxia are being studied and may become therapeutic targets. Advances in studying the neuroanatomy, pathophysiology, and molecular biology of the cerebellum (CE) contribute to a better understanding of the mechanisms behind the development of this disorder. In this study, Wistar rats aged 30 to 35 days were injected intraperitoneally with 3-acetylpyridine (3-AP) and/or metformin (for AMP-activated protein kinase (AMPK) enzyme activation) and euthanized in 24 hours and 4 days after injection. We analyzed the neuromodulatory role of the AMPK on cerebellar ataxia induced by the neurotoxin 3-AP in the brain stem (BS) and CE, after pre-treatment for 7 and 15 days with metformin, a pharmacological indirect activator of AMPK. The results shown here suggest that AMPK activation in the BS and CE leads to a significant reduction in neuroinflammation in these regions. AMPK was able to restore the changes in fatty acid composition and pro-inflammatory cytokines caused by 3-AP, suggesting that the action of AMPK seems to result in a possible neuroprotection on the cerebellar ataxia model.
Assuntos
Proteínas Quinases Ativadas por AMP , Ataxia Cerebelar , Modelos Animais de Doenças , Metformina , Fármacos Neuroprotetores , Ratos Wistar , Metformina/farmacologia , Metformina/uso terapêutico , Animais , Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/metabolismo , Ataxia Cerebelar/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Neurotoxinas/toxicidade , Ativação Enzimática/efeitos dos fármacos , Ratos , Cerebelo/efeitos dos fármacos , Cerebelo/patologia , Cerebelo/metabolismo , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/metabolismo , Tronco Encefálico/patologia , Citocinas/metabolismo , PiridinasRESUMO
Current understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features, highlighting atypical presentations and gaps of knowledge. Following the PRISMA guidelines, we systematically screened Pubmed/MEDLINE, Embase, Scopus, and Web of Science from inception to April 2022 for all case reports and series concerning anti-Yo antibody-associated cerebellar ataxia. We collected data on clinical presentation, investigation findings, and treatment outcomes. Of 379 included patients, 96% were female with gynecologic cancer (82%). Among men, 87% had an associated tumor, mainly of gastrointestinal origin. The median age was 60 years old. Pancerebellar ataxia was the main clinical feature, but extracerebellar findings were frequent during the disease course. Vertigo and imbalance can be present early in the disease course in about two thirds of patients, as a prodromal phase. Although neuroimaging usually is normal or shows cerebellar atrophy, inflammatory changes may also be present. More than half of the patients reported some improvement after immunotherapy. However, despite treatment, 84% of survivors were unable to walk unassisted on follow-up. Our study provides objective data and advances in current knowledge of anti-Yo antibody-associated cerebellar ataxia such as the description of prodromal symptoms, extracerebellar findings, and its presentations in males.
Assuntos
Ataxia Cerebelar , Doenças Cerebelares , Neoplasias , Degeneração Paraneoplásica Cerebelar , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Ataxia Cerebelar/patologia , Degeneração Paraneoplásica Cerebelar/terapia , Células de Purkinje/patologia , Doenças Cerebelares/patologia , Neoplasias/patologia , Autoanticorpos , Progressão da DoençaRESUMO
Neuropathy is a common associated feature of different types of genetic or sporadic cerebellar ataxias. The pattern of peripheral nerve involvement and its associated clinical features can be an invaluable aspect for narrowing the etiologic diagnosis in the investigation of cerebellar ataxias. In this review, we discuss the differential diagnosis of the intersection between peripheral nerve and cerebellar involvement, and classify them in accordance with the predominant features. Genetics, clinical features, neuroimaging, and neurophysiologic characteristics are discussed. Furthermore, a diagnostic approach for cerebellar ataxia with neuropathy is proposed according to the different clinical characteristics. This is an Educational and Descriptive review with the aim of medical education for the approach to the patients with cerebellar ataxia and neuropathy. The diagnostic approach to the patient with cerebellar ataxia with neuropathy requires a detailed medical history, phenotyping, characterization of disease progression and family history. Neuroimaging features and the neurophysiological findings play pivotal roles in defining the diagnosis. Establishing an organized classification method for the disorders based on the clinical features may be very helpful, and could be divided as those with predominant cerebellar features, predominant neuropathic feature, or conditions with both cerebellar ataxia and neuropathy. Second, determining the mode of inheritance is critical on cerebellar ataxias: autosomal dominant and recessive cerebellar ataxias, mitochondrial or sporadic types. Third, one must carefully assess neurophysiologic findings in order to better characterize the predominant pattern of involvement: damage location, mechanism of lesion (axonal or demyelinating), motor, sensory or sensory motor compromise, large or small fibers, and autonomic system abnormalities.
Assuntos
Ataxia Cerebelar , Doenças do Sistema Nervoso Periférico , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Cerebelo/patologia , Diagnóstico Diferencial , Humanos , Nervos PeriféricosRESUMO
This article reports a patient with acquired hepatocerebral degeneration that presented with progressive cerebellar ataxia, cerebellar atrophy, and middle cerebellar peduncle lesions. He had a marked improvement after liver transplantation. We reinforce that hepatic failure should be investigated in patients with pure cerebellar syndrome, resembling neurodegenerative diseases.
Assuntos
Doenças Cerebelares/etiologia , Encefalopatia Hepática/etiologia , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/patologia , Falência Hepática/etiologia , Atrofia/patologia , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/patologia , Doenças Cerebelares/patologia , Encefalopatia Hepática/cirurgia , Humanos , Falência Hepática/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Pedúnculo Cerebelar Médio/patologiaRESUMO
Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.
Assuntos
Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/etiologia , Doença Aguda , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Ataxia Cerebelar/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância MagnéticaRESUMO
ABSTRACT Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.
RESUMO A ataxia cerebelar é um achado comum na prática neurológica e tem uma grande variedade de causas, desde a degeneração cerebelar crônica e lentamente progressiva à lesão cerebelar aguda devido a infarto, edema ou hemorragia, configurando uma verdadeira emergência neurológica. Ataxia cerebelar aguda é uma síndrome que ocorre em menos de 72 horas em indivíduos previamente saudáveis. A ataxia aguda geralmente resulta em hospitalização e extensa investigação laboratorial. Os clínicos são frequentemente confrontados com a decisão sobre a extensão e o momento dos testes de rastreio iniciais, em particular para detectar as causas tratáveis. O principal grupo de doenças que podem causar ataxias agudas discutidas neste artigo são: acidente vascular cerebral, infecciosas, tóxicas, imunomediadas, paraneoplásicas, deficiência de vitaminas, lesões estruturais e doenças metabólicas. Esta revisão enfoca a etiologia e considerações diagnósticas para a ataxia aguda.
Assuntos
Humanos , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/etiologia , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ataxia Cerebelar/patologia , Doença Aguda , Diagnóstico DiferencialRESUMO
: The cerebellum has long been recognized as a fundamental structure in motor coordination. Structural cerebellar abnormalities and diseases involving the cerebellum are relatively common in children. The not always specific clinical presentation of ataxia, incoordination, and balance impairment can often be a challenge to attain a precise diagnosis. Continuous advances in genetic research and moreover the constant development in neuroimaging modalities, particularly in the field of magnetic resonance imaging, have promoted a better understanding of cerebellar diseases and led to several modifications in their classification in recent years. Thorough clinical and neuroimaging investigation is recommended for proper diagnosis. This review outlines an update of causes of cerebellar disorders that present clinically with ataxia in the pediatric population. These conditions were classified in 2 major groups, namely genetic malformations and acquired or disruptive disorders recognizable by neuroimaging and subsequently according to their features during the prenatal and postnatal periods.
Assuntos
Ataxia Cerebelar/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Diagnóstico Pré-Natal/métodos , Adolescente , Ataxia Cerebelar/patologia , Cerebelo/embriologia , Cerebelo/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , GravidezRESUMO
Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual disability. The typical iris anomaly is considered necessary to the diagnosis of GS. Recently, variants in ITPR1 were described causing GS. Non-neurological features were reported in few patients. Here we describe two consanguineous siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They also present a cardiac defect (pulmonary valve stenosis) and one sib had a genitourinary malformation (ureteropelvic junction obstruction). Our report reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the development of other organs.
Assuntos
Aniridia/genética , Aniridia/patologia , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Homozigoto , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Mutação , Brasil , Pré-Escolar , Consanguinidade , Feminino , Humanos , Lactente , Masculino , Linhagem , IrmãosRESUMO
Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive cerebellar ataxia associated with mutations in SETX, which encodes the senataxin protein, a DNA/RNA helicase. We describe the clinical phenotype and molecular characterization of a Colombian AOA2 patient who is compound heterozygous for a c.994 C>T (p.R332W) missense mutation in exon 7 and a c.6848_6851delCAGA (p.T2283KfsX32) frameshift deletion in SETX exon 21. Immunocytochemistry of patient-derived fibroblasts revealed a normal cellular distribution of the senataxin protein, suggesting that these mutations do not lead to loss or mis-localization of the protein, but rather that aberrant function of senataxin underlies the disease pathogenesis. Furthermore, we used the alkaline comet assay to demonstrate that patient-derived fibroblast cells exhibit an increased susceptibility to oxidative DNA damage. This assay provides a novel and additional means to establish pathogenicity of SETX mutations.
Assuntos
Ataxia Cerebelar/fisiopatologia , Síndrome de Cogan/fisiopatologia , Dano ao DNA/fisiologia , Fibroblastos/fisiologia , Estresse Oxidativo/fisiologia , Apraxias/congênito , Encéfalo/patologia , Núcleo Celular/metabolismo , Células Cultivadas , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Síndrome de Cogan/genética , Síndrome de Cogan/patologia , Colômbia , DNA Helicases , Feminino , Antebraço/fisiopatologia , Mutação da Fase de Leitura , Humanos , Pessoa de Meia-Idade , Enzimas Multifuncionais , Mutação de Sentido Incorreto , Linhagem , Fenótipo , RNA Helicases/genética , RNA Helicases/metabolismoRESUMO
Ataxia is the principal symptom of many common neurologic diseases in childhood. Ataxias caused by dysfunction of the cerebellum occur in acute, intermittent, and progressive disorders. Most of the chronic progressive processes are secondary to degenerative and metabolic diseases. In addition, congenital malformation of the midbrain and hindbrain can also be present, with posterior fossa symptoms related to ataxia. Brain MR imaging is the most accurate imaging technique to investigate these patients, and imaging abnormalities include size, shape, and/or signal of the brain stem and/or cerebellum. Supratentorial and cord lesions are also common. This review will discuss a pattern-recognition approach to inherited cerebellar ataxia in childhood. The purpose is to provide a comprehensive discussion that ultimately could help neuroradiologists better manage this important topic in pediatric neurology.
Assuntos
Encéfalo/patologia , Ataxia Cerebelar/congênito , Ataxia Cerebelar/patologia , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Criança , HumanosRESUMO
Familial hemiplegic migraine type 1 (FMH-1) is a rare form of migraine with aura, which is characterized by transient hemiparesis, sensory loss and visual disturbances. This monogenic disease shares many common features with classic migraine, suggesting a similar molecular pathophysiology. Migraine is triggered by activation and sensitization of the trigeminovascular system, specifically the trigeminal nociceptive afferents innervating the meninges. Aura migraine is associated with cortical spreading depression (CSD), which is a short-lasting intense wave of neuronal and glial cell depolarization that slowly progresses over the cortex and is followed by long-lasting neuronal activity depression.
Assuntos
Canais de Cálcio/metabolismo , Ataxia Cerebelar/metabolismo , Cefaleia/metabolismo , Transtornos de Enxaqueca/metabolismo , Animais , Canais de Cálcio/genética , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Humanos , Camundongos , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/patologia , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Neuropsychiatric manifestations are commonly observed in systemic lupus erythematosus (SLE) patients; however, cerebellar involvement has rarely been reported. In the presence of acute cerebellar ataxia, etiologies related (focal edema and ischemia) and not related (infections, malignancy and paraneoplastic syndromes) to lupus have to be considered and they imply different treatment strategies. We report the clinical and radiological features of 3 SLE patients who presented with acute cerebellar ataxia. A review of the literature was performed by documenting cases of cerebellar ataxia in SLE and the importance of neuroimaging in the evaluation of these patients.
Assuntos
Ataxia Cerebelar/etiologia , Ataxia Cerebelar/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Doença Aguda , Adolescente , Adulto , Cerebelo/irrigação sanguínea , Cerebelo/patologia , Feminino , Humanos , Imageamento por Ressonância MagnéticaAssuntos
Encefalopatias/patologia , Encéfalo/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Proteínas de Bactérias , Encefalopatias/genética , Ataxia Cerebelar/patologia , Criança , Humanos , Leucoencefalopatia Multifocal Progressiva/genética , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana Transportadoras , MutaçãoAssuntos
Criança , Humanos , Masculino , Encefalopatias/patologia , Encéfalo/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Proteínas de Bactérias , Encefalopatias/genética , Ataxia Cerebelar/patologia , Leucoencefalopatia Multifocal Progressiva/genética , Imageamento por Ressonância Magnética , Proteínas de Membrana Transportadoras , MutaçãoRESUMO
A congenital progressive cerebellar disorder is described in Holstein calves. The clinical signs were progressive and were characterized by ataxia, hypermetria, a wide stance and fine head tremors. When the affected cattle were forced to run, the signs were exacerbated, leading to epileptiform attacks. Histological lesions consisted of a very selective cerebellar cortical degeneration, almost exclusively affecting the Purkinje cells. The disease affected 6 out of 200 Holstein calves from the same bull. However, results of mating tests of the bull with his daughters and granddaughters suggested that it was not hereditary (p = 0.0062) although an environmental-genetic interaction could not be ruled out.
Assuntos
Doenças dos Bovinos/congênito , Córtex Cerebelar/patologia , Doenças Cerebelares/veterinária , Animais , Ataxia/veterinária , Bovinos , Doenças dos Bovinos/patologia , Ataxia Cerebelar/congênito , Ataxia Cerebelar/patologia , Ataxia Cerebelar/veterinária , Doenças Cerebelares/congênito , Doenças Cerebelares/patologia , Feminino , Histocitoquímica/veterinária , Masculino , Células de Purkinje/patologiaRESUMO
We report on a Mexican girl who developed cerebellar ataxia at age 3 years and pancytopenia at age 13 years. Cerebral computed tomography scan and magnetic resonance imaging showed evidence of severe cerebellar atrophy. Telangiectasias were not present; immunoglobulins and alpha-fetoprotein levels were normal. Cytogenetic studies showed no evidence of spontaneous chromosome aberrations, a normal rate of diepoxybutane (DEB) and mitomycin C (MMC)-induced chromosome aberrations, but an increased response to bleomycin. The phenotype support the diagnosis of ataxia-pancytopenia syndrome, although monosomy of chromosome 7 was not found in bone marrow. The cytogenetic studies suggest that this may be a chromosomal instability disorder.
Assuntos
Ataxia Cerebelar/patologia , Pancitopenia/patologia , Adulto , Ataxia Telangiectasia/diagnóstico , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Diagnóstico Diferencial , Anemia de Fanconi/diagnóstico , Feminino , Humanos , Cariotipagem , Pancitopenia/diagnóstico , Pancitopenia/genética , SíndromeRESUMO
Autosomal dominant cerebellar ataxia type I was diagnosed in three unrelated families from Martinique (French West Indies), and linkage to the locus for spinocerebellar ataxia 2 (SCA2) was established. Neuropathological findings in two patients were those of olivopontocerebellar atrophy without oligodendroglial cytoplasmic inclusions. Cerebellar ataxia was associated with hyporeflexia in 68% of 31 examined patients, with slowed and/or limited eye movements in 65% and with dementia in 29%. No patients had optic atrophy, pigmentary retinal degeneration, spasticity or parkinsonism. Mean age at onset was 33 +/- 16 years, and onset before the age of 20 years was correlated with a more rapid and severe course of the disease. Movement disorders, oculomotor disturbances, sphincter disturbances and cognitive impairment were significantly more frequent in early than in late onset patients. This explains why the phenotype was strikingly different in one family, in which mean age at onset was much earlier. Comparison with previously described SCA2 families indicated similarities, such as reduced saccade velocity, supranuclear ophthalmoplegia and decreased reflexes, although phenotypic heterogeneity remains the outstanding feature of this disorder.
Assuntos
Ataxia Cerebelar/genética , Genes Dominantes , Adolescente , Adulto , Idade de Início , Idoso , Encéfalo/patologia , Ataxia Cerebelar/patologia , Ataxia Cerebelar/fisiopatologia , Criança , Feminino , Humanos , Masculino , Martinica , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
The patogenesis and etiology of acute ataxia in childhood is not well known. It may occur without previous symptoms or may be the expression of specific infectious diseases. Forty patients hospitalized at the Hospital de Niños de Buenos Aires en 1972-1978, were studied. The neurological manifestations showed an acute onset, being ataxia the main sign, associate to tremor, nystagmus, dysartria, oculo-motor paresia, muscular weakness, and hyporeflexia. Most of the patients (82%) became cured within the first four weeks. It is advisable to establish a follow-up with periodic controls, mainly in those patients in whom an association with previous infectious diseases did not exist to be able to detect an association with degenerative or desmyelinizing diseases.