RESUMO
Familial Dysautonomia (FD) is an autosomal recessive disorder caused by a splice site mutation in the gene ELP1, which disproportionally affects neurons. While classically characterized by deficits in sensory and autonomic neurons, neuronal defects in the central nervous system have also been described. Although ELP1 expression remains high in the normal developing and adult cerebellum, its role in cerebellar development is unknown. To explore the role of Elp1 in the cerebellum, we knocked out Elp1 in cerebellar granule cell progenitors (GCPs) and examined the outcome on animal behavior and cellular composition. We found that GCP-specific conditional knockout of Elp1 (Elp1cKO) resulted in ataxia by 8 weeks of age. Cellular characterization showed that the animals had smaller cerebella with fewer granule cells. This defect was already apparent as early as 7 days after birth, when Elp1cKO animals also had fewer mitotic GCPs and shorter Purkinje dendrites. Through molecular characterization, we found that loss of Elp1 was associated with an increase in apoptotic cell death and cell stress pathways in GCPs. Our study demonstrates the importance of ELP1 in the developing cerebellum, and suggests that loss of Elp1 in the GC lineage may also play a role in the progressive ataxia phenotypes of FD patients.
Assuntos
Cerebelo , Disautonomia Familiar , Camundongos Knockout , Fenótipo , Animais , Disautonomia Familiar/genética , Disautonomia Familiar/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Camundongos , Modelos Animais de Doenças , Ataxia/genética , Ataxia/patologia , Ataxia/metabolismo , Células-Tronco Neurais/metabolismo , Apoptose/fisiologia , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Only five children with pathogenic PMPCB gene variants have been described and all carried missense variants. Clinical features included a Leigh-like syndrome of developmental regression, basal ganglia lesions and ataxia with or without dystonia and epilepsy. Three of the five died in childhood and none was older than age six when described. We report the first splice site variant in the PMPCB gene in a 39-year old individual who experienced developmental regression and ataxia following otitis media in childhood. A minigene assay confirms this variant results in aberrant splicing and skipping of exon 12.
Assuntos
Doença de Leigh , Splicing de RNA , Adulto , Feminino , Humanos , Ataxia/genética , Ataxia/patologia , Doença de Leigh/genética , Doença de Leigh/patologia , Splicing de RNA/genéticaRESUMO
The association of early-onset non-progressive ataxia and miosis is an extremely rare phenotypic entity occasionally reported in the literature. To date, only one family (two siblings and their mother) has benefited from a genetic diagnosis by the identification of a missense heterozygous variant (p.Arg36Cys) in the ITPR1 gene. This gene encodes the inositol 1,4,5-trisphosphate receptor type 1, an intracellular channel that mediates calcium release from the endoplasmic reticulum. Deleterious variants in this gene are known to be associated with two types of spinocerebellar ataxia, SCA15 and SCA29, and with Gillespie syndrome that is associated with ataxia, partial iris hypoplasia, and intellectual disability. In this work, we describe a novel individual carrying a heterozygous missense variant (p.Arg36Pro) at the same position in the N-terminal suppressor domain of ITPR1 as the family previously reported, with the same phenotype associating early-onset non-progressive ataxia and miosis. This second report confirms the implication of ITPR1 in the miosis-ataxia syndrome and therefore broadens the clinical spectrum of the gene. Moreover, the high specificity of the phenotype makes it a recognizable syndrome of genetic origin.
Assuntos
Receptores de Inositol 1,4,5-Trifosfato , Miose , Feminino , Humanos , Ataxia/genética , Ataxia/patologia , Heterozigoto , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Miose/genética , Miose/patologia , Mutação de Sentido Incorreto/genética , Linhagem , Fenótipo , IdosoRESUMO
Cerebellar ataxias are a wide heterogeneous group of movement disorders. Within this broad umbrella of diseases, there are both genetics and sporadic forms. The clinical presentation of these conditions can exhibit a diverse range of symptoms across different age groups, spanning from pure cerebellar manifestations to sensory ataxia and multisystemic diseases. Over the last few decades, advancements in our understanding of genetics and molecular pathophysiology related to both dominant and recessive ataxias have propelled the field forward, paving the way for innovative therapeutic strategies aimed at preventing and arresting the progression of these diseases. Nevertheless, the rarity of certain forms of ataxia continues to pose challenges, leading to limited insights into the etiology of the disease and the identification of target pathways. Additionally, the lack of suitable models hampers efforts to comprehensively understand the molecular foundations of disease's pathophysiology and test novel therapeutic interventions. In the following review, we describe the epidemiology, symptomatology, and pathological progression of hereditary ataxia, including both the prevalent and less common forms of these diseases. Furthermore, we illustrate the diverse molecular pathways and therapeutic approaches currently undergoing investigation in both pre-clinical studies and clinical trials. Finally, we address the existing and anticipated challenges within this field, encompassing both basic research and clinical endeavors.
Assuntos
Ataxia Cerebelar , Degenerações Espinocerebelares , Humanos , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Ataxia/patologia , Cerebelo/patologiaRESUMO
Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity was unaltered in the mutant mice, although their sleep parameters and ECoG patterns were modified. The L7Cre;Vgatfx/fx mutant mice had decreased wakefulness and rapid eye movement (REM) sleep, whereas non-REM sleep was increased. The mutants had an extended latency to REM sleep, which is also observed in human patients with ataxia. Spectral analysis of ECoG signals revealed alterations in the power distribution across different frequency bands defining sleep. Therefore, Purkinje cell dysfunction may influence wakefulness and equilibrium of distinct sleep stages in ataxia. Our findings posit a connection between cerebellar dysfunction and disrupted sleep and underscore the importance of examining cerebellar circuit function in sleep disorders.
Assuntos
Ataxia , Células de Purkinje , Vigília , Animais , Células de Purkinje/patologia , Vigília/fisiologia , Ataxia/fisiopatologia , Ataxia/patologia , Sono/fisiologia , Sono REM/fisiologia , Camundongos , Ritmo Circadiano , Modelos Animais de Doenças , MasculinoRESUMO
BACKGROUND: Biallelic variants in the major facilitator superfamily domain containing 8 gene (MFSD8) are associated with distinct clinical presentations that range from typical late-infantile neuronal ceroid lipofuscinosis type 7 (CLN7 disease) to isolated adult-onset retinal dystrophy. Classic late-infantile CLN7 disease is a severe, rare neurological disorder with an age of onset typically between 2 and 6 years, presenting with seizures and/or cognitive regression. Its clinical course is progressive, leading to premature death, and often includes visual loss due to severe retinal dystrophy. In rare cases, pathogenic variants in MFSD8 can be associated with isolated non-syndromic macular dystrophy with variable age at onset, in which the disease process predominantly or exclusively affects the cones of the macula and where there are no neurological or neuropsychiatric manifestations. METHODS: Here we present longitudinal studies on four adult-onset patients who were biallelic for four MFSD8 variants. RESULTS: Two unrelated patients who presented with adult-onset ataxia and had macular dystrophy on examination were homozygous for a novel variant in MFSD8 NM_152778.4: c.935T>C p.(Ile312Thr). Two other patients presented in adulthood with visual symptoms, and one of these developed mild to moderate cerebellar ataxia years after the onset of visual symptoms. CONCLUSIONS: Our observations expand the knowledge on biallelic pathogenic MFSD8 variants and confirm that these are associated with a spectrum of more heterogeneous clinical phenotypes. In MFSD8-related disease, adult-onset recessive ataxia can be the presenting manifestation or may occur in combination with retinal dystrophy.
Assuntos
Degeneração Macular , Humanos , Adulto , Masculino , Feminino , Degeneração Macular/genética , Degeneração Macular/patologia , Idade de Início , Ataxia/genética , Ataxia/patologia , Alelos , Pessoa de Meia-Idade , Mutação , Proteínas de Membrana Transportadoras/genética , FenótipoRESUMO
BACKGROUND: MT-ATP6 is a mitochondrial gene which encodes for the intramembrane subunit 6 (or A) of the mitochondrial ATP synthase, also known asl complex V, which is involved in the last step of oxidative phosphorylation to produce cellular ATP through aerobic metabolism. Although classically associated with the NARP syndrome, recent evidence highlights an important role of MT-ATP6 pathogenic variants in complicated adult-onset ataxias. METHODS: We describe two unrelated patients with adult-onset cerebellar ataxia associated with severe optic atrophy and mild cognitive impairment. Whole mitochondrial DNA sequencing was performed in both patients. We employed patients' primary fibroblasts and cytoplasmic hybrids (cybrids), generated from patients-derived cells, to assess the activity of respiratory chain complexes, oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential. RESULTS: In both patients, we identified the same novel m.8777 T > C variant in MT-ATP6 with variable heteroplasmy level in different tissues. We identifed an additional heteroplasmic novel variant in MT-ATP6, m.8879G > T, in the patients with the most severe phenotype. A significant reduction in complex V activity, OCR and ATP production was observed in cybrid clones homoplasmic for the m.8777 T > C variant, while no functional defect was detected in m.8879G > T homoplasmic clones. In addition, fibroblasts with high heteroplasmic levelsof m.8777 T > C variant showed hyperpolarization of mitochondrial membranes. CONCLUSIONS: We describe a novel pathogenic mtDNA variant in MT-ATP6 associated with adult-onset ataxia, reinforcing the value of mtDNA screening within the diagnostic workflow of selected patients with late onset ataxias.
Assuntos
Ataxia , ATPases Mitocondriais Próton-Translocadoras , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ataxia/genética , Ataxia/patologia , DNA Mitocondrial/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Itália , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismoRESUMO
BACKGROUND: RFC1-related disorder (RFC1/CANVAS) shares clinical features with other late-onset ataxias, such as spinocerebellar ataxias (SCA) and multiple system atrophy cerebellar type (MSA-C). Thinning of cranial nerves V (CNV) and VIII (CNVIII) has been reported in magnetic resonance imaging (MRI) scans of RFC1/CANVAS, but its specificity remains unclear. OBJECTIVES: To assess the usefulness of CNV and CNVIII thinning to differentiate RFC1/CANVAS from SCA and MSA-C. METHODS: Seventeen individuals with RFC1/CANVAS, 57 with SCA (types 2, 3 and 6), 11 with MSA-C and 15 healthy controls were enrolled. The Balanced Fast Field Echo sequence was used for assessment of cranial nerves. Images were reviewed by a neuroradiologist, who classified these nerves as atrophic or normal, and subsequently the CNV was segmented manually by an experienced neurologist. Both assessments were blinded to patient and clinical data. Non-parametric tests were used to assess between-group comparisons. RESULTS: Atrophy of CNV and CNVIII, both alone and in combination, was significantly more frequent in the RFC1/CANVAS group than in healthy controls and all other ataxia groups. Atrophy of CNV had the highest sensitivity (82%) and combined CNV and CNVIII atrophy had the best specificity (92%) for diagnosing RFC1/CANVAS. In the quantitative analyses, CNV was significantly thinner in the RFC1/CANVAS group relative to all other groups. The cutoff CNV diameter that best identified RFC1/CANVAS was ≤2.2 mm (AUC = 0.91; sensitivity 88.2%, specificity 95.6%). CONCLUSION: MRI evaluation of CNV and CNVIII using a dedicated sequence is an easy-to-use tool that helps to distinguish RFC1/CANVAS from SCA and MSA-C.
Assuntos
Atrofia de Múltiplos Sistemas , Ataxias Espinocerebelares , Humanos , Ataxia/patologia , Atrofia/patologia , Cerebelo/patologia , Nervos Cranianos/patologia , Atrofia de Múltiplos Sistemas/diagnóstico , Ataxias Espinocerebelares/diagnósticoRESUMO
Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ10. Poor outcomes result from low absorption and bioavailability of CoQ10 and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ10 supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency.
Assuntos
Modelos Animais de Doenças , Doenças Mitocondriais , Parabenos , Ubiquinona , Animais , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/patologia , Doenças Mitocondriais/metabolismo , Parabenos/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/metabolismo , Ubiquinona/deficiência , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Humanos , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Debilidade Muscular/tratamento farmacológico , Debilidade Muscular/metabolismo , Debilidade Muscular/patologia , Ataxia/tratamento farmacológico , Ataxia/patologia , Ataxia/metabolismoRESUMO
COQ7 pathogenetic variants cause primary CoQ10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ10 supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ10 levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ10 (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ10 deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.
Assuntos
Doenças Mitocondriais , Ubiquinona , Humanos , Ubiquinona/análogos & derivados , Ubiquinona/deficiência , Ubiquinona/genética , Masculino , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Doenças Mitocondriais/diagnóstico , Feminino , Linhagem , Lactente , Mutação , Ataxia/genética , Ataxia/patologia , Ataxia/diagnóstico , Oftalmoplegia/genética , Oftalmoplegia/patologia , Oftalmoplegia/diagnóstico , Debilidade Muscular/genética , Debilidade Muscular/patologia , Cardiomiopatias/genética , Cardiomiopatias/patologia , Cardiomiopatias/diagnóstico , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/diagnósticoRESUMO
OBJECTIVE: Mitochondrial impairments have been implicated in the pathogenesis of Fragile X-associated tremor/ataxia syndrome (FXTAS) based on analysis of mitochondria in peripheral tissues and cultured cells. We sought to assess whether mitochondrial abnormalities present in postmortem brain tissues of patients with FXTAS are also present in plasma neuron-derived extracellular vesicles (NDEVs) from living carriers of fragile X messenger ribonucleoprotein1 (FMR1) gene premutations at an early asymptomatic stage of the disease continuum. METHODS: We utilized postmortem frozen cerebellar and frontal cortex samples from a cohort of eight patients with FXTAS and nine controls and measured the quantity and activity of the mitochondrial proteins complex IV and complex V. In addition, we evaluated the same measures in isolated plasma NDEVs by selective immunoaffinity capture targeting L1CAM from a separate cohort of eight FMR1 premutation carriers and four age-matched controls. RESULTS: Lower complex IV and V quantity and activity were observed in the cerebellum of FXTAS patients compared to controls, without any differences in total mitochondrial content. No patient-control differences were observed in the frontal cortex. In NDEVs, FMR1 premutation carriers compared to controls had lower activity of Complex IV and Complex V, but higher Complex V quantity. INTERPRETATION: Quantitative and functional abnormalities in mitochondrial electron transport chain complexes IV and V seen in the cerebellum of patients with FXTAS are also manifest in plasma NDEVs of FMR1 premutation carriers. Plasma NDEVs may provide further insights into mitochondrial pathologies in this syndrome and could potentially lead to the development of biomarkers for predicting symptomatic FXTAS among premutation carriers and disease monitoring.
Assuntos
Ataxia , Vesículas Extracelulares , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Mitocôndrias , Tremor , Humanos , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , Síndrome do Cromossomo X Frágil/patologia , Síndrome do Cromossomo X Frágil/fisiopatologia , Tremor/genética , Tremor/metabolismo , Tremor/fisiopatologia , Tremor/patologia , Vesículas Extracelulares/metabolismo , Ataxia/genética , Ataxia/metabolismo , Ataxia/patologia , Ataxia/fisiopatologia , Masculino , Idoso , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/patologia , Lobo Frontal/metabolismo , Lobo Frontal/patologiaRESUMO
FMR1 premutation carriers (55-200 CGG repeats) are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. In the general population, enlarged perivascular spaces (PVS) are biomarkers of small vessel disease and glymphatic dysfunction and are associated with cognitive decline. Our aim was to determine if premutation carriers show higher ratings of PVS than controls and whether enlarged PVS are associated with motor and cognitive impairment, MRI features of neurodegeneration, cerebrovascular risk factors and CGG repeat length. We evaluated 655 MRIs (1-10 visits/participant) from 229 carriers (164 with FXTAS and 65 without FXTAS) and 133 controls. PVS in the basal ganglia (BG-EPVS), centrum semiovale, and midbrain were evaluated with a semiquantitative scale. Mixed-effects models were used for statistical analysis adjusting for age. In carriers with FXTAS, we revealed that (1) BG-PVS ratings were higher than those of controls and carriers without FXTAS; (2) BG-PVS severity was associated with brain atrophy, white matter hyperintensities, enlarged ventricles, FXTAS stage and abnormal gait; (3) age-related increase in BG-PVS was associated with cognitive dysfunction; and (4) PVS ratings of all three regions showed robust associations with CGG repeat length and were higher in carriers with the MCP sign than carriers without the sign. This study demonstrates clinical relevance of PVS in FXTAS especially in the basal ganglia region and suggests microangiopathy and dysfunctional cerebrospinal fluid circulation in FXTAS physiopathology.
Assuntos
Ataxia , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Sistema Glinfático , Imageamento por Ressonância Magnética , Tremor , Humanos , Masculino , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/diagnóstico por imagem , Síndrome do Cromossomo X Frágil/patologia , Pessoa de Meia-Idade , Idoso , Proteína do X Frágil da Deficiência Intelectual/genética , Tremor/genética , Tremor/diagnóstico por imagem , Tremor/patologia , Ataxia/genética , Ataxia/diagnóstico por imagem , Ataxia/patologia , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Fatores de Risco , Heterozigoto , Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
Background: Ataxia can be classified as genetic, sporadic or acquired. Aim: To report the clinical features of a group of patients with ataxia. Material and Methods: Review of medical records of patients consulting in a specialized center in movement disorders. Those records in which the diagnosis of "ataxia" or "ataxic syndrome" appeared, were selected for the review. Results: Of 4,282 records surveyed, the diagnosis of ataxia appeared in 95. After eliminating repeated or incomplete records, 63 were reviewed. Results: Ataxia was sporadic, genetic and acquired in 27, 22 and 14 patients, respectively. The mean age at presentation for genetic, acquired and sporadic ataxia was 24, 46 and 53 years respectively. All autosomal dominant ataxias were type 3 spinocerebellar ataxia (SCA). Friedrich's ataxia was the most common recessive form. Most sporadic forms of ataxia were multiple system atrophy with predominant cerebellar ataxia (MSA-C) subtype. Conclusions: Considering the heterogeneity of patients with ataxia, we propose a method to approach them.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Ataxia/etiologia , Ataxia/epidemiologia , Ataxia/patologia , Chile/epidemiologia , Fatores Sexuais , Prontuários Médicos , Estudos Retrospectivos , Análise de Variância , Fatores Etários , Distribuição por Sexo , Distribuição por IdadeRESUMO
La microangiopatía cerebral retiniana con calcificaciones y quistes es una enfermedad poco frecuente, caracterizada por alteraciones cerebrales, retinianas y óseas, así como por predisposición al sangrado gastrointestinal. Existen pocos reportes de casos de esta condición, especialmente en adultos, en quienes la incidencia es baja. Los hallazgos por medio de neuroimágenes son característicos, con calcificaciones bilaterales y múltiples formaciones quísticas. El propósito de este artículo fue hacer una revisión bibliográfica e ilustrar dos casos cuyo diagnóstico fue posible con la ayuda de neuroimágenes.
Cerebroretinal microangiopathy with calcifications and cysts is a rare condition characterized by brain, retinal and bone anomalies, as well as a predisposition to gastrointestinal bleeding. There are few reported cases of this condition in adults, among whom the incidence is low. Neuroimaging findings are characteristic, with bilateral calcifications, leukoencephalopathy and intracranial cysts. The purpose of this article was to do a literature survey and illustrate two cases diagnosed with the aid of neuroimaging.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Ataxia/patologia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Calcinose/patologia , Cistos do Sistema Nervoso Central/patologia , Doenças de Pequenos Vasos Cerebrais/patologia , Leucoencefalopatias/patologia , Imageamento por Ressonância Magnética , Espasticidade Muscular/patologia , Neuroimagem/métodos , Doenças Retinianas/patologia , Convulsões/patologia , Ataxia/diagnóstico , Neoplasias Encefálicas/diagnóstico , Calcinose/diagnóstico , Cistos do Sistema Nervoso Central/diagnóstico , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Diagnóstico Diferencial , Cor de Cabelo , Hipopigmentação/etiologia , Deficiência Intelectual/etiologia , Leucoencefalopatias/diagnóstico , Espasticidade Muscular/diagnóstico , Quadriplegia/etiologia , Doenças Retinianas/diagnóstico , Convulsões/diagnóstico , Doenças do Nervo Troclear/etiologiaRESUMO
É relatado aqui o caso de uma mulher de 38 anos com AIDS que desenvolveu a síndrome de opsoclonia-mioclonia-ataxia em um período diferente dos outros casos já relatados na literatura. A síndrome de opsoclonia-mioclonia-ataxia já tinha sido relatada como manifestação inicial de AIDS, assim como no momento da soroconversão de HIV e na síndrome de reconstituição imune. Este caso é único, uma vez que a paciente tinha contagem elevada de CD4 e carga viral negativa no momento em que a síndrome de opsoclonia-mioclonia-ataxia ocorreu.
We report the case of a 38-year-old woman with AIDS who developed opsoclonus-myoclonus-ataxia syndrome during a period different from other cases reported in literature. Opsoclonus-myoclonus-ataxia syndrome had already been reported as the initial neurological presentation of AIDS, as well as at the time of HIV-seroconversion and immune reconstitution syndrome. Our case is unique since the patient had an elevated CD4 count and negative viral load in the period when the opsoclonus-myoclonus-ataxia syndrome occurred.
Assuntos
Adulto , Feminino , Humanos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Ataxia/induzido quimicamente , Infecções por HIV/complicações , Síndrome de Opsoclonia-Mioclonia/induzido quimicamente , Transtornos Parkinsonianos/induzido quimicamente , Ataxia/patologia , Encéfalo/patologia , Infecções por HIV/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/complicações , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Imageamento por Ressonância Magnética , Síndrome de Opsoclonia-Mioclonia/diagnóstico , Transtornos Parkinsonianos/diagnóstico , Carga ViralRESUMO
Resumen. La toxicidad neurológica de muchos antibióticos se ha documentado en numerosos artículos y notas clínicas. En esta revisión se clasifican los antibióticos en función del mecanismo fisiopatogénico por el que pueden provocar un trastorno de la marcha, teniendo en cuenta tanto datos clínicos como experimentales. Se ha realizado una búsqueda exhaustiva en Google Scholar y PubMed con el objetivo de encontrar revisiones, artículos y casos clínicos acerca de trastornos de la marcha secundarios a distintos antibióticos. Se han separado los diferentes antibióticos en función del mecanismo fisiopatogénico por el cual podrían producir una alteración de la marcha. Se han clasificado en antibióticos capaces de producir ataxia cerebelosa, ataxia vestibular, ataxia sensitiva o un trastorno de la marcha extrapiramidal. El principal objetivo era agrupar todos los fármacos que pueden provocar un trastorno de la marcha, para facilitar la sospecha clínica y, en consecuencia, el tratamiento de los pacientes (AU)
Summary. The neurological toxicity of many antibiotics has been reported in a number of articles and clinical notes. In this review antibiotics are classified according to the physiopathogenic mechanism that can give rise to a gait disorder, taking both clinical and experimental data into account. An exhaustive search was conducted in Google Scholar and PubMed with the aim of finding reviews, articles and clinical cases dealing with gait disorders secondary to different antibiotics. The different antibiotics were separated according to the physiopathogenic mechanism that could cause them to trigger a gait disorder. They were classified into antibiotics capable of producing cerebellar ataxia, vestibular ataxia, sensitive ataxia or an extrapyramidal gait disorder. The main aim was to group all the drugs that can give rise to a gait disorder, in order to facilitate the clinical suspicion and, consequently, the management of patients (AU)
Assuntos
Humanos , Masculino , Feminino , Antibacterianos/administração & dosagem , Ataxia/congênito , Ataxia/patologia , Polineuropatias/congênito , Polineuropatias/patologia , Isoniazida/administração & dosagem , Cloroquina/administração & dosagem , Macrolídeos/metabolismo , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/metabolismo , Antibacterianos/provisão & distribuição , Antibacterianos/uso terapêutico , Ataxia/complicações , Ataxia/diagnóstico , Polineuropatias/complicações , Polineuropatias/diagnóstico , Isoniazida/metabolismo , Cloroquina/metabolismo , Aminoglicosídeos/provisão & distribuição , Aminoglicosídeos/normasRESUMO
A late onset neurological syndrome in carriers of premutation in FMR1 gene was recently described. The condition was named fragile-X-associated tremor/ataxia syndrome (FXTAS) and includes intentional tremor, cerebellar ataxia, parkinsonism, and cognitive deficit. We ascertained the contribution of FMR1 premutation to the phenotypes ataxia, tremor and/or parkinsonism. Sixty-six men over 45 years old presenting these symptoms, isolated or combined, were tested. Also, 74 normal men, randomly chosen in the population, formed the control group. In the patient group, no premutation carrier was found, which is in agreement with other observed frequencies reported elsewhere (0-5% variation). No significant differences were found when comparing gray zone allele frequencies among target and control groups. The FXTAS contribution in patients with phenotypic manifestations of FXTAS was 15/748 (2%). The presence of gray zone alleles is not correlated with FXTAS occurrence.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Ataxia/diagnóstico , Doença de Parkinson/diagnóstico , Frequência do Gene , Proteína do X Frágil da Deficiência Intelectual/genética , Tremor/diagnóstico , Alelos , Ataxia/fisiopatologia , Ataxia/genética , Ataxia/patologia , Estudos de Casos e Controles , Doença de Parkinson/fisiopatologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Predisposição Genética para Doença , Tremor/fisiopatologia , Tremor/genética , Tremor/patologiaRESUMO
La Malformación de Arnold-Chiari fue descrita por primera vez en Praga, en el año 1891 por el patólogo alemán Hans Chiari. Comprende un grupo de raras malformaciones congénitas del Cerebro, Cerebelo, y Médula Espinal en la base del cerebro. Algunas de las manifestaciones clínicas comprenden cefalea, vértigo, disfonía, apnea, nistagmus, trastornos de la deglución yataxia. La intención de este reporte es describir el espectro de síntomas comunes en una enfermedad infrecuente de tratamiento neuroquirúrgico
Arnold-Chiari Malformation was described for the first time in Prague, in 1891 by the German pathologist Hans Chiari. It includes a group of congenital malformations that affect the Brain, Cerebellum, Spinal Cord and adjacent bone structures. Some of the clinical manifestations of Malformations include headache, vertigo, dysphonia, apnea, nystagmus, swallowing difficulties and ataxia. The aim of this report is to show the spectrum of common manifestations in an infrequent disease which is surgically treated
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Malformação de Arnold-Chiari , Ataxia/patologia , Transtornos de Deglutição/patologia , Vertigem/patologiaRESUMO
Presentamos el caso una paciente con síndrome de Miller Fisher, una entidad neurológica infrecuente considerada como una variante del síndrome de Guillain-Barre. El pronóstico aún sin terapéutica parece ser favorable. Se realiza una revisión bibliográfica haciendo particular énfasis en la ubicación de la lesión, métodos paraclínicos y tratamiento actual