RESUMEN
BACKGROUND: Intracranial calcification (ICC) is an important diagnostic clue in pediatric neurology. Considering the radiation-induced cancer risk associated with computed tomography (CT), we aim to define the diagnostic value of magnetic resonance imaging (MRI) sequences sensitive to paramagnetic/diamagnetic substances in the detection of ICC, comparing with CT scanning. MATERIALS AND METHODS: We selected MRI and CT scans performed in children affected by neurological conditions associated with ICC referred to the participating centers between 2005 and 2018. Inclusion criteria were age at neuroradiological investigation < 18 years, availability of good quality CT positive for calcification, and MRI scan that included GE or/and SWI sequences, performed no more than 6 months apart. RESULTS: Eighty-one patients were included in the study. CT and MRI scans were reviewed by consensus. MRI failed to detect ICC in 14% of the cases. Susceptibility-weighted imaging (SWI) was the best MRI sequence to use in this setting, followed by gradient echo imaging. In 19% of the cases, CT could have been avoided because the identification or monitoring of ICC has not been necessary for the clinical management of the patient. CONCLUSION: In the diagnostic workup of pediatric-onset neurological disorders of unknown cause, the first step to look for ICC should be an MRI that includes SWI and GE sequences. If ICC is absent on MRI, brain CT scanning should be performed at least once. When the identification or monitoring of ICC is unlikely to add information useful for patient's follow-up or treatment, we recommend not performing CT scanning.
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Calcinosis , Enfermedades del Sistema Nervioso , Calcinosis/complicaciones , Calcinosis/diagnóstico por imagen , Niño , Humanos , Imagen por Resonancia Magnética/métodos , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Enfermedades del Sistema Nervioso/etiología , Neuroimagen , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To assess by magnetic resonance spectroscopy (MRS) the N-acetylaspartate, myo-inositol, choline, sum of glutamate and glutamine (Glx), and creatine (Cr) content in the anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) and in the occipital cortex (OCC) (control region) in patients with functional motor symptoms (FMS) and healthy controls, and to determine whether neurochemical limbic changes as estimated by MRS correlate with FMS-related motor symptom severity, alexithymia, anxiety, depression, and quality of life. METHODS: This case-control study enrolled 10 patients with FMS and 10 healthy controls. Participants underwent MRS and were tested with the Mini-Mental State Examination, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, 20-Item Toronto Alexithymia Scale, and EuroQol 5D. RESULTS: In patients with FMS, MRS showed increased Glx/Cr in the ACC/mPFC but normal content in the control OCC. All the other metabolites tested were normal in both regions. The increased Glx/Cr content in the ACC/mPFC correlated with alexithymia, anxiety, and severity of symptoms. CONCLUSIONS: The abnormal limbic Glx increase could have a crucial pathophysiologic role in FMS, possibly by altering limbic-motor interactions, ultimately leading to abnormal movements.
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Sistema Límbico/diagnóstico por imagen , Sistema Límbico/metabolismo , Espectroscopía de Resonancia Magnética , Trastornos del Movimiento/diagnóstico por imagen , Trastornos del Movimiento/metabolismo , Adulto , Síntomas Afectivos/diagnóstico por imagen , Síntomas Afectivos/metabolismo , Ansiedad/diagnóstico por imagen , Ansiedad/metabolismo , Estudios de Casos y Controles , Creatina/metabolismo , Depresión/diagnóstico por imagen , Depresión/metabolismo , Femenino , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/psicología , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes.
RESUMEN
BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare genetic leukoencephalopathy related to inappropriate activation of type I interferon. Neuroradiological findings are typically characterized by white matter abnormalities, cerebral atrophy and cerebral calcification. The disease usually manifests itself during the first year of life in the form of an initial "encephalitic-like" phase followed by a chronic phase of stabilization of the neurological signs. Recently new therapeutic strategies have been proposed aimed at blocking the abnormal activation of the interferon cascade. MATERIALS AND METHODS: We reviewed clinical and MRI findings in three young RNASEH2B-mutated patients studied with serial CT and MRI studies. RESULTS: All three patients presented clinical and MRI features consistent with AGS but, very unexpectedly, an improving neuroradiological course. In patient 1, the MRI improvement was noted some months after treatment with high-dose steroid and IVIg treatment; in patients 2 and 3 it occurred spontaneously. Patient 2 did not show cerebral calcification on CT images. CONCLUSIONS: Our series highlights the possibility of spontaneous neuroradiological improvement in AGS2 patients, as well as the possibility of absence of cerebral calcification in AGS. The study underlines the need for extreme caution when using MRI as an outcome measure in therapeutic trials specific for this disease. MRI follow-up studies in larger series are necessary to describe the natural course of AGS.
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Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Calcinosis , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Enfermedades Autoinmunes del Sistema Nervioso/genética , Encéfalo/patología , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Mutación , Malformaciones del Sistema Nervioso/genética , Neuroimagen , Ribonucleasa H/genética , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the frequency and types of upper cervical spine injuries in asymptomatic elderly patients undergoing computed tomography (CT) for the investigation of minor head trauma. MATERIALS AND METHODS: This was a prospective study of 2613 asymptomatic elderly patients with minor head trauma seen between January 2015 and December 2016. We adopted a dedicated head CT protocol that included the C1-C2 region. RESULTS: Of the 2613 patients analyzed, 33 (1.26%) had upper cervical spine injuries, corresponding to 8.37% of the 394 patients with trauma-related findings. Of those 33 patients, 6 had C1 fractures and 27 had C2 fractures. The use of 16- and 128-slice scanners increased the CT dose by 25.0% and 23.7%, respectively. CONCLUSION: Inclusion of the C1-C2 region in head CT scans allowed us to identify upper cervical spine injuries in 1.26% of asymptomatic elderly patients with minor head trauma. The protocol evaluated helps detect potentially life-threatening injuries and could be adopted for routine use in elderly individuals with minor head trauma.
OBJETIVO: Avaliar a frequência e os tipos de lesões da coluna cervical superior em pacientes idosos assintomáticos submetidos a tomografia computadorizada (TC) para investigação de trauma leve na cabeça. MATERIAIS E MÉTODOS: De janeiro de 2015 a dezembro de 2016, analisamos prospectivamente 2613 pacientes idosos assintomáticos com pequeno traumatismo na cabeça. com protocolo de TC dedicado incluindo a região de C1-C2. RESULTADOS: Trinta e três dos 2613 pacientes apresentaram lesões na coluna cervical superior, com frequência de 1,26% em toda a população e de 8,37% (33/394) em pacientes com achados relacionados ao trauma. Seis dos 33 pacientes apresentaram fratura de C1 e 27/33 pacientes apresentaram fratura de C2. A dose de TC aumentou 25% e 23,68% com scanner de 16 e 128 fileiras, respectivamente. CONCLUSÃO: A inclusão de C1-C2 na TC de cabeça revelou uma taxa de lesões da coluna cervical superior de 1,26% em pacientes idosos assintomáticos com lesão pequena na cabeça. O protocolo ajuda a detectar potencialmente lesões fatais e pode ser adotado para pessoas idosas com trauma leve na cabeça.
RESUMEN
Abstract Objective: To evaluate the frequency and types of upper cervical spine injuries in asymptomatic elderly patients undergoing computed tomography (CT) for the investigation of minor head trauma. Materials and Methods: This was a prospective study of 2613 asymptomatic elderly patients with minor head trauma seen between January 2015 and December 2016. We adopted a dedicated head CT protocol that included the C1-C2 region. Results: Of the 2613 patients analyzed, 33 (1.26%) had upper cervical spine injuries, corresponding to 8.37% of the 394 patients with trauma-related findings. Of those 33 patients, 6 had C1 fractures and 27 had C2 fractures. The use of 16- and 128-slice scanners increased the CT dose by 25.0% and 23.7%, respectively. Conclusion: Inclusion of the C1-C2 region in head CT scans allowed us to identify upper cervical spine injuries in 1.26% of asymptomatic elderly patients with minor head trauma. The protocol evaluated helps detect potentially life-threatening injuries and could be adopted for routine use in elderly individuals with minor head trauma.
Resumo Objetivo: Avaliar a frequência e os tipos de lesões da coluna cervical superior em pacientes idosos assintomáticos submetidos a tomografia computadorizada (TC) para investigação de trauma leve na cabeça. Materiais e Métodos: De janeiro de 2015 a dezembro de 2016, analisamos prospectivamente 2613 pacientes idosos assintomáticos com pequeno traumatismo na cabeça. com protocolo de TC dedicado incluindo a região de C1-C2. Resultados: Trinta e três dos 2613 pacientes apresentaram lesões na coluna cervical superior, com frequência de 1,26% em toda a população e de 8,37% (33/394) em pacientes com achados relacionados ao trauma. Seis dos 33 pacientes apresentaram fratura de C1 e 27/33 pacientes apresentaram fratura de C2. A dose de TC aumentou 25% e 23,68% com scanner de 16 e 128 fileiras, respectivamente. Conclusão: A inclusão de C1-C2 na TC de cabeça revelou uma taxa de lesões da coluna cervical superior de 1,26% em pacientes idosos assintomáticos com lesão pequena na cabeça. O protocolo ajuda a detectar potencialmente lesões fatais e pode ser adotado para pessoas idosas com trauma leve na cabeça.
Asunto(s)
Leucoencefalopatías/complicaciones , Migraña con Aura/complicaciones , Adolescente , Adulto , Factores de Edad , Femenino , Humanos , Leucoencefalopatías/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Migraña con Aura/diagnóstico por imagen , Estudios Retrospectivos , Factores Sexuales , Adulto JovenRESUMEN
A 56-year-old man with behavioural disorders and facial-brachio-crural right hemiparesis presented with a brain lesion studied with computed tomography, magnetic resonance imaging and brain biopsy, leading to the diagnosis of cerebral vasculitis. Hepatitis C virus (HCV) infection in a phase of activity, without cryoglobulins, was also detected. Brain biopsy, laboratory analysis and response to a specific therapy supported the diagnosis of central nervous system vasculitis that was HCV related.
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Hepatitis C/complicaciones , Imagen por Resonancia Magnética , Vasculitis del Sistema Nervioso Central/diagnóstico por imagen , Vasculitis del Sistema Nervioso Central/virología , Biopsia , Crioglobulinas/análisis , Diagnóstico Diferencial , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
We studied a 9-year-old boy, affected with the Parry-Romberg syndrome, during a period of 32 months, by means of clinical evaluations and neuroradiological magnetic resonance imaging. Over this time we observed a clinical progression of the cutaneous disease without a simultaneous progression of the neurological alterations. Conventional and advanced magnetic resonance imaging techniques showed white matter alterations which proved to be stable during the follow-up.
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Hemiatrofia Facial/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Niño , Diagnóstico Diferencial , Progresión de la Enfermedad , Hemiatrofia Facial/tratamiento farmacológico , Humanos , Imagenología Tridimensional , Espectroscopía de Resonancia Magnética , MasculinoRESUMEN
Several studies report the presence of white matter lesions on brain magnetic resonance imaging in patients with migraine. The aim of our study was to detect the entity of white matter T2-hyperintensities in 90 high selected patients affected by migraine with aura, compared to a group of 90 healthy controls. We found no significant difference of incidence of white matter alterations comparing these two groups.
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Imagen por Resonancia Magnética , Migraña con Aura/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The bilateral transfer of a motor skill is a physiological phenomenon: the development of a motor skill with one hand can trigger the development of the same ability of the other hand. OBJECTIVE: The purpose of this study was to verify whether bilateral transfer is associated with a specific brain activation pattern using functional magnetic resonance imaging (fMRI). METHODS: The motor task was implemented as the execution of the Nine Hole Peg Test. Fifteen healthy subjects (10 right-handers and five left-handers) underwent two identical fMRI runs performing the motor task with the non-dominant hand. Between the first and the second run, each subject was intensively trained for five minutes to perform the same motor task with the dominant hand. RESULTS: Comparing the two functional scans across the pool of subjects, a change of the motor activation pattern was observed. In particular, we observed, in the second run, a change in the activation pattern both in the cerebellum and in the cerebral cortex. We found activations in cortical areas involved in somatosensory integration, areas involved in procedural memory. CONCLUSIONS: Our study shows, in a small group of healthy subjects, the modification of the fMRI activation pathway of a motor task performed by the non-dominant hand after intensive exercise performing the same task with the dominant hand.
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Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética , Destreza Motora/fisiología , Transferencia de Experiencia en Psicología/fisiología , Adulto , Encéfalo/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Oxígeno/sangreRESUMEN
OBJECTIVE: To perform an updated characterization of the neuroradiologic features of Aicardi-Goutières syndrome (AGS). METHODS: The neuroradiologic data of 121 subjects with AGS were collected. The CT and MRI data were analyzed with a systematic approach. Moreover, we evaluated if an association exists between the neuroradiologic findings, clinical features, and genotype. RESULTS: Brain calcifications were present in 110 subjects (90.9%). Severe calcification was associated with TREX1 mutations and early age at onset. Cerebral atrophy was documented in 111 subjects (91.8%). Leukoencephalopathy was present in 120 children (99.2%), with 3 main patterns: frontotemporal, diffuse, and periventricular. White matter rarefaction was found in 54 subjects (50.0%), strongly associated with mutations in TREX1 and an early age at onset. Other novel radiologic features were identified: deep white matter cysts, associated with TREX1 mutations, and delayed myelination, associated with RNASEH2B mutations and early age at onset. CONCLUSIONS: We demonstrate that the AGS neuroradiologic phenotype is expanding by adding new patterns and findings to the classic criteria. The heterogeneity of neuroradiologic patterns is partly explained by the timing of the disease onset and reflects the complexity of the pathogenic mechanisms.
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Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico por imagen , Enfermedades Autoinmunes del Sistema Nervioso/genética , Imagen por Resonancia Magnética , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Malformaciones del Sistema Nervioso/genética , Tomografía Computarizada por Rayos X , Sustancia Blanca/diagnóstico por imagen , Adolescente , Niño , Preescolar , Exodesoxirribonucleasas/genética , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Fosfoproteínas/genética , Adulto JovenRESUMEN
Aicardi-Goutières syndrome is an inherited leukodystrophy with calcifying microangiopathy and abnormal central nervous system myelination. As fewer diagnostic computed tomographic (CT) scans are being performed due to increased availability of magnetic resonance imaging (MRI), there is a potential for missed diagnoses on the basis of calcifications. We review a series of patients with MRIs selected from IRB-approved leukodystrophy biorepositories to identify MRI patterns for recognition of early-onset Aicardi-Goutières syndrome and scored for a panel of radiologic predictors. Each individual predictor was tested against disease status using exact logistic regression. Features for pattern recognition of Aicardi-Goutières syndrome are temporal lobe swelling followed by atrophy with temporal horn dilatation, early global cerebral atrophy and visible calcifications, as evidenced by 94.44% of cases of Aicardi-Goutières syndrome correctly classified with a sensitivity of 90.9% and specificity of 96.9%. We identify a panel of MRI features predictive of Aicardi-Goutières syndrome in young patients that would differentiate it from other leukoencephalopathies.
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Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/patología , Encéfalo/patología , Imagen por Resonancia Magnética , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/patología , Edad de Inicio , Preescolar , Humanos , Lactante , Modelos Logísticos , Imagen por Resonancia Magnética/métodos , Tamaño de los Órganos , Sensibilidad y EspecificidadRESUMEN
Aicardi-Goutières syndrome (AGS) is a genetic inflammatory disease. The classic neuroradiological picture mimics that of congenital infections in that Aicardi-Goutières syndrome is characterized by leukoencephalopathy, brain atrophy and intracranial calcifications. To date, bilateral striatal necrosis has not been reported in patients with AGS. We report on two patients with clinical diagnosis of Aicardi-Goutières syndrome in which brain MRI and CT scans demonstrated bilateral striatal necrosis. The diagnosis of Aicardi-Goutières syndrome in these two patients was genetically confirmed after the recent discovery that mutations in the ADAR1 (AGS6) gene may cause Aicardi-Goutières syndrome. This is the first report of bilateral striatal necrosis in association with Aicardi-Goutières syndrome. These results expand the neuroradiological phenotype of Aicardi-Goutières syndrome.
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Adenosina Desaminasa/genética , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/genética , Cuerpo Estriado/patología , Mutación , Necrosis , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/genética , Encéfalo/patología , Preescolar , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Proteínas de Unión al ARN , Tomografía Computarizada por Rayos XRESUMEN
Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of ß2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits ß2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.
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Amiloidosis/tratamiento farmacológico , Artralgia/tratamiento farmacológico , Doxiciclina/uso terapéutico , Dolor Intratable/tratamiento farmacológico , Placa Amiloide/patología , Diálisis Renal/efectos adversos , Amiloidosis/etiología , Amiloidosis/metabolismo , Amiloidosis/patología , Artralgia/etiología , Artralgia/metabolismo , Artralgia/patología , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Doxiciclina/farmacocinética , Humanos , Ligamentos Articulares/efectos de los fármacos , Ligamentos Articulares/metabolismo , Ligamentos Articulares/patología , Masculino , Persona de Mediana Edad , Dolor Intratable/etiología , Dolor Intratable/metabolismo , Dolor Intratable/patología , Placa Amiloide/etiología , Placa Amiloide/metabolismo , Articulación del Hombro/efectos de los fármacos , Articulación del Hombro/metabolismo , Articulación del Hombro/patología , Microglobulina beta-2/antagonistas & inhibidores , Microglobulina beta-2/química , Microglobulina beta-2/metabolismoRESUMEN
Spinal cord calcifications are an unusual finding in pediatric neurology. We here describe a young child who presented severe psychomotor delay, tetraplegia, deafness, and anemia. Neuroradiological investigations revealed severe leukodystrophy and unusual calcifications in the cerebral white matter and all along the medullary pathways. Common infectious and metabolic diseases were ruled out. A mild reduction in the activity of several respiratory chain complexes was documented on muscle biopsy. Of interest, we found an intronic variant in DARS2, a gene involved in mitochondrial DNA translation, responsible for the syndrome of leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate. In our opinion, our case, and probably 2 previously reported Japanese siblings with a picture very similar to that of our patient, could represent a new, progressive leukoencephalomyelopathy.
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Calcinosis/patología , Leucoencefalopatías/patología , Enfermedades Mitocondriales/patología , Médula Espinal/patología , Calcinosis/genética , Progresión de la Enfermedad , Resultado Fatal , Humanos , Lactante , Leucoencefalopatías/genética , Leucoencefalopatías/metabolismo , Masculino , Enfermedades Mitocondriales/genética , Médula Espinal/metabolismoRESUMEN
Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.