RESUMEN
BACKGROUND: To examine structural connectivity of white matter tracts in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) dystonia and identify those ones which correlate negatively to severity of symptoms. METHODS: In a group of 41 patients suffering from PKAN dystonia and an age- and gender-matched control group, white matter tractography was carried out, based on diffusion tensor imaging magnetic resonance data. Postprocessing included assessment of Quantitative Anisotropy (QA) using q-space diffeomorphic reconstruction in order to reduce influence of iron accumulation in globus pallidus of patients. RESULTS: Whole brain tractography presented significantly reduced QA values in patients (0.282 ± 0.056, as compared to controls (0.325 ± 0.046, p < 0.001). 9 fiber clusters of tracts correlated negatively to the dystonia score of patients: the middle cerebellar peduncle and the tracts of both cerebellar hemispheres as well as corpus callosum, forceps minor, the superior cortico-striate tracts and the superior thalamic radiations of both cerebral hemispheres (False Discovery Rate FDR = 0.041). CONCLUSION: The finding of a reduced global structural connectivity within the white matter and of negative correlation of motor system-related tracts, mainly those between the basal ganglia, cortical areas and the cerebellum, fits well to the concept of a general functional disturbance of the motor system in PKAN.
Asunto(s)
Distonía , Leucoaraiosis , Neurodegeneración Asociada a Pantotenato Quinasa , Sustancia Blanca , Encéfalo/patología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Imagen de Difusión Tensora/métodos , Distonía/patología , Humanos , Leucoaraiosis/patología , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico por imagen , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
El Síndrome de Hallervorden-Spatz es una afección neurodegenerativa rara, autosómica recesiva, caracterizada por depósitos en gran cantidad de hierro en los ganglios de base, lo que ocasiona gran pérdida motora y mental. Presenta dos formas de manifestación: la clásica, que aparece en la infancia a lo largo de la primera década de vida, y la atípica, cuyas manifestaciones clínicas aparecen de forma tardía, entre la segunda y tercera décadas de vida. El objetivo del presente estudio es describir un caso clínico de tratamiento endodóntico, en ambulatorio, de una paciente del sexo femenino, de 28 años, con manifestaciones clásicas de dicho síndrome, con cambio de color en el elemento 11 y lesión periapical, que justifica la indicación de endodoncia. La atención odontológica de una enfermedad neurodegenerativa rara, realizada en forma ambulatoria, requiere el conocimiento del dentista para que se conduzca de forma eficiente y segura
A síndrome de Hallervorden-Spatz é uma afecção neurodegenerativa rara, autossômica recessiva, caracterizada por depósitos em grande quantidade de ferro nos gânglios de base, o que ocasiona grande perda motora e mental. Apresenta duas formas de manifestações: a clássica, que surge na infância na primeira década de vida; e a atípica, cujas manifestações clínicas surgem mais tardiamente, entre a segunda e terceira décadas de vida. O objetivo desse estudo foi descrever um caso clínico de tratamento endodôntico, ambulatorial, de uma paciente do sexo feminino, 28 anos, com manifestações clássicas da síndrome, apresentando mudança de cor no elemento 11 com lesão periapical, justificando a indicação para endodontia. O atendimento odontológico de uma doença neurodegenerativa rara; realizado em ambiente ambulatorial, requer o conhecimento do dentista para que seja conduzido de forma eficiente e segura.
Hallervorden-Spatz syndrome is a rare, autosomal recessive neurodegenerative disorder characterized by large deposits of iron in the basal ganglia, which causes great motor and mental loss. It presents two forms of manifestations: the classic, which arises in childhood in the first decade of life; and the atypical, whose clinical manifestations appear later, between the second and third decades of life. The objective of this study was to describe a clinical case of endodontic outpatient treatment of a female patient, 28 years old, with classic manifestations of the syndrome, showing color change in element 11 with periapical lesion, justifying the indication for endodontics. The dental care of a rare neurodegenerative disease in an outpatient setting requires the dental surgeon's knowledge so that it is conducted efficiently and safely.
Asunto(s)
Humanos , Femenino , Adulto , Enfermedades Neurodegenerativas , Neurodegeneración Asociada a Pantotenato Quinasa , Pacientes Ambulatorios , Síndrome , Ganglios Basales , Atención Odontológica , EndodonciaRESUMEN
The proband in this study was a 16-year-old Mexican girl with psychotic and dyskinetic symptoms, and brain MRI showed at the basal ganglia the 'eye-of-the-tiger' sign. DNA direct sequencing identified a novel compound heterozygous mutation in the PANK2 gene. The diagnosis of pantothenate kinase-associated neurodegeneration (PKAN) disorder was made. This novel change increases the pool of PANK2 mutations. It supports the published data suggesting that PANK2 plays a significant role in patients expressing psychiatric phenotypes in the PKAN syndrome. When a patient presents with dyskinesia and psychiatric symptoms, PANK2 should be investigated as a possible diagnosis, and genetic consultation should be recommended.
Asunto(s)
Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adolescente , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , México , Mutación , Fenotipo , Análisis de Secuencia de ADN , SíndromeRESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to look for deviations of cerebral perfusion in patients suffering from pantothenate kinase-associated neurodegeneration, where the globus pallidus is affected by severe accumulation of iron. MATERIAL AND METHODS: Under resting conditions, cerebral blood flow was measured by the magnetic resonance imaging technique of arterial spin labelling in cortical areas and basal ganglia in eight pantothenate kinase-associated neurodegeneration patients and 14 healthy age-matched control subjects and correlated to T2* time of these areas and - in patients - to clinical parameters. RESULTS: Despite highly significant differences of T2* time of the globus pallidus (20 vs 39 ms, p < 0.001), perfusion values of this nucleus were nearly identical in both groups (32 ± 3.3 vs 31 ± 4.0 ml/min/100 g) as well as in total brain gray matter (both 62 ± 6.7 resp. ±10.3 ml/min/100 g), putamen (41 ± 5.4 vs 40 ± 6.1 ml/min/100 g), in selected cortical regions, and the cerebellum. Correlations between perfusion and T2* time to clinical data did not reach significance (p > 0.05). CONCLUSION: The absence of any obvious deviations of perfusion in the group of patients during a resting condition does not support the view that (non-functional) vascular pathology is a major pathogenic factor in pantothenate kinase-associated neurodegeneration in the younger age group. The findings underline the value of the arterial spin technique to measure cerebral blood flow in areas of disturbed susceptibility.
Asunto(s)
Circulación Cerebrovascular , Angiografía por Resonancia Magnética/métodos , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico por imagen , Adolescente , Adulto , Distonía/etiología , Femenino , Humanos , Masculino , Neurodegeneración Asociada a Pantotenato Quinasa/complicaciones , Estudios ProspectivosRESUMEN
Relatou-se o caso de um paciente com a Síndrome de Hallervorden Spatz, acolhida no programa domiciliar do Hospital Regional da Asa Norte (HRAN), Brasília, DF e discutir a terapia nutricional instituída para melhoria de qualidade de vida da mesma. Trata-se de um estudo de caso clínico compreendido entre o período de 01/09/2017 a 30/10/2017 onde se averiguou toda a evolução clínica e nutricional do paciente durante o período de internação. Após a introdução adequada de uma conduta dietoterápica para a situação da paciente, ocorreram mudanças em seu diagnóstico nutricional, levando-a a sair do nível de desnutrição com consequente ganho ponderal, além de aliviar a constipação intestinal crônica e promover a cicatrização da lesão por pressão. A partir de uma elaboração dietoterápica, pode-se notar que a terapia nutricional instituída demonstrou benefícios para a qualidade de vida da paciente com a Síndrome de Hallervorden Spatz
Asunto(s)
Neurodegeneración Asociada a Pantotenato QuinasaRESUMEN
ABSTRACT The atypical form of Pantothenate Kinase-Associated Neurodegeneration (PKAN) tends to present at around the age of 14 years, has a heterogeneous presentation with extrapyramidal symptoms, and approximately one third of patients exhibit psychiatric problems. This paper reports the case of a patient with apparent typical symptoms of Tourette syndrome. However, the severity and poor response to treatment led to further investigation and the diagnosis of PKAN as a secondary cause of Tourettism was reached.
RESUMO A forma atípica de PKAN costuma se apresentar por volta dos 14 anos de idade, possui uma sintomatologia heterogênea, com sintomas extrapiramidais e, em cerca de um terço dos pacientes, também com a manifestação de sintomas psiquiátricos. O presente artigo relata o caso de uma paciente com sintomatologia típica da Síndrome de Tourette à primeira vista. Entretanto, a gravidade do quadro e pouca resposta ao tratamento levaram a uma maior investigação e ao diagnóstico de PKAN como causa secundária do Tourettismo.
Asunto(s)
Humanos , Informes de Casos , Síndrome de Tourette , Neurodegeneración Asociada a Pantotenato QuinasaAsunto(s)
Trastornos del Metabolismo del Hierro/genética , Distrofias Neuroaxonales/genética , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Edad de Inicio , Progresión de la Enfermedad , Humanos , Trastornos del Metabolismo del Hierro/patología , Distrofias Neuroaxonales/patología , Neurodegeneración Asociada a Pantotenato Quinasa/patologíaRESUMEN
Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.
Asunto(s)
Trastornos del Metabolismo del Hierro/diagnóstico por imagen , Trastornos del Metabolismo del Hierro/genética , Mutación , Distrofias Neuroaxonales/diagnóstico por imagen , Distrofias Neuroaxonales/genética , Neuroimagen/métodos , Alopecia/diagnóstico por imagen , Alopecia/genética , Arritmias Cardíacas/diagnóstico por imagen , Arritmias Cardíacas/genética , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/genética , Ceruloplasmina/deficiencia , Ceruloplasmina/genética , Coenzima A Ligasas/genética , Diabetes Mellitus/diagnóstico por imagen , Diabetes Mellitus/genética , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico por imagen , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Humanos , Hipogonadismo/diagnóstico por imagen , Hipogonadismo/genética , Discapacidad Intelectual/diagnóstico por imagen , Discapacidad Intelectual/genética , Imagen por Resonancia Magnética/métodos , Proteínas de la Membrana/genética , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/genética , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico por imagen , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/genética , Fosfolipasas A2/genéticaAsunto(s)
Humanos , Distrofias Neuroaxonales/genética , Trastornos del Metabolismo del Hierro/genética , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Edad de Inicio , Progresión de la Enfermedad , Distrofias Neuroaxonales/patología , Trastornos del Metabolismo del Hierro/patología , Neurodegeneración Asociada a Pantotenato Quinasa/patologíaRESUMEN
ABSTRACT Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutation in the PANK2 gene. It is characterized by abnormal brain iron accumulation, mainly in the globus pallidus. PKAN is included in a group of disorders known as neurodegeneration with brain iron accumulation (NBIA). We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. Brain MRI has great diagnostic importance in this group of disorders and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed the diagnosis.
RESUMO Neurodegeneração associada à pantotenato-quinase (PKAN) é uma entidade autossômica recessiva causada pela mutação do gene PANK2. Caracteriza-se por depósito cerebral anormal de ferro, particularmente nos globos pálidos. PKAN faz parte de um grupo de desordens conhecidas como neurodegeneração com acúmulo cerebral de ferro (NBIA). Relatamos um caso de PKAN atípica com sua apresentação mais característica, sendo evidentes sintomas psiquiátricos marcados, distúrbio da fala e distonia focal. A ressonância magnética de crânio possui grande importância diagnóstica neste grupo de desordens, e neste caso, demonstrou o sinal do olho de tigre. O teste genético confirmou o diagnóstico.
Asunto(s)
Humanos , Distrofias Neuroaxonales , Neurodegeneración Asociada a Pantotenato QuinasaRESUMEN
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients. Therefore PKAN is also classified together with other rare neurodegenerative diseases like Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) into the Neuroacanthocytosis (NA) syndromes. It has not been investigated yet whether acanthocytosis in PKAN is associated with a specific subset of Pank2 mutations. In this study, we analyzed acanthocytosis of a cohort of 25 PKAN patients from the Dominican Republic that are homozygous for the c.680 A>G mutation in the PANK2 gene as compared to control donors that are heterozygous or wild-type with respect to this mutation. 3D modeling of this mutation indicated that the replacement of a tyrosine by a cysteine at position 227 in Pank2 disrupts a polar interaction within the A domain of the enzyme. Mean acanthocyte count was elevated in the cohort of patients, however, acanthocytosis varied among the patients with nearly half of them showing high (>20%) or elevated acanthocytosis and the rest showing mild (6-10%) or no (<6%) acanthocytosis. Heterozygous control donors revealed a tendency to mild acanthocytosis. Based on the insight that Pank2 is a normal constituent of red blood cells and de novo biosynthesis of coenzyme A is likely to take place in the erythrocyte cytosol we propose a hypothetical model that accounts for the variability in the occurrence of acanthocytic cells in PKAN.
Asunto(s)
Abetalipoproteinemia/diagnóstico , Acantocitos/patología , Neurodegeneración Asociada a Pantotenato Quinasa/complicaciones , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Polimorfismo de Nucleótido Simple , Abetalipoproteinemia/genética , Abetalipoproteinemia/patología , Adolescente , Adulto , Niño , Estudios de Cohortes , República Dominicana , Estabilidad de Enzimas , Homocigoto , Humanos , Modelos Moleculares , Neurodegeneración Asociada a Pantotenato Quinasa/sangre , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Adulto JovenRESUMEN
Neurodegeneration with brain iron accumulation type 1 (NBIA-1) is a rare disorder characterized by progressive extrapyramidal dysfunction and dementia. NBIA-1 encompasses typical iron brain accumulation, mostly in the globus pallidus with secondary dementia, spasticity, rigidity, dystonia, and choreoathetosis. Treatment remains mostly symptomatic and is challenging. We present the case of a 14-year-old boy diagnosed with NBIA-1, presenting intractable progressive generalized dystonia leading to unresponsive status dystonicus (SD). The patient received a SynchroMed II (model 8637) programmable system pump (Medtronic®, Inc.) implant with an Ascenda intrathecal catheter for intrathecal morphine therapy (IMT). The initial dose of morphine was 1.0 mg/day. Overall, we observed no complications with IMT treatment and important improvement of the patient's motor function with stabilization of his incapacitating dystonia and his quality of life. On the Global Dystonia Severity Rating Scale, he presented 52% improvement, 30% improvement on the Unified Dystonia Rating Scale, and 38% improvement on the Fahn-Marsden Rating Scale after 10 months, when the dose was 1.7 mg/day. IMT should be considered as a potential palliative treatment in the management of intractable dystonia and SD secondary to NBIA-1.
Asunto(s)
Trastornos Distónicos/tratamiento farmacológico , Morfina/farmacología , Neurodegeneración Asociada a Pantotenato Quinasa/tratamiento farmacológico , Adolescente , Trastornos Distónicos/etiología , Humanos , Bombas de Infusión Implantables , Masculino , Morfina/administración & dosificación , Neurodegeneración Asociada a Pantotenato Quinasa/complicacionesRESUMEN
Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by iron accumulation in the brain, because of mutations in the PANK2 gene. Phenotypic and genotypic characteristics of 11 patients from five Mexican families with PKAN disease are reported. Sequencing of PANK2 confirmed the diagnosis. The 11 patients had dysarthria associated with dystonia and Parkinsonism in six. Brain magnetic resonance imaging (MRI) showed the 'eye-of-the-tiger' sign in all patients. Three different mutations were identified, a novel one (p.A469P) and two (p.G219V and p.N404I) very rare. Homozygous sibs for the p.G219V mutation had a severe disease progression with early death. Dystonia predominated in the p.A469P/p.N404I compound heterozygous patients. Homozygous for p.N404I showed Parkinsonism, tics and personality and speech disorders. Early and late disease onset and variable expression was present in carriers of the different identified mutations. The 'eye-of-the-tiger' is an excellent neuroimaging hallmark to predict PANK2 mutations. We detected a 'cluster' of patients harboring the p.N404I mutation, strongly suggesting a founder effect for this mutation. This is the first familial clinical-genetic PKAN disease study accomplished in Mexico.
Asunto(s)
Familia , Imagen por Resonancia Magnética , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Adolescente , Encéfalo/patología , Niño , Preescolar , Femenino , Efecto Fundador , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , México , Mutación , Linaje , Fenotipo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Análisis de Secuencia de ADNRESUMEN
Pantothenate kinase-associated neurodegeneration (PKAN) disease is an autosomal recessive neurodegenerative disorder with iron storage in the brain due to PANK2 gene mutations. Brain magnetic resonance imaging (MRI) shows the typical "eye-of-the-tiger" sign. The aim of the present study was to describe clinical, MRI and molecular findings in a 26-year-old male with atypical PKAN disease in whom, brain MRI scans showed bilateral pallidal T2-hypointensity with a small central region of T2-hyperintensity, resembling the "eye-of-the-tiger" typical image. Genetic analysis identified two mutations in PANK2: c.1561G>A and c.1663G>A, being the latter never described before. Due to limited phenotype-genotype correlation among patients with movement disorders, if "eye-of-the-tiger" brain MRI is present, PANK2 mutations investigation are needed to confirm PKAN disease.
Asunto(s)
Mutación Missense , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adulto , Genotipo , Humanos , Masculino , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , FenotipoRESUMEN
PURPOSE: To quantify involvement of globus pallidus and two midbrain nuclei (substantia nigra and red nucleus) in Pantothenate Kinase-Associated Neurodegeneration (PKAN). MATERIAL AND METHODS: We performed T2 and T2* weighted imaging with calculation of the corresponding relaxation times on a subset of 5 patients from a larger group of 20 patients with PKAN from the southwest part of the Dominican Republic. Examinations were carried out on a 3T scanner and included a multi-echo spin-echo as well as a multi-echo gradient echo sequence. Results were compared to a control group of 19 volunteers. RESULTS: T2 and T2* weighted sequences showed abnormal signal reduction in the globus pallidus of all patients. On T2* weighted imaging, abnormal signal in the substantia nigra could reliably be detected in 75% of cases, but differentiation from normal was less reliable in T2 weighted scans. Correspondingly, relaxation times differed from normal with very high significance (p < 0.0001) in the globus pallidus, but with with less significance in the substantia nigra (p ≤ 0.03). The red nucleus was not affected. CONCLUSIONS: Signal reduction in the globus pallidus, which probably is due to abnormal accumulation of iron, is severe in PKAN and can be differentiated from normal with high reliability. The substantia nigra is affected to a lesser degree, and the red nucleus is not involved. The reason for this selective susceptibility of normally iron-rich brain structures for pathological accumulation of iron remains speculative. Our quantitative results might be helpful to assess the value of an iron chelation approach to therapy.
Asunto(s)
Globo Pálido/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Mesencéfalo/patología , Neurodegeneración Asociada a Pantotenato Quinasa/patología , Adolescente , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: In a variety of dystonias, functional magnetic resonance imaging has shown deviations of cortical and basal ganglia activations within the motor network, which might cause the movement disturbances. Because these investigations have never been performed in secondary dystonia due to Pantothenate-Kinase Associated Neurodegeneration, we report our results in a small group of such patients from the Dominican Republic. METHODS: Functional magnetic resonance imaging was carried out in 7 patients with a genetically confirmed mutation of the PANK2 gene and a non-affected control group (matched pairs) using an event-related motor activation paradigm (hand movements). RESULTS: Compared to the control group (p ≤ 0.01), patients showed a larger amount of activated voxels starting in the contralateral cerebellum and contralateral premotor cortex 2 s before the actual hand movement. Whereas these "hyperactivations" gradually diminished over time, activations in the contralateral primary motor cortex and the supplementary motor area peaked during the next second and those of the contralateral putamen at the time of the actual hand movement. In a multiple regression analysis, all these areas correlated positively with the degree of dystonia of the contralateral arm as judged by the Burke-Fahn-Marsden-scale (p ≤ 0.001). CONCLUSION: As in other forms of dystonia, the increased activations of the motor system found in our patients could be related to the origin of the dystonic movements. Because in this condition the primary lesion affects the pallidum, a defect of the feed-back control mechanism between basal ganglia and cortex might be the responsible factor.
Asunto(s)
Cerebelo/irrigación sanguínea , Imagen por Resonancia Magnética , Corteza Motora/irrigación sanguínea , Movimiento/fisiología , Neurodegeneración Asociada a Pantotenato Quinasa/patología , Neurodegeneración Asociada a Pantotenato Quinasa/fisiopatología , Adolescente , Mapeo Encefálico , Estudios de Casos y Controles , Cerebelo/fisiopatología , Femenino , Mano/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Corteza Motora/fisiopatología , Oxígeno/sangre , Adulto JovenRESUMEN
Introducción: La PKAN (Neurodegeneración Asociada a Pantotenato Kinasa) es una enfermedad autosómica recesiva caracterizada clinicamente por presentarse en la primera infancia, regresión en el desarrollo psicomotor, compromiso extrapiramidal, piramidal y neuro-oftalmológico, de curso progresivo y fatal. La alteración genética se encuentra en el cromosoma 20p12.3-p13 que codifica la pantotenato kinasa, que regula el metabolismo del pantotenato, fundamental en la síntesis de ácidos grasos. Su alteración resulta en un aumento de la concentración de cisteína y el depósito de hierro en los ganglios basales. Casos Clínicos: Se presentan cuatro pacientes, dos de ellos con antecedente de consanguinidad, que iniciaron síntomas neurológicos entre los 3 a 6 años de edad, caracterizados por distonía, coreoatetosis, regresión psicomotora, compromiso visual y piramidalismo, de curso progresivo, que fallecieron antes de los 10 años de edad. La RM de encéfalo mostró las características imágenes de ôojos de tigreõ, correspondientes al depósito de hierro en los globos pallidus, concluyéndose en el diagnóstico de PKAN. Conclusión: Se presentan cuatro pacientes peruanos que por sus características hereditarias, clínicas y radiológicas corresponden al diagnóstico de PKAN.
Introduction: PKAN is an autosomal recessive disorder clinically characterized by delayed motor involvement, pyramidal and extrapyramidal symptoms, and neuro-ophthalmologic involvement with a progressive course and fatal outcome.The causal gene is localized to chromosome 20pI2.3-pI3 which encodes forpanthothenate kinase. Pantothenate kinase regulates panthothenate metabolism and is integral to fatty acids synthesis. Its alteration may result in an elevated concentration of cysteine and iron accumulation in the basal ganglia. Case Report: We report four patients between the ages of 3 and 6 with a history ofconsanguinity who presented with a specific constellation of neurological symptoms, characterized by dystonia, choreoatetosis, psychomotor regression, visual involvement, pyramidalism, and a progressive course culminating in death prior to the age of 10. MRI showed the "eye-of-the-tiger" sign related to iron deposits at the globus pallidus, consistent with the diagnosis of PKAN.Conclusion: We report four Peruvian cases that according to inheritance, clinical and imaging characteristics correspond with a diagnosis of PKAN.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Aberraciones Cromosómicas , Neurodegeneración Asociada a Pantotenato Quinasa , PerúRESUMEN
PURPOSE: To present some unusual MR findings in a group of patients from the south-west of the Dominican Republic suffering from Pantothenate Kinase Associated Neurodegeneration (PKAN). MATERIALS AND METHODS: Twenty patients and one preclinical case homozygous for the PANK2 mutation, 13 heterozygous gene carriers and 14 healthy volunteers were scanned prospectively using a 3 Tesla system. RESULTS: All patients showed the typical signal reduction within the globus pallidus and the substantia nigra. A surprising finding was the absence of the bright spot ("tiger's eye") in the medial part of the pallidum in 6 patients, but not in the preclinical case. Both fractional anisotropy (FA) and mean diffusivity (MD) were increased with high significance in the globus pallidus, whereas a reduction of FA in the anterior parts of the internal capsule was accompanied by an elevation of MD. CONCLUSION: Our findings support the hypothesis that the absence of the "tiger's eye" in PKAN might be secondary, probably caused by an increased accumulation of iron. This could artificially increase FA and MD values and change fiber tracking results. Except for the fronto-basal tracts, white matter was preserved well. This encouraging finding might support efforts to develop further therapeutic strategies in this devastating dystonia.