Amyotrophic Lateral Sclerosis with Pallidonigroluysian Degeneration: A Clinicopathological Study.
Ann Neurol
; 87(2): 302-312, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31773773
ABSTRACT
OBJECTIVE:
The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype.METHODS:
From a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions, we selected those with PNLD and analyzed their clinicopathological features.RESULTS:
Eleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution (1) extensive type (n = 6), showing widespread TDP-43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneider's staging or Nishihira's typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP-43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP-43 aggregates from the cerebral cortex to the substantia nigra.INTERPRETATION:
The PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP-43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87302-312.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Substância Negra
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Núcleo Subtalâmico
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Globo Pálido
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Esclerose Lateral Amiotrófica
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2020
Tipo de documento:
Article