Dados do Trabalho

Título

White matter hyperintensities in a sporadic case of semantic variant primary progressive aphasia: a clue to GRN genotype

RESUMO

Case Report

A previously healthy 66-year-old woman presented with a four-year history of progressive difficulty in communication. The patient’s chief complaint was a “very bad voice”. She initially had occasional problems in understanding single words and often asked for sentences to be repeated. Gradual worsening of the symptoms led to severe impairment in comprehension. She eventually stopped reading and praying. There were no memory, orientation or behavioral problems. There was no family history of neuropsychiatric disorders. On the neurological examination, she had no signs of motor neuron involvement, nor parkinsonism. She exhibited aphasia with severe loss of fluency, very poor object naming and single-word comprehension combined with surface dyslexia. The patient scored 14 points at the Mini-Mental State Examination (MMSE) (16 years of education), 10/20 points at the Boston Naming Test and 6 and 3 points at Verbal Fluency Test for animals and fruits, respectively. Brain magnetic resonance imaging (MRI) revealed asymmetric left temporal atrophy, prominent left parietal atrophy and white matter hyperintensities. The clinical diagnosis was semantic variant primary progressive aphasia (svPPA). A next generation sequencing panel for dementias identified a pathogenic variant in GRN gene (c.1252C>T - p.Arg418*).

Discussion:

The hallmark of the Primary Progressive Aphasias (PPA) is the insidious deterioration of language, with relative preservation of other cognitive functions. This group of disorders is clinically heterogeneous, and comprises at least three subtypes: nonfluent, semantic and logopenic. SvPPA is characterized by anomia associated with loss of semantic knowledge, and severe impairment in single-word comprehension. Familial cases of svPPA have been linked to pathogenic variants in GRN gene, which encodes the protein progranulin. However, sporadic cases of svPPA harboring pathogenic variants in this gene are extremely rare. Our patient had a clinical phenotype consistent with svPPA, and no family history. White matter hyperintensities, in combination with asymmetric temporoparietal atrophy have raised the suspicion for a GRN genotype, which was subsequently confirmed by the molecular study.

Final comments:

GRN genotype is rare among sporadic svPPA cases, but white matter hyperintensities and asymmetric temporoparietal atrophy should reduce the threshold for molecular investigation.