Afasia primaria progresiva y sus variantes: diagnóstico, evolución, características imagenológicas y manejo / Progressive primary aphasia and its variants: diagnosis, evolution, imaging characteristics and management

RESUMEN INTRODUCCIÓN: Las demencias son un conjunto de trastornos neurocognitivos, en personas con edad menor a 65 años sobresale la demencia frontotemporal, síndrome neurodegenerativo heterogéneo que tiene dos grandes variantes: conductual y afasia primaria progresiva. En esta última se describen tres variantes: no fluente, semántica y logopénica, que exigen en la práctica conocimientos actualizados para su diferenciación y comprensión. El objetivo de este escrito es hacer una revisión narrativa sobre las tres variantes clínicas de la afasia primaria progresiva, profundizando en diagnóstico, evolución, características imagenológicas y manejo. MATERIALES Y MÉTODOS: Artículo de revisión narrativa a partir del estado del arte en literatura biomédica sobre demencia frontotemporal, afasia primaria progresiva y sus variantes. RESULTADOS: El compromiso del lenguaje y de otras funciones cognitivas, así como los hallazgos imagenológicos, son heterogéneos en las tres variantes. Semiológicamente, la afasia primaria progresiva no fluente se caracteriza por apraxia del habla, la variante logopénica por fallas en la nominación y la variante semántica por fallas en el significado del mensaje. El compromiso imagenológico en la afasia primaria progresiva no fluente es más frontoinsular y corticosubcortical; en la variante semántica es habitualmente temporal del lado dominante; y en la variante logopénica priman alteraciones temporoparietales. No hay tratamiento específico, pero se puede vincular algunas opciones farmacológicas con procesos/técnicas de rehabilitación del lenguaje. CONCLUSIÓN: Si bien se trata de una forma heterogénea de demencia, tiene características clínicas (síntomas, signos y evolución) e imagenológicas importantes a la hora de su detección y diagnóstico en ambientes clínicos.

ABSTRACT INTRODUCTION: Dementias are a group of neurocognitive disorders, and in people under 65 years of age, frontotemporal dementia stands out, a heterogeneous neurodegenerative syndrome that has two major variants: behavioral and primary progressive aphasia. In the latter, three variants are described: non-fluent, semantic and logopenic, which require up-to-date knowledge in practice for their differentiation and understanding. The objective is to carry out a narrative review on the three clinical variants of primary progressive aphasia, delving into diagnosis, evolution, imaging characteristics and management. MATERIALS AND METHODS: Narrative review article based on the state of the art in biomedical literature on frontotemporal dementia, primary progressive aphasia and its variants. RESULTS: The compromise of language and other cognitive functions, as well as the imaging findings, are heterogeneous in the three variants. Semiologically, non-fluent progressive primary aphasia is characterized by apraxia of speech, the logopenic variant by failures in the nomination and the semantic variant by failures in the meaning of the message. Imaging involvement in non-fluent progressive primary aphasia is mainly frontoinsular and cortico-subcortical; in the semantic variant it is usually temporary on the dominant side; and in the logopenic variant, temporo-parietal alterations prevail. There is no specific treatment, but some pharmacological options can be linked with language rehabilitation processes / techniques. CONCLUSION: although Frontotemporal dementia is an heterogenous disorder, there are important clinical and imagenologic features that are useful to the diagnostic approach in the clinical field.

Heterogeneity of repetition abilities in logopenic variant primary progressive aphasia / Heterogeneidade das habilidades de repetição na afasia progressiva primária variante logopênica

ABSTRACT. The differential diagnosis of primary progressive aphasia (PPA) is challenging due to overlapping clinical manifestations of the different variants of the disease. This is particularly true for the logopenic variant of PPA (lvPPA), in which such overlap was reported with regard to impairments in repetition abilities. In this study, four individuals with lvPPA underwent standard neuropsychological and language assessments. The influence of psycholinguistic variables on their performance of in word, nonword and sentence repetition tasks was also specifically explored. Some level of heterogeneity was found in cognitive functions and in language. The four participants showed impairment in sentence repetition in which their performance was negatively affected by semantic reversibility and syntactic complexity. This study supports the heterogeneity of lvPPA with respect to the cognitive and linguistic status of participants. It also shows that sentence repetition is influenced not only by length, but also by semantic reversibility and syntactic complexity, two psycholinguistic variables known to place additional demands on phonological working memory.

RESUMO. O diagnóstico diferencial da afasia progressiva primária (APP) é desafiador devido às sobreposições das manifestações clínicas das diferentes variantes da doença. Isso é particularmente verdadeiro para a variante logopênica do APP (APPlg), em que tal sobreposição foi relatada em relação à deficiências nas habilidades de repetição. No presente estudo, quatro indivíduos com APPlg foram submetidos à avaliações neuropsicológica e de linguagem. A influência de variáveis psicolinguísticas em seu desempenho de palavras, não-palavras e tarefas de repetição de frases também foi especificamente explorada. Certo nível de heterogeneidade foi encontrado nas funções cognitivas e na linguagem. Os quatro participantes apresentaram prejuízo na repetição de frases em que seu desempenho foi afetado negativamente pela reversibilidade semântica e complexidade sintática. O estudo apoia a heterogeneidade do APPlg no que diz respeito ao status cognitivo e linguístico dos participantes. Mostra também que a repetição de sentenças é influenciada não apenas pelo comprimento, mas também pela reversibilidade semântica e complexidade sintática, duas variáveis psicolinguísticas conhecidas por colocarem demandas adicionais na memória operacional fonológica.

Curso clínico y perfil neuropsicológico de un caso de trastorno neurocognitivo frontotemporal mayor variante lingüística / Clinical course and neuropsychological profile of Frontotemporal Neurocognitive Disorder Linguistic Language Variant

Resumen El trastorno neurocognitivo frontotemporal es una enfermedad neurodegenerativa que incluye manifestaciones clínicas de subtipo comportamental y lingüística. La afasia progresiva primaria (APP) es un síndrome en el que aparecen alteraciones del lenguaje que comprende tres tipos de variantes: no fluente, semántica y logopénica. Este estudio describe la evolución clínica y las características neuropsicológicas de una mujer de 63 años que presenta un deterioro progresivo del lenguaje. Se evalúan las funciones de atención, memoria, lenguaje y funciones ejecutivas. La paciente obtuvo un bajo rendimiento en memoria, velocidad de procesamiento y funciones ejecutivas. Su lenguaje se caracteriza por presentar baja fluidez, agramatismo, parafasias verbales y dificultades en denominación. Se concluye que la paciente presenta características de la APP no fluente, que varía a través del tiempo y afecta su funcionamiento; características de un curso clínico de un trastorno neurocognitivo mayor posible debido a una degeneración del lóbulo frontotemporal.

Abstract Mild cognitive impairment, frontotemporal dementia (FTD) is a neurodegenerative disease characterized by clinical manifestations of behavior and linguistic subtypes. Primary Progressive Aphasia (APP) is a syndrome in which language alterations appear that include three types of variations: Non - fluent, Semantic and Logopenic. This study describes the clinical evolution and the neurophysiological characteristics of a 63 years old woman that started with a progressive language impairment. The functions which are evaluated are attention, memory, language and executive functions. The patient obtained a low performance in memory, processing speed and executive functions. The language is characterized by low fluency, agramatism, paraphasias and denomination difficulties. It is concluded, that the patient has characteristics of APP non-fluent which varies throughout the time and it affects her performance; characteristics of a clinical course of a greater neurocognitive disorder might be due to a lobe frontotemporal degeneration.

Análisis preliminar del efecto de la edad y la escolaridad en adultos sanos en el rendimiento del Sydney Language Battery (Sydbat) en español de Chile / Preliminary analysis of the effect of age and education in healthy adults on the performance of the Sydney Language Battery (Sydbat) in Chilean Spanish

Existen 3 variantes de afasia progresiva primaria (APP), que se distinguen según el dominio lingüístico predominantemente alterado: no fluente, logopénica y semántica. Una herramienta que ayuda a su clasificación es el Sydney Language Battery (Sydbat), el cual no se encuentra validado en Chile. El objetivo del presente trabajo es analizar la posible relación entre edad, años de escolaridad y rendimiento obtenido en las subpruebas del Sydbat en adultos sanos. Participaron 38 adultos sanos a losque se les aplicó el test.El promedio de edad fue 56,8 años (DE = 8,3) y tenían una media de 13,8 años de escolaridad (DE = 3,9). Todos provenían de la Región Metropolitana. Se realizaron correlaciones de Pearson y Spearman, para explorar la correlación entre el rendimiento en las subpruebas, la edad y la escolaridad. Considerando la variabilidad en el rendimiento en las subpruebas, se realizaron modelos uni y multivariados. Se encontraron correlaciones significativas entre edad y la subprueba comprensión (p<0,05) y los años de escolaridad con las subpruebas asociación semántica (p<0,001) y nominación (p<0,01). En personas con más de 12 años de escolaridad, el puntaje en la subprueba asociación semántica varió aproximadamente 2 puntos, con respecto a personas con menos de 12 años de escolaridad (p<0,01). Se concluye que las variaciones en el rendimiento del test, dependen la edad y la escolaridad. A mayor edad, menor es el rendimiento en la subprueba de comprensión. A mayor escolaridad, mayor es el rendimiento en las subpruebas de asociación semántica y nominación. El efecto mencionado debe ser considerado en el proceso de validación de Sydbat.

There are 3 variants of primary progressive aphasia (APP), which are distinguished according to the predominantly altered linguistic domain: non-fluent, logopenic, and semantic. A tool that helps in its classification is the Sydney Language Battery (Sydbat), which is not validated in Chile. The objective of this work is to analyze the possible relationship between age, years of schooling and performance obtained in the Sydbat subtests in healthy adults. 38 healthy adults participated in the test. The average age was 56.8 years (SD = 8.3) and they had a mean of 13.8 years of schooling (SD = 3.9). They all came from the Metropolitan Region. Pearson and Spearman correlations were performed to explore the correlation between subtest performance, age, and schooling. Considering the variability in performance in the subtests, univariate and multivariate models were performed. Significant correlations were found between age and the comprehension subtest (p <0.05) and the years of schooling with the semantic association (p <0.001) and nomination (p <0.01) subtests. In participants with more than 12 years of schooling, the score in the semantic association subtest varied approximately 2 points, with respect to people with less than 12 years of schooling (p <0.01). It is concluded that the variations in test performance depend on age andeducation. The older participants are, the lower their performance on the comprehension subtest. The higher the schooling, the higher the performance on the semantic association and nomination subtests. The mentioned effect must be considered in the Sydbat validation process.

Advance in Genetic Mechanism of Primary Progressive Aphasia (review) / 中国康复理论与实践

Primary progressive aphasia (PPA) is a common neurodegenerative speech disease. Earlier studies on PPA merely observed preliminary pathogenic factors at the brain level. Based on genetic technology, almost 20% to 30% patients with autosomal dominant inheritance reveals that this deficit is closely relevant to gene mutation. C9 gene mutation is the primary factor related to amyotrophic lateral sclerosis and frontotemporal dementia, which is attributed to the main causes of PPA. Repeating expansion of C9 gene may influence the expression of C9 gene, block the combination of RNA and protein, and destroy RNA function.

Language impairment in primary progressive aphasia and other neurodegenerative diseases

Primary progressive aphasia (PPA) is a progressive neurodegenerative disease that disrupts the language capacity of an individual by selectively affecting the language network of brain. Although aphasic literature is replete with reports of brain damage responsible for various types of PPA, it does not provide a comprehensive understanding of whether PPA is an independent pathological condition or an atypical syndrome of neurodegenerative diseases (NDD). To address this ambiguity, we provide a detailed description of PPA, its variants and their brain anatomy. Subsequently, we unravel the relationship between PPA and NDDs like Alzheimer’s, Parkinson’s and Dyslexia. To substantiate the relationship further, we also provide a brief account of their genetic aetiology. In the final section, we offer an exhaustive approach towards the treatment of PPA by combining the existing language the rapies with clinical and pharmacological interventions.

Relationships between ¹⁸F-THK5351 Retention and Language Functions in Primary Progressive Aphasia

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Rate and rhythm control strategies for apraxia of speech in nonfluent primary progressive aphasia / Estratégias de controle de ritmo e taxa de fala para a apraxia de fala na afasia progressiva primária não-fluente

ABSTRACT The nonfluent/agrammatic variant of primary progressive aphasia is characterized by apraxia of speech and agrammatism. Apraxia of speech limits patients' communication due to slow speaking rate, sound substitutions, articulatory groping, false starts and restarts, segmentation of syllables, and increased difficulty with increasing utterance length. Speech and language therapy is known to benefit individuals with apraxia of speech due to stroke, but little is known about its effects in primary progressive aphasia. This is a case report of a 72-year-old, illiterate housewife, who was diagnosed with nonfluent primary progressive aphasia and received speech and language therapy for apraxia of speech. Rate and rhythm control strategies for apraxia of speech were trained to improve initiation of speech. We discuss the importance of these strategies to alleviate apraxia of speech in this condition and the future perspectives in the area.

RESUMO A variante não-fluente/agramática da afasia progressiva primária caracteriza-se por apraxia de fala e agramatismo. A apraxia de fala limita a comunicação devido a redução no fluxo de fala, substituição de sons, tentativas articulatórias, falsos inícios de fala e reinícios, segmentação de sílabas, e aumento da dificuldade conforme o aumento do enunciado. A terapia fonoaudiológica é benéfica em casos de apraxia de fala decorrentes de acidente vascular cerebral, porém pouco se sabe sobre seus efeitos na afasia progressiva primária. Este artigo é um relato de caso de uma mulher de 72 anos, analfabeta e trabalhadora do lar, que foi diagnosticada com afasia progressiva não-fluente e recebeu terapia fonoaudiológica para apraxia de fala. Estratégias de controle do ritmo e da taxa de fala foram utilizadas a fim de melhorar a iniciação da fala. A importância de estratégias para minimizar a apraxia de fala e as perspectivas futuras na área são discutidas neste artigo.

Role of Positron Emission Tomography as a Biologic Marker in the Diagnosis of Primary Progressive Aphasia: Two Case Reports / 대한핵의학회잡지

Primary progressive aphasia (PPA) is a heterogenous neurodegenerative disorder characterized by declining language and speech ability. Various underlying neuropathologies can induce PPA, and the disorder is divided into three subtypes—progressive non-fluent aphasia, semantic variant aphasia, and logopenic aphasia—according to clinical features. Accurate disease classification and prediction of underlying diseases are necessary for appropriate treatment, but proper use of imaging tests is important because clinical information alone often makes it difficult to make accurate decisions. Because there is a characteristic metabolic pattern according to the subtypes, F-18 fluorodeoxyglucose positron emission tomography (PET) can indicate subtype classification. In addition, PETstudies for imaging amyloid or dopamine transporters play an important role in demonstrating underlying disease. The present case showed that PET imaging studies are useful in diagnosis and could be used as a biomarker in PPA.

Corticobasal Degeneration Presenting as Non-Fluent/Agrammatic Primary Progressive Aphasia: A Case Report

BACKGROUND: Non-fluent agrammatic primary progressive aphasia (naPPA) is characterized by progressive non-fluent speech disorder and might be associated with taupathy such as corticobasal degeneration (CBD) and progressive supranuclear palsy. We report a case of overlap syndrome presented with language impairment, and diagnosed as naPPA with possible CBD. CASE REPORT: A 58-year-old woman visited a memory and dementia clinic, with a 10-month history of progressive language disturbance. She was diagnosed as naPPA and overlapping CBD, based on the clinical features and neuroimaging findings including florbetaben PET. CONCLUSIONS: naPPA is pathologically caused by taupathy, and might progress to asymmetrical parkinsonism and apraxia, suggestive of CBD. Overlapping clinical features in our case represent various phenotypes of taupathy.

A fluência na afasia progressiva primária logopênica / Fluency in primary progressive aphasia - logopenic variant

Esta pesquisa é um estudo de caso que tem como objetivo analisar, longitudinalmente, a fluência de um sujeito com Afasia Progressiva Primária (APP) Logopênica. O método de análise baseou-se em sete sessões de atendimento fonoaudiológico de uma paciente com 61 anos de idade, diagnosticada com APP. Os dados foram analisados de forma qualitativa, a partir da Neurolinguística Enunciativo-Discursiva. Os resultados sugerem que a paciente apresentava a variante Logopênica da APP, com as seguintes características: fala com estrutura gramatical reservada, manutenção da compreensão de palavras isoladas e de frases preservadas, durante a conversação na interação dialógica. As dificuldades de fluência referiram-se às ocorrências de repetição em palavras longas e menos cotidianas, parafasias fonológicas, pausas disfluentes e anomia. A análise também apontou modificação progressiva nos sintomas, com aumento do número de repetições e alteração de sua forma de ocorrência. Essas modificações parecem indicar uma relação inversamente proporcional entre fluência de fala e avanço da doença, em que a fluência tende à deterioração. Esse cenário assume aspecto relevante na linguagem do sujeito na medida em que influencia na sua interação e papel social, ou seja, quanto menos fluente é o discurso, mais essa condição afeta sua posição de falante.

This research is a case report which aims to perform a longitudinal analysis of fluency of a subject with Primary Progressive Aphasia (PPA), Logopenic variant. The method of analysis was based on seven speech therapy sessions of a 61-year-old patient diagnosed with PPA. The data was analyzed qualitatively in light of Enunciative-Discursive Neurolinguistics. The results showed that the patient has the logopenic variant of PPA, with the following characteristics: preservation of speech grammar structure, preserved comprehension of single words and phrases during conversation in dialogical interaction. Speech flow difficulties were marked by occurrences of repetitions of longer and more unusual words, phonological paraphasias, non-fluent pauses and anomies. The analysis also pointed to a progression of symptoms, with increasing number of repetitions of different forms of occurrence. These modifications suggest an inversely proportional relationship between oral fluency and disease progression in which speech flow tends to decay. This scenario is relevant for subjects' language because it influences their social interaction, i.e., the less fluent their speech, the more affected they are as speakers.

Positive impact of speech therapy in progressive non-fluent aphasia / Impacto positivo de la terapia del lenguaje en afasia progresiva no fluente / Impacto positivo da terapia da linguagem em afasia progressiva não fluente

The aim of this paper is to analyze the effects of intensive speech therapy intervention in a case of progressive non-fluent aphasia (PNFA). This is a dementia syndrome characterized by a progressive deficit in expressive language fluency and syntactic analysis, and by agrammatism and phonemic paraphasias. Although in the early stages there are no alterations in memory, comprehension, or visual processing, personality changes can slightly occur. To analyze the effects of speech therapy in this syndrome, a single case design with pre- and post-test was used. The participant was a male patient of 84 years with PNFA, who for twelve months received weekly speech therapy to stimulate the phonological, lexical and syntactic processing. He underwent neuropsychological assessment in three stages: six months before the onset of therapy, six months after therapy started and after completing 12 months of intervention. Assessment involved linguistic processing, general cognition, neuropsychiatric symptoms, quality of life (QOL) and activities of daily living (ADL). As a result of therapy, the patient showed a slight improvement in language prosody, fluency, and content of spontaneous speech, and a significant improvement in repetition, reading aloud, and oral-phonatory praxis. Other aspects of cognitive functioning (orientation, verbal naming, praxis, and memory) remained stable; ADLs and QOL improved. It is concluded that prolonged speech therapy can improve language processing and have a positive impact on other cognitive and socio-emotional processes in PNFA. This 12-month therapeutic stimulation not only slowed cognitive decline, but allowed to see maintenance of achievements and improvement of symptoms, which can be regarded as a success in PNFA treatment, considering the rapid progression of the disease.

El objetivo de este artículo es analizar los efectos de una intervención intensiva de terapia del lenguaje en un caso de afasia progresiva no fluente (APNF). Este es un síndrome demencial caracterizado por un déficit progresivo en la fluidez del lenguaje expresivo y el análisis sintáctico, y por agramatismo y parafasias fonémicas. Aunque en las primeras etapas no presenta alteraciones en la memoria, la comprensión o el procesamiento visual, sí pueden presentarse ligeros cambios en la personalidad. Para analizar los efectos de la terapia del lenguaje en este síndrome, se utilizó un diseño de caso único con pre y post prueba. El participante fue un paciente masculino de 84 años con APNF, quien durante doce meses recibió una terapia de lenguaje semanal para estimular el procesamiento fonológico, léxico y sintáctico. Se le realizó una evaluación neuropsicológica en tres etapas: seis meses antes del inicio de la terapia, después de seis meses de intervención, y al completar 12 meses de esta. Específicamente se evaluó el procesamiento lingüístico, la cognición general, los síntomas neuropsiquiátricos, la calidad de vida (CdV) y las actividades de la vida diaria (AVD). Como resultado de la terapia, el paciente mostró ligeras mejorías en la prosodia, la fluidez y el contenido del lenguaje espontáneo, y una mejoría significativa en la repetición, la lectura en voz alta y las praxias orofonatorias. Otros aspectos cognitivos (orientación, denominación verbal, praxias y memoria) se mantuvieron estables; las AVD y la CDV mejoraron. Se concluye que la terapia del lenguaje prolongada puede mejorar el procesamiento lingüístico y también tener un impacto positivo en otros procesos cognitivos y socio-emocionales en la APNF. La intervención no solo disminuyó la velocidad del deterioro cognitivo, sino que permitió ver el mantenimiento de los logros y la mejoría de los síntomas, lo cual es un éxito en el tratamiento de la APNF, debido a su rápida progresión.

O objetivo deste artigo é analisar os efeitos de uma intervenção intensiva de terapia da linguagem em um caso de afasia progressiva não fluente (APNF). Esta é uma síndrome demencial caracterizada por um déficit progressivo na fluência da linguagem expressiva e da análise sintática, e por agramatismo e parafasias fonêmicas. Ainda que nas primeiras etapas não presenta alterações na memória, na compreensão ou no processamento visual, podem aparecer pequenas mudanças na personalidade. Para analisar os efeitos da terapia da linguagem nesta síndrome, utilizou-se um desenho de caso único com testes antes e depois. O participante foi um paciente masculino de 84 anos com APNF, que durante doze meses recebeu uma terapia de linguagem semanal para estimular o processamento fonológico, léxico e sintático. Realizou-se uma avaliação neuropsicológica em três etapas: seis meses antes do início da terapia, depois de seis meses de intervenção, e ao completar 12 meses desta. Avaliou-se especificamente o processamento linguístico, a cognição geral, os sintomas neuropsiquiátricos, a qualidade de vida (QdV) e as atividades da vida diária (AVD). Como resultado da terapia, o paciente mostrou pequenas melhorias na prosódia, na fluência e no conteúdo da linguagem espontânea, e uma melhoria significativa na repetição, na leitura em voz alta e nas praxias orofonatórias. Outros aspectos cognitivos (orientação, denominação verbal, praxias e memória) mantiveram-se estáveis; as AVD e a QdV melhoraram. Conclui-se que a terapia da linguagem prolongada pode melhorar o processamento linguístico e também ter um impacto positivo em outros processos cognitivos e sócio emocionais na APNF. A intervenção diminuiu não somente a velocidade da deterioração cognitiva, senão que permitiu ver a manutenção dos êxitos e a melhoria dos sintomas, o que representa um sucesso no tratamento da APNF, devido a sua rápida progressão.

Longitudinal Clinical Changes of Non-Fluent/Agrammatic Primary Progressive Aphasia as Tau Spectrum Disorder: A Case Report

BACKGROUND: Tauopathies are a group of diseases caused by the accumulation of hyperphosphorylated tau protein in the central nervous system. Previous studies have revealed that there is considerable overlap in clinical, pathological, and genetic features among different taupathies. CASE REPORT: We report a patient with non-fluent/agrammatic primary progressive aphasia at the initial assessment. Over time, other symptoms belonging to corticobasal degeneration and progressive supranuclear palsy appeared in this patient. CONCLUSIONS: Clinical overlapping features in these disorders may represent different phenotypes of a single disease process.

Brief intervention for agrammatism in Primary Progressive Nonfluent Aphasia: a case report / Intervenção breve para agramatismo em Afasia Progressiva Primária Não Fluente: relato de caso

The non-fluent and agrammatic variant of Primary Progressive Aphasia (NFPPA) is characterized by reduced verbal production with deficits in building grammatically correct sentences, involving dysfunctions in syntactic and morphological levels of language. There are a growing number of studies about non-pharmacological alternatives focusingon the rehabilitation of functional aspects or specific cognitive impairments of each variant of PPA. This study reports a shortterm treatment administered to a patient with NFPPA focusing on the production of sentences. The patient had significant reduction in verbal fluency, use of keywords, phrasal and grammatical simplifying as well as anomia. Using the method of errorless learning, six sessions were structured to stimulate the formation of sentences in the present and past with the cloze technique. The patient had improvement restricted to the strategy, with 100% accuracy on the trained phrases and generalization to untrained similar syntactic structure after training. These results persisted one month after the treatment.

A variante não fluente e agramática da Afasia Progressiva Primária (APPNF) caracteriza-se por redução da produção verbal com falhas para construir sentenças gramaticalmente corretas, envolvendo disfunções nos níveis sintático e morfológico da linguagem. É crescente o número de pesquisas sobre alternativas não farmacológicas enfocando areabilitação de aspectos funcionais ou comprometimentos cognitivos específicos de cada variante das APP. Relatar um tratamento de curta-duração administrado a um paciente com APPNF enfocando a produção de sentenças. O paciente apresentava redução importante da fluência verbal, uso de palavras-chave, simplificação frasal e gramatical, além deanomia. Utilizando o método de aprendizado sem erros, foram estruturadas seis sessões para estimular a formação de frases no presente e no passado com a técnica de cloze. O paciente apresentou melhora restrita à estratégia, com 100% de acerto nas frases treinadas e generalização para as não-treinadas de estrutura sintática semelhante após o treinamento.Os resultados foram mantidos um mês após o tratamento.

Logopenic aphasia or Alzheimer's disease: different phases of the same disease? / Afasia logopênica ou doença de Alzheimer: diferentes fases da mesma doença?

The logopenic variant of Primary Progressive Aphasia, or logopenic aphasia, is a the most recently described variant of Primary Progressive Aphasia and also the least well defined. This variant can present clinical findings that are also common to Alzheimer?s disease, given they both share the same cytopathologic findings. This article reports the clinical case of a patient for whom it proved difficult to define a clinical diagnosis, being split between the logopenic variant and Alzheimer?s disease at different phases of the disease. Using this case as an example and drawing on the latest evidence from the literature on the logopenic variant, we postulate the hypothesis that this variant may present as an initial symptom of Alzheimer?s disease in some atypical cases.

A variante logopênica da Afasia Progressiva Primária, ou afasia logopênica, é a variante mais recentemente descrita entre todas as variantes da Afasia Progressiva Primária e, também por isso, a menos definida. Essa variante pode apresentar achados clínicos em comum com a doença de Alzheimer pelo fato de compartilharem o mesmo achado citopatológico. Este artigo descreve o caso clínico de uma paciente na qual se evidenciou uma dificuldade em assumir o diagnóstico clínico que se dividia entre a variante logopênica e a doença de Alzheimer em determinadas fases da doença. Utilizando este caso como exemplo e as atuais evidências que a literatura apresenta sobre a variante logopênica, levantamos a hipótese de que essa variante pode apresentar-se como uma manifestação inicial da doença de Alzheimer em alguns casos menos típicos.

Primary progressive aphasia: Classification of variants in 100 consecutive Brazilian cases / Afasia Progressiva Primária: classificação das variantes em 100 casos consecutivos brasileiros

ABSTRACT Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterized primarily by progressive language impairment. Recently, consensus diagnostic criteria were published for the diagnosis and classification of variants of PPA. The currently recognized variants are nonfluent/agrammatic (PPA-G), logopenic (PPA-L) and semantic (PPA-S). Objective: To analyze the demographic data and the clinical classification of 100 PPA cases. Methods: Data from 100 PPA patients who were consecutively evaluated between 1999 and 2012 were analyzed. The patients underwent neurological, cognitive and language evaluation. The cases were classified according to the proposed variants, using predominantly the guidelines proposed in the consensus diagnostic criteria from 2011. Results: The sample consisted of 57 women and 43 men, aged at onset 67.2±8.1 years (range of between 53 and 83 years). Thirty-five patients presented PPA-S, 29 PPA-G and 16 PPA-L. It was not possible to classify 20% of the cases into any one of the proposed variants. Conclusion: It was possible to classify 80% of the sample into one of the three PPA variants proposed. Perhaps the consensus classification requires some adjustments to accommodate cases that do not fit into any of the variants and to avoid overlap where cases fit more than one variant. Nonetheless, the established current guidelines are a useful tool to address the classification and diagnosis of PPA and are also of great value in standardizing terminologies to improve consistency across studies from different research centers.

RESUMO A afasia progressiva primária (APP) é uma síndrome clínica neurodegenerativa caracterizada pelo comprometimento predominante e progressivo da linguagem. Recentemente, foi publicado um consenso clínico para o diagnóstico e classificação das variantes da APP. As variantes reconhecidas atualmente são: não-fluente/agramática (APP-G), logopênica (APP-L) e semântica (APP-S). Objetivo: Analisar os dados demográficos e classificar as variantes de uma amostra de 100 casos de APP. Métodos: Foram analisados os achados de 100 pacientes de APP que foram encaminhados consecutivamente para avaliação fonoaudiológica entre 1999 e 2012. Os pacientes foram submetidos à avaliação neurológica, cognitiva e de linguagem. A partir, principalmente, dos critérios elaborados pelo consenso clinico de APP, os casos foram classificados em uma das variantes. Resultados: Cem casos, 43 homens e 57 mulheres, foram avaliados. A idade de início variou entre 53 e 83 anos (x=67.2 (±8.1). Foram identificados 35 casos de APP-S, 29 de APP-G e 16 de APP-L. Vinte casos não se enquadraram em nenhumas das três variantes. Conclusão: Foi possível classificar distúrbio de linguagem em 80% da amostra em uma das três variantes de APP. A recomendação atual estabelecida pelo consenso clínico é uma ferramenta útil para direcionar a classificação e diagnóstico da APP e também é de grande valor para uniformidade das terminologias entre os diferentes centros de pesquisa. Porém, alguns ajustes seriam interessantes para contemplar os casos que não se encaixam em nenhuma das variantes e para evitar a sobreposição de casos que poderiam se encaixar em mais de uma variante.

Nonpharmacological interventions for cognitive impairments following primary progressive aphasia: A systematic review of the literature / Intervenções não-farmacológicas para distúrbios cognitivos na Afasia Progressiva Primária: uma revisão sistemática da literatura

ABSTRACT This study provided a systematic review on nonpharmacological interventions applied to patients diagnosed with Primary Progressive Aphasia (PPA) and its variants: Semantic (SPPA), Nonfluent (NFPPA) and Logopenic (LPPA) to establish evidence-based recommendations for the clinical practice of cognitive rehabilitation for these patients. Methods: A PubMed and LILACS literature search with no time restriction was conducted with the keywords PPA (and its variants) AND rehabilitation OR training OR intervention OR therapy OR treatment OR effectiveness. To develop its evidence-based recommendations, a research committee identified questions to be addressed and determined the level of evidence for each study according to published criteria (Cicerone et al., 2000). Overall evidence for treatments was summarized and recommendations were derived. Results: Our search retrieved articles published from 1995 to 2013: 21 for SPPA, 8 for NFPPA, 3 for LPPA and 8 for PPA with no specification. Thirty-five studies were rated as Class III, consisting of studies with results obtained from one or more single-cases and that used appropriate single-subject methods with adequate quantification and analysis of results. The level of evidence of three functional interventions could not be established. One study was rated as Class II and consisted of a nonrandomized case-control investigation. Conclusion: Positive results were reported in all reviewed studies. However, in order to be recommended, some investigation regarding the intervention efficacy was required. Results of the present review allows for recommendation of some nonpharmacological interventions for cognitive deficits following PPA as Practice Options. Suggestions for further studies on PPA interventions and future research are discussed.

RESUMO Este estudo ofereceu uma revisão sistemática de intervenções não-farmacológicas aplicadas a pacientes com Afasia Progressiva Primária (APP) e suas variantes: Semântica (APPS), Não-fluente (APPNF) e Logopênica (APPL) com o objetivo de estabelecer recomendações baseadas em evidências para a prática clínica de reabilitação cognitiva para estes pacientes. Métodos: Conduziu-se busca por literatura, sem restrição de período, no PubMed e LILACS com as palavras-chave PPA (e variantes) AND rehabilitation OR training OR intervention OR therapy OR treatment OR effectiveness. Para desenvolver recomendações baseadas em evidências um comitê de pesquisadores identificou as questões relevantes para investigação e determinou o nível de evidência para cada estudo de acordo com critérios publicados (Cicerone et al., 2000). A evidência total para os tratamentos foi sumarizada e recomendações redigidas. Resultados: Foram encontrados artigos publicados de 1995 a 2013: 21 para APPS, 8 para APPNF, 3 para APPL e 8 para APP sem especificações. Trinta e cinco estudos foram classificados como Classe III, consistindo de resultados obtidos com um ou mais indivíduos e utilizando metodologia apropriada para estudo de casos. O nível de evidência de três intervenções funcionais não pôde ser estabelecido. Um estudo foi classificado como Classe II e consistiu de pesquisa caso-controle não-randomizada. Conclusão: Resultados positivos foram reportados em todos os trabalhos analisados mas, para serem recomendados, os tratamentos requerem investigação em relação a sua eficácia. Resultados da presente revisão permitiram recomendação de algumas intervenções como Opções Práticas. Ademais, apresentamos sugestões para futuros estudos de intervenção em APP.

Afasia logopénica: presentación de un caso y revisión de la literatura / Logopenic Aphasia: a case report an review of the literature

With the progressive aging of the Chilean population the diagnosis of neurodegenerative disorders is increasingly common, and among them is Primary Progressive Aphasia (PPA), with specific symptoms but late consultation. PPA is a clinical syndrome characterized by the degeneration of language regions in the dominant hemisphere that determines an insidious and progressive loss of language. Two types of PPA were recognized: Progressive non-fluent Aphasia (APnF) and Progressive Semantic Aphasia (DS), and was recently identified as a new type, Logopénica Progressive Aphasia (APL). We describe a case evaluated at the University of Chile Clinical Hospital of a woman of 54 years who have a history of 2-3 years of fluent speech with reduced speed due to the difficulty in finding words, had shortcomings in repetition of complex words, phrases and sentences, presence of phonemic paraphasias and impaired episodic memory. What in the phonological assessment supports a diagnosis of APL. Despite the above, the neurological examination was normal. The APL has been associated with Alzheimer's disease because it presents impaired episodic memory and the neuropathological changes most frequently encountered are amyloid plaques and neurofibrillary tangles. Through this article you may learn more about this disease and who to go if you or some colleague have symptoms to receive some guidance.

Con el progresivo envejecimiento de la población Chilena el diagnóstico de enfermedades neurodegenerativas es cada vez más com ún, y entre ellas está la afasia progresiva primaria (PPA), de síntomas específicos pero consulta tardía. PPA es un síndrome clínico caracterizado por la degeneración de las regiones del lenguaje en el hemisferio dominante que determina una pérdida insidiosa y progresiva del lenguaje. Fueron reconocidos dos tipos de PPA: Afasia Progresiva no fluente (APnF) y Afasia Progresiva Semántica (DS), y recientemente fue identificado un nuevo tipo como, Afasia Progresiva Logopénica (APL). Se describe un caso evaluado en el Hospital Clínico Universidad de Chile de una mujer de 54 años que presenta una historia de 2-3 años de habla fluida, con disminución de la velocidad debido a la dificultad para encontrar palabras, presentaba fallas en repetición de palabras complejas, frases y oraciones, presencia de parafasias fonémicas y problemas de memoria episódica. Lo que en la evaluación fonológica es compatible con un diagnóstico de APL. A pesar de todo lo anterior el examen neurológico fue normal. La APL se ha asociado con la enfermedad de Alzheimer, ya que presenta deterioro de la memoria episódica y los cambios neuropatológicos más frecuentes son las placas amiloides y los ovillos neurofibrilares. A través de este artículo podrán conocer más acerca de esta enfermedad y a quien acudir en caso de presentar síntomas usted o algún conocido para recibir alguna orientación.

Afasias progresivas primarias: las afasias de lenta evolución a demencia / Primary progressive aphasias: the slowly evolving aphasias to dementia

La afasia progresiva primaria (APP) es un síndrome clínico neurodegenerativo caracterizado por compromiso progresivo del lenguaje, diagnosticado cuando completa tres criterios nucleares. Primero, debe existir compromiso del lenguaje, que interfiera con el uso o comprensión de las palabras. Segundo, el plan de trabajo diagnóstico debe demostrar que la enfermedad es neurodegenerativa, y además progresiva. Tercero, la afasia debe progresar relativamente aislada, sin afectación del comportamiento o de memoria episódica. El compromiso del lenguaje puede ser fluente o no fluente y puede o no interferir con la comprensión de las palabras. La memoria para hechos recientes está preservada, sin embargo los puntajes de memoria obtenidos en las pruebas mediadas verbalmente pueden ser anormales. Pueden presentarse cambios menores en personalidad o en la conducta, pero no llevan al paciente a la consulta médica y no limitan las actividades de vida diaria. Este patrón clínico es más conspicuo en los estadios iniciales de la enfermedad, y es consecuencia de la atrofia relativamente selectiva de los circuitos del lenguaje, usualmente localizado en el hemisferio izquierdo. Existen diferentes variantes clínicas de APP, cada una con un patrón característico de atrofia. Las enfermedades neuropatológicas subyacentes son heterogéneas y pueden incluir enfermedad de Alzheimer así como degeneración lobar fronto-temporal.

Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterized by progressive language impairment diagnosed when three core criteria are met. First, there should be a language impairment (i.e., aphasia) that interferes with the usage or comprehension of words. Second, the neurological work-up should determine that the disease is neurodegenerative, and therefore progressive. Third, the aphasia should arise in relative isolation, without equivalent deficits of comportment or episodic memory. The language impairment can be fluent or non fluent and may or may not interfere with word comprehension. Memory for recent events is preserved although memory scores obtained in verbally mediated tests may be abnormal. Minor changes in personality and behavior may be present but are not the leading factors that bring the patient to medical attention or that limit daily living activities. This distinctive clinical pattern is most conspicuous in the initial stages of the disease, and reflects a relatively selective atrophy of the language network, usually located in the left hemisphere. There are different clinical variants of PPA, each with a characteristic pattern of atrophy. The underlying neuropathological diseases are heterogeneous and can include AlzheimerÆs disease as well as frontotemporal lobar degeneration.

Primary progressive aphasia patients evaluated using diffusion tensor imaging and voxel based volumetry-preliminary results / Avaliação de pacientes com afasia primária progressiva com imagem tensor de difusão e volumetria baseada em voxels

There are individuals who have a progressive language deficit without presenting cognitive deficits in other areas. One of the diseases related to this presentation is primary progressive aphasia (PPA). OBJECTIVE: Identify by means of diffusion tensor imaging (DTI) and measurements of cortical volume, brain areas that lead to dysphasia when presenting signs of impaired connectivity or reduced volume. METHOD: Four patients with PPA were evaluated using DTI, and measurements of cortical volumes in temporal areas. These patients were compared with two normal volunteers. RESULTS: There is a trend to a difference in the number and volume of related fibers between control group and patients with PPA. Comparing cortical volumes in temporal areas between groups yielded a trend to a smaller volume in PPA patients. CONCLUSION: Patients with PPA have a trend to impairment in cortical and subcortical levels regarding relevant areas.

Existem indivíduos que apresentam deterioração progressiva da linguagem sem apresentar déficits em outros domínios cognitivos; estes pacientes em geral apresentam afasia primária progressiva (APP). OBJETIVO: Identificar, pela imagenologia, áreas cerebrais que quando sofrem atrofia, ou quando seu sistema de conexões apresenta alterações, levam a disfasia. MÉTODO: Foram avaliados quatro pacientes com APP, utilizando-se ressonância magnética com as técnicas de imagem por tensores da difusão (DTI) e medida do volume cortical em áreas de interesse previamente definidas. Estes pacientes foram comparados com um grupo controle constituído por dois voluntários. RESULTADOS: Redução da média dos volumes dos giros temporais esquerdos no grupo de pacientes, em relação ao grupo controle, e alterações quanto ao volume e número de fibras nos tratos correspondentes. CONCLUSÃO: Pacientes com APP têm tendência a apresentar danos tanto ao nível cortical quanto subcortical.