Behavioral variant frontotemporal dementia in patients with previous severe mental illness: a systematic and critical review / Demência frontotemporal variante comportamental em pacientes com transtorno mental grave prévio: revisão sistemática e crítica

ABSTRACT Objectives: To explore the relationship between severe/serious mental illness (SMI) and the behavioral variant of frontotemporal dementia (bvFTD), as the patterns of symptoms and cognitive performance that characterize both disorders share similarities. Methods: We performed a systematic review investigating what has already been published regarding the relationship between bvFTD and SMI. Studies were selected from PubMed and LILACS databases, including those published up to February 12, 2018. The search strategy included the following terms: "frontotemporal dementia" plus "bipolar", OR "frontotemporal dementia" plus "schizophrenia", OR "frontotemporal dementia" plus "schizoaffective". Publications without abstracts, case reports with absent genetic or histopathological confirmation, reviews and non-English language papers were excluded across the search process. Results: The search on PubMed retrieved 186 articles, of which 42 met eligibility criteria. On the LILACS database, none met the requirements. Generally, three major research aims were identified: 1) to look for frontotemporal lobar degeneration-associated genetic abnormalities in patients with prior SMI; 2) to compare the cognitive profile between patients affected by neurodegenerative disorders and schizophrenic patients; 3) to highlight the association between bvFTD and preceding psychiatric conditions and/or distinguish them both. The investigated mutations were found infrequently in the studied SMI samples. Cross-sectional studies comparing cognitive performance between bvFTD and psychiatric disorders mostly found no remarkable differences. There were only a few case reports identifying definite frontotemporal lobar degeneration in patients with previous psychiatric diagnoses. Conclusions: The available evidence demonstrates how fragile the current understanding is regarding the association between bvFTD and prior SMI.

RESUMO Objetivos: Explorar a relação entre doença mental grave (DMG) e a variante comportamental da demência frontotemporal (DFTvc), uma vez que os padrões de sintomas e de desempenho cognitivo que caracterizam ambos os transtornos compartilham semelhanças. Métodos: Revisão sistemática investigando estudos publicados sobre a relação entre DFTvc e DMG. Os estudos foram selecionados nas bases de dados PubMed e LILACS, incluindo aqueles publicados até 12 de fevereiro de 2018. A estratégia de busca incluiu os seguintes termos: "demência frontotemporal" e "bipolar", OU "demência frontotemporal" e "esquizofrenia" OU "demência frontotemporal" e "esquizoafetivo". Publicações sem resumos, relatos de casos sem confirmação genética ou histopatológica, revisões e artigos escritos em idiomas que não fossem o inglês não foram selecionados na busca sistemática. Resultados: A pesquisa no PubMed encontrou 186 artigos, dos quais 42 alcançaram critérios de elegibilidade. Na base de dados LILACS, nenhum dos nove artigos identificados atendeu aos requisitos. Foram identificados três objetivos de pesquisa principais: buscar anormalidades genéticas associadas à degeneração lobar frontotemporal (DLFT) em pacientes com SMI prévia; comparar o perfil cognitivo entre pacientes acometidos por doenças neurodegenerativos e esquizofrênicos; destacar a associação entre DFTvc e condições psiquiátricas precedentes e/ou distinguir ambos. As mutações investigadas foram encontradas infrequentemente nas amostras estudadas. Os estudos transversais comparando o desempenho cognitivo entre DFTvc e os transtornos psiquiátricos não encontraram diferença, e houve apenas relatos de casos confirmando de DLFT em pacientes com diagnósticos psiquiátricos prévios. Conclusões: A evidência disponível demonstra quão frágil é o entendimento atual sobre a associação entre DFTvc e DMG.

Ludopatía y epilepsia en demencia frontotemporal: Reporte de dos casos / Pathological gambling and epilepsy in patients with frontotemporal dementia: Two case reports

RESUMEN La demencia frontotemporal es un trastorno neurodegenerativo cuyo subtipo más común es la variante conductual. Es considerada la causa de demencia más frecuente en menores de 60 años. Se presentan dos casos no emparentados cuyos síntomas típicos fueron: deterioro progresivo de la cognición, del comportamiento, alteraciones psiquiátricas como desinhibición, actos impulsivos, apatía, falta de empatía, estereotipias y cambios en los hábitos de alimentación. La resonancia magnética cerebral, en ambos casos, mostró atrofia frontotemporal a predominio izquierdo; en la evaluación neuropsicológica se evidenció alteraciones de las funciones ejecutivas. El primer caso cursó con ludopatía como síntoma inicial, motivo por el cual permaneció por un año en un centro psiquiátrico, siendo el segundo en Latinoamérica y uno de los pocos casos reportados en el mundo. El segundo caso presentó crisis epilépticas en su evolución.

ABSTRACT Frontotemporal dementia is a neurodegenerative disorder of which the behavioral variant is most common. This condition is currently considered the most common cause of dementia in people younger than 60 years. Here, we present two unrelated cases in which the typical symptoms were cognitive and behavioral progressive deterioration and psychiatric disorders such as disinhibition, impulsive acts, apathy, lack of empathy, stereotypies, and changes in eating habits. The first case exhibited pathological gambling as the initial symptom and resided in a psychiatric facility for a year. Notably, this was the second such case in Latin America and one of only a few such cases reported worldwide. The second case presented with epileptic seizures during evolution. In both cases, brain magnetic resonance revealed left-predominant frontotemporal atrophy, and alterations in executive function were evident during neuropsychological assessments.

Demencia frontotemporal y esclerosis lateral amiotrófica: presentación de un caso clínico / Frontotemporal dementia and amyotrophic lateral sclerosis: a case report

For a long time amyotrophic lateral sclerosis was seen as an exclusively motor disease, however, a lot of investigations have proved the existence of cognitive symptoms similar to frontotemporal dementia that could precede, coexist or appear after the motor symptoms. We report the case of a 69 years old hispanic man who consults about progressive swallowing impairments. In the speech languagepathologist assessment, we detected cognitive impairments that made necessary to complete the workout with specific test. The results of the assessment, shown disturbance in swallowing with suggestive symptomatology of motor neuron disease, besides cognitive impairments in executive functions, visuospatial abilities, memory, language and behaviors and conductual abnormalities. A few months after speech language pathologist assessment, the diagnosis of amyotrophic lateral sclerosis was given. This case emphasize in the importance of a exhaustive anamnesis and clinical assessment, as well as early diagnosis focused on opportune interventions. Additionally, it’s important to note the need for professionals with update knowledge in neuropsychology, to support interventions.

Durante mucho tiempo se pensó que la esclerosis lateral amiotrófica era una enfermedad exclusivamente motora, sin embargo, diversos estudios han mostrado la existencia de síntomas cognitivos que pueden manifestarse antes, durante o después de los síntomas motores y que serían compatibles con una demencia frontotemporal. Se presenta un caso de un hombre de 69 años que consulta por dificultades de deglución de carácter progresivo. En la evaluación fonoaudiológica se pesquisan dificultades cognitivas, por lo cual se decide aplicar diversas pruebas con el objetivo de aclarar estas alteraciones. Los resultados de la evaluación revelan alteraciones a nivel de deglución, con sintomatologia sugerente de enfermedad de motoneurona, además de alteraciones cognitivas a nivel de funciones ejecutivas, habilidades visuoespaciales, memoria, lenguaje y alteraciones en conducta y comportamiento. En el transcurso de unos meses, posterior a la evaluación fonoaudiológica, se realiza el diagnóstico de esclerosis lateral amiotrófica. Se enfatiza en la importancia de la anamnesis y evaluación clínica, el diagnóstico precoz enfocado en la intervención oportuna y la relevancia de contar con profesionales competentes y capaces, con conocimientos sobre neuropsicología que puedan ser de apoyo para la intervención.

Valoración de prosodia espontánea afectiva y análisis de discurso en pacientes con esquizofrenia y demencia frontotemporal (DFT) variante lingüística / Spontaneous speech prosody and discourse analysis in schizophrenia and Fronto Temporal Dementia (FTD) patients

La esquizofrenia y la demencia frontotemporal (DFT) variante lingüística comparten características de lenguaje tales como la dificultad para acceder al léxico, la desorganización del discurso con múltiples interrupciones, reformulaciones, pausas y retractaciones. En el caso de los pacientes esquizofrénicos, estas dificultades revelan fallas para expresar el afecto, mientras que en los pacientes con DFT variante lingüística refleja un problema lingüístico. Métodos: El presente estudio, a través de un análisis de una serie de casos valorados tanto en la Clínica de memoria como en la Unidad de Salud Mental del HUSI-PUJ (Hospital Universitario de San Ignacio), con evaluación lingüística adicional (análisis de discurso y análisis acústico), presenta características distintivas de la DFT en sus variantes lingüísticas y la esquizofrenia que permiten guiar al especialista en la búsqueda de marcadores tempranos de un diagnóstico diferencial. Resultados: En el 100%de los pacientes con DFT variante lingüística, hay dificultades para comprender estructuras lingüísticas de tipo complejo e importantes problemas de fluidez del discurso. En los pacientes con esquizofrenia se encuentran importantes alteraciones en la expresión de los elementos suprasegmentales del habla e interrupciones en el discurso. Conclusiones: Se presenta como una evaluación lingüística en profundidad permite revaluar algunas de las modalidades de valoración del discurso y la prosodia de los pacientes con demencia y esquizofrenia; indica que algunos elementos del discurso son útiles para orientar el diagnóstico y correlacionar el deterioro funcional en la cotidianidad de la práctica del psiquiatra.

Patients with schizophrenia and Frontotemporal Dementia (FTD) in their linguistic variants share some language characteristics such as the lexical access difficulties, disordered speech with disruptions, many pauses, interruptions and reformulations. For the schizophrenia patients it reflects a difficulty of affect expression, while for the FTD patients it reflects a linguistic issue. Methods: This study, through an analysis of a series of cases assessed Clinic both in memory and on the Mental Health Unit of HUSI-PUJ (Hospital Universitario San Ignacio), with additional language assessment (analysis speech and acoustic analysis), present distinctive features of the DFT in its linguistic variants and schizophrenia that will guide the specialist in finding early markers of a differential diagnosis. Results: In patients with FTD language variants, in 100% of cases there is a difficulty understanding linguistic structure of complex type; and important speech fluency problems. In patients with schizophrenia, there are significant alterations in the expression of the suprasegmental elements of speech, as well as disruptions in discourse. Conclusions: We present how depth language assessment allows to reassess some of the rules for the speech and prosody analysis of patients with dementia and schizophrenia; we suggest how elements of speech are useful in guiding the diagnosis and correlate functional compromise in everyday psychiatrist's practice.

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.