Beneficial effects of pharmacological treatment in post-stroke dynamic aphasia: a behavioural and neuroimaging study

Introduction : Dynamic Aphasia (DA) is a rare form of language disorder characterized by reduced spontaneous speech with preservation of other language functions. Two types of DA have been described: language-specific type (type I DA) and domain-general type (type II DA). In type I DA, deficits are selective for word and sentence generation, whereas in type II DA impairments affect discourse generation, narrative, fluency, and non-verbal generation tasks. There is little information on the treatment of DA. Although treatment with a cognitive enhancing drug (bromocriptine) improved outcome in previous studies, pharmacological interventions combining two drugs acting on other neurotransmitter systems in DA have not been reported so far. Methods : We report an open-label pharmacological single case study (n = 1) in a male patient with a chronic type I/II DA secondary to an ischemic infarction in the left fronto-opercular and insular regions. After baseline evaluation, the patient received donepezil 5 mg/day (2 months), donepezil 10 mg/day (2 months), donepezil 10 mg/day plus memantine 20 mg/day (4½ months) followed by a washout period (1½ months). No speech-language therapy was used. A comprehensive cognitive and language evaluation was carried out at baseline and at different endpoints. 18FDG-PET was performed at the four timepoints. Results : Donepezil (5 mg/day) significantly improved type I DA features (normalization of verbs generation, p = 0.01), whereas donepezil (10 mg/day) improved some type II features (normalizing spontaneous speech, verbal fluency and improving generation of novel thoughts, p = 0.004), along with improvement of executive-attentional functioning. Combined therapy further enhanced cognitive function, but did not additionally improved DA. 18 FDG-PET revealed significant reductions of perilesional hypometabolic activity mainly after donepezil (10 mg/day) and washout. Discussion : Treatment with donepezil improved language deficits in a patient with chronic post-stroke type I/II DA. Combined therapy (donepezil plus memantine) further enhanced executive-attentional functioning. Beneficial changes were associated with improvements in perilesional metabolic activity. References : Luria AR et al.Acta Neurologica et Psychiatrica (1967). Robinson G et al. Brain (1998). Keywords : Language; patients; single case study; adults; cerebrovascular; behavioural, functional imaging.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Correlatos cerebrales y cognitivos de la potenciación farmacológica en un caso de afasia dinámica

Introducción. La afasia dinámica (AD) es un tipo raro de alteración del lenguaje caracterizada por una reducción del habla espontánea. La AD tipo lingüístico (AD I) se caracteriza por dificultades en la generación de palabras/frases, mientras que la AD tipo general (AD II) se caracteriza por problemas en la generación del discurso y la fluencia. Nuestro objetivo fue evaluar el efecto de dos fármacos combinados (donepezilo y memantina) que actúan sobre los sistemas de neurotransmisión colinérgico y dopaminérgico, respectivamente, en la recuperación de la AD. Descripción y resultados. Reportamos un estudio abierto de caso único de un paciente con AD I/II post-ictus. Se realizaron 5 evaluaciones cognitivas/lingüísticas y 18FDG-PET en 5 momentos: línea base, donepezilo-5mg/día (2 meses) , donepezilo-10mg/día (2 meses9, donepezilo-10mg/día más memantina-20mg/día (4½ meses) y período de lavado (1½ mes). Donepezilo-5mg/día mejoró la sintomatología de la AD I, mientras que el donepezilo-10mg/día mejoró la sintomatología AD II y las funciones ejecutivas/atencionales. El 18FDG-PET mostró un restablecimiento de la actividad metabólica perilesional después del donepezilo-10mg/día y del periodo de lavado. Conclusiones. El tratamiento con donepezilo mejoró los déficits lingüísticos en un paciente con AD I/II post-ictus. La terapia combinada produjo mejorías principalmente en funciones ejecutivas/atención, y estos beneficios, estaban asociados a mejorías de la actividad metabólica perilesional.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Controlling the past, owning the present, and future: cholinergic modulation decreases semantic perseverations in a person with post-stroke aphasia

Las perseveraciones en tareas de producción del habla son un síntoma común de la afasia crónica. Las perseveraciones semánticas (PS) se definen como la producción repetitiva e inconsciente de formas lingüísticas previamente utilizadas, relacionadas semánticamente con la palabra objetivo. Neuroquímicamente, se atribuyen a una debilitada activación de la palabra objetivo debido a la disminución de sistemas de neurotransmisores (acetilcolina y dopamina) en presencia de competidores semánticos. Este estudio piloto evalúa la efectividad de un fármaco que mejora el sistema colinérgico, combinado con terapia de lenguaje, para reducir las PS y otros errores semánticos en la afasia crónica post-ictus. Durante 16 semanas, se administró donepezilo (inhibidor de la colinesterasa) junto con terapia de lenguaje (2 horas/semana). Se realizaron evaluaciones en cuatro momentos: al inicio, después de donepezilo 5 mg, donepezilo 10 mg y tras un periodo de lavado de 4 semanas. Se analizó la frecuencia de las PS y su curso temporal para evaluar los efectos del tratamiento. Los resultados mostraron una reducción significativa de las PS desde la segunda evaluación en adelante, junto con una mejora notable en la gravedad de la afasia, especialmente con dosis altas de donepezilo, manteniéndose incluso tras el periodo de lavado. La comunicación diaria mejoró con dosis bajas. Estos hallazgos sugieren que la disminución de la actividad colinérgica favorece la aparición de PS y destacan la importancia de combinar agentes colinérgicos con terapia de lenguaje para reducir estas perseveraciones y mejorar otros déficits del lenguaje en la afasia

Olfactory function and viral recovery in COVID-19

Olfactory and taste disorders were reported in up to 30%-80% of COVID-19 patients. The purpose of our study was to objectively assess smell impairment in COVID-19 patients and to correlate olfactory function with viral recovery

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.

BackgroundNeurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome.MethodsWe conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models.ResultsWe included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region.InterpretationNeurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission