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2.
Artigo em Inglês | MEDLINE | ID: mdl-34279169

RESUMO

Objective. Up to 50% of patients affected by amyotrophic lateral sclerosis (ALS) show behavioral changes within the spectrum of frontotemporal degeneration (FTD). Behavioral dysfunctions in ALS patients negatively impact on management, prognosis and survival. It is, thus, crucial to develop ALS-specific psychometric tools for early detecting alterations in behavior. This study aimed at investigating psychometric properties and feasibility of the Beaumont Behavioral Impairment (BBI), a proxy-report questionnaire designed to screen for FTD-like behavioral symptoms in ALS patients.Methods. Ninety ALS patients were compared to 100 healthy participants (HPs) on the BBI. ALS patients underwent clinical, cognitive, mood/anxiety and further behavioral (Frontal System Behavior Scale, FrSBe; Frontal Behavioral Inventory, FBI) evaluation. Validity, reliability, sensitivity and specificity of the BBI were assessed.Results. The BBI was significantly related to FrSBe and FBI scores, whereas not to other measures. A Principal Component Analysis yielded a mono-component structure; Cronbach's α was .93. The BBI proved to be sensitive to changes in behavior as well as to discriminate between different degrees of dysfunction. By addressing the FrSBe as the gold standard, the BBI reached optimal sensitivity (85.7%) and specificity (79.7%) at a cutoff of 10.5. Moreover, the BBI proved to be more accurate than the FrSBe and the FBI in clinical classifications.Conclusion. The BBI showed high internal consistency, as well as good construct, convergent and divergent validity. Its clinical usability is encouraged in ALS patients as being able to sensitively and specifically detect FTD-like behavioral changes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33860702

RESUMO

Objective: To assess patients Quality of life (QoL) and the burden of their caregivers during Covid-19 pandemic and specifically the impact of two-month lockdown period. Methods: In April 2020, a total of 60 patients and 59 caregivers were administered by phone scales assessing patients' QoL (McGill QoL Questionnaire), general health status (EQ-5D-5L), and caregiver burden (Zarit Burden Interview). The administration was repeated one month after the end of lockdown measures, with the addition of a qualitative questionnaire (COVID-QoL Questionnaire) exploring family reorganization and personal perception of lock down. Results: QoL and perceived health status did not worsen during lockdown, while caregiver burden increased (p = 0.01). Patient's QoL and caregiver burden were inversely correlated at T1 (ZBI total score mildly correlated with Mc Gill existential subscore, p = 0.02, rho = 0.30 and with Mc Gill total score, p = 0.05, rho = 0.265). No significant correlations were found at T2. According to the COVID-QoL questionnaire, caregivers perceived lower family help compared to patients (p < 0.001). Conclusions: Restricted measures of lockdown period during COVID-19 pandemic did not result in a significant reduction of QoL in our cohort of ALS patients, while caregiver burden significantly increased. ALS motor impairment may have played a role in the unchanged life conditions of patients. Instead, the restriction of family help for primary caregivers could be responsible of their increased burden, reflecting the importance of a wide social support in the management of this clinical condition.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32924624

RESUMO

We describe the telemedicine experience of an Italian ALS tertiary Center during COVID-19 pandemic. A total of 144 visits were scheduled between 6th March and 6th April 2020. These mostly consisted of neurological or psychological visits (139, 96.5%). One hundred thirty-nine (96.5%) visits were performed as telemedicine and mostly via phone call (112, 80.6%). Three (2.1%) visits were considered as urgent and maintained as outpatient care. Additionally, patients were still able to telephone, being put through directly to their neurologists. Many requests of contact were addressed at getting information about the scheduled visits or examinations (45, 43.3%). Globally, patients and caregivers were satisfied with the telemedicine service. However, the majority (85, 65.9%) would prefer a face-to-face visit. In conclusion, telemedicine could be considered a good complement to face-to-face care, even after social restrictions have been eased.


Assuntos
Esclerose Amiotrófica Lateral/terapia , COVID-19 , Neurologia , Preferência do Paciente , Satisfação do Paciente , Psicologia , Telemedicina/métodos , Idoso , Esclerose Amiotrófica Lateral/fisiopatologia , Esclerose Amiotrófica Lateral/psicologia , Gerenciamento Clínico , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , SARS-CoV-2 , Fonoterapia , Centros de Atenção Terciária
5.
Neurology ; 96(1): e141-e152, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33106391

RESUMO

OBJECTIVE: To determine whether the neuropsychological profiles of patients with amyotrophic lateral sclerosis (ALS) with (ALSC9+) and without (ALSC9-) C9orf72 expansion are different, we administered a battery of neuropsychological tests to 741 patients with ALS (68 ALSC9+ and 673 ALSC9-) and 129 controls. METHODS: The study population includes 741 patients with ALS who were consecutively diagnosed at the Turin ALS expert center in the 2010-2018 period and who underwent both cognitive/behavioral and genetic testing. Patients' neuropsychological patterns were compared (1) at the same degree of cognitive and behavioral deficit according to the revised ALS-Frontotemporal Dementia Consensus Criteria and (2) at the same level of motor impairment according to the King staging system. RESULTS: Despite being about 7 years younger, ALSC9+ patients had significantly lower scores in tests exploring executive function and verbal memory both when classified as cognitively normal and when diagnosed in the intermediate cognitive categories. Considering the clinical perspective, ALSC9+ patients showed significantly lower scores compared to ALSC9- patients at King stage 1 and 3 in almost all the examined neuropsychological domains; at King stage 2, ALSC9+ patients were more severely affected only in the verbal memory domain. Behavioral function was comparably impaired in the 2 cohorts. CONCLUSIONS: ALSC9+ patients show a different neuropsychological profile compared to ALSC9- patients, being more impaired in executive functions and verbal memory domains at all King stages. Verbal memory emerged as a particularly vulnerable function in ALSC9+, with worse performances even when patients were still classified as cognitively normal.


Assuntos
Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/genética , Proteína C9orf72/genética , Transtornos Cognitivos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos
6.
Eur J Neurol ; 28(3): 745-753, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33175462

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to evaluate brain metabolic correlates of apathy in amyotrophic lateral sclerosis (ALS). METHODS: A total of 165 ALS patients underwent 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG-PET) and Frontal Systems Behaviour Scale (FrSBe) evaluation. FrSBe provides "before" and "after" apathy subscores, referring to premorbid and morbid conditions. "After" apathy subscore and "before-after" gap, i.e. the difference between "before" and "after" subscores, were regressed against whole-brain metabolism. Among patients with a pathological "after" apathy subscore (i.e., ≥65), we compared patients with "before" apathy subscores ≥65 and <65, and patients with "before-after" gaps of <22 and ≥22. RESULTS: In the whole sample, the "after" apathy subscore negatively correlated with metabolism in the dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), ventrolateral prefrontal cortex (VLPFC), premotor cortex (PMC) and anterior cingulate cortex (ACC), and insula bilaterally. A positive correlation was found in the cerebellum and pons. The "before-after" gap negatively correlated with metabolism in bilateral DLPFC, DMPFC and PMC, and left VLPFC and ACC, and positively correlated with cerebellar and pontine clusters. Among patients with an "after" apathy subscore ≥65, we found no difference between those with "before" apathy subscores ≥65 and <65. Patients with a "before-after" gap ≥22, compared to patients with a gap <22, showed relative hypometabolism in bilateral DLPFC and DMPFC, and left ACC and PMC, and relative cerebellar and pontine hypermetabolism. CONCLUSION: No studies on brain 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography correlates of apathy have been performed in ALS. We found that FrSBe "after" apathy subscore correlated with metabolic changes in brain regions known as neuroanatomical correlates of apathy. Furthermore, our findings support the relevance of the gap between premorbid and morbid conditions to detect behavioural changes due to the neurodegenerative process underlying ALS.


Assuntos
Esclerose Amiotrófica Lateral , Apatia , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons
7.
Artigo em Inglês | MEDLINE | ID: mdl-32856494

RESUMO

OBJECTIVES: To validate and assess the reliability of the Italian version of self-administered ALSFRS-R, considering patients' clinical and cognitive features and caregiver's help. Methods: During the COVID-19 pandemic, by analyzing the results of 70 paired self-administered vs standard telephone-administered ALSFRS-R, we calculated overall score, single item scores, ALSFRS-R domain scores, King's and MiToS stage inter-rater agreement and reliability using different validated methods. We created the Italian version of self-administered ALSFRS-R following ENCALS recommendation. Results: Correlation between the two scales was 0.94 and no systematic directional bias was found. The intraclass correlation coefficient (ICC) was very high (>0.90) for the vast majority of the considered classification criteria, especially King's total score (0.96) and MiToS score (0.94). A higher ICC was found when the patients answered the questionnaire with the caregiver's help (0.95). Conclusions: Online self-administered ALSFRS-R scale is a valid tool to stratify ALS patients into clinical stages and to implement telemedicine monitoring.


Assuntos
Atividades Cotidianas , Esclerose Amiotrófica Lateral/epidemiologia , COVID-19/epidemiologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Telemedicina/normas , Atividades Cotidianas/psicologia , Idoso , Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/psicologia , COVID-19/psicologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Telemedicina/métodos
8.
Neurobiol Aging ; 98: 205-213, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33316576

RESUMO

We tested the Cognitive Reserve (CR) hypothesis in Amyotrophic Lateral Sclerosis (ALS), enrolling 111 patients, using education as CR proxy, 18F-FDG-PET to assess brain damage, and ECAS to measure cognition. Education was regressed out against brain metabolism, including age, sex, spinal/bulbar onset, ALSFRS-R, and ECAS as covariates. Clusters showing a significant correlation were used as seed regions in an interregional correlation analysis (IRCA) in the ALS group and in 40 controls. In the ALS group, we found a negative correlation between brain metabolism and education in the right anterior cingulate and bilateral medial frontal gyrus. In the IRCA in the ALS group, the medial frontal cluster metabolism positively correlated with that of frontotemporal regions (right > left), bilateral caudate nuclei, and right insula, and negatively correlated with that of corticospinal tracts, cerebellum, and pons. In controls, the IRCA showed significant positive correlations in the same regions but less extended. Our results agree with the CR hypothesis. The negative correlation between the medial frontal cluster and the cerebellum found only in ALS patients might reflect cerebellar compensation.


Assuntos
Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/psicologia , Encéfalo/metabolismo , Disfunção Cognitiva/etiologia , Reserva Cognitiva , Escolaridade , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Esclerose Amiotrófica Lateral/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Dano Encefálico Crônico/diagnóstico por imagem , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
9.
Artigo em Inglês | MEDLINE | ID: mdl-33229451

RESUMO

OBJECTIVE: To identify the metabolic changes related to the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) imaging. METHODS: 274 ALS patients underwent neuropsychological assessment and brain 18F-FDG-PET at diagnosis. According to the criteria published in 2017, cognitive status was classified as ALS with normal cognition (ALS-Cn, n=132), ALS with behavioural impairment (ALS-Bi, n=66), ALS with cognitive impairment (ALS-Ci, n=30), ALS with cognitive and behavioural impairment (ALS-Cbi, n=26), ALS with frontotemporal dementia (ALS-FTD, n=20). We compared each group displaying some degree of cognitive and/or behavioural impairment to ALS-Cn patients, including age at PET, sex and ALS Functional Rating Scale-Revised as covariates. RESULTS: We identified frontal lobe relative hypometabolism in cognitively impaired patients that resulted more extensive and significant across the continuum from ALS-Ci, through ALS-Cbi, to ALS-FTD. ALS-FTD patients also showed cerebellar relative hypermetabolism. ALS-Bi patients did not show any difference compared with ALS-Cn. CONCLUSIONS: These data support the concept that patients with cognitive impairment have a more widespread neurodegenerative process compared with patients with a pure motor disease: the more severe the cognitive impairment, the more diffuse the metabolic changes. Otherwise, metabolic changes related to pure behavioural impairment need further characterisation.

10.
Brain Sci ; 10(9)2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32961718

RESUMO

(1) Background: Cognitive features of patients with amyotrophic lateral sclerosis (ALS) have never been specifically analyzed according to the lateralization of motor impairment. In the present study we investigated the cognitive performances of ALS patients to describe the relationship between motor and cognitive dysfunction, according to site and side of disease onset. (2) Methods: Six-hundred and nine ALS patients underwent a comprehensive neuropsychological evaluation at diagnosis in Turin ALS Centre Tests included-mini-mental state examination (MMSE), frontal assessment battery (FAB), trail-making test A/B (TMT A-B), digit span forward and backward (digit span FW/digit span BW), letter fluency test (FAS), category fluency test (CAT), Rey auditory verbal learning test (RAVLT), Babcock story recall test (BSRT), Rey-Osterrieth complex figure test (ROCFT), Wisconsin card sorting test (WCST), Raven's coloured progressive matrices (CPM47). Cognitive performances of patients, grouped by side and site of onset, were statistically compared using z-scores, as appropriate. (3) Results: Bulbar patients and bilateral spinal onset patients (Sbil) were generally characterized by lower cognitive performances in most neuropsychological tests, when compared to patients with lateralized onset (right-side spinal onset, Sri and left-side spinal onset, Sle). Digit span backward and visual memory task (ROCFT) median z-scores were significantly higher, reflecting a better cognitive performance, in Sri patients when compared to bulbar/Sbil patients, while verbal memory tasks (RAVLT and BRST) resulted in significantly higher scores in Sle patients. Our results are in keeping with hemispheric functional lateralization of language and visuospatial abilities. (4) Conclusions: In ALS patients, as in other neurodegenerative diseases, we found a direct relationship between lateralized motor and cognitive features.

11.
Neuroimage Clin ; 27: 102312, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32622315

RESUMO

OBJECTIVE: To evaluate the metabolic correlates of lifetime sport practice in ALS through brain 18F-FDG-PET. METHODS: 131 patients completed a questionnaire about lifetime exposures, including physical activity related to sports, hobbies and occupations, and underwent brain 18F-FDG-PET. Exposure to sports was expressed as MET (Metabolic Equivalent of Task). We considered only regular practice (at least 2 h/week, for at least three months). We compared brain metabolism between two groups: subjects who did not report regular sport practice during life (N-group) and patients who did (Y-group). The resulting significant clusters were used in each group as seed regions in an interregional correlation analysis (IRCA) to evaluate the impact of lifetime sport practice on brain networks typically involved by the neurodegenerative process of ALS. Each group was compared to healthy controls (HC, n = 40). RESULTS: We found a significant, relative cerebellar hypermetabolism in the N-group compared to the Y-group. The metabolism of such cerebellar cluster resulted correlated to more significant and widespread metabolic changes in areas known to be affected by ALS (i.e. frontotemporal regions and corticospinal tracts) in the N-group as compared to the Y-group, despite the same level of disability as expressed by the ALS FRS-R. Such findings resulted independent of age, sex, site of onset (bulbar/spinal), presence/absence of C9ORF72 expansion, cognitive status and physical activity related to hobbies and occupations. When compared to HC, the N-group showed more widespread metabolic changes than the Y-group in cortical regions known to be relatively hypometabolic in ALS patients as compared to HC. CONCLUSIONS: We hypothesize that patients of the N-group might cope better with the neurodegenerative process, since they show more widespread metabolic changes as compared to the Y-group, despite the same level of disability. Nevertheless, further studies are necessary to corroborate this hypothesis.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos
12.
Artigo em Inglês | MEDLINE | ID: mdl-32484726

RESUMO

Background: A cognitive impairment, ranging from frontotemporal dementia (FTD) to milder forms of dysexecutive or behavioral dysfunction, is detected in 30-50% of patients affected by amyotrophic lateral sclerosis (ALS) at diagnosis. Such condition considerably influences the prognosis, and possibly impacts on the decision-making process with regards to end-of-life choices. The aim of our study is to examine the changes of cognitive and behavioral impairment in a large population of ALS from the time of diagnosis to a 6-month follow-up (IQR 5.5-9.0 months), and to examine to what extent the progression of cognitive impairment affects survival time and rate of disease progression.Methods: We recruited 146 ALS patients classified according to revised criteria of ALS and FTD spectrum disorder. In a multidisciplinary setting, during two subsequent visits we examined clinical features with ALSFRS-r score, FVC% and BMI, and cognitive status with an extensive neuropsychological evaluation.Results: At second examination, one-third of patients showed a worsening of cognitive impairment, namely 88% of ALSbi, 27% of ALSci, 40% of ALScbi, and, interestingly, also 24% of cognitive normal ALS developed a significant cognitive dysfunction. We find that those who changed their cognitive status presented a lower ALSFRS-r score at t1 and a shorter survival time compared to those who did not change, regardless of the type of cognitive impairment.Conclusion: We show how cognitive disorders in ALS patients can not only be present at diagnosis, but also manifest during disease and influence the progression of motor deficit and the prognosis.


Assuntos
Esclerose Amiotrófica Lateral , Demência Frontotemporal , Esclerose Amiotrófica Lateral/complicações , Cognição , Demência Frontotemporal/complicações , Humanos , Estudos Longitudinais , Testes Neuropsicológicos
13.
Neurology ; 94(8): e802-e810, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-31907290

RESUMO

OBJECTIVE: To assess the determinants of amyotrophic lateral sclerosis (ALS) phenotypes in a population-based cohort. METHODS: The study population included 2,839 patients with ALS diagnosed in Piemonte, Italy (1995-2015). Patients were classified according to motor (classic, bulbar, flail arm, flail leg, predominantly upper motor neuron [PUMN], respiratory) and cognitive phenotypes (normal, ALS with cognitive impairment [ALSci], ALS with behavioral impairment [ALSbi], ALSci and ALSbi combined [ALScbi], ALS-frontotemporal dementia [FTD]). Binary logistic regression analysis was adjusted for sex, age, and genetics. RESULTS: Bulbar phenotype correlated with older age (p < 0.0001), women were more affected than men at increasing age (p < 0.0001), classic with younger age (p = 0.029), men were more affected than women at increasing age (p < 0.0001), PUMN with younger age (p < 0.0001), flail arm with male sex (p < 0.0001) and younger age (p = 0.04), flail leg with male sex with increasing age (p = 0.008), and respiratory with male sex (p < 0.0001). C9orf72 expansions correlated with bulbar phenotype (p < 0.0001), and were less frequent in PUMN (p = 0.041); SOD1 mutations correlated with flail leg phenotype (p < 0.0001), and were less frequent in bulbar (p < 0.0001). ALS-FTD correlated with C9orf72 (p < 0.0001) and bulbar phenotype (p = 0.008), ALScbi with PUMN (p = 0.014), and ALSci with older age (p = 0.008). CONCLUSIONS: Our data suggest that the spatial-temporal combination of motor and cognitive events leading to the onset and progression of ALS is characterized by a differential susceptibility to the pathologic process of motor and prefrontal cortices and lower motor neurons, and is influenced by age, sex, and gene variants. The identification of those factors that regulate ALS phenotype will allow us to reclassify patients into pathologically homogenous subgroups, responsive to targeted personalized therapies.


Assuntos
Esclerose Amiotrófica Lateral/classificação , Esclerose Amiotrófica Lateral/epidemiologia , Proteína C9orf72/genética , Disfunção Cognitiva/epidemiologia , Demência Frontotemporal/epidemiologia , Transtornos Motores/epidemiologia , Superóxido Dismutase-1/genética , Fatores Etários , Idoso , Esclerose Amiotrófica Lateral/genética , Disfunção Cognitiva/genética , Comorbidade , Feminino , Demência Frontotemporal/classificação , Demência Frontotemporal/genética , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Motores/classificação , Transtornos Motores/genética , Mutação , Fenótipo , Fatores Sexuais
14.
Neurology ; 93(10): e984-e994, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31409738

RESUMO

OBJECTIVE: To assess the association of the degree of severity of motor impairment to that of cognitive impairment in a large cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: This is a population-based cross-sectional study on patients with ALS incident in Piemonte, Italy, between 2007 and 2015. Cognitive status was classified according to the revised ALS-FTD Consensus Criteria. The King system and the Milano Torino Staging system (MiToS) were used for defining the severity of motor impairment. RESULTS: Of the 797 patients included in the study, 163 (20.5%) had ALS-frontotemporal dementia (FTD), 38 (4.8%) cognitive and behavioral impairment (ALScbi), 132 (16.6%) cognitive impairment (ALSci), 63 (7.9%) behavioral impairment (ALSbi), 16 (2.0%) nonexecutive impairment, and 385 (48.2%) were cognitively normal. According to King staging, the frequency of cases with ALS-FTD progressively increased from 16.5% in stage 1-44.4% in stage 4; conversely, the frequency of ALSci, ALSbi, and ALScbi increased from King stage 1 to King stage 3 and decreased thereafter. A similar pattern was observed with the MiToS staging. ALS-FTD was more frequent in patients with bulbar involvement at time of cognitive testing. Patients with C9ORF72 expansion (n = 61) showed more severe cognitive impairment with increasing King and MiToS stages. CONCLUSION: Our findings suggest that ALS motor and cognitive components may worsen in parallel, and that cognitive impairment becomes more pronounced when bulbar function is involved. Our data support the hypothesis that ALS pathology disseminates in a regional ordered sequence, through a cortico-efferent spreading model.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Progressão da Doença , Vigilância da População , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/genética , Proteína C9orf72/genética , Disfunção Cognitiva/genética , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Vigilância da População/métodos , Estudos Prospectivos , Sistema de Registros
15.
J Neurol ; 266(7): 1633-1642, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30949819

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by a spectrum of phenotypes, but only a few studies have addressed the presence of parkinsonian (PK) symptoms. The aim of our study was to investigate the occurrence of PK features in a prospective population-based cohort of ALS patients, determining their demographic, clinical, neuropsychological and genetic characteristics, and identifying their morphological and functional imaging correlates. METHODS: A consecutive series of ALS patients were enrolled and prospectively followed for 2 years. Patients were classified according to the presence (ALS-PK) or absence (ALS) of PK signs, and they underwent neuropsychological testing, genetic analysis for the main ALS and PD genes, brain MRI and 18F-FDG-PET. ALS-PK patients underwent 123I-ioflupane SPECT. RESULTS: Out of 114 eligible patients, 101 (64 men; mean age at onset 65.1 years) were recruited. Thirty-one patients (30.7%) were classified as ALS-PK. Compared to ALS patients, ALS-PK patients were more frequently male, but did not differ for any other clinical, demographic or neuropsychological factors. 123I-ioflupane SPECT was normal in all but two ALS-PK patients. At 18F-FDG-PET, ALS-PK patients showed a relative hypometabolism in left cerebellum and a relatively more preserved metabolism in right insula and frontal regions; MRI fractional anisotropy was reduced in the sagittal stratum and increased in the retrolenticular part of the internal capsule. CONCLUSIONS: In our study, about 30% of ALS patients showed PK signs. Neuroimaging data indicate that PK signs are due to the involvement of brain circuitries other than classical nigrostriatal ones, strengthening the hypothesis of ALS as a complex multisystem disease.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico por imagem , Esclerose Amiotrófica Lateral/epidemiologia , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/epidemiologia , Vigilância da População , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
J Neurol Neurosurg Psychiatry ; 90(7): 734-739, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733331

RESUMO

OBJECTIVE: In 2017, the diagnostic criteria for cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (ALSFTD-1) have been modified (ALSFTD-2) with the inclusion of a novel category (ALS with combined cognitive and behavioural impairment, ALScbi) and with changes of operational criteria of the other categories (ALS with cognitive impairment (ALSci), ALS with behavioural impairment (ALSbi) and ALS with frontotemporal dementia (ALS-FTD)). We compared the two sets of criteria to assess the effect of the revised criteria on the cognitive classification of patients with ALS. METHODS: Two cohorts of patients with ALS were included in this study: a population-based cohort including patients identified through the Piemonte/Valle d'Aosta register for ALS in the 2014-2017 period (n=321), and a referral cohort recruited at the Turin ALS centre and at the ALS centre of the Maugeri Institute in Milan in the same period (n=205). Cognitive function was classified in blind by two neuropsychologists expert in ALS. RESULTS: ALSFTD-2 criteria determined a shift of about 15% of patients from their original category to a new one. In both cohorts, about 9% of patients were reclassified to the novel category ALScbi. Among patients previously classified as cognitively normal, 14 (4.3%, population-based cohort) and 19 (9.3%, referral cohort) were reclassified as ALSbi or ALSci. The median survival of the different categories was significantly different with both with sets of criteria. CONCLUSIONS: The new ALSFTD-2 criteria, compared with the old ones, have positive effects on the clinical practice being more sensitive to the early cognitive impairment and having a better prognostic yield.


Assuntos
Esclerose Amiotrófica Lateral , Disfunção Cognitiva , Demência Frontotemporal , Idoso , Esclerose Amiotrófica Lateral/classificação , Esclerose Amiotrófica Lateral/diagnóstico , Estudos de Coortes , Feminino , Demência Frontotemporal/classificação , Demência Frontotemporal/diagnóstico , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
17.
JAMA Neurol ; 73(4): 425-30, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26903389

RESUMO

IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a wide spectrum of involvement of cognitive functions. The mechanisms of this heterogeneity are still largely unknown, but genetic variants may account for this variability. OBJECTIVE: To assess the influence of the apolipoprotein E (APOE) and C9ORF72 genotypes on cognitive impairment in a population-based series of Italian patients with ALS. DESIGN, SETTING, AND PARTICIPANTS: All 504 patients with ALS living in Piemonte, Italy, diagnosed between January 1, 2009, and December 31, 2013, and identified through the Piemonte and Valle d'Aosta register for ALS, were eligible to participate in the study. Controls were 223 age- and sex-matched individuals identified through the patients' general practitioners. Data analysis was performed from June 1 to December 31, 2014. MAIN OUTCOMES AND MEASURES: The presence of APOE and C9ORF72 genotypes was assessed. Patients were cognitively classified as having ALS with normal cognition, ALS with frontotemporal dementia (FTD), ALS with executive or nonexecutive impairment, and ALS with behavioral impairment. RESULTS: Of the 504 patients with incident ALS, 357 (70.8%) were included in the study; 154 were women, 203 were men, they had a mean (SD) age at onset of 64.8 (10.2) years, and 37 of them carried a C9ORF72 repeat expansion. Cognitive testing revealed that 184 patients (51.5%) had ALS with normal cognition, 51 (14.3%) had ALS with FTD, 103 (28.9%) had ALS with executive or nonexecutive impairment, and 19 (5.3%) had ALS with behavioral impairment. Distribution of APOE haplotypes did not significantly differ between patients and controls or among patients with different levels of cognitive impairment. According to multivariate logistic regression, the presence of C9ORF72 repeat expansions was the strongest determinant of FTD (odds ratio, 13.08; 95% CI, 4.75-36.02; P < .001); however, the presence of an APOE ε2 allele significantly increased the risk of FTD (odds ratio, 2.61; 95% CI, 1.14-6.10; P = .03). Presence of an APOE ε4 allele was ineffectual. CONCLUSIONS AND RELEVANCE: C9ORF72 repeat expansions have a primary role in increasing the risk of cognitive impairment in patients with ALS; the APOE ε2 allele, to a lesser extent, also increases the risk of FTD. These study findings highlight the importance of considering the genetic background of patients with ALS when analyzing the putative effect of genetic modifiers.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/genética , Apolipoproteína E2/genética , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/genética , Marcadores Genéticos/genética , Idoso , Esclerose Amiotrófica Lateral/diagnóstico , Apolipoproteínas E/genética , Proteína C9orf72 , Estudos de Coortes , Feminino , Demência Frontotemporal/diagnóstico , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteínas/genética
18.
Neurology ; 86(1): 44-9, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26590270

RESUMO

OBJECTIVE: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET). METHODS: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n = 94), full-blown frontotemporal dementia (ALS-FTD; n = 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n = 37), prevalent behavioral changes (n = 9), or nonclassifiable impairment (n = 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. RESULTS: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. CONCLUSIONS: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico por imagem , Esclerose Amiotrófica Lateral/psicologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/psicologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Idoso , Esclerose Amiotrófica Lateral/epidemiologia , Transtornos Cognitivos/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
19.
J Neurol Neurosurg Psychiatry ; 86(2): 168-73, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24769471

RESUMO

BACKGROUND: There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. METHODOLOGY: Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), non-classifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients' general practitioners. RESULTS: Out of the 281 incident patients, 207 (71.9%) underwent the neuropsychological testing; of these, 19 were excluded from the analysis due previous conditions affecting cognition. Ninety-one (49.7%) patients were cognitively normal, 23 (12.6%) had ALS-FTD, 36 (19.7%) ALS-ECI, 10 (5.5%) ALS-NECI, 11 (6.0%) ALS-Bi and 11 (6.0%) non-classifiable cognitive impairment, 1 had comorbid Alzheimer's disease. Patients with ALS-FTD were older, had a lower education level, and had a shorter survival than any other cognitive group. Of the nine cases with C9ORF72 mutation, six had ALS-FTD, two ALS-ECI and one was cognitively normal; one of the five patients with SOD1 mutations and one of the five patients with TARBDP mutations had ALS-Bi. CONCLUSIONS: About 50% of Italian patients with ALS had some degree of cognitive impairment, in keeping with a previous Irish study, despite the largely different genetic background of the two populations. The lower educational attainment in patients with ALS-FTD indicated a possible role of cognitive reserve in ALS-related cognitive impairment. ALS-ECI and ALS-NECI may represent discrete cognitive syndromes in the continuum of ALS and FTD.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/psicologia , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Idoso , Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/genética , Proteína C9orf72 , Estudos de Casos e Controles , Transtornos Cognitivos/classificação , Transtornos Cognitivos/complicações , Transtornos Cognitivos/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Itália/epidemiologia , Masculino , Mutação , Testes Neuropsicológicos , Proteínas/genética , Fatores de Risco , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Análise de Sobrevida
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