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2.
Artigo em Inglês | MEDLINE | ID: mdl-34590504

RESUMO

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King's Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34348536

RESUMO

Objective: To investigate the role of arterial blood gas (ABG) analysis parameters (blood carbon dioxide, pCO2; oxygen, pO2; carbonate, HCO3-; standard base excess, SBE) in monitoring respiratory function and ventilation compliance after noninvasive mechanical ventilation (NIV) adaptation, predicting survival in ALS patients. Methods: We selected the first ABG performed after NIV start in ALS patients followed from 2000 to 2015 in Turin ALS Center. Correlations between ABG parameters and survival were calculated. Risk for death/tracheostomy was computed at modifying ABG parameters by using Cox regression models, adjusted for the main prognostic factors. Kaplan-Meier curves were then performed and compared. Results: A total of 186 post-NIV ABGs were included. HCO3- and SBE showed a significant correlation with survival after NIV (respectively, R = -0.183, p = 0.018 and R = -0.200, p = 0.010). Risk for death/tracheostomy after NIV was significantly higher at increasing HCO3- and SBE blood levels, especially when HCO3- was >29 mmol/L and SBE >4 mmol/L (respectively, HR 1.466, 95% CI 1.068-2.011, p = 0.018 and HR = 1.411, 95% CI 1.030-1.32, p = 0.032). Survival in NIV was higher in patients with HCO3- < 29.0 mmol/L and SBE < 4.0 mmol/L. Conclusions: HCO3- and SBE blood levels are markers of ventilation compliance, tolerance and efficacy, being able to predict survival after NIV start in ALS.


Assuntos
Esclerose Amiotrófica Lateral , Ventilação não Invasiva , Insuficiência Respiratória , Esclerose Amiotrófica Lateral/terapia , Gasometria , Carbonatos , Humanos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia
4.
Artigo em Inglês | MEDLINE | ID: mdl-34355622

RESUMO

Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients' mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease onset: (1) ≤12 months; (2) ≤18 months; (3) ≤24 months; (4) ≤36 months. Date of spirometry corresponded to date of trial entry, while time interval onset-spirometry to disease duration at enrollment. Mortality rates from inclusion were computed at different time intervals. Based on progression rates, patients were stratified in slow, intermediate and fast progressors. Survival from recruitment was calculated depending on FVC, disease duration and progression rate. Results: We included 659 patients in group 1, 888 in group 2, 1019 in group 3 and 1102 in group 4. Mortality rates were higher in each group at reducing the FVC cutoff used for recruitment (p < 0.001). Median survival decreased when lowering FVC and disease duration cutoffs (p < 0.001); a higher median disease progression rate of included patients led to lower median survival from recruitment. The proportion of recruited fast progressors raised when shortening disease duration and lowering FVC cutoff. Conclusions: This is a simple model for setting eligibility criteria, based on mortality rates of patients depending on FVC and disease duration, to select the best population for RCTs, tailored to trials' primary endpoints and duration.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34365891

RESUMO

Objective: To assess the frequency and predictors of plateaus in ALS progression as assessed by the Medical Research Council (MRC) Scale. Methods: All patients attending the ALS Center of Turin, with a diagnosis between 2007 and 2014 were considered. At each visit, muscle strength was evaluated in several muscles and assessed using the MRC scale. Concomitant ALSFRSr scores were retrieved. Plateaus were calculated as a stable overall MRC or ALSFRSr score lasting at least 6, 12 or 18 months. Results: According to MRC scale scores, 122 (22.8%), 71 (13.2%) and 59 (11.0%) patients experienced a plateau lasting at least 6, 12 and 18 months. ALSFRSr scores revealed similar estimates [134, (25.0%), 89 (16.6%) and 67 (12.5%), respectively]. Plateaus were more frequent at high scores and appeared a median of 24.6 months (IQR 6.7-47.7) after the diagnosis. Only the predominant upper motor neuron phenotype (OR 4.06, 95% CI 2-06-8.10, p-value <0.001) and diagnostic delay OR 1.03, 95% CI 1.01-10.5, p-value = 0.005) were significantly correlated with their appearance. Discussion: Plateaus in ALS progression as assessed using either ALSFRSr or MRC scale are not infrequent and should be expected especially in less aggressive phenotypes. Similar results were found both using the MRC scale and the ALSFRSr scores, suggesting a comparable reliability of these scales in grasping the disease progression.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34151660

RESUMO

Objective: To assess amyotrophic lateral sclerosis (ALS) prevalence and to analyze how this estimate vary according to the historical depth of data collection. Methods: Data from the PARALS register have been used. Crude prevalence ratio was estimated on 31 December 2015 for the period 2015-2013 and then repeated extending the time interval by 3 years each time. For each time interval, prevalence ratio was calculated globally and stratified by sex, age at diagnosis, and phenotype. Prevalence was also calculated considering patients who underwent tracheostomy during the same study period. Results: Prevalence ratios increased proportionally to the length of the time period considered, ranging from 6 (95% CI 5.3-6.7) for a 3-year period to 12.1 (95% CI 11.1-13.1) per 100,000 population for a 21-year period. Prevalence ratio increase was inversely proportional to age at diagnosis, being null in the >85 years class and maximal in the 25-35 age class (+1700%). Among phenotypes, predominant UMN showed the highest increase (from 0.5, 95% CI 0.3-0.8, to 2.1, 95% CI 1.7 - 2.6, +320%). Discussion: Because of the variability of ALS survival, prevalence ratio strongly depends on the length of the follow-up period. A 12-year period should be sufficient to get a reliable estimate of ALS prevalence including long-survival patients.

7.
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.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33879000

RESUMO

Objective: To investigate the impact of a novel heterozygous FUS mutation in the acceptor splice site of intron 14 (c.1542 - 1 g > t) on protein expression in Peripheral Blood Mononuclear Cells (PBMC) from a familial ALS patient. Methods: PBMC were isolated for mRNA analysis (cDNA synthesis, sequencing and one-step RT-PCR), Western Immunoblot (WI), and Immunofluorescence (IF). Results: cDNA analysis revealed the skipping of exon 15 and a premature stop codon at c.228. RT-PCR showed reduced FUS mRNA by more than half compared to a healthy control (HC) and an ALS patient without genetic mutations (wtALS). In WI FUS band intensity in the proband was 30-50% compared to HC and wtALS. An antibody expected to detect only the wild-type protein did not reveal any reduction of FUS band intensity compared to the other antibodies. IF showed no difference among HC, wtALS, and the proband. Discussion: The reduction of FUS mRNA and protein in PBMC suggests the absence of the truncated protein, probably due to nonsense-mediated decay, leading to loss of function.

9.
Neurobiol Aging ; 103: 130.e1-130.e7, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33637330

RESUMO

We report a case of childhood-onset ALS with a FUS gene mutation presenting cognitive impairment and a rapid clinical progression. The patient, an 11-year-old girl, presented with right distal upper limb weakness and mild intellectual disability at the Griffith Mental Development Scales. The disease rapidly worsened and the patient became tetraplegic and bed-ridden 2 years after symptom onset. A c.1509_1510delAG mutation in exon 14 of the FUS gene was detected, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. The levels of FUS mRNA in the proband were not significantly different compared to controls. Western immunoblot analysis showed that one antibody (500-526) detected in the proband ~50% of the amount of FUS protein compared to controls, while 3 other antibodies (2-27, 400-450 and FUS C-terminal), which recognize both wild type and the mutated FUS, detected 60% to 75% of the amount of the protein. These findings indicate that p.G504Wfs*12 FUS is more prone to undergo post-translational modification respect to wild type FUS.

11.
Eur J Nucl Med Mol Imaging ; 48(4): 1124-1133, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33029654

RESUMO

PURPOSE: To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). METHODS: Three hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates. RESULTS: Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3. CONCLUSIONS: Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.


Assuntos
Esclerose Amiotrófica Lateral , Fluordesoxiglucose F18 , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Glucose , Humanos , Tomografia por Emissão de Pósitrons
12.
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
13.
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
14.
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
15.
Eur J Neurol ; 28(3): 745-753, 2021 Mar.
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.

16.
Neurology ; 96(4): e600-e609, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33208543

RESUMO

OBJECTIVE: To assess the burden of rare genetic variants and to estimate the contribution of known amyotrophic lateral sclerosis (ALS) genes in an Italian population-based cohort, we performed whole genome sequencing in 959 patients with ALS and 677 matched healthy controls. METHODS: We performed genome sequencing in a population-based cohort (Piemonte and Valle d'Aosta Registry for ALS [PARALS]). A panel of 40 ALS genes was analyzed to identify potential disease-causing genetic variants and to evaluate the gene-wide burden of rare variants among our population. RESULTS: A total of 959 patients with ALS were compared with 677 healthy controls from the same geographical area. Gene-wide association tests demonstrated a strong association with SOD1, whose rare variants are the second most common cause of disease after C9orf72 expansion. A lower signal was observed for TARDBP, proving that its effect on our cohort is driven by a few known causal variants. We detected rare variants in other known ALS genes that did not surpass statistical significance in gene-wise tests, thus highlighting that their contribution to disease risk in our cohort is limited. CONCLUSIONS: We identified potential disease-causing variants in 11.9% of our patients. We identified the genes most frequently involved in our cohort and confirmed the contribution of rare variants in disease risk. Our results provide further insight into the pathologic mechanism of the disease and demonstrate the importance of genome-wide sequencing as a diagnostic tool.


Assuntos
Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/genética , Análise Mutacional de DNA/métodos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Vigilância da População , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/diagnóstico , Proteína C9orf72/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
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
18.
Eur J Neurol ; 28(4): 1181-1187, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314477

RESUMO

BACKGROUND AND PURPOSE: The purpose was to assess the prognostic role of neck muscle weakness at diagnosis in amyotrophic lateral sclerosis (ALS) patients with respect to survival and respiratory impairment. METHODS: A retrospective cohort study was conducted. All ALS patients seen in the Turin ALS Centre from 2007 to 2014 were included. Muscle strength at diagnosis was evaluated using the Medical Research Council (MRC) scale. Survival was considered as the time from diagnosis to death or tracheostomy; time to respiratory impairment was considered as the interval from diagnosis to the first event amongst an ALS Functional Rating Scale revised item 10 <4, forced vital capacity <70%, start of non-invasive ventilation or tracheostomy. Time from diagnosis to dysarthria, dysphagia and walking impairment were considered as secondary outcomes. Cox proportional hazard regression models adjusted for sex, age at diagnosis, diagnostic delay, onset site, genetics status and the MRC scores of other muscle groups were used to assess the prognostic role of neck muscles. RESULTS: A total of 370 patients were included in the study. Fifty-nine (15.9%) patients showed neck flexor weakness at diagnosis; MRC values were mostly in agreement for neck extensors. Neck flexors were the only muscles able to predict survival (hazard ratio 0.49, 95% confidence interval 0.28-0.86; p = 0.01). Furthermore, neck flexor normal strength decreased the risk of respiratory impairment (hazard ratio 0.46, 95% confidence interval 0.22-0.96; p = 0.04) but did not influence any secondary outcomes. DISCUSSION: Neck flexor weakness at diagnosis predicts survival and respiratory impairment in ALS. This result could be valuable for both planning of patients' interventions and clinical trials' design.


Assuntos
Esclerose Amiotrófica Lateral , Insuficiência Respiratória , Idoso , Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/diagnóstico , Diagnóstico Tardio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Estudos Retrospectivos
19.
Eur Neurol ; 83(6): 626-629, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296894

RESUMO

Cervical spondylogenic myelopathy (CSM) represents a common differential diagnosis for spinal onset Amyotrophic Lateral Sclerosis (ALS). Identifying occurrence of ALS in patients with CSM may be challenging. We evaluated the accuracy of Awaji criteria in the diagnosis of ALS in a cohort of patients with CSM. We screened all patients attending Turin ALS Center during the 2006-2018 period. We selected only patients for whom cervical cord MRI showed radiological signs of CSM. All patients underwent electromyography (EMG), and Awaji criteria were used for diagnosis of clinically probable ALS. All patients were followed up clinically for at least 6 months, and ALS diagnosis was eventually confirmed according to El-Escorial revised criteria, based on disease progression. Of 2,059 patients screened, in 42 cases, MRI showed signs of CSM; CSM incidence and prevalence risks were 0.16 and 2.04%, respectively. Based on clinical progression, 72.7% of patients were diagnosed as CSM and 27.3% as CSM + ALS. At EMG 6 (18.2%) patients fulfilled the criteria for ALS, 5 of them (83.3%) during clinical follow-up were diagnosed as clinical definite ALS + CSM. Accuracy of Awaji criteria in diagnosing ALS was good (AUC = 0.757, p = 0.03). Sensitivity and specificity of Awaji criteria were, respectively, 55.6 and 95.8%. Positive predictive value was 83.3%, while negative predictive value was 85.2%. CSM-ALS comorbidity is a relatively common problem in clinical practice. To better choose patients who could benefit from surgery, EMG should be performed in CSM patients, due to its good accuracy in recognizing ALS.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/epidemiologia , Doenças da Medula Espinal/epidemiologia , Adulto , Idoso , Estudos de Coortes , Comorbidade , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
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.

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