Objective: To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based ...cohort of Italian patients. Methods: A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). Results: At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. Conclusions: This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeat expansion in
C9orf72
gene (
C9orf72
-HRE) is the most frequent genetic ...cause of ALS. Since many ALS pedigrees showed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in
NIPA1
(non-imprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for
C9orf72
-HRE patients with contrasting findings. To disclose the possible role of
NIPA1
GCG repeat length as modifier of the disease risk in
C9orf72
-HRE carriers, we analyzed a large cohort of 532 Italian ALS cases enriched in
C9orf72
-HRE carriers (172 cases) and 483 Italian controls. This sample size is powered (92% power,
p
= 0.05) to replicate the modifier effect observed in literature. We did not observe higher frequency of
NIPA1
long alleles (> 8 GCG) in
C9orf72
-HRE carriers (3.5%) compared with
C9orf72
-HRE negative patients (4.1%) and healthy controls (5%). For the latter comparison, we meta-analyzed our data with currently available literature data, and no statistically significant effect was observed (
p
= 0.118). In conclusion, we did not confirm a role of
NIPA1
repeat length as a modifier of the
C9orf72
ALS disease risk.
Background
Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the ...patient’s right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV).
Objective
To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice.
Methods
We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology.
Results
Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (
p
0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team.
Conclusions
Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved.
A case of late-onset OCD developing PLS and FTD Bersano, Enrica; Sarnelli, Maria Francesca; Solara, Valentina ...
Amyotrophic lateral sclerosis and frontotemporal degeneration,
08/2018, Letnik:
19, Številka:
5-6
Journal Article
Recenzirano
We describe a 64-year-old woman, suffering from late-onset obsessive-compulsive disorder (OCD) from the age of 57, who developed dysarthria and dysphagia, spastic diplegic, and proximal muscles ...weakness. Needle electromyography showed no active denervation. Neuropsychological evaluation showed intact cognitive functioning. We diagnosed upper motor neuron disease (MND), with no known genetic correlates. Brain magnetic resonance (MRI) detected bilateral hippocampal atrophy with sclerosis of right hippocampus. 18F-FDG positron emission tomography (PET) showed moderate right temporal cortex thinning. Six months later, motor and behavioral symptoms worsened. Neuropsychological examination revealed long-term memory deficit and executive dysfunction. MRI and PET evidenced severe worsening of atrophy in temporal and frontal lobes. Four years later a definitive diagnosis of primary lateral sclerosis (PLS) and FTD was made. To our knowledge, this is the first report of PLS and FTD with OCD at onset.
To analyze the frequency and clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) with intermediate-length (CAG) expansion (encoding 27-33 glutamines, polyQ) in the ATXN2 ...gene, in a population-based cohort of Italian patients with ALS (discovery cohort), and to replicate the findings in an independent cohort of consecutive patients from an ALS tertiary center (validation cohort).
PolyQ repeats were assessed in 672 patients with incident ALS in Piemonte and Valle d'Aosta regions, Italy, in the 2007-2012 period (discovery cohort); controls were 509 neurologically healthy age- and sex-matched subjects resident in the study area. The validation cohort included 661 patients with ALS consecutively seen between 2001 and 2013 in the ALS Clinic Center of the Catholic University in Rome, Italy.
In the discovery cohort, the frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (19 patients vs 1 control, p = 0.0001; odds ratio 14.8, 95% confidence interval 1.9-110.8). Patients with an increased number of polyQ repeats had a shorter survival than those with <31 repeats (median survival, polyQ ≥31, 1.8 years, interquartile range IQR 1.3-2.2; polyQ <31, 2.7 years, IQR 1.6-5.1; p = 0.001). An increased number of polyQ repeats remained independently significant at multivariable analysis. In the validation cohort, patients with ≥31 polyQ repeats had a shorter survival than those with <31 repeats (median survival, polyQ ≥31, 2.0 years, IQR 1.5-3.4; polyQ <31, 3.2 years, IQR 2.0-6.4; p = 0.007).
ATXN2 polyQ intermediate-length repeat is a modifier of ALS survival. Disease-modifying therapies targeted to ATXN2 represent a promising therapeutic approach for ALS.
In the isolated population of Sardinia, a Mediterranean island, ∼25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of ...the C9ORF72 gene.
To describe the co-presence of two genetic mutations in two Sardinian ALS patients.
We identified two index ALS cases carrying both the p.A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene.
The index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p.A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus.
Our data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course.
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