Blepharospasm (BSP) represents one of the most common idiopathic adult-onset dystonia. A few longitudinal observations indicated progression and worsening of BSP severity within 16 years of onset. ...Information is lacking about the trend of BSP severity in the later stages of the disease.
The study comprised 15 women and 3 men that underwent a standardized video protocol at two time points: 14 ± 9 years after BSP onset and 11 ± 2 years later. BSP severity was rated by the Blepharospasm Severity Rating Scale (BSRS). Two independent observers reviewed 36 videos in a pseudo-randomized order, yielding satisfactory agreement.
Mean total severity score was 7.6 ± 3.9 years at baseline, 6.4 ± 2.5 at the last examination (p = 0.14). The last video examination showed a stable BSRS score in 14/18 patients, while the score of 4 patients decreased by two points or more, due to disappearance (n.3) or reduction (n.1) of prolonged spasms with complete rim closure. Over the long term, the BoNT dosage increased in those who improved, but remained stable in the other patients. On follow-up examination, dystonia spread to the lower face or neck in two new patients. No significant correlations emerged between disease duration and BSP severity. The presence of sensory trick significantly correlated with disease duration but not with BSP severity.
This study provides novel information on the long-term prognosis in patients with idiopathic BSP, showing that severity of BSP may not worsen in the later stages of the disease.
•The natural history of idiopathic blepharospasm is not fully known.•An earlier study shown that severity of blepharospasm increases in the initial and intermediate stages of the disease.•Our long-term longitudinal study suggests that severity may not worsen in more advanced stages of the disease.
Background
Common genes implicated in amyotrophic lateral sclerosis (ALS) development may also influence its progression rate. The C9orf72 mutations featured a faster progression rate while the ...European SOD1 mutations were associated with a slower progression. In this study, we assessed the relationship between TARDBP and ALS progression/survival.
Methods
ALS incident patients (2010–2019) were diagnosed by El Escorial revised criteria and staged over the disease course by the King’s staging system. Disease progression was analysed by Kaplan–Meier survival curves and Cox regression models, with survival measured from symptom onset to death/tracheostomy or censor date.
Results
The study population included 76 patients carrying TARDBP mutations (A382T/G295S), 28 patients carrying the C9orf72 GGGGCC expansion, and 158 patients who had no evidence of causative genetic mutations (nmALS group). TARDBP patients reached death/tracheostomy later than C9orf72 and nmALS patients, independently of possible prognostic indicators (sex, age at ALS onset, diagnostic delay, phenotype at onset, and family history of ALS). On King’s staging, the time elapsed between disease onset (King’s stage 1) and involvement of the second body region (King’s stage 2B) was similar in TARDBP and nmALS patients but longer in TARDBP than in C9orf72 patients. TARDBP patients reached King’s stages 3 and 4 later than C9orf72 and nmALS patients.
Conclusions
TARDBP patients have a better survival/prognosis than C9orf72-positive and nmALS patients. King’s staging also suggested that the higher survival rate and the slower progression associated with the TARDBP mutation could mainly be attributed to the longer time elapsed between King’s stages 2B to 3.
Introduction/Aims
Several microgeographic clusters of higher/lower incidence of amyotrophic lateral sclerosis (ALS) have been identified worldwide. Differences in the distribution of local factors ...were proposed to explain the excess ALS risk, whereas the contribution of known genetic/epigenetic factors remains unclear. The aim is to identify restricted areas of higher risk in Sardinia and to assess whether age, sex, and the most common causative genetic mutations in Sardinia (C9orf72 and TARDBP mutations) contributed to the variation in the ALS risk.
Methods
We performed an ad hoc analysis of the 10‐y population‐based incident cohort of ALS cases from a recent study of a large Sardinian area. Cluster analysis was performed by age‐ and sex‐adjusted Kulldorff's spatial scan statistic.
Results
We identified a statistically significant cluster of higher ALS incidence in a relatively large area including 34 municipalities and >100,000 individuals. The investigated genetic mutations were more frequent in the cluster area than outside. Regardless of the genetic mutations, the excess of ALS risk was significantly associated with either sex or with age ≥ 65 y. Finally, an additive interaction between older age and male sex contributed to the excess of ALS risk in the cluster area but not outside.
Discussion
Our analysis demonstrated that known genetic factors, age, and sex may contribute to microgeographic variation in ALS incidence. The significant additive interaction between older age and male sex we found in the high‐incidence cluster could suggest the presence of a third factor connecting the analyzed risk factors.
Background
While amyotrophic lateral sclerosis (ALS) incidence has increased during the last decades, structured evidence on increased prevalence is lacking. After reporting a significant yearly ...increase of ALS incidence over a 10-year period, we checked for increased prevalence in Southern Sardinia over a quinquennium.
Methods
ALS patients (El Escorial Criteria) recruited from the study area and followed at ALS Centre, University of Cagliari, were included. Prevalence was computed for January 1, 2015 and January 1, 2019 and was calculated for the overall ALS population as well as for tracheostomized and non-tracheostomized patients.
Results
We observed a non-significant trend for greater ALS prevalence in 2019 than in 2015 (18.31 per 100,000 vs. 15.26 per 100,000; rate ratio: 1.83,
p
= 0.01). By contrast, a significantly raising 2015 to 2019 ALS prevalence was observed in tracheostomized patients. No significant difference could be detected in non-tracheostomized.
Conclusions
We provided the highest prevalence rate to date reported in the worldwide literature, and also showed a non-significant raising ALS prevalence in the Sardinian population over a quinquennium. The trend in raising ALS prevalence was likely due to extended survival due to invasive interventions.
Objective
Several studies have demonstrated a higher frequency of seizures and epilepsy in Alzheimer's disease and other forms of dementia as compared with healthy elderly individuals. However, ...incidence and prevalence of epilepsy in the general population of dementia are unknown since most previous studies were performed in secondary‐tertiary referral centres. In addition, all prior studies but one provided “period” rather than “point” prevalence estimates.
Methods
We assessed point prevalence estimate of epileptic manifestations requiring antiepileptic medication in patients Alzheimer's disease, vascular dementia, and fronto‐temporal dementia from a secondary clinical setting.
Results
Point prevalence estimates were 6.4% (95% CI: 1.5 to 11.3) in Alzheimer's disease, 8.9% (95% CI: 1.4 to 16.4), in vascular dementia, and 6% (95% CI: 1.3 to 10.7) in fronto‐temporal dementia, rates that were greater than those observed in the healthy elderly population. Regardless of the etiology of dementia, epilepsy was characterized by unprovoked seizures that lacked distinguishing clinical features.
Significance
These findings support epilepsy as part of the spectrum of dementia. The similar point prevalence of definite epilepsy requiring AED treatment in Alzheimer's disease and non Alzheimer dementias raised the possibility of similar underlying mechanism of epileptogenesis. Although this was not a population‐based study, accurate point prevalence data from clinic setting would be important to better define the burden of epilepsy in dementia and the demands on health services to manage the condition.
