Clinical phenotypes and trajectories of disease progression in type 1 spinal muscular atrophy

Sanctis, Roberto De; Pane, Marika; Coratti, Giorgia; Palermo, Concetta; Leone, Daniela; Pera, Maria Carmela; Abiusi, Emanuela; Fiori, Stefania; Forcina, Nicola; Fanelli, Lavinia; Lucibello, Simona; Mazzone, Elena; Tiziano, Francesco Danilo

doi:10.1016/j.nmd.2017.09.015

Cited by 50 publications

(65 citation statements)

References 12 publications

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“…The analysis of the onset of clinical signs in our large cohort of SMA patients confirmed previous reports [3,28,29] that in the great majority of type I patients clinical signs are generally identified before 6 months of age, and less than 10% were identified after 6 months. The patients with relatively later-onset had all achieved head control and can be classified as 1.9 according to the Dubowitz decimal classification [3].…”

Section: Discussionsupporting

confidence: 90%

Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

et al. 2020

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Background The advent of new therapies has increased the need to achieve early diagnosis in Spinal Muscular Atrophy (SMA). The aim of the present study was to define the age of diagnosis in the three main types of SMA with pediatric-onset and the timing between the recognition of clinical signs and confirmed genetic diagnosis. Methods All patients with a confirmed diagnosis of type I, II, III SMA followed in 5 Italian centers were included in this study, assessing age at symptoms onset, presenting sign or symptom, age at diagnosis, interval between clinical onset and diagnosis and type of medical investigations conducted in order to obtain the diagnosis. Results The cohort included 480 patients, 191 affected by SMA type I, 210 by type II and 79 by type III. The mean age at diagnosis was 4.70 months (SD ±2.82) in type I, 15.6 months (SD ±5.88) in type II, and 4.34 years (SD±4.01) in type III. The mean time between symptom onset and diagnosis was 1.94 months (SD±1.84) in type I, 5.28 months (SD±4.68) in type II and 16.8 months (SD±18.72) in type III. Conclusions Our results suggest that despite improved care recommendations there is still a marked diagnostic delay, especially in type III. At the time new therapies are becoming available

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Section: Discussionsupporting

confidence: 90%

Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

et al. 2020

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“…The overall results in age group show a clear trend of improvement on both the CHOP INTEND and HINE-2 that is different from the negative changes observed in the untreated group in the ENDEAR study 1 and in the recent natural history studies. 15,16 An improvement was, however, also found in the infants treated between 7 and 24 months on both scales, and some improvement could also be found in the older children on the CHOP INTEND. Other factors also appeared to be important in determining the possibility of an improvement.…”

Section: Discussionmentioning

confidence: 85%

“…[13][14][15][16] In contrast, over 60% of the 84 patients improved 2 points, and over 50% improved more than 2 points. This is different from what was reported in untreated infants and children in natural history studies.…”

Section: Discussionmentioning

confidence: 92%

“…This is different from what was reported in untreated infants and children in natural history studies. [13][14][15][16] In contrast, over 60% of the 84 patients improved 2 points, and over 50% improved more than 2 points. The improvements on their CHOP INTEND were more obvious after 6 months, but a further smaller increase was also found between 6 and 12 months.…”

Section: Discussionmentioning

confidence: 92%

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Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Pane

Coratti

Sansone

et al. 2019

Annals of Neurology

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Objective: The aim of the study was to report 12-month changes after treatment with nusinersen in a cohort of 85 type I spinal muscular atrophy patients of ages ranging from 2 months to 15 years and 11 months. Methods: All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination-Section 2 (HINE-2). Results: Two of the 85 patients had 1 SMN2 copy, 61 had 2 copies, and 18 had 3 copies. In 4 patients the SMN2 copy number was not available. At baseline, the mean CHOP INTEND scores ranged between 0 and 52 (mean = 15.66, standard deviation [SD] = AE13.48), and the mean HINE-2 score was between 0 and 5 (mean = 0.69, SD = AE1.23). There was a difference between baseline and the 12-month scores on both the CHOP INTEND and the HINE-2 for the whole group (p < 0.001), the subgroups with 2 SMN2 copies (p < 0.001), and those with 3 SMN2 copies (p < 0.001). The difference was found not only in patients younger than 210 days at baseline (p < 0.001) but also in those younger than 5 years on the CHOP INTEND and younger than 2 years on the HINE-2. Interpretation: Our results, expanding the age range and the severity of type I patients treated with nusinersen over 1 year, provide additional data on the range of efficacy of the drug that will be helpful in making an informed decision on whether to start treatment in patients of different ages and severity.

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“…1.1, the more severe end of the spectrum with early, severely reduced mobility, respiratory and bulbar di culties; 1.5, the most common phenotype, with inability to raise the legs against gravity or to maintain the head posture but no overt feeding or respiratory di culties at diagnosis; 1.9, the mildest phenotypes, infants may achieve head control (2,3). The three subgroups grossly overlap with the subtypes 1 A, B and C, proposed in another classi cation more based on age of onset (3,4).…”

Section: Introductionmentioning

confidence: 99%

Oral and Swallowing Abilities Test (Orsat) for Type 1 Sma Patients: Development and Application of a New Module.

Berti¹,

Fanelli²,

Sanctis³

et al. 2020

Preprint

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Background: Swallowing is one of the most important aspects in the care of type 1 spinal muscular atrophy. Main text:The aim of this paper is to describe the development of a new tool specifically designed to record different aspects related to oral abilities, swallowing and feeding in young type1 SMA patients. We also report its application to a cohort of type 1 infants to identify possible changes during the first 24 months of life. The new tool includes a checklist with 12 questions for carers and a classification of levels of impairment.The scale was retrospectively used in 24 type 1 patients (8 females and 16 males,age range from2.3 to 24.1 months (average age: 10.8 months), classified according to the Dubowitz's decimal classification into 1.1 (n=8); 1.5 (n=8); 1.9 (n=8). There was a significant difference among the 3 subtypes both at baseline and at follow up (p<0.001). Type 1 infants had very low scores from the age of 3 months and a rapid deterioration already by 6 months; type 1.5 infants had a more variable progression but by 9 months 80% had the lowest scores. Patients with type 1.9 had better scores until the age of 1 year and had an overall better outcome. Conclusion: Our results suggest that the new tool may help to routinely capture changes over time in type 1 infants and that the trajectories of progression reflect the overall severity of the disease. The items assessing fatigue during the nursing sessions were the most frequently impaired even in infants who did not have any other obvious clinical sign of swallowing difficulties.

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Clinical phenotypes and trajectories of disease progression in type 1 spinal muscular atrophy

Cited by 50 publications

References 12 publications

Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Oral and Swallowing Abilities Test (Orsat) for Type 1 Sma Patients: Development and Application of a New Module.

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