Cerebrospinal Fluid and Clinical Profiles in Adult Type 2–3 Spinal Muscular Atrophy Patients Treated with Nusinersen: An 18-Month Single-Centre Experience

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

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Understanding the relationship between the 32-item motor function measure and daily activities from an individual with spinal muscular atrophy and their caregivers’ perspective: a two-part study

BMC Neurology ◽

10.1186/s12883-021-02166-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tina Duong ◽

Jessica Braid ◽

Hannah Staunton ◽

Aurelie Barriere ◽

Fani Petridis ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Function ◽

Online Survey ◽

Muscular Atrophy ◽

Qualitative Interviews ◽

Functional Abilities ◽

Type 3 ◽

The Relationship ◽

Function Measure

Abstract Background The 32-item Motor Function Measure (MFM32) is a clinician-reported outcome measure used to assess the functional abilities of individuals with neuromuscular diseases, including those with spinal muscular atrophy (SMA). This two-part study explored the relationship between the functional abilities assessed in the MFM32 and activities of daily living (ADLs) from the perspective of individuals with Type 2 and Type 3 (non-ambulant and ambulant) SMA and their caregivers through qualitative interviews and a quantitative online survey. Methods In-depth, semi-structured, qualitative interviews were conducted with individuals with SMA and caregivers from the US. Subsequently, a quantitative online survey was completed by individuals with SMA or their caregivers from France, Germany, Italy, Poland, Spain, Canada, the United States (US) and the UK. In both parts of the study, participants were asked to describe the ADLs considered to be related to the functional abilities assessed in the MFM32. Results from the qualitative interviews informed the content of the quantitative online survey. Results Qualitative interviews were conducted with 15 adult participants, and 217 participants completed the quantitative online survey. From the qualitative interviews, all of the functional abilities assessed in the patient-friendly MFM32 were deemed as related to one or more ADL. The specific ADLs that participants considered related to the patient-friendly MFM32 items could be grouped into 10 key ADL domains: dressing, mobility/transferring, self-care, self-feeding, reaching, picking up and holding objects, physical activity, writing and technology use, social contact/engagement, toileting and performing work/school activities. These results were confirmed by the quantitative online survey whereby the ADLs reported to be related to each patient-friendly MFM32 item were consistent and could be grouped into the same 10 ADL domains. Conclusion This study provides in-depth evidence from the patient/caregiver perspective supporting the relevance of the patient-friendly MFM32 items to the ADLs of individuals with Type 2 and Type 3 SMA.

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Natural history of Type 2 and 3 spinal muscular atrophy: 2‐year NatHis‐SMA study

Annals of Clinical and Translational Neurology ◽

10.1002/acn3.51281 ◽

2020 ◽

Author(s):

Mélanie Annoussamy ◽

Andreea M. Seferian ◽

Aurore Daron ◽

Yann Péréon ◽

Claude Cances ◽

...

Keyword(s):

Natural History ◽

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

History Of

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Regular Exercise Prolongs Survival in a Type 2 Spinal Muscular Atrophy Model Mouse

Journal of Neuroscience ◽

10.1523/jneurosci.1245-05.2005 ◽

2005 ◽

Vol 25 (33) ◽

pp. 7615-7622 ◽

Cited By ~ 68

Author(s):

C. Grondard

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Regular Exercise ◽

Model Mouse

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Improvement in Fine Manual Dexterity in Children with Spinal Muscular Atrophy Type 2 after Nusinersen Injection: A Case Series

Children ◽

10.3390/children8111039 ◽

2021 ◽

Vol 8 (11) ◽

pp. 1039

Author(s):

Minsu Gu ◽

Hyun-Ho Kong

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Function ◽

Daily Living ◽

Muscular Atrophy ◽

Case Series ◽

Manual Dexterity ◽

Gross Motor ◽

Spinal Muscular Atrophy Type ◽

Gross Motor Function

Although nusinersen has been demonstrated to improve motor function in patients with spinal muscular atrophy (SMA), no studies have investigated its effect on fine manual dexterity. The present study aimed to investigate the ability of nusinersen to improve fine manual dexterity in patients with SMA type 2. A total of five patients with SMA type 2 were included. The Hammersmith Functional Motor Scale (expanded version) (HFMSE) and Purdue Pegboard (PP) tests were used to evaluate gross motor function and fine manual dexterity, respectively, until 18 months after nusinersen administration. HFMSE scores improved by 3–10 points (+13–53%) in all patients following nusinersen administration. PP scores also improved in all patients, from 4 to 9 points (+80–225%) in the preferred hand and from 3 to 7 points (+60–500%) in the non-preferred hand. These results suggest that nusinersen treatment improved both gross motor function and fine manual dexterity in children with SMA type 2. Addition of the PP test may aid in evaluating the fine manual dexterity essential for activities of daily living in these patients.

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