Cognitive Impairment in Adult Patients with 5q-Associated Spinal Muscular Atrophy

Kizina, Kathrin; Akkaya, Yakup; Jokisch, Daniel; Stolte, Benjamin; Totzeck, Andreas; Munoz-Rosales, Juan; Thimm, Andreas; Bolz, Saskia; Brakemeier, Svenja; Pul, Refik; Aslan, Derya; Hackert, Jana; Kleinschnitz, Christoph; Hagenacker, Tim

doi:10.3390/brainsci11091184

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…Recent comparative studies with ALS patients and controls have reported no considerable cognitive impairment in adult patients with SMA [ 9 , 10 ]. However, a trend towards lower cognitive performance in comparison to healthy controls was supposed, emphasizing SMA as a multi-systemic disorder [ 11 ]. Yet, there is little information about the effect of nusinersen on neuropsychological functions.…”

Section: Discussionmentioning

confidence: 99%

“…However, executive function inversely correlated with motor function, suggesting a compensation to physical restrictions in SMA [ 10 ]. In contrast, lower IQ index scores were found for working memory and perceptual reasoning in patients with SMA type 2 than in general population, encouraging SMA as a multi-systemic disease and disapproving the hypothesis of improved cognitive skills as a compensation for physical impairment [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

et al. 2023

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Background Spinal muscular atrophy (SMA) is a genetic neuromuscular disease caused by mutations of the SMN1 gene. Deficient SMN protein causes irreversible degeneration of alpha motor neurons characterized by progressive muscle weakness and atrophy. Considering that SMA is a multi-systemic disorder and SMN protein was found to be expressed in cortical structures, the cognitive profile of adult patients with SMA has recently been of particular interest. With nusinersen, a novel, disease-modifying drug has been established, but its effects on neuropsychological functions have not been validated yet. Aim of this study was to investigate the cognitive profile of adult patients with SMA during treatment initiation with nusinersen and to reveal improvement or deterioration in cognitive performance. Methods This monocentric longitudinal study included 23 patients with SMA type 2 and 3. All patients were assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) before and after 14 months of treatment initiation with nusinersen. Additionally, motor function was evaluated by Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Results Of the treatment-naive patients, only three were below the age- and education-matched cut-off for cognitive impairment in the ECAS total score. Significant differences between SMA type 2 and 3 were only detected in the domain of Language. After 14 months of treatment, patients showed significant improvement of absolute scores in all three ALS-specific domains, in the non-ALS-specific domain of Memory, in both subscores and in the ECAS total score. No associations were detected between cognitive and functional outcome measures. Conclusions In some adult patients with SMA abnormal cognitive performance in ALS-specific functions of the ECAS was evident. However, the presented results suggest no clinically significant cognitive changes during the observed treatment period with nusinersen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

et al. 2023

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“…Interestingly, similar to ALS, SMA exhibits SMN protein deficiency on the pathogenetic molecular pathway that is thought to play a crucial role in brain development (38). In a study by Kizina et al the Wechsler Adult Intelligence Scale (Fourth edition), an internationally recognized and validated intelligence quotient (IQ) test, was used to measure major intelligence components of adult SMA patients (10). In their study, SMA type III patients showed a trend of lower IQ scores.…”

Section: Discussionmentioning

confidence: 99%

“…However, similar to Amyotrophic Lateral Sclerosis (ALS), which is characterized by a progressive deterioration and neurodegeneration of motor neurons, patients with SMA may also have cognitive deficits. Recent studies reported that the cognitive performance of SMA patients was below average (10,11). Although SMA is widely known as a spinal motor neuron disease, recent evidence has indicated that it is a multiorgan disease with disease involvement of several non-motor regions (12).…”

Section: Introductionmentioning

confidence: 99%

Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment

Hu,

Wei,

et al. 2023

Front. Neurol.

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ObjectiveSpinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the spinal cord. It remains uncertain whether the cognitive performance of adult patients with SMA is impaired. The objective of this study was to assess the cognitive profile of adult Chinese patients with SMA and the association between clinical features and cognitive ability, particularly executive function.MethodsThis cross-sectional study included 22 untreated adult patients with type III SMA and 20 healthy subjects. The following variables were assessed: general intelligence, memory, attention, language, executive function, depression, anxiety, and other demographic and clinical parameters. In addition, physical function was evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT).ResultsSMA patients had lower scores than healthy subjects in the Verbal Fluency Test, Stroop effect, Total Errors, Perseverative Responses, Perseverative Errors, and Non-perseverative Errors in the Wisconsin Card Sorting Test, showing impaired abilities of SMA patients in executive function. In the Attention Network Test (ANT), the results indicated that the SMA patients also had selective deficits in their executive control networks. Ambulant patients had better executive function test performance than non-ambulant ones. Compromised executive abilities in patients with SMA were correlated with a younger age at onset, poorer motor function, and higher levels of anxiety and depression.ConclusionOur study presented the distribution of cognitive impairment in a Chinese cohort with SMA. Patients with type III SMA showed selective deficits in executive function, which may be associated with disease severity, physical impairment, depression and anxiety. Future cognitive studies, accounting for motor and emotional impairment, are needed to evaluate if executive impairment is driven by specific brain changes or by those confounding factors.

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“…Existing data show that a reduction of SMNprotein does not have a severe effect on the development of cognitive function in adults with SMA. Nevertheless, the mean intelligence quotient (IQ) in SMA patients has been contradictorily described as above [33] or below average compared to healthy subjects [15,17,28].…”

Section: Introductionmentioning

confidence: 99%

Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening

Kölbel,

Kopka,

Modler

et al. 2023

Journal of Neuromuscular Diseases

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Objective: Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains largely unknown. Methods: 40 of 47 eligible SMA patients (23 females/17 males) from 39 families identified through newborn screening between January 2018 and December 2020 underwent developmental testing using Bayley III (BSID) after the 2 years of age. The mean age was 29.25 months (23–42 months). 17 patients had 2, 11 patients had 3 and 12 patients had ≥4 copies of SMN2. Results: cognitive scale: mean 94.55 (SD 24.01); language scale: mean 86.09 (SD 26.41); motor scale: 81.28 (SD 28.07). Overall, the cognitive scales show that 14 children were below average, 20 children were average and 6 children were above average. 10/14 children with below average scores had 2 SMN2 copies. The post-hoc pairwise comparisons showed that the cognition main scale was significantly more sensitive to the number of SMN2 copies than the motor main scale of the BSID (MΔ= 10.27, p = 0.014). There is also evidence that cognition scored higher than the language main scale (MΔ= 7.11, p = 0.090). Conclusion: The impaired cognitive development of SMA children with 2 SMN2 copies, despite early initiation of therapy, underscores the critical role of the SMN protein in the early stages of brain development.

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Cognitive Impairment in Adult Patients with 5q-Associated Spinal Muscular Atrophy

Cited by 11 publications

References 34 publications

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment

Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening

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