Clinical and radiological profile of patients with spinal muscular atrophy type 4

Abstract

Background and purposeSpinal muscular atrophy (SMA) is the most important cause of motor neuron disease in childhood, and continues to represent the leading genetic cause of infant death. Adulthood‐onset SMA (SMA type 4) is rare, with few isolated cases reported. The objective of the present study was to describe a cohort of patients with SMA type 4.MethodsA cross‐sectional study was conducted to characterize clinical, genetic, radiological and neurophysiological features of patients with adulthood‐onset SMA. Correlation analysis of functional assessment with genetic, radiological and neurophysiological data was performed.ResultsTwenty patients with SMA type 4 were identified in a Brazilian cohort of 227 patients with SMA. The most common clinical symptom was limb‐girdle muscle weakness, observed in 15 patients (75%). The most frequent neurological findings were absent tendon reflexes in 18 (90%) and fasciculations in nine patients (45%). Sixteen patients (80%) had the homozygous deletion of exon 7 in the SMN1 gene, with 12 patients (60%) showing four copies of the SMN2 gene. The functional scales Hammersmith Functional Motor Scale Expanded, Amyotrophic Lateral Sclerosis Functional Rating Scale Revised, Revised Upper Limb Module and Spinal Muscular Atrophy Functional Rating Scale, as well as the six‐minute walk and the Time Up and Go tests showed a correlation with duration of disease. Motor Unit Number Index was correlated both with duration of disease and with performance in functional assessment. Radiological studies exhibited a typical pattern, with involvement of biceps femoris short head and gluteus minimus in all patients.ConclusionThis study represents the largest cohort of patients with SMA type 4 and provides functional, genetic, radiological and neurophysiological features that can be used as potential biomarkers for the new specific genetic therapies for SMA.

The Importance of Digging into the Genetics of SMN Genes in the Therapeutic Scenario of Spinal Muscular Atrophy

“…This model only differs from Calucho's correlations in type III patients, since it establishes the expected SMN2_CN to be 4 instead of 3 and 4 indistinctly [9]. In the recent literature, the correlation described by Calucho et al (2018) is mainly maintained [28][29][30][31][32], although some exceptions can be found. Interestingly, the proportion of type I patients with 3 SMN2 genes was increased in some cohorts, reaching 57% among SMA I patients, while Calucho's compilation reported only 23% [33,34].…”

Muscle MRI in motor neuron diseases: a systematic review

“…Among these 28 articles, there were 14 MND/ ALS (18-31), 13 SMA (32-44) and three SBMA (20,29,45) patient groups. There were eight multiple-region (21,(24)(25)(26)28,29,37,45), 13 lower-limb (19,20,(32)(33)(34)(35)(36)38,(40)(41)(42)(43)(44), one paraspinal (30), three bulbar (18,22,23) and three whole-body (27,31,39) studies. These papers are summarized in Tables 1 and 2.…”

“…Studies in motor neuron diseases have applied quantitative (18,19,(22)(23)(24)29,(31)(32)(33)35,39,(42)(43)(44)(45), qualitative (18,20,21,25,26,(28)(29)(30)(32)(33)(34)(36)(37)(38)(39)(40)(41)45), and semi-quantitative (27,31) techniques, often in combination, and imaging protocols vary between studies. Most qualitative studies used the fivepoint Mercuri scale, which grades change from an early moth-eaten appearance to muscle replacement by connective tissue and fat (46).…”

“…The risk of bias tools revealed a generally robust study design. Frequent issues identified were omission of a control group (32,33,36,37,(39)(40)(41)43), lack of blinding (18)(19)(20)23,31,(34)(35)(36)(39)(40)(41)(42)(43)45) and inadequate ascertainment of disease status (23,25,40). Only four studies justified the sample size (22,27,31,38).…”

“…Despite small sample sizes, these studies provided proof-of-concept for muscle MRI applications in therapeutic trials. In 2021, fatty infiltration and atrophy were qualitatively assessed in 20 genetically-confirmed SMA IV patients (34). Relative preservation of tibialis posterior, fibular and extensor digitorum longus, and sparing of the medial thigh compartment was seen.…”