OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.
Male ; Female ; Humans ; Child ; Albuterol/therapeutic use* ; Prospective Studies ; Muscular Atrophy, Spinal/drug therapy* ; Spinal Muscular Atrophies of Childhood/drug therapy* ; Treatment Outcome

Consensus ; Humans ; Muscular Atrophy, Spinal/therapy* ; Spinal Muscular Atrophies of Childhood

OBJECTIVES: To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA. METHODS: A retrospective analysis was performed on the medical data and survival status of 117 children with SMA. RESULTS: Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis ( CONCLUSIONS There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.
Child ; Homozygote ; Humans ; Infant ; Muscular Atrophy, Spinal/genetics* ; Retrospective Studies ; Sequence Deletion ; Spinal Muscular Atrophies of Childhood/genetics*

We report two pediatric cases with Hirayama disease—a 16-year-old boy with a left wrist drop and a 14-year-old-boy with weakness and muscle atrophy of right hand. Motor nerve conduction study revealed decreased motor nerve action potential amplitudes in the ulnar nerve and radial nerve of the affected hands. The former patient showed normal magnetic resonance imaging (MRI) of the cervical spine, but the latter showed mild, asymmetric thinning of the anterior spinal cord at levels C5 to C7. Following active rehabilitation and avoidance of neck flexion, no further progression of neurological findings was noticed. These clinical findings were typical of Hirayama disease. We show that timely and accurate diagnosis for Hirayama disease is possible with awareness of disease history, careful physical examination, and the use of neurophysiological studies and MRI studies.
Action Potentials ; Adolescent ; Diagnosis ; Hand ; Humans ; Magnetic Resonance Imaging ; Male ; Muscular Atrophy ; Neck ; Neural Conduction ; Physical Examination ; Radial Nerve ; Rehabilitation ; Spinal Cord ; Spinal Muscular Atrophies of Childhood ; Spine ; Ulnar Nerve ; Wrist

Hirayama disease, juvenile muscular atrophy of the distal upper limb, is a rare disease predominantly affecting the anterior horn cells of the cervical spinal cord in young men. This cervical myelopathy is associated with neck flexion. It should be suspected in young male patients with a chronic history of weakness and atrophy involving the upper extremities followed by clinical stability in few years. Herein, we report 2 cases of Hirayama disease on emphasis of diagnostic approach and describe the pathognomonic findings at flexion magnetic resonance imaging.
Anterior Horn Cells ; Atrophy ; Cervical Cord ; Humans ; Magnetic Resonance Imaging ; Male ; Motor Neuron Disease* ; Motor Neurons* ; Neck ; Rare Diseases ; Spinal Cord Diseases ; Spinal Muscular Atrophies of Childhood ; Upper Extremity

BACKGROUNDAmyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders.

METHODSWe compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls.

RESULTSThe ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients.

CONCLUSIONSThe different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

Action Potentials ; Adult ; Aged ; Amyotrophic Lateral Sclerosis ; pathology ; physiopathology ; Diagnosis, Differential ; Female ; Hand ; pathology ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; physiopathology ; Muscular Atrophy ; pathology ; physiopathology ; Retrospective Studies ; Spinal Muscular Atrophies of Childhood ; pathology ; Spondylosis ; pathology

OBJECTIVETo identify whether there is significant changes between the cervical neutral F-waves and cervical flexion F-waves in the patients with Hirayama disease.

METHODSThis study was performed on 25 normal subjects and 22 male patients with identified Hirayama disease (age: 15 to 44 years; height: 165 to 183 cm; duration: 6 to 240 months) between May 2010 and March 2014. Both cervical flexion F-wave (cervical flexion 45 °, 30 minutes) and conventional F-waves to median nerve stimulation and to ulnar nerve stimulation were performed in all subjects bilaterally.

RESULTSwere analyzed by t-test or Fisher exact probability.

RESULTSIn the normal subjects, all measurements of the bilateral F-waves didn't have any difference between the cervical flexion position and the cervical neutral position. On the cervical neutral position, the persistence (t = 5.209, P = 0.000), average latencies (t = 4.731, P = 0.022) and minimal latencies (t = 23.843, P = 0.006) of ulnar F-wave on the symptomatic heavier side from the patients with identified Hirayama disease were significantly lower or longer than those from the normal subjects, and the repeat F-waves were found in 3 patients (13.6%). On the symptomatic lighter side, the ulnar F-waves only had lower persistence (t = 22.306, P = 0.001) along with 5 repeat F-waves. Only lower persistence were found in the median F-wave on the both side (higher side t = 23.696, P = 0.000; lighter side t = 23.998, P = 0.000), along with 5 (22.7%) repeat F-waves on the symptomatic heavier side and 6 (27.3%) ones on the symptomatic lighter side. After cervical flexion maintaining 30 minutes, the increased maximal amplitudes (t = -2.552, P = 0.019), average amplitudes (t = -3.322, P = 0.003), duration (t = -3.323, P = 0.00), persistence (t = -2.604, P = 0.017) and frequency of repeat F-waves (9/22, 41%) (P = 0.044) were found on the symptomatic heavier side of ulnar F-wave, and 5 of 10 absent ulnar F-wave on the cervical neutral position were also recover. The median F-wave on the symptomatic heavier side mainly had increased maximal amplitude (t = -3.847, P = 0.001), average amplitudes (t = -2.188, P = 0.040) and persistence (t = -2.421, P = 0.025), and 1 of 6 absent median F-wave on the cervical neutral position were also recover after cervical flexion.

CONCLUSIONThe cervical flexion F-waves have significant regular changes compared to the cervical neutral F-waves in patients with Hirayama diseases, especially maximal and average amplitudes of F-waves.

Adolescent ; Adult ; Humans ; Male ; Neck ; Range of Motion, Articular ; Spinal Muscular Atrophies of Childhood ; physiopathology ; Ulnar Nerve ; Young Adult

Monomelic amyotrophy (MMA), also known as Hirayama disease, is a sporadic juvenile muscular atrophy in the distal upper extremities. This disorder rarely involves proximal upper extremities and presents minimal sensory symptoms with no upper motor neuron (UMN) signs. It is caused by anterior displacement of the posterior dural sac and compression of the cervical cord during neck flexion. An 18-year-old boy visited our clinic with a 5-year history of left upper extremity pain and slowly progressive weakness affecting the left shoulder. Atrophy was present in the left supraspinatus and infraspinatus. On neurological examination, positive UMN signs were evident in both upper and lower extremities. Electrodiagnostic study showed root lesion involving the fifth to seventh cervical segment of the cord with chronic and ongoing denervation in the fifth and sixth cervical segment innervated muscles. Cervical magnetic resonance imaging (MRI) showed asymmetric cord atrophy apparent in the left side and intramedullary high signal intensity along the fourth to sixth cervical vertebral levels. With neck flexion, cervical MRI revealed anterior displacement of posterior dural sac, which results in the cord compression of those segments. The mechanisms of myelopathy in our patient seem to be same as that of MMA. We report a MMA patient involving proximal limb with UMN signs in biomechanical concerns and discuss clinical importance of cervical MRI with neck flexion. The case highlights that clinical variation might cause misdiagnosis.
Adolescent ; Atrophy ; Biological Assay ; Denervation ; Diagnostic Errors ; Extremities ; Humans ; Lower Extremity ; Magnetic Resonance Imaging ; Male ; Motor Neurons* ; Muscles ; Neck ; Neurologic Examination ; Shoulder ; Spinal Cord Diseases ; Spinal Muscular Atrophies of Childhood ; Upper Extremity

OBJECTIVETo assess the association of copy number variations of SMN1, SMN2, NAIP, GTF2H2 and H4F5 genes with clinical classification of spinal muscular atrophy in children, and determine the copy number of the SMN gene among pregnant women. A carrier screening was also performed in Sichuan province.

METHODSThe copy number variations of the above genes among 53 confirmed SMA patients were determined with MLPA technique. The copy number variations were analyzed by the Fisher's exact test. Deletion of exon 7 in the SMN1 gene was screened with denaturing high performance liquid chromatography (DHPLC) for 427 pregnant women.

RESULTSAmong the 53 cases of type I, II, and III SMA patients, the rate of homozygous deletion of both exons 7 and 8 of the SMN1 gene were 100%, 94.44% and 87.50%, respectively, whereas those of homozygous deletion of exon 7 of SMN1 gene were 0, 5.56%, and 12.50%, respectively. The patients with 1, 2, 3, and 4 copies of exon 7 of the SMN2 gene were 11.32%, 67.92%, 13.21% and 7.55%, respectively. The patients with 0, 1, and 2 copies of exon 5 of NAIP gene were 11.32%, 62.26%, and 26.42%, respectively. No deletion was detected in GTF2H2 or H4F5 genes. The heterozygous loss rate of exon 7 in SMN gene in the pregnant women population of Sichuan region was approximately 2.11%.

CONCLUSIONCopy number variations of SMN2 and NAIP genes in patients are related to SMA clinical types (P < 0.05). In contrast, there was no relationship between SMA clinical types and deletion of exons 7 and 8 in the SMN1 gene (P > 0.05). Analysis of copy number change in SMN1 gene can assist SMA carrier screening. However, when the general population without SMA family history is screened for disease-causing genes, it should be noted that the type "2+0" carriers may affect the screening result, and the result should be interpreted with caution.

Adolescent ; Child ; Child, Preschool ; DNA Copy Number Variations ; Female ; Genetic Carrier Screening ; Humans ; Infant ; Male ; Neuronal Apoptosis-Inhibitory Protein ; genetics ; Spinal Muscular Atrophies of Childhood ; genetics ; Survival of Motor Neuron 1 Protein ; genetics

BACKGROUNDHirayama disease is a juvenile muscular atrophy of the distal upper extremities and affects mainly young males. The present study aimed to investigate the neuroelectrophysiological characteristics of Hirayama disease.

METHODSWe retrospectively analyzed the neural conduction velocity (NCV) parameters and needle-electrode electromyograms (EMG) of 14 patients with Hirayama disease. According to the clinical features of the patients, NCV was performed on affected upper-limb including median nerves and ulnar nerves, while EMG was selectively performed on upper and lower extremities, sternocleidomast and thoracic paraspinal muscles.

RESULTSThe median nerves of all affected upper limbs of patients with Hirayama disease had normal conduction velocities and compound motor action potentials (CMAPs). The ulnar nerves of all affected upper limbs also had normal conduction velocities. Of the 16 measured ulnar nerves of the affected upper limbs, eight had normal CMAPS, while the other eight showed CMAPs below the normal value by < 20%. All patients had neurogenic injury on the affected side in muscles innervated by anterior horn cells at the lower cervical region (C7-8, T1). Four patients had unilateral upper-limb muscle neurogenic injury on the affected side. Seven patients had bilateral upper-limb muscle neurogenic injury, while only two patients experienced bilateral upper-limb muscle atrophy/weakness. The other three patients showed extensive neurogenic injury (unilateral upper-limb muscle atrophy/weakness in one patient, bilateral symptoms in the other two patients).

CONCLUSIONSElectromyographic examination showed that the majority of Hirayama disease patients exhibited characteristic segmental injury in the anterior horn of the lower cervical region, while a few patients exhibited extensive neurogenic injury. These data suggest that the actual influence of Hirayama disease may be more extensive than indicated by the clinical presentations.

Adolescent ; Adult ; Electromyography ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Conduction ; physiology ; Retrospective Studies ; Spinal Muscular Atrophies of Childhood ; physiopathology ; Young Adult