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Spinal muscle atrophy Shady Mahmoud Assistant lecturer Orthopaedic surgery department - Ain Shams University

Spinal muscle atrophy

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Spinal muscle atrophy

Shady MahmoudAssistant lecturer

Orthopaedic surgery department - Ain Shams University

A neuromuscular disease of infancy, childhood, and adulthood, that effects the survival and function of the anterior horn cells of the spinal cord.

It is characterized by progressive, predominantly proximal and symmetric muscle weakness.

Sensation and cognition are preserved,

It is one of the leading genetic causes of infant mortality, with an incidence of 1 in 6,000 to 1 in 10,000 reported in a European population.

Genetics  A deletion of the telomeric gene survival motor neuron 1 (SMN1)

located on chromosome 5 (5q13) was found in 98.6% of patients (AR disease)

There are two copies of SMN genes (telomeric and centromeric) that encodes neuronal apoptosis inhibitory protein.

Spinal muscular atrophy involves the telomeric one (SMN 1).

The SMN protein is critical to RNA metabolism, and patients with SMA have a shortage of SMN protein, leading to motor neuron death.

The severity of disease is mitigated by the number of copies of SMN2 gene in each cell. Multiple copies of SMN2 gene allow for production of SMN proteins, reducing disease severity, and allowing the disease to present later in life.However, predicting SMA type based on SMN2 levels is not recommended because of poor correlation between genotype and phenotype.

Classification (based on age of onset)

Type Name Presentation prognosis

Type 1 Acute Werdnig-Hoffman disease

Present < 6 monthsClassic floppy baby Poor head control, difficulty of swallowing and feeding Tongue atrophy and fasciculations Limb and trunk hypotonia, absent deep tendon reflexes, and intercostal muscle weakness

Poor, usually die by 2 yrs

Type 2 Chronic Werdnig-Hoffman disease

Present 6 -18 months Delayed motor milestones, the functional ability to maintain a sitting position without support Scoliosis, joint contractures, and intercostal muscle weakness

Expected to live into their twenties and beyond

Type 3 Kugelberg-Welander disease

Present > 18 months Ambulant, hand tremors, muscle fasciculations Scoliosis, hip abductor weakness, resulting in Trendelenburg gait or hip extensor weakness that results in increased lumbar lordosis  

Those who maintain ambulation is not markedly different from that of the non SMA population

Type 4 present in 2nd - 3rd decade mild motor impairment

As type 3

ClinicallyIt is a pure LMNL Suspected in any child with hyotonia, areflexia, bilateral symmetrical

proximal weakness, and fasciculations

Main considerations: 1) Non orthopaedic:a) Developmental delayb) Gastroeneterologyc) Pulmonary

2) Orthopaedic:a) Scoliosisb) Contrcturesc) Hip disloction

Investigations Blood tests: a) Targeted mutation analysis:

deletions of exon 7 and 8, SMN1 gene (95-98%) SMN2 copy countresults of this blood tests are available in an average of 2 to 4 wks

b) Creatine kinase enzyme: normal

Electrodiagnostic studies:a) Motor nerve conduction study: abnormal b) Sensory nerve conduction study: normalc) EMG: denervation potentials

Biopsy (rare): a) skeletal muscle: atrophic fibres with islands of group hypertrophy,3 b) spinal cord: shows severe loss of motor neuron in the anterior horn

region

The spinal cord anterior horn region shows an absence of motor neurons in a patient (B) compared with those in the healthy control (A).

Skeletal muscle of a patient (D) shows hypertrophic fibres (hollow arrowhead) surrounded by group atrophy (green arrowhead) compared with healthy fibres with uniform

morphology in normal infantile muscle (C).

Developmental delay Intelligence is normal

Gross motor milestonesSMA1: no significant milestones are achievedSMA2 and 3: may lose mobility as they age

Fine motor skillsVariable – based on upper extremity

involvement

Gastroeneterology

Failure to thriveDysphagia: poor coordination of swallow and

airway closureChewing difficulties: masticators and facial

weaknessFatigue: decreased efficiency of pre-oral, oral

and pharyngeal phases

Gastroesophageal reflux: Increased risk of aspiration

Pulmonary

Major cause of morbidity and mortality in SMA 1 and 2.

Risk factors: Weak inspiratory and expiratory muscles Scoliosis – older SMA 2 and 3 Progressive restrictive lung disease Swallowing dysfunction and reflux Progression to respiratory failure via recurrent

infection and nocturnal desaturation and hypoventilation

Management: mainly supportive Formal swallow evaluation (OPM) G-tube placement Dietary modifications Medication management for reflux

School modifications to accommodate physical disabilities

PT/OT – functional skills Pulmonary evaluation every 6 months is

recommended

Scoliosis

Prevalence of scoliosis in patients with SMA ranges from 60% to 95% in several series.

patients with type 1 or 2 SMA have larger spinal curves and more rapidly progressive scoliosis.

curves are typically right sided thoracolumbar long and C-shaped.

AP (A) and lateral (B) radiographs of the spine demonstrating a long, C-shaped thoracolumbar curve measuring 93° in a 12-year-old girl with type 2 spinal muscular atrophy

Non-operative: a) Observation: for small curvesb) Bracing: for larger, progressive curves. several series have reported that bracing is ineffective in

halting curve progression and may worsen the respiratory function but it may provide limited sitting support in those with collapsing curves.

The benefits of supported sitting must be weighed against the limitation of chest wall excursion caused by bracing.

Operative:Surgery is indicated for progressive deformity in spite of orthotics, and curves >70 degree

In children with a skeletal age ≤9 years a growing rod anchored distally to the pelvis is preferred.

patients with open triradiate cartilage with skeletal age >10 years PSF with pedicle screws inserted at most levels from T2 to the pelvis is done

AP (C) and lateral (D) radiographs demonstrating a thoracolumbar curve of 10° following posterior spinal fusion from T2-S1 and pelvic fixation with S2 alar iliac screws.

Contrctures Common in the hip and knee TreatmentPhysical therapy.Surgical release: controversial as the function in non-

walkers is rarely improved and recurrence is common.

Hip disloction Ambulatory patients with the mild form of SMA have a better chance

of maintaining a concentric hip than do those with severe or intermediate forms.

Hip pathology may be caused by muscle weakness, imbalance, and pelvic obliquity.

In general, attempts to reduce the hip surgically in patients with SMA have been unsuccessful (high recurrence rate if open reduction attempted).

Many theoretical concerns regarding maintenance of a non-concentric hip, including problems with sitting imbalance, difficulty with perineal care, and pain with hip range of motion relate to spastic hip and have not been found in neuromuscular disorders presenting with low tone, such as SMA.

However, further research is required to determine whether hip dislocation in patients with SMA can be tolerated over the entire lifespan or not.

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