Question 1 of 10

    Adult Spinal Muscular Atrophy (Atrophy Myelopathic Muscular)

    Adult spinal muscular atrophy is a genetic neurodegenerative disorder characterized by muscle wasting and weakness. In adults, normal life expectancy is achieved, as only mild weakness may be encountered. The diagnosis rests on confirming genetic mutations.

    This disorder is caused by the following process: hereditary.

    Presentation

    Adult spinal muscular atrophy or spinal muscular atrophy (SMA) type 4 usually begins to appear at 30 years of age and has a relatively benign course [1]. The clinical features of this disease are very similar to SMA type 3, although the adult version is less severe. Life expectancy is normal in such patients [2]. Type 1 and type 2 SMA can occur at any age between birth and 2 years.

    Patients classically present with an asymmetric weakness of the proximal muscles of the arms and legs, resulting in hampering of the quality of life [3]. Over time, the muscle wasting spreads to the other limb muscles before involving the central portions of the body. The weakness is associated with pain, in both the normal and affected muscles. Tremors and twitchings are also known to occur [4].

    Involvement of the muscles of the thorax may result in respiratory compromise. The affliction of the brainstem may lead to bulbar symptoms such as dysphagia and dysarthria. There are usually no other central nervous system manifestations present. Reports have shown that these patients exhibit a higher degree of intelligence.

    The examination may show all the characteristic findings of a lower motor neuron disease, namely absent/decreased reflexes, hypotonia, flaccid paralysis and muscle fasciculations.

    musculoskeletal
    Muscular Atrophy
    Muscle Weakness
    • OMIM : 54 Spinal muscular atrophy is characterized by degeneration of the anterior horn cells in the spinal cord, leading to symmetric muscle weakness and wasting.[malacards.org]
    • SMA IV manifests as muscle weakness usually in the second or third decade of life.[encyclopedia.com]
    • SMAPAD is characterized by proximal muscle weakness that begins in the lower limbs and then progresses to upper limbs, onset in late adulthood (after third decade) and a benign course.[uniprot.org]
    • Spinal Muscular Atrophies SMA type I – Acute infantile or Werdnig-Hoffman disease The condition is usually evident by the time the infant reaches 6 months of age Diffuse muscle weakness and hypotonia (severely reduced muscle tone), causing difficulties[thehumanthebody.com]
    • weakness and hypotonia Symmetrical involvement of proximal muscles, mostly of the lower extremities Intercostal muscle weakness with initial sparing of the diaphragm paradoxical breathing Diminished or absent deep tendon reflexes Severe bulbar palsy[amboss.com]
    Myopathy
    • , Multicore myopathy, Multiminicore myopathy, Minicore myopathy with hand involvement, antenatal onset minicore myopathy with arthrogryposis, Minicore myopathy with external ophthalmoplegia, Multicore myopathy with external ophthalmoplegia, Multiminicore[orphananesthesia.eu]
    • Differential diagnosis Motor neurone disease Primary lateral sclerosis Muscular dystrophy Congenital myopathies Disorders of carbohydrate metabolism ( glycogen storage diseases ) Myasthenia gravis Poliomyelitis Investigations Blood tests Creatine kinase[patient.info]
    • Differential diagnosis In general, the most important differential diagnostic conditions for an infant presenting with hypotonia and/or weakness are congenital myopathies, i.e. myopathies with typical structural or ultrastructural features (rods, cores[ojrd.biomedcentral.com]
    • […] defects in synaptic vesicles, mitochondria, active zones, neurofilaments & microtubules Axonogenesis: May be related to spliced isoform of SMN protein Presynaptic motor axon terminals: Postnatal organization & maintenance 84 Muscle: SMN knockout produces myopathy[neuromuscular.wustl.edu]
    Muscle Twitch
    • twitching first noted in late teens or early adulthood There are other diseases that are similar to spinal muscular atrophy, but have different genetic causes.[togetherinsma.com]
    • twitches and weakness of limb muscles As the condition progresses: Weakness of the face and tongue muscles which may cause difficulties when swallowing and speaking Recurring pneumonia Some patients also develop enlarged male breasts (gynaecomastia),[thehumanthebody.com]
    • twitching first noted in late teens or adulthood To learn how different aspects of care may relate to the signs and symptoms of SMA, click here .[togetherinsma-hcp.com]
    • The initial symptoms of Kennedy’s syndrome may include tremor (shaking) of the hands, muscle cramps on exertion, muscle twitches and weakness of the muscles of the limbs.[your.md]
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  • gastrointestinal
    Dysphagia
    • Dysphagia may be present.[merckmanuals.com]
    • Eye Optic atrophy (90%) Most: Normal eye movements External ophthalmoplegia: 1 patient Motor Weakness Especially: Arms & Hands, Neck (Extension) & Trunk Respiratory failure : More severe cases Gait disorder Dysphagia: Some patients Tone: Reduced Muscle[neuromuscular.wustl.edu]
    • As the condition progresses, it may cause other symptoms, including: weakness of the facial and tongue muscles, which may cause difficulty swallowing ( dysphagia ) and slurred speech recurring pneumonia (infection of lung tissue) Some people with Kennedy[your.md]
    • […] associated with names of investigators such as Santavuori-Haltia, Jansky-Bielschowsky, Batten, Spielmeyer-Vogt, Kufs Opitz G/BBB Syndrom ( 1 Files ) Erkrankung : Opitz G/BBB Syndrom ICD 10: Q87.8 Synonyme : Hypertelorism-hypospadias syndrome, hypospadias-dysphagia[orphananesthesia.eu]
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  • neurologic
    Tremor
    • […] usually able to sit unattended, but cannot stand or walk without assistance Weak respiratory muscles, which can inhibit coughing Breathing problems Weakness in the muscles of the arms and especially of the legs Swallowing and feeding problems Slight tremor[thehumanthebody.com]
    • Fine tremors of the face are present in over 90% of patients.[encyclopedia.com]
    • The nerve cells tend to cause muscle weakness, tremor, and twitching.[patientslikeme.com]
    • Symptoms of adult-onset SMA are usually mild to moderate and include muscle weakness, tremor and twitching.[genome.gov]
    • […] after 35 years old, although some people may have symptoms as early as their later teenage years. 2 These patients usually are ambulatory until around age 60. 1 Symptoms of SMA type 4 include mild muscle weakness , scoliosis (curvature of the spine), tremor[smanewstoday.com]
    Limb Weakness
    • As the disease progresses patients may notice limb weakness starting in the pelvis or shoulders, or weakness of the facial and tongue muscles.[cedars-sinai.edu]
    • The condition is also called bulbospinal muscular atrophy and Kennedy's disease. ... more » Symptoms of Adult SMA Progressive limb weakness Limb muscle atrophy Difficulty speaking Difficulty swallowing Respiratory problems more symptoms...»[rightdiagnosis.com]
    • […] reported so far) Etiology : defect in VRK1 gene on chromosome 14q atrophy of the cerebral cortex, cerebellar and brain stem hypoplasia, absent dendate nucleus, loss of neurons in the basal ganglia Clinical features Onset at 0–6 months Early Arthrogryposis Limb[amboss.com]
    • In addition to muscle weakness, clinical features include head lag, poor sucking and swallowing, weak cry, proximal limb weakness, and lack of reflexes.[encyclopedia.com]
    • : Mean 27 to 43 years; Range 14 to 75 years Early symptoms & signs: Adolescence 32 Muscle discomfort: Cramps or Pain Fatigue: General; Chewing Gynecomastia: May be asymmetric Weakness: Not common early; May be distal Symptoms at 30 years Lower Upper limb[neuromuscular.wustl.edu]
    Flaccid Paralysis
    • Genetic testing for non-5q spinal muscular atrophy References: [1] Differential diagnoses Certain viral infections ( polio , coxsackievirus, echovirus, West Nile virus ) much more acute onset of flaccid paralysis, ascending paralysis (i.e., starts distally[amboss.com]
    • These patients have profound hypotonia, symmetrical flaccid paralysis, and often no head control.[ojrd.biomedcentral.com]
    • […] years Laboratory TDP 43 brain pathology: 1 patient ALS-FTD 101 Chromosome 16p12.1–q12.2; Dominant Epidemiology: 2 families Genetics Possible gene variants: CYLD; RPGRIP1L Similar locus to: ALS-FTD CCNF Clinical Onset age: 30 to 62 years ALS Weakness: Flaccid[neuromuscular.wustl.edu]
    Absent Deep Tendon Reflex
    • Results in muscle weakness and atrophy The onset varies from before birth until adulthood The weakness is symmetric and progressive Contractures, usually mild Anterior horn cell involvement, apparent due to tongue fasciculations and absent deep tendon[en.wikibooks.org]
    • deep tendon reflexes Severe bulbar palsy Respiratory failure Atrophy and fasciculations in the tongue Weak cry and cough Inability to swallow difficulty feeding, drooling, risk of aspiration Delayed motor milestones Poor weight gain Weak cough Fine hand[amboss.com]
    Areflexia
    • Patients typically present during infancy or early childhood with progressive weakness, hypotonia , muscle atrophy , hyporeflexia/areflexia, and varying degrees of bulbar weakness.[amboss.com]
    • Signs and symptoms below are most common in the severe SMA type 0/I: [7] [ medical citation needed ] Areflexia , particularly in extremities Overall muscle weakness , poor muscle tone , limpness or a tendency to flop Difficulty achieving developmental[en.wikipedia.org]
    Average Intelligence
    • The brain is not affected, and they have been tested to have at least average to above average intelligence.[smasupport.com]
    Dysarthria
    • […] at 30 years Lower Upper limb weakness Occasionally cramps Weakness Distribution Proximal Symmetric or Asymmetric (55%; Dominant side 70%) Legs Arms Face: Upper & Lower Tongue: Weakness; Atrophy; Fasciculations Bulbar dysfunction Dysphagia: Aspiration Dysarthria[neuromuscular.wustl.edu]
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  • Entire body system
    Difficulty Walking
    • Someone with the condition may have: weakness in the hands and feet difficulty walking shaking and twitching muscles Type 4 SMA gets slowly worse over time, but doesn't normally cause problems with breathing or swallowing.[nhs.uk]
    • These children show signs of clumsiness, difficulty walking, mild muscle weakness, and may be developmentally delayed.[chw.org]
    Difficulty Climbing Stairs
    • climbing stairs & rising from chair Waddling gait Course: Non-progressive Wasting: Quadriceps & Distal legs; Small hand muscles Tendon reflexes: Reduced at knees; Others normal Sensation: Normal Contractures: None Laboratory Muscle MRI: Thigh Early involvement[neuromuscular.wustl.edu]
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  • Workup

    Diagnosis of this disease is dependent on the anamnestic data. Amongst laboratory tests that may be performed, creatine kinase is the most useful, with elevated levels of the enzyme found. In some patients, the enzyme levels may be normal.

    Genetic tests may be performed both prenatally and postnatally to check for deletions involving the SMN1 gene [5].

    Electrocardiograms (ECGs) are usually normal in these patients [6].

    A variety of other neuromuscular diseases may present in a similar manner. Differentiation is done by electrophysiological tests that demonstrate a reduction of transmitted nerve signals [7] [8]. Sensory signals are usually normal in adult spinal muscular atrophy. Tests involving compound motor action potential may also be performed for diagnosis.

    Muscle biopsy is another test that may help in differentiating adult spinal muscular atrophy from other similar muscular diseases [9] [10]. These characteristically show atrophy of the muscle fibers with compensatory hypertrophy.

    Differential diagnosis usually involves the other spinal muscle atrophies which include the X-linked spinal muscular atrophy, distal spinal muscular atrophy, autosomal dominant spinal muscular atrophy and juvenile asymmetric segmental spinal muscular atrophy. Postpolio syndrome and multifocal motor neuropathy are the other conditions that may present in a similar fashion.

    There is a potential for patients with adult spinal muscular atrophy to be misdiagnosed due to the overlapping of clinical features. Over the years, patients labeled earlier as SMA have had their diagnoses revised to more treatable conditions including syringomyelia, amyotrophic lateral sclerosis, myopathy, axonal neuropathies and herniated lumbar discs. It is hence, recommended that patients be followed up for a long duration to establish the correct diagnosis.

    Pathology

    Other Pathologies
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  • Biopsy
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  • Treatment

    Prognosis

    Complications

    Amyotrophic Lateral Sclerosis
    • . : Motor neuron disease (Amyotrophic lateral sclerosis) .[link.springer.com]
    • lateral sclerosis 2016 2017 2018 Billable/Specific Code Adult Dx (15-124 years) spinal G12.25 ICD-10-CM Diagnosis Code G12.25 Progressive spinal muscle atrophy 2018 - New Code Billable/Specific Code adult G12.1 adult G12.1 spinal G12.9 ICD-10-CM Diagnosis[icd10data.com]
    • Differential diagnosis Differential diagnoses include the amyotrophic lateral sclerosis, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms).[orpha.net]
    • Differentiating this disorder from amyotrophic lateral sclerosis that involves predominantly lower motor neurons may be difficult.[merckmanuals.com]
    Motor Neuron Disease
    • Electrophysiological studies showed patterns of lower motor neuron disease and genetic test showed P56S mutation of VAPB gene.[neurology.org]
    • In: Human motor neuron diseases p. 1–11.[link.springer.com]
    • neuron disease G12.21 Amyotrophic lateral sclerosis G12.22 Progressive bulbar palsy G12.23 Primary lateral sclerosis G12.24 Familial motor neuron disease G12.25 Progressive spinal muscle atrophy G12.29 Other motor neuron disease G12.8 Other spinal muscular[icd10data.com]
    • ADULT-ONSET SPINAL MUSCULAR ATROPHY: PDF Only Source CONTINUUM: Lifelong Learning in Neurology3(1, Motor Neuron Diseases):33-40, January 1997.[journals.lww.com]
    • Clinical science Abstract Spinal muscular atrophy (SMA) refers to a group of autosomal recessive motor neuron diseases that are caused by apoptosis of lower motor neurons .[amboss.com]

    Etiology

    Epidemiology

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    References

    1. Wang CH1, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049.
    2. Baioni MT, Ambiel CR. Spinal muscular atrophy: diagnosis, treatment and future prospects. J Pediatr (Rio J). 2010;86(4):261-270.
    3. Prior TW, Russman BS. Spinal Muscular Atrophy. 2000 Feb 24 [Updated 2013 Nov 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
    4. Joynt R, Griggs R. Clinical Neurology. Philadelphia: Lippincott; 1997. Vol 4: 11-5.
    5. Arnold WD, Kassar D, Kissel JT. Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era. Muscle Nerve. 2015;51(2):157-167.
    6. Palladino A, Passamano L, Taglia A, et al. Cardiac involvement in patients with spinal muscular atrophies. Acta Myol. 2011 Dec. 30(3):175-8.
    7. Hausmanowa-Petrusewicz I, Karwanska A. Electromyographic findings in different forms of infantile and juvenile proximal spinal muscular atrophy. Muscle Nerve. 1986 Jan. 9(1):37-46.
    8. Krivickas LS. Electrodiagnosis in neuromuscular disease. Phys Med Rehabil Clin N Am. 1998 Feb. 9(1):83-114, vi.
    9. Buchthal F, Olsen PZ. Electromyography and muscle biopsy in infantile spinal muscular atrophy. Brain. 1970. 93(1):15-30.
    10. Dubowitz V. Muscle disorders in childhood. Major Probl Clin Pediatr. 1978. 16:iii-xiii, 1-282.

    • A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle - TK Rajendra, GB Gonsalvez, MP Walker - The Journal of cell , 2007 - jcb.rupress.org
    • Vulnerability of motor neurons and dissociation of pre-and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy - LM Murray, LH Comley, D Thomson - Human molecular , 2008 - Oxford Univ Press
    • A controlled trial of riluzole in amyotrophic lateral sclerosis - G Bensimon, L Lacomblez - New England Journal of , 1994 - Mass Medical Soc
    • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
    • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
    • Degeneration in Portuguese families of the Azores Islands A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions - P Coutinho, C Andrade - Neurology, 1978 - AAN Enterprises
    • A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis - AL Nishimura, M Mitne-Neto, HCA Silva - The American Journal of , 2004 - Elsevier
    • Benign spinal muscular atrophy arising in childhood and adolescence - D Gardner-Medwin, P Hudgson, JN Walton - Journal of the neurological , 1967 - Elsevier
    • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
    • Vulnerability of motor neurons and dissociation of pre-and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy - LM Murray, LH Comley, D Thomson - Human molecular , 2008 - Oxford Univ Press
    • A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis - AL Nishimura, M Mitne-Neto, HCA Silva - The American Journal of , 2004 - Elsevier
    • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
    • A mouse model of spinal and bulbar muscular atrophy - , PJ Crack, I Kola, SS Cheema, MK Horne - Human molecular , 2002 - Oxford Univ Press
    • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier

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