Progressive Muscular Atrophy

Progressive Muscular Atrophy

1. Progressive muscular atrophy Ade Wijaya, MD – April 2019

2. Outline: Introduction Epidemiology Clinical presentation Patophysiology Diagnosis Electrophysiology testing Differential diagnosis Management and prognosis Summary

3. Introduction Is a rare, sporadic, adult-onset, clinically isolated LMN syndrome due to the degeneration of LMNs, including anterior horn cells and brainstem motor nuclei The term PMA was first coined by the French neurologist Aran in 1850 to describe patients with progressive muscle atrophy of presumed myopathic cause Later, Duchenne also claimed the first description of PMA Therefore , PMA is sometimes referred to as Aran-Duchenne or Duchenne-Aran disease In 1853, Cruveilhier provided the first evidence of PMA being a neurogenic disorder based on the atrophy of the ventral spinal roots and the motor nerves found on autopsy of Aran’s patients. Visser J, de Jong JM, de Visser M. The history of progressive muscular atrophy: syndrome or disease? Neurology 2008;70:723–7

4. Epidemiology PMA accounts for 2.5% to 11% of MND Incidence: 0.02 per 100,000 Male/female ratio, 3:1 – 7.5:1 Age of onset : 63.4 + 11.7 years Liewluck T, Saperstein DS. Progressive muscular atrophy. Neurologic clinics. 2015 Nov 1;33(4):761-73.

5. Clinical presentation LMN features, distal asymmetric Symmetric proximal in 20 % cases Bulbar involvement in 40 % cases at a later time About 22% to 35% of patients with the initial diagnosis of PMA develop UMN features at a later time Visser J, van den Berg-Vos RM, Franssen H, et al. Disease course and prognostic factors of progressive muscular atrophy. Arch Neurol 2007;64:522–8 . Kim WK, Liu X, Sandner J, et al. Study of 962 patients indicates progressive muscular atrophy is a form of ALS. Neurology 2009;73:1686–92 Statland JM, Barohn RJ, McVey AL, et al. Patterns of weakness, classification of motor neuron disease & clinical diagnosis of sporadic ALS. Neurol Clin 2015, in press.

6. Patophysiology Anterior horn cell degeneration Corticospinal degeneration (1) ALS-like pathology (combined UMN and LMN degeneration with TDP-43-positive cytoplasmic inclusions) in 61.5% of patients (2 ) isolated LMN degeneration with TDP- 43-positive inclusions in 23% of patients ( 3) combined UMN and LMN degeneration with FUS-positive inclusions in 15.5% of patients Genetic mutation Liewluck T, Saperstein DS. Progressive muscular atrophy. Neurologic clinics. 2015 Nov 1;33(4):761-73.

7. Diagnosis Clinical and electrophysiologic features of LMN dysfunction in 2 or more different myotomal distributions (bulbar, cervical, thoracic, and lumbosacral) Evidence of disease progression over time Exclusion of other LMN syndromes Liewluck T, Saperstein DS. Progressive muscular atrophy. Neurologic clinics. 2015 Nov 1;33(4):761-73.

8. Electrophysiology testing Electrophysiologic features of LMN dysfunction in 2 or more different myotomal distributions (bulbar, cervical, thoracic, and lumbosacral ) Needle electromyography (EMG) could help to show fasciculations in deep muscles that are not visible on examination and provide evidence of LMN dysfunction (large polyphasic motor unit potentials with reduced recruitment) in clinically affected and nonaffected areas Liewluck T, Saperstein DS. Progressive muscular atrophy. Neurologic clinics. 2015 Nov 1;33(4):761-73.

9. Differential diagnosis Other MNDs Motor neuropathies Neuromuscular junction disorders Myopathies Liewluck T, Saperstein DS. Progressive muscular atrophy. Neurologic clinics. 2015 Nov 1;33(4):761-73.

10. Management and prognosis No definitive treatment  supportive treatment The rate of progression in patients with PMA varies from slow (over years and decades) to very rapid (months to a year ) The median survival duration after onset in patients with PMA is about 12 months longer than in patients with ALS (48.3 vs 36 months) Kim WK, Liu X, Sandner J, et al. Study of 962 patients indicates progressive muscular atrophy is a form of ALS. Neurology 2009;73:1686–92.

11. Summary Rare; difficult to diagnose MND with isolated LMN features Supportive treatment