Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.
Highlights
Amyotrophic lateral sclerosis (ALS) is a term used to cover the spectrum of neurodegenerative syndromes character
Other syndromes related to this spectrum of disorders include, Progressive bulbar palsy (PBP), Progressive muscular atrophy (PMA), Primary lateral sclerosis (PLS), Flail arm syndrome (Vulpian-Bernhardt syndrome), Flail leg syndrome (Pseudopolyneuritic form) and ALS with multi-system involvement (e.g., ALSDementia)
ALS can be defined as a neurodegenerative disorder characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, brainstem and spinal cord
Summary
Electrophysiological studies Patients in whom a diagnosis of ALS is suspected on clinical grounds should have electrophysiological studies primarily to document lower motor dysfunction in clinically involved and uninvolved regions, and secondarily to exclude other disease processes. Abbreviations (ALS): Amyotrophic lateral sclerosis; (UMN): upper motor neurone; (LMNs): lower motor neurone; (Ub-IR): ubiquitin-immunoreactive; (TDP43-IR): TDP-43 immunoreactive; (EMG): electromyography; (PMA): progressive muscular atrophy; (PLS): primary lateral sclerosis, (MND): motor neurone disease; (PBP): progressive bulbar palsy; (PMA): progressive muscular atrophy; (CSF): cerebrospinal fluid; (WFN): World Federation of Neurology; (FALS): familial ALS; (SALS): sporadic ALS; (jALS): juvenile onset ALS; (ALS-PD complex): ALS associated with the Parkinsonism and dementia; (TLS): 'totally locked-in state'; (FTLD): fronto-temporal dementia; (RR): relative risk; (OR): odds ratio; (VEGF): vascular endothelial growth factor; (ROS): reactive oxygen species; (SOD1): superoxide dismutase 1; (NFH): neurofilament heavy; (IAPs): inhibitor family of proteins; (UBIs): ubiquitinated inclusions; (SLIs): skein-like inclusions; (TDP43): TAR DNA binding protein 43; (HCIs): hyaline conglomerate inclusions; (FTLD-MND): frontotemporal lobar degeneration with MND; (FTLD-U): frontotemporal lobar degeneration with ubiquitin inclusions; (DML): distal motor latency; (MCV): motor conduction velocity; (TMS): transcranial magnetic stimulation; (CMCT): central motor conduction time; (MUNE): motor unit number estimation; (DWI): diffusion weighted imaging; (DTI): diffusion tensor imaging; (FVC): forced vital capacity; (SVC): slow vital capacity; (SNIP): sniff nasal inspiratory pressure; (AAN): American Academy of Neurology; (NIV): non-invasive ventilation; (BiPAP): bi-level positive pressure devices; (CPAP): continuous positive pressure; (PEG): percutaneous endoscopic gastrostomy; (PRG): percutaneous radiologic gastrostomy; (RIG): radiologically inserted gastrostomy; (MRI): magnetic resonance imaging; (NGT): nasogastric tube; (NMDA): N-methyl-Daspartate; (AAV): adeno-associated viruses; (iPS): induced pluripotent stem cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
