Degenerative motor neuron disease evolving to
progressive muscle weakness resulting in paralysis.
ALS; Lou Gehrig Disease (named after a famous American
baseball player with New York Yankees who succumbed to amyotrophic lateral
sclerosis in 1941).
Described in 1869 by Jean-Martin Charcot, a French
Annually, approximately five new cases per 100,000 in
the general population, mainly male patients (male-to-female ratio 1.5:1)
age 40 to 60 years.
Etiology is not known. Approximately 10% of
cases are inherited in an autosomal dominant fashion. The remaining cases
are believed to be caused by an unknown slow virus infection. Despite
extensive searches for infectious causative agents, no viral or bacterial
etiology has been identified. Oxidative stress may be relevant.
Degenerative motor neuron disease may include
cortical neuron degeneration (primary lateral sclerosis), central nuclei
(pseudobulbar palsy), and/or motor neurons (progressive spinal amyotrophia).
The hypothesis that excitotoxicity, oxidative stress, and mitochondrial
dysfunction are involved in the process of neuronal cell death is supported
at least in part by research reporting discovery of mutations of superoxide
dismutase-1 in approximately 10% of patients with familial ALS. Anterior
horn cells in the spinal cord and cranial motor nerves are predominantly
involved in ALS. Patients may present with bulbar palsy or (commonly
symmetrical and distal) weakness of single or multiple muscle groups of the
limbs. The primarily bulbar form of ALS is associated with a worse prognosis
with regard to severity and survival time. Fasciculations of the intrinsic
hand muscles, which are an early and characteristic sign, later progress to
weakness and atrophy and eventually spread proximally to the forearms and
shoulder girdle muscles. Typically, both upper and lower motor neurons are
affected. Clinically limb or tongue fasciculations, hyperreflexia, clonus,
and spasticity are found. An inflammatory response with activated microglia,
reactive astrocytes, and IgG antibodies can be found in affected areas of
the spinal cord. However, how these changes are related to neuronal cell
death is not known. Autoimmune phenomena may be involved in the pathogenesis
of ALS. Corticospinal and corticobulbar tracts may show signs of wallerian
Progressive adult-onset muscular weakness with muscular
spasms and fasciculations (although a few cases have been reported in
children). Initially, the disease is localized but rapidly spreads to all muscles.
In addition to the clinical examination, electromyography studies are used to identify lower
motor neuron dysfunction. Long-lasting, polyphasic fasciculation potentials
and signs of chronic partial denervation are characteristic of ALS.
Initially the disease may present with
fasciculations of the intrinsic hand muscles, which later change to weakness
and atrophy and then spread proximally to the shoulder girdle. However,
involvement of the various muscle groups is inhomogeneous. As the disease
progresses, atrophy and weakness involve most of the skeletal muscles,
including those of the tongue, pharynx, larynx, and chest. Swallowing
problems, with frequent choking and bronchopulmonary aspirations, are common.
The sensibility is not affected. Serum creatine phosphokinase levels are