Dr. Rahul Chakor Neurologist
Special Interest in Neuroimmunology, Epilepsy

It is a group of progressive degenerative disorders of motor neurons in the spinal cord, brainstem, and motor cortex. It manifests clinically by muscular weakness, atrophy, and corticospinal tract signs in varying combinations.

Motor neuron disease is subdivided into several subtypes based on particular symptoms and signs. The most frequent form, in which amyotrophy and hyperreflexia are combined, is called amyotrophic lateral sclerosis, or ALS. Charcot was the first to describe the disease. ALS is a common disease with an incidence rate of 0.4 to 1.76 per 100,000 population.

It progresses to death in a matter of 2 to 5 years or longer in exceptional cases

Symptoms and signs

The onset is with weakness in a distal part of one limb. This may be noted first as an unexplained tripping because of slight foot drop. There may be awkwardness in tasks requiring fine finger movements (in handling buttons and automobile ignition keys), stiffness of the fingers. The patient simultaneously notices slight weakness or wasting of the hand muscles. With progression over months, the other hand and arm may be similarly affected. An atrophic weakness of the hands, forearms, calves, tongue, slight spasticity of the arms and legs, and generalized hyperreflexia in the absence of sensory change confirms the diagnosis of ALS. The muscles of the upper arm and shoulder girdles are typically involved later. Later the atrophic weakness spreads to the neck, tongue, pharyngeal, and laryngeal muscles, and eventually those in the trunk and lower extremities. Coarse fasciculations (twitching of muscles) are usually obvious in the weakened muscles but may not be noticed by the patient until the physician calls attention to them.

Progressive bulbar palsy, progressive muscular atrophy, primary lateral sclerosis are different manifestations of MND.

Causes

The precise cause of MND is unknown. It is a combination of genetic and environmental factors. Various etiological factors are implicated as mentioned below:

• exposure to viruses
• toxins and chemicals
• auto immune, inflammation
• impaired nerve growth factors
• ageing of motor neurons.

Familial (hereditary) MND accounts for about 5 to 10 percent of cases. Several gene mutations have been identified as causative for MND. Hexanucleotide (GGGGCC) repeat expansion in C9ORF72, variants in SOD1, FUS, TARDBP and VAPB are genetic causes of ALS.

Spinal muscular atrophy type1,2,3,4, Kennedy syndrome, Fazio-Londe are other genetic MNDs.

Laboratory features

Investigation provides confirmatory evidence even in the typical clinical syndrome. The EMG, displays widespread fibrillations (evidence of active denervation) and fasciculations and enlarged motor units (denoting reinnervation). Motor nerve conduction studies reveal only slight slowing, without focal motor conduction block. Denervation has to be demonstrated in at least 3 limbs before concluding that the process is ALS as per the El-Escoril criteria. Widespread denervation of the paraspinal, tongue, limb or facial muscles in the presence of brisk reflexes is highly suggestive of ALS.

Pathology

In ALS there is loss of nerve cells in the anterior horns of the spinal cord and motor nuclei of the lower brainstem. The muscles show denervation atrophy. There are TDP-43 and ubiquitin inclusions in the alpha motor neurons. There is corticospinal tract degeneration and loss of Betz cells in the motor cortex. 97% of ALS cases (familial or sporadic) have neuronal and glial cytoplasmic aggregates of phosphorylated TDP-43 at postmortem.

Treatment

The available treatment for any of the motor neuron diseases is highly unsatisfactory. A small number of drugs, however, have been developed: riluzole, edaravone, and masitinib. Supportive treatment is exceedingly important. The seriousness of the condition has to be revealed in a set wise manner, gradually over few visits after the diagnosis is confirmed. Physical therapy, Occupational therapy, periodic monitoring of respiratory function, care of nutrition are all of importance in treatment of MND.