Motor neuron diseases are characterized by selective degeneration of motor neurons, both upper and lower, namely of the pyramidal fibers in cerebral cortex, of ventral horn cells and of cranial motor nerve nuclei. In different cases relative incidence of degeneration varies. In some the change is maximal in the ventral horn cells, in others in the cranial nerve nuclei, in others pyramidal fiber sclerosis is severe and adds the appropriate clinical picture.

Aeteology: – About 5 % of cases are familial, showing autosomal dominant inheritance. In many such families genetic defects lies on chromosome 21, the enzyme involved being a superoxide dismutase (SOD1).

For the remaining 95 %, probable causes includes
1. Chronic Aluminium toxicity
2. Slow virus infection
3. Auto immunity
4. Trauma
5. Electrical shock

Another suggestive hypothesis is that glutamate which is a primary excitatory neurotransmitter in the CNS, accumulates at synapses and causes the neurons to die, probably through a calcium dependent mechanism. Prevalence of this disease is about 5/100000.

Pathology:-
The motor neurons in the cerebral cortex, brainstem and spinal cord show atrophy and their axons show degenerative changes. Muscles show groups of atrophic fibres amidst the groups of normal fibres.

Classification:
A. Classical type and
B. Non classical type

A. Classical type:
1. Predominant LMN involvement
a) Bulbar form: Progressive bulbar palsy
b) Spinal form: Progressive muscular atrophy
2. Predominant UMN involvement
a) Bulbar form: Pseudo bulbar palsy (spastic bulbar palsy)
b) Spinal form: Primary lateral sclerosis.
3. Combination of upper and lower motor involvement.
Amyotrophic lateral sclerosis.

B. Non classical type:
1 Werding – Hoffmann disease
2 Kugelberg – Welander disease
3 Spinal muscular atrophy described from south India (Madras )
4 Motor neuron disease – dementia – parkinsonian complex described from Guam Island

Clinical feature of motor neuron disease
Patient s present with a combination of lower and upper motor neuron signs with out sensory involvement. The presence of brisk reflexes in wasted limb muscles is typical

Common presenting features are
Age of onset
Usually after age 50 years
Very uncommon before 30 years
Males are common than females.
Symptoms:
Limbs muscle weakness, cramps, occasionally fasciculation.
Disturbance of speech and swallowing (dysarthria and dysphagia )
Signs
Wasting and fasciculation of muscles
Weakness of muscles of limbs and tongue, face and palate.
Pyramidal tract involvement causes spasticity, exaggerated tendon reflexes and extensor plantar responses.
External occular muscles and sphincters usually remain intact.
No objective sensory deficit.
No intellectual impairment in most cases.
Course
Symptoms often begin focally in one part and spread gradually but relentlessly to become widespread.

BULBAR FORMS
There are two types:
1. Progressive bulbar palsy
2. Pseudobulbar palsy

Apart from the causes mentioned earlier, there are certain other causes leads to these types of palsies. They are:

Progressive Bulbar Palsy
This is the most serious form since it terminates life within a period of one year. There are spastic and atrophic variants of chronic bulbar palsy. In a very few cases the spastic element so far predominates that little wasting may be seen. In some atrophic element is predominating, evidenced by wasting of muscles of tongue, muscles of mastication and face. There is progressive involvement of palatal pharyngeal and laryngeal muscles. Usually patient seeks advice for a slowly increasing difficulty in articulation, shortly followed by difficulty in deglutition. On examination, fasciculation can be seen in the muscles in the region of tongue and chin. As the malady progresses, the lips are slightly open and saliva trickles from the corners of the mouth. Patient can not purse the lips and whistle.

The mucous membrane of the tongue may be wrinkled. The range of movement of the tongue is limited and the protrusion beyond the lips may be impossible. On phonation, the excursion of soft palate is diminished. Swallowing is slow and laboured because of the weak muscles of the tongue and floor of the mouth. Patient can not push the food bolus back into the fauces and pharyngeal deglutition is impaired owing to the weakness of the hyoid muscle. The larynx is not fixed, moves up and down. The nasopharynx is not shut off. Articulation is grossly disturbed and the voice nasal in quality and monotonous. Finally, the patient can make only inarticulate noises, swallowing becomes virtually impossible and aspiration pneumonia results. This will lead to termination of life within one or two years of the time of onset.
When the spastic element is prominent, the face moves as a whole, slowly and in exaggerated degree and there may be tendency to spasmodic weeping and laughter of the type found in pseudobulbar palsy, with which this variant of chronic bulbar palsy may be confused if the fact of its slowly progressive onset be overlooked. In pseudobulbar palsy the onset is usually sudden after two or more cerebral ischaemic attacks. Chronic bulbar palsy may also occur along with amyotrophic lateral sclerosis.

Pseudobulbar palsy:
This results from small bilateral softening in the region of internal capsule. There is usually a history of two or more mild apoplectiform seizures, neither of which has been followed by severe hemiplegia. In this form of palsy affection of bulbar muscles is of UMN type. There is weakness of bulbar muscles. The palatal muscles, tongue and pharyngeal muscles are spastic. There is dysarthria, sometimes so gross as to render the patient’s speech unintelligible. The tongue is small and spastic and usually can not be protruded beyond the line of teeth. Swallowing and mastication are laboured and imperfect. The lips hang apart and saliva trickles from between them. Palatal movements are slow, but the gag reflex is brisk. Jaw jerk is exaggerated. Emotional movements of the face are apt to be grossly exaggerated, the whole face being contorted in to smile or into an expression of woe. Spasmodic and uncontrollable laughter or weeping occurs from time to time. The limbs show some measures of spasticity. Fibrillation of the tongue may occur in later stage.

Amyotropic Lateral sclerosis
This is the most common type. Important features are:
• Combination of distal and proximal muscles wasting, weakness and fasciculation.
• Spasticity, exaggerated reflexes and extensor plantar reflexes.
• Bulbar and pseudobulbar palsy follow eventually.
• Pyramidal tract features may predominates .

SPINAL FORM
Progressive muscular atrophy: Weakness and wasting starts in one upper extremity (75%) or one lower extremity (25%) and this become generalized over a period of 3-5years. Fasciculation are visible. Despite the marked wasting, reflexes are preserved normally or may even be brisk.
Primary lateral sclerosis: UMN signs in the lower limbs with LMN signs in upper limbs.

VARIANT TYPES OF MND:
Werding-Hoffmann disease: This form of progressive muscular atrophy is seen in infancy and runs a more acute course.
Kugelberg-Welander disease: This is one of the form of spinal muscular atrophy characterized by affection of the proximal muscles of all four limbs. Starting at adolescence and has a benign course. It follows a chronic course.

Other Forms Of Spinal Muscular Atrophy: These occur at any age after infancy. They manifest as asymmetrical uni. or bilateral weakness and wasting of muscles with predominantly LMN features.
Geographic Variant (Madras form):Weakness and wasting may be uni or bilateral, proximal or distal, and asymmetrical. Bulbar muscles may be involved in 60% of cases. Uni. or bilateral nerve deafness is an associated feature.
Another Variant Of MND Described From Guam Island: Demonstrates the picture of ALS, parkinsonism, and dementia.

Diagnosis: MND has to be suspected under the following circumstances:
1) Insidious onset of selective motor system involvement characterized by  affection of the lower and upper motor neurons.
2) Weakness, atrophy of muscles and fasciculation
3) Electromyographic abnormalities as
a) fibrillation and fasciculation at rest
b) reduction in the number of motor unit potentials
c) giant potentials with increased duration and amplitude
4) Sensory nerve conduction and motor nerve conduction studies are normal, but there is evidence of loss of axons.
5) Spinal imaging and brain scanning may be necessary to exclude focal spinal or cerebral disease.
6) CSF examination is usually normal, but a slight elevation of protein concentration may be found.

Prognosis:
Motor neuron disease is progressive. Mean time from the diagnosis to death is one year. Most of the patients dying within 3-5 years of onset of the disease symptoms.
Younger patients and those with early bulbar symptoms tend to show more rapid course.
Death is usually due to respiratory infections, respiratory failure and the complication of immobility.

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