Motor neurone disease

Motor neurone disease is the term applied to a group of degenerative disorders characterized pathologically by involvement of motor neurones of the spinal cord, medulla and motor cortex with sparing of peripheral nerves and sensory system.

Involvement of cortical neurones gives rise to predominant upper motor neurone lesion while that of brain stem and spinal cord gives rise to lower motor neurone lesion.

Often this demarcation may be blurred and a combination of both groups is seen. The incidence of motor neurone disease varies from 3 to 5 per cent of all neurological illnesses.

It has world wide distribution and is common in the age group of 40-60 years, with males predominating over females.

Classification

Motor neurone disease is classified into classical and non-classical forms.

Classical forms

1. Predominant upper motor neurone involvement:

(a) Pseudobulbar palsy

(b) Primary lateral sclerosis

2. Predominant lower motor neurone involvement

(a) Progressive muscular atrophy

(b) Progressive bulbar palsy

3. Combined upper and lower motor neurone involvement

(a) Amyotrophic lateral sclerosis (ALS)

(b) Non-classical forms of motor neurone disease

This group includes uncommon forms like Werding Hoffmann disease, Kugelberg-Welander disease, Moebius syndrome and Madras Pattern of Motar Neurone Disease.

Aetiology

A number of factors have been suggested:

1. Genetic factors: Familial occurrence of MND is considered as an autosomal dominant trait.

2. Mutations of the gene encoding a free radical scavenging enzyme called copper/zinc superoxide dismutase (SODI) could be one of the factors.

3. Certain occupations like leather workers, workers exposed to heavy metals (Lead, Tin, Mercury) or pesticides may predispose to the condition.

4. Free radicals may be neurotoxic and contribute to the pathogenesis of disease. Cumulative effects of somatic mutations and oxidative stress may cause MND along with death of motor neurone cells with age.

5. Glutamate is an important neurotransmitter and motor neurones are fired into action by its release which acts on surface receptors. Excess glutamate activity contributes to motor neurone injury in MND.

6. Other risk factors include virus, a toxin found in cycod nut, mitochondrial dysfunction, and protein aggregation.

Motor neurone disease

Amyotrophic lateral sclerosis (ALS)

This is the commonest form of motor neurone disease and usually presents in the 4th and 5th decades of life. Most patients present with weakness and wasting starting in the upper limbs and then spreads to other parts of body.

Cramps may be an early symptom and may predate wasting and muscle weakness. An early symptom may be inability to manipulate objects with the hands. There is wasting and flaccidity of muscles with absent or diminished tendon reflexes. Sensory loss is absent.

Fasciculations are present in the affected and unaffected muscles. Lower limbs involvement leads to difficulty in walking. Because of wasting, patient may develop pes cavus and foot drop. Reflexes of the limb are grossly exaggerated. Bladder and bowel functions remain normal.

Bulbar involvement occur in 20% cases of MS. Paralysis of vocal cords results in hoarseness of voice. Because of weakness of palate, patient develops a nasal twang. There is difficulty in swallowing and dysarthria.

There is spillage of fluids from the mouth and as a result of weakness and in coordination of swallowing, patient has coughing spells. Nasal regurgitation and drooling of saliva are common. Speech may be affected as the disease progresses.

Clinically patient has both upper and lower motor neurone lesions in the extremities but there is no sensory loss. Characteristic features are wasting of interosseus muscles of the hands and it may be an early sign.

Brisk jerks are persent in the presence of muscle atrophy and wasting. Fasciculations, the diagnostic feature of ALS, are most marked in large muscles such as biceps and quadriceps.

As the disease progresses bulbar involvement occurs and there are both upper and lower motor neurone lesion involvement signs. Patient may complain of breathlessness. There is impairment of emotional control. Advanced cases may develop urinary retention or incontinence.

Prognosis

Amyotrophic lateral sclerosis is a progressive disease. Older age at onset, respiratory difficulties and dysphagia are bad signs.

Death is due to intercurrent respiratory infections. Dysphagia limits food intake and patient suffers from malnutrition. Progressive weakness of limbs as of bulbar muscles results in extreme degree of disability. Once the disease develops survival is not mor& than 4-5 years though ten per cent of patients may survive for 10 years.

Pseudobulbar Palsy (Spastic Bulbar Type)

It is involvement of the bulbar muscles of the upper motor neurone type. It involves the muscles of the face, jaw, tongue and pharaynx, which become spastic.

There is slurring of speech, palatal moveents become slow while palatal and pharyngeal reflexes become brisk. Jaw jerk is exaggerated. There is emotional instability.

Progressive bulbar palsy

There is lower motor neurone type of involvement of cranial nerves (IX, X, XI and XII) leading to weakness and wasting of the muscles of the jaw, face and tongue. Tongue shows fasciculations which are most marked. There is difficulty in swallowing and nasal regurgitation of food.

As the disease progresses patient complains of difficulty in speech. There is drooling of saliva. Breathlessness may occur on minimal exertion after a full meal. Sneezing and coughing may become weak.

Progressive dysphagia leads to dehydration, malnutrition and aspiration pneumonia. Respiratory failure will occur when patients vilal capacity approaches 30-40 per cent.

Progressive muscular atrophy

There is lower motor neurone type of lesion characterized by wasting and weakness which begins in the small muscles of the hand on one side and soon involves the other limb. There are wide spread fasciculations.

Tendon reflexes are often preserved or exaggerated despite widespread wasting of muscles. Initially upper limbs are involved but gradually it involves the lower limbs as well and in period of 3-4 years, it becomes generalized.

Madras variety of motor neurone disease (MND)

This is atypical form of motor neurone disease

described from South India. Its salient features are:

1. Younger age of onset (10-30 years)

2. Male preponderance (2: 1)

3. Non-familial, insidious onset, benign progression.

4. Persistent asymmetrical involvement for many years in > 50% cases. It gradually involves all four limbs and features become like of ALS. There is both Hyporeflexia and hyperreflexia. Fasciculations are more marked. Babinski sign common.

5. Unilateral or bilateral nerve deafness.

6. High incidence of lower cranial nerve involvement.

7. High incidence of bulbar and facial weakness.

8. Glucose laterance test shows abnormal lag curve, Fasting serum pyruvate levels are raised while serum citrate levels are low.

Diagnosis of motor neurone disease

It is based on clinical picture of upper and lower motor neurone lesions characterized with marked wasting and weakness of muscles along with fasciculations but no sensory loss.

Investigations include motor and sensory nerve conduction studies which are normal. Biochemical studies show abnormal glucose and normal serum pyruvate and citrate levels.

Most important diagnostic test is electromyography which will show fibrillations and fasoiculations at rest along with reduction in the number of motor unit potentials and giant potentials with increased duration and amplitude, CSF is normal.

Treatment

It is mainly supportive since there is no cure for motor neurone disease.

Palliative measures include physiotherapy for prevention of joint contractures. Speech therapy helps the patient in communication. Food should be of soft consistency which can be swallowed easily. Where there is severe degree of dysphagia an gastrostomy may be considered.

When respiratory difficulty arises, non-invasive intermittent positive pressure ventilation (NIPPV) may improve quality of life.

There is little hope in drug riluzole, a sodium channel blocker which inhibits presynaptic release of glutamate and may help in prolonging life. Other drug found to be of use is ‘Vit. E, though its exact mode of action is ALS can not be explained.

Motor neurone disease is a progressive disease associated with number of complications and carries high degree of morbidity and mortality.

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