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About Motor Neuron Disease

Motor neuron disease is a disease of nerves that selectively damages the nerves controlling the muscles of the body and sparing the nerves that are responsible for sensations like touch, pain, temperature and movement. It is a progressive disease and sometimes the progression is slow but it may progress very rapidly with the life expectancy of mere 3 to 5 years since diagnosis. The disease rapidly weakens every muscle in the body leaving a conscious mind trapped in a crippled body.

The term motor neuron disease encompasses different disorders. These disorders are classified based on the kind of neurons that are damaged i.e upper motor neurons or lower motor neurons and the progression of the disease. The diseases that come under the group of motor neuron disease are

  1. Amyotrophic lateral sclerosis (ALS) (One of faster progressing diseases)
  2. Primary Lateral Sclerosis (PLS)
  3. Psuedobulbar palsy
  4. Progressive muscular atrophy (PMA)
  5. Progressive bulbar palsy (PBP)
  6. Kennedy disease

The main symptom of the disease is increasing weakness of the muscles. The symptoms can begin either in Upper limbs, Lower limbs, trunk and respiratory muscles or bulbar region (Speech and swallowing). Depending upon the type of the disease progression of symptoms may vary. The symptoms start in one region and progress to other regions as the disease progresses.

Common symptoms seen in disease with lower motor neuron involvement are fasciculations in the muscles including tongue muscles that progress from one region to another. Flail muscles with progressive weakness.

Common symptoms seen in diseases with upper motor neuron involvement are severe muscles cramps. Tightness in the muscles that restricts movements causing slowness and progresses from one region to another.

Apart from this common symptoms that are observed in these diseases are –

  1. Foot drop – due muscle weakness foot becomes flail and floppy and drops down while walking making it difficult to walk.
  2. Wasting of muscles – Thinning of muscles that gives hollow appearance to the body contours like flattening of shoulders, hollowness below clavicles and flattening of hand prominences.
  3. Fine motor impairment – loss of ability to use fingers to perform tasks of precision like writing, buttoning etc.
  4. Emotional disturbances – Uncontrolled emotions like laughing fits, crying spells, temper tantrums are also one of the symptoms of the disease.
  5. Speech disturbances – As the disease progresses to the neck and bulbar region speech difficulties start it may start as additional effort while talking to slurring of speech and eventually lead to complete loss of useful speech.
  6. Neck drop - Neck drop occurs due to weakness of the neck extensors persons with MND find it difficult to hold their neck up even for a few seconds.
  7. Drooling – Due to weakness of the muscles in the mouth region their can be drooling of saliva in patients with MND
  8. Swallowing difficulty – Patients may find it difficult to swallow as the bulbar muscle weakness progresses. Initially it starts as coughing while drinking liquids and subsequently progresses with difficulty of swallowing solid as well as liquids and eventually causing inability to swallow.
  9. Inability to perform rapid eye movements - In the advanced stage of the disease weakness muscles can cause inability to perform rapid eye movements.
  10. Facial muscle weakness
  11. Difficulty of breathing while sleeping in supine position (Orthopnoea)
  12. Difficulty of breathing while performing day to day tasks (Dysapnoea)
  13. Eventually the weakness of respiratory muscles leads to inability to breath and patients are dependent on support of an artificial ventilatory systems.

There are no known causes of motor neuron disease. So far there have been some studies implying genetic etiology and a few genes have been identified, however the exact cause remains unknown. Some risk factors have been identified which are male gender, age above 50 years and existing family history of the disease. Some pathophysiological mechanisms like glutamate toxicity, oxidative stress and chronic inflammation have been postulated in MND.

Currently, MND is treated with a combination of medical, surgical and rehabilitative treatments. Pharmacological management consists of Riluzole. Riluzole inhibits the release and modulates the post-synaptic activity of Glutamate which is found to cause excitotoxicity in MND. It is the only medicine that has shown effect on the survival duration. With no pharmacological means of altering the disease process current management of MND is widely palliative and symptom oriented. Regular moderate intensity physical exercise with various rehabilitative therapies like physiotherapy, occupational therapy, speech therapy and respiratory therapy and in the later stages of the disease artificial ventilatory support, management of swallowing difficulty and percutaneous endoscopic gastrotomy (PEG) are routinely used.

Marked progressive axonal degeneration of motor neurons in the spinal cord and motor cortex is noted in MND. Currently the aim of stem cell therapy is to protect the existing motor neurons and attempt to bring about regeneration and repair in the damaged motor neurons. Stem cells have a potential to regenerate nerve cells as well as have a positive effect of preserving the existing nerve cells. Stem cells can effectively find their way to the site of damage and bring about successful repair and prevent further damage.

They further demonstrate immunomodulatory, anti-inflammatory and cytoprotective properties. The growth factors like vascular endothelial growth factor, secreted by these cells bring about neoangiogenesis. These paracrine effects of stem cell transplantation lead to neuroprotection and subsequent alteration in the disease course and progression.

Stem cell therapy has been shown to be beneficial in the animal studies showing improved motor function. The safety of autologous stem cells transplantation has been established and allogenic cells transplantation is being studied. Stem cell therapy has been shown to be beneficial in prolonging survival, improving respiratory function, muscle strength and bulbar impairment. It also has been shown to slow down the disease progression and rate of decline of the respiratory function. Stem cell therapy has been tested widely and has been repeatedly found to be safe and beneficial in MND.

Motor neuron disease unlike other disorders is a rapidly progressive disease and therefore the aim of stem cell therapy is to halt or slow down the progression of the disease. We conducted a study in Neurogen brain and spine institute where in the survival and rate of disease progression of patients with MND that underwent stem cell therapy was compared with the patients that did not take stem cell therapy. We found that there was significant benefit in survival which means that the survival was prolonged in patients that underwent stem cell therapy and the disease progressed slowly. The patients that were treated with stem cell therapy also found some symptomatic benefits like clearer and louder speech, improved tongue movements, reduced speech fatigability, reduced choking, improved swallowing, reduced saliva drooling, increase respiratory capacity, better neck control, better limb function, better ambulation, fine motor activities, static and dynamic standing and sitting balance.

A 38 year old female was admitted at out center with a diagnosis of definite MND according to El-escorial criteria. When she visited our center ,she had hypertonicity in all 4 limbs. Right lower extremity had severe spasticity with modified Ashworth grading of 3 while all other limbs it was 1. Voluntary control was also affected. Reflexes were exaggerated. Speech was unclear with intelligibility score of 3. She was independent in her activities of daily living with some modifications and moderate support. Functional independence measure score was 98/126. She underwent Autologous bone marrow mononuclear cells intrathecal and intramuscular transplantation 3 years after the onset of the disease. She was advised to take rilutor and a short course of Lithium for 6 weeks. She demonstrated significantly positive changes suggestive of slowing of disease progression. At 6 months due to the beneficial effects noted she underwent repeat stem cell transplantation. Frequency of falls while walking reduced from 15 – 18 times in three months to 2-3 times on three months. The voluntary control improved from fair to good. Strength of distal wrist muscles improved from grade 2++ to a functional grade of 3++ and distal hand muscles from 0 to 1. Speech was clearer and louder. Inspiratory capacity improved from 450 ml to 500 ml. It is interesting to note that the muscle strength in her distal hand muscles improved. De Carvahelo et al 2005 report a 17% decline of ALS-FRS scores every 6 months. The rate of drop of ALS-FRS score in this case was much slower suggesting slowing of disease progression. She had not deteriorated in the span of 9 months which was an improvement in itself as MND is a progressive condition and there is timely deterioration of function.