Stabilisation and functional improvement in ALS with a bulbar phenotype

History

The disease developed over several years, gradually involving both bulbar and motor functions.

As it progressed, her independent mobility declined considerably. By the time of the last specialist assessment the patient was confined to a wheelchair, could no longer stand unaided and had lost the ability to feed herself. The neurological status described marked weakness of the limbs, anarthria, drooling and marked weakness of the neck muscles with head drop.

The bulbar component of the disease remained particularly severe. Swallowing assessment confirmed marked dysphagia with impairment of the oral and pharyngeal phases, repeated swallowing attempts and a risk of aspiration.

Electromyography showed widespread chronic neurogenic muscle weakness involving the cranial musculature and all four limbs, with signs of reinnervation, loss of motor units and active denervation.

Before treatment

The patient's main functional problems were:

• marked tetraparesis, with no independent mobility; function of the right arm was the best preserved
• marked weakness of the neck muscles and inability to hold the head up properly
• severe pain in the neck, collar and shoulder region
• anarthria
• marked dysphagia
• constant drooling
• impaired respiratory function

The respiratory component required separate monitoring. A marked restrictive ventilatory deficit had already been recorded, and later signs of nocturnal hypoventilation, so non-invasive ventilatory support was under discussion.

Before the programme, then, this was a patient with an already marked motor and bulbar deficit, for whom the first priority was to stabilise further deterioration as far as possible and preserve the functional capacity that remained.

The programme

Given the clinical picture, a personalised combined programme of cell, immunoregulatory and neuroregenerative therapy was designed.

The programme included:

• therapy with mesenchymal stromal cells
• use of regulatory T cells
• systemic and neurally targeted components of the cell therapy
• concentrated exosome therapy
• intranasal peptide support

The specific doses and the sequence of procedures formed part of an individual internal protocol and were set after clinical assessment of the patient.

Course after treatment

After the programme, no further marked clinical deterioration was seen over the follow-up period, which was particularly significant given how the disease had been progressing beforehand.

Motor function

The patient noted increased strength in the limbs. Movement came more easily and the motor activity she retained improved.

Positive change in the neck muscles was noted separately – her ability to hold her head up and control its position improved.

Pain

One of the most noticeable subjective results was a considerable reduction in pain in the neck, shoulder and collar region.

Before treatment, head drop and marked weakness of the neck musculature had been accompanied by severe pain; this problem was set out directly in the medical records as well.

Drooling

The patient and those close to her also noted less pronounced drooling, which before treatment had been one of the constant features of the bulbar syndrome.

Respiratory function

Particular attention was paid to respiratory status. Despite the respiratory impairment present at the outset and the risk of further decline in ventilatory function, no marked progression of respiratory symptoms occurred over the follow-up period.

Beyond stabilisation, the patient reported some subjective easing of her breathing. We regard the main result in this area, however, as preservation of respiratory function without the further deterioration that would have been expected.