Unmasking of incipient amyotrophic lateral sclerosis by botulinum toxin therapy

A 65 year old female was treated with Onyx embolisation of a superior cerebellar aneurysm for subarachnoid haemorrhage, resulting in mild residual left leg spasticity, but independent mobility. Eight years later, her left ankle started to turn inwards, and gradually the foot became inverted, ultimately becoming fixed due to tendon shortening from spasticity. There was no fluctuation in the position of the foot and it could not be easily corrected with passive stretching, as might be expected in dystonia. Examination revealed weakness of left ankle dorsiflexion, with normal sensation, reflexes and a flexor plantar response. MRI/MRA of the brain showed a treated aneurysm with no evidence of recurrence. Her weakness continued to progress and over the next 6 months she went on to develop brisk left knee and ankle jerks and a left extensor plantar response. Though there was no clinical evidence of wasting or fasciculation, an EMG of the left lower limb showed active denervation. A diagnosis of ALS was suspected, but with changes only confined to one limb there was insufficient evidence for an unequivocal diagnosis. In an attempt to alleviate severe pain associated with fixed flexion deformity, she was treated with 1,000 units of botulinum toxin A (Dysport) into the left plantar flexor muscles. Four days later, she rapidly deteriorated, developing generalised limb weakness with loss of ambulation, dysphagia and dysarthria. Her clinical course over the next year was entirely consistent with ALS, involving progressive weakness of all four limbs and respiratory failure, and ultimately requiring hospice care. In ALS a pre-clinical phase of motor neuron degeneration is likely to occur before motor symptoms develop. Botulinum toxin prevents acetylcholine-containing vesicles from binding to the pre-synaptic membrane. In its use in the treatment of sialorrhoea in ALS, there are no published reports of generalised exacerbation of limb muscle weakness. Anecdotal side effects include bilateral temporomandibular joint subluxation [1] and facial weakness [2]. In one case a woman with ALS who received botulinum toxin for sialorrhoea became anarthric and aphagic [3]. Botulinum toxin injection has also unmasked Lambert– Eaton myasthenic syndrome [4] and caused clinical deterioration in myasthenis gravis [5] and mitochondrial cytopathies [6]. The fact that symptoms were remote to the treatment site suggests a systemic effect of the toxin, a well-recognised phenomenon that has been demonstrated electrophysiologically in patients without clinical weakness [7]. Denervation and incomplete re-innervation in ALS may predispose to decompensation of the neuromuscular junction even with small amounts of toxin. It is perhaps surprising that more frequent side effects have not been reported in ALS, and the clinical course in this case may relate to the fact that this patient was treated for spasticity with a much larger dose than that generally used for sialorrhoea [8]. Clinicians should be aware of this potentially serious complication of the use of high-dose botulinum toxin in ALS. L. Kent P. Davies R. Kennett S. Wimalaratna R. Kerr M. R. Turner K. Talbot (&) Department of Neurology, John Radcliffe Hospital, Oxford, UK e-mail: Kevin.talbot@ndcn.ox.ac.uk