Motor neuron disease with malignancy: Clinical and pathophysiological insights.

OBJECTIVE

While some regard an association between motor neuron disease (MND) and malignancy as co-incidental, others have argued that it could represent a distinct clinical entity. The present study undertook in depth phenotyping along with assessment of cortical function to further explore disease pathophysiology in MND with malignancy (MND-M) patients.

METHODS

Clinical features along with assessment of peripheral and cortical function was undertaken in 13 MND-M and results were compared to sporadic and familial MND cohorts.

RESULTS

From a cohort 13 patients (10 males; aged 65.2 ± 2.0 years), 38.5% were diagnosed with a haematological malignancy. The lower motor neuron phenotype predominated in the in the MND-M patients (χ2 = 10.8, P < 0.01), with the upper motor neuron (UMN) score being significantly reduced in MND-M patients compared to sporadic and familial MND cohorts (χ2 = 6.84, P < 0.01). The neurological deficits did not respond to treatment of the underlying malignancy in the majority of MND-M (92%) patients, and as such there were no significant differences in survival between the cohorts. Despite a paucity of UMN signs, cortical hyperexcitability was evident in MND-M patients, as indicated by reduction in short interval intracortical inhibition (P < 0.01) and increase in motor evoked potential amplitude (P < 0.01), that were similar to findings in sporadic and familial MND cohorts.

CONCLUSIONS

The present study suggests that MND-M falls within the spectrum of MND.

SIGNIFICANCE: The concept of a co-incidental association between MND and malignancy is supported through the present study by the presence of cortical dysfunction, combined with clinical findings that can be explained within the spectrum of abnormality evident in classical MND phenotypes.