Mills’ disease is a rare condition characterized by slowly progressive spastic hemiparesis. Typically, there are no prominent lower motor neuron signs but the disease may still be part of amyotrophic lateral sclerosis spectrum (ALS).

This is a retrospective chart review study of 12 patients with Mills’ Syndrome who met criteria of gradual unilateral ascending/descending spastic hemiparesis. Progression of symptoms, signs, pulmonary function tests (PFTs) and amyotrophic lateral sclerosis functional-rating scale- revised (ALSFRS-R) score were monitored at initial and last visits.  Diagnostic workup and death prevalence were collected.

11 patients with Mills had ultimately primary lateral sclerosis (PLS) and 1 patient had ALS diagnosis. All PLS patients developed spasticity within 4 years average from symptom onset. All PLS patients had non-dominant side as initial symptom and none progressed to involve contralateral side. Of PLS patients, 36%, 46% and 18 % had left arm, leg and hemi-side involvement at onset respectively. If symptoms started in the arm, an average of 9-years elapsed before weakness occurs in the leg. If onset was in the leg, an average of 2-years until weakness occurs in the arm. 27% and 18% of PLS patients developed dysarthria and choking within an average of 5 and 7 years of onset respectively. Cervical MRI showed evidence of central canal stenosis in 2 patients. Electromyography showed acute and chronic denervation changes in ALS patient. 50% of PLS patients had worsening PFTs but none required bilevel-positive-airway-pressure (BiPAP), whereas the ALS patient required BiPAP within 3 years of symptom onset. In PLS patients, ALSFRS-R score worsened by 0.5 points/year. None died over 10 year follow-up period.

ALS Mills’ Disease is rare. PLS Mill’s variant has slower progression if it starts in the nondominant upper-extremity with mild bulbar and respiratory symptoms.