Mills’ syndrome is a unique entity of upper motor neuron disease with N-shaped progression: Three case reports

Table 1 Patient clinical characteristics

Characteristics	Case 1	Case 2	Case 3
Sex	F	F	M
Age at onset, yr	65	71	54
Duration of disease from onset, mo	36	6	7
Site of disease onset	LLL	RLL	LLL
Evolution of symptoms	LLL-LUL-RLL	RLL-RUL-LLL-LUL-bulbar symptoms	LLL-LUL-RLL-RUL-bulbar symptoms
Bulbar symptoms	None	Yes	Yes
Sensory symptoms	None	None	None
Tone	Hypertonia in left side	Hypertonia in right side	Hypertonia in left side
Power (MRC grade)	Left side (grade 3/5)	Right side (grade 4/5)	LLL (grade 1/5); LUL (grade 4/5)
Reflexes	Hyperreflexia in left side	Hyperreflexia in all limbs right ankle clonus	Hyperreflexia in left side, left ankle clonus
Babinski’s sign	Negative	Positive in right side	Negative
Laboratory test	Normal	Normal	Normal
EMG	Increased polyphonic motor unit potentials	Unremarkable	Minor chronic denervation
Follow-up	Mobility with the help of a cane	Died from respiratory failure 32 mo after the onset of symptoms	Died from respiratory failure 44 mo after the onset of symptoms

F: Female; M: Male; RUL: Right upper limb; RLL: Right lower limb; LUL: Left upper limb; LLL: Left lower limb; EMG: Electromyography; MRC: Medical Research Council.

Table 2 Differential diagnosis of Mills’ syndrome from amyotrophic lateral sclerosis and primary lateral sclerosis

	Mills’ syndrome	ALS	PLS
Upper motor neuron signs	Positive	Positive	Positive
Lower motor neuron signs	Negative	Positive	Negative
Initial site of disease onset	Unilateral lower limb	Commonly bilateral	Commonly bilateral
Progression manner	One side lower limb - the same side upper limb - contralateral lower limb - contralateral upper limb	From one segment to the others (cranial, cervical, thoracic, and lumbosacral)	Usually ascending
Bulbar involvement	Late stage	Middle or late stage	Late stage
Symmetry of the symptom	Significant asymmetry	Could be symmetric or asymmetric	Commonly symmetric
Electrophysiological examination	Non-special	Positive	Non-special
Prognosis	Uncertain, probably rapid progression	Rapid progression, poor prognosis	Relatively benign

ALS: Amyotrophic lateral sclerosis; PLS: Primary lateral sclerosis.