Mills Syndrome with Dementia

Introduction: charles karsner mills (1845–1931) and his syndrome

In 1900, Charles Karsner Mills (1845–1931), a neurologist working in Philadelphia, first described a patient with a slowly progressive ascending hemiplegia without significant sensory involvement 1. He considered the differential diagnosis to include an unusual form of unilateral disseminated sclerosis (multiple sclerosis), unilateral amyotrophic sclerosis, a focal cerebral lesion, a degenerative motor neuritis, and a functional hemiparesis, but he concluded, “I cannot but feel that the case may represent a somewhat unusual form of amyotrophic lateral sclerosis” although he acknowledged the absence of localized atrophy and spasticity 1. In a long and distinguished neurological career marked by contributions to the understanding of many neurological disorders 2, 3, Mills twice returned to the subject of progressive hemiplegia, acknowledging that this could be not only an ascending but also a descending process 4, 5. In the latter paper, dating from 1906, he stressed that unilateral hemiplegia might result from several causal mechanisms including not only primary pyramidal tract degeneration but also multiple sclerosis, amyotrophic lateral sclerosis (ALS), paralysis agitans (Parkinson's disease), focal cerebral and spinal lesions, neurosyphilis, and hysterical affections 5.

Abstract

In the first decade of the twentieth century, the American neurologist Charles Karsner Mills described a syndrome of slowly progressive ascending or descending hemiplegia without significant sensory involvement, which now bears his name. The nosology and etiology of this rare syndrome has remained uncertain, but certainly some cases result from a localized form of amyotrophic lateral sclerosis (ALS). Since cognitive impairments, sometimes amounting to a dementia, are increasingly recognized to be a feature of ALS, it might be expected that Mills syndrome might also be attended with cognitive impairments, as first reported in 2005. This review article examines the original publication of Mills, the nosology of his syndrome, its relation to ALS, and the cognitive phenotype seen in this condition, as well as suggesting how to classify this disorder within the current nomenclature for frontotemporal lobar degenerations.

Keywords

Mills Syndrome, Dementia, amyotrophic lateral sclerosis, primary lateral sclerosis, frontotemporal lobar degeneration