Parkinsonism and Motor Neuron Diseases: Twenty-Seven Patients with Diverse Overlap Syndromes
ABSTRACT It has long been recognized that signs of motor neuron disease (MND) may accompany clinical evidence of parkinsonism in different neurodegenerative conditions. By using the Columbia University Division of Movement Disorders database, we reviewed data from 5,500 cases of parkinsonism and recorded the presence of upper motor neuron (UMN) dysfunction, lower motor neuron (LMN) dysfunction, or both. Among the 27 patients so identified, we counted those with autonomic dysfunction, cerebellar dysfunction, or dementia. Among the 27 cases, seven had UMN signs and LMN signs as well as parkinsonism and were diagnosed with amyotrophic lateral sclerosis (ALS)-parkinsonism (Brait-Fahn disease). Three of the seven had dementia that was not deemed to be frontotemporal dementia (FTD). Six other patients had no LMN signs but had UMN signs and parkinsonism and were classified as having primary lateral sclerosis (PLS)-parkinsonism. Four patients had both UMN and LMN signs with parkinsonism as well as the characteristic dementia of FTD; they were diagnosed with FTD-parkinsonism-ALS. Seven patients had MND, parkinsonism, and autonomic or cerebellar dysfunction, a combination compatible with multiple system atrophy (MSA). Three patients had syndromes compatible with hereditary spastic paraplegia (HSP). In sum, we found that MND occurs in association with diverse parkinsonian syndromes; some are heritable, others sporadic and causes are uncertain. Having MND may be a risk factor for parkinsonism. A prospective study may elucidate this possibility.
SourceAvailable from: Maria Stamelou[Show abstract] [Hide abstract]
ABSTRACT: Atypical parkinsonism comprises typically progressive supranuclear palsy, corticobasal degeneration, and mutilple system atrophy, which are distinct pathologic entities; despite ongoing research, their cause and pathophysiology are still unknown, and there are no biomarkers or effective treatments available. The expanding phenotypic spectrum of these disorders as well as the expanding pathologic spectrum of their classic phenotypes makes the early differential diagnosis challenging for the clinician. Here, clinical features and investigations that may help to diagnose these conditions and the existing limited treatment options are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.Neurologic Clinics 11/2014; 33(1). DOI:10.1016/j.ncl.2014.09.012 · 1.61 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Objective: Autopsy studies show widespread pathology in amyotrophic lateral sclerosis (ALS), but clinical surveys of multisystem disease in ALS are rare. We investigated ALS-Plus syndrome, an understudied group of patients with clinical features extending beyond pyramidal and neuromuscular systems with or without cognitive/behavioral deficits. Methods: In a large, consecutively-ascertained cohort of 550 patients with ALS, we documented atypical clinical manifestations. Genetic screening for C9orf72 hexanucleotide expansions was performed in 343 patients, and SOD1, TARDBP, and VCP were tested in the subgroup of patients with a family history of ALS. Gray matter and white matter imaging was available in a subgroup of 30 patients. Results: Seventy-five (13.6%) patients were identified with ALS-Plus syndrome. We found disorders of ocular motility, cerebellar, extrapyramidal and autonomic functioning. Relative to those without ALS-Plus, cognitive impairment (8.0% vs 2.9%, p = 0.029), bulbar-onset (49.3% vs 23.2%, p < 0.001), and pathogenic mutations (20.0% vs 8.4%, p = 0.015) were more than twice as common in ALS-Plus. Survival was significantly shorter in ALS-Plus (29.66 months vs 42.50 months, p = 0.02), regardless of bulbar-onset or mutation status. Imaging revealed significantly greater cerebellar and cerebral disease in ALS-Plus compared to those without ALS-Plus. Conclusions: ALS-Plus syndrome is not uncommon, and the presence of these atypical features is consistent with neuropathological observations that ALS is a multisystem disorder. ALS-Plus syndrome is associated with increased risk for poor survival and the presence of a pathogenic mutation. (C) 2014 Elsevier B.V. All tights reserved.Journal of the Neurological Sciences 07/2014; 345(1-2). DOI:10.1016/j.jns.2014.07.022 · 2.26 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3-5 years after onset-a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. Here, we review the phenotypic variability of ALS and how it is reflected in familial and sporadic ALS, in the degree of upper and lower motor neuron involvement, in motor and extramotor involvement, and in the spectrum of ALS and frontotemporal dementia. Furthermore, we discuss some unusual clinical characteristics regarding presentation, age at onset and disease progression. Finally, we address the importance of this variability for understanding the pathogenesis of ALS and for the development of therapeutic strategies.Nature Reviews Neurology 10/2014; 10(11). DOI:10.1038/nrneurol.2014.184 · 14.10 Impact Factor