Differentiation of Hereditary Spastic Paraparesis From Primary Lateral Sclerosis in Sporadic Adult-Onset Upper Motor Neuron Syndromes

Brugman, Frans; Veldink, Jan H.; Franssen, Hessel; Visser, Marjolein; Jong, J.M.B.V. de; Faber, Carin G.; Kremer, Berry; Schelhaas, H. Jurgen; Doorn, Pieter A. van; Verschuuren, Jan J.; Bruyn, R.P.M.; Kuks, Jan B. M.; Robberecht, Wim; Wokke, John H. J.; Berg, Leonard H van den

doi:10.1001/archneurol.2009.19

Cited by 67 publications

(37 citation statements)

References 43 publications

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“…Patients with signs of UMN and LMN involvement were classified as having definite, probable or possible ALS using the revised El Escorial criteria after excluding other conditions 1. Patients with a ‘clinical UMN phenotype’ did not have any LMN findings on clinical examination or electromyography as described previously 13. Seven of these 19 patients had a disease duration longer than 4 years and were diagnosed as having primary lateral sclerosis 14.…”

Section: Methodsmentioning

confidence: 99%

Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Walhout

Westeneng

Verstraete

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

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Section: Methodsmentioning

confidence: 99%

Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Walhout

Westeneng

Verstraete

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

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“…Frontotemporal dementia (FTD), cognitive impairment and altered behavior occur in PLS comparably to ALS (14). Ultimately, PLS is a clinical diagnosis that relies upon exclusion of other known causes of progressive spasticity, such as apparently sporadic presentations of hereditary spastic paraparesis (15). …”

Section: Clinical Phenotypesmentioning

confidence: 99%

Deciphering amyotrophic lateral sclerosis: What phenotype, neuropathology and genetics are telling us about pathogenesis

Ravits¹,

Appel²,

Baloh³

et al. 2013

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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150

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Amyotrophic lateral sclerosis (ALS) is characterized phenotypically by progressive weakness and neuropathologically by loss of motor neurons. Phenotypically, there is marked heterogeneity. Typical ALS has mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Primary lateral sclerosis has predominant UMN involvement. Progressive muscular atrophy has predominant LMN involvement. Bulbar and limb ALS have predominant regional involvement. Frontotemporal dementia has significant cognitive and behavioral involvement. These phenotypes can be so distinctive that they would seem to have differing biology. However, they cannot be distinguished, at least neuropathologically or genetically. In sporadic ALS (SALS), they are mostly characterized by ubiquitinated cytoplasmic inclusions of TDP-43. In familial ALS (FALS), where phenotypes are indistinguishable from SALS and similarly heterogeneous, each mutated gene has its own genetic and molecular signature. Overall, since the same phenotypes can have multiple causes including different gene mutations, there must be multiple molecular mechanisms causing ALS – and ALS is a syndrome. Since, however, multiple phenotypes can be caused by one single gene mutation, a single molecular mechanism can cause heterogeneity. What the mechanisms are remain unknown, but active propagation of the pathology neuroanatomically seems to be a principal component. Leading candidate mechanisms include RNA processing, cell-cell interactions between neurons and non-neuronal neighbors, focal seeding from a misfolded protein that has prion-like propagation, and fatal errors introduced during neurodevelopment of the motor system. If fundamental mechanisms could be identified and understood, ALS therapy could rationally target progression and stop the disease – a goal that seems increasingly achievable.

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“…The strong family history supported HSP, while the prominent bulbar symptoms, lack of urinary urgency or impaired vibration sensation bolstered a PLS diagnosis. These subtle clinical clues have been used to differentiate the two [12], yet genetic testing remains a superior tool [13]. Subsequent genetic testing for common HSP variants did not reveal any clinically relevant mutations, and thus a verdict of PLS was reached.…”

Section: Introductionmentioning

confidence: 99%

Functional Neuroprostheses for Foot Drop Improve Gait Outcomes in Primary Lateral Sclerosis

Bedlack¹

2015

CSMC

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Differentiation of Hereditary Spastic Paraparesis From Primary Lateral Sclerosis in Sporadic Adult-Onset Upper Motor Neuron Syndromes

Abstract: To study whether clinical characteristics can differentiate sporadic presentations of hereditary spastic paraparesis (HSP) from primary lateral sclerosis (PLS). Differentiation between these diseases is important for genetic counseling and prognostication.

Cited by 67 publications

References 43 publications

Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Deciphering amyotrophic lateral sclerosis: What phenotype, neuropathology and genetics are telling us about pathogenesis

Functional Neuroprostheses for Foot Drop Improve Gait Outcomes in Primary Lateral Sclerosis

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