Amyotrophic lateral sclerosis-plus syndrome with TAR DNA-binding protein-43 pathology.
BACKGROUND
Amyotrophic lateral sclerosis (ALS)-Plus syndromes meet clinical criteria for ALS but also include 1 or more additional features such as dementia, geographic clustering, extrapyramidal signs, objective sensory loss, autonomic dysfunction, cerebellar degeneration, or ocular motility disturbance.


METHODS
We performed a whole-brain and spinal cord pathologic analysis in a patient with an ALS-Plus syndrome that included repetitive behaviors along with extrapyramidal and supranuclear ocular motility disturbances resembling the clinical phenotype of progressive supranuclear palsy.


RESULTS
There was motoneuron cell loss and degeneration of the corticospinal tracts. Bunina bodies were present. TAR DNA-binding protein-43 pathology was diffuse. Significant tau pathology was absent.


CONCLUSIONS
TAR DNA-binding protein-43 disorders can produce a clinical spectrum of neurodegeneration that includes ALS, frontotemporal lobar degeneration, and ALS with frontotemporal lobar degeneration. The present case illustrates that isolated TAR DNA-binding protein-43 disorders can produce an ALS-Plus syndrome with extrapyramidal features and supranuclear gaze palsy resembling progressive supranuclear palsy.
McCluskey
Leo F
LF
Department of Neurology, University of Pennsylvania School of Medicine, 330 S 9th St, Philadelphia, PA 19107, USA. lfmcclusky@pahosp.com
Elman
Lauren B
LB
Martinez-Lage
Maria
M
Van Deerlin
Vivianna
V
Yuan
Wuxing
W
Clay
Dana
D
Siderowf
Andrew
A
Trojanowski
John Q
JQ
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D017809:Fatal Outcome; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D008297:Male; D009046:Motor Neurons / Q000473:pathology; D009154:Mutation / Q000235:genetics; D015835:Ocular Motility Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000473:pathology
D004268:DNA-Binding Proteins; D005819:Genetic Markers