Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2009 Jan;66(1):121-4.
doi: 10.1001/archneur.66.1.121.

Amyotrophic lateral sclerosis-plus syndrome with TAR DNA-binding protein-43 pathology

Leo F McCluskey  1 , Lauren B Elman, Maria Martinez-Lage, Vivianna Van Deerlin, Wuxing Yuan, Dana Clay, Andrew Siderowf, John Q Trojanowski
Affiliations
Case Reports

Amyotrophic lateral sclerosis-plus syndrome with TAR DNA-binding protein-43 pathology

Leo F McCluskey et al. Arch Neurol. 2009 Jan.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
TAR DNA-binding protein-43 pathology in the amygdala and midbrain (substantia nigra). A, Representative section of the amygdala stained with TDP-43 shows severe pathologic findings with abundant neuronal and some glial cytoplasmic inclusions. Note the characteristic nuclear clearing of the involved cells in contrast with the normal nuclear staining of a spared cell (arrow). This pattern was present in other brain areas such as the basal ganglia. B, In the substantia nigra, there were occasional round dense cytoplasmic inclusions (Lewy body–like inclusions) as well as glial cytoplasmic inclusions, as shown here in high power, adjacent to the affected dopaminergic neuron (arrowhead).
Figure 2
Figure 2
Extent and distribution of TAR DNA-binding protein-43 pathology. SN indicates substantia nigra. For disease severity, 1 is mild; 2, moderate; and 3, severe.
See this image and copyright information in PMC

References

    1. Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916–919. - PubMed
    1. Van Deerlin VM, Wood EM, Moore P, et al. Clinical, genetic, and pathologic characteristics of patients with frontotemporal dementia and progranulin mutations. Arch Neurol. 2007;64(8):1148–1153. - PubMed
    1. Van Deerlin VM, Leverenz JB, Bekris LM, et al. TARDP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histological analysis. Lancet Neurol. 2008;7(5):409–416. - PMC - PubMed
    1. Brooks BR, Miller RG, Swash M, Munsat TL. World Federation of Neurology Research Group on Motoneuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motoneuron Disord. 2000;1(5):293–299. - PubMed
    1. Ward C. Characteristics and symptom management of progressive supra-nuclear palsy: a multidisciplinary approach. J Neurosci Nurs. 2006;38(4):242–247. - PubMed

Publication types

MeSH terms