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01-05-2019 | Dementia | Original Communication

Hereditary primary lateral sclerosis and progressive nonfluent aphasia

Authors: José Gazulla, Isidro Ferrer, Silvia Izquierdo-Alvarez, Sara Alvarez, Rocío Sánchez-Alcudia, María Bestué-Cardiel, María Seral, Isabel Benavente, Esther Sierra-Martínez, José Berciano

Published in: Journal of Neurology | Issue 5/2019

Abstract

Objective

To report a kindred with an association between hereditary primary lateral sclerosis (PLS) and progressive nonfluent aphasia.

Patients and methods

Six members from a kindred with 15 affected individuals spanning three generations, suffered from spasticity without muscle atrophy or fasciculation, starting in the lower limbs and spreading to the upper limbs and bulbar musculature, followed by effortful speech, nonfluent language and dementia, in 5 deceased members. Disease onset was during the sixth decade of life, or later. Cerebellar ataxia was the inaugural manifestation in two patients, and parkinsonism, in another.

Results

Neuropathological examination in two patients demonstrated degeneration of lateral corticospinal tracts in the spinal cord, without loss of spinal, brainstem, or cerebral motor neurons. Greater loss of corticospinal fibers at sacral and lumbar, rather than at cervical or medullary levels was demonstrated, supporting a central axonal dying-back pathogenic mechanism. Marked reduction of myelin and nerve fibers in the frontal lobes was also present. Argyrophilic grain disease and primary age-related tauopathy were found in one case each, and considered incidental findings. Genetic testing, including exome sequencing aimed at PLS, ataxia, hereditary spastic paraplegia, and frontotemporal lobe dementia, triplet-repeated primed polymerase chain reaction aimed at dominant spinocerebellar ataxias, and massive sequencing of the human genome, yielded negative results.

Conclusion

A central distal axonopathy affecting the corticospinal tract, exerted a pathogenic role in the dominantly inherited PLS-progressive nonfluent aphasia association, described herein. Further molecular studies are needed to identify the causative mutation in this disease.

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Title: Hereditary primary lateral sclerosis and progressive nonfluent aphasia
Authors: José Gazulla
Isidro Ferrer
Silvia Izquierdo-Alvarez
Sara Alvarez
Rocío Sánchez-Alcudia
María Bestué-Cardiel
María Seral
Isabel Benavente
Esther Sierra-Martínez
José Berciano
Publication date: 01-05-2019
Publisher: Springer Berlin Heidelberg
Keywords: Dementia
Dementia
Aphasia
Published in: Journal of Neurology / Issue 5/2019
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-019-09235-x

At a glance: The STEP trials

Springer Medicine

Hereditary primary lateral sclerosis and progressive nonfluent aphasia

Abstract

Objective

Patients and methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Patients and methods

Results

Conclusion

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