Objective: To describe the clinical and neuropathological findings of a patient carrier of a mutation in the SPG4 gene.

Background: Hereditary spastic paraplegia (HSP) linked to mutations in the SPG4 gene is basically characterized by lower extremity weakness and spasticity. A few cases with cognitive impairment have been described. Nevertheless, the etiopathogenic mechanisms of this cognitive decline are unknown.

Method: A 70 year old woman presented with a late-onset cognitive decline. After ancillary tests, she was diagnosed of Alzheimer’s disease. The patient and her son, affected by a HSP, were heterozygous carriers of the mutation NM_014946.3: c.1291C> in exon 10 of the SPG4 gene. She died at the age of 84 due to urinary tract infection.

Results: The neuropathological study showed beta-amyloid inclusions in the limbic system and the majority of cortical areas studied, as well as Tau-related neurofibrillary pathology in the limbic system, deep nuclei, subcortical white matter, parahipocampal and prefrontal cortex. Argyrophilic grain disease was also observed, with involvement of amygdala and hippocampus, nucleus accumbens, entorhinal, insular and focally cingular cortex. She also presented mild chronic cerebrovascular disease with arteriosclerosis and mild-moderate arteriolohyalinosis, as well as moderate amyloid angiopathy. No axonal degeneration was found in the corticospinal tracts or in the fibers of the gracile fascicle. No pathological inclusions of polyglutamine, C9RANT or FUS have been observed.

Conclusion: The neuropathological findings in this patient are compatible with Alzheimer’s disease, argyrophilic grain disease and chronic cerebrovascular disease. Cognitive decline in this patient probably has a multifactorial etiology. The etiopathogenic role of mutations in the SPG4 gene on cognitive impairment is still undetermined.

References: 1. Faber et al. Cognitive dysfunction in hereditary spastic paraplegias and other motor neuron disorders. Dement Neuropsychol 2016 December;10(4):276-279. 2. Murphy S et al. Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence. Neurology. 2009;73:378-84. 3. White KD et al. Clinical and pathological findings in hereditary spastic paraparesis with spastin mutation. Neurology 2000;55:89 –94.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/neuropathological-findings-in-a-spg4-gene-mutation-carrier/