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Towards a neurocognitive profile in familial cerebral cavernous malformations
Cristiana Silva1, João Durães2,3,4, Marisa Lima1,5,6
1Neurology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Professor Mota Pinto, 3004-561, Coimbra, Portugal.
Background:
Familial cerebral cavernous malformations (FCCM) is a rare autosomal dominant disease, characterized by vascular malformations that can lead to macro and microhemorrhages. The neurocognitive impact of FCCM is still underrecognized.
Methods:
We report the clinical, neurocognitive, imaging and genetic data of a three generation family with FCCM.
Results:
A 63-year-old man (proband) had progressive memory impairment since the last year. Neurologic exam was unremarkable. Brain MRI showed multiple large cavernomas (mainly in the pons, left temporal, and right temporo-parietal) and scattered microhemorrhages. Neuropsychological assessment mainly revealed left frontal and right temporo-parietal dysfunction. A 41-year-old daughter, presented with headache, vertigo and memory complaints in the last 2 years. Neurological examination revealed left central facial paralysis. Brain MRI showed two small right parietal and internal capsule cavernomas, as well as microhemorrhages. Neuropsychological assessment showed moderate temporal neocortical left dysfunction. A 34-year-old daughter had recurrent headache and memory complaints, with unremarkable neurological exam. Brain MRI revealed two large cavernomas (left fronto-orbitary and inferior temporal), with few microhemorrhages. Neuropsychological assessment was normal. A granddaughter had mild headaches and a small right cerebellar cavernoma, without microhemorrhages. Neuropsychological assessment showed mild temporal neocortical left dysfunction. A nonsense variant, c.55C > T; p.R19* generating a premature stop codon in CCM2 gene shared by all affected family members was identified.
Conclusions:
Neuropsychological evaluation showed that memory complaints and cognitive impairment could be an important unrecognized finding in FCCM. Its pathophysiological mechanisms are still unknown but the role of recurrent microhemorrhages could provide an interesting hypothesis.
Insights
Familial cerebral cavernous malformations (FCCM) can cause significant cognitive impairment, particularly memory problems. Early neurocognitive evaluation is crucial for understanding and managing this underrecognized aspect of FCCM.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Familial cerebral cavernous malformations (FCCM) is a rare autosomal dominant disorder.
- Characterized by vascular malformations leading to hemorrhages, FCCM's neurocognitive impact is often overlooked.
Observation:
- A three-generation family with FCCM presented with varied symptoms including memory loss, headaches, and vertigo.
- Brain imaging revealed multiple cavernomas and microhemorrhages in affected individuals.
- Genetic analysis identified a shared nonsense variant in the CCM2 gene.
Findings:
- Neuropsychological assessments indicated cognitive deficits, particularly in memory and executive functions, correlating with lesion location.
- Severity of cognitive impairment varied among family members, with some showing normal assessments despite imaging findings.
- A specific CCM2 gene variant (c.55C>T; p.R19*) was identified in all affected individuals.
Implications:
- Cognitive impairment, especially memory complaints, may be a significant and underrecognized feature of FCCM.
- Recurrent microhemorrhages are hypothesized to play a role in the pathophysiology of cognitive decline in FCCM.
- Further research into the neurocognitive impact and mechanisms of FCCM is warranted.
