Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)
Updates to Article Attributes
Cathepsin-A A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is a very rare monogenic cererbalautosomal dominant cerebral small-vessel disease.
Epidemiology
CARASAL is considered extremely rare, with less than thirty cases reported in the literature 1-5. The condition tends to clinically manifest in the third to fifth decades of life 2.
Clinical presentation
The potential clinical manifestations are varied and may be mild for the degree of radiographic changes 1-5:
focal neurological deficits from stroke
migraine-like headache
cognitive impairment and dementia
movement disorders, e.g. gait disorder, dystonia
vestibulocochlear symptoms
Extra-cranial clinical manifestations may also be seen, although, given the rarity of the condition, it is unclear if these are due to CARASAL or are simply seen in association 1-5:
sicca symptoms
hearing issuesatypical facial painmuscle cramps
systemic hypertension
Pathology
CARASAL is caused by a point mutation (c.973C>T) in the CTSA gene, located within chromosome 20q13.12, which encodes for cathepsin-A 1-4. This mutation is inherited in an autosomal dominant pattern 1-5. It is yet to be fully elucidated how this mutation leads to the clinicoradiolgoical syndrome that is observed in CARASAL 1,5.
Notably, this is condition is very distinct from autosomal recessive mutations in CTSA implicated in the lysosomal storage disorder galactosialidosis 2.
Radiographic features
MRI is the imaging modality of choice and demonstrates the following features 1-5:
-
leukoencephalopathy and lacunar infarcts
extensive subcortical white matter involvement sparing subcortical U-fibres, typically in frontoparietal regions and sparing temporal white matter
deeper structures such as in the basal ganglia, thalamus, pons, and dentate nuclei
-
deep cerebral microhaemorrhages
uncommon feature
deep intracerebral (macro)haemorrhage is very rare
Treatment and prognosis
No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended 1. It is thought that life expectancy is similar to that of an unaffected individual 4.
Differential diagnosis
-<p><strong>Cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)</strong> is a very rare monogenic cererbal small-vessel disease.</p><h4>Epidemiology</h4><p>CARASAL is considered extremely rare, with less than thirty cases reported in the literature <sup>1</sup>. The condition tends to clinically manifest in the third to fifth decades of life <sup>2</sup>.</p><h4>Clinical presentation</h4><p>The potential clinical manifestations are varied and may be mild for the degree of radiographic changes <sup>1-5</sup>:</p><ul>- +<p><strong>Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)</strong> is a very rare monogenic autosomal dominant cerebral small-vessel disease.</p><h4>Epidemiology</h4><p>CARASAL is considered extremely rare, with less than thirty cases reported in the literature <sup>1-5</sup>. The condition tends to clinically manifest in the third to fifth decades of life <sup>2</sup>.</p><h4>Clinical presentation</h4><p>The potential clinical manifestations are varied and may be mild for the degree of radiographic changes <sup>1-5</sup>:</p><ul>
- +<li><p>vestibulocochlear symptoms</p></li>
-<li><p>hearing issues</p></li>- +<li><p>atypical facial pain</p></li>
-<li><p>subcortical white matter sparing <a href="/articles/subcortical-u-fibres-3" title="Subcortical U-fibres">subcortical U-fibres</a>, typically in frontoparietal regions and sparing temporal white matter</p></li>- +<li><p>extensive subcortical white matter involvement sparing <a href="/articles/subcortical-u-fibres-3" title="Subcortical U-fibres">subcortical U-fibres</a>, typically in frontoparietal regions and sparing temporal white matter</p></li>
-<li><p><a href="/articles/intracerebral-haemorrhage">intracerebral (macro)haemorrhage</a> is very rare</p></li>- +<li><p>deep <a href="/articles/intracerebral-haemorrhage">intracerebral (macro)haemorrhage</a> is very rare</p></li>
References changed:
- 1. Mancuso M, Arnold M, Bersano A et al. Monogenic Cerebral Small-Vessel Diseases: Diagnosis and Therapy. Consensus Recommendations of the European Academy of Neurology. Eur J Neurol. 2020;27(6):909-27. <a href="https://doi.org/10.1111/ene.14183">doi:10.1111/ene.14183</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/32196841">Pubmed</a>
- 2. Bugiani M, Kevelam S, Bakels H et al. Cathepsin A-Related Arteriopathy with Strokes and Leukoencephalopathy (CARASAL). Neurology. 2016;87(17):1777-86. <a href="https://doi.org/10.1212/WNL.0000000000003251">doi:10.1212/WNL.0000000000003251</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/27664989">Pubmed</a>
- 3. Hervé D, Chabriat H, Rigal M et al. A Novel Hereditary Extensive Vascular Leukoencephalopathy Mapping to Chromosome 20q13. Neurology. 2012;79(23):2283-7. <a href="https://doi.org/10.1212/WNL.0b013e3182768954">doi:10.1212/WNL.0b013e3182768954</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/23175731">Pubmed</a>
- 4. Finsterer J, Scorza C, Scorza F, Wakil S. Update on Hereditary, Autosomal Dominant Cathepsin-A-Related Arteriopathy with Strokes and Leukoencephalopathy (CARASAL). Acta Neurol Belg. 2019;119(3):299-303. <a href="https://doi.org/10.1007/s13760-019-01158-8">doi:10.1007/s13760-019-01158-8</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/31177426">Pubmed</a>
- 5. Budhdeo S, de Paiva A, Wade C et al. A Rare Cause of Monogenic Cerebral Small Vessel Disease and Stroke: Cathepsin A-Related Arteriopathy with Strokes and Leukoencephalopathy (CARASAL). J Neurol. 2022;269(12):6673-7. <a href="https://doi.org/10.1007/s00415-022-11302-9">doi:10.1007/s00415-022-11302-9</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/35904593">Pubmed</a>
Tags changed:
- cases
Systems changed:
- Central Nervous System
Unable to process the form. Check for errors and try again.