Cerebral transthyretin-associated amyloidoses
Updates to Article Attributes
Cerebral involvement can be seen transthyretin-associated amyloidoses and presents as a neurodegenerative disease.
Epidemiology
Age of presentation is very wide, ranging from adolescence to old age 1.
Clinical presentation
Clinical presentation is variable, but includes 1:
dementia
spastic paresis
seizures
recurrent parenchymal and subarachnoid haemorrhages
The diagnosis is often not made during life, unless specific gene testing is performed, once the diagnosis is suspected.
Pathology
Cerebral transthyretin-associated amyloidoses have been linked to a rare mutation of the transthyretin gene (chromosome 18q11.2-12.1), the product of which is a transport protein by the same name, responsible for transport of thyroxin-binding and retinol-binding peptides. Dysfunction of transthyretin results in accumulation of these peptides and the formation of amyloid deposits 1.
Radiographic features
MRI
Unfortunately, no specific features exist, and appearances are similar to those of sporadic cerebral amyloid angiopathy (CAA) 1. Features therefore may include2:
multiple parenchymal haemorrhages of various age and size
cortical superficial siderosis
duedue to repeated convexal subarachnoid haemorrhagemicroinfarcts
While these features exist, it is worth noting that many patients with transthyretin-associated amyloidoses may have cardiac devices, which may preclude them from having an MRI 3.
Differential diagnosis
-
cerebral amyloid angiopathy (CAA)
indistinguishable on imaging
usually only seen in elderly patients
-<p><strong>Cerebral involvement </strong>can be seen <a href="/articles/transthyretin-associated-amyloidoses">transthyretin-associated amyloidoses</a> and presents as a <a href="/articles/neurodegenerative-disease">neurodegenerative disease</a>. </p><h4>Epidemiology</h4><p>Age of presentation is very wide, ranging from adolescence to old age <sup>1</sup>. </p><h4>Clinical presentation</h4><p>Clinical presentation is variable, but includes<sup> 1</sup>:</p><ul>-<li>dementia</li>-<li>spastic paresis</li>-<li>seizures</li>-<li>recurrent parenchymal and <a href="/articles/subarachnoid-haemorrhage">subarachnoid haemorrhages</a>-</li>-</ul><p>The diagnosis is often not made during life, unless specific gene testing is performed, once the diagnosis is suspected. </p><h4>Pathology</h4><p>Cerebral transthyretin-associated amyloidoses have been linked to a rare mutation of the transthyretin gene (chromosome 18q11.2-12.1), the product of which is a transport protein by the same name, responsible for transport of thyroxin-binding and retinol-binding peptides. Dysfunction of transthyretin results in accumulation of these peptides and the formation of amyloid deposits <sup>1</sup>. </p><h4>Radiographic features</h4><p>Unfortunately, no specific features exist, and appearances are those of <a href="/articles/cerebral-amyloid-angiopathy-1">cerebral amyloid angiopathy (CAA)</a> <sup>1</sup>. Features therefore include:</p><ul>-<li>multiple parenchymal haemorrhages of various age and size</li>-<li>-<a href="/articles/superficial-siderosis">superficial siderosis</a> due to repeated <a href="/articles/subarachnoid-haemorrhage">subarachnoid haemorrhage</a>-</li>-</ul><h4>Differential diagnosis</h4><ul><li>-<a href="/articles/cerebral-amyloid-angiopathy-1">cerebral amyloid angiopathy (CAA)</a><ul>-<li>indistinguishable on imaging</li>-<li>usually only seen in elderly patients</li>- +<p><strong>Cerebral involvement </strong>can be seen <a href="/articles/transthyretin-associated-amyloidoses">transthyretin-associated amyloidoses</a> and presents as a <a href="/articles/neurodegenerative-disease">neurodegenerative disease</a>. </p><h4>Epidemiology</h4><p>Age of presentation is very wide, ranging from adolescence to old age <sup>1</sup>. </p><h4>Clinical presentation</h4><p>Clinical presentation is variable, but includes<sup> 1</sup>:</p><ul>
- +<li><p>dementia</p></li>
- +<li><p>spastic paresis</p></li>
- +<li><p>seizures</p></li>
- +<li><p>recurrent parenchymal and <a href="/articles/subarachnoid-haemorrhage">subarachnoid haemorrhages</a></p></li>
- +</ul><p>The diagnosis is often not made during life, unless specific gene testing is performed, once the diagnosis is suspected. </p><h4>Pathology</h4><p>Cerebral transthyretin-associated amyloidoses have been linked to a rare mutation of the transthyretin gene (chromosome 18q11.2-12.1), the product of which is a transport protein by the same name, responsible for transport of thyroxin-binding and retinol-binding peptides. Dysfunction of transthyretin results in accumulation of these peptides and the formation of amyloid deposits <sup>1</sup>. </p><h4>Radiographic features</h4><h5>MRI</h5><p>Unfortunately, no specific features exist, and appearances are similar to those of sporadic <a href="/articles/cerebral-amyloid-angiopathy-1">cerebral amyloid angiopathy (CAA)</a> <sup>1</sup>. Features therefore may include <sup>2</sup>:</p><ul>
- +<li><p>multiple parenchymal haemorrhages of various age and size</p></li>
- +<li><p><a href="/articles/cortical-superficial-siderosis" title="Cortical superficial siderosis">cortical superficial siderosis</a> due to repeated <a href="/articles/convexal-subarachnoid-haemorrhage" title="Convexal subarachnoid haemorrhage">convexal subarachnoid haemorrhage</a></p></li>
- +<li><p>microinfarcts</p></li>
- +</ul><p>While these features exist, it is worth noting that many patients with <a href="/articles/transthyretin-associated-amyloidoses">transthyretin-associated amyloidoses</a> may have <a href="/articles/cardiac-conduction-devices" title="ICD-pacemaker">cardiac devices</a>, which may preclude them from having an MRI <sup>3</sup>.</p><h4>Differential diagnosis</h4><ul><li>
- +<p><a href="/articles/cerebral-amyloid-angiopathy-1">cerebral amyloid angiopathy (CAA)</a></p>
- +<ul>
- +<li><p>indistinguishable on imaging</p></li>
- +<li><p>usually only seen in elderly patients</p></li>
References changed:
- 2. Taipa R, Sousa L, Pinto M et al. Neuropathology of Central Nervous System Involvement in TTR Amyloidosis. Acta Neuropathol. 2023;145(1):113-26. <a href="https://doi.org/10.1007/s00401-022-02501-9">doi:10.1007/s00401-022-02501-9</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/36198883">Pubmed</a>
- 3. Maia L, Magalhães R, Freitas J et al. CNS Involvement in V30M Transthyretin Amyloidosis: Clinical, Neuropathological and Biochemical Findings. J Neurol Neurosurg Psychiatry. 2015;86(2):159-67. <a href="https://doi.org/10.1136/jnnp-2014-308107">doi:10.1136/jnnp-2014-308107</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/25091367">Pubmed</a>
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