Early Detection of Cardiac Amyloidosis in Transthyretin Mutation Carriers.

Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

[A case of encephalopathy showing various psychiatric and autonomic symptoms with positive anti-ganglionic acetylcholine receptor (gAChR) antibody].

An 84-year-old woman developed spontaneous recurring mutism. During the periods in which she was able to speak, she described that she had a peculiar delusion where her body was melting away. She did not obey orders although she was able to move her limbs spontaneously. Severe fluctuations in blood pressure measurements were observed; they were unaffected by postural changes. She also had urinary retention and constipation. Her psychiatric and autonomic symptoms showed marked daily and diurnal fluctuations. The brain MRI showed no abnormality in the limbic system or temporal lobes. The cerebrospinal fluid showed slightly elevated protein with normal cells counts. This case was initially thought to be an encephalopathy of unknown etiology. On subsequent testings she was shown to have positive anti-ganglionic acetylcholine receptor (gAChR) antibodies. Although the initial steroid pulse and intravenous immunoglobulin therapies markedly improved both psychiatric and autonomic symptoms, they turned ineffective in subsequent recurrences. We were not able to treat her with plasmapheresis or with other immunisuppressive drugs because of her poor general status, thus their effectiveness could not be determined. Judging from her clinical course, in which immunotherapy was effective although somewhat limited, a possible involvement of an autoimmune mechanism was suspected; however, the exact pathogenesis remains undetermined. It is possible that in this case there may have been an involvement of the immune system and that the patient might have had an encephalopathy with anti-gAChR antibodies.