Background & Aims

Due to its (supposed) rarity and heterogeneous clinical presentation, hereditary transthyretin (ATTRv) amyloidosis is either not diagnosed or diagnosed with significant delay in the majority of cases (1). This delay in diagnosis is particularly devastating as there are specific treatments available for early stages of the disease that can slow or even halt the rapidly progressing, fatal course of the disease. Early identification of affected patients is therefore of the utmost importance. In addition to cardiac dysfunction, length-dependent polyneuropathy with sensorimotor and autonomic symptoms is one of the main manifestations of ATTRv amyloidosis. This study aimed to develop and validate a new screening tool for early identification of ATTRv amyloidosis with polyneuropathy (AmyloScan®).

Methods

In the initial item selection phase, potential disease characteristics were identified via literature analysis, interviews with affected patients and detailed examination of ATTRv amyloidosis patients (n=10) and controls (chronic inflammatory demyelinating polyneuropathy (CIDP), n=16; diabetic polyneuropathy, n=16) using validated questionnaires, autonomic and sensory testing. Based on these results a preliminary AmyloScan version was developed and further assessed in the second, validation phase in 83 patients with polyneuropathy caused by ATTRv amyloidosis (n=21), CIDP (n=19) or others (n=43). Sensitivity and discriminant analyses were used to determine the most characteristic item combinations for ATTRv amyloidosis. For ease of use, a simplified function with only yes/no items was created. Receiver Operator Curves were plotted and the most optimal cut-off values were determined.

Results

The final version of the AmyloScan® included 12 questions and two sensory bedside tests. In particular, the course of the disease, the presence of carpal tunnel syndrome, cardiac and ocular concomitant symptoms, muscle atrophy, various autonomic symptoms and the family history were queried. Both bedside tests (22°C metal cube temperature perception; 4 mL pressure pain) were performed in an individually defined border zone area.
All questions could be answered with a simple yes or no, resulting in a total score of 0-14 points, with higher scores being more indicative of ATTRv amyloidosis. Two cut-off values were determined: A value of ? 4 indicated an increased chance of amyloidosis (sensitivity: 95.2%, specificity: 72.6%) and a value of ? 6 indicated a high chance of amyloidosis (sensitivity: 81.0%, specificity: 93.5%).

Conclusions

The AmyloScan® is the first screening instrument for the early detection of ATTRv amyloidosis with polyneuropathy. It consists of a short questionnaire and two simple bedside tests, that can be easily applied in daily clinical practice. The AmyloScan® shows a good discriminative value to identify patients with ATTRv amyloidosis in patients with a polyneuropathy of other causes. Depending on the test result, further diagnostic steps can be initiated and, if the disease is confirmed, appropriate treatment can be started at an early stage.

References

(1) Adams D, Koike H, Slama M, Coelho T. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol. 2019 Jul;15(7):387-404. doi: 10.1038/s41582-019-0210-4. Epub 2019 Jun 17. PMID: 31209302

Presenting Author

Manon Sendel

Poster Authors

Juliane Sachau

Dr.

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

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Lena Rhode

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

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Manon Sendel

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

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Maike F. Dohrn

Department of Neurology, RWTH Aachen, University Hospital, Aachen, Germany

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Stefanie Rehm

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

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Jan Vollert

Pain Research, Department of Surgery and Cancer, Imperial College London

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Klarissa Stürner

Department for Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

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Ralf Baron

University Medical Center Schleswig-Holstein

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Topics

  • Assessment and Diagnosis

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