Adapted Modified Toronto Clinical Neuropathy Score and Erasmus Polyneuropathy Symptom Score Validated by Quantitative Sensory Testing and Nerve Conduction Studies for Kidney Transplant Recipients

Sensory polyneuropathy is one of the most prevalent neurological disorders. A Dutch study observed an incidence of all types of polyneuropathy of 77 per 100.000 person-years, which increases with age. Besides, previous studies evaluated the impact of polyneuropathy on quality of life in different patient populations and showed that accompanying symptoms affect daily living and influence morbidity and mortality of patients adversely.

We can classify sensory polyneuropathies broadly into either small fibre neuropathies, large fibre neuropathies or mixed small and large fibre neuropathies. In small fibre neuropathies the thinly myelinated A delta and unmyelinated C fibres are affected. Therefore, the transmission of thermal and noxious sensory input is disturbed translating to symptoms of sharp, painful, or burning paraesthesia, sensory loss or numbness, and the inability to discriminate between hot and cold sensation. Disorders affecting the large myelinated A delta fibres lead to an impaired vibration sensation and proprioception. Patients will complain about a combination of symptoms of sensory loss, paraesthesia, and gait imbalance.

Sensory polyneuropathy is a common finding in kidney transplant recipients (KTR), but little is known about prevalence, course, or underlying aetiology in this specific group. It is known that patients are at a high risk to develop polyneuropathy before kidney transplantation due to chronic kidney disease. Therefore, related to the previous state of chronic kidney disease uremic and diabetic polyneuropathy are probable underlying aetiologies in KTR. Furthermore, the use of immunosuppressive medication after transplantation, in particular tacrolimus, may result in polyneuropathic symptoms and signs. These circumstances may explain the high prevalence of polyneuropathy in KTR but in order to gain more understanding, it is necessary to diagnose and stage polyneuropathy in an easy and convenient way in KTR. Furthermore, early diagnosis and treatment of certain types of polyneuropathy can prevent further worsening of neuropathic symptoms and signs, or even reverse the neurologic deficits.

The diagnostic approach to polyneuropathy differs depending on the type of affected nerve fibre and the distribution of nerve damage in the respective type of polyneuropathy. The diagnosis of polyneuropathy is generally based on the presence of distal sensory and sensorimotor symptoms and signs, and loss of function, which is consistent with the clinical picture. Nevertheless, to reveal an underlying large fibre aetiology, nerve conduction studies (NCS) are needed. With the help of NCS, it is possible to categorize polyneuropathy as primary axonal or primary demyelinating. This standard diagnostic test, however, exclusively enables the measurement of large fibres and patients with pure small fibre neuropathies will not show any nerve conduction abnormalities. Hence, quantitative sensory testing (QST) is required to assess the function of small sensory nerve fibres. However, NCS and QST are time-consuming, fairly expensive, and the investigator needs a certain level of expertise. Alternatively, different clinical scores exist that aim to detect and stage polyneuropathy based on symptoms and signs. The Toronto Clinical Neuropathy Score (TCNS) was designed for diabetic sensorimotor polyneuropathy but it was shown that its usefulness extends beyond diabetic polyneuropathy. These results were based on correlations of the TCNS with clinical, electrophysiological and disability parameters in non-diabetic polyneuropathies. The same study confirmed that reliability and accuracy were excellent. Eventually, the TCNS was modified (into the mTCNS) to better capture a scale of simple sensory tests representative of early-stage dysfunction and reflex testing was removed due to its high inter-rater variability. The mTCNS was demonstrated to maintain an acceptable correlation with the precursor score. In the University Medical Center Groningen (UMCG) a large population of KTR is followed within the scope of the TransplantLines cohort study and biobank. For this purpose, the mTCNS was further adapted by omitting testing of temperature sense due to practical reasons (adapted into the amTCNS). The E-PSS was designed to diagnose chronic polyneuropathy and was previously validated in a cohort of patients with chronic idiopathic axonal polyneuropathy.

To be able to study prevalence, course, and underlying aetiology in this specific population of KTR it is crucial to reveal whether the E-PSS and amTCNS correlate with the golden standards of diagnosing polyneuropathy, NCS and QST. In the long term, both clinical scores have great potential to help clinicians from various disciplines without the specific expertise needed for NCS and QST to diagnose polyneuropathy.