Treatment-Induced Neuropathy of Diabetes (TIND) in Pediatrics: A Case Report and Review of the Literature

Abstract

Context Treatment-induced neuropathy of diabetes (TIND) is a rarely reported but important consideration in patients presenting with an acute onset of neuropathic symptoms following rapid correction of hyperglycemia in diabetes. Although it has been reported in children, the preponderance of literature focuses on adults with TIND. Case Description We report an 18-year-old male with this condition and his clinical course. We then discuss the proposed pathophysiology of TIND and review the literature. We also provide a standard workup for the diagnosis of TIND. Conclusion In both pediatric and adult populations, TIND should be considered in diabetic patients who develop neuropathy acutely following rapid correction of hyperglycemia. Because the pathophysiology of TIND remains poorly understood, there is insufficient information regarding how to target susceptible individuals and prevent the development of TIND.

Treatment-Induced Neuropathy of Diabetes in Youth: Case Series of a Heterogeneous and Challenging Complication

“…Neuropathic symptoms are described as either burning, freezing, tingling, stinging, or allodynia, follow a symmetric distribution, and are worse distally. Risk factors include higher baseline HbA1c (>10% or 86 mmol/mol), diabetic anorexia or weight loss, and female gender [ 3 , 4 ]. TIND is distinct from diabetic polyneuropathy (DPN), given its acute onset and often reversible nature.…”

“…TIND is distinct from diabetic polyneuropathy (DPN), given its acute onset and often reversible nature. TIND is also associated with autonomic dysfunction and microvascular complications, underscoring the importance of an interdisciplinary approach to care [ 4 , 5 ]. Current management, including gabapentinoids, tricyclics, or serotonin reuptake inhibitors, is limited by our understanding of TIND pathophysiology [ 4-6 ], of which there are a few postulated mechanisms.…”

“…TIND is also associated with autonomic dysfunction and microvascular complications, underscoring the importance of an interdisciplinary approach to care [ 4 , 5 ]. Current management, including gabapentinoids, tricyclics, or serotonin reuptake inhibitors, is limited by our understanding of TIND pathophysiology [ 4-6 ], of which there are a few postulated mechanisms. One theory relates to hyperglycemia-induced microcirculatory changes that cannot remodel at the same rate of decline in serum glucose, leading to ischemic conditions within the endoneurium.…”

“…One theory relates to hyperglycemia-induced microcirculatory changes that cannot remodel at the same rate of decline in serum glucose, leading to ischemic conditions within the endoneurium. Another thought is that acute glucose deprivation leads to cellular apoptosis and, once a normoglycemic state is achieved, the subsequent firing of regenerating axons results in the development of neuropathic symptoms [ 4 ]. Treatment response in TIND is variable with a gradual (but sometimes incomplete) resolution of symptoms over 3 to 24 months [ 4-6 ].…”

“…Another thought is that acute glucose deprivation leads to cellular apoptosis and, once a normoglycemic state is achieved, the subsequent firing of regenerating axons results in the development of neuropathic symptoms [ 4 ]. Treatment response in TIND is variable with a gradual (but sometimes incomplete) resolution of symptoms over 3 to 24 months [ 4-6 ]. Cases of TIND are well described in adult literature, and a recent report has shown that 11% of patients (n = 954) referred to a diabetic neuropathy clinic had presentations consistent with TIND [ 3 ].…”