Abstract
Summary
The etiology of foot drop is diverse from various diseases to mechanic injuries and includes neuropathy of the peroneal nerve. Peroneal neuropathy might also be one of the forms of diabetic neuropathy, very rarely reported as the first sign of diabetes. We describe three cases of children with newly diagnosed type 1 diabetes (TID) who developed unilateral peroneal nerve palsies and tibial nerve palsies, presenting clinically as a foot drop. In two of our cases, the symptoms of foot drop occurred shortly after starting treatment for severe diabetes ketoacidosis. In the third patient, food drop was a reason for the initial medical consultation, but eventually, TID was diagnosed. The presented cases highlight that neuropathy can be observed not only as a chronic complication of T1D, but it can also appear at the time of disease manifestation. The incorrect position of the lower limb during a keto coma may contribute to the development of neuropathy.
Learning points
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Neuropathy can be observed not only as a chronic complication of type 1 diabetes (T1D), but it can also appear at the time of disease manifestation.
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The incorrect position of the lower limb causing external pressure during a keto coma may contribute to the development of neuropathy.
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It is important to examine the glycemia in patients with acute peroneal neuropathy, as this kind of peripheral neuropathy can be associated with newly diagnosed T1D. Normalization of glycemia might lead to rapid neuronal recovery.
Background
The etiology of foot drop is diverse from various diseases to mechanic injuries. Although anterior horn cell disease, L5 radiculopathy, or partial sciatic neuropathy might be a cause of foot drop, peroneal neuropathy due to external pressure is considered to be the most frequent reason for this condition. This type of neuropathy may result from the seemingly blissful pressure from the habitual crossing of the legs, prolonged squatting, or even positioning during surgery or prolonged bed rest (1). Peroneal neuropathy might also be one of the forms of diabetic neuropathy, but it is very rarely reported as the first sign of diabetes. We describe three cases of children with newly diagnosed type 1 diabetes (T1D) who developed unilateral peroneal and tibial nerve palsies, presenting clinically as a foot drop. In two children, the neurological problem appeared shortly after the treatment of severe diabetes ketoacidosis (DKA), but in one case, the onset of peroneal neuropathy was simultaneous with the occurrence of mild symptoms of hyperglycemia.
Case presentation
Case 1
A 7-year-old girl was diagnosed with T1D complicated by severe DKA with altered consciousness and shock requiring dopaminę treatment. Preliminary laboratory tests showed elevated random glucose level (22.61 mmol/L = 407 mg/dL), capillary blood pH: 6.95, HCO3: 7.2 mmol/L, base excess (BE): − 27.3. During hospitalization in the pediatric intensive care unit (PICU), the girl was intubated and needed sedation for several hours. As she developed cerebral edema, with optic nerve sheath of 5 mm (CT scan of the brain was not performed), anti-edematous treatment was administered, with mannitol and furosemide in appropriate doses. The DKA was resolved completely; however, 2 days later, the patient was found to have paresis of the right foot with hypoesthesia, preceded by a transient pain in the medial surface of the foot. Neurological examination revealed the absence of the right ankle reflex and no dorsiflexion and plantar flexion of the right foot.
Case 2
An 11-year-old boy was diagnosed with T1D complicated by severe DKA. Preliminary laboratory tests showed an extremely elevated glucose level (105.0 mmol/L = 1890 mg/dL), capillary blood pH: 6.92, BE: − 27.3 mmol/L. It was likely that the patient had been lying in one position on his right side for several hours before admission to the PICU. Due to suspicion of cerebral edema, CT scan of the brain performed on the first day of hospitalization, which was normal. The patient was sedated and mechanically ventilated. The DKA resolved completely, allowing the transfer to the pediatric endocrinology and diabetology department. Two days following the diagnosis of T1D, the patient presented with pressure ulcer lesions on the right buttock and side surface of the heel. Further, he exhibited decreasedmobility in the knee and ankle joints with accompanying knee pain, no dorsiflexion and plantar flexion of the right foot, and reduced sensation in the lower anterior area of the right lower leg. The disturbances in sensation clarify whether this is a reduced or absent sensation.
Case 3
An 11.5-year-old girl was diagnosed with T1D. Few weeks before the diagnosis of T1D, she was observed to have gait disturbances with right foot drop. For this reason, the patient was hospitalized in the pediatric neurology department. Nerve conduction studies (NCS) confirmed damage to the right common peroneal nerve at the level of the popliteal fossa. The patient and her parents denied trauma or spending longer time in a squat position. An in-depth history of the patient revealed that during the previous month she suffered from polyuria and polydipsia; furthermore, the girl had lost 15 kg over the past 6 months.
Investigation and treatment
Case 1
Imaging examinations, including ultrasound of the popliteal fossa as well as the radiography of the lower right limb, showed no irregularities. The NCS revealed no response after stimulating the motor fibers of the peroneal and tibial nerves of the right lower limb; however, conduction in the sensory nerves (sural and superficial peroneal) was normal. The girl was diagnosed with unilateral peroneal and tibial nerve palsies. Galantamine, magnesium, and vitamins B1, B6, and B12 were commenced. After 7 days of hospitalization, the patient developed painful paresthesia within the right foot and in the popliteal fossa, and carbamazepine was introduced to the therapeutic regimen. Intensive physiotherapy was undertaken.
Case 2
The ultrasound examination of the right leg revealed confluent fluid spaces up to a depth of 1.5 cm under the skin in the half of the distal thigh and in the area of the gastrocnemius muscle. Thrombosis was excluded. NCS revealed severe damage to the motor fibers of the peroneal nerve and axonal damage to the tibial nerve, and no sensory response from the superficial peroneal and sural nerves on the right side. Vitamins B1, B6, and B12 were commenced. Intensive physiotherapy was undertaken.
Case 3
Hyperglycemia 28.9 mmol/L (520 mg/dL) was confirmed, followed by an increased level of HbA1c (155 mmol/mol = 16.3%). Due to the typical symptoms and high glucose level, the patient was diagnosed with diabetes. At presentation, the capillary blood gases revealed no abnormalities. She was treated with subcutaneous insulin and administered α-lipoic acid and benfotiamine. Intensive physiotherapy was undertaken.
Clinical presentation and results of NCS examinations of our patients are presented in Table 1.
Clinical presentation and NCS of the patients.
| Case 1 | Case 2 | Case 3 | |
|---|---|---|---|
| Year evaluated | 2014 | 2020 | 2022 |
| Gender | Female | Male | Female |
| Age, years | 7 | 11 | 11.5 |
| Clinical presentation | |||
| Severe DKA | No DKA | ||
| Glucose | |||
| mmol/L | 22.6 | 105 | 28.9 |
| mg/dL | 407 | 1890 | 520 |
| pH | 6.95 | 6.92 | |
| HCO3, mmol/L | 7.2 | ||
| BE, mmol/L | −27.3 | −27.3 | |
| Sedation and intubation | Yes | Yes | |
| Anti-edematous treatment | Yes | ||
| Subcutaneous insulin | Yes | ||
| Patient condition | Good | ||
| Neuropathy | |||
| Symptom appearance | 2 days after T1D diagnosis | 2 days after T1D diagnosis | |
| Symptoms | Hypoesthesia of the right foot, no dorsiflexion and plantar flexion of the right foot, the absence of the right ankle reflex | Bedsores on the right buttock and heel; disturbances in mobility in the knee and ankle joints with accompanying knee pain, no dorsiflexion and plantar flexion of the right foot, disturbances in the sensation of the lower anterior area of the right lower leg | Gait disturbances with right foot drop. It seems that the onset of peroneal neuropathy was simultaneous with the onset of mild symptoms of diabetes. |
| NCS at baseline abnormality | |||
| Right lower limb | No response from the motor fibers of the peroneal and tibial nerves | Severe damage to the motor fibers of the peroneal nerve and axonal damage to the tibial nerve | Damage to the right common peroneal nerve |
| No sensory response from the superficial peroneal and sural nerves |
Outcome and follow-up
Case 1
Six months after diagnosis of T1D, the girl was able to lift her foot and move her toes. NCS performed a year later, in addition to the previously described disorders, found no sensory response from the superficial peroneal and sural nerves on the right side. The girl continued intensive rehabilitation. Six years after the T1D diagnosis, her neurological condition was normal, apart from mild sensory disorders in the right lower leg. However, in NCS, the features of axonal-demyelinating damage to the right peroneal and tibial nerve motor fibers were still present.
Case 2
According to neurological opinion, the presented complaints were most likely to be entrapment neuropathy, and secondary to acute diabetic neuropathy. The treatment led to improvement of the motor function, but 2 years after the T1D diagnosis, the neurological changes did not resolve completely (NCS was not rechecked).
Case 3
The neurological symptoms decreased gradually with the improvement of metabolic control of diabetes and resolved completely after 5 months of observation. As other possible causes of acute mononeuropathy were excluded, it was considered that diabetes was the reason for the neuropathy in this patient.
Discussion
Clinical courses of diabetic neuropathies vary depending on the type and size of fibers involved, their distribution, and the mechanisms leading to neuronal damage. The pathogenesis of diabetic neuropathy is not fully understood. Neurological complications in diabetes are usually associated with long-lasting hyperglycemia. However, diabetic mononeuropathies can occur at any stage of the disease and may also be associated with the appearance of sudden neurological symptoms at the time of diagnosis of diabetes. In two of our patients, diabetic neuropathies in the form of peroneal and tibial nerve palsies, presenting clinically as a foot drop, developed shortly after treatment of severe DKA in the course of newly diagnosed T1D. In our third patient, the onset of peroneal neuropathy was simultaneous with the presentation of hyperglycemia symptoms.
Several cases of acute presentation of a foot drop at the time of diagnosis of T1D in children have already been reported. Reviewing the literature, we found cases of damage of the sciatic or peroneal/tibial nerves as a neurological complication of severe DKA in two children. Giza et al. described a case of an 8-year-old girl hospitalized with severe DKA (pH 7.09, HCO3 1.7 mmol/L) in whom, on the 7th day of treatment of T1D, a right foot drop was observed due to severe axonal damage of the right sciatic nerve (2). Unfortunately, the neurological changes were irreversible. Baszyńska-Wilk et al. also described a girl at the age of 9 with newly diagnosed T1D and DKA (glucose level: 63.1 mmol/L = 1136 mg/dL, pH 7.1). Because of her severe general condition, the child needed to be intubated. Computed tomography scan of this patient revealed cerebral edema and multifocal vasogenic brain lesions. After 4 days, when the girl was extubated, bilateral lower limb peripheral paresis was observed. NCS revealed damage to the motor neurons in both the peroneal and the right tibial nerves. It was considered that the presence of peripheral ischemia together with DKA were the probable factors leading to the development of neuropathy in this child (3).
Pathogenesis of acute neuropathy of the peroneal and tibial nerves following severe DKA may be ambiguous and multifactorial.
The study performed in the group of 37 patients aged 3–19 years with newly diagnosed T1D, who underwent NCS of the median, ulnar, tibial, peroneal, and sural nerves annually for 5 years, showed that the peroneal motor nerve appeared abnormal in 46% of cases and was the most affected nerve (4). It was shown in an experimental rodent model of diabetes that the most severe molecular consequences of hyperglycemia in the peripheral nervous system were observed in the distal sciatic nerve, possibly due to a failure of energy homeostasis and/or oxidative stress specifically in the distal axon/Schwann cell-rich sciatic nerve (5). This data provide a possible molecular description of the different effects of hyperglycemia on the distinct regions of the peripheral nervous system.
The possible causes of peroneal neuropathy in patients with diabetes are susceptibility to external pressure or ischemic alterations (1, 6). As a result of altered glucose metabolism, nerves show both functional impairment and structural changes, mainly swelling, which makes them more prone to entrapment neuropathies (6). A simultaneous entrapment of the common peroneal and the tibial nerve can be located at the knee level. In the second case presented by us, the incorrect position of the lower limb during the diabetic coma might have contributed to the development of neuropathy, with bedsores and confluent fluid spaces under the skin pointing to the external pressure.
Our third patient is an example of a child in whom the first symptom perceived was right foot drop. Although polydipsia, polyuria, and weight loss preceded the appearance of neurological symptoms, they remained unnoticed or rather underestimated by the family. As such, the main complaint with which the patient consulted a physician was gait disturbance. Similar cases, with foot drop and a newly diagnosed T1D (in laboratory tests, mild DKA or ketones level slightly above the range) can also be found in the literature. In all these cases, the foot drop started to improve after commencing insulin therapy with complete recovery over a period of 2–4 months, which indicates functional rather than structural damage of the peroneal nerve (7, 8, 9, 10).
The above mentioned cases indicate that if the presentation of diabetes accompanied by foot drop is not complicated by diabetic ketoacidosis, then neuropathy seems to be reversible. It has to be underlined, however, that in children with severe DKA, the different course of neuropathy might be due to other factors affecting the neuronal damage, for example, additional external pressure, which together with severe metabolic disorders might contribute to irreversible injury of the nerves or at least need more time to recover.
As a unique case, we would like to emphasize that the food drop can overtake the symptoms of TID, and correct treatment of hyperglycemia can lead to completely resolved neuropathy.
Moreover, in the case of an unconscious patient with DKA, the correct position of the lower limb is a key to avoiding the development of neuropathy.
Declaration of interest
There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding
This study did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
Patient consent
Written consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used.
Author contribution statement
J C and M S wrote the first draft (equally contributing to this work) which was reviewed by A Z-K., who edited and finalized the version. BS and A Z-K were involved in patient management.
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