Introduction

Diabetic ketoacidosis (DKA) is a severe acute complication of type 1 diabetes (T1D) that can be associated with neurological complications, including cerebral oedema, as well as ischaemic and haemorrhagic strokes [1]. Horner’s syndrome (HS) is a neurological disorder resulting from disruption of the oculosympathetic pathway, which leads to a characteristic triad of homolateral miosis, ptosis and anhidrosis [2]. We present the first reported case of HS accompanying DKA in children.

Case report

A 16-year-old patient with DKA in the course of newly diagnosed T1D was admitted to the hospital with a serious clinical condition and severe dehydration. The patient was assessed at 14 points on the Glasgow Coma Scale (GCS) on physical examination. Kussmaul respiration was present, with a respiratory rate of up to 50 breaths per minute, and the patient exhibited tachycardia at 140 beats per minute. Pupils were equal, round, and reactive to light. Initial laboratory findings revealed severe metabolic acidosis, with a pH of 6.86, a standard base excess (SBE) of –26.1 mmol/l, and a bicarbonate (HCO₃^–) level of 5.6 mmol/l. Marked hyperglycaemia was observed, with a serum glucose concentration measuring 513 mg/dl. Glycated haemoglobin (HbA_1c) was 12.9%. Initial intravenous fluid therapy was administered, and intravenous insulin therapy was introduced in an initial dose of 0.05 units/kg/h.

During the hospitalisation, the following electrolyte abnormalities were observed: hypokalaemia with a minimum potassium level of 2.4 mmol/l, hypophosphataemia with a minimum phosphate level of 0.24 mmol/l, and hypomagnesaemia down to 0.63 mmol/l.

Throughout treatment, disturbances in electrolyte balance, ketoacidosis, and hyperglycaemia were effectively managed, resulting in a marked improvement in the patient’s clinical status. Results of laboratory tests are shown in Table I.

On the fourth day of treatment, anisocoria was observed with the right pupil larger than the left, along with ptosis of the left upper eyelid. The features of HS were observed. Eye fundus examination revealed a slight oedema and elevation of the left optic nerve head on the medial side. No other abnormalities were found on neurological examination. Treatment was initiated with intravenous mannitol at a dose of 1 g/kg body weight. In the brain computed tomography (CT), no signs of intracranial haemorrhage or oedema were observed.

Additionally, a brain MRI was performed, and no abnormalities were confirmed. In search of other causes of HS, a chest CT scan was conducted, which also revealed no pathological changes. In the follow-up ophthalmic examination in the subsequent days, features of HS persisted, while fundoscopic examination showed no elevation of the optic nerve heads.

The patient was discharged from the hospital in good general condition with a recommendation for follow-up at the ophthalmology outpatient clinic.

During neurological and ophthalmological follow-up 6 months after the diagnosis, features of HS were still present. However, at the 12-month follow-up, gradual resolution of symptoms was noted. Throughout the observation period, the patient was treated with continuous subcutaneous insulin infusion and maintained satisfactory metabolic control, with glycated haemoglobin (HbA_1c) levels ranging from 5.8% to 7.1%.

Discussion

Acute neurological complications of DKA are severe clinical problems. We present the first reported case of HS in a child during DKA.

Horner’s syndrome is a rare condition that presents with partial ptosis, miosis, and facial anhidrosis due to a disruption in the oculosympathetic pathway (OSP). The oculosympathetic pathway comprises three neurons. The first-order neuron originates in the hypothalamus and descends to the spinal cord’s ciliospinal centre of Budge. The second-order neuron exits the spinal cord, traverses the sympathetic chain, and ascends over the lung apex to the synapse in the superior cervical ganglion. The third-order neuron travels along the internal carotid artery, joins the ophthalmic division of the trigeminal nerve in the cavernous sinus, and reaches the dilator pupillae via the long ciliary nerves. It also innervates Müller’s muscle of the upper eyelid [3].

The most often affected in adults is either the first- or third-order neuron in the sympathetic chain. In contrast, children usually have pathologies affecting the second-order or preganglionic neurons within the neck. Aetiologies comprise birth trauma, mediastinal tumours, or benign neck masses. One of the more common and serious causes is a neuroblastoma involving the neurons of the ascending sympathetic chain [4].

Horner’s syndrome in the course of diabetes is very rare. Bilateral HS has been described as a symptom associated with autonomic neuropathy, a chronic complication of diabetes [5]. Meanwhile, Pishdad et al. [6] described a patient with HS as an initial manifestation of type 2 diabetes. The anisocoria resolved with the treatment of hyperglycaemia.

We hypothesise that acute autonomic neuropathy during DKA might be one of the causes of HS in our patient. The literature includes case reports of acute peripheral neuropathy associated with severe DKA [7].

Diabetic ketoacidosis may contribute to neuronal damage through peripheral ischaemia and haemodynamic and metabolic alterations. Diabetic ketoacidosis is accompanied by abnormalities in coagulation factors, platelet activation and vascular reactivity [8]. This procoagulant state may cause vascular endothelial dysfunction, resulting in hypoperfusion of peripheral nerves. The oxidative stress induced by hyperglycaemia and ketosis can also affect nerve function [8–10].

Another possible cause of HS in the patient may be treatment-induced neuropathy, also known as insulin neuritis. It is defined as the acute onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a significant improvement in glycaemic control, specified as a decrease in HbA_1c of ≥ 2% points over 3 months [11].

Hypophosphataemia was considered as a potential cause of neuropathy. Hypophosphataemia is usually asymptomatic; however, its severe form (less than 0.32 mmol/l) can result in peripheral neuropathy. Hypophosphataemia leads to decreased intracellular adenosine triphosphate (ATP) and failing cellular functions that rely on energy-rich phosphate compounds [12].

Conclusions

Neurological complications may occur during DKA, with cerebral oedema representing the most frequently encountered manifestation.

Nonetheless, less common sequelae of DKA should also be considered, including intracranial haemorrhage, ischaemic stroke, and HS. Close monitoring of serum phosphate, calcium, and magnesium levels is essential during DKA management, as disturbances may contribute to neurological complications. Neurological assessments are warranted in all patients with DKA, even after clinical improvement.