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A 9-year-old girl with newly diagnosed Type 1 DM, DKA, brain oedema, multifocal vasogenic brain lesions and lower limb paresis was presented for treatment. She had reported polydipsia and polyuria over the past week and weight loss of 3 kg over the last month with severe dehydration. She experienced agitation and motor restlessness followed by upper limb spasms. CT scan revealed a hypodense lesion in the left temporal region and brain oedema. Nerve conduction studies showed dysfunction in both the right tibial nerve and peroneal nerves, which results in damage of motor neurons in both lower limbs.
What will most likely explain the pathogenesis of acute neuropathy in this case?
Neuropathy associated with diabetic ketoacidosis is rare. It
presents severe clinical complications. The most common complication is brain
oedema, specifically related to central nervous system (CNS) which is prevalent
in approximately 0.5-1% of cases with diabetic ketoacidosis (DKA) and has a 20%
mortality rate. Other less frequent complications are hemorrhagic and ischemic
strokes, accounting for 10% of intracerebral complications. Among all these
complications, sinus thrombosis and cerebral vein are less frequent than brain
oedema.
In a child with newly diagnosed
diabetes type 1 the diabetic ketoacidosis led to neuropathy. The Alpha-lipoic
acid and vitamins B1, B6 and B12 were initiated to manage the neuropathy and
for ketoacidosis, the patient was kept under careful observation.
The laboratory examination included evaluation of Blood glucose
levels (mg/dL), Osmolarity levels (mOsm/kg H2O), Base excess
(mEq/L), Corrected sodium levels (mmol/L), Potassium levels (mmol/L), Phosphate
levels (mmol/L), CRP levels (mg/dL),
D-dimer levels(ug/L), Fibrinogen levels(g/L). Other investigations made
were Computed Tomography Scan, Brain Magnetic Resonance Imaging and lower limb
nerve conduction studies.
The blood glucose level initially was found to be 1136 mg/dL, and
severe acidosis was also present (pH 7.1; BE-25.9). Intravenous fluid therapy
and insulin therapy did not show any improvement in her medical and
neurological state. Glasgow Coma Scale (GCS) scores depleted from 13 points to
7 points. CT scan showed hypodense lesion in the left temporal region and brain
oedema. An anti-edematous treatment helped to improve her medical condition,
but she had developed symmetric lower limbs paresis. Brain MRI and nerve
conduction studies indicated numerous, diffuse lesions and damaged motor
neurons in both lower limbs.
Treatment included intravenous initial fluid therapy containing 1250
mL 0.9% sodium chloride (NaCI) and 1000 mL of 5% dextrose with 0.9% NaCl (2:1
proportion, sodium concentration-51.34 mEq/L) to restore fluid loss due to
excessive dehydration. Insulin was infused at a slower rate to prevent a rapid
decrease in glycaemia. No improvement was observed in patient medical
condition. After CT scan, an anti-edematous therapy with mannitol 0.3
g/kg/dose, three times a day was introduced for brain oedema; also alpha lipoic
acid, vitamins B1, B6 and B12 were added to the therapeutic regimen that helped
in improving her medical condition. The patient's health gradually improved with
treatment and physiotherapy.
Diabetic neuropathy affects approximately 54-59% patients with T1DM and 45% of patients with T2DM. It is the most common complication of diabetes mellitus and viewed as an independent entity comprising many types of nerve dysfunction due to various symptoms, clinical courses and pathogenic mechanisms. About 80% of patients with symptomatic DN suffers from various generalised symmetric, chronic polyneuropathy including motor, sensory and autonomic nerve dysfunctions. In most of the cases, DN develops in patients with hyperglycemia. Evidence report the occurrence of neuropathy related to newly diagnosed DM1. It can be classified as hyperglycemic neuropathy, acute painful DN, and neuropathy after ketoacidosis. Asymptomatic as well as symptomatic changes were observed in nerve function at the time of DM1 diagnosis.
Previous studies suggested that diabetes mellitus was responsible for mononeuropathy as the onset of neuropathy and motor dysfunction was dependent on the start of DM1 and glycemic control respectively. In the present case, patient suffered from acute motor peripheral neuropathy which may occur as a result of the peripheral ischemia, haemodynamic and metabolic changes associated with ketoacidosis.
One hypothesis explains that the procoagulent state during DKA may lead to nerve damage through dysfunction in vascular endothelial, which is the first line of defense against thrombosis. Endothelial dysfunction results in the activation of coagulation factor and platelet. Elevated levels of fibrinogen, factors VII, VIII, XI, XII and von Willebrand were found in DKA. Disrupted anticoagulant mechanisms such as a low protein C level can lead to worsening of a procoagulant state. Impairment of fibrinolysis may occur due to various factors such as an increased concentration of plasminogen activator inhibitor type 1 and more severe degradation of the thrombi. There was an elevation in d-Dimer levels as indicated by the study, but there is a need for further diagnostic tests.
In the present case study, other etiologies of neuropathy, such as hypophosphatemia were also observed and considered during admission to hospital. Hypophosphatemia is generally asymptomatic, but its severity can cause peripheral polyneuropathy that can be both sensory and motor. After normalisation of the phosphate levels, neurological symptoms remains that suggests another alternative mechanism for the pathogenesis of neuropathy.
Diabetic neuropathy treatment includes the use of strong
antioxidants such as alpha lipoic acid. The efficacy of this therapy has been
proved in the meta analysis. The use of Benfotiamine, a derivative of vitamin
B1, is also utilised, although less effective than alpha lipoic acid.
Neuropathy
can be developed any time after or even before Diabetes mellitus diagnosis.
Acute neuropathy after ketoacidosis is rare, but its cause is not apparent yet.
It is suggested that patients with DKA need careful monitoring of neurological
conditions even after normalization of glycemic parameters.
J Clin Res Pediatr Endocrinol
Peripheral Neuropathy as a Complication of Diabetic Ketoacidosis in a Child with Newly Diagnosed Diabetes Type 1: A Case Report
Baszyńska-Wilk M et al.
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