Pediatric osmotic demyelination syndrome in a case of type 1 diabetes mellitus with diabetic ketoacidosis.

Cautious treatment of hyponatremia in diabetic ketoacidosis is necessary in order to avoid the development of osmotic demyelination syndrome which is a demyelinating disorder. Individualized supportive therapy would be fruitful for the management of such cases but there is a need for larger studies to guide the management.

INTRODUCTION

Diabetic ketoacidosis (DKA) is a common acute medical emergency in patients with type 1 diabetes mellitus characterized by the triad of ketosis(urine and serum ketone positive), hyperglycemia (blood sugar level >250 mg/dl), and metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L). Osmotic demyelination syndrome (ODS) is a rare complication of DKA and is characterized by the loss of myelin sheath involving pontine and extrapontine areas manifesting with quadriparesis and neurocognitive changes with characteristic changes in magnetic resonance imaging(MRI). Here, we report a unique case of a 19‐year‐old woman with DKA complicated with severe sepsis, metabolic acidosis, mild hypokalemia, and ODS, which to the best of our knowledge, is being reported for the first time from this country.

CASE DESCRIPTION

A 19‐year‐old girl was referred to our setting from another hospital with a diagnosis of type 1 diabetes mellitus with DKA with severe sepsis with severe metabolic acidosis with mild hypokalemia. Prior to this, the patient had a history of vomiting, abdominal pain, chest pain, and lower back pain 12 days back for which she was admitted where she had been treated along the line of management of diabetic ketoacidosis. One day prior to her admission to our hospital, her reports showed hyponatremia (126 mEq/L) which increased to 137 mEq/L and then to 154 mEq/L (increase by 28 mEq/L) within a period of 24 h.

On presentation, the patient was disoriented. Her vital signs on arrival were temperature of 97 Fahrenheit, respiratory rate of 32 breaths per minute, pulse rate of 102 beats per minute, and the blood pressure was not accessible. Her oxygen saturation was 78% in room air and the Glasgow Coma Score was 7/15. Both the pupils were reactive to light. She had a central line in situ. She was treated with isotonic normal saline, noradrenaline, potassium chloride, insulin, and oxygen after which the blood pressure was noted as 80/50 mm Hg.

Workup on the same day showed a complete blood count of 18,400/cumm, neutrophils 83%, lymphocytes 10%, random blood glucose 171 mg/dl, serum urea 56.1 mg/dl, serum creatinine 1.8 mg/dl, sodium 145.5 mEq/L, potassium 3.3 mEq/L, serum chloride 114.7 mEq/L, ALP 250 U/L, and urine for acetone was positive in dipstick test which showed (+++) indicative of 80 mg/dl. Other findings were unremarkable. She was then intubated after which her SpO2 was 100% with bagging, pulse rate—100 beats per minute, respiratory rate—24 breaths per minute, and blood pressure—118/76 mm Hg. Her laboratory workups are highlighted in Table 1.

TABLE 1

Important laboratory workups

	One day prior to presentation (report from previous hospital)	At the day of presentation (Day 0)	At the time of onset of ODS symptoms (Day 4)	At (Day 31)
Sodium (mEq/L)	126 and 137	154 and 145.5	140	138
Potassium (mEq/L)	–	3.3 and 3.1	3.6	3.6
Chloride (mEq/L)	–	114.6 and 118	111	109
Hemoglobin (g/dl)	–	13.3	11.4	8.9
Random Glucose (mg/dl)	–	171	132	‐

The patient was quadriplegic, with features suggestive of lower cranial nerve paralysis, mutism and preserved consciousness, all of which implied locked‐in syndrome but she had no eye movement. Her pupils were fixed (3 mm). She had flaccid paralysis, and reflexes were absent.

On 4th day of admission, plain MRI of the brain (Figure 1) was done which reported:

FIGURE 1

Features suggestive of ODS seen in the MRI of the brain

Gyriform pattern T2/FLAIR hyperintensity in the right frontal lobe with diffusion restriction.

An area of T1 hypointensity and an area of T2/FLAIR hyperintensity in the central part of the pons without diffusion restriction.

These findings along with clinical scenarios were suggestive of osmotic pontine and extra pontine myelinolysis. She was then managed conservatively with hypotonic fluids, antibiotics, and methylprednisolone. She also required a tracheostomy for prolonged ventilation.

She showed gradual improvement and had a normal motor function with considerable improvement in her cognitive and functional status at the end of her 40 days of admission after which she was discharged from the hospital. After this, the patient was asked to follow‐up in one month, but she was lost to follow‐up.

The key limitation of this report is the lack of availability of proper documentation of the management and workup of the patient in other hospital from where she was referred.

DISCUSSION

Our case presented a 19‐year‐old girl diagnosed with type 1 diabetes mellitus with diabetic ketoacidosis with severe sepsis with severe metabolic acidosis with mild hypokalemia who was later diagnosed with ODS which is a rare, , , acute, demyelinating disorder, usually occurring several days after a rapid increment in the serum osmolality. ODS in pediatric age group is even more uncommon than it is in adults. Additionally, pediatric ODS is more common in between the age of 1 and 5 years (35%) with its prevalence decreasing with an increase in age group.

The explanation for the pathophysiology of the development of ODS has commonly centered around the rapid correction of hyponatremia or a rise in the serum sodium levels causing the movement of water into the extracellular space leading to the shrinkage of endothelial cells and glial cells of the brain. This could result in the disruption of the blood‐brain barrier and eventually to inflammatory demyelination. , Other factors besides the rapid correction of hyponatremia could be chronic alcoholism,  hypernatremia,  hypokalemia, , hypophosphatemia, anorexia nervosa, and diabetes mellitus. The possible factors at interplay that could have led to ODS in our case could be overcorrection of hyponatremia leading to hypernatremia; hypokalemia secondary to insulin therapy; and malnourishment and uncontrolled diabetes mellitus. Among these, the most remarkable factor could be the rapid overcorrection of hyponatremia as she had already received a significant amount of fluid at another hospital resulting in an increase of serum sodium level from 126 mEq/L to 154 mEq/L corresponding to a rise of 28 mEq/L in a span of 24 h.

Osmotic myelinolysis is frequently observed in the central pons and other central nervous system regions where maximum admixture of gray and white matter is seen. A review by Bansal LR, et al showed that among 106 pediatric ODS cases, isolated central pontine myelinolysis (CPM) was reported in 46% (49), isolated extra pontine myelinolysis (EPM) in 28% (30), and combined CPM and EPM in the rest, that is, 25% (27). Our case reported the involvement of both the central pontine and extra pontine regions of the central nervous system.

Osmotic demyelination syndrome, clinically can be presenting with symptoms, including but not limited to progressive spastic quadriparesis, pseudobulbar affect, pseudobulbar palsy, dysarthria, ophthalmoplegia, dysphagia, nystagmus, ataxia, and cranial nerve paralysis. “Locked‐in” syndrome or death may be the features of severe cases of ODS.  MRI of the brain remains the diagnostic modality of choice for the demonstration of CPM and EPM which could show T2 hyperintensity in the central pons with hypointensity on T1 as reported in the MRI findings of this case. Although there have been reports of asymmetrical lesions, pontine lesions are commonly symmetrical.

For the management of a case with ODS, an effective specific treatment has not yet been identified. Hence, the current treatment modality consists of general supportive care and treatment of the underlying etiology, which was all that was done for the treatment of our patient. Depending on the case, slow correction of electrolyte imbalance,  steroids, intravenous immunoglobulin (IVIG), plasmapheresis, thyroid‐releasing hormone (TRH), minocycline, lovastatin, and myoinositol are the various options for the treatment, most of which are still under study and lacking enough evidence. , , ,

CONCLUSION

We reported an interesting and rare case of ODS in case of pediatric DKA possibly secondary to the rapid overcorrection of hyponatremia also linked to hypokalemia which may very well be considered to reinforce a warning emphasizing on cautious correction of electrolyte imbalances to prevent irreversible consequences. As an effective standard treatment for the case is not yet available, prevention of ODS with a proper approach to hyponatremia should be more focused on.

CONFLICT OF INTEREST

None.

AUTHOR CONTRIBUTIONS

Ashlesha Chaudhary is the corresponding author, who followed up the patient and involved in the data collection, interpretation, literature review, and manuscript preparation. Radhay Shyam Yadav contributed in data collection and interpretation and revision of the manuscript. Aashutosh Chaudhary contributed in the literature review, data interpretation, and manuscript preparation. Yashaswi Shrestha and Ritu Shah contributed in the literature review and manuscript preparation.

ETHICAL APPROVAL

No ethical limits were crossed during reporting of this article.

CONSENT

Informed written consent was obtained from the patient's husband.