Exploring Uncommon Neurologic Complication in Young Diabetics with Osmotic Demyelination Syndrome: A Case Series and Literature Review

Abstract

Osmotic demyelination syndrome (ODS) is well known to be associated with the rapid correction of hyponatremia. However, there is limited literature on its link to persistent or corrected hyperglycemic states in diabetic patients. We report two young patients with ODS and hyperglycemia. Neuroimaging and blood tests indicated central pontine and extrapontine myelinolysis with a hyperglycemic hyperosmolar state (HHS). These unusual cases provide insight into the neurologic complications of hyperglycemia.

Introduction

Extrapontine demyelination and central pontine myelinolysis (CPM), known as osmotic demyelination syndrome (ODS), are well-documented complications of acute hyponatremia correction and have been rarely observed with hyperglycemia. ODS can occur during rapid hyperglycemia correction or at any stage of complicated diabetes mellitus (DM), with symptoms ranging from encephalopathy to quadriparesis.[1] We report two cases of ODS in young diabetic patients and reviewed literature from 2020 to 2024 in the PubMed database.

Case Reports

Case 1

A 26-year-old man presented with progressive speech and walking difficulties for the past month. He had no history of headache, altered sensorium, seizures, swallowing issues, visual complaints, motor or sensory deficits, fever, or rashes. He had been on alternative diabetic medication for a year and had a history of chronic heavy alcohol intake. His vitals were stable and systemic examinations were normal. He was alert and conscious with normal mental function, but had slightly slow pursuits, hypometric saccades, and ataxic speech. Motor and sensory examinations were unremarkable, but he exhibited hypotonia in all limbs with normal deep tendon reflexes, except for sluggish ankle jerks, predominant appendicular and gait ataxia. Plantar reflexes were mute, and the remaining neurologic examination was normal. His modified Rankin scale (mRS) and brief ataxia rating scale (BARS) scores were 3 and 17, respectively.

On evaluation, hemogram, arterial blood gas (ABG), thyroid, renal, and liver function tests, serum electrolytes (sodium- 135 mEq/l), lactate, coagulation, and fasting lipid profiles were within normal limits. Initial plasma glucose and glycosylated hemoglobin (HbA1c) were 452 mg/dl and 18.2 gm%, respectively. Serum osmolality was raised (418 mOsm/kg). Urine routine had 3 + sugars and no proteinuria or bacteriuria. Viral markers (anti-hepatitis C virus, hepatitis B surface antigen, and anti-human immunodeficiency virus antibodies) were negative. Magnetic resonance imaging (MRI) indicated central pontine T2/fluid attenuated inversion recovery (FLAIR) hyperintensity with diffusion restriction and normal angiogram [Figure 1a–d], suggesting CPM. Contrast-enhanced computed tomography revealed chronic calcific pancreatitis with mild hepatomegaly. Despite treatment efforts, random blood sugar (RBS) varied from 230 to 800 mg/dl. Discharged with various medications and therapies, the patient’s gait and speech significantly improved at 3-month follow-up (mRS and BARS improving to 1 and 5, respectively), with controlled follow-up sugars. Financial constraints prevented a repeat MRI.

Figure 1.

(a-d) Case 1. (a, b) MRI brain axial sections show T1-hypointense and FLAIR-hyperintense signal in the central pons (white arrow). (c, d) There is diffusion restriction with ADC having signal loss (white arrow). (e–h) Case 2. (e–g) MRI brain axial sections show T2/FLAIR-hyperintense signal in the central pons and high ADC signal (white arrow). (h) FLAIR hyperintensity is also seen bilateral ventrolateral thalamus (white star)

ADC: apparent diffusion coefficient, FLAIR: fluid attenuated inversion recovery, MRI: magnetic resonance imaging

Case 2

A 17-year-old girl with a history of diabetes, sickle cell disease, and a splenectomy presented with progressive dysarthria, dysphagia, and gait ataxia, followed by a dry cough, breathing difficulty, and quadriparesis. She developed altered sensorium 2 days before admission. On Mixtard insulin for a year, she had no history of headache, seizures, visual complaints, fever, or rashes. Examination revealed reduced left lower lobe air entry, stupor, slow pursuits, hypometric saccades, and mixed dysarthria. Right-sided tone and motor power were slightly reduced, sensory examination was unremarkable, and reflexes were brisk in the upper limbs but absent in the lower limbs, with bilateral flexor plantar responses. She had predominant appendicular and gait ataxia. mRS and BARS scores were 5 and 27, respectively.

She was anemic (hemoglobin- 9.5 g/dl) with normal thyroid, renal, and liver function tests, serum electrolytes (sodium = 139 mEq/l), coagulation, ABG, and fasting lipid profiles. Initial plasma glucose and HbA1c were 318 mg/dl and 15.3 gm%, respectively. Serum osmolality was raised (378 mOsm/kg). Urine routine had 3+ sugars. Viral markers were negative. Neuroimaging indicated T2/FLAIR hyperintensity in the central pontine and bilateral ventrolateral thalamus with diffusion restriction and normal angiogram [Figure 1e–h], suggesting osmotic demyelination. Due to financial constraints, some planned investigations could not be completed. Ranging from 80 to 530 mg/dl, her RBS levels in the hospital led to treatment with regular insulin and antibiotics. Discharged with insulin, antibiotics, and dalfampridine, telephonic follow-up after 10 days reported the patient’s sudden death, likely due to aspiration.

Discussion

Herein, we observed a rare complication of hyperglycemia manifesting as ODS in young diabetic patients. These patients presented with elevated blood glucose levels and had not undergone rapid hyperglycemia treatment elsewhere, leading to ODS. The suggested pathogenic mechanisms for ODS in hyperglycemia include (1) subacute cellular dysfunction from prolonged hyperglycemia, (2) osmotic demyelination due to rapid correction of osmolality with fluctuating glucose levels, and (3) demyelination from hypertonic insult related to hyperglycemia.[2]

PubMed database was searched using the terms “hyperglycemia,” or “hyperglycemic” or “diabetes mellitus” or “diabetic ketoacidosis” and “osmotic demyelination,” or “myelinolysis” for systematic review, meta-analysis, and case reports or series in the past 5 years. After removing duplicates, a total of 32 articles were found [Supplementary Figure 1 ^{(114.9KB, tif)} ]. Literature reports with adult cases (>18 years) and published in English were included. We excluded cases with baseline deranged sodium levels (as it may act as a confounding factor) or ODS occurring from rapid correction of hyperglycemia. We found few case reports relevant to the current scenario, focusing on hyperosmolar hyperglycemia syndrome (HHS) with normal serum sodium at presentation [Supplementary Table 1].[2,3,4,5,6,7,8,9,10] Nine cases involved both type 1 and type 2 diabetes, often with uncontrolled blood sugar due to medication noncompliance. Most of them presented with gait ataxia and progressive quadriparesis, with symptoms lasting up to 7 months. ODS was rarely the initial diagnosis; it was often misdiagnosed as metabolic encephalopathy or Guillain–Barré syndrome, leading to unrelated treatments, including potentially harmful steroids. MRI has been beneficial, showing symmetrical hyperintensity with peripheral sparing on T2/FLAIR sequences, known as the “trident-shape” sign, and hypointense nonenhancing T1-weighted lesions without mass effect.[3] Most patients showed significant improvement over time.

Supplementary Table 1.

A literature review on adult case reports of Osmotic Demyelination Syndrome and hyperosmolar hyperglycemic state spanning the last five years (2020-2024)

Author, year [reference]	Country	Age/Gender	Clinical presentation	Comorbidities	HbA1c (gm%), Blood glucose (mg/dl), Corrected Serum sodium (mmol/L) at presentation	Initial/differential diagnosis	Treatment	Outcome
Kim et al., 2020 [3]	Korea	61/Male	Progressive quadriparesis, dysphagia and dysarthria for 1 day	T2DM on medication*, liver cirrhosis, HTN, dementia	18.1, 627, 133	CPM	Insulin infusion	Improved
Mir et al., 2021[4]	United States	34/Female	Progressive quadriparesis for 7 months followed by recent dysphagia	T2DM since 13 years initially on insulin follwed by OHA	12.3, 278, 138	GBS	Pulse Methylprednisolone (1g/d) followed by discontinuation. Continuing insulin infusion followed by glargine and lispro	improved power
Jalalzadeh et al., 2021[5]	United States	28/Female	Gait ataxia and altered sensorium for 2 days	T1DM*, end stage renal disease	HbA1c not mentioned, 105, 135	NCSE, metabolic encephalothy	ASM, pulse methylprednisolone	No improvement
Shi XY et al., 2021[2]	China	49/Male	Progressive paraparesis for 6months, dysphagia and blurring for 2 weeks	T2DM*, Right foot gangrene 2 weeks prior	8.9, 270, 140.8	Glioma, tumefactive demyelination	Pulse Methyprednisolone (1g/d) followed by oral steriods.	Improved except mild gait ataxia
Olowoporoku et al., 2022[6]	United States	48/Male	Two episodes of progressive quadriparesis, emotional lability and ataxia over 3 months	T2DM de novo during 1st episode	12.4, 391, 136	1st episode- pontine hyperintensity? Cause 2nd episode- MND, diabetic polyneuropathy	1st episode- OHA 2nd episode- medications#	Improved ambulation
Ghosh, et al., 2022[7]	India	65/Female	Altered sensorium for 1 day followed akinetic mute state	T2DM*, simultaneous SARS-CoV-2 infection	HbA1c not mentioned, 652, 136	Diabetic striatopathy, metabolic encephalopathy, Autoimmune/SARS-CoV-2 encephalitis	Glycemic control#, levodopa/carbidopa and pramipexole for akinetic mute state	Mutism improved
Shrestha et al., 2023[8]	Nepal	44/Male	Progressive paraparesis ataxia and dysphagia for 1.5 months followed by altered sensorium	T2DM* with chronic liver disease since 1 year	15.5, 271, 140	Hepatic or Wernicke’s encepalopathy, Osmotic Demyelination	Insulin glargine and Metformin	Mild gait impairment
Sun, et al., 2023[9]	China	66/Male	Gait ataxia, dysphagia and dysarthria for 2 weeks	T2DM since 1 week	15, 499, 137	Central pontine myelinolysis	Insulin according to sliding scale followed by fixation of dose	Fully recovered
Murao et al., 2023[10]	Japan	39/Male	First episode-Altered sensorium for 1 day Second episode- Altered sensorium and right sided hypokinesia	T1DM since 10 years	First episode-9.9, 569, 136 Second episode- Blood glucose-1056, Corrected serum sodium- 143	Osmotic Demyelination	Fluid and insulin replacement in both episodes	Fully recovered

*Duration and medication details for comorbidities not mentioned. ^#Treatment details not mentioned. HbA1c: Glycosylated haemoglobin; T2DM: Type 2 Diabetes mellitus; HTN: Hypertension; OHA: Oral hypoglycemic agent; GBS: Guillain-Barré syndrome; T1DM: Type 1 Diabetes mellitus; NCSE: Non-convulsive status epilepticus; ASM: Antiseizure drugs; MND: Motor neuron disease; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2, CPM: Central pontine myelinolysis

There were also cases where hospital correction of blood sugars led to osmotic demyelination, particularly in diabetic ketoacidosis or HHS patients.[11,12] Other cases describe HHS with deranged sodium levels, and correcting both conditions resulted in ODS.[1,12] Rare manifestations of hyperglycemia, such as craniofacial dyskinesia and nonconvulsive status epilepticus, are also known.[13,14] These unusual presentations expand our understanding of neurologic complications associated with hyperglycemia.

Although there is no specific treatment for ODS, advancements in diagnosis and medical management have improved outcomes. Recent studies show 33%–50% of cases with positive results. However, 33%–55% of patients may still need ongoing care, face dependency, or, in some cases, mortality.[15]

Conclusion

A vigilant approach is essential in cases of ODS, as treatment and prognosis remain cautious. It is crucial to consider HHS as a syndrome with diverse and sometimes rare manifestations, and conversely, ODS may stem from causes beyond the correction of sodium levels.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Supplementary Figure 1

Flow diagram of literature screening