Atypical Hypoglycemia-Induced Stroke Mimic: A Case Report and Literature Review

Abstract

This case describes an uncommon presentation of a hypoglycemia-related stroke mimic in a patient with poorly controlled type 2 diabetes, in whom acute neurological symptoms developed despite a blood glucose level above the conventional hypoglycemic threshold. A 72-year-old woman presented with acute fatigue, drowsiness, and dysarthria after initiation of an intensified glucose-lowering regimen. Her blood glucose level was 4.1 mmol/L at symptom onset and increased after glucose administration; however, her neurological symptoms persisted. Because acute ischemic stroke could not be confidently excluded during the emergency evaluation, intravenous alteplase was administered. Her symptoms subsequently improved approximately 9.5 hours after symptom onset. Comprehensive neurovascular and brain imaging, including computed tomography, computed tomography angiography, magnetic resonance imaging, and transcranial Doppler ultrasonography, showed no evidence of acute ischemic lesions or significant vascular occlusion. After adjustment of her glucose-lowering therapy, her neurological condition remained stable, and no permanent neurological deficits were observed. This case highlights the diagnostic challenge of distinguishing hypoglycemia-related stroke mimic from acute ischemic stroke, particularly in patients with poorly controlled diabetes and fluctuating glucose levels. It also suggests that relative or rapidly declining glucose levels may contribute to stroke-like neurological symptoms even when absolute glucose values do not meet the conventional definition of hypoglycemia. Careful clinical assessment, timely glucose measurement, and urgent stroke evaluation remain essential when acute ischemic stroke cannot be reliably excluded.

Plain Language Summary

Stroke is a medical emergency that requires rapid diagnosis and treatment. However, some conditions can closely resemble a stroke but are not caused by blocked or bleeding blood vessels in the brain. These conditions are known as stroke mimic. One well-known stroke mimic is low blood sugar, which can cause temporary neurological symptoms. Usually, these symptoms occur only when blood sugar levels are clearly low. In this report, we describe an unusual case in which stroke-like symptoms occurred even though the patient’s blood sugar was not severely low. A 72-year-old woman with poorly controlled type 2 diabetes developed sudden tiredness, drowsiness, and slurred speech shortly after starting a new medication to lower her blood sugar. At the time her symptoms began, her blood glucose level was slightly low but still above the level typically associated with hypoglycemia-related brain symptoms. Although her blood sugar returned to normal after receiving glucose, her neurological problems did not immediately improve. Because her symptoms were consistent with an acute stroke and no clear alternative explanation could be confirmed, doctors treated her with a clot-dissolving medication that is commonly used for ischemic stroke. After treatment, her symptoms gradually improved. Detailed brain and blood vessel imaging performed later showed no evidence of a stroke, confirming that her condition was a stroke mimic rather than true brain damage. This case highlights that stroke-like symptoms can occur in people with diabetes even when blood sugar levels are not markedly low. It emphasizes the difficulty clinicians face when trying to rapidly distinguish between true stroke and stroke mimics. Importantly, it supports careful clinical decision-making and suggests that timely stroke treatment may still be appropriate when a stroke cannot be confidently ruled out, especially in high-risk patients.

Introduction

Stroke is an acute cerebrovascular condition characterized by sudden neurological dysfunction caused by interrupted cerebral blood flow or intracranial hemorrhage. It remains one of the leading causes of mortality and long-term disability worldwide, with ischemic stroke comprising the majority of cases. Distinguishing true ischemic stroke from “stroke mimic” remains a significant clinical challenge. Stroke mimic is condition that initially resemble acute ischemic stroke because they present with sudden focal neurological deficits, but subsequent evaluation reveals a non-cerebrovascular cause, such as metabolic disturbance, seizure, functional or psychiatric disorder, or infection. ¹ They account for approximately 20%–50% of patients initially evaluated for suspected acute stroke. ² Among metabolic causes, hypoglycemia is a prominent contributor to stroke-like presentations in diabetic patients, typically producing transient neurological deficits such as dysarthria, weakness, or confusion that rapidly improve following glucose correction.^2,3

The purpose of this case report is to describe an atypical presentation of hypoglycemia-related stroke mimic in which stroke-like symptoms occurred despite blood glucose levels remaining above conventional hypoglycemic thresholds. Rather than reflecting only an absolute glucose threshold, the development of neurological symptoms may also relate to the rate and magnitude of glucose decline, the duration of relative glucose deprivation, and the patient’s previous glycemic exposure. ⁴ This mechanism is consistent with the concept of relative hypoglycemia, in which individuals with chronic hyperglycemia may experience hypoglycemia-like symptoms at glucose levels that would not typically be considered hypoglycemic. ⁵ To contextualize the clinical relevance and rarity of this phenomenon, a literature review was conducted using PubMed and Web of Science with the search terms “stroke mimic,” “hypoglycemia,” “diabetes mellitus,” and “neurological deficits.” Previous studies have reported that hypoglycemia-related neurological deficits typically occur at markedly reduced glucose levels and often improve after glucose correction, highlighting the atypical nature of cases that deviate from this pattern.

This case introduces a patient who developed persistent dysarthria and drowsiness despite near-normal glucose levels, leading to diagnostic uncertainty and time-sensitive management under suspicion of acute ischemic stroke. By presenting this case, we aim to expand current understanding of hypoglycemia-associated stroke mimic and highlight the importance of recognizing atypical metabolic presentations in diabetic patients to minimize misdiagnosis while ensuring timely therapeutic decisions when true stroke cannot be excluded.

Case Description

A 72-year-old Asian female with a six-year history of type 2 diabetes mellitus presented with a two-month history of progressively worsening numbness and paresthesia in both lower extremities. At presentation, she reported no limb weakness, gait disturbances, dizziness, or visual symptoms. Her medical history was notable for hypertension, hypercholesterolemia, and carotid atherosclerosis, with no prior history of stroke, transient ischemic attacks, seizure, or hepatic and renal disease. Her family history included diabetes mellitus in her sisters and gestational diabetes mellitus in her daughter. Upon admission, physical examination revealed a body mass index (BMI) of 29.0 kg/m² and a blood pressure of 169/80 mmHg. The systemic examination was otherwise unremarkable, including motor function and sensory level on neurological examination.

Initial laboratory investigations indicated poorly controlled type 2 diabetes mellitus, with a fasting plasma glucose level of 18.0 mmol/L, an HbA1c of 13.7%, and a random plasma glucose of 25.4 mmol/L. Further metabolic evaluation showed an FPG of 13.38 mmol/L, fasting insulin level of 6.39 μU/mL, and fasting C-peptide level of 1.98 ng/mL. Diabetes-related autoantibodies (ICA, GADA, IAA) were negative. Renal function was also evaluated, with serum creatinine of 68.1 μmol/L, blood urea nitrogen of 6.92 mmol/L, and estimated glomerular filtration rate of 78.99 mL/min/1.73 m², indicating normal renal function. Carotid duplex ultrasound demonstrated bilateral atherosclerotic plaques, and lower-extremity vascular ultrasonography showed peripheral atherosclerotic changes. Baseline non-contrast cranial MRI and chest radiography showed no acute or significant abnormalities.

The patient was initially managed with intensive subcutaneous insulin therapy (basal-bolus regimen: insulin glargine 22 IU qn and insulin aspart 8-8-8 IU) and metformin 1000 mg twice daily. Five days later, the regimen was adjusted to metformin 1000 mg twice daily, dapagliflozin 10 mg once daily, semaglutide 0.25 mg weekly, and insulin glargine 28 IU at bedtime.

On the second night after this treatment adjustment, at 21:00, following this adjustment, the patient developed acute fatigue, hunger, sweating, and nausea. A capillary blood glucose level of 4.1 mmol/L was recorded. Despite immediate administration of 20 mL of 50% intravenous glucose, the patient’s clinical condition did not fully normalize, subsequently progressing to drowsiness and speech difficulty by 01:00 AM. Neurological examination during this episode revealed persistent speech impairment and slowed word retrieval, with a National Institutes of Health Stroke Scale (NIHSS) score of 2. Laboratory tests excluded electrolyte abnormalities. An emergency head CT ruled out intracranial hemorrhage. Given the persistence of neurological deficits, the presence of cardiovascular risk factors, and presentation within the thrombolytic time window, a presumptive diagnosis of acute ischemic stroke was made. Intravenous alteplase (rtPA) was administered (6.9 mg bolus followed by a 62.1 mg infusion). By 06:30 AM, four hours following the initiation of thrombolytic therapy, the patient’s speech function and level of consciousness had completely recovered.

Extensive post-thrombolysis neuroimaging was performed to clarify the underlying etiology. A repeat cranial MRI with diffusion-weighted imaging (DWI) performed 12 hours after symptom onset demonstrated no restricted diffusion (Figure 1A). Computed tomography angiography (CTA) showed no evidence of intracranial or carotid artery stenosis (Figure 1B). Transcranial Doppler ultrasonography and repeat carotid ultrasonography showed no evidence of new vascular compromise. The overall clinical course, including treatment adjustment, onset of hypoglycemic symptoms, neurological deterioration, thrombolytic therapy, subsequent symptom resolution, and negative neuroimaging findings, is summarized in Table 1.

Figure 1.

Neuroimaging findings 12 hours after the onset of stroke-like symptoms. (A) Representative axial diffusion-weighted MRI images at multiple supratentorial levels showed no restricted diffusion suggestive of acute ischemic infarction. (B) CTA images, including an axial source image and three-dimensional angiographic reconstruction views, showed patent major intracranial arteries without obvious vascular stenosis or occlusion

Table 1.

Timeline of the Hypoglycemia-Induced Stroke Mimic Event and Subsequent Diagnostic Evaluation

Time point	Clinical events, investigations, and management
2 months before admission	Progressive bilateral lower-extremity numbness and paresthesia.
1 month before admission	Poor glycemic control identified (fasting glucose 18 mmol/L; HbA1c 13.7%).
Day 0 (Admission)	Severe hyperglycemia (random glucose 25.4 mmol/L); basal–bolus insulin plus metformin initiated; baseline neuroimaging negative.
Day 5	Antihyperglycemic regimen adjusted (metformin, dapagliflozin, semaglutide, insulin glargine).
Day 6 evening (21:00)	Symptomatic hypoglycemia (glucose 4.1 mmol/L) with persistent drowsiness and dysarthria despite intravenous glucose correction.
Day 7 early morning (01:00–02:00)	Stroke mimic suspected; hemorrhagic and electrolyte causes excluded. Despite normalization of blood glucose, drowsiness and dysarthria persisted. Intravenous alteplase was administered within the thrombolytic time window.
Day 7 morning (06:30)	The patient became clear-minded with fluent speech.
Post-event imaging and follow-up	MRI and CTA were negative for acute infarction, confirming hypoglycemia-induced stroke mimic.

Based on the transient nature of the symptoms, the preceding hypoglycemic event, and the negative multimodal imaging, the event was finalized as a hypoglycemia-induced stroke mimic. The patient’s glycemic management was subsequently optimized, and no further hypoglycemic episodes occurred. The patient was discharged in a stable condition with no residual neurological deficits and referred for outpatient follow-up in endocrinology and neurology.

Discussion

Stroke mimic presents a significant clinical challenge, as conditions such as hypoglycemia often lead to misdiagnosis.^1,6 Seizures, syncope, sepsis, migraine, space-occupying lesions, functional neurological disorders, and metabolic disturbances represent the seven most common differential diagnoses in patients presenting with suspected stroke. ⁷ Hypoglycemia is commonly observed in diabetic patients, particularly those on insulin or sulfonylureas, and can result in focal neurological deficits that are frequently misinterpreted as ischemic stroke. Symptoms of hypoglycemia include seizures, autonomic signs, decreased consciousness, and focal deficits such as hemiparesis and visual disturbances.^3,8 The pathophysiology of hypoglycemia-induced stroke-like symptoms is associated with energy metabolic disturbances in the nervous system due to a lack of glucose, which is the brain’s primary energy source. Hypoglycemia can affect both the central and peripheral nervous systems, leading to cognitive impairment, seizures, and regionally selective neuronal loss, particularly in the cerebral cortex and hippocampus, while also increasing the vulnerability of peripheral axons. ⁹ Hypoglycemia leads to neuronal dysfunction, particularly affecting the cerebral cortex and basal ganglia. This ischemic-like injury typically manifests as cytotoxic edema, which is evident on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences. ² Recurrent hypoglycemia can induce cellular adaptations and oxidative stress in vulnerable brain regions, impairing hypoglycemia awareness and potentiating long-term neuronal injury through heightened glycemic variability. ¹⁰ A key distinguishing feature of hypoglycemia-induced stroke mimic is the absence of a clear vascular distribution, with bilateral lesions often pointing to a metabolic disorder rather than ischemic stroke. Early recognition and appropriate treatment of hypoglycemia are essential, as prompt glucose correction typically resolves the neurological deficits. ³

A summary of eight cases of hypoglycemia-induced stroke mimic is presented in Table 2.^11-17 Compared with patients with true ischemic stroke, individuals with ischemic stroke mimic generally exhibit fewer vascular risk factors, are younger in age, have a higher proportion of females, present with blood pressure values closer to normal ranges, and tend to demonstrate absent or milder neurological deficits.^18,19 Hypoglycemia-induced stroke mimic can present with a wide range of neurological symptoms, including hemiparesis, dysarthria, and confusion. Patients with a history of diabetes mellitus, particularly those on insulin or sulfonylureas, are at increased risk for these episodes. Decreased consciousness has been identified as a clinical feature that increases the likelihood of a stroke mimic, whereas a history of angina appears to reduce this likelihood. ²⁰ Notably, blood glucose levels during these episodes typically fall below 3.0 mmol/L. In these reported cases, neurological symptoms resolved rapidly after intravenous or oral glucose administration, supporting hypoglycemia as the primary cause of the transient neurological deficits. The typical neurological manifestations of stroke mimic in hypoglycemic episodes include slurred speech, hemiparesis (often unilateral), and altered mental status, such as drowsiness or confusion. In some cases, patients may also experience additional symptoms, including aphasia, defined as impaired language comprehension or expression; hemichorea, characterized by involuntary irregular movements on one side of the body; or sensory loss, referring to reduced or absent sensation. ¹⁵ Recovery is generally swift, with symptoms typically improving within minutes to hours after glucose administration. Recurrence of symptoms is uncommon after appropriate glucose correction and adjustment of medication regimens, such as reducing sulfonylureas or adjusting insulin doses. Despite the acute neurological symptoms, long-term outcomes are favorable with no permanent deficits if treated promptly. This highlights the importance of monitoring and adjusting diabetic therapies to prevent hypoglycemic events and related neurological manifestations.

Table 2.

Cases of Hypoglycemia-Induced Stroke Mimic

Case	Age	Sex	History of DM	Therapeutic regimen	Blood glucose during stroke mimic episode	Symptoms	Treatment	Outcome
1 12	69Y	M	T2DM	Glyburide	1.39 mmol/L at first episode;	Slurred speech, motor weakness progressing to dense hemiplegia, facial weakness.	50% dextrose i.v.; subsequent 5% dextrose i.v.; glyburide discontinuation.	Rapid resolution of neurologic deficits; no recurrence of symptoms.
				5mg qd	1.89 mmol/L at recurrence
2 13	75Y	F	T2DM	Metformin 500 mg bid;	1.9 mmol/L	Drowsiness, slurred speech, right-sided haemiparesis, dysphasia, dysarthria.	1 mg glucagon i.m.; intravenous dextrose stabilized blood glucose.	neurological symptoms resolved and no permanent neurological damage.
				Gliclazide 80 mg bid
3 14	47Y	M	T2DM	Metformin 1g bid; Glipizide 5 mg qd	2.06 mmol/L	Sudden right-sided hemiparesis with weakness in the right arm and leg, slurred speech with mild to moderate dysarthria, and mild confusion.	Intravenous dextrose administration immediately. Additional dextrose dose 2 hours later (for blood glucose 3.33 mmol/L).	Symptoms significantly improved within 5 minutes.
4 15	64Y	F	T1DM	45 units NPH insulin qd	3.89 mmol/L	Sudden right hemiparesis, right hemisensory loss, aphasia mutism.	Intravenous 50% dextrose; NPH insulin was adjusted to 20 units.	Complete resolution of neurologic deficits; no further episodes occurred.
5 15	62Y	M	T1DM	Insulin therapy	1.61 mmol/L	Generalized weakness, diaphoresis, abnormal speech.	Oral glucose (first episode); intravenous dextrose (recurrence).	Complete resolution of symptoms; no hemiparesis.
6 16	72Y	F	No clear	Not available	2.44 mmol/L	Poor appetite, initial drowsiness, progressive loss of consciousness, mild incontinence.	Intravenous glucose supplementation.	Regained consciousness without motor function deficits.
7 17	67Y	M	T1DM	Insulin therapy (total 79 units/day)	3.1 mmol/L at first episode; 2.7 mmol/L at recurrence	Right incomplete hemiplegia, dysarthria, paresthesia in right limbs.	Oral glucose administration; adjusted insulin dose.	Symptoms resolved within hours or minutes after glucose administration.
8 11	69Y	M	No clear	Not available	2.5 mmol/L	Sudden left hemiplegia, dizziness; Continuous involuntary movement of left limbs After hypoglycaemia correction.	Oral glucose water supplementation; Intramuscular injection of haloperidol 10 mg bid for 1 week.	Hemiplegia resolved 3 hours after oral glucose supplementation; no recurrence 1 year after onset.

Abbreviations: M: Male; F: Female; Y: Years; DM: diabetes mellitus; i.v.: Intravenous; i.m.: intramuscular.

In this case, the patient exhibited common hypoglycemic symptoms, such as fatigue, hunger, sweating, nausea, and drowsiness, when blood glucose was 4.1 mmol/L. After intravenous administration of 20 mL of 50% glucose, the blood glucose level increased to 5.1 mmol/L, at which point neurological symptoms began to emerge. Despite the blood glucose rising to 6.9 mmol/L, the neurological symptoms were not alleviated. Because the focal neurological deficits persisted after glucose correction, acute ischemic stroke could not be excluded, and thrombolytic therapy was subsequently initiated. The uniqueness of this case lies in the fact that the patient developed stroke-like neurological symptoms even before meeting the criteria for hypoglycemia, and the symptoms did not resolve despite the normalization of blood glucose. Capillary blood glucose measurements were obtained in temporal correspondence with symptom assessment, as summarized in Table 3.

Table 3.

Blood Glucose and Corresponding Symptoms of This Case

Blood glucose (mmol/L)	Symptom
4.1	Fatigue, hunger, sweating, nausea
5.1	Palpitation, hunger, drowsiness. Dysarthria began to occur; limb muscle strength and activity were normal; pathological reflexes (-)
6.9	Drowsy and dysarthria unrelieved
6.7	Clear-minded and fluent in speech

Because metformin is primarily cleared by the kidneys, impaired renal function may increase the risk of drug accumulation and excessive glucose-lowering effects. In this case, renal function was preserved, with an eGFR of 78.99 mL/min/1.73 m² and no clinically significant albuminuria, making clinically significant metformin accumulation due to reduced renal clearance unlikely. Nevertheless, the combined glucose-lowering regimen, particularly bedtime insulin glargine together with other antidiabetic agents, may have contributed to the glucose decline and the development of relative hypoglycemia.

Despite the restoration of systemic euglycemia, the persistence of neurological deficits in hypoglycemic stroke mimics can be attributed to a hypothesized cascade of excitotoxic injury and selective regional vulnerability. Severe neuroglycopenia triggers massive glutamate efflux and impaired reuptake, leading to lethal intracellular calcium influx and mitochondrial dysfunction. ²¹ Consequently, cytotoxic edema or metabolic stunning in highly metabolic regions explains why neurological recovery may lag behind biochemical correction. In addition, Sirtuin 1 (SIRT1), a regulator of glucose metabolism and cellular stress responses, has been implicated in metabolic and neurological disorders, and its potential role in modulating neural vulnerability during marked glycemic fluctuations warrants further investigation. ²²

Although the clinical course suggested an atypical hypoglycemia-associated stroke mimic, the patient’s advanced age, long-standing diabetes mellitus, hypertension, and atherosclerotic plaques increased the pretest probability of true ischemic stroke. Diabetes is a well-established risk factor for stroke and may contribute to ischemic stroke through mechanisms including large artery atherosclerosis, cerebral small vessel disease, and cardiac embolism. ²³ Therefore, due to the persistence of neurological symptoms following blood glucose recovery, the possibility of an ischemic stroke could not be excluded, and thrombolytic therapy was administered. A study proposed the ROSIER scale, which can effectively aid in the preliminary differentiation between acute stroke and stroke mimic in emergency settings. Although it demonstrates relatively high specificity, the scale has not yet been widely adopted in clinical practice. ²⁴ For patients with stroke mimic, intravenous thrombolysis has been shown to be highly safe. ²⁵ Research indicates that in cases of diagnostic uncertainty, it is preferable to initiate intravenous thrombolysis rapidly, followed by further diagnostic investigations. This approach aligns with the principle of clinical benefit, as delaying treatment due to concerns about ruling out stroke mimic may be more detrimental than providing timely treatment. ²⁶ The decision to proceed with thrombolysis in this case was in line with clinical guidelines, optimizing the patient’s potential for recovery while minimizing the risks associated with delayed intervention.

After symptom resolution, the patient underwent further imaging examinations, including CT, CTA, MRI, and transcranial Doppler, all of which did not support the diagnosis of ischemic stroke. Brain CT was used to assess gross structural abnormalities, including intracranial hemorrhage or obvious parenchymal lesions, and showed no abnormal density within the brain parenchyma. Brain MRI indicated no significant abnormal high signal on Diffusion Weighted Imaging (DWI) in the brain parenchyma, a sequence sensitive to restricted water diffusion and commonly used to detect acute ischemic infarction. No abnormal low signal was observed on Susceptibility Weighted Imaging (SWI), which is sensitive to hemorrhage, blood products, and susceptibility-related vascular abnormalities. Contrast-enhanced CTA and vascular reconstruction were used to evaluate the patency and morphology of the intracranial arteries and revealed no intracranial arterial stenosis or occlusion. A study investigating the use of DWI MRI to screen for stroke mimic showed that among patients diagnosed as stroke mimic via DWI, all exhibited negative DWI findings, with no features suggesting acute ischemia, such as DWI hyperintensity lesions with corresponding low signal on apparent diffusion coefficient maps. ²⁷ The signal changes in stroke mimic caused by hypoglycemia primarily involve white matter, with early DWI high signal and decreased ADC, while T2/FLAIR high signal appears later. After correction of blood glucose levels, the MRI signal may completely resolve. Performing brain MRI as an initial evaluation in patients presenting with acute neurological symptoms is of particular importance for distinguishing vascular neurological dysfunction from stroke mimic.^28,29 Pre-diagnostic use of MRI (DWI + PWI) screening can reduce the risk of misadministration of thrombolytic therapy.

This case has several limitations. First, the absence of continuous glucose monitoring prevents precise characterization of the glucose fluctuations preceding symptom onset. Second, given the transient nature of symptoms and normal imaging, definitive exclusion of a very small ischemic event is not possible. Third, the literature cases summarized in Table 2 were limited and heterogeneous, precluding meaningful assessment of the effects of sex, age, or anti-diabetic regimen. Nonetheless, the temporal relationship between fluctuating glucose levels and symptoms, the resolution of deficits, and the absence of imaging abnormalities support the validity of the diagnosis.

Conclusion

This case highlights an atypical presentation of hypoglycemia-induced stroke mimic, in which stroke-like neurological deficits developed before blood glucose reached classical hypoglycemic thresholds and persisted despite subsequent glucose normalization. These findings suggest that blood glucose levels alone may not reliably exclude metabolic stroke mimic. In diabetic patients presenting with acute focal neurological deficits, clinicians should integrate metabolic assessment, neuroimaging findings, and clinical judgment. When ischemic stroke cannot be confidently excluded, timely thrombolytic therapy remains clinically appropriate. Further studies are needed to clarify metabolic thresholds, imaging biomarkers, and diagnostic strategies for distinguishing ischemic stroke from hypoglycemic stroke mimics.

ORCID iD

XiaoJing Wang https://orcid.org/0000-0002-1819-3782

Ethical Considerations

This study is a case report describing the clinical course and management of a single patient. The requirement for ethics approval was waived for this single-patient case report according to institutional policies and national regulations.

Consent for Publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. All identifying information has been anonymized to protect patient confidentiality.

Data Availability Statement

All relevant data supporting the conclusions of this case report are included within the article.*