Hypoglycemic hemiparesis as stroke mimic with transient splenial lesion and internal capsule involvement: A reversible clinico-radiological concurrence.

Hypoglycemia presents with a spectrum of neurological manifestations ranging from lightheadedness to confusion and coma. We report here the case of a 61-year-old woman with right hemiparesis presenting within the window period for stroke thrombolysis. MRI brain showed diffusion restriction in posterior limb of left internal capsule and splenium. Patient had documented hypoglycemia of 38 mg/dL. Patient's hemiparesis resolved after glucose correction, and radiological findings completely resolved after 10 days. We present this case to highlight the rare radiological finding of simultaneous internal capsule and splenium involvement in hypoglycemic hemiparesis and the importance to rule out stroke mimics to avoid unwanted thrombolysis.

Introduction

Brain tissue is highly susceptible to hypoglycemic injury because of its incapacity for internal glucose synthesis and limited glucose/glycogen stores. The effect of hypoglycemia on brain varies depending on the blood glucose levels. Autonomic symptoms such as sweating, irritability, and tremulousness appear at blood glucose levels of 68 mg/dL, followed by severe neuroglycopenic symptoms like confusion, seizure, and cognitive disturbance at 50 mg/dL. Below this level, hypoglycemic coma appears, and neuron death occurs below 18 mg/dL causing irreversible brain damage.[1] Hypoglycemia has predilection for posterior and deeper regions of brain like parieto-occipital and temporal gyri, hippocampus, and basal ganglia.[2]

We report here the case of a 61-year-old woman presenting as stroke mimic. Stroke mimics presenting in the window period remain a therapeutic challenge to investigate all reversible differentials of mimics, and thrombolytic treatment is time-sensitive.

Case History

A 61-year-old woman, hypertensive and type 2 diabetic, and on oral hypoglycemic agents (metformin 1 gm bd, glimepiride 2 mg bd) presented to the emergency at 7.00 a.m. with sudden-onset right hemiparesis since 1 hour. There was no history of trauma, fever, or seizure-like activity. On initial assessment, patient was conscious and oriented. BP was 130/80 mmHg. Cranial nerves and speech were normal. On motor system examination, tone was decreased in right upper limb and lower limb, power in right upper limb and lower limb was 3/5, and deep tendon reflexes were normal bilaterally symmetrical. Right plantar was mute. There was no sensory deficit. Rest of the systemic examination was normal. Blood sugar level was 38 mg/dL at 7.10 a.m. Glucose correction with 25% dextrose was started immediately. Repeat sugar levels were 189 mg/dL at 7.20 a.m. Patient improved in her weakness to grade 5/5 after glucose correction. Patient was transferred to radiology department for MRI brain at 7.30 a.m. to rule out acute stroke. MRI brain showed diffusion restriction with corresponding reduced ADC (apparent diffusion coefficient) in the splenium of corpus callosum and left posterior limb of internal capsule. FLAIR (fluid-attenuated inversion recovery) was normal. MRA brain showed mild narrowing of left proximal middle cerebral artery with hypoplastic right vertebral artery [Figure 1a-c]. As patient completely recovered in her motor power with NIHSS (National Institute of Health Stroke Scale) score of 0, decision to defer thrombolytic treatment was made at 7.55 a.m. Patient was admitted and treated for both glycemic control and stroke with antiplatelets and statins. Echocardiography was normal study. Carotid doppler showed mild intimomedial thickening in bilateral carotids. Follow-up MRI brain done 10 days later showed complete resolution of abnormal signal in splenium and internal capsule [Figure 1d and 1e]. The patient has had no recurrence of symptoms.

Figure 1

(a) MRI brain showing diffusion restriction in the left posterior limb of internal capsule and splenium (white arrows); (b) with corresponding ADC fall (white arrow heads); (c) axial FLAIR image showing no signal change; (d-f) follow-up MRI brain showing complete resolution of abnormal signals

Discussion

Stroke mimic refers to a pathological condition within or outside the central nervous system that shows a stroke-like clinical picture due to a symptom caused by a disease other than cerebrovascular diseases.[3] The common stroke mimics include brain tumors, toxic or metabolic disorders, infectious disorders, psychological disorders, migraine, seizures, and demyelinating disorders. Hypoglycemia is one of the common metabolic causes of stroke mimic.[4] Hypoglycemic hemiparesis (HH) is a well-described clinical presentation of hypoglycemia with rising incidence from 2% to 4.2% in the past 3 decades. Exact pathophysiology of HH is not known, but various hypotheses suggest cerebral vasospasm, asymmetric cerebral blood flow, and selective neuronal vulnerability as possible mechanisms for asymmetrical involvement of brain.[56] Left-hemisphere involvement is more commonly reported with right hemiparesis (66% vs. 34%), as in the present case. HH is usually reported at blood glucose levels of ≤1.8 mmol/L (32.4 mg/dL).[5]

This particular clinical and radiological scenario carries diagnostic and therapeutic challenges along with dilemma in prognosis estimation. There is no definite way to differentiate between infarct and hypoglycemic injury on brain imaging, especially when the lesion is focal, unilateral, and corresponding to hemiparesis as in the present case. The process of asynchronous cerebral iso-electricity explains asymmetric brain imaging findings in hypoglycemia.[7] Common areas of involvement in HH with abnormal brain imaging are basal ganglia, hippocampus, temporal and occipital gray matter, insular cortex, corona radiata, and splenium which usually reverse radiologically within 10 days.[8] In various studies on HH with abnormal brain imaging, internal capsule is involved in 65% of the cases, splenium in 30%, and even both together is not uncommon.[5910] Three imaging patterns in hypoglycemia have been described. These include: 1) predominant gray matter; 2) predominant white-matter involvement affecting the periventricular white matter, internal capsule, and splenium of corpus callosum; and 3) mixed pattern, involving both the gray matter and the white matter. Pattern 2 follows good prognosis secondary to early resolution of imaging findings consistent with the present case.[7] The mechanism of reversibility of hypoglycemic brain injury is explained by the phenomenon of axon-sparing excitotoxic injury. Glucose deprivation induces ionic pumping failure in cell membrane, which causes glutamate and non-N-methyl-D-aspartate receptors–mediated edema (fluid accumulation) in the surrounding myelin sheaths and glial cells. Separation of motor neurons from the myelin layers by intramyelinic clefts and edema protects axons from intracellular edema and irreversible damage. The severity and duration of hypoglycemia govern the extent of reversibility.[11]

In this era of interventional stroke therapies with potential adverse effects, it is important to differentiate stroke from stroke mimics. On an average, complete clinical recovery of HH can take over a period of 1 hour to 3 days once normoglycemia is maintained.[12] Partial recovery after corrections of blood sugar level can pose a therapeutic dilemma for intravenous thrombolysis. As per stroke guidelines, in circumstances where patient does not make neurological improvement, and diagnostic dilemma in stroke mimic is more in favor of stroke, then thrombolysis can be carried out in preference over delaying treatment to pursue additional diagnostic studies with IIa class of recommendation.[13] Various studies on thrombolysis in stroke mimics prefer intravenous thrombolytic therapy in cases of strong suspicion of stroke on clinical and imaging findings rather than delay in treatment. Stroke thrombolysis protocols were followed as per guidelines in suspected strokes that turned out to be stroke mimics post-thrombolysis. A lower rate of symptomatic intracranial hemorrhage and better mRS at 3 months suggest favorable outcome of intravenous thrombolysis in stroke mimics.[1415]

The present case presented within the window period for the stroke, but the neurological deficit completely recovered after glucose correction. Furthermore, apart from the posterior limb of internal capsule, transient splenial lesion was present as well, which was not indicative of vascular territory stroke. Transient splenial lesions are more characteristic of metabolic disturbance, infections, epilepsy, malignancy, drugs, and toxins.[16] Internal capsule and splenium have been reported as areas vulnerable to hypoglycemia-induced reversible cytotoxic brain edema.[9] Similarly in the present case with diffusion restriction in internal capsule with corresponding neurological deficit, the presence of transient splenial lesion was more favorable for a metabolic etiology.

Conclusion

The present case highlights that hypoglycemia should be excluded in all suspected stroke cases even in the absence of history of diabetes to prevent permanent neurological damage. This is particularly important in satellite centers that follow the drip-and-ship policy to comprehensive stroke center. Cases with strong clinical and radiological suspicion of stroke should be thrombolyzed if patient is fulfilling the criteria for intravenous thrombolysis, despite presence of hypoglycemia or partial recovery after glucose correction.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

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Conflicts of interest

There are no conflicts of interest.