Acute stroke-like deficits associated with nonketotic hyperglycemic hyperosmolar state: an illustrative case and systematic review of literature

Abstract

Introduction: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet.

Methods: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation.

Results: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years; p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL; p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3-10) days, following aggressive treatment and glucose normalization.

Conclusions: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings.

Keywords: Hyperglycemia; Hyperosmolarity; Neurological deficits; Nonketotic hyperglycemic hyperosmolar state; Stroke; Stroke mimic.

Fig. 1

Electroencephalography (EEG). Right hemisphere slow wave activity without epileptic abnormalities (P2 montage with electrocardiography, 1.5 cm/s speed, 7.0 uV/mm sensitivity, 70.0 Hz frequency)

Fig. 2

Brain magnetic resonance imaging (MRI). A, B Multifocal right hemispheric subcortical T2-fluid attenuated recovery (FLAIR) hypointensities and C disseminated hyperintensities on diffusion weight imaging (DWI) with D restricted apparent diffusion coefficient (ADC)

Fig. 3

Events and investigation timeline. Abbreviations: CT computed tomography; CTA computed tomography angiography; ED emergency department; EEG electroencephalography; MRI magnetic resonance imaging; TCD transcranial Doppler

Fig. 4

PRISMA flowchart

Fig. 5

Suggested mechanisms leading to neurological symptoms in nonketotic hyperglycemic hyperosmolar state (NKHHS). Positive symptoms (e.g., seizures) may result from neuronal depletion of gamma aminobutyric acid (GABA), secondary to Kreb’s cycle disruption (GABA shunt). Negative symptoms, such as focal deficits (e.g., hemianopia), may be related to glial dehydration due to hyperosmolarity, enhancing metabolic or ischemic disruption of neuronal function