Clinical characterization of non-ketotic hyperglycemia-related seizures: A systematic review and individual participant data meta-analysis. (March 2023)

• Record Type: Journal Article
• Authors: Licchetta, Laura; Ferri, Lorenzo; Morsillo, Filomena; Faustini-Fustini, Marco; Toni, Francesco; Pondrelli, Federica; Nonino, Francesco; Bisulli, Francesca; Tinuper, Paolo
• Is Part Of: Seizure. Volume 106(2023)
• Page Start: 50
• Page End: 57
• Publication Date: 2023-03
• Subjects: Non-ketotic hyperglycemia -- Diabetes mellitus type II -- Acute symptomatic seizure -- Epilepsia partialis continua -- Reflex seizures -- Systematic review; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2023.01.018
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: Acute symptomatic seizures are the most frequent manifestations of non-ketotic hyperglycemia (NKH), a complication of diabetes mellitus. We conducted a systematic review of the PubMed, Embase, and Cochrane Library databases including 130 publications reporting 332 patients. Ictal manifestations mainly consist of clustering focal aware seizures from motor (49.4%)/posterior (16.9%) cortices; 10.5% had reflex seizures. Higher osmolarity levels were associated with newly-diagnosed diabetes mellitus and other neurological symptoms at presentation beside seizures. Glycemic values were higher in patients with focal aware seizures with motor onset. Lower glycemic values were associated with reflex seizures. Abstract: New-onset epileptic seizures and status epilepticus (SE) are the most frequent neurological manifestations of non-ketotic hyperglycemia (NKH), an acute complication of diabetes mellitus (DM). Treatment consists of the correction of the underlying metabolic disorder, whereas anti-seizure medications (ASMs) may even worsen seizures. Evidence on NKH-related seizures is currently restricted to case reports and small case-series. We conducted a systematic review of the PubMed, Embase, and Cochrane Library databases to provide a comprehensive description of NKH-related seizures. Statistical analyses were performed to explore possible associations of glycemic and osmolarity levels with clinical variables. We selected 130 publications and 332 patients (186 males, mean age: 61.1 years). DM was newly-diagnosed in 40%. Mean glycemia and osmolarity levels at presentation were 529.7 mg/dL and 309.6 mmol/mol, respectively; 22.6% showed other neurological symptoms besides seizures. Focal motor seizures were the prominent seizure type (49.4%); non-motor focal seizures (23.2%) most commonly manifested as visual symptoms. Reflex seizures occurred in 10.5%. Brain MRI in 48.7% of cases showed focal T2 subcortical hypodensity and/or overlying cortical T2 hyperintensity with DWI restriction. ASMs were administered in 54.2% of cases, achieving seizure control in just 18.3%. Higher osmolarity levels were associated with newly-diagnosed DM ( p = 0.002) and other symptoms at presentation ( p < 0.001). Glycemic values were higher in patients with focal aware seizures with motor onset compared to those with focal seizures without motor onset ( p = 0.0046) or focal seizures with impaired awareness ( p = 0.0306). Lower glycemic values were associated with reflex seizures ( p = 0.036) and ASM administration ( p < 0.001). NKH-related seizures should be suspected in adults with new-onset clustering focal seizures arising from the motor or posterior cortices, even in the absence of a history of DM. Typical focal changes on brain MRI, while not pathognomonic, can drive the clinical diagnosis. Statistical associations suggest a key role of hyperglycemia in the excitability of higher-energy-demanding cortical areas.