Hyperglycemia with occipital seizures: images and visual evoked potentials

PURPOSE: Hyperglycemia may rarely be seen with visual seizures. Observation of both visual evoked potentials (VEPs) and magnetic resonance imaging (MRI) in visual status epilepticus (SE) has not been reported. We describe acute and follow-up VEP and MRI findings of a patient with hyperglycemia-related visual SE of occipital origin. METHODS: In a 59-year-old diabetic woman, complex visual hallucinations and illusions developed with < or =10 seizures per hour as an initial manifestation of nonketotic hyperglycemia. RESULTS: Neurologic examination revealed ictal nystagmus to the right and continuous right hemianopsia. Ictal electroencephalography (EEG) and Tc-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT) revealed an epileptogenic focus in the left occipital lobe. MRI with fluid-attenuated inversion recovery showed focal subcortical hypointensity and gyral hyperintensity. Follow-up MRI showed only minimal gyral hyperintensity at 6 months. The P100 amplitude of VEP was significantly higher at the right occipital area during SE, but slightly higher on the left after the patient had been seizure free for 6 months. CONCLUSIONS: Occipital seizures and hemianopsia can be caused by hyperglycemia and may be accompanied by special MRI and VEP findings.     

Glycine cleavage system in neurogenic regions

The glycine cleavage system (GCS) is the essential enzyme complex for degrading glycine and supplying 5,10-methylenetetrahydrofolate for DNA synthesis. Inherited deficiency of this system causes nonketotic hyperglycinemia, characterized by severe neurological symptoms and frequent association of brain malformations. Although high levels of glycine have been considered to cause the above-mentioned problems, the detailed pathogenesis of this disease is still unknown. Here we show that GCS is abundantly expressed in rat embryonic neural stem/progenitor cells in the neuroepithelium, and this expression is transmitted to the radial glia-astrocyte lineage, with prominence in postnatal neurogenic regions. These data indicate that GCS plays important roles in neurogenesis, and suggest that disturbance of neurogenesis induced by deficiency of GCS may be the main pathogenesis of nonketotic hyperglycinemia.     

Glycinelserine ratios in amniotic fluid: an unreliable indicator for the prenatal diagnosis of nonketotic hyperglycinemia

A series of 183 amniotic fluid samples from pregnancies with normal outcome were examined to assess the validity of the glycine/serine ratio in the prenatal diagnosis of nonketotic hyperglycinemia. The glycine/serine ratios in our series span a range of values which includes those of the previously reported control group as well as those values of a fetus with nonketotic hyperglycinemia. These data indicate that the glycine/serine ratio in the amniotic fluid of a pregnancy at risk for nonketotic hyperglycinemia is not a reliable indicator for the prenatal diagnosis of this disorder.     

NONKETOTIC HYPERGLYCINEMIA Clinical, Biochemical and Therapeutic Aspects

Abstract. A patient exhibiting progressive cerebral depression from the first days of life is described. The diagnosis of nonketotic hyperglycinemia was established on the typical clinical presentation, elevated glycine concentrations in body fluids and diminished glycine cleavage activity in liver tissue. A series of therapatic trials, including strychnine treatment, was tried on this patient without apparent effect on the clinical course.     

Nonketotic hyperglycinemia: Functional assessment of missense variants in GLDC to understand phenotypes of the disease

The rapid analysis of genomic data is providing effective mutational confirmation in patients with clinical and biochemical hallmarks of a specific disease. This is the case for nonketotic hyperglycinemia (NKH), a Mendelian disorder causing seizures in neonates and early‐infants, primarily due to mutations in the GLDC gene. However, understanding the impact of missense variants identified in this gene is a major challenge for the application of genomics into clinical practice. Herein, a comprehensive functional and structural analysis of 19 GLDC missense variants identified in a cohort of 26 NKH patients was performed. Mutant cDNA constructs were expressed in COS7 cells followed by enzymatic assays and Western blot analysis of the GCS P‐protein to assess the residual activity and mutant protein stability. Structural analysis, based on molecular modeling of the 3D structure of GCS P‐protein, was also performed. We identify hypomorphic variants that produce attenuated phenotypes with improved prognosis of the disease. Structural analysis allows us to interpret the effects of mutations on protein stability and catalytic activity, providing molecular evidence for clinical outcome and disease severity. Moreover, we identify an important number of mutants whose loss‐of‐functionality is associated with instability and, thus, are potential targets for rescue using folding therapeutic approaches.     

胃肠内补液在老年非酮症糖尿病高渗性昏迷治疗中的应用

目的 探讨胃肠内补液对老年非酮症糖尿病高渗性昏迷（NKHDC）的疗效。方法 15例NKHDC老年患者，8例采用胃肠内补液联合静脉补液的方法治疗（胃肠内补液组），7例采用单纯性静脉补液法治疗（常规治疗组），观察血生化及血渗透压等指标。结果 胃肠内补液组治疗24h后的血糖、钾、钠、氯和血浆渗透压较治疗前明显下降（P＜0.05），48h后恢复正常水平。与常规治疗组相比，胃肠内补液组的电解质和血浆渗透压较快恢复正常，患者清醒早，静脉补液量少，无一例发生脑水肿、肺水肿、溶血和低血钾等并发症。结论 对老年NKHDC患者采用胃肠内补液法简单易行、安全高效。     

非酮症高血糖性偏侧舞蹈病-偏侧投掷症的临床和影像学特征分析

目的 分析非酮症高血糖性偏侧舞蹈病-偏侧投掷症(HC-HB)患者的临床特征.方法 回顾性分析第二军医大学长海医院收治的5例非酮症高血糖诱发的HC-HB患者的临床表现、实验室检查和影像学资料.患者年龄65～83(76.6±7.2)岁,其中女性4例、男性1例.结果 5例患者均为急性起病,4例表现为单侧肢体粗大的舞蹈样或投掷样不自主运动,1例表现为全身性舞蹈症.病程中最高血糖18.6～44.6 (26.6±10.5)mmol/L,尿酮体阴性.脑MRI检查显示4例对侧基底节T1加权像呈高信号、1例双侧基底节T1加权像呈高信号,无水肿或占位效应,T2加权像多为等信号.3例行脑脊液检查,蛋白水平均增高,细胞数正常;其中2例IgG指数或IgG鞘内合成率增高,经积极控制血糖和服用氟哌啶醇等药物治疗后症状基本缓解.结论 非酮症高血糖性HC-HB表现为非酮症高血糖、偏侧舞蹈症-偏侧投掷症,MRI显示对侧基底节T1加权像高信号,偶累及双侧;早期诊治预后良好.     

Hyperglycemic hyperosmolar syndrome at the onset of type 2 diabetes mellitus in an adolescent male

Hyperglycemic hyperosmolar state (HHS) is rare in the paediatric population. The diagnosis and management of HHS presents a challenge in paediatric patients who may present with a mixed picture of HHS and diabetic ketoacidosis (DKA).A 15-year-old obese African American male was brought to the emergency department following a two-day history of feeling unwell. The patient was obtunded, hypotensive and tachypneic. Initial investigations revealed the following: pH 6.97 (normal 7.35 to 7.41), HCO₃⁻ 5 mEq/L (normal 20 mEq/L to 25 mEq/L), glucose 90.9 mmol/L (normal 3.4 mmol/L to 6.3 mmol/L), serum osmolality 454 mOsm/kg (normal 275 mOsm/kg to 295 mOsm/kg), Na⁺ 141 mEq/L (normal 135 mEq/L to 145 mEq/L), corrected Na⁺ 165 mEq/L, K⁺ 8.4 mEq/L (normal 3.5 mEq/L to 5.0 mEq/L), urinalysis revealed 1+ ketones and 4+ glucose. The patient’s clinical course was complicated by severe hyperkalemia, acute renal failure, refractory status epilepticus, rhabdomyolysis, pancreatitis and hypertension.The present case emphasizes the complexity of managing patients with a mixed DKA/HHS presentation and associated morbidities. It is very important to disseminate and implement screening guidelines for type 2 diabetes mellitus, so as to prevent this potentially devastating complication.     

神经外科高渗高血糖非酮症昏迷(附6例报告)

目的:探讨高渗高血糖非酮症昏迷(HHNC)病人的诊断和治疗。方法:报告6例病人的临床表现、诊断和治疗。结果:6例病人均痊愈出院。结论:神经外科病人并发HHNC主要是丘脑下部损害和较长时间大量脱水剂使用引起。根据血糖、血清钠增高情况分为高糖型、高钠型、高糖高钠型和普通型4种。提出在中心静脉压(CVP)监测下按上述分型确定合理的治疗计划,取得较好的疗效。     

Chorea-ballism associated with nonketotic hyperglycaemia or diabetic ketoacidosis: characteristics of 25 patients in Korea

Chorea-ballism is a rare form of movement disorder complicated by severe hyperglycaemia and in association with a contralateral basal ganglia lesion. We analysed the clinical characteristics of 25 Korean patients with chorea-ballism associated with nonketotic hyperglycaemia or diabetic ketoacidosis. Possible mechanisms of disease are also discussed.