Clinical characteristics and ketogenic diet therapy of glucose transporter type 1 deficiency syndrome in children: a multicenter clinical study

ObjectiveTo identify the relationship between preoperative cerebrospinal fluid (CSF) leukocyte, chloride, glucose, aspartate aminotransferase, lactate dehydrogenase, adenosine deaminase, lactic acid and protein levels and ventriculoperitoneal shunt infection.MethodsRecords of 671 consecutive adult patients who underwent ventriculoperitoneal shunt surgery for the treatment of hydrocephalus at Zhujiang Hospital affiliated with Southern Medical University from January 2011 to March 2022 were reviewed. The patients were divided into infection and non-infection groups based on the presence of postoperative infection. For all patients, we analyzed age; sex; primary disease; preoperative CSF leukocyte, chloride, glucose, aspartate aminotransferase, lactate dehydrogenase, adenosine deaminase, lactic acid and protein levels; postoperative temperature; and postoperative infection.ResultsA total of 397 patients were included, 28 (7.05%) of whom had an infection within 6 months of the operation and the remaining had no infection. There was no significant difference in age, sex, primary disease, leukocyte, chloride ion, aspartate aminotransferase, lactate dehydrogenase, adenosine deaminase and protein levels in CSF between infection group and non-infection group (p > 0.05). The postoperative infection rate of patients with CSF glucose < 2.8 mmol/L (x2 = 11.650, p = 0.001) and CSF lactic acid >2.8 mmol/L (x2 = 12.455, p < 0.001) was higher than that of patients with CSF glucose level ≥2.8 mmol/L and CSF lactic acid level in the range of (1–2.8) mmol/L, respectively, with statistical difference. Compared with the non-infection group, the level of CSF glucose (t = 4.113, p < 0.001) was significantly lower, and the level of CSF lactic acid (t = 6.651, p < 0.001) was significantly higher in the infection group. Multivariate logistic regression analysis showed that preoperative cerebrospinal fluid glucose < 2.8 mmol/L (OR = 3.911, 95% CI: 1.653~9.253, p = 0.002) and cerebrospinal fluid lactate >2.8 mmol/L (OR = 4.712, 95% CI: 1.892~11.734, p = 0.001) are risk factors for infection after ventriculoperitoneal shunt. ROC analysis revealed that the area under the curve (AUC) for CSF glucose and lactic acid level were 0.602 (95% CI: 0.492–0.713) and 0.818 (95% CI: 0.738–0.898), respectively. The infection group had higher rates of fever and body temperature on postoperative day 3–7 (p < 0.05).ConclusionsFor adult hydrocephalus patients without clinical manifestations of intracranial infection but only with simple abnormality of cerebrospinal fluid, when the content of glucose in cerebrospinal fluid is < 2.8 mmol/L, and the content of lactic acid is >2.8 mmol/L, it is recommended to perform ventriculoperitoneal shunt after further improvement of cerebrospinal fluid indicators, otherwise, hasty operation will increase the postoperative infection rate. The postoperative fever rate of ventriculoperitoneal shunt surgery is high and the body temperature drops rapidly. If there is still fever after day 3 after surgery, whether there is intracranial infection should be considered.

BackgroundMutations in the SLC2A1 gene cause glucose transporter type 1 deficiency syndrome (Glut1DS). This study aimed to investigate the clinical and molecular genetics characteristics of Chinese patients with Glut1DS.MethodsThe clinical data of patients with Glut1DS were analyzed retrospectively. SLC2A1 mutation analysis was performed using Sanger sequencing or next-generation sequencing (NGS). Multiplex ligation-dependent probe amplification (MLPA) was conducted in patients with negative results.ResultsA total of 90 patients were diagnosed with Glut1DS, including 63 (70%) classic type and 27 (30%) non-classic type. Seizures occurred in 69 patients (77%), movement disorders were observed in 58 (68%), and episodic eye–head movements were noted in 17 (19%). Cerebrospinal fluid (CSF) glucose levels were available for 73 patients (81%), ranging from 1.0 to 2.6 mmol/L (median 1.9 mmol/L), with 90% (66/73) of patients showing levels below 2.2 mmol/L. Additionally, CSF-to-blood glucose ratios measured in 71 patients (79%) ranged from 0.20 to 0.63 (median 0.37), with 87% (62/71) of patients having ratios below 0.45. Genetic analysis identified 69 variants of the SLC2A1 gene including 39 previously reported and 30 unreported variants. The two most common variants were c.997C > T (p.Arg333Trp) and c.988C > T (p.Arg330*). Following ketogenic diet therapy, seizures were controlled in 47 of 57 patients (82%), movement disorders resolved in 18 of 47 patients (38%), and improved in 26 of 47 patients (55%).ConclusionsThe clinical manifestations of Glut1DS primarily include seizures, movement disorders, and developmental delay. Most affected children had CSF glucose levels below 2.2 mmol/L, with CSF-to-blood glucose ratios under 0.45. Two of the most common SLC2A1 variants were identified in our cohort. Ketogenic diet therapy was effective in controlling seizures, improving movement disorders, and was well tolerated.Graphical abstract

BACKGROUND The prognostic significance of cerebrospinal fluid (CSF) glucose and protein levels among patients with leptomeningeal disease (LMD) is unknown. This single-institution retrospective study aims to investigate the association of CSF glucose and protein levels with overall survival (OS) among metastatic breast cancer (MBC) patients with LMD. METHODOLOGY MBC patients diagnosed with LMD between Jan 1st, 2010, and Jan 1st, 2023, were included. Patients without known CSF glucose or protein levels at the time of LMD diagnosis were excluded. OS was evaluated using the Kaplan-Meier method and compared using the log-rank test. For multivariate analysis, a step-wise model selection was performed after the inclusion of sub-type of interest, and variables meeting entry (p&amp;lt;0.10) and staying criteria (p&amp;lt;0.05). Median glucose and protein levels were compared using the Wilcoxon rank-sum test. RESULTS 28 patients met inclusion criteria. Positive CSF cytology samples (CSF+) had significantly lower glucose levels vs CSF cytology negative samples (CSF-) [median (IQR) 40 (18-58) vs. 64 (53-92) mg/dl, p=0.006]. Prior study from this data set had shown that the CSF- group was associated with better OS vs the CSF+ group. Hence, four groups were created based on the CSF (+/-) and glucose (Low vs High/Normal). Median OS (months), 95% confidence Interval (CI) for CSF+/Glucose_Low, CSF+/Glucose_Normal/High, CSF-/Glucose_Low and CSF-/Glucose_High/Normal were 3.4(0.23-NE), 16.5(2.9-NE), 3.1(1.28-NE), 51.5(4.9-NE), p=0.03. Glucose_Low overall was associated with shorter OS in multivariate analysis [hazard ratio (HR), 95%CI 4.64 (1.71, 13.2)]. Median CSF protein was not different between CSF+/– groups. Median OS (months), 95%CI for Protein_High and Protein_Low /Normal groups were 28.5 (2.9, 51.5) vs. 6.5 (0.85, 8.0), p=0.36. In multivariate analysis, CSF protein level was not associated with OS. CONCLUSION The association between low CSF glucose level and worse survival among patients with MBC LMD was observed.

The classical GLUT-1 deficiency syndrome (GLUT-1 DS, De Vivo disease) was described over 2 decades ago as a metabolic encephalopathy characterized by developmental delay, secondary microcephaly paroxysmal neurological symptoms (epilepsy) and movement disorders. The biochemical parameters of this disease, used in diagnosis, are low levels of glucose in the cerebrospinal fluid, normal level of glucose in the blood and consequent low ratio of cerebrospinal fluid vs. blood glucose levels (<40-45%). So far, more than 200 cases of the classical GLUT-1 DS have been described in the literature. Genetic research demonstrated that this disease is caused by mutations in SLC2A1 gene coding for GLUT-1, a transporter of glucose across the blood brain barrier. Over the last few years the clinical spectrum of GLUT-1 deficiencywas expanded to include other rare diseases such as paroxysmal exertional dyskinesia and early-onset absence epilepsy, but also some more common diseases such as idiopathic generalised epilepsy (1-2%). GLUT-1 deficiency is an important pathophysiological basis of these diseases as early diagnosis (aided by DNA mutation testing) and treatment (ketogenic diet) could lead to improved disease outcomes.

Disclosure: M.U. Raza: None. K.H. Chhabra: None. Diabetes doubles the risk of cognitive decline and Alzheimer’s disease (AD). Whether this is mediated by an increase in blood glucose or cerebrospinal fluid (CSF) glucose levels, or by other metabolic factors such as changes in plasma insulin levels is unclear. To clarify the contribution of high blood glucose versus high CSF glucose levels toward increasing the risk of cognitive decline in mice, we have developed a method through which glucose concentration can be increased selectively in CSF. We implanted 8 weeks old male mice (n= 7-8 / group) with cannula attached to osmotic minipumps to directly infuse either artificial CSF (aCSF/sham group) or 50% glucose solution (treatment group) into the right lateral ventricle for eight weeks at a flow rate of 0.25ul/hr. CSF glucose was measured two and eight weeks after initiating the infusion in these mice. We also performed oral glucose tolerance tests (OGTT) in these mice to assess their peripheral glucose metabolism and uptake. Moreover, these mice were tested through the Morris water maze (MWM) to investigate the effects of high CSF glucose on learning and memory. Mice in the treatment group showed a significant increase (p&amp;lt;0.0001, unpaired t-test) in CSF glucose levels (mean=328±30.15 and 358±15.03mg/dl post-2, and 8 weeks of implantation, respectively) as compared to the sham group (mean=56±2.63 and 73±8.61mg/dl post-2, and 8 weeks of implantation, respectively). There was no significant change in body weight and food intake during the study. In OGTT, the treatment group showed significantly lower blood glucose levels (p&amp;lt;0.05, two-way ANOVA repeated measures design, Bonferroni’s multiple comparisons) at 15 minutes post-gavage (mean=336.3±24.41mg/dl) as compared to the sham group (mean=478.6±30.06 mg/dl). Mice in the treatment group made significantly fewer entries to the correct quadrant (i.e. the quadrant where the hidden platform was placed during training) (mean=12.43±1.55 entries, p&amp;lt;0.05, unpaired t-test) in the MWM test, as compared to the sham group (mean=18.4±1.84 entries). Additionally, mice in the treatment group were significantly less likely to revisit the correct quadrant (mean=10.7±1.50 revisits, p&amp;lt;0.05, unpaired t-test) than the mice in the sham group (mean=16.8±1.78 revisits). Importantly, there was no significant difference in the overall locomotor activity between the groups as measured through the open field test. To summarize, we have developed a method to test the effects of high CSF glucose levels on learning and memory in mice. Our results show that high CSF glucose levels for up to two months cause memory deficits in mice. This mouse model of chronically high CSF glucose presents a useful tool to investigate how diabetes-associated dysregulation of glucose homeostasis in the brain may contribute to AD and other neurodegenerative disorders. Presentation: Saturday, June 17, 2023

Objective To investigate the clinical features of glucose transporter 1 deficiency syndrome(GLUT1-DS) and summarize the characteristics of GLUT1-DS through reviewing related references. Methods The clinical data including manifestation, cerebrospinal fluid(CSF) glucose, electroencephalogram, MRI and gene mutation of a patient with GLUT1-DS was collected and the related literatures were reviewed. Results The patient was a 6 years old boy.The patient, whose seizures occurred at the age of 9 month-old and prolonged to 6 year-old, attacked before breakfast.Physical examination showed microcephaly with head circumference 47.5 cm.Laboratory tests showed that CSF glucose decreased(1.87 mmol/L) and CSF-serum ratio was 0.36.And meantime the MRI was normal and electroencephalogram showed general spike and slow wave complex paroxysm.Mutation of SLC2A1 gene, c.350_385del, was found in the patient.There were 219 cases with GLUT1-DS had been reported and the age of onset was 15.69 months.In 219 patients, 159 cases(72%)suffered seizures, 105 cases(47%) had motor abnormalities, 61 cases(27%) suffered intellectual disability.The CSF glucose values were(1.92±0.31) mmol/L, CSF-serum ratio was 0.36±0.07.SLC2A1 gene mutations were detected in 183 patients(96%)in which missense mutation was the most mutation. Conclusion A wide range of phenotypes of GLUT1-DS include seizures, motor abnormalities, mental retardation.The diagnosis is confirmed when CSF glucose and CSF-serum ratio are continuously decreased which in the absence of meningitis.The SLC2A1 gene should be detected in suspicion of GLUTI-DS patients.Early diagnosis and treatment may improve the prognosis of those GLUTI-DS patients. Key words: Glucose transporter 1 deficiency syndrome; SLC2A1 gene; Seizures; Motor abnormalities

Objective To study the significance of the cerebrospinal fluid (CSF)lactate level in diagnosing neonatal bacterial meningitis(BM). Methods The CSF samples were collected from neonates admitted to Neonatal Ward of Children's Hospital of Fudan University between January 2014 and March 2015.CSF lactate and glucose concentrations were measured with blood-gas analyzer.CSF and serum glucose levels were measured with glucometer.The enrolled neonates were divided into 2 groups based on CSF culture, CSF white blood cells(WBCs)and clinical presentation: observation group (neonates with BM)and control group (neonates without BM). Statistical analysis of data was performed with Stata 12.0. Results A total of 93 infants (16 assigned to observation group and 77 assigned to control group)met the inclusion criteria.Neonates in observation group had higher median CSF lactate level (4.2 mmol/L)and CSF lactate/glucose ratio (L/Gcsf)(2.32 mmol/L), than those in control group (1.3 mmol/L, 0.52), and there were significant differences (Z=-6.19, -5.92, all P<0.05). CSF glucose levels were lower in observation group (me-dian, 1.25 mmol/L)than those in control group (median, 2.5 mmol/L), and the difference was significant(Z=4.97, P<0.05); CSF/serum glucose ratio (CSF/Sglu)were lower in observation group (median, 0.44 vs 0.81 in control group), and the difference was significant(Z=4.43, P<0.05). The optimal CSF lactate cutoff point of 2.2 mmol/L had a positive predictive value (PPV)of 72.7% and negative predictive value (NPV)of 100.0% for bacterial meningitis.The optimal L/Gcsf cutoff point of 1.24 had a PPV of 94.1% and NPV of 100.0%.The optimal CSF glucose cutoff point of 2.0 mmol/L had a PPV of 65.0% and NPV of 95.9%.The optimal CSF/Sglu cutoff point of 0.6 had a PPV of 60.0% and a NPV of 96.9%. Conclusion CSF lactate may be an excellent biomarker for early diagnosis of neonatal BM. Key words: Bacterial meningitis; Cerebrospinal fluid lactate; Cerebrospinal fluid/serum glucose ratio

Effects of age and glucose levels on lactate levels in cerebrospinal fluid examination of neurodegenerative diseases

This article describes 4 clinical cases of glucose transporter type 1 deficiency syndrome (GLUT1, De Vivo disease) in children admitted to the neuropsychiatric department of Scientific and Practical Center of children medical care. The drug-resistant epilepsy, movement disorders, psychomotor and intellectual disabilities, decrease of glucose levels in the cerebrospinal fluid (CSF) were diagnosed in children. The different types of mutations in the SLC2A1 gene, responded for the development of GLUT1 deficiency syndrome were detected by targeted sequencing in all patients. De Vivo disease is characterized by the infantile-onset encephalopathy, symptomatic drug-resistant epilepsy, microcephaly, delayed psychomotor development with spasticity, ataxia, dysarthria and alternating hemiplegia and decrease the level of glucose in the CSF. Currently, the ketogenic diet is highly effective method of pathogenesis therapy, which can reduce the clinical manifestations: controlling the seizures, improving the movement disorder and speech.

BackgroundGlucose transporter type 1 deficiency syndrome (Glut1DS) is a treatable neurogenetic metabolic disorder caused by pathogenic variants in the SLC2A1 gene. The relationship between genotype and phenotype has not been extensively studied in large cohorts within China. This study aimed to analyze the clinical and genetic characteristics and the genotype-phenotype correlation in Chinese children with Glut1DS.MethodsClinical data of Glut1DS patients, including age of onset, clinical manifestations, cerebrospinal fluid (CSF) analysis, and SLC2A1 gene variants, were collected and analyzed.ResultsA total of 93 patients with Glut1DS were included, among whom 65 (70%) were classical phenotypes (including 55 early-onset classical cases and 10 late-onset classical cases), and 28 (30%) were non-classical phenotypes. Significant differences were observed among early-onset classical, late-onset classical, and non-classical groups in terms of age of onset (p < 0.001), episodic psychiatric/behavioral abnormalities (p = 0.012), CSF glucose levels (p < 0.001), and the ratio of CSF glucose to blood glucose (p = 0.003). Genetic variant analysis identified 40 previously reported and 32 novel SLC2A1 variants. These variants were classified into three types: Type A (missense and in-frame indel variants, n = 52), Type B (frameshift, nonsense, splicing site, and initiation codon variants, n = 32), and Type C (single/multiple exon or whole-gene deletions, n = 9). No statistically significant difference was found in the distribution of these three genotypes across early-onset classical, late-onset classical, and non-classical phenotype. However, there were differences in age of onset among the three genetic variant groups (p = 0.009), with Type A variants showing a later age of onset compared to Type B variants (p = 0.014). No significant differences were observed among the three variant groups regarding CSF glucose levels, the ratio of CSF glucose to blood glucose, or CSF lactate levels. Furthermore, patients with identical variants exhibited phenotypic variability, for example, among eight patients (9%) harboring the c.997C>T (p.Arg333Trp) variant, six had early-onset classical phenotypes, while two had non-classical phenotypes.ConclusionGlut1DS predominantly manifests as the classical phenotype, with the early-onset classical phenotype presenting at the youngest age and exhibiting the most severe clinical symptoms. Patients with this type also showed lower CSF glucose levels and a lower CSF glucose to blood glucose ratio compared to other types. Missense and in-frame indel variants were associated with a later age of onset compared to other types of genetic variants. No significant correlations were found between genotype and clinical classification or CSF glucose levels.

Developmental outcomes and prevalence of SLC2A1 variants in young infants with hypoglycorrhachia

This study aimed to explore the relationships between diabetes mellitus and Guillain-Barré syndrome (GBS) progression and short-term prognosis. This retrospective cohort analysis included 330 patients with GBS. The study was performed at the Department of Neurology, Kasturba Medical College, Manipal, from January 2016 to December 2023. Diabetes mellitus was present in 31.8% of the 330 GBS patients. The degree of disability was assessed according to the GBS Disability Scale (GDS). Compared with patients with normal glycosylated hemoglobin A1c (HbA1c) and cerebrospinal fluid (CSF) glucose levels, patients in the high HbA1c and high CSF glucose groups were characterized by severe disability (GDS ≥ 3) at admission (52.4 vs. 75.2, P = 0.001; 80 vs. 53.4, P = 0.001), at nadir (63.1 vs. 83.8, P = 0.02; 84.5 vs. 60.6, P = 0.03), and at discharge (52.4 vs. 31.1, P = 0.04; 57.8 vs. 27.8, P = 0.03). Older age, gastrointestinal tract infection, and axonal subtype were significantly associated with severe disability at admission, at nadir, and at discharge. Elevated blood levels of HbA1c were significantly correlated with worse disability at admission (OR = 0.64) and at nadir (OR = 0.74) but not at discharge. Elevated CSF glucose levels were significantly correlated with severe disability at admission (OR = 0.68), at nadir (OR = 0.62), and at discharge (OR = 0.72). The present study revealed that elevated glucose levels in the blood and CSF were correlated with disease severity at admission, nadir and discharge and might predict the short-term prognosis of GBS patients.

Pediatric Blood & CancerEarly View e30399 LETTER TO THE EDITOR Vacuolization of large myeloid lineage and absence of erythroblast and megakaryocyte: Clues to the diagnosis of hereditary transcobalamin II deficiency Xiaojuan Luo, Xiaojuan Luo Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, ChinaSearch for more papers by this authorZhenhu Lin, Zhenhu Lin Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, ChinaSearch for more papers by this authorMeizhu Luo, Meizhu Luo Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, ChinaSearch for more papers by this authorFuping Shen, Fuping Shen School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaSearch for more papers by this authorKe Cao, Corresponding Author Ke Cao [email protected] Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, China Correspondence Ke Cao, Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, China. Email: [email protected] Jinlin Liu, Department of Clinical Laboratory, South China Hospital, 1 Fuxin Rd, Shenzhen, 518111, Guangdong, China. Email: [email protected]Search for more papers by this authorJinlin Liu, Corresponding Author Jinlin Liu [email protected] orcid.org/0000-0003-0502-4813 Department of Clinical Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, China Correspondence Ke Cao, Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, China. Email: [email protected] Jinlin Liu, Department of Clinical Laboratory, South China Hospital, 1 Fuxin Rd, Shenzhen, 518111, Guangdong, China. Email: [email protected]Search for more papers by this author Xiaojuan Luo, Xiaojuan Luo Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, ChinaSearch for more papers by this authorZhenhu Lin, Zhenhu Lin Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, ChinaSearch for more papers by this authorMeizhu Luo, Meizhu Luo Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, ChinaSearch for more papers by this authorFuping Shen, Fuping Shen School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaSearch for more papers by this authorKe Cao, Corresponding Author Ke Cao [email protected] Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, China Correspondence Ke Cao, Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, China. Email: [email protected] Jinlin Liu, Department of Clinical Laboratory, South China Hospital, 1 Fuxin Rd, Shenzhen, 518111, Guangdong, China. Email: [email protected]Search for more papers by this authorJinlin Liu, Corresponding Author Jinlin Liu [email protected] orcid.org/0000-0003-0502-4813 Department of Clinical Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, China Correspondence Ke Cao, Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen, Guangdong, China. Email: [email protected] Jinlin Liu, Department of Clinical Laboratory, South China Hospital, 1 Fuxin Rd, Shenzhen, 518111, Guangdong, China. Email: [email protected]Search for more papers by this author First published: 09 May 2023 https://doi.org/10.1002/pbc.30399 Xiaojuan Luo, Zhenhu Lin, Meizhu Luo, and Fuping Shen contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issuee30399 RelatedInformation

Objective This study aimed to explore the correlation of elevated glucose levels in the blood and cerebrospinal fluid with the progression and short-term prognosis of Guillain-Barré syndrome (GBS). Methods The medical records of 982 patients who were diagnosed with GBS in 31 representative tertiary hospitals, located in 14 provinces in southern China, were collected and retrospectively reviewed. Patients were grouped according to the levels of fasting plasma glucose (FPG) and cerebrospinal fluid (CSF) glucose, as well as the concentration of blood hemoglobinAlc (HbA1c). The Hughes grade scale was used to quantify functional outcomes. Results Compared to patients with normal FPG and CSF glucose levels, those in the high FPG and high CSF glucose groups were characterized by a higher proportion of severe patients (HFGS ≥ 3) at admission (58.8 vs. 73.1, P = 0.000; 57.6 vs. 71.2, P = 0.000), at nadir (67.4 vs. 83.0, P = 0.000; 66.2 vs. 80.4, P = 0.000), and at discharge (29.8 vs. 46.3, P = 0.000; 26.4 vs. 45.0, P = 0.000). Patients in the high HbA1c group also had more severe disability at admission (74.6 vs. 56.1, P = 0.005) and at nadir (80.3 vs. 64.3, P = 0.012) compared to the normal HbA1c group. Moreover, elevated levels of FPG and CSF glucose were significantly correlated with more severe disability at admission, at nadir, and at discharge. Conclusions The present study showed that elevated glucose levels in the blood and cerebrospinal fluid were associated with the severity and short-term prognosis of GBS. Trial registration chicTR-RRc-17,014,152. Abbreviations GBS, Guillain-Barré syndrome; FPG, fasting plasma glucose; CSF, cerebrospinal fluid; HFGS, Hughes Functional Grading Scale; HbA1c, hemoglobin A1c. DM, diabetes mellitus; NCS, nerve conduction study; AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor sensory axonal neuropathy; MV, mechanical ventilation.

GLUT1 deficiency syndrome is a treatable neurometabolic disorder, characterized by a low concentration of glucose in cerebrospinal fluid (CSF) and a decreased CSF to blood glucose ratio. Reports of patients with apparently normal CSF glucose levels, however, have raised the question whether CSF analysis is a reliable screening tool for GLUT1 deficiency syndrome. To determine the value of CSF analysis in the workup of GLUT1 deficiency syndrome. PubMed was searched until July 2012 by using the terms glucose transporter 1 (GLUT-1) deficiency syndrome, glucose transporter defect, and SLC2A1-gene. Relevant references mentioned in the articles were also included. The CSF results of all patients with genetically proven GLUT1 deficiency syndrome described in literature were reevaluated. The levels of glucose in CSF, the CSF to blood glucose ratios, and the levels of lactate in CSF were reported for 147 (94%), 152 (97%), and 73 (46%) of 157 patients, respectively. The CSF glucose levels ranged from 16.2 to 50.5 mg/dL and were at or below the 10th percentile for all 147 patients. The CSF to blood glucose ratios ranged from 0.19 to 0.59 and were at or below the 10th percentile for 139 of 152 patients (91%), but they could be within the normal range as well. The CSF lactate levels ranged from 5.4 to 13.5 mg/dL and were at or below the 10th percentile for 59 of 73 patients (81%). A typical CSF profile for GLUT1 deficiency syndrome, which is defined as a CSF glucose level at or below the 10th percentile, a CSF to blood glucose ratio at or below the 25th percentile, and a CSF lactate level at or below the 10th percentile, was found in only 35 of 4099 CSF samples (0.9%) present in our CSF database of patients who received a diagnosis other than GLUT1 deficiency syndrome. We conclude that if age-specific reference values are applied, CSF glucose and lactate levels are adequate biomarkers in the diagnostic workup of GLUT1 deficiency syndrome. Future availability of whole-exome sequencing in clinical practice will make the existence of a reliable biomarker for GLUT1 deficiency syndrome even more important, in order to interpret genetic results and, even more importantly, not to miss SLC2A1-negative patients with GLUT1 deficiency syndrome.