Normal Cerebrospinal Fluid Glucose Research Articles

Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway

Aims/hypothesisDuring hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations.MethodsThis observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels.ResultsGroups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels.Conclusions/interpretationHyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities.Graphical abstract

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

Objective: To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT). Methods: Clinical data of 19 children with GLUT1 DS admitted to Children's Hospital of Fudan University, Tianjin Children's Hospital, Shenzhen Children's Hospital, Children's Hospital of Nanjing Medical University and Jiangxi Provincial Children's Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed. Results: Among the 19 cases, 13 were males and 6 females. The age of onset was 11.0 (1.5-45.0) months,the age of diagnosis was 54.0 (2.8-132.0) months. Epilepsy was the first onset symptom of 13 cases. Different forms of tonic-clonic seizures were the most common types of epilepsy (7 cases with generalized tonic-clonic seizures, 5 cases with focal tonic or clonic seizures, 4 cases with generalized tonic seizures). Antiepileptic drugs were effective in 4 cases. Paroxysmal motor dysfunction was present in 12 cases and ataxia was the most common one. All patients had different degrees of psychomotor retardation. Among 17 patients received cerebrospinal fluid examination, cerebrospinal fluid (CSF) glucose level was lower than 2.2 mmol/L and CSF glucose/glycemic index was<0.45 in 16 cases, only 1 case presented normal CSF glucose level (2.3 mmol/L) and normal CSF glucose/glycemic index(0.47). SLC2A1 gene mutations were found in 16 patients, missense, frameshift and nonsense mutations were the common types with 5 cases, 5 cases and 3 cases respectively. All 19 patients were treated with ketogenic diet, which was effective in 18 cases in seizure control, 11 cases in dyskinesia improvement and 18 cases in cognitive function improvement. No serious side effects were reported in any stage of KDT. Conclusions: The diagnosis of GLUT1 DS is often late. It is necessary to improve the early recognition of the disease and perform CSF glucose detection and genetic testing as early as possible. The KDT is an effective and safe treatment for GLUT1 DS, but a small number of patients have not response to diet therapy.

Lactate dehydrogenase as a prognostic marker in neoplastic meningitis

This study aimed to establish the prognostic utility of lactate dehydrogenase (LDH) levels in the cerebrospinal fluid (CSF) of patients with neoplastic meningitis (NM). Patients with a confirmed diagnosis of NM at a cancer referral center were included. Data on demographic and oncological background, clinical symptoms, diagnostic tests, treatment, and survival were analyzed. In total, 119 patients were included, 74% of whom were females. The mean age was 44.2 years at the time of cancer diagnosis and 46.6 years at the time between NM diagnosis. Primary cancers were mostly breast cancer, lung cancer, or hematologic malignancies. The mean Karnofsky performance score (KPS) was 65. Frequent clinical symptoms were visual complaints, headache, cranial neuropathy, focal weakness, and decreased awareness. Diagnosis was made based on clinical symptoms, cytological CSF analysis results, and/or magnetic resonance imaging findings. The median overall survival (OS) was 4 months (95% CI 2.48–5.52). Prognostic variables associated with a better OS were hematopoietic malignancies, KPS ≥ 70, absence of meningeal signs, receiving any form of treatment, normal CSF glucose levels, and normal CSF LDH levels. After bivariate analysis, high LDH in the CSF remained statistically significant as a poor prognostic indicator.The LDH level is a useful parameter to assess the prognosis of patients with NM. Other factors associated with the prognosis of these patients were tumor type, CSF glucose levels, performance status, and receiving any form of treatment.

Clinical and laboratory features of HTLV-I asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis from the Brazilian Amazon.

ABSTRACTClinical and laboratory parameters including blood and cerebrospinal fluid (CSF) neopterin were investigated in human-T-lymphotropic-virus-type-I associated-myelopathy/tropical-spastic-paraparesis-HAM/TSP and in HTLV-I carriers. HAM/TSP (n = 11, 2 males/9 females, median age = 48 years), recently diagnosed HTLV-I carriers (n = 21, 15 females/6 males, median age = 44 years), healthy individuals (n = 20, 10 males/10 females, median age = 34.6 years) from the Brazilian Amazon (Manaus, Amazonas State) were investigated. Neopterin was measured (IBL ELISA Neopterin, Germany) in serum samples of all the participants, in CSF of 9 HAM/TSP patients as well as in 6 carriers. In HAM/TSP patients, CSF cell counts, protein and glucose were measured, the Osame’s motor-disability-score/OMDS was determined, and brain/spinal cord magnetic-resonance-imaging (MRI) was performed. HAM/TSP patients had normal CSF glucose, leukocyte counts; and normal protein levels predominated. Brain-MRI showed white-matter lesions in 7 out of 11 HAM/TSP patients. OMDS varied from 2-8: 9 were able to walk, 2 were wheel-chair-users. The median serum neopterin concentration in HAM/TSP patients was 6.6 nmol/ L; min. 2.8- max. 12.5 nmol/ L); was lower in carriers (4.3 nmol/L; min. 2.7- max. 7.2 nmol/ L) as well as in healthy participants (4.7 nmol/ L; min. 2.7- max. 8.0 nmol/ L) (p < 0.05). CSF neopterin concentrations in HAM/TSP patients were higher than in serum samples, and higher compared to carriers (p < 0.05). Carriers had similar serum-CSF neopterin concentrations compared to healthy participants. Variable clinical and laboratory profiles were seen in HAM/TSP patients, however our results support the neopterin measurement as a potential biomarker of disease activity.

Scrub Typhus: A Clinico-Laboratory Differentiation of Children with and without Meningitis.

Neurological involvement in the form of meningitis or meningoencephalitis, although well documented in scrub typhus, has not been extensively studied in the pediatric population. We report the clinical and laboratory profile of 96 children with scrub typhus and compared those with and without meningitis. Twenty seven (28%) children had clinical and laboratory evidence of meningitis. The most frequent presenting features were fever (100%), meningeal signs (66.6%), nausea and vomiting (56.3%), seizures (55.5%) and altered sensorium (51.8%). The children with meningitis presented early and had significantly lower respiratory and renal impairments when compared with the non-meningitis group. Cerebrospinal fluid (CSF) analysis revealed elevated total leukocyte count (86.73 ± 94.50 cells/mm(3)), mononuclear pleocytosis (lymphocyte percentage of 76.85 ± 15.86), elevated proteins (108.33 ± 52.63 mg%) and normal CSF glucose (64.18 ± 15.92 mg%). We conclude that meningitis is a common and early complication of childhood scrub typhus. The CSF reveals a lymphocytic pleocytosis, raised proteins and a normal glucose level. These children respond promptly to appropriate antibiotics as do children without meningitis.

Cerebrospinal Fluid Analysis in the Workup of GLUT1 Deficiency Syndrome

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.

Facial herpes zoster complicated by varicella zoster virus (VZV) encephalitis: The diagnostic significance of atypical lymphocytes in cerebrospinal fluid (CSF)

Background In general, viral infections of the central nervous system (CNS) manifest as encephalitis and, less commonly, as meningoencephalitis or aseptic meningitis. Varicella zoster virus (VZV) is an uncommon cause of encephalitis. Methods Herpes zoster (shingles) is a cutaneous reactivation of previous chickenpox infection due to VZV. Herpes zoster may be dermatomal (ie, <3 dermatomes) or disseminated (ie, >3 dermatomes). Decreased cell-mediated immunity from stress, steroids, or immunosuppressive drugs often precede dermatomal/disseminated herpes zoster. With herpes zoster, the closer the dermatomal involvement is to the CNS (ie, head/neck shingles), the more likely a patient will have symptomatic CNS involvement (eg, encephalitis). Except for the association of the herpes zoster rash and the simultaneous/subsequent encephalitis, there are few clinical features that distinguish VZV encephalitis from that due to other viruses. The cerebrospinal fluid (CSF) profile of VZV encephalitis is usually clinically indistinguishable from that due to of other causes of viral encephalitis. In VZV meningoencephalitis or encephalitis, the CSF typically shows a modest lymphocytic pleocytosis with normal CSF glucose levels, variably elevated CSF protein levels, and normal CSF lactic acid levels. Atypical lymphocytes are rare in the CSF with VZV encephalitis. Results We present the case of a 75-year-old woman who developed VZV encephalitis after having herpes zoster on her forehead. Except for facial herpes zoster, there were no clinically distinguishing features to determine the cause of her encephalitis. Her CSF had 800 white blood cells/high power field with 26% lymphocytes (17% atypical lymphocytes). The patient’s CSF glucose and CSF lactate dehydrogenase levels were normal, and her CSF protein was elevated. The CSF lactic acid was minimally elevated secondary to red blood cells in the CSF. Electroencephalogram showed general background slowing bilaterally, typical of viral encephalitis. The absence of unilateral focal frontotemporal/parietal lobe focus on electroencephalogram argued against the diagnosis of herpes simplex encephalitis. CSF atypical lymphocytes provided the key clue to the etiology of her encephalitis. CSF atypical lymphocytes are not uncommon in Epstein–Barr virus or cytomegalovirus encephalitis. Less commonly, atypical lymphocytes may be present in the CSF with enteroviruses, West Nile encephalitis, and Japanese encephalitis. VZV is a rare cause of atypical lymphocytes in the CSF but was the clue to the diagnosis before CSF polymerase chain reaction results for VZV were available. Her CSF polymerase chain reaction was negative for Mycobacterium tuberculosis, herpes simplex virus, human herpesvirus-6, cytomegalovirus, enteroviruses, and West Nile virus, but was positive for VZV. She made an uneventful recovery with acyclovir. Conclusion CSF atypical lymphocytes, if present, are an important diagnostic clue in some causes of viral encephalitis. The most common cause of nonseasonal viral encephalitis is herpes simplex virus, which is not associated with CSF atypical lymphocytes. Patients with Epstein–Barr virus, cytomegalovirus, West Nile encephalitis, and enteroviruses usually have extra-CNS signs and symptoms which should suggest the cause of the patient’s encephalitis. CSF atypical lymphocytes limit the differential diagnostic possibilities in patients with viral encephalitis and may be the key clue to the diagnosis, as in the case presented.

Chemical meningitis following cerebellopontine angle tumor surgery

Postoperative chemical meningitis mimics bacterial meningitis, complicating the diagnosis until results of cerebrospinal fluid (CSF) cultures can be obtained. We analyzed clinical and laboratory data from a series of 1146 patients to identify findings that could exclude bacterial meningitis. We reviewed the charts of patients who developed meningitis after cerebellopontine angle surgery. Lumbar puncture data from asymptomatic postoperative patients were our control. Clinical symptoms, CSF profiles, and serum white blood cell (WBC) counts were compared between patients with chemical meningitis, bacterial meningitis, and asymptomatic patients. The incidence of meningitis in our series of 1146 patients was 4.54 percent; 0.87 percent was culture-proven bacterial meningitis. The patients with bacterial meningitis had significantly higher CSF and serum WBC counts, and lower CSF glucose. The major difference between asymptomatic patients and those with chemical meningitis was the significantly lower ratio of CSF WBCs to red blood cells (RBCs) in asymptomatic patients. Patients with mild CSF leukocytosis and normal CSF glucose without high serum WBC counts or focal neurological deficits may be treated for chemical meningitis.

Acute Bacterial Meningitis in Adults: A 12-Year Review

One hundred three episodes of acute bacterial meningitis in adults hospitalized in Edmonton's 2 largest hospitals from 1985 to 1996 were reviewed. Cases complicating neurosurgery were excluded. Most cases were community-acquired (87%). Twenty-three cases remained culture-negative, and there was no statistical relation between culture negativity and antibiotic pretreatment. Streptococcus pneumoniae was the predominant pathogen (52.5%), but Listeria monocytogenes was the second most common isolate, accounting for 12.5% of culture-positive cases. Compared to non-listerial meningitis, those with listeriosis were more likely to have negative cerebrospinal fluid (CSF) Gram stains (p = 0.07), CSF leukocyte counts < 1,000 cells/mm3 (p < 0.003), and normal CSF glucose (p = 0.006). Bacterial antigen detection was found to be of low sensitivity: 33% in all patients, but only 9% in cases with negative CSF Gram stains. The overall mortality was 18%, with 15 deaths directly attributable to acute meningitis; the case-fatality rates for S. pneumoniae and L. monocytogenes were 24% and 40%, respectively. Mortality was significantly higher among those with seizures (34% versus 7%, respectively; p < 0.001; OR = 17.6). Despite the urgency of acute bacterial meningitis, there were considerable delays in the institution of empiric antibiotics; mortality rates were slightly higher in those who experienced such a delay (16% versus 7% respectively; p = 0.18).