Varicella-zoster virus meningitis with hypoglycorrhachia: A case report.

BACKGROUND: Varicella-zoster virus (VZV) is a common viral infection, but meningitis is a rare complication of VZV infection. The cerebrospinal fluid glucose of viral meningitis is usually within the normal range, which is different from bacteria, fungi, and cancerous meningitis. This paper reports a case of VZV meningitis with hypoglycorrhachia and the relevant literature was reviewed. CASE SUMMARY: We report a case of an immunocompetent 39-year-old male, presenting with severe headache and fevers, without meningeal signs or exanthem, found to have VZV meningitis by the metagenomic next-generation sequencing of cerebrospinal fluid. The cerebrospinal fluid analysis revealed hypoglycorrhachia (cerebrospinal fluid glucose of 2.16) and he was treated successfully with intravenous acyclovir. Our literature review identified only ten cases diagnosed with VZV meningitis with hypoglycorrhachia previously reported to date in the English literature whose cerebrospinal fluid glucose was from 1.6 to 2.7mmol/L, with a ratio of cerebrospinal fluid to serum glucose from 0.30 to 0.49. CONCLUSION: Although rare, the cerebrospinal fluid of patients with VZV meningitis may have hypoglycorrhachia, which broadens the understanding of the disease.

Persistent Intracranial Hypertension and Severe Hypoglycorrhachia in an Adult With Giant Congenital Melanocytic Naevi.

A 29-year-old female, with giant congenital melanocytic naevi (GCMN) presented with a-year history of symptoms and signs of intracranial hypertension. Investigations revealed raised cerebrospinal fluid (CSF) pressure and severe hypoglycorrhachia (low CSF glucose) without pleocytosis. Initial contrast-enhanced brain MRI was normal, but a repeat MRI after a year showed meningeal enhancement with mild communicating hydrocephalus. The raised intracranial pressure was treated with a lumbar-peritoneal shunt. Intraoperative CSF cytology revealed an abundance of squamous epithelia and degenerative cells, but no malignant cells. Her symptoms recovered with CSF diversion via shunt placement, but the hypoglycorrhachia remained. This case highlights the rare occurrence of a non-inflammatory cause of both intracranial hypertension and severe hypoglycorrhachia in a GCMN adult patient, with progressive radiological changes over time, consistent with a diagnosis of neurocutaneous melanosis.

The clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.

Glucose transporter 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder caused by haploinsufficiency of the GLUT1 glucose transporter (encoded by SLC2A1) leading to defective glucose transport across the blood-brain barrier. This work describes the genetic analysis of 56 patients with clinical or biochemical GLUT1DS hallmarks. 55.4% of these patients had a pathogenic variant of SLC2A1, and 23.2% had a variant in one of 13 different genes. No pathogenic variant was identified for the remaining patients. Expression analysis of SLC2A1 indicated a reduction in SLC2A1 mRNA in patients with pathogenic variants of this gene, as well as in one patient with a pathogenic variant in SLC9A6, and in three for whom no candidate variant was identified. Thus, the clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.

Abnormal gait and hypoglycorrhachia in a toddler with seizures.

Introduction: Glucose transporter type 1 (Glut1) deficiency syndrome is a treatable neurometabolic disorder characterized by seizures, developmental delay, and hypoglycorrhachia. Due to the rareness and non-specific clinical manifestations, it is usually mis- or underdiagnosed. Case presentation: We report the case of a toddler who presented with afebrile epileptic seizures and abnormal gait. Brain imaging and electroencephalogram were normal. Further investigation of the cerebrospinal fluid revealed hypoglycorrhachia that was the clue to the diagnosis of Glut1 deficiency syndrome and the initiation of treatment with ketogenic diet. Conclusion: Our case highlights the importance of lumbar puncture while investigating a child with epileptic seizures and abnormal gait or developmental delay, in order not to miss treatable neurometabolic conditions, such as Glut1 deficiency syndrome.

Alteraciones atípicas del líquido cefalorraquídeo en el Síndrome de Guillain-Barré: Reporte de casos / Atypical Alterations of cerebrospinal fluid in Guillain Barré Syndrome: Cases Reports

RESUMEN El síndrome de Guillain-Barré se caracteriza por presentar una disociación albúmino-citológica en la mayoría de pacientes. La presencia de pleocitosis o hipoglucorraquia puede alejar el diagnóstico, por lo que se recomienda descartar, principalmente, causas infecciosas. Se presentan tres casos cuyos estudios de líquido cefalorraquídeo mostraron pleocitosis linfocítica e hiperproteinorraquia persistente y uno de ellos, además, hipoglucorraquia; fue solamente en análisis posteriores que los tres pacientes presentaron la clásica disociación albuminocitológica. El estudio neurofisiológico en todos ellos demostró asimismo un compromiso axonal. Las alteraciones atípicas en el contexto de parálisis flácida aguda justificarían repetir el análisis de líquido cefalorraquídeo y descartar otras etiologías, pero sin posponer en modo alguno el tratamiento.

SUMMARY Guillain-Barré syndrome shows a cyto-albuminologic dissociation in most patients. Pleocytosis or hypoglycorrhachia may defer the diagnosis, a reason for which an infectious etiology must be ruled out. Three cases of Guillain-Barré are described, whose cerebrospinal fluid tests showed limphocytic pleocytosis and persistently elevated protein concentration, while one of the cases also showed hypoglycorrhachia, and the classic cyto-albuminologic dissociation was only demonstrated in subsequent analysis. The neurophysiologic evaluation revealed an axonal disruption in all the patients. The atypical alterations in the context of acute flaccid paralysis warrant a retesting of the cerebrospinal fluid in order to rule out other etiologies, but without postponing the start of treatment.

The Impact of Hyponatremia on the Severity of Childhood Tuberculous Meningitis.

Introduction: Hyponatremia and/or hypoglycorrhachia are commonly encountered biochemical derangements during the acute stage of childhood tuberculous meningitis (TBM). Few studies have explored the correlation between these derangements and the staging of TBM disease (severity), or explored their role as biomarkers for vascular ischemic events, hydrocephalus, or seizures. Methods: We aimed to identify the prevalence and the correlation between serum hyponatremia (mild, moderate and severe) and/or hypoglycorrhachia in relation to clinical TBM features such as stage of disease, seizures and stroke in children diagnosed with definite and probable TBM, between 1985 and 2015, at Tygerberg Hospital, Cape town, South Africa. Results: The prevalence of hyponatremia was 344 out of 481 (71.5%) patients; 169 (49.1%) had mild hyponatremia, 146 (42.4%) moderate hyponatremia and 29 (8.4%) severe hyponatremia. Children with severe hyponatremia had higher frequency of stroke [odds ratio (OR) 4.36, 95% confidence interval (CI) 1.24-15.35; p = 0.01], brainstem dysfunction (OR 7.37, 95% CI 2.92-18.61; p < 0.01), cranial nerve palsies (OR 2.48, 95% CI 1.04-5.91; p = 0.04) and non-communicating hydrocephalus (OR 2.66, 95% CI 1.09-6.44; p = 0.03). Children with moderate hyponatremia and mild hyponatremia compared to those without hyponatremia similarly were more likely to exhibit signs of brainstem dysfunction (OR 1.91, 95% CI 1.11-3.28; p = 0.02) and hydrocephalus (OR 3.18, 95% CI 1.25-8.09; p = 0.01), respectively. On multivariable analysis only brainstem dysfunction was significantly associated with severe hyponatremia [adjusted odds ratio (aOR) 4.46, 95% CI 1.62-12.30; p < 0.01]. Children with hypoglycorrhachia compared to normoglycorrhachia were more likely to have had longer symptom duration prior to admission (OR 1.87, 95% CI 1.09-3.20; p = 0.02), non-communicating hydrocephalus (OR 1.64, 95% CI 0.99-2.71; p = 0.05), higher cerebrospinal white cell counts (OR 3.00, 95% CI 1.47-6.12; p < 0.01) and higher CSF protein concentrations (OR 2.51, 95% CI 1.49-4.20; p < 0.01). On multivariable analysis raised CSF protein concentration >1 g/L was significantly associated with hypoglycorrhachia (aOR 2.52, 95% CI 1.44-4.40; p < 0.01). Death rates did not differ by sodium level category or presence of hypoglycorrachia, however an increasing trend of children that had demised was noted the more severe the sodium category. Conclusion: Hyponatremia and/or hypoglycorrhachia occur in more than two-thirds of children with TBM. Severe TBM disease complications such as brainstem dysfunction was associated with moderate hyponatremia, while severe hyponatremia was associated with brainstem dysfunction, stroke, cranial nerve palsies and non-communicating hydrocephalus. Cerebrospinal fluid (CSF) glucose depletion correlated with non-communicating hydrocephalus and increased CSF inflammation.

Diagnostic yield of capillary compared to venous glucose in the diagnosis of hypoglycorrhachia in children: A prospective, observational study.

INTRODUCTION: The ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population. METHODS: Prospective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia. RESULTS: 97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%. CONCLUSION: Glucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children.

Transient hypoglycorrhachia with paroxysmal abnormal eye movement in early infancy.

Paroxysmal abnormal eye movement in early infancy is one of the initial symptoms of glucose transporter 1 deficiency syndrome (GLUT1DS). We describe four early infants with transient hypoglycorrhachia presenting with abnormal eye movements. Their symptoms disappeared after the introduction of a ketogenic diet (KD), and their development was normal. Since no variants in SLC2A1 were detected, the CSF-to-blood glucose ratios (C/B) were re-examined, and within normal range. None of the four patients displayed recurrent symptoms after withdrawal from the KD. Because long-term KD has potential adverse effects and could affect the quality of life of patients and their families, re-examination of CSF glucose during late infancy should be considered in the case of absence of the SLC2A1 pathogenic variant.

Varicella-Zoster Meningitis With Hypoglycorrhachia in an Immunocompetent Patient Presenting With Disseminated Varicella-Zoster Infection.

Varicella-zoster virus (VZV) infection is rarely reported in immunocompetent hosts. We report the case of a 40-year-old male who presented with altered mental status. One week prior, he was seen at his outpatient physician's office for a rash along the lateral right thigh. Erythema of the right gluteal region was noted, but no vesicles were present. He was treated for shingles rash with acyclovir with improvement. After a period of initial improvement in the rash, the patient developed a persistent headache. Given his migraine history, he overlooked the headache. He then developed fever, followed by confusion and was brought to the ED for further evaluation. CT head was unremarkable. Lumbar puncture revealed aseptic meningitis. This case highlights the unusual presentation of disseminated VZV infection in an immunocompetent host. It stresses the importance of maintaining high suspicion for disseminated VZV infection despite the patient being immunocompetent.

[Case of isolated neurosarcoidosis requiring differentiation from tuberculous meningitis].

A 62-year-old woman was transported to our hospital for management of generalized clonic seizures. Cerebrospinal fluid examination showed an increased monocyte-dominant cell count, high protein concentration, and low glucose concentration that was 17% of the plasma glucose concentration. Contrast-enhanced cranial magnetic resonance imaging revealed diffuse leptomeningeal enhancement with multiple nodular lesions. She underwent examinations that ruled out the following conditions: tuberculous meningitis, systemic sarcoidosis, malignant lymphoma, carcinomatous meningitis, and central nervous system vasculitis. On hospital day 13, dural and brain biopsies revealed neurosarcoidosis, for which steroid therapy was administered. Thereafter, imaging examinations showed marked improvement. Because isolated neurosarcoidosis is difficult to diagnose, early pathologic diagnosis may be essential.

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

INTRODUCTION: The neurodevelopmental outcomes of young infants with hypoglycorrhachia that is comparable to glucose transporter 1 deficiency syndrome (GLUT1DS), i.e. cerebrospinal fluid (CSF) glucose ≤40 mg/dL and CSF lactate <2.2 mM without causes of secondary hypoglycorrhachia are unknown. This study investigated the developmental outcomes and possibility of GLUT1DS in infants with hypoglycorrhachia, or low CSF glucose concentration. MATERIAL AND METHODS: 1655 neurologically asymptomatic infants aged <4 months had CSF examinations for fever workup from 2006 to 2016. Among the infants with normal CSF cell counts and without isolated pathogens, there were hypoglycorrhachia group who had CSF glucose levels that were comparable to GLUT1DS, and age- and gender-matched non-hypoglycorrhachia group. Both groups were at a mean age of 5.9 ±â€¯2.4 years (ranged 1-10 years) at neurodevelopmental evaluation in 2017. Mutational analysis of solute-carrier-family 2, which facilitated the glucose transporter member 1 (SLC2A1) gene was performed. RESULTS: Among the 722 infants with normal CSF cell counts and without isolated pathogens, 30 (4.2%) had hypoglycorrhachia that was comparable to GLUT1DS. In the 25 infants with hypoglycorrhachia available for follow-up, 4 (16%) had abnormal outcomes, of which 3 (12%) had the history of mixed-type developmental delay before age 6 and 1 (4%) had type 1 diabetes mellitus. In the non-hypoglycorrhachia control group (n = 50), 2 patients (4%) showed abnormal outcomes, both with the history of pure speech delay. The hypoglycorrhachia group had a higher rate of the history of mixed-type of developmental delay than the control group (12% vs. 0%, P = 0.034). No SLC2A1 pathogenic variants were observed in the hypoglycorrhachia group. CONCLUSION: Hypoglycorrhachia may be a potential biomarker for neurodevelopmental delay instead of for GLUT1DS in neurologically asymptomatic young infants.

[A case of secondary central nervous system lymphoma presenting marked hypoglycorrhachia].

A 67-year-old male was transferred to our hospital with diplopia, decreased deep tendon reflex and ataxia. He had been suspected Fisher syndrome because of previous upper respiratory tract infection. A cerebrospinal fluid examination showed marked hypoglycorrhachia, pleocytosis and elevated protein, and cytological examination suggested malignant lymphoma. Abdominal computed tomography revealed a left adrenal mass. A biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. He was treated with a combination of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisolone) and intrathecal administration of methotrexate, cytarabine and prednisolone. Neurological symptoms were gradually improved. Malignancy should be considered in addition to bacterial, fungal or tuberculous meningitis in a case with marked hypoglycorrhachia.

Screening of SLC2A1 in a large cohort of patients suspected for Glut1 deficiency syndrome: identification of novel variants and associated phenotypes.

Glucose transporter type 1 deficiency syndrome (Glut1 DS) is a rare neurological disorder caused by impaired glucose delivery to the brain. The clinical spectrum of Glut1 DS mainly includes epilepsy, paroxysmal dyskinesia (PD), developmental delay and microcephaly. Glut1 DS diagnosis is based on the identification of hypoglycorrhachia and pathogenic mutations of the SLC2A1 gene. Here, we report the molecular screening of SLC2A1 in 354 patients clinically suspected for Glut1 DS. From this cohort, we selected 245 patients for whom comprehensive clinical and laboratory data were available. Among them, we identified 19 patients carrying nucleotide variants of pathological significance, 5 of which were novel. The symptoms of onset, which varied from neonatal to adult age, included epilepsy, PD or non-epileptic paroxysmal manifestations. The comparison of the clinical features between the 19 SLC2A1 mutated and the 226 non-mutated patients revealed that the onset of epilepsy within the first year of life (when associated with developmental delay or other neurological manifestations), the association of epilepsy with PD and acquired microcephaly are more common in mutated subjects. Taken together, these data confirm the variability of expression of the phenotypes associated with mutation of SLC2A1 and provide useful clinical tools for the early identification of subjects highly suspected for the disease.

Varicella-zoster virus meningitis with hypoglycorrhachia in a young immunocompetent adult without rash: A case report and literature review.

Overt aseptic meningitis rarely complicates varicella-zoster virus (VZV) reactivation in young and immunocompetent adults. Many of the cases of VZV meningitis are associated with an exanthem. We describe an otherwise healthy 36-year-old adult who had aseptic meningitis without skin rash, caused by reactivation of varicella-zoster virus. Cerebrospinal fluid (CSF) analysis revealed lymphocytosis, increased total protein, and low glucose. Diagnosis was made by polymerase chain reaction in CSF. The present case highlights the fact that VZV should be considered as a cause of aseptic meningitis with hypoglycorrhachia in healthy and young individuals, even in the absence of an exanthem.

A frame-shift deletion in the PURA gene associates with a new clinical finding: Hypoglycorrhachia. Is GLUT1 a new PURA target?

PURA is a DNA/RNA-binding protein known to have an important role as a transcriptional and translational regulator. Mutations in the PURA gene have been documented to cause mainly a neurologic phenotype including hypotonia, epilepsy, development delay and respiratory alterations. We report here a patient with a frame-shift deletion in the PURA gene that apart from the classical PURA deficiency phenotype had marked hypoglycorrhachia, overlapping the clinical findings with a GLUT1 deficiency syndrome. SLC2A1 (GLUT1) mutations were discarded, so we hypothesized that GLUT1 could be downregulated in this PURA deficient scenario. We confirmed reduced GLUT1 expression in the patient's peripheral blood cells compared to controls predicting that this could also be happening in the blood-brain barrier and in this way explain the hypoglycorrhachia. Based on PURA's known functions as a transcriptional and translational regulator, we propose GLUT1 as a new PURA target. Further in vitro and in vivo studies are needed to confirm this and to uncover the underlying molecular mechanisms.

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

OBJECTIVES: Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. METHODS: This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. RESULTS: Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). CONCLUSION: Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis.

Rapidly progressive dementia with hypoglycorrhachia.

We report a woman who presented with rapidly progressive dementia and hypoglycorrhachia and discuss the approach and differential diagnosis for her condition. Rapidly progressive dementia poses a variety of challenges to the treating clinician, not only due to the speed of disease progression, but also due to the poor prognosis if intervention is delayed. The differential diagnosis of a patient presenting with rapid cognitive and functional decline is broad and includes degenerative, infectious, toxic, and neoplastic etiologies, some of which can be identified clinically through history and physical examination. Diagnostic evaluation using gadolinium-enhanced MRI, electroencephalography, and serum and cerebrospinal fluid testing is often required. The utility of testing for cerebrospinal fluid 14-3-3 antigen and tau is also reviewed.