GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.
Apnea ; Ataxia ; Cerebrospinal Fluid ; Child ; Clothing ; Cognition ; Dyskinesias ; Dystonia ; Early Diagnosis ; Epilepsy ; Epilepsy, Absence ; Female ; Glucose ; Humans ; Infant, Newborn ; Ketogenic Diet ; Microcephaly ; Movement Disorders ; Phenotype ; Quality of Life ; Retrospective Studies ; Seizures

OBJECTIVE: To compare the contrast-enhanced fluid-attenuated inversion recovery (CE-FLAIR), the CE T1-weighted (CE-T1W) sequence with fat suppression (FS) and magnetization transfer (MT) for early detection and characterization of infectious meningitis. MATERIALS AND METHODS: Fifty patients and 10 control subjects were evaluated with the CE-FLAIR and the CE-T1W sequences with FS and MT. Qualitative assessment was done by two observers for presence and grading of abnormal leptomeningeal enhancement. Quantitative assessment included computation of net meningeal enhancement, using single pixel signal intensity software. A newly devised FLAIR based scoring system, based on certain imaging features including ventricular dilatation, ependymal enhancement, infarcts and subdural effusions was used to indicate the etiology. Data were analysed using the Student's t test, Cohen's Kappa coefficient, Pearson's correlation coefficient, the intraclass correlation coefficient, one way analysis of variance, and Fisher's exact test with Bonferroni correction as the post hoc test. RESULTS: The CE-FLAIR sequence demonstrated a better sensitivity (100%), diagnostic accuracy (95%), and a stronger correlation with the cerebrospinal fluid, total leukocyte count (r = 0.75), protein (r = 0.77), adenosine deaminase (r = 0.81) and blood glucose (r = -0.6) values compared to the CE-T1W sequences. Qualitative grades and quantitative meningeal enhancement on the CE-FLAIR sequence were also significantly greater than those on the other sequences. The FLAIR based scoring system yielded a diagnostic accuracy of 91.6% and a sensitivity of 96%. A strong inverse Pearson's correlation (r = -0.95) was found between the assigned score and patient's Glasgow Coma Scale at the time of admission. CONCLUSION: The CE-FLAIR sequence is better suited for evaluating infectious meningitis and could be included as a part of the routine MR imaging protocol.
Adenosine Deaminase ; Blood Glucose ; Cerebrospinal Fluid ; Dilatation ; Glasgow Coma Scale ; Humans ; Leukocyte Count ; Magnetic Resonance Imaging ; Meningitis*

Acute cerebellitis is a rare inflammatory disorder that occurs most frequently in children. The typical clinical course of acute cerebellitis is benign. However, in some cases of acute cerebellitis, fulminant cerebellar swelling with obliteration of the fourth ventricle causes brain stem compression and acute obstructive hydrocephalus, which can be life-threatening and require emergent neurosurgical procedures. We describe the case of a 4-year-old girl whose acute cerebellitis caused brain stem compression, acute obstructive hydrocephalus, and death. The patient was admitted to the emergency department because of a severe headache that had persisted for 5 days. Neurological examinations revealed no specific abnormality. Brain magnetic resonance imaging (MRI) demonstrated diffuse swelling and high signal intensity lesions in the cerebellar hemispheres and vermis, obliteration of the fourth ventricle, and brain stem compression on T2-weighted images in conjunction with mild hydrocephalus. Cerebrospinal fluid (CSF) analysis revealed white blood cell and red blood cell counts of 180/mm³ and 0/mm³, respectively; protein and glucose concentrations of 263.6 mg/dL and 37 mg/dL, respectively; and negative culture results. Despite aggressive treatment, the patient developed sudden cardiorespiratory arrest on day 2. Although emergency neurosurgery was performed after cardiopulmonary resuscitation, her condition progressed to brain death, and she died on day 29. This case suggests that timely and appropriate neurosurgery should be actively considered to relieve increased intracranial pressure in the early phases of acute cerebellitis.
Brain Death ; Brain Stem* ; Brain* ; Cardiopulmonary Resuscitation ; Cerebrospinal Fluid ; Child ; Child, Preschool ; Emergencies ; Emergency Service, Hospital ; Erythrocyte Count ; Female ; Fourth Ventricle ; Glucose ; Headache ; Humans ; Hydrocephalus* ; Intracranial Hypertension ; Intracranial Pressure ; Leukocytes ; Magnetic Resonance Imaging ; Neurologic Examination ; Neurosurgery ; Neurosurgical Procedures

PURPOSE: To explore clinical features and neurologic complications of pediatric enteroviral meningitis, and to evaluate risk factors according to the presence of cerebrospinal fluid (CSF) pleocytosis and neurologic complications. METHODS: Retrospective review of medical records of patients aged between 1 month and 18 years who were found positive for CSF enterovirus reverse transcription polymerase chain reaction in Dankook University Hospital from March 2009 to February 2015. RESULTS: A total of 151 children was enrolled in the study. Ninety four patients were males and the age at diagnosis was 40.9±47.0 months. Most common season of admission was summer (n=99, 65.6%). Most frequent presenting symptom was fever followed by poor oral intake, decreased activity, and headache. Fifty five (36.4%) patients had no CSF pleocytosis. Complications were observed in 4 (2.6%). Mean blood white blood cell, CSF protein levels were higher, and CSF glucose levels were lower in group with pleocytosis (P < 0.05). There were more seizure development and mental changes, higher peak body temperature, longer fever duration, and longer duration from symptom onset to CSF tapping in group with complications (P < 0.05). All were boys and mean age at admission was younger in group with complications, without statistically significant difference. CONCLUSION: Relatively high proportion of children with enteroviral meningitis showed no pleocytosis. Complications such as meningoencephalitis, refractory status epilepticus, or recurrent seizure rarely occurred, although most had good clinical outcomes.
Body Temperature ; Cerebrospinal Fluid ; Child ; Diagnosis ; Enterovirus ; Fever ; Glucose ; Headache ; Humans ; Leukocytes ; Leukocytosis ; Male ; Medical Records ; Meningitis* ; Meningoencephalitis ; Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcription ; Risk Factors ; Seasons ; Seizures ; Status Epilepticus

BACKGROUND: Varicella-zoster virus (VZV) is one of the most common etiologies of aseptic meningitis. The severest manifestation of VZV meningitis is occasionally confused with tuberculous meningitis (TBM). Thus, we investigated the clinical manifestations of VZV meningitis as compared with those of TBM. MATERIALS AND METHODS: All adult patients who were diagnosed with VZV meningitis or TBM were enrolled at a tertiary hospital in Seoul, South Korea, during an 8-year period. The clinical characteristics and cerebrospinal fluid (CSF) profile of patients were analyzed. RESULTS: Seventy-nine patients with VZV meningitis and 24 patients with TBM were enrolled in this study. Of the 79 patients with VZV meningitis, 63 (80%) did not received empirical anti-tuberculous therapy (Group 1) and the remaining 16 (20%) received empirical anti-tuberculous therapy (Group 2), compared with 24 patients with TBM (Group 3). Altered mental status, intensive care unit (ICU) admission, neurologic sequelae, CSF protein levels, and CSF adenosine deaminase levels revealed a trend of being higher in Group 3 than Group 2, which was higher than Group 1. However, the CSF/serum glucose ratio was significantly lower in Group 3 than in Group 1 or Group 2. CONCLUSION: About one fifth of VZV meningitis cases presented as severe manifestations, mimicking TBM. The CSF/serum glucose ratio might be useful to differentiate VZV meningitis from TBM until definite diagnostic tests are available. Physicians should keep in mind that a differential diagnosis between severe VZV meningitis and TBM is needed.
Adenosine Deaminase ; Adult ; Cerebrospinal Fluid ; Diagnosis, Differential ; Diagnostic Tests, Routine ; Glucose ; Herpesvirus 3, Human ; Humans ; Intensive Care Units ; Korea ; Meningitis* ; Meningitis, Aseptic ; Seoul ; Tertiary Care Centers ; Tuberculosis, Meningeal

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is the second most common cause of viral meningitis and the most common cause of recurrent meningitis. Although the incidence of HSV-2 meningitis is high, its clinical characteristics are not well known. The purpose of this study was to review the clinical characteristics and prognosis of HSV-2 meningitis. METHODS: We analyzed patients who were admitted to the Department of Neurology at Severance Hospital with a final diagnosis of HSV-2 meningitis, as confirmed by applying the polymerase chain reaction to the cerebrospinal fluid (CSF) of patients. RESULTS: The study involved 998 patients with aseptic meningitis and 60 patients diagnosed with HSV-2 meningitis. The mean age at meningitis presentation was 32.5 years (range 18-54 years), and 72% of the patients were female. Common clinical symptoms were headache (100%), nausea and/or vomiting (83%), meningismus (57%), and fever (55%). Six patients had a history of genital herpes infection, and 11 had a past history of recurrent meningitis. The CSF study was notable for elevated protein (111.0±53.5 mg/dL, mean±standard deviation) and white cell count (332.0±211.3 cells/µL). The CSF/serum glucose ratio was 0.52±0.90. Various treatments were applied, including conservative care, antiviral agents, empirical antibiotics, and combined treatments. All patients recovered without serious neurologic sequelae. CONCLUSIONS: HSV-2 meningitis is relatively common, as are recurrent episodes. The clinical characteristics of HSV-2 meningitis are similar to those of other types of aseptic meningitis. HSV-2 meningitis is treated using antiviral therapy, and the prognosis is favorable even with conservative treatment.
Anti-Bacterial Agents ; Antiviral Agents ; Cell Count ; Cerebrospinal Fluid ; Diagnosis ; Female ; Fever ; Glucose ; Headache ; Herpes Genitalis ; Herpes Simplex* ; Herpesvirus 2, Human* ; Humans ; Incidence ; Meningism ; Meningitis ; Meningitis, Aseptic ; Meningitis, Viral ; Nausea ; Neurology ; Polymerase Chain Reaction ; Prognosis ; Retrospective Studies* ; Simplexvirus* ; Vomiting

Vernet syndrome associated with varicella zoster virus (VZV) has been rarely reported. The diagnosis is established based on typical symptoms such as dysphagia, hoarseness, and unilateral difficulty in neck movement. Lack of skin lesions is common and makes it harder to consider VZV infection. A 53-year-old woman presented with left neck pain, dysphagia, hoarseness, and headache, with an erythematous vesicle on her neck. Laryngoscopy revealed paralysis of her left-soft palate and left-vocal cord. Upon cerebrospinal fluid (CSF) examination, her white blood cell (WBC) count, protein levels, glucose levels, and VZV antibody titer were elevated; moreover, VZV-DNA was detected. Magnetic resonance imaging (MRI) showed no sign of brain tumor, aneurysm or fracture. The patient was diagnosed with Vernet syndrome associated with VZV infection, having presented with a skin lesion involving the cervical segment.
Aneurysm ; Brain Neoplasms ; Cerebrospinal Fluid ; Chickenpox* ; Deglutition Disorders ; Diagnosis ; Female ; Glucose ; Headache ; Herpesvirus 3, Human* ; Hoarseness ; Humans ; Laryngoscopy ; Leukocytes ; Magnetic Resonance Imaging ; Middle Aged ; Neck ; Neck Pain ; Palate ; Paralysis ; Skin*

BACKGROUND: The clinical usefulness of flow cytometry (FCM) for the diagnosis of leptomeningeal diseases (LMD) in non-Hodgkin lymphomas has been suggested in previous studies but needs to be further validated. With this regards, we evaluated the use of FCM for LMD in a series of Korean patients with non-Hodgkin lymphoma. METHODS: FCM and cytomorphology were conducted using samples obtained from clinically suspected LMD patients, follow-up LMD patients, and those with high risk of developing tumorigenic diseases. We then compared results of FCM and cytomorphology. In total, 55 and 47 CSF samples were analyzed by FCM and cytomorphology, respectively. RESULTS: Of the samples analyzed, 25.5% (14/55) and 12.8% (6/47) were positive by FCM and cytomorphology, respectively. No samples were determined as negative by FCM but positive by cytomorphology. Seven patients were positive only by FCM and negative by cytomorphology, and six among them were clinically confirmed to have LMD either by follow-up cytomorphology or imaging study. CONCLUSIONS: We observed a high detection rate of tumor cells by FCM compared with cytomorphology. FCM study can be useful in early sensitive detection of LMD.
Adult ; Aged ; Female ; Flow Cytometry ; Glucose/cerebrospinal fluid ; Humans ; Leukocytes/cytology ; Lymphoma, Large B-Cell, Diffuse/diagnosis/mortality ; Lymphoma, Non-Hodgkin/*complications ; Male ; Meningeal Neoplasms/cerebrospinal fluid/complications/*diagnosis ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate

Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures. Here, we describe the case of a patient with GLUT-1 deficiency who developed infantile spasms and showed delayed development at 6 months of age. She had intractable epilepsy despite receiving aggressive antiepileptic drug therapy, and underwent a metabolic workup. Cerebrospinal fluid (CSF) examination showed CSF-glucose-to-blood-glucose ratio of 0.38, with a normal lactate level. Bidirectional sequencing of SLC2A1 identified a missense mutation (c.1198C>T) at codon 400 (p.Arg400Cys) of exon 9.
Cerebrospinal Fluid ; Codon ; Drug Resistant Epilepsy ; Drug Therapy ; Exons* ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; Glucose* ; Humans ; Infant ; Infant, Newborn ; Lactic Acid ; Movement Disorders ; Mutation, Missense ; Myoclonus ; Seizures ; Spasms, Infantile*

OBJECTIVE: Enteroviruses are major causes of aseptic meningitis in children. This study aimed to describe the clinical manifestations of enteroviral meningitis according to the presence of cerebrospinal fluid (CSF) pleocytosis, and to investigate the factors influencing the CSF pleocytosis in children with this condition. METHODS: Eighty children with enteroviral meningitis treated at Soonchunhyang University Hospitals in Seoul and Bucheon between July 2012 and August 2013 were enrolled. The patients were diagnosed by reverse transcription-polymerase chain reaction (RT-PCR), and the clinical variables were compared according to the presence of CSF pleocytosis. RESULTS: Of the 80 patients, 54 (67.5%) and 26 (32.5%) patients had and did not have CSF pleocytosis, respectively. Forty-eight (60%) patients were male, and the median age was 63 months (range, 2 to 192 months). Seventy-six (95%), 67 (83.7%), 51 (63.7), and 2 (2.5%) patients presented with fever, headache, vomiting, and seizure, respectively. Increased CSF protein and pressure were associated with CSF pleocytosis. However, age, peripheral white blood cell count, C-reactive protein, CSF glucose, CSF/serum glucose ratio, and onset-puncture time interval were not associated with the presence of CSF pleocytosis. CONCLUSION: This study demonstrated a high proportion of non-pleocytic enteroviral meningitis in children, and identified several clinical manifestations that were associated with CSF pleocytosis. The findings of this study may help us better understand the characteristics of the disease and facilitate early diagnosis and treatment of enteroviral meningitis. During the outbreak seasons of enteroviral meningitis, the importance of continuous surveillance of enteroviruses and rapid RT-PCR testing should be emphasized.
C-Reactive Protein ; Cerebrospinal Fluid* ; Child* ; Early Diagnosis ; Enterovirus ; Fever ; Glucose ; Gyeonggi-do ; Headache ; Hospitals, University ; Humans ; Leukocyte Count ; Leukocytosis* ; Male ; Meningitis* ; Meningitis, Aseptic ; Pediatrics ; Seasons ; Seizures ; Seoul ; Vomiting