Diagnosing Glucose Transporter 1 Deficiency at Initial Presentation Facilitates Early Treatment.

OBJECTIVE: To profile the initial clinical events of glucose transporter 1 deficiency syndrome (Glut1 DS) in order to facilitate the earliest possible diagnosis. STUDY DESIGN: We retrospectively reviewed 133 patients with Glut1 DS from a single institution. Family interviews and medical record reviews identified the first clinical event(s) reported by the caregivers. RESULTS: Average age of the first event was 8.15 ± 11.9 months (range: 0.01-81). Ninety-one patients experienced the first symptom before age 6 months (68%). Thirty-three additional patients (25%) presented before age 2 years. Only 9 patients (7%), reported the first event after age 2 years. Seizures were the most common first event (n = 81, 61%), followed by eye movement abnormalities (n = 51, 38%) and changes in muscle strength and tone (n = 30, 22%). Eye movement abnormalities, lower cerebrospinal fluid glucose values, and lower Columbia Neurological Scores correlated with earlier onset of the first event (r: -0.17, 0.22, and 0.25 respectively, P < .05). There was no correlation with age of first event and red blood cell glucose uptake or mutation type. CONCLUSIONS: Glut1 DS is a treatable cause of infantile onset encephalopathy. Health care providers should recognize the wide spectrum of paroxysmal events that herald the clinical onset of Glut1 DS in early infancy to facilitate prompt diagnosis, immediate treatment, and improved long-term outcome.

Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency.

RATIONALE: (18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism. METHODS: (18)F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results. RESULTS: Visual analysis of the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score. CONCLUSION: Quantitative analysis of (18)F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy.

Gelastic seizure with tectal tumor, lobar holoprosencephaly, and subependymal nodules: clinical report.

Gelastic seizures are characterized by inappropriate, stereotyped laughter and are often first recognized when other epileptic manifestations occur. They are frequently associated with hypothalamic hamartomas. Central nervous system developmental abnormalities are rarely reported with gelastic seizures. There is only one case report of gelastic seizure caused by holoprosencephaly. We report a 2-year-old girl with multiple brain structural abnormalities including tectal tumor (possibly hamartoma), multiple subependymal nodules, and holoprosencephaly. She developed seizures during the newborn period and presented with gelastic seizure and simple partial seizure at 3 months of age.

Mitochondrial DNA deletion in a child with megaloblastic anemia and recurrent encephalopathy.

A 3 1/2-year-old boy presented with megaloblastic anemia and recurrent episodes of severe lactic acidosis and coma. At age 4 years, he developed sepsis and died; postmortem examination failed to show any gross abnormality in any tissue. Biochemical analysis of muscle showed decreased activities for all respiratory chain enzymes except complex II. Muscle histochemistry revealed diffuse cytochrome c oxidase deficiency. Southern blot analysis of mitochondrial DNA from muscle, liver, and blood showed a heteroplasmic single mitochindrial DNA deletion of 2.4 kb, which removed the genes for cytochrome c oxidase I and II and the transfer ribonucleic acid genes for serine and aspartic acid. Single large-scale deletions in mitochondrial DNA have been associated with Pearson's syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. This patient's presentation is unusual and suggests an overlap between Pearson's syndrome and Kearns-Sayre syndrome.

Nonconvulsive status epilepticus and continuous spike and slow wave of sleep in children.

Nonconvulsive status epilepticus (NCSE) is a special epileptic state that can be more common than previously thought in children and adult patients. Currently, there is no universally accepted definition for NCSE. Early and accurate diagnosis depends on a high index of suspicion and rapid availability of electroencephalographic recording. The clinical presentation of NCSE can vary from a mild confusional state to a coma. The underlying etiology is also quite diverse. In critically ill patients, NCSE has been reported with convulsive status epilepticus (CSE), hypoxemia, acute ischemic or hemorrhagic stroke, encephalitis, or trauma. The estimated incidence of NCSE is 15% to 40% in post-CSE, 8% in subarachnoid hemorrhage, and 8% to 10% in coma. As seen in CSE, there is a bimodal distribution with NCSE in critically ill patients; children (age <1 year) and elderly appear to be at great risk. NCSE has also been reported in a number of epilepsy syndromes, such as childhood absence epilepsy, Panayiotopoulos syndrome, Lennox-Gastaut syndrome, and Dravet syndrome. However, it is difficult to determine the incidence of NCSE in an ambulatory setting because of the great variation in clinical presentation and underlying etiology. This review examines the clinical features, outcome, and treatment approach for NCSE in 2 different clinical settings, in ambulatory and critically ill patients. NCSE is reviewed in children and adults to distinguish similarities and differences in their clinical presentation.

Seizure frequency in children with epilepsy: factors influencing accuracy and parental awareness.

RATIONALE: The objective of this study was to ascertain the accuracy of clinical reports to determine the seizure frequency in children diagnosed with epilepsy. METHODS: We reviewed the clinical record of 78 children (January-May of 2006) admitted to the EEG-video monitoring with epilepsy diagnosis. Clinical reports of parents and the files of EEG-video monitoring were reviewed to determine parents' awareness for seizures. RESULTS: During video-EEG monitoring, 1244 were recorded on 78 children. Seizures were confirmed in 1095 of which 472 were correctly reported (38%) by parents whereas 623 remained under-reported (50%). Parents' report thus had a sensitivity of 43%, positive predictive value of 76% to identify seizures. Based on the EEG-video monitoring, seizures were reported accurately in 22 (28%) and under-reported in 38 (49%) children. In the under-reported group, none of the seizures were recognized in 10 (13%), only a portion identified in 28 children. The parents' report describing seizure frequency has limited value for young children (p=0.01) and children with absence seizures (p=0.03). However, clinical reports were accurate for the children with developmental delay (p<0.06) or not being on any anticonvulsant drug (AED) therapy (p=0.02). CONCLUSION: Our results indicate that a significant number of seizures remain under-reported by parents of children with epilepsy. The current study underscores that the seizure frequency should be interpreted with caution for young children and children with absence seizures. Video-EEG recording has a complimentary role to the clinical observation for the accurate assessment of seizure frequency in children.

The effect of lamotrigine on the EEGs of children and adolescents with epilepsy.

Lamotrigine (LTG) is one of the newer-generation antiepileptic drugs (AEDs) with broad-spectrum efficacy against a variety of seizures and epileptic syndromes. We retrospectively evaluated the effects of LTG as add-on therapy on EEGs of children and adolescents. The EEGs of 53 patients (mean age: 12.5 years) with primarily pharmacoresistant epilepsy were reviewed prior to and after LTG add-on therapy. Multiple seizure types were seen in 25, generalized seizures in 15, and complex partial seizures in 13 of the patients. Preceding LTG therapy, the baseline EEG was abnormal because of slow background in 60.3% and localized spikes in 35.8%, generalized spikes in 28.3%, or both in 24.5%. The EEG analysis during the 2-year follow-up period showed improvement in the background in 21.9%, interictal activity in 37.8%, and ictal pattern in 41.1% of the EEG recordings. Overall, LTG resulted in improvement in electrographic features which paralleled the clinical improvement.

The influence of cognitive reserve on seizure-induced injury.

Status epilepticus (SE) is associated with a significant risk of cognitive impairment. While many factors likely determine cognitive outcome following SE, there is evidence that cognitive ability prior to a neurological insult may be an important determinant of outcome. Patients with greater cognitive abilities or so-called cognitive reserve may be less vulnerable to injury than patients with limited cognitive ability. Here we tested the hypothesis that cognitive abilities prior to SE would be predictive of cognitive outcome. Immature rats were tested in the water maze, a test of visual-spatial memory, and divided into fast and slow learners. Animals were then subjected to SE and retested in the water maze 23 days later. Control rats were tested in the same manner but not subjected to SE. SE resulted in marked impairment in water maze performance. However, no statistical difference was noted in performance between slow and fast learners in either the SE or control group. Likewise, no differences were seen in the histopathology of the slow and fast learners. This study demonstrates that SE adversely effects visual-spatial memory equally in both fast and slow learners and does not support the theory that cerebral reserve plays a major role in cognitive function following a cerebral insult.