Guillermo Agosta

Long-term follow-up of the ketogenic diet for refractory epilepsy: multicenter Argentinean experience in 216 pediatric patients.

PURPOSE In this Argentinean retrospective, collaborative, multicenter study, we examine the efficacy and tolerability of the ketogenic diet (KD) for different epilepsy syndromes. MATERIALS AND METHODS we evaluated the clinical records of 216 patients started on the KD between March 1, 1990 and December 31, 2010. RESULTS One hundred forty of the initial patients (65%) remained on the diet at the end of the study period. Twenty-nine patients (20.5%) became seizure free and 50 children (36%) had a 75-99% decrease in seizures. Thus, 56.5% of the patients had a seizure control of more than 75%. The best results were found in patients with epilepsy with myoclonic-astatic seizures, Lennox-Gastaut syndrome, and West syndrome. Good results were also found in patients with Dravet syndrome, in those with symptomatic focal epilepsy secondary to malformations of cortical development, and in patients with tuberous sclerosis. Seizures were significantly reduced in four patients with fever-induced refractory epileptic encephalopathy in school-age children and in two patients with epileptic encephalopathy with continuous spikes and waves during slow sleep. The median period of follow-up after discontinuation of the diet was 6 years. Twenty patients who had become seizure free discontinued the diet, but seizures recurred in five (25%). Of 40 patients with a seizure reduction of more than 50% who discontinued the diet, 10 presented with recurrent seizures. CONCLUSION The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.

Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury.

Objective To assess the association between neurologic outcome and the alterations of jugular venous oxygen saturation (Sjvo2) or the increase in arteriovenous difference of lactate content (AVDL) in children with severe traumatic brain injury. Design Observational prospective cohort study. Setting Multidisciplinary pediatric intensive care unit of a university hospital. Patients A total of 27 pediatric patients with severe traumatic brain injury, with a Glasgow Coma Scale after resuscitation of <9, who were admitted to the pediatric intensive care unit within 36 hrs after injury. Interventions Intermittent measurement of Sjvo2 and AVDL. Measurements and Main Results Sjvo2 and AVDL were assessed simultaneously every 6 hrs. The primary dependent variable measured was assessed independently 3 months after trauma according to the Pediatric Cerebral Performance Category. Patients were classified into two groups: group 1 (favorable outcome, Pediatric Cerebral Performance Category 1–3) and group 2 (unfavorable outcome, Pediatric Cerebral Performance Category 4–6); 81% were included in group 1 and 19% in group 2. A total of 354 measurements of Sjvo2 and AVDL were made, with a mean of 13.1 ± 7.9 per patient. The number of abnormal measurements of Sjvo2 and increased AVDL used to predict the neurologic outcome was selected according to the area under the receiver operating characteristic curve. Mortality was 15% (four patients). The strongest association was found between a poor neurologic outcome and two or more pathologic AVDL measurements (higher than −0.37 mmol/L; relative risk, 17.6; 95% confidence interval, 2.5–112.5;p = .001). The presence of two or more measurements of Sjvo2 of ≤55% was significantly associated with a poor neurologic outcome (relative risk, 6.6; 95% confidence interval, 1.5–29.7;p = .003). The frequency of measurements of Sjvo2 of ≥75% was not different between groups 1 and 2. Conclusion In children with severe traumatic brain injury, two or more measurements of Sjvo2 of ≤55% or two or more pathologic AVDL measurements were associated with a poor neurologic outcome. Further studies are needed to recommend the use of these variables as a guideline to optimize treatment.

Identifying the trigeminal nerve branches for transovale radiofrequency thermolesion: "no pain, no stress".

BACKGROUND: Radiofrequency thermorhizotomy of the trigeminal nerve is a known treatment of trigeminal neuralgia. Analysis of verbal responses to electric stimulation of the trigeminal rootlets has been the only method available to localize the affected branch, but patient discomfort may lead to unreliable verbal responses, resulting in increased morbidity or even therapeutic failure. Orthodromically elicited evoked potentials of the trigeminal nerve have also been used, but their application is tedious and results may vary. OBJECTIVE: To develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches. METHODS: A series of 55 patients under general anesthesia during radiofrequency thermorhizotomy were studied. The trigeminal nerve root was stimulated through the foramen ovale with the RF electrode. Antidromic responses were recorded from the 3 divisions of the trigeminal nerve in the face. Effectiveness rate, pain relief, recurrence, complications, and patient comfort after the procedure were analyzed. RESULTS: Reproducible and easily obtained antidromic responses were clearly recorded in every subdivision of the trigeminal nerve in all patients. Ninety-four percent of patients experienced immediate pain relief after the procedure. The recurrence rate was 12.72%, and the surgical morbidity was 20%. CONCLUSION: This method proved to be useful to determine the exact localization of individual subdivisions of the trigeminal nerve in anesthetized patients, making this procedure safer and more comfortable for them. ABBREVIATION: RF-TL, radiofrequency thermolesioning

CSF and Blood Levels of GFAP in Alexander Disease

Abstract Alexander disease is a rare, progressive, and generally fatal neurological disorder that results from dominant mutations affecting the coding region of GFAP, the gene encoding glial fibrillary acidic protein, the major intermediate filament protein of astrocytes in the CNS. A key step in pathogenesis appears to be the accumulation of GFAP within astrocytes to excessive levels. Studies using mouse models indicate that the severity of the phenotype correlates with the level of expression, and suppression of GFAP expression and/or accumulation is one strategy that is being pursued as a potential treatment. With the goal of identifying biomarkers that indirectly reflect the levels of GFAP in brain parenchyma, we have assayed GFAP levels in two body fluids in humans that are readily accessible as biopsy sites: CSF and blood. We find that GFAP levels are consistently elevated in the CSF of patients with Alexander disease, but only occasionally and modestly elevated in blood. These results provide the foundation for future studies that will explore whether GFAP levels can serve as a convenient means to monitor the progression of disease and the response to treatment.

5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The childs neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

Epilepsia partialis continua associated with levamisole.

Epilepsia partialis continua is defined as a spontaneous regular or irregular clonic muscular twitching affecting a limited part of the body, occurring for a minimum of 1 hour and recurring at intervals of less than 10 seconds. Levamisole is used as an immunomodulating medication in patients with recurrent aphthous ulcers. Evidence suggests that it can induce multifocal inflammatory leukoencephalopathy. We describe the clinical neuroimaging and ictal electroencephalographic findings in an adolescent with epilepsia partialis continua caused by the administration of levamisole with cortical and subcortical lesions. To our knowledge, this is the first report that describes the association of epilepsia partialis continua cortical lesions detected by magnetic resonance imaging and levamisole that were not previously described.

CSF and Blood Levels of GFAP in Alexander Disease(1,2,3).

Abstract Alexander disease is a rare, progressive, and generally fatal neurological disorder that results from dominant mutations affecting the coding region of GFAP, the gene encoding glial fibrillary acidic protein, the major intermediate filament protein of astrocytes in the CNS. A key step in pathogenesis appears to be the accumulation of GFAP within astrocytes to excessive levels. Studies using mouse models indicate that the severity of the phenotype correlates with the level of expression, and suppression of GFAP expression and/or accumulation is one strategy that is being pursued as a potential treatment. With the goal of identifying biomarkers that indirectly reflect the levels of GFAP in brain parenchyma, we have assayed GFAP levels in two body fluids in humans that are readily accessible as biopsy sites: CSF and blood. We find that GFAP levels are consistently elevated in the CSF of patients with Alexander disease, but only occasionally and modestly elevated in blood. These results provide the foundation for future studies that will explore whether GFAP levels can serve as a convenient means to monitor the progression of disease and the response to treatment.

Pacientes con neurofibromatosis tipo 1: perfil cognitivo y trastornos en funciones cerebrales superiores en la edad pediátrica ☆

INTRODUCTION Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome often associated with specific cognitive deficits that are rarely monitored during follow-up of these patients. OBJECTIVE The purpose of our study is two-fold. First, we aimed to describe the cognitive profile of patients with NF1 and detect disorders in higher brain functions associated with the disease. Second, we identified the reasons for consultation associated with school performance in these patients. METHODS We conducted a descriptive cross-sectional study of 24 paediatric patients (ages 5 to 16) with NF1 who underwent neuropsychological assessment. RESULTS The most frequent reasons for consultation were attention deficits (58.33%), learning disorders (25%), poor motor coordination (25%), and language impairment (0.8%). Although 96% of the patients displayed impairments in at least one of the assessed areas, only 83.34% of the parents had reported such impairments. Attention-deficit/hyperactivity disorder was present in 58.33% of the patients, whereas 33.33% had nonverbal learning disabilities, 20.83% had expressive language disorder, 8.33% had borderline intellectual functioning, 4.16% had mental retardation, and only 4.16% showed no cognitive impairment. CONCLUSION Higher brain functions are frequently impaired in paediatric patients with NF1. Although many parents report such disorders, they can go undetected in some cases. Neuropsychological assessment is recommended for all paediatric patients with NF1 to detect cognitive impairment and provide early, effective rehabilitation treatment.

Fluencia verbal: un test neuropsicológico breve para la detección de trastornos cognitivos en pediatría

RESUMEN IntroduccIón: la fluencia verbal es un test psicométrico breve utilizado en evaluaciones neuropsicológicas para estudiar funciones ejecutivas y verbales. El desempeño en la población pediátrica en esta prueba no ha sido profundamente estudiado. Tampoco encontramos estudios en pediatría que analicen la fluidez verbal fonológica (FF) en relación al nivel intelectual utilizando la versión española con letras iniciales “P” y “M”.

Cerebrospinal fluid and blood levels of GFAP in Alexander disease

Abstract Alexander disease is a rare, progressive, and generally fatal neurological disorder that results from dominant mutations affecting the coding region of GFAP, the gene encoding glial fibrillary acidic protein, the major intermediate filament protein of astrocytes in the CNS. A key step in pathogenesis appears to be the accumulation of GFAP within astrocytes to excessive levels. Studies using mouse models indicate that the severity of the phenotype correlates with the level of expression, and suppression of GFAP expression and/or accumulation is one strategy that is being pursued as a potential treatment. With the goal of identifying biomarkers that indirectly reflect the levels of GFAP in brain parenchyma, we have assayed GFAP levels in two body fluids in humans that are readily accessible as biopsy sites: CSF and blood. We find that GFAP levels are consistently elevated in the CSF of patients with Alexander disease, but only occasionally and modestly elevated in blood. These results provide the foundation for future studies that will explore whether GFAP levels can serve as a convenient means to monitor the progression of disease and the response to treatment.