Diagnosis of pediatric anti-NMDAR encephalitis at the onset: A clinical challenge.

BACKGROUNDS: To investigate the clinical and instrumental features at the onset addressing to the diagnosis of anti-NMDAR encephalitis. METHODS: Twenty children (age: 15 months-17 years; 7 males, 13 females) with initial suspected diagnosis of autoimmune encephalitis, observed between January 2008 and March 2018, were included. The final diagnosis was anti-NMDAR encephalitis in 7 children, other/probable autoimmune encephalitis in 7 children, and primary psychosis in the remaining 6 children. RESULTS: At the clinical onset, anxiety disorder was the main symptom that helped in distinguishing the group of psychotic children from children with non-infectious encephalitis (P = 0.05 OR = 0.001), while epileptic seizures strongly predicted anti-NMDAR encephalitis (P = 0.04 OR = 28.6). At the onset, anti-NMDAR encephalitis could be distinguished from other/probable autoimmune encephalitis for the presence of sleep/wake rhythm alteration (P = 0.05 OR = 15). Among the symptoms occurring during the hospitalization, movement disorders (P = 0.031 OR = 12) were predictive of non-infectious encephalitis rather than primary psychosis. More specifically, the occurrence of language impairment (P = 0.03 OR = 33), epileptic seizures (P = 0.04 OR = 28.6) and catatonia (P = 0.03, OR = 33), were predictive of anti-NMDAR encephalitis. Also at this stage, anxiety disorder (P = 0.03 OR = 0.033) was predictive of primary psychosis. CONCLUSION: Our findings suggest that at the clinical onset epileptic seizures and sleep/wake rhythm alteration represent the main features addressing to the diagnosis of anti-NMDAR encephalitis rather than primary psychosis and other/probable autoimmune encephalitis, while anxiety disorder could be a solid predictor of primary psychosis.

Cross-neutralization of the coagulant activity of Crotalus durissus terrificus venom from the northeast of Argentina by bivalent bothropic antivenom

Cross-neutralization of Crotalus durissus terrificus venom coagulant activity was tested using bivalent horse antivenom against Bothrops alternatus and Bothrops diporus venoms. Our in vitro and in vivo experiments showed that bothropic antivenom neutralizes the thrombin-like activity of crotalic snake venom and this cross-reaction was demonstrated by immunoassays either with whole venom or a purified thrombin-like enzyme. These results suggest common antigenic properties and, consequently, similar molecular structure among venom thrombin-like enzymes. Besides, they provide information that could be further used in the development of new antivenom formulations.

The role of extracellular conditions during CaCo-2 cells growth: a preliminary study for numerical model validation.

OBJECTIVES: One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. MATERIAL AND METHODS: We studied the variation of extracellular parameters--such as medium volume, buffer system, nutrient concentrations and temperature on human colon carcinoma cells (CaCo-2) "in vitro culture"--pursuing the goal of understanding in deeper details cellular processes such as growth, metabolic activity, survival and pH0. RESULTS: Results showed that CaCo-2 cells growth and mortality increase after two days in culture when cells were suspended in 3.5 ml volume to respect of 10 ml volume. Different temperature values influenced CaCo-2 cells growth and metabolic activity showing a direct relationship with the volume of the medium. CONCLUSIONS: Our results describe as CaCo-2 cell growth, metabolic activity, mortality and extracellular pH were influenced by extracellular parameters, enabling us to develop and validate a numerical model to be use to predict cells engraftment and proliferation.

Indications for surgical treatment of epilepsy in childhood: a clinical and neurophysiological approach.

Resistant epilepsy is defined as the persistence of unacceptable seizures, despite correct drug treatment, or control of seizures at the cost of excessive side effects. About 30% of partial seizures are resistant to treatment; many of them is potentially a candidate for surgical treatment. Selection of patients is based fundamentally on precise identification of the epileptogenic area and on the evaluation that possible removal of that area will not be followed by serious neurological or neuropsychological deficits, or by onset of seizures in another part of the brain. To this end, careful clinical, neurophysiological and functional studies are conducted. Compared with adults, video-electroencephalographic (EEG) study of seizures in childhood is more difficult because of the lack of patient cooperation and, therefore, the lack of every subjective element in the seizures. Furthermore, the criteria for defining drug resistance in childhood are still under discussion, as many epilepsies are age dependent and seizures stop with growth. Despite this, the age at time of surgery has been steadily decreasing, in the conviction that the persistence of intractable partial epilepsy is detrimental to cognitive development and can damage brain areas that are apparently healthy. The clinical and EEG criteria for epilepsies that are secondary to some specific disorders have been defined, e.g. hemimegalencephalia and focal cortical dysplasias often produce epilepsy with onset in the first days of life characterized by partial seizures and subintrant spasms, EEG record of focal or hemispheric burst suppression and drug resistance that can be defined within the first months of life. Prolonged video-EEG monitoring is always necessary to establish congruence between the area in which the seizure originates and the brain lesion evidenced at neuroimaging. Correct monitoring of seizures means close cooperation between neurologist, neurophysiology technician and the patient, if the child is at least 5-6 y old. Absence of cooperation also limits the use of in-depth recording. Neuropsychological assessment of the child can be of great help in defining the area damaged by the epileptogenic site as well as the state of the other brain areas. Close cooperation between neurologist, radiologist, neuropsychologist and brain surgeon is necessary for a case-by-case assessment of indication for surgical treatment.

Experience with immunomodulatory treatments in Rasmussen's encephalitis.

The authors investigated immunomodulatory treatments in 15 patients with Rasmussen encephalitis (RE) (14 with childhood and one with adolescent onset RE). Positive time-limited responses were obtained in 11 patients using variable combinations of corticosteroids, apheresis, and high-dose IV immunoglobulins. Although surgical exclusion of the affected hemisphere is the only treatment that halts disease progression, immunomodulation can be considered when early surgery is not feasible, in late-onset patients with slower disease progression, and in the few cases of bilateral disease.

Video/EEG aspects of early-infantile epileptic encephalopathy with suppression-bursts (Ohtahara syndrome).

Early-infantile epileptic encephalopathy (EIEE) with suppression-bursts is a severe neonatal epileptic encephalopathy. The etiology is multiple, with cerebral malformations as the more frequent. We review the clinical and video/EEG aspects of eight infants with EIEE. These infants, aged between 4 and 70 days at the time of video/EEG recordings, were studied in relation to their clinical and video/EEG characteristics, evolution, persistence of suppression-burst pattern and etiology. Seven of the eight infants showed an ictal clinical sign correlated to the burst of the suppression-burst pattern, four of whom died within 11 months of age. The other three are alive. One, now aged 4 years, underwent surgery for hemimegalencephaly and is seizure-free, with good neurological outcome. One, now aged 9 months, was pyridoxine-dependent and she is seizure-free, and with normal neurological evolution under pyridoxine therapy. One, now aged 3 years and 9 months, is seizure-free, but with severe neurological and cognitive impairment. The only child who did not show a clinical ictal correlation of burst is also alive, now aged 3 years and 9 months, with drug-resistant epilepsy, and severe neurological and cognitive deficits. With regard to the etiology, three showed structural abnormalities, two more showed some signs of prenatal origin of neurological disease, and three had metabolic etiology. Our study confirms that EIEE is a severe age-dependent early epileptic encephalopathy. The etiology is mostly malformative. The prognosis is poor regarding motor and cognitive development, seizures, as well as life expectancies. The presence of an ictal burst of the suppression-burst pattern usually correlates with a negative outcome.

Reversible operculum syndrome caused by progressive epilepsia partialis continua in a child with left hemimegalencephaly.

In a child with left hemimegalencephaly and seizures, a reversible operculum syndrome developed when continuous epileptic discharges spread from the left hemisphere to the contralateral central regions. The operculum syndrome lasted for three months until left hemispherectomy was performed. Soon after surgery the seizures and the operculum syndrome resolved. The operculum syndrome is a facio-pharyngo-glosso-masticatory diplegia usually due to structural lesions in both opercular regions. The reversibility of the syndrome in the reported case demonstrates that the operculum syndrome is sometimes functional rather than lesional.