Paraoxonase (PON) is a liver protein with hydrolase activity that is released into the blood stream. Paraoxonase may serve as an index of liver function because it is drastically reduced in chronic liver damage. Sixty-seven periparturient dairy cows were used to evaluate the relationship between plasma PON, health problems, inflammatory conditions, and liver function. Baseline plasma PON concentrations during the first 30 d in milk (DIM) were retrospectively used to group cows into quartiles. Metabolic profile, lipid metabolites (e.g., nonesterified fatty acids, beta-hydroxybutyrate), inflammatory indices (haptoglobin, ceruloplasmin), low and high density lipoprotein cholesterol, vitamin A, vitamin E, reactive oxygen metabolites, total antioxidants, and PON in plasma were measured 2 wk before to 8 wk after calving. Weekly milk yield, body condition score, and all health problems were recorded. After parturition (7 DIM), cows in the lower PON group had the lowest plasma concentrations of negative acute phase proteins compared with the higher PON group for retinol binding protein (23.2 +/- 2.86 vs. 36.0 +/- 2.96 microg/dL of vitamin A), albumin (31.6 +/- 0.73 vs. 33.9 +/- 0.75 g/L), total cholesterol (2.04 +/- 0.30 vs. 2.45 +/- 0.42 mmol/L), and the highest concentrations of haptoglobin (0.67 vs. 0.24 +/- 0.03 g/L; positive acute phase protein) and globulins (37.2 vs. 32.3 +/- 1.4 g/L). Plasma bilirubin was highest in the cows (10.1 vs. 6.2 +/- 0.6 micromol/L) in the lowest PON quartile. Plasma PON was negatively correlated with haptoglobin (r = -0.39) and bilirubin (r = -0.42) and positively correlated with retinol binding protein (r = 0.54), albumin (r = 0.38), and cholesterol (r = 0.55) fractions. A total of 82.3% of cows in the lower quartile and no cows in the upper quartile experienced serious inflammation. Lower quartile cows produced 28.1 +/- 10.3 kg of milk/d; whereas upper quartile cows produced 38.3 +/- 7.7 kg of milk/d during the first 30 DIM. A reduction in the ability of the liver to cope with the increased metabolic demand near parturition in dairy cows can be diagnosed using changes in baseline plasma PON.

We studied 10 neurologically normal patients (8 females, 2 males) aged 8-30 years (mean 17 years) who had recurrent episodes if visually induced occipital seizures. Television and computer screens were the main triggers. Seizure onset occurred between the ages of 5 and 17 years (mean 11 years). All seizures were stimulus related and began with elementary visual symptoms, followed in most patients by a slow clustering of cephalic pain, epigastric discomfort, and vomiting, with either normal of only mildly impaired responsiveness. EEG features included normal background activity, occipital spikes and waves, and a photoparoxysmal response which could be occipital, generalized, or both. Four patients also showed spontaneous generalized epileptiform abnormalities, and 3 had rolandic spikes. An Oz electrode was critical in identifying epileptiform activity in some patients. Complete seizure control was achieved in most patients with monotherapy, although occasional stimulus-related seizures occurred in 3 patients who showed a wider range of photosensitivity. These patients have an idiopathic localization-related epilepsy with age-related onset and specific mode of precipitation. Although this type of epilepsy has been reported previously, it has remained underrecognized, probably because it is difficult to differentiate clinically from migraine or from nonreflex childhood idiopathic occipital epilepsy.

Summary:Purpose: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotypegenotype correlations with SCN1A alterations.Methods: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients.Results: We classified patients as: SMEI/SMEB = 55; GEFS+ = 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations.Conclusion: We obtained a frequency of 71% SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes. Key Words: SMEI-GEFS+-SCN1A-Fever-provoked seizures-MLPA.Mutations in the gene coding for the α1 subunit of the neuronal sodium channel (SCN1A) have been associated with various types of epilepsy. SCN1A abnormalities have been found in about 5-10 % of generalized

PCDH19 is emerging as a major gene for infantile-onset familial or sporadic epilepsy in female patients with or without mental retardation. In our cohort, epileptic encephalopathy with DS-like features and focal epilepsy of variable severity were the associated phenotypes and were equally represented.