Phenytoin intoxication associated with omeprazole administration in a child with defective CYP2C9.

Adverse drug reactions occur at a high rate in hospitalized children, frequently due to antiepileptic drug administration. Phenytoin is a commonly used drug, and its metabolism is mediated by a specific cytochrome-P450 isoform, CYP2C9, which is encoded by a polymorphic gene. It is worth noting that very frequently administered drugs, such as proton pump inhibitors, compete with phenytoin for CYP2C19-mediated metabolism. Here we describe a case of phenytoin intoxication in a child with defective CYP2C9, after omeprazole administration.

Improved pan-specific MHC class I peptide-binding predictions using a novel representation of the MHC-binding cleft environment.

Major histocompatibility complex (MHC) molecules play a key role in cell-mediated immune responses presenting bounded peptides for recognition by the immune system cells. Several in silico methods have been developed to predict the binding affinity of a given peptide to a specific MHC molecule. One of the current state-of-the-art methods for MHC class I is NetMHCpan, which has a core ingredient for the representation of the MHC class I molecule using a pseudo-sequence representation of the binding cleft amino acid environment. New and large MHC-peptide-binding data sets are constantly being made available, and also new structures of MHC class I molecules with a bound peptide have been published. In order to test if the NetMHCpan method can be improved by integrating this novel information, we created new pseudo-sequence definitions for the MHC-binding cleft environment from sequence and structural analyses of different MHC data sets including human leukocyte antigen (HLA), non-human primates (chimpanzee, macaque and gorilla) and other animal alleles (cattle, mouse and swine). From these constructs, we showed that by focusing on MHC sequence positions found to be polymorphic across the MHC molecules used to train the method, the NetMHCpan method achieved a significant increase in the predictive performance, in particular, of non-human MHCs. This study hence showed that an improved performance of MHC-binding methods can be achieved not only by the accumulation of more MHC-peptide-binding data but also by a refined definition of the MHC-binding environment including information from non-human species.

Primary headache pathophysiology in children: the contribution of clinical neurophysiology.

Although primary headaches are very prevalent also in pediatric age, most neurophysiologic studies in these diseases concerned only the adulthood. The neurophysiologic investigation of the pathophysiological mechanisms subtending migraine and tension-type headache in children and adolescents could be particularly interesting, since during the developmental age the migrainous phenotype is scarcely influenced by many environmental factors that can typically act on adult headache patients. The neurophysiologic abnormality most frequently found in adult migraineurs, that is the reduced habituation of evoked potentials, was confirmed also in migraine children, although it was shown to involve also children with tension-type headache. Some studies showed abnormalities in the maturation of brain functions in migraine children and adolescents. While the visual system maturation seems slowed in young migraineurs, the psychophysiological mechanisms subtending somatosensory spatial attention in migraine children are more similar to those of healthy adults than to those of age-matched controls. There are some still unexplored fields that will have to be subjects of future studies. The nociceptive modality, which has been investigated in adult patients with primary headaches, should be studied also in pediatric migraine. Moreover, the technique of transcranial magnetic stimulation, not yet used in young migraineurs, will possibly provide further elements about brain excitability in migraine children.

Current practice of brain death determination and use of confirmatory tests in an Italian University hospital: a report of 66 cases.

BACKGROUND: Time to final brain death (BD) determination is fundamental to rapidly identify donors without organ deterioration. Guidelines for BD determination are different from country to country and, through years, they have been subjected to several revisions, to simplify the procedure. The aim of this study was to describe a one-year experience according to the latest Italian Guidelines for BD in our University hospital and to focus on timing of final BD declaration according to the ancillary tests executed. METHODS: Sixty-six consecutive inpatients with BD diagnosis were enrolled. Etiological factors, ancillary tests and timing to final declaration were analyzed. RESULTS: Electroencephalogram (EEG) could be performed without artifacts in all the patients. Time to BD procedure starting depended on whether the demonstration of cerebral circulatory arrest was required, being shorter with EEG only (40±17 min), longer with cerebral blood flow evaluation (175±95 min), minimal with transcranial Doppler (83±32 min), maximal with angiography (165±20 min). None of the patients who initiated BD procedure were found to recover cerebral or brainstem function at the second observation. CONCLUSIONS: In Italy, the same guidelines ensure the same approach in every hospital, with multi-specialist cooperation. The EEG is mandatory and prompt recognition of the first, flat EEG is fundamental to reduce time to the final procedure. A multimodal neurophysiological approach with trained specialists, neurosonologists and monitoring devices in intensive care units may represents a valid help to further reduce time for BD diagnosis.

Advantages and pitfalls of three-dimensional ultrasound imaging of carotid bifurcation.

OBJECTIVES: Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. METHODS: Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. RESULTS: Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. CONCLUSIONS: 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course 'at a glance'. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.

EEG patterns and epileptic seizures in acute phase stroke.

BACKGROUND: The rate of early post-stroke epileptic seizures ranges from 2 to 33%. This wide range is likely due to differences in study design, patient selection and type of neurophysiological monitoring. Electroencephalography (EEG), which is not used in the routine work-up of acute stroke, is the best neurodiagnostic technique for detecting epileptic activity, especially in patients with non-convulsive post-stroke epileptic activity. The aim of this study was to analyze patterns on EEGs performed within 24 h of stroke onset, and to investigate correlations between these patterns and the occurrence of early epileptic seizures and status epilepticus (SE), vascular risk factors, stroke subtypes and short-term outcome. METHODS: We prospectively studied 232 patients (mean age 71 ± 12 years; 177 ischemic strokes and 55 hemorrhagic). EEG recording was performed within 24 h from hospitalization. The follow-up lasted 1 week. RESULTS: Fifteen patients (6.5%) had early seizures within 24 h; 10 of these patients had focal SE with or without secondary generalization. EEG revealed sporadic epileptiform focal abnormalities in 10% and periodic lateralized epileptiform discharges (PLEDs) in 6%. SE was recorded in 71.4% of patients with PLEDs. At the multivariate analysis, only early epileptic manifestations (p < 0.001) were independently associated with PLEDs. CONCLUSIONS: Our study confirms that seizures are not frequent in the early phase of acute stroke and occur prevalently as focal SE at onset. EEG may help to detect specific patterns, such as PLEDs, that are closely related to early seizures. EEG monitoring should be performed in order to detect purely electrographic seizures.

Combined transcranial Doppler and EEG recording in vasovagal syncope.

BACKGROUND: In neurally mediated syncope a 'typical' EEG pattern during hyperventilation (HV) may be observed. This study aimed to investigate transcranial Doppler (TCD) and EEG variations in response to hyper- and hypocapnia using simultaneous recording. METHODS: Syncope patients with a typical EEG pattern during HV (SEEG+, n = 15) and those without abnormalities (SEEG-, n = 16) were compared with healthy controls (n = 20). Simultaneous TCD and EEG recordings were performed at rest (baseline), during 2 apnea tests and during HV. Cerebrovascular vasoreactivity, index for hypocapnia, total vasomotor reserve and time to flow velocity normalization after HV (t-norm) were recorded. RESULTS: With TCD, a reduction in Vasomotor reserve was observed in SEEG+ compared with the other 2 groups (control: 67 +/- 8%; SEEG-: 67 +/- 10%; SEEG+: 57 +/- 8%; p < 0.0001). t-norm was longer in all syncopal patients and in particular in SEEG+ (control: 20.2 +/- 3 s; SEEG-: 40 +/- 7 s; SEEG+: 123 +/- 45s; p < 0.0001). Quantitative EEG showed an increase in slow bands in all subjects during HV, small and nonsignificant in controls and SEEG-, higher and significant in SEEG+, related with flow reduction. CONCLUSIONS: Changes in the sympathetic modulation of cerebral vasoconstriction may explain both the pathophysiology of vasovagal syncope and the typical paroxysmal EEG findings.

Chromatic modulation of luminance visual evoked potential latencies in healthy subjects and patients with mild vision disorders.

OBJECTIVE: To study whether and how color modulates luminance visual evoked potentials (VEPs). METHODS: We studied pattern-reversal luminance VEPs to red/black and blue/black checkerboards with identical luminance contrast values (mixed luminance and chromatic components) (isocontrast color VEP, in brief, IVEPs) in 25 healthy subjects and two groups of patients with mild vision disorders (23 with glaucoma and 25 with optic neuritis). We then compared these with the standard color VEPs to pure chromatic contrast red/green and blue/yellow gratings (CVEPs). RESULTS: In healthy subjects, VEPs to red/black checkerboards and red/green gratings were slower than those obtained with blue/black checkerboards and blue/yellow gratings. Both procedures (IVEPs and CVEPs) differentiated patients with vision disorders from healthy subjects and distinguished between the two different vision disorders. Red/black checkerboards and red-green gratings elicited slower VEPs in patients with optic neuritis and blue/black checkerboards and blue/yellow gratings elicited slower VEPs in patients with glaucoma. IVEPs appeared more stable and ample than CVEPs. The contrast indices normalized CVEP and IVEP latencies in the same subject and showed a positive correlation between CVEP and IVEP latencies in healthy subjects and in patients with optic neuritis, but not in patients with glaucoma. CONCLUSIONS: Our study confirms the usefulness of CVEPs in detecting and differentiating mild vision disorders. IVEPs to colored pattern-reversal luminance checkerboards are equally effective in distinguishing between various vision disorders possibly because colors can modulate VEP latencies to luminance contrast stimuli. SIGNIFICANCE: IVEPs can be useful in differentiating the various vision disorders and are easier than CVEPs to test in a routine clinical setting.

Luminance and chromatic visual evoked potentials in type I and type II diabetes: relationships with peripheral neuropathy.

The objective of the study was to investigate the subclinical visual deficit in type I and II diabetes, and its relationship with peripheral neuropathy. Thirty-two healthy volunteers, 20 patients with type I diabetes and 30 patients with type II diabetes were studied in a clinical neurophysiology setting. Luminance (VEPs) and chromatic visual evoked potentials (CVEPs) were recorded, with white-black, grey-black, red-green and blue-yellow sinusoidal gratings. The peak latencies of the VEP positive wave and CVEP negative wave were recorded. Ten patients with type I and 8 with type II diabetes had peripheral neuropathy. VEPs were slower in patients with type II diabetes and CVEPs were slower in patients with type I and type II diabetes than in controls. Blue-yellow CVEPs were slower in type II than in type I diabetes. VEPs and red-green CVEPs were slower in patients with diabetes with neuropathy than in those without. In conclusion, we found that visual system impairment differs in diabetes with and without peripheral neuropathy.