Hypnotic recall: a positive criterion in the differential diagnosis between epileptic and pseudoepileptic seizures

PURPOSE: Because the diagnosis of pseudoepileptic seizures (PESs) is mostly made by excluding epilepsy, availability of a positive criterion for PESs is of great importance. This study was aimed at the validation of a diagnostic technique that intends to provide in such a positive criterion. METHODS: In 17 patients with epileptic seizures (ESs) and 20 patients with PESs, a hypnotic procedure was performed by an investigator blind to other data to recover amnesia for the ictus. If recall was obtained, the experimental diagnosis PES was given; if not, ES was diagnosed. The experimental diagnoses were compared with the clinical, EEG-confirmed diagnoses. Hypnotizability was measured to determine the relation between the outcome of the test and hypnotizability of the patients. RESULTS: Recall for the ictus was obtained in 17 patients. Each of these had a clinical diagnosis of PES. Seventeen patients with "no recall" had a clinical diagnosis of ES, and three patients had PESs. This result yields a specificity of 100% and a sensitivity of 85% for the recall technique. Hypnotizability was significantly higher in patients with PESs than in patients with ESs. In some "low hypnotizables," recall was obtained, and in some "high hypnotizables," no recall was obtained. CONCLUSIONS: A positive recall test indicates PES. A sub-group of patients with PESs is characterized by a high level of hypnotizability. Hypnotizability is not crucial for outcome of the recall test. High hypnotic abilities are especially found in disorders in which it is supposed that "dissociation" is involved. It can be speculated that PES may be one of the dissociative phenomena.     

Reactive oxidant species in piriform cortex extracellular fluid during seizures induced by systemic kainic acid in rats

Kainic acid (KA) administered systemically to rats produces seizures and brain damage. We measured an increase in reactive oxidant species (ROS) during KA-induced seizures in the extracellular fluid (ECF) of the piriform cortex, a brain region known to be subsequently damaged. Intracerebral microdialysis samples were collected and assayed for isoluminol-dependent chemiluminescence before and after injection of KA (16 mg/kg, ip). Hydrogen peroxide (H₂O₂) concentrations were calculated from catalase-sensitive chemiluminescence, the difference between total and catalase-resistant chemiluminescence. During generalized tonic-clonic seizures, both total and catalase-resistant chemiluminescence increased significantly in samples from brain ECF. Catalase-resistant chemiluminescence, most likely produced by ascorbic acid, increased for a full hour during sustained seizure activity. H₂O₂ concentrations showed a trend towards elevation during seizures. Increased ROS suggest that oxidative stress occurs in brain ECF during sustained seizure activity.     

Epilepsies with astatic seizures of late onset.

In 17 patients with a long course of epilepsy astatic seizures became apparent after the age of 14 years. In the patients' childhood astatic seizures had not been observed. The patients suffered from epilepsies with absences and awakening grand mal or psychomotor fits and sleeping grand mal. The EEG revealed spike-wave variant and spike-and-wave complexes as in the Lennox-Gastaut syndrome. Age dependency of Lennox-Gastaut syndrome is discussed. The described type of epilepsy can be understood as a "Lennox-Gastaut syndrome of late onset".     

Seizures and civilian head injuries

Although several studies have reported on the risk of "early seizures" (seizures occurring within 7 days following a head injury), the reported proportions of patients experiencing these seizures vary from 1.4 to 15%. This wide divergence may be due to problems with methodology such as case selection and definitions of head injury and early seizures. In a series of 702 patients admitted with a head injury to Cook County Hospital (CCH), Chicago, Illinois, 29 (4.1%) had early seizures. This proportion is twice as high as one previously reported in a comparable series. This may reflect an actual difference between the two series or a case selection bias serving to elevate the proportion of patients with early seizures at CCH.     

Generation and propagation of 4-AP-induced epileptiform activity in neonatal intact limbic structures in vitro

We examined the generation, propagation and pharmacology of 4-aminopyridine (4-AP)-induced epileptiform activity (EA) in the intact interconnected limbic structure of the newborn (P0-7) rat in vitro. Whole-cell recordings of CA3 pyramidal cells and multisite field potential recordings in CA3, CA1, dentate gyrus, and lateral and medial entorhinal cortex revealed 4-AP-induced EA as early as P0-1. At this age, EA was initiated in the CA3 region and propagated to CA1, but not to the entorhinal cortex. Starting from P3-4, EA propagated from CA3 to the entorhinal cortex. Along the CA3 septo-temporal axis, EA arose predominantly from the septal pole and spread towards the temporal site. Whereas the onset of 4-AP-induced EA decreased with age from 21.2 +/- 1.6 min at P0-1 to 4.7 +/- 0.63 min at P6-7, the seizure duration increased in the same age groups from 98 +/- 14 s to 269.4 +/- 85.9 s, respectively. The EA was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not by DL-2-amino-5-phosphonovaleric acid (APV), (+)-MK-801 hydrogen maleate (MK-801) or (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG), suggesting that they were mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor activation. We conclude that: (i) the septal pole of the hippocampal CA3 region plays a central role in the generation of EA in the neonatal limbic system; and (ii) AMPA/kainate receptor-mediated EA can be generated in CA3 already at birth. Therefore, the recurrent collateral synapses and circuits required for the generation of EA are developed earlier than previously suggested on the basis of studies on hippocampal slices.     

In vivo and in vitro effects of melatonin or ganglioside GT1B on L-cysteine-induced brain mitochondrial DNA damage in mice.

The effects of L-cysteine on mitochondrial DNA (mtDNA) in mouse brain were investigated both in vivoandin vitro. An intracerebroventricular (icv) injection of L-cysteine (1.25 micromol/animal) caused mtDNA damage in brain frontal and central portions of the cortex, broad-spectrum limbic and severe sustained seizures in mice, and increased lipid peroxidation in the whole brain. The L-cysteine-mediated effects were prevented by an intraperitoneal (ip) preinjection of melatonin (20 mg/kg) or an intracerebroventricular preinjection of ganglioside GT1b (90 nmol/animal). Furthermore, in in vitroexperiments, L-cysteine (0.05, 0.5, or 1.0 mM) caused damage to brain mtDNA and increased lipid peroxidation in a concentration-dependent manner when incubated at 37 degrees C for 20 or 60 min with a homogenate prepared from whole mouse brains. However, the mtDNA damage and the increased lipid peroxidation were completely abolished by a cotreatment with melatonin (1.5 mM), a potent scavenger of the hydroxyl radical (*OH), or ganglioside GT1b (60 microM), a potent inhibitor of glutamate-receptor-mediated activation and translocation of protein kinase C and lipid peroxidation. These results suggest that reactive oxygen species including the *OH may be involved in l-cysteine-induced brain mtDNA damage, lipid peroxidation, and development of seizures in mice. Therefore, we concluded that *OH scavengers, such as the pineal hormone melatonin and ganglioside GT1b, can protect against brain mtDNA damage, seizures, and lipid peroxidation induced by reactive oxygen species producers such as L-cysteine.     

Proteus syndrome

Abstract: This female Asian (Malay) baby had clinical features of Proteus syndrome. She had a large right facial lipolymphangioma with hyperpigmentation of the overlying skin. There was a smaller lymphangioma over the left side of her neck with excess nuchal folds, macrodactyly and bilateral talipes equinovarus. Despite the extensive hemifacial swelling, there was no evidence of upper respiratory tract obstruction. Generalized seizures developed on the sixth day of life which were controlled with phenobarbital. The lymphangiomas were excised without recurrence.     

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies.

The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based.

Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered.

Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit.

Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy.

The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning.

Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenyítoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies.

Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance.

In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.

This Position Statement was drafted by JA Vale, EP Krenzelok, and GD Barceloux.