Patterns of prescription of antiepileptic drugs in patients with refractory epilepsy at tertiary referral centres in Italy.

PURPOSE: To evaluate the pattern of prescription of antiepileptic drugs (AEDs) and other medications in a representative population of patients with refractory epilepsy attending tertiary referral centres in Italy. METHODS: Descriptive analysis of data obtained at baseline from 933 adults and 191 children with refractory epilepsy enrolled consecutively in an observational study at 11 tertiary referral centres in Italy. Multivariate logistic regression analysis was used to assess predictors of utilization of the most commonly prescribed AEDs. RESULTS: Polytherapy was used in 79% of adults and 75% of children, with over one-third of adults and children being prescribed ≥3 AEDs. In adults, the most commonly used AEDs were levetiracetam (35%), carbamazepine (34%) and lamotrigine (30%). In children, valproic acid was by far the most commonly used AED (46%), followed by carbamazepine (27%), topiramate (21%), and phenobarbital (20%). The most common AED in partial epilepsy was carbamazepine (331 out of 893 patients, 37%), followed by levetiracetam (33%) and lamotrigine (26%). In generalized or undetermined epilepsies, the AEDs most commonly used were valproic acid (139 out of 223 patients, 62%), lamotrigine (33%) and levetiracetam (28%). Second generation AEDs were prescribed in 81% of adults and 54% of children. Comedications used for indications other than epilepsy were used by 32% of adults and 17% of children. CONCLUSIONS: Prescription patterns were consistent with current evidence about the spectrum of efficacy of individual AEDs in different epilepsy syndromes. The high prevalence of polytherapy, including combinations of three or more AEDs, is a cause for concern.

Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs.

PURPOSE: Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. METHODS: Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. RESULTS: Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm]. DISCUSSION: Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

A de novo 11p12-p15.4 duplication in a patient with pharmacoresistant epilepsy, mental retardation, and dysmorphisms.

We report a 22-year-old male patient with pharmacoresistant epilepsy, mental retardation and dysmorphisms. Standard cytogenetic analysis revealed a de novo interstitial duplication of the short arm of chromosome 11 (11p). High density array-CGH analysis showed that the rearrangement spans about 35Mb on chromosome 11p12-p15.4. Duplications of 11p are rare and usually involve the distal part of the chromosome arm (11p15), being not associated with epilepsy, whereas our patient showed a unique epileptic phenotype associated with mental retardation and dysmorphic features. The role of some rearranged genes in epilepsy pathogenesis in this patient is also discussed.

Severe pulmonary congestion in a near miss at the first seizure: further evidence for respiratory dysfunction in sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is the most important direct seizure-related cause of death, and most cases usually occur in patients with intractable, longstanding epilepsy. Suspected mechanisms for SUDEP include central and obstructive apnea, cardiac arrhythmia, postictal respiratory arrest, and primary cessation of brain activity. We report a patient who experienced a near SUDEP following his first prolonged tonic-clonic seizure requiring intubation. Chest X-ray examination showed severe bilateral congestion of the middle and superior pulmonary fields and an enlarged heart. Observations of pulmonary compromise in near-miss patients are extremely rare. Our patient showed marked cyanosis and respiratory distress after the index seizure, in agreement with the view that respiratory distress was the primary etiology in this case. Moreover, this observation confirms that SUDEP is not exclusively an issue for patients with chronic, uncontrolled epilepsy.

Hyperhomocysteinemia and retinal vascular changes in patients with epilepsy.

The possible occurrence of asymptomatic retinal vascular damage was investigated in 87 hyperhomocysteinemic (plasma total homocysteine >13micromol/L) adult epileptic patients (46 M, 41 F; age 34.2+/-7.5 years; mean plasma homocysteine levels 29.8+/-15.4micromol/L; duration of epilepsy 11.5+/-2.4 years) with no other risk factors for atherosclerosis. Plasma total homocysteine (t-Hcy) levels were assayed by high performance liquid chromatography. Retina vascular status was assessed by fundus oculi ophthalmoscopy performed in blind conditions by two skilled ophthalmologists and compared with that obtained from 102 randomly chosen epileptic patients and 94 healthy subjects, matched for age and sex, showing normal t-Hcy levels. No retina abnormality was detected in any of the subjects belonging to the three groups. Based on these results, we conclude that epileptic patients with mild to intermediate hyperhomocysteinemia are not at risk to develop retinal vascular disease.

Familial mesial temporal lobe epilepsy (FMTLE) : a clinical and genetic study of 15 Italian families.

INTRODUCTION: Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. PATIENTS AND METHODS: FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. RESULTS: Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. DISCUSSION: FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.

Life-threatening status epilepticus following gabapentin administration in a patient with benign adult familial myoclonic epilepsy.

We report the case of a 57-year-old man who experienced life-threatening myoclonic status after the administration of gabapentin. Based on familial data, the patient was determined to be a member of a previously described family with benign adult familial myoclonic epilepsy (BAFME). The myoclonic status did not respond to benzodiazepines, but resolved after discontinuing the gabapentin. As for other idiopathic generalized epilepsies, gabapentin may precipitate myoclonic status in a benign syndrome, such as BAFME, as is reported herein for the first time. A correct diagnosis and prompt discontinuation of the drug may reverse a potentially severe, life-threatening condition.