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Familial adult myoclonus epilepsy (FAME) is an autosomal dominant condition characterized by the association of myoclonic tremor and epilepsy mainly with onset in adulthood. The clinical course is non‐progressive or slowly progressive, as epilepsy is commonly controlled with appropriate antiseizure medication and individuals have a normal life expectancy. However, the myoclonus severity increases with age and leads to some degree of disability in the elderly. Because the non‐coding repeat expansions responsible for FAME are not detected by routine genetic tests being used at this time, a clinical diagnosis accompanied by neurophysiological testing remains essential to guide the geneticist on the selection of the specific genetic technique. [ABSTRACT FROM AUTHOR]

Objective: Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy characterized by auditory symptoms. Two genes, LGI1 and RELN, encoding secreted proteins, are implicated in the etiology of ADLTE, but half of the affected families remain genetically unsolved, and the underlying molecular mechanisms are yet to be clarified. We aimed to identify additional genes causing ADLTE to better understand the genetic basis and molecular pathway underlying this epileptic disorder.Methods: A cohort of Italian ADLTE families was examined by whole exome sequencing combined with genome-wide single-nucleotide polymorphism-array linkage analysis.Results: We identified two ADLTE-causing variants in the MICAL-1 gene: a p.Gly150Ser substitution occurring in the enzymatically active monooxygenase (MO) domain and a p.Ala1065fs frameshift indel in the C-terminal domain, which inhibits the oxidoreductase activity of the MO domain. Each variant segregated with ADLTE in a single family. Examination of candidate variants in additional genes excluded their implication in ADLTE. In cell-based assays, both variants significantly increased MICAL-1 oxidoreductase activity and induced cell contraction in COS7 cells, which likely resulted from deregulation of F-actin dynamics.Interpretation: MICAL-1 oxidoreductase activity induces disassembly of actin filaments, thereby regulating the organization of the actin cytoskeleton in developing and adult neurons and in other cell types. This suggests that dysregulation of the actin cytoskeleton dynamics is a likely mechanism by which MICAL-1 pathogenic variants lead to ADLTE. Ann Neurol 2018;83:483-493. [ABSTRACT FROM AUTHOR]

Gelastic seizures, usually with onset in early infancy, are the hallmark manifestation of hypothalamic hamartoma. This seizure type is directly generated by hamartoma itself, intrinsically epileptogenic because of its anatomofunctional organization. Other types of seizures, focal or generalized, may appear during the evolution, probably resulting from mechanisms of secondary epileptogenesis. Nevertheless, the clinical expression and the severity of the syndrome, ranging from a focal drug-resistant epilepsy to a catastrophic generalized encephalopathy with severe cognitive and behavioral impairments, depends on the size and the site of attachment of the hamartoma. Early suspicion, timely diagnosis, and appropriate treatment are mandatory to reverse a potential catastrophic evolution of this condition. [ABSTRACT FROM AUTHOR]

Mutations in the DEPDC5 ( DEP domain-containing protein 5) gene are a major cause of familial focal epilepsy with variable foci ( FFEVF) and are predicted to account for 12-37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy ( ADLTE) or familial mesial temporal lobe epilepsy ( FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected members, clinically classified as FMTLE. The proband had temporal lobe seizures with prominent psychic symptoms (déjà vu, derealization, and forced thoughts); her mother had temporal lobe seizures, mainly featuring visceral epigastric auras and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies. [ABSTRACT FROM AUTHOR]

Objective To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy. Methods Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory- II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values. Results Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug ( AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers. Significance Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common presentations associated with chromosome aberrations. Detailed descriptions of some aberration-specific epileptic and electroencephalographic (EEG) phenotypes have been reported (i.e., Angelman syndrome, ring 20 etc.). However there is limited and mixed information about the characteristics of epilepsy related to trisomy 18. Thus a common seizure phenotype has not been characterized yet. Here we describe in detail a patient with refractory epilepsy and partial 18q trisomy. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective Autosomal dominant lateral temporal epilepsy ( ADLTE) is a focal epileptic syndrome characterized by auditory or aphasic auras. Mutations in the LGI1 gene account for <50% of ADLTE families. To identify copy number variants ( CNVs) related to ADLTE, we examined a collection of ADLTE families without LGI1 mutations. Methods Twenty-one families were included based on a history of focal seizures with auditory and/or receptive aphasic symptoms in two or more individuals, absence of brain abnormalities, and negative LGI1 test. DNA suitable for single nucleotide polymorphism-array analysis was genotyped using the high-density HumanOmni1-Quad v1.0 beadchip (Illumina). CNVs were inferred using the Penn CNV algorithm. Selected CNVs were validated by real-time quantitative polymerase chain reaction (q PCR). Results We analyzed 62 affected and 114 unaffected members of our study families and identified a total of 11,214 CNVs, corresponding to 1,890 unique regions with an average size of 67.3 kb. Most CNVs were <50 kb, whereas a small proportion (1.2%) exceeded 500 kb. We identified 12 rare CNVs that segregated with lateral temporal epilepsy in single families. Particularly, we found rare microdeletions within or near two genes, RBFOX1 and NRXN1, previously shown to harbor deletions associated with idiopathic generalized epilepsy, and a microduplication in the proximal region of chromosome 1q21.1, where duplications have been associated with various neurodevelopmental disorders and epilepsy. We also found numerous polymorphic CNVs in the affected members of one or more families, including a deletion of the PCDHA8/10 genes, which was enriched in the patients of our family cohort. Significance Our results provide clues on genes for susceptibility to ADLTE, particularly in those families where the inheritance pattern is less compatible with autosomal dominance. Some of these genes also confer risk for other epilepsy syndromes. [ABSTRACT FROM AUTHOR]

There has been increased interest in a possible association between epilepsy channelopathies and cardiac arrhythmias, such as long QT syndrome ( LQTS). We report a kindred that features LQTS, idiopathic epilepsy, and increased risk of sudden death. Genetic study showed a previously unreported heterozygous point mutation (c.246T>C) in the KCNH2 gene. Functional studies showed that the mutation induces severe loss of function. This observation provides further evidence for a possible link between idiopathic epilepsy and LQTS. [ABSTRACT FROM AUTHOR]

15q.13.3 microdeletion has been described in a variety of neurodevelopmental disorders. Epilepsy appears to be a common feature and, specifically, the 15q13.3 microdeletion is found in about 1% of patients with idiopathic generalized epilepsy. Recently, absence seizures with intellectual disability ( ID) have been reported in patients carrying this mutation. We describe two families in which several affected members carry a 15q13.3 microdeletion in a pattern suggestive of autosomal dominant inheritance. Their phenotype includes mainly absence epilepsy and mild ID, suggesting only similarities with genetic/idiopathic generalized epilepsies but not typical features. The importance of studying such families is crucial to broaden the phenotype and understand the long-term outcome of patients with this condition. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Autosomal dominant lateral temporal epilepsy (ADTLE) is an inherited epileptic syndrome characterized by ictal auditory symptoms or aphasia, negative MRI findings, and relatively benign evolution. Mutations responsible for ADLTE have been found in the LGI1 gene. The functions of the Lgi1 protein apparently are mediated by interactions with members of the ADAM protein family: it binds the postsynaptic receptor ADAM22 to regulate glutamate-AMPA currents at excitatory synapses and also the ADAM23 receptor to promote neurite outgrowth in vitro and dendritic arborization in vivo. Because alteration of each of these neuronal mechanisms may underlie ADLTE, ADAM22 and ADAM23 are candidate genes for this syndrome. In a previous work, we excluded a major role of ADAM22 in the aetiology of ADLTE. Here, we performed linkage analysis between microsatellite markers within or flanking the ADAM23 gene and ADLTE in 13 Italian families. The results exclude ADAM23 as major causative gene for ADLTE. [ABSTRACT FROM AUTHOR]

The characteristics of 1,124 consecutive adults and children with refractory epilepsy attending 11 tertiary referral centers in Italy were investigated at enrollment into a prospective observational study. Among 933 adults (age 16–86 years), the most common syndromes were symptomatic (43.7%) and cryptogenic (39.0%) focal epilepsies, followed by idiopathic (8.1%) and cryptogenic/symptomatic generalized (6.2%) epilepsies. The most common syndrome among 191 children was symptomatic focal epilepsy (35.1%), followed by cryptogenic focal (18.8%), cryptogenic/symptomatic generalized (18.3%), undetermined whether focal or generalized (16.8%), and idiopathic generalized (7.3%). Primarily and secondarily generalized tonic–clonic seizures were reported in 27.8% of adults and 16.8% of children. The most commonly reported etiologies were mesial temporal sclerosis (8.0%) and disorders of cortical development (6.2%) in adults, and disorders of cortical development (14.7%) and nonprogressive encephalopathies (6.8%) in children. More than three-fourths of subjects in both age groups were on antiepileptic drug (AED) polytherapy. [ABSTRACT FROM AUTHOR]

: 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. : Patients 18–50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B12, 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. : 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 μm; physiologic range 5–13 μm] 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) μm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) μm]. : 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. [ABSTRACT FROM AUTHOR]

A 22-year-old girl presented with convulsive status epilepticus and a previous history of recurrent seizures, myoclonus, ataxia and impaired cognitive functions. Neurological examination revealed rest and action-induced myoclonus, pyramidal signs and opposition hypertonia. Testing revealed severe metabolic acidosis, elevated transaminases and creatine kinase, and respiratory insufficiency. After intubation and ventilation, thiopental was introduced but the patient's condition worsened dramatically with death in a few hours. Autopsy showed profuse periodic acid-Schiff (PAS) positive intracellular inclusions in the CNS (Lafora bodies), most abundant in thalamus, cerebellum, and brainstem, as well as in other organs. Genetic testing revealed a homozygous missense mutation (c.205C > G, P69A) in the EPM2B (NHLRC1) gene, confirming the diagnosis of progressive myoclonic epilepsy Lafora-type. [ABSTRACT FROM AUTHOR]

: To investigate the neurochemical pattern in patients with benign adult familial myoclonic epilepsy (BAFME/FAME), an inherited form of myoclonic epilepsy, by proton magnetic resonance (MR) spectroscopy (1H-MRS). : Eleven BAFME patients from three families showing linkage to 2p11.1-q12.2 were compared with 11 age-matched healthy control subjects. : MR imaging of all the patients and healthy subjects exhibited no structural abnormalities on detailed visual assessment. However, compared with healthy subjects, patients with BAFME displayed elevated choline/creatine ratio in the cerebellar cortex (p = 0.01), whereas there was no significant difference for the other ratios. No 1H-MRS values in the frontal and occipital cortex differed significantly in the patients compared with the healthy controls. No correlation was detected between 1H-MRS values and disease duration (p = −0.35) as well as myoclonus severity (p = −0.48). : Our findings suggest that the cerebellum is a prominent site of dysfunction in BAFME. The abnormal choline concentrations could reflect changes in the chemical and functional nature of cell membranes. 1H-MRS was able to detect brain changes also in patients with recent disease onset and may be a useful tool supporting the diagnosis based on familial and electrophysiologic data. The relationship between cortical tremor and the cerebellum is also discussed. [ABSTRACT FROM AUTHOR]

This retrospective study aims to review the electroclinical features of patients presenting with eyelid myoclonia (EM) with and without absences. The Italian chapter of the International League Against Epilepsy (ILAE) has been conducting an electroclinical study of patients with EM. Among these, we searched for and selected the patients presenting with both impairment of intellectual functions and a peculiar ictal electroencephalography (EEG) pattern, that is, a discharge of fast generalized polyspikes/polyspikes and waves. We found 18 patients matching this electroclinical picture. All the patients were photosensitive. All of them had associated generalized, mostly nocturnal, tonic–clonic seizures. During the evolution, 13 patients presented episodes of EM status. Despite adequate antiepileptic treatment, the patients remained drug resistant for many years or throughout the evolution. The degree of impairment of intellectual functions varied from borderline level to moderate mental retardation. The patients we described herein can be considered a homogeneous group in the more heterogeneous group of patients presenting with EM. Further clinical and, more probably, genetic studies will clarify whether this condition could be considered a specific and homogeneous condition in the more heterogeneous group of patients presenting with EM. [ABSTRACT FROM AUTHOR]

Eyelid myoclonia with absences (EMA), or Jeavons syndrome, is a generalized epileptic condition clinically characterized by eyelid myoclonia (EM) with or without absences, eye closure-induced electroencephalography (EEG) paroxysms, and photosensitivity; in addition, rare tonic–clonic seizures may also occur. Although first described in 1977 and widely reported by several authors within the last few years, EMA has not been yet recognized as a definite epileptic syndrome. However, when strict criteria are applied to the diagnosis, EMA appears to be a distinctive condition that could be considered a myoclonic epileptic syndrome, with myoclonia limited to the eyelids, rather than an epileptic syndrome with absences. [ABSTRACT FROM AUTHOR]

Hypothalamic hamartoma (HH) is the pathologic hallmark of a spectrum of epileptic conditions, ranging from a mild form of epilepsy, whose seizures are an urge to laugh without cognitive defects, to the fully developed syndrome of early onset gelastic seizures (GS) associated with precocious puberty and the evolution to a catastrophic epilepsy syndrome. However, a refractory focal or generalized epilepsy develops during the clinical course in nearly all cases. Neurophysiologic and neuroimaging studies have assessed the role of HH in the generation of the GS as well as in the process of secondary epileptogenesis. Electrophysiologic properties of small γ-aminobutyric acid (GABA)ergic, spontaneously firing neurons might explain the intrinsic epileptogenicity of HH. Surgical ablation of the HH can reverse both epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery can be useful and safe approaches for treatment, in particular of small HH. [ABSTRACT FROM AUTHOR]

Transient epileptic amnesia (TEA) is a distinct neurologic condition occurring in late-middle/old age and presenting with amnesic attacks of epileptic nature and interictal memory disturbances. For many years this condition has been associated with the nonepileptic condition of transient global amnesia (TGA) and still today is poorly recognized by clinicians. Despite the clinical and laboratory findings that distinguish TEA from TGA, differential diagnosis may be difficult in the individual patient. Every effort must be employed for an early diagnosis, since antiepileptic treatment may readily control both ictal episodes and memory disturbances. [ABSTRACT FROM AUTHOR]

Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure-induced EEG paroxysms, and photosensitivity. We conducted an open-label trial of levetiracetam in EMA. : Patients were recruited in different Italian Epilepsy Centres. Levetiracetam was administrated at starting dose of 10 mg/kg/day up to 50–60 mg/kg/day in two doses. Treatment period included a 5–6 week up-titration phase and a 12-week evaluation phase. The number of days with EM (i.e., days with seizures, DwS) and number of generalized tonic–clonic seizures (GTCS) were evaluated. Analysis of intent-to-treat population was performed using Fisher's and Wilcoxon tests. : Thirty-five patients (23 F) with a mean age of 19 ± 6 years were recruited. Twenty-seven had previously undergone one to five adequate trials of antiepileptic drugs. The median number of DwS/month was 12 ± 8.2. Twenty-one patients experienced GTCS (median number/month: 1 ± 0.2). Thirty-four subjects completed the trial. Levetiracetam was well tolerated (mean dose: 1985 mg/day). Responders were 28/35 (80%) patients, nine taking levetiracetam as monotherapy. Six patients were seizure-free, 15 had ≥75% and seven >50% seizure reduction. GTCS remitted in 14 out of 21 (66.6%) patients. The number/month of DwS (median: 12 vs 5; p = 0.0001) and of GTCS (median: 1 vs 0; p = 0.0001) decreased compared to baseline period. Disappearance or clear reduction in paroxysmal abnormalities at eye closure occurred in 20 of the responders and photoparoxysmal response in 19. Mean follow-up was 23.9 ± 18.5 months. : Levetiracetam is effective and well tolerated in EMA. Placebo-controlled studies should confirm these findings. [ABSTRACT FROM AUTHOR]

We describe a case of adult-onset biphasic Rasmussen's encephalitis who presented seizures and left dyskinesias at the onset and, after 1 year, language disorder. Serial MRI and [(18)F] FDG-PET scans were performed showing involvement of the right cerebral hemisphere in the first phase and of the contralateral one in the second. [ABSTRACT FROM AUTHOR]

The influence of antiepileptic drugs (AEDs) and/or common polymorphisms (677C → T, 1298A → C) of the methylene-tetrahydrofolate-reductase (MTHFR) gene on the recurrence time of hyper-total-homocysteinemia (tHcy > 13 μmol/L) was investigated in 59 hyper-homocysteinemic patients (34M/25F, 20–49 years). Plasma tHcy and folate were assayed before and after 1-month folate supplementation (5mg/day), and after 2, 4, and 6 months. Four MTHFR polymorphism groups were identified with the following tHcy (μmol/L) and folate (nmol/L) levels (mean ± SD): (a) MTHFR677TT/1298AA, 24 patients, 36.0 ± 4.8, 4.1 ± 0.7; (b) MTHFR677CT/1298AC 27.1 ± 2.7, 5.3 ± 1.0 (n = 15); (c) MTHFR677CT/1298AA 16.6 ± 3.6, 6.8 ± 1.0 (n = 11), all taking enzyme-inducing AEDs; and (d) MTHFR677TT/1298AA 24.5 ± 3.2, 5.6 ± 1.1 (n = 9), treated with new AEDs. After folate therapy, plasma t-Hcy and folate were normal in all patients. At 6 months, 43 patients (72.9%) exhibited hyper-tHcy, the greater proportion belonging to the EI-AED-MTHFR677TT/1298AA (39%). Knowledge of the hyper-tHcy recurrence time after folate therapy discontinuation may help in optimizing folate supplementation pulses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To describe the semiological features of auditory aura and to assess their possible lateralizing value in partial epilepsy. Methods: Out of a series of 8,000 patients with epilepsy, we investigated 121 cases with partial seizures in whom auditory features were the first ictal symptom. According to the dominant type of aura, patients were divided into four subgroups—1A (67 cases), 1B (22 cases), 2A (14 cases), and 2B (18 cases)—corresponding to the presence of simple or complex hallucinations and positive or negative illusions, respectively. The side of the epileptic zone (EZ) was defined based on available data: surgical/presurgical study or presence of a neuroradiological lesion, corresponding interictal epileptiform EEG and ictal semiology (level 1); a left EZ was also hypothesized in right-handed patients with ictal aphasia plus a left neuroradiological lesion or a left interictal EEG focus (level 2). Results: Forty-five patients (37%) described the aura as unilateral. The side of epileptogenic zone (EZ) was definable in 36 patients (level 1: 24; level 2: 12). Overall, a unilateral auditory aura was contralateral to the EZ in half of the cases (8/16), but always contralateral in patients studied for presurgical evaluation (4/4). Simple hallucinations lateralized seizure onset on the right side in nine cases, on the left in 12. Among 1B patients (either musical and verbal contents), the EZ was on the left side in all cases (5/5). Positive illusions were associated with right foci in two cases, and left foci in two. Negative illusions always lateralized seizure onset to the dominant hemisphere (6/6). Conclusions: Auditory aura is a rare symptom in partial epilepsy. The perception of the auditory sensation referred to one ear is not a unique lateralizing sign for the contralateral temporal neocortex. Complex hallucinations with verbal content and negative illusion may lateralize seizure onset in the dominant hemisphere. The role of laterality for musical hallucinations remains unclear as it depends on individual musical ability and hemispheric dominance for music. [ABSTRACT FROM AUTHOR]

Purpose: Mental retardation, facial dysmorphisms, and neurologic and brain abnormalities are features of 6q terminal deletions. Epilepsy is frequently associated with this chromosome abnormality, but electroclinical findings are not well delineated. We report five unrelated patients with 6q terminal deletions and a peculiar clinical, EEG, and neuroradiologic picture of epilepsy, mental retardation, and colpocephaly. Methods: These three male and two female patients underwent general and neurologic examinations, repeated awake and sleep EEGs, and brain magnetic resonance imaging (MRI). A cytogenetic study and fluorescent in situ hybridization (FISH) with chromosome-specific subtelomeric probes were carried out in all cases. Results: All subjects had seizures characterized by vomiting, cyanosis, and head and eye version, with and without loss of consciousness. In four cases, EEGs showed posterior spike-and-wave complexes, which were activated by sleep. No patient had status epilepticus or prolonged seizures. Brain MRI revealed colpocephaly and dysgenesis of the corpus callosum and brainstem in four patients; three of them also had hypertrophic massa intermedia. FISH analysis revealed a 6q terminal deletion in all patients, which ranged between 9 Mb (cases 2 and 3) and 16 Mb (case 4). Conclusions: We suggest that epilepsy associated with 6q terminal deletions is a new entity. Patients with dysmorphic features associated with focal occipital epilepsy, colpocephaly, and dysgenesis of the corpus callosum, thalami, and brainstem should be considered candidates for testing for 6q subtelomere deletions. [ABSTRACT FROM AUTHOR]

Purpose: EPM2B mutations have been found in a variable proportion of patients with Lafora disease (LD). Genotype–phenotype correlations suggested that EPM2B patients show a slower course of the disease, with delayed age at death, compared with EPM2A patients. We herein report clinical and genetic findings of 26 Italian LD patients. Methods: Disease progression was evaluated by means of a disability scale based on residual motor and cognitive functions and daily living and social abilities, at 4 years from the onset. Mutational analysis was performed by sequencing the coding regions of the EPM2A and EPM2B genes. Results: Age at onset ranged from 8.5 to 18.5 years (mean, 13.7 ± 2.6). The mean duration of follow-up was 7.1 ± 3.9 years. Daily living activities and social interactions were preserved in five of 24 patients. The remaining patients showed moderate to extremely severe limitations of daily living and social abilities. Sixteen (72%) of 22 families showed mutations in the EPM2B gene, and five (22%), in the EPM2A gene. One family showed no mutations. A novel EPM2B mutation also was identified. Conclusions: In our series, EPM2B mutations occurred in 72% of families, thus indicating that EPM2B is the major gene for LD in the Italian population. Moreover, we found that six of 17 EPM2B patients preserved daily living activities and social interactions at 4 years from onset, suggesting a slow disease progression. Additional clinical and functional studies will clarify whether specific mutations may influence the course of the disease in LD patients. [ABSTRACT FROM AUTHOR]

Levetiracetam is a new antiepileptic agent that exerts antimyoclonic effects. We conducted an open‐label trial to evaluate the effect of levetiracetam in chronic cortical myoclonus of diverse etiologies and to determine whether levetiracetam affects electrophysiological findings. Sixteen patients, aged between 19 and 72 years, with refractory, chronic, cortical myoclonus were recruited. We assessed myoclonus severity with the Unified Myoclonus Rating Scale (UMRS). The electrophysiological study comprised jerk‐locked averaging, somatosensory evoked potentials (SEPs), and long loop reflex I. Levetiracetam was administered add‐on at a starting dose of 500 mg twice per day up to the target dose of 50 mg/kg/day. Patients were reevaluated clinically and electrophysiologically 2 weeks after the titration phase. Fourteen patients completed the trial. Posttreatment UMRS scores showed an improvement of myoclonus in all cases. Pretreatment, 9 patients had "giant" SEPs. Posttreatment, the amplitude of these SEPs was reduced by more than 50% in 3 of 9 patients, and the mean N20‐P25 amplitude was reduced significantly. Pre‐ and posttreatment SEP amplitude was not related to myoclonus severity or duration. Levetiracetam is a promising and a relatively easy‐to‐test antimyoclonic agent, which has the potential to improve significantly the patient's disability; however, its long‐term efficacy should be verified in larger controlled studies. © 2005 Movement Disorder Society [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented that discusses an article on epilepsy syndrome, one on the syndrome of malignant migrating partial seizures in infancy, and one on the etiology of hypothalamic hamartoma.

We report a five-generation family showing cortical tremor, myoclonus, and epilepsy, originating from Naples, Italy. Eleven members, aged 24–56 years (mean: 39.2 years), suffered from hand tremor and myoclonus, whereas generalized seizures occurred in six. Electrophysiological study confirmed the presence of cortical reflex myoclonus in all affected members. In addition, giant somatosensory-evoked potential components and enhanced long loop reflex I were found also in three presymptomatic members who manifested hand tremor and myoclonus at upper limbs after 1.5 years of follow-up. Genetic study of the pedigree revealed a significant linkage on chromosome 2p (maximum lod score = 5.9). Further observations are needed to clarify the pathophysiology of this condition. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the partial epilepsy.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant condition characterized by cortical tremor and generalized seizures, mapped on chromosome 8q24 by Japanese authors. Recently the same phenotype also was reported in European families, with linkage on chromosome 2. We present a new family with suggestion of linkage to chromosome 2p11.1-2q12.2 (lod score value, 1.55). This observation would confirm that BAFME is a worldwide, genetically heterogeneous condition, probably with Japanese families linked to 8q24 and European families to 2p11.1-q12.2. [ABSTRACT FROM AUTHOR]

The article focuses on study related to effect of nonsense mutation of DEP Domain Containing 5 (DEPDC5) gene on epilepsy diagnosis. Topics discussed include screening of mutation for epilepsy determination, description of familial mesial temporal lobe epilepsy and autosomal dominant lateral temporal epilepsy, determination of symptoms related with focal epilepsy, involvement of auditory symptoms, and inclusion of familial epilepsies with genetic entity of recurrent disorders.

A letter to the editor is presented in response to the article "Factors Influencing Clinical Features of Absence Seizures," by L.G. Sadleir that was published in a previous issue.

We report on a 30-year-old patient with advanced cerebellar degeneration due to SCA2. He presented with severe myoclonus, which was resistant to conventional therapy and dramatically improved after administration of 12-18 gm/die piracetam. Piracetam may be considered in the treatment of refractory myoclonus in spinocerebellar degenerations. © 2005 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Summary Purpose: To evaluate the relative contribution of demographic and epilepsy-related variables, depressive symptoms, and adverse effects (AEs) of antiepileptic drugs (AEDs) to health-related quality of life (HRQOL) in adults with pharmacoresistant epilepsy. Methods: Individuals with epilepsy whose seizures failed to respond to at least one AED were enrolled consecutively at 11 tertiary referral centers. HRQOL was assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), AEs by the Adverse Event Profile (AEP), and depressive symptoms by the Beck Depression Inventory-II (BDI-II). Multivariate linear regression models were used to identify variables associated with QOLIE-31 total score and subscale scores. Key Findings: Of 933 enrolled individuals aged 16 years or older, 809 (87%) were able to complete the self-assessment instruments and were included in the analysis. Overall, 61% of the variance in QOLIE-31 scores was explained by the final model. The strongest predictors of HRQOL were AEP total scores (β = −0.451, p < 0.001) and BDI-II scores (β = −0.398, p < 0.001). These factors were also the strongest predictors of scores in each of the seven QOLIE-31 subscales. Other predictors of HRQOL were age (β = −0.060, p = 0.008), lack of a driving license (β = −0.053, p = 0.018), pharmacoresistance grade, with higher HRQOL in individuals who had failed only one AED (β = 0.066, p = 0.004), and location of the enrolling center. Epilepsy-related variables (seizure frequency, occurrence of tonic-clonic seizures, age of epilepsy onset, disease duration) and number of AEDs had no significant predictive value on HRQOL. The AEP total score was the strongest negative predictor of HRQOL in the subgroup of 362 patients without depressive symptoms (BDI-II score <10), but even in this subgroup the BDI-II score was retained as a significant predictor. Significance: In individuals with pharmacoresistant epilepsy, AEs of medication and depressive symptoms are far more important determinants of HRQOL than seizures themselves. When seizure freedom cannot be achieved, addressing depressive comorbidity and reducing the burden of AED toxicity is likely to be far more beneficial than interventions aimed at reducing the frequency of seizures. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Epileptogenesis Due to Peripheral Injury As a Cause of Focal Epilepsy," by A. E. Spiller, A. Guberman and F. Bartolomei in the previous issue.

A response by S. S. O'Sullivan and J. Redmond to a letter to the editor about their article "Insulinoma Presenting as Refractory Late-Onset Epilepsy" in the previous issue is presented.

Mental retardation, facial dysmorphisms, seizures, and brain abnormalities are features of 6q terminal deletions. We have ascertained five patients with 6q subtelomere deletions (four de novo, one as a result of an unbalanced translocation) and determined the size of the deletion ranging from 3 to 13 Mb. Our patients showed a recognizable phenotype including mental retardation, characteristic facial appearance, and a distinctive clinico-neuroradiological picture. Focal epilepsy with consistent electroencephalographic features and with certain brain anomalies on neuroimaging studies should suggest 6q terminal deletion. The awareness of the distinctive clinical picture will help in the diagnosis of this chromosomal abnormality.