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Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8-9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome.

Purpose: To disclose clinical, electrophysiologic, and neuroradiologic factors correlated to prognosis in patients with mesial temporal lobe epilepsy (MTLE)., Methods: One hundred thirty-six MTLE patients were studied for family history, clinical characteristics, instrumental data [electroencephalography (EEG), video-EEG, neuroimaging], and outcome. The population was divided into drug-resistant (DR: 108 patients, 79.4%) and non-drug-resistant (NDR: 28 patients, 20.6%) groups; all variables were analyzed in the two groups., Results: The comparison between the two groups shows a relation between resistance to therapy and febrile seizures (FS) (DR 43.5% vs. NDR 17.8%, p = 0.008), mesial temporal sclerosis (MTS) (DR 64.8% vs. NDR 32.1%, p = 0.0025), early age at seizure onset (DR 23.1% vs. NDR 3.6% p = 0.0160), and epileptiform interictal abnormalities (DR 89.7% vs. NDR 68%, p = 0.010). FS were more frequent in patients with MTS than in patients without (46.28% vs. 26.3%, p = 0.0199). Sixty-nine patients underwent surgery and 85.3% of them had a good outcome., Conclusion: MTLE is a heterogeneous syndrome. Establishing the factors responsible for and associated with drug resistance is important for therapeutic purposes, as prompt diagnosis of drug resistance must lead to early surgical management. This study shows that FS, MTS, early age at seizure onset, and epileptiform interictal abnormalities are negative prognostic factors and that FS are related to MTS.

A 36-year-old right-handed man, who had experienced partial seizures since the age of 24 every time he played or listened to music with a strong emotional charge, underwent videopolygraphic recording, including autonomic variables, and brain fMRI study during which he listened to both "neutral" and "emotionally charged" music. Three right temporal seizures recorded during videopolygraphic monitoring were elicited by listening to the triggering song. The fMRI study disclosed activation in right acoustic areas during "neutral music," whereas an "emotionally charged melody" provoked widespread activation over the right fronto-temporo-occipital area before seizure onset. The literature review disclosed 110 published cases of musicogenic epilepsy that seemed to suggest a right-sided predominance of the epileptogenic zone. Our results support the role of the right temporal lobe in musicogenic epilepsy and demonstrate that the cerebral areas activated during the period of strong emotion leading to the seizures encompass the auditory cortex activated by neutral music.

Limbic encephalitis (LE) is a neurological syndrome that may present in association with cancer, infection, or as an isolate clinical condition often accompanying autoimmune disorders. Here we have characterized the clinical and laboratory features of two patients presenting with subacute onset, and chronic evolution, of anterograde amnesia and drug-resistant epilepsy associated with thyroid autoimmunity and in absence of tumoral pathology despite long follow-up. Antibodies against onconeural antigens, voltage gated potassium channel and glutamate receptors, which may accompany paraneoplastic as well as non-paraneoplastic LE, were negative. However, biochemical studies showed high titers, and sustained intrathecal synthesis, of antibodies directed against neuronal glutamic acid decarboxylase (GAD). In one patient, plasma exchange determined a dramatic improvement of the neurological deficits along with the decrease of autoantibodies.

Mutations in the LGI1 gene are linked to autosomal dominant lateral temporal epilepsy (ADTLE) in about half of the families tested, suggesting that ADLTE is genetically heterogeneous. Recently, the Lgi1 protein has been found associated with different protein complexes and two distinct molecular mechanisms possibly underlying ADLTE have been hypothesized: the one recognizes Lgi1 as a novel subunit of the presynaptic Kv1 potassium channel implicated in the regulation of channel inactivation, the other suggests that Lgi1 acts as a ligand that selectively binds to the postsynaptic receptor ADAM22, thereby regulating the glutamate-AMPA neurotransmission. Both mechanisms imply that LGI1 mutations result in alteration of synaptic currents, though of different types. Since their protein products have been found associated with Lgi1, the Kv1 channel subunit genes KCNA1, KCNA4, and KCNAB1 and ADAM22 can be considered strong candidates for ADLTE. We sequenced their coding exons and flanking splice sites in the probands of 9 carefully ascertained ADLTE families negative for LGI1 mutations. We failed to detect any mutation segregating with the disease, but identified several previously unreported polymorphisms. An association study of four non-synonymous variants (three found in ADAM22, one in KCNA4) in a population of 104 non-familial lateral temporal epilepsy cases did not show any modification of susceptibility to this disorder. Altogether, our results suggest that neither ADAM22 nor any of the three Kv1 channel genes are major causative genes for ADLTE.

Autosomal dominant lateral temporal epilepsy (ADTLE) is a genetically transmitted epileptic syndrome characterized by focal seizures with predominant auditory symptoms likely originating from the lateral region of the temporal lobe. Mutations in coding region or exon splice sites of the leucine-rich, glioma-inactivated 1 (LGI1) gene account for about 50% of ADLTE families. De novo LGI1 mutations of the same kind have also been found in about 2.5% of non-familial cases with idiopathic partial epilepsy with auditory features (IPEAF). In both conditions, mutations in the LGI1 promoter region have not been reported. We sequenced the minimal promoter region of LGI1 in the probands of 16 ADLTE families and in 104 sporadic IPEAF patients and no mutations clearly linked to the disease were found. However, two polymorphisms, -500G>A and -507G>A, with potential functional implications were identified and analysed in the cohort of sporadic IPEAF patients but their frequencies did not differ from those found in a control population of similar age, gender and geographic origin. We also analysed in our study population the GABA(B) receptor 1 c.1465G>A and the prodynorphin promoter 68-bp repeat polymorphisms, previously associated with temporal lobe epilepsy. None of these polymorphisms showed a significant association with IPEAF, whereas a tendency towards association with the prodynorphin low expression (L) alleles was found in the small group of ADLTE index cases, in agreement with previous studies suggesting that this polymorphism is a susceptibility factor in familial forms of temporal lobe epilepsy.

Seizures, namely in certain epileptic conditions, may be precipitated by sleep. Nocturnal frontal lobe epilepsy seizures, characterized by bizarre motor behaviour and autonomic activation, appear almost exclusively during sleep. The differential diagnosis between this condition and sleep-related non-epileptic paroxysmal motor phenomena, in particular the parasomnias, is arduous. Moreover, accepted criteria for the diagnosis of nocturnal frontal lobe seizures are lacking and even ictal scalp EEG recording could fail to disclose paroxysmal abnormalities. The clinical and polygraphic features of the different types of seizures in nocturnal frontal lobe epilepsy and of the more common non-epileptic paroxysmal events during sleep are described. The main differentiating features characterizing nocturnal frontal seizures are: onset at any age, several attacks per night at any time during the night, brief duration (s) with stereotyped motor pattern. As video-polysomnographic recordings of the attack, the gold-standard for diagnosis, are expensive and not readily available everywhere, home-made video recordings may be helpful. Further investigations on pathophysiology, genetics and epidemiology are needed to clarify the relationship between epileptic and non-epileptic sleep related paroxysmal phenomena.

Background: Nocturnal frontal lobe seizures (NFLS) show one or all of the following semeiological patterns: (1) paroxysmal arousals (PA: brief and sudden recurrent motor paroxysmal behavior); (2) hyperkinetic seizures (HS: motor attacks with complex dyskinetic features); (3) asymmetric bilateral tonic seizures (ATS: motor attacks with dystonic features); (4) epileptic nocturnal wanderings (ENW: stereotyped, prolonged ambulatory behavior)., Objective: To estimate the interobserver reliability (IR) of video-recording diagnosis in patients with suspected NFLS among sleep medicine experts, epileptologists, and trainees in sleep medicine., Methods: Sixty-six patients with suspected NFLS were included. All underwent nocturnal video-polysomnographic recording. Six doctors (three experts and three trainees) independently classified each case as "NFLS ascertained" (according to the above specified subtypes: PA, HS, ATS, ENW) or "NFLS excluded". IR was calculated by means of Kappa statistics, and interpreted according to the standard classification (0.0-0.20 = slight agreement; 0.21-0.40 = fair; 0.41-0.60 = moderate; 0.61-0.80 = substantial; 0.81-1.00 = almost perfect)., Results: The observed raw agreement ranged from 63% to 79% between each pair of raters; the IR ranged from "moderate" (kappa = 0.50) to "substantial" (kappa = 0.72). A major source of variance was the disagreement in distinguishing between PA and nonepileptic arousals, without differences in the level of agreement between experts and trainees., Conclusions: Among sleep experts and trainees, IR of diagnosis of NFLS, based on videotaped observation of sleep phenomena, is not satisfactory. Explicit video-polysomnographic criteria for the classification of paroxysmal sleep motor phenomena are needed.

This observational study was performed to identify the clinical reasons leading physicians to opt for immediate or progressive procedures when switching patients from carbamazepine to oxcarbazepine, and to evaluate the clinical feasibility of the two procedures in a general unselected patient population. Five hundred and twenty-seven patients (aged 14 years or older, treated with carbamazepine as monotherapy or in combination therapy) were recruited at 50 Italian centres and freely assigned to immediate (n=361) or progressive (n=166) switch procedures. Vital and clinical data (including seizure frequency) were comparable in the two groups at baseline. The proportion of patients with simple partial seizures only was significantly higher in the immediate group (immediate: 33.0% vs progressive: 23.5%, p=0.0275), whereas the proportion of patients on combination therapy was slightly higher in the progressive group (immediate: 47.1 vs progressive: 55.4%, p=0.0756). At the end of the switch period, overall treatment satisfaction was greater in the immediate switch group, both in patients (p<0.002) and physicians (p<0.0005). Physicians preferred the immediate over the progressive switch procedure. The only clinical features of patients found to relate to the physician?s choice of switch procedure were simple partial seizures only (favouring the immediate switch) and, possibly, combination therapy with other anti-epileptic drugs (favouring the progressive switch). "Overnight" switching from carbamazepine to oxcarbazepine also appears feasible in most patients on polytherapy.

Purpose: Cortical tremor, a form of rhythmic cortical myoclonus (rhythmic CM), and epilepsy have been described in families with autosomal dominant inheritance. Linkage analyses revealed two putative loci on chromosome 2p and 8q. Clinical photosensitivity was not a prominent feature in such families. We describe a large Italian family with rhythmic CM, photosensitivity, and epilepsy., Methods: Twenty-three individuals of a five-generation family were studied. Linkage analyses for the loci on chromosome 2p11.1 and 8q23.3 were performed., Results: Of the 23 studied family members, 16 were affected. Rhythmic CM of childhood onset was present in all 16 individuals (onset ranging from 3 to 12 years), was associated with photic-induced myoclonic jerks in seven, and with epileptic seizures in six (onset ranging from 23 to 34 years). Five children of the V generation manifested also episodes of arousal with generalized tremor in early infancy ("tremulous arousals"). Jerk-locked back-averaging of rhythmic CM of six affected individuals, documented a premyoclonic EEG correlate. C-reflex at rest was present in two affected adults. Linkage analyses excluded mapping to the 2p11.1 and 8q23.3 loci., Conclusions: Clinical variability and severity of the phenotypes in this family are in line with those of previously described pedigrees with autosomal dominant cortical myoclonus and epilepsy. In this family, a progression of symptoms was found: rhythmic CM and tremulous arousals occurred in childhood, whereas visually induced manifestations and epileptic seizures occurred during adolescence-adulthood. Exclusion of linkage to the two known loci is consistent with genetic heterogeneity of such familial clustering of symptoms.

Purpose: This is the first report comparing intrasubject lamotrigine (LTG) plasma concentrations between hormonal contraceptive (HC) intake and week-off phases in epilepsy patients receiving combined LTG and HC treatment. We describe the variation in LTG plasma concentrations with hormonal contraceptive (HC) monthly intake cycles in a series of eight patients with epilepsy., Methods: Venous blood samples were prospectively drawn from patients before their first morning dose of LTG, once between days 18 and 21 of HC intake and once between days 5 and 7 of the HC-free week., Results: Median LTG plasma concentrations were significantly higher during the HC washout week than during the phase of HC intake (p = 0.02). The median value of intrasubject percentage increase was 27%, with a wide interpatient variability., Conclusions: These findings are in line with a preliminary report on healthy volunteers. Standardization of blood sampling in relation to HC intake cycles is advisable when planning LTG therapeutic monitoring in patients receiving HC.

Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.

Purpose: Nocturnal frontal lobe epilepsy (NFLE) may be associated with sleep fragmentation and reduced sleep efficiency. Daytime sleepiness and disturbed sleep quality have been reported in some patients. We investigated the occurrence of daytime sleepiness-related symptoms and subjective sleep quality in patients with NFLE in comparison with matched controls., Methods: Patients with NFLE at a single epilepsy center and matched controls randomly selected from the general population self-administered questionnaires on daytime sleepiness-related symptoms and subjective sleep quality [Epworth sleepiness scale (ESS), Bologna questionnaire on sleepiness-related symptoms (BQS), Berlin questionnaire]., Results: Thirty-three patients with NFLE and 27 controls were enrolled. "Tiredness after awakening" and "spontaneous mid-sleep awakenings" were more frequent in NFLE patients than in controls (36.4% versus 11.1%, p = 0.04, and 50.0% versus 22.2%, p = 0.03). The frequency of excessive daytime sleepiness (EDS) did not differ between groups. Posthoc analysis showed that patients with a complaint of "midsleep awakenings" had higher ESS and BQS scores than those without (7.3 versus 4.3, p = 0.004, and 5.0 versus 2.2, p = 0.001, respectively) and more frequent "tiredness after awakening" (56.3% versus 18.8%, p = 0.03)., Conclusions: Patients with NFLE have no pathological level of EDS with respect to controls. However, daytime sleepiness-related symptoms could be more frequent in a subgroup of patients with subjective disturbed sleep quality, irrespective of the perceived frequency of seizures.

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.

Nocturnal frontal lobe epilepsy is a syndromic entity that includes paroxysmal episodes with variable semeiology, intensity and duration, representing different aspects of the same epileptic condition. In a large series studied by videopolysomnographic recording at the Department of Neurological Sciences in Bologna, we disclosed four main semeiological patterns: the paroxysmal arousals, brief simple motor phenomena, similar to a sudden arousal, recurring several times per night; the hypermotor seizures, more complex motor episodes with violent motor behaviour, vocalisation, screaming, fearful and repetitive movements of the trunk and limbs; asymmetric, bilateral tonic seizures, which can evoke the seizures from the frontal mesial area; and epileptic nocturnal wanderings, which can mimic sleepwalking episodes.

Objective: To estimate the interobserver reliability (IR) of the minimal diagnostic criteria for the parasomnias provided in the International Classification of Sleep Disorders Revised (ICSD-R)., Methods: Fifty consecutive subjects underwent a structured interview by three doctors based on the ICSD-R minimal criteria for the diagnosis of 13 parasomnias at any time in life. IR was calculated by Kappa statistics and interpreted according to conventional categories., Results: In the group of Arousal Disorders, IR was "substantial" (kappa 0.74) for confusional arousals, "slight" (kappa 0.36) for sleepwalking, "fair" (kappa -0.02) for sleep terrors. In the group of Wake-Sleep Transition Disorders, IR was "substantial" to "almost perfect", but "moderate" for sleep starts (kappa 0.41). In the group of Parasomnias usually associated with REM Sleep, IR was "substantial" (kappa 0.69) for sleep paralysis, "moderate" (kappa 0.46) for RBD, "fair" (kappa 0.25) for nightmares. In the group of Other Parasomnias, IR was "substantial" to "almost perfect" (kappa between 0.73 and 0.93)., Conclusions: When the clinical diagnosis of parasomnias is based on the ICSD-R: 1) the majority of Arousal Disorders and REM sleep parasomnias showed only a "fair" to "moderate" IR; 2) all of the other parasomnias showed a "substantial" to "almost perfect" IR. Nosological entities with unsatisfactory IR share complex motor phenomenology associated with a mental state difficult for the patient to define. The source of disagreement probably lies in the difficulty in interpreting patients' reports. For these parasomnias IR must be verified and possibly improved with training.

Objectives: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH., Methods: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2-40 years)., Results: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities., Conclusions: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis.

The purpose of our study was to describe the clinical characteristics of sporadic (S) cases of partial epilepsy with auditory features (PEAF) and pinpoint clinical, prognostic and genetic differences with respect to previously reported familial (F) cases of autosomal dominant partial epilepsy with auditory features (ADPEAF). We analysed 53 patients (24 females and 29 males) with PEAF diagnosed according to the following criteria: partial epilepsy with auditory symptoms, negative family history for epilepsy and absence of cerebral lesions on NMR study. All patients underwent a full clinical, neuroradiological and neurophysiological examination. Forty patients were screened for mutations in LGI1/epitempin, which is involved in ADPEAF. Age at onset ranged from 6 to 39 years (average 19 years). Secondarily generalized seizures were the most common type of seizures at onset (79%). Auditory auras occurred either in isolation (53%) or associated with visual, psychic or aphasic symptoms. Low seizure frequency at onset and good drug responsiveness were common, with 51% of patients seizure-free. Seizures tended to recur after drug withdrawal. Clinically, no major differences were found between S and F patients with respect to age at onset, seizure frequency and response to therapy. Analysis of LGI1/epitempin exons failed to disclose mutations. Our data support the existence of a peculiar form of non-lesional temporal lobe epilepsy closely related to ADPEAF but without a positive family history. This syndrome, here named IPEAF, has a benign course in the majority of patients and could be diagnosed by the presence of auditory aura. Although LGI1 mutations have been excluded, genetic factors may play an aetiopathogenetic role in at least some of these S cases.

Video-EEG is an indispensable and widely used technique for studying paroxysmal phenomena. We present a method of processing video recordings to compare the sequence of ictal manifestations of different episodes. Five presentations of two seizures recorded in each of five patients are shown, in which apparently different ictal features are strongly superimposed and stereotyped. Split-screen synchronized display is a simple and valid technique for studying and presenting particular semeiological aspects of epileptic seizures. (Published with videosequences).

Purpose: To report a new form of reflex epilepsy in which the seizures are repeatedly and exclusively triggered by answering the telephone., Methods: Three patients with a history of telephone-induced seizures were studied in detail by means of clinical, EEG, and neuroradiologic investigations. Intensive video-EEG monitoring to record the reflex seizures also was performed in all cases., Results: The patients (two men, one woman, aged 21 to 30 years) had the onset during early adulthood of complex partial and secondarily generalized seizures exclusively triggered by answering the telephone. The seizures were stereotyped, with subjective auditory or vertiginous auras and inability to speak or understand the spoken voices. In one patient, a telephone-induced seizure arising from the dominant temporal lobe was recorded by means of video-EEG technique. In the interictal EEGs, temporal abnormalities were detected in all cases. The patients had a normal neurologic examination and normal magnetic resonance imaging or computed tomography scans., Conclusions: We suggest that telephone epilepsy is a previously unrecognized form of reflex epilepsy induced by a complex auditory stimulus involving the lateral temporal areas.

Purpose: [corrected] To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE)., Methods: A personal and family history was obtained from each affected and unaffected member, along with a physical and neurologic examination. Routine and sleep EEGs, computed tomography (CT), or magnetic resonance imaging (MRI) were performed in almost all the patients. DNAs from family members were typed with several microsatellite markers localized on either side of LGI1 at 10q24 and screened for LGI1 mutations., Results: The seven families included a total of 34 affected individuals (10 deceased). The age at onset ranged between 8 and 50 years (average, 22 years). Twenty-six patients had clear-cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Less frequent ictal symptoms were visual, psychic, or aphasic seizures, the latter occurring in isolation in one family. The attacks were rare and well controlled by antiepileptic drug treatment but recurred after drug discontinuation. Interictal EEGs were usually unrevealing. MRI or CT scans were negative. Analysis of LGI1/Epitempin exons failed to show mutations in three pedigrees. Linkage analysis strongly suggested exclusion of linkage in one of these families. We found two novel missense mutations, a T-->C substitution in exon 6 at position 598, and a T-->A transition in exon 8 at position 1295, the latter being detected in a family with aphasic seizures., Conclusions: Our data confirm the inclusion of aphasic seizures within the ADLTE clinical spectrum, suggest the existence of locus heterogeneity in ADLTE, and provide new familial cases with LGI1 missense mutations associated with the disease.

Few studies have focused on the clinical, neurophysiological and prognostic features of adult epileptic patients with malformation of cortical development. We reviewed the clinical data of a series of sixty adult epileptic patients with different types of malformation of cortical development, who had been followed at the Epilepsy Centre of the Department of Neurological Sciences of the University of Bologna, with particular attention to age at seizure onset, mental retardation, response to therapy, and EEG features. The heterogeneity of our population, especially when divided into the different groups of malformation of cortical development, precluded any general conclusions, but we stress the following aspects: 1). epilepsy due to malformation of cortical development may begin in adolescents and young adults; 2). epileptic seizures with clinical and polygraphic features of infantile spasms may persist into adulthood; 3). complex cortical malformation is not necessarily associated with severe epileptic encephalopathy. In periventricular nodular heterotopias, the largest in our series (nine patients), age at onset of seizures, response to therapy and mental deterioration differed according to the presence of nodules confined to the ventricular wall ('pure' form) or periventricular nodules associated with other cerebral cortical malformations ('plus' form)., (Copyright John Libbey Eurotext 2003.)

Purpose: To investigate ictal muscular phenomena characterizing symptomatic infantile spasms (ISs) and their relation to ictal EEG., Methods: Four children with severe encephalopathy, neurologic impairment, and refractory ISs related to different dysplastic lesions, underwent videopolygraphic recordings collecting surface electromyogram (EMG) activity from several cranial and limb muscles to evaluate the pattern of muscular recruitment, duration, and side-to-side asymmetry of ISs. Acquired data were stored for off-line analysis by a computerized polygraphic system., Results: Spasms were characterized by a complex pattern of muscular activation. A constant or rostrocaudal propagation pattern was lacking in all patients. Intervals between the onset of EMG activity in different muscles in each spasm were very long:

Autosomal dominant partial epilepsy with auditory features (ADPEAF) has been identified as a distinct genetic syndrome. Several families have been described linked to chromosome 10q24, which carries mutations in the LGI1 gene. We report a small new pedigree with partial epilepsy with auditory symptoms. We performed a detailed clinical study of the family, constructed an extended pedigree comprising 106 individuals, and obtained blood samples for genetic analysis. Individuals with seizures also underwent neurophysiological and neuroradiological investigations. Genetic analysis was performed with six microsatellite markers spanning to the critical region of chromosome 10q24. Mutation analysis of the coding sequence of LGI1 was performed in two patients. Five members of the family in generation IV had seizures. Three individuals had auditory auras, followed by generalised seizures in two and brief loss of contact in one, one had nocturnal tonic-clonic seizures with an EEG suggestive of right temporal lobe onset, and one only had febrile seizures. In addition, a deceased woman was said to have had seizures. Haplotype analysis of this region of chromosome 10q24 failed to disclose a common haplotype in affected family members and no disease-associated mutations were detected in the LGI1 gene, suggesting that this locus is not associated with the disease in our family. Our small sample with partial epilepsy with auditory symptoms, clinically resembles previously described ADPEAF families. However, the low number of patients is compatible with either autosomal dominant or other inheritance patterns. In the case of the former, the lack of segregation with 10q24 suggests that a second locus is involved in the aetiology of ADPEAF; in the latter, an epileptic syndrome also characterized by auditory features, but distinct from ADPEAF, could be transmitted in this family.

Ictal bradycardia is a rare, probably underestimated, manifestation of epileptic seizures whose pathophysiology is still debated. Autonomic modifications may result either from a sympathetic inhibition or from a parasympathetic activation probably due to the ictal discharge arising from or spreading to the structures of the central autonomic network. We review 60 cases of ictal bradycardia from the available literature and present three additional cases associated with left temporal lobe seizures studied by autonomic polygraphic ictal monitoring. Only 47 of the 63 reported cases were documented by simultaneous EEG and ECG recordings during an attack. About 76% of patients in whom well-localized ictal discharges were recorded had temporal or frontotemporal lobe seizures. Forty-five cases included information allowing confident localization of the side of ictal onset, and a 26 : 19 ratio of the left versus right side was evident. Simultaneous monitoring of ECG and other autonomic parameters during EEG recording in partial seizures should be performed to gain more insight into ictal semiology. Correlation of the symptoms referred to by patients with changes in autonomic parameters could avoid erroneous diagnosis of non-epileptic attacks and disclose a potentially lethal condition. Our cases confirm the preferential role of the left hemisphere in the genesis of ictal bradycardia and shed light on the relationship between suprabulbar control of autonomic function and partial epileptic seizures.

Objectives: To evaluate the efficacy of lamotrigine (LTG) add-on therapy in drug-resistant, partial epilepsy with epileptic drop attacks (EDA) and secondary bilateral synchrony (SBS) on EEG., Methods: We carried out a single-center, open-label, prospective study on a restricted group of patients experiencing an EDA frequency of at least one/month during the previous year regardless of multiple antiepileptic drug (AED) trials. Study design consisted of three phases: a 3-month baseline period, a 4-month period in which LTG was titrated and a 9-month maintenance dose observational period. LTG add-on therapy depended on valproate (VPA) association, with a maximum of 200 mg/day with VPA and 600 mg/day in the absence of VPA. Every three months, patients underwent clinical, hematological and EEG evaluation including plasma level of AEDs. To assess the efficacy of LTG add-on therapy, patients were required to keep a detailed seizure diary throughout the study., Results: Fourteen patients (nine men and five women), aged from 21 to 51, were included in the study. All of them had complex partial seizures (CPS), besides EDA, and half of them had secondarily generalized seizures (SGS). Two of the 14 patients had to stop LTG due to side effects, although one of them was seizure-free after LTG. Twelve patients completed the study. The improvement was more than 50% for every type of seizure. SGS disappeared in three cases and improved by more than 50% in another three cases. EDA disappeared in six patients; and improved with more than 50% EDA reduction in five patients. CPS disappeared in two patients and improved by more than 50% in eight. EEG improved in nine cases, with SBS disappearing in six patients., Conclusions: We have demonstrated a good efficacy of LTG adjunctive therapy on EDA. Results include control of SGS and improvement of EEG tracing.

Epileptic negative myoclonus (ENM) is an epileptic motor dysfunction characterised by brief lapses of postural tone provoked by paroxysmal cortical discharges. We report the electrophysiological and video-polygraphic findings in a patient presenting with the unusual association of ENM and brief asymmetric tonic-postural seizures of cryptogenetic origin. Focal EMG silent periods in the left deltoid muscle (mean duration 81.2 +/- 16.4 ms), time-locked with vertex spikes were present. The time lag between spikes and ENM was 33.1 +/- 4.6 ms. We suggest the involvement of mesial frontal areas in the genesis of both negative and positive motor phenomena.

Different types of neoplastic and non neoplastic lesions can affect the orbit causing ocular damage. Aim of the present study was that to review a series of endoorbital neoplastic and non neoplastic space occupying lesions. All the cases of endoorbital lesions, seen during the period January 1980-September 1996, were retrieved from the files of the Department of Pathology of the Ospedale Bellaria of Bologna (Italy). All the cases were reviewed and reclassified according to the WHO criteria. One hundred-twenty-six cases of orbital lesions were selected; of these 88 were benign, 36 malignant and 2 borderline. The cases were then subdivided into the following categories: benign lesions of soft tissues (37 cases), malignant lesions of soft tissues (5 cases), lymphoid tumors and pseudotumors (12 cases), other primitive endoorbital tumors (18 cases), secondary and metastatic tumors (43 cases), tumors of the optic nerve (6 cases) and non neoplastic lesions (3 cases). A great variety of lesions can affect the orbit, most of which are benign in nature. Thus a correct diagnosis followed by a correct treatment of the patients can avoid severe ocular damage.

The unusual case of a patient presenting with gaze-evoked amaurosis as an early and isolated sign of orbital angiomyoma is reported. Computed tomography or magnetic resonance of the orbits need to be expeditiously performed in patients with gaze-evoked amaurosis in order to identify or rule out the possible presence of an underlying tumor.