Neonatal seizure automatism and human inborn pattern of quadrupedal locomotion.

Seizures in newborns do not always show a clear electro-clinical correlation. The real epileptic nature of some stereotyped rhythmic movements, included in the 'subtle seizures' and considered as brainstem release phenomena, is still debated. We report a brain injured newborn, who displayed several episodes of repetitive limb movements. The ictal EEG discharge, during one of these episodes, was associated with a motor pattern modification, which was endowed with quadrupedal locomotion kinematic features. This might represent an indirect evidence of cervical and lumbar Central Pattern Generators interconnection with in-phase coordination between diagonal limbs since the first hours of life in humans.

SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure.

OBJECTIVE: Mutations in SCARB2 were recently described as causing action myoclonus renal failure syndrome (AMRF). We hypothesized that mutations in SCARB2 might account for unsolved cases of progressive myoclonus epilepsy (PME) without renal impairment, especially those resembling Unverricht-Lundborg disease (ULD). Additionally, we searched for mutations in the PRICKLE1 gene, newly recognized as a cause of PME mimicking ULD. METHODS: We reviewed cases of PME referred for diagnosis over two decades in which a molecular diagnosis had not been reached. Patients were classified according to age of onset, clinical pattern, and associated neurological signs into "ULD-like" and "not ULD-like." After exclusion of mutations in cystatin B (CSTB), DNA was examined for sequence variation in SCARB2 and PRICKLE1. RESULTS: Of 71 cases evaluated, 41 were "ULD-like" and five had SCARB2 mutations. None of 30 "not ULD-like" cases were positive. The five patients with SCARB2 mutations had onset between 14 and 26 years of age, with no evidence of renal failure during 5.5 to 15 years of follow-up; four were followed until death. One living patient had slight proteinuria. A subset of 25 cases were sequenced for PRICKLE1 and no mutations were found. INTERPRETATION: Mutations in SCARB2 are an important cause of hitherto unsolved cases of PME resembling ULD at onset. SCARB2 should be evaluated even in the absence of renal involvement. Onset is in teenage or young adult life. Molecular diagnosis is important for counseling the patient and family, particularly as the prognosis is worse than classical ULD.

Neuroethological approach to frontolimbic epileptic seizures and parasomnias: The same central pattern generators for the same behaviours.

The aim of this report is not to make a differential diagnosis between epileptic nocturnal seizures and non-epileptic sleep-related movement disorders, or parasomnias. On the contrary, our goal is to emphasize the commonly shared semiological features of some epileptic seizures and parasomnias. Such similar features might be explained by the activation of the same neuronal networks (so-called 'central pattern generators' or CPG). These produce the stereotypical rhythmic motor sequences - in other words, behaviours - that are adaptive and species-specific (such as eating/alimentary, attractive/aversive, locomotor and nesting habits). CPG are located at the subcortical level (mainly in the brain stem and spinal cord) and, in humans, are under the control of the phylogenetically more recent neomammalian neocortical structures, according to a simplified Jacksonian model. Based on video-polygraphic recordings of sleep-related epileptic seizures and non-epileptic events (parasomnias), we have documented how a transient "neomammalian brain" dysfunction - whether epileptic or not - can 'release' (disinhibition?) the CPG responsible for involuntary motor behaviours. Thus, in both epileptic seizures and parasomnias, we can observe: (a) oroalimentary automatisms, bruxism and biting; (b) ambulatory behaviours, ranging from the classical bimanual-bipedal activity of 'frontal' hypermotor seizures, epileptic and non-epileptic wanderings, and somnambulism to periodic leg movements (PLM), alternating leg muscle activation (ALMA) and restless legs syndrome (RLS); and (c) various sleep-related events such as ictal fear, sleep terrors, nightmares and violent behaviour.

Neuropathy in multiple myeloma treated with thalidomide: a prospective study.

BACKGROUND: Thalidomide is effective as a first-line therapy for the treatment of multiple myeloma (MM), but its use is limited by peripheral neurotoxicity. OBJECTIVE: To study the occurrence of both myeloma-related neuropathy and thalidomide-induced neuropathy in 31 patients with newly diagnosed MM. METHODS: Clinical and electrophysiologic examinations were performed in 31 patients with newly diagnosed MM before and after 4 months of therapy with thalidomide (200 mg/day, total dose: 21 g) aimed at debulking MM, before autologous transplantation. After transplantation, the patients took thalidomide, 200 mg/day for another 3 months (total dose over three months: 18 g) and then underwent a final clinical and electrophysiologic checkup. RESULTS: At baseline, four patients presented a mild sensorimotor peripheral neuropathy related to MM, which tended to worsen slightly during treatment with thalidomide. At the end of treatment, 83% of the patients had clinical and electrophysiologic evidence of a mild sensory rather than motor, axonal, length-dependent polyneuropathy, whereas 100% of the patients showed improvement to the basic pathology (>or=partial response). CONCLUSIONS: Peripheral neuropathy, sometimes subclinical, and mild in our patients, is a common, early side effect of thalidomide therapy. The high doses (21 g) used in all patients for a relatively short time (4 months) rule out any correlations between neuropathy, total dose, and duration of treatment.

Whole-brain histogram and voxel-based analyses of apparent diffusion coefficient and magnetization transfer ratio in celiac disease, epilepsy, and cerebral calcifications syndrome.

BACKGROUND AND PURPOSE: Diffusion and magnetization transfer (MT) techniques have been applied to the investigation with MR of epilepsy and have revealed changes in patients with or without abnormalities on MR imaging. We hypothesized that also in the coeliac disease (CD), epilepsy and cerebral calcifications (CEC) syndrome diffusion and MT techniques could reveal brain abnormalities undetected by MR imaging and tentatively correlated to epilepsy. MATERIALS AND METHODS: Diffusion and MT weighted images were obtained in 10 patients with CEC, 8 patients with CD without epilepsy and 17 healthy volunteers. The whole brain apparent diffusion coefficient (ADC) and MT ratio (MTR) maps were analyzed with histograms and the Statistical Parametric Mapping 2 (SPM2) software. We employed the non-parametric Mann-Whitney U test to assess differences for ADC and MTR histogram metrics. Voxel by voxel comparison of the ADC and MTR maps was performed with 2 tails t-test corrected for multiple comparison. RESULTS: A significantly higher whole brain ADC value as compared to healthy controls was observed in CEC (P = 0.006) and CD (P = 0.01) patients. SPM2 showed bilateral areas of significantly decreased MTR in the parietal and temporal subcortical white matter (WM) in the CEC patients. CONCLUSION: Our study indicates that diffusion and MT techniques are also capable of revealing abnormalities undetected by MR imaging. In particular patients with CEC syndrome show an increase of the whole brain ADC histogram which is more pronounced than in patients with gluten intolerance. IN CEC patients, voxel-based analysis demonstrates a localized decrease of the MTR in the parieto-temporal subcortical WM.

Negative myoclonus. An overview of its clinical features, pathophysiological mechanisms, and management.

Negative myoclonus (NM) is an unspecific motor disorder that can characterize a variety of neurological conditions. From the clinical point of view, NM appears as a shock-like involuntary jerky movement caused by a sudden, brief interruption of muscle activity. Asterixis is a type of NM that occurs typically in toxic-metabolic encephalopathies. NM of epileptic nature, or epileptic negative myoclonus (ENM), is defined as an interruption of tonic muscle activity, which is time-locked to an epileptic EEG abnormality, without evidence of an antecedent positive myoclonia in the agonist-antagonist muscles. ENM can be observed in idiopathic, cryptogenic, and symptomatic epileptic disorders. Pathophysiological hypotheses on the origin of NM involve subcortical as well as cortical mechanisms. Recent neuroimaging and neurophysiologic investigations, including intracerebral recordings and electrical stimulation procedures in epileptic patients, suggest the participation of premotor, primary motor, primary sensory, and supplementary motor areas in the genesis of NM. Polygraphic monitoring is essential for the diagnosis of NM, allowing the demonstration of brief interruptions of a tonic EMG activity, not preceded by a positive myoclonus in the agonist and antagonist muscles of the affected limb. Simultaneous EEG-EMG monitoring demonstrating the association of NM with an epileptic potential is consistent with the diagnosis of ENM. Evolution and prognosis of NM is mainly related to aetiology. In childhood idiopathic partial epilepsy, ENM can respond to some drugs (in particular, ethosuximide), whereas other medications (such as carbamazepine or phenytoin) have been reported to induce or worsen it.

Central pattern generators for a common semiology in fronto-limbic seizures and in parasomnias. A neuroethologic approach.

Central pattern generators (CPGs) are genetically determined neuronal aggregates in the mesencephalon, pons and spinal cord subserving innate motor behaviours essential for survival (feeding, locomotion, reproduction etc.). In higher primates CPGs are largely under neocortical control. We describe how certain motor events observed in parasomnias and epileptic seizures could have similar features and resemble motor behaviours, which can be the expression of the same CPG. Both epilepsy and sleep can lead to a temporary loss of control of neomammalian cortex that facilitates through a common platform (arousal) the emergences of stereotyped inborn fixed action patterns. Therefore we suggest that, independently from the nature of the trigger, be it a seizure or a parasomnia, the same CPGs can be involved, "caught up", leading to a common motor semiology (the "Carillon theory").

Early onset aggressive hereditary amyloidosis: report of an Italian family with TTR Arg47 mutation.

Arg47 is a rare transthyretin-related (TTR) amyloidosis variant that is characterised by polyneuropathy and autonomic failure. We describe an Italian family with this mutation whose members (two women and their father) showed a rapid progression of the peripheral nervous system involvement and died within 5 years of clinical onset. Patients with Arg47 or other aggressive TTR amyloidoses should be considered high priority patients for orthotopic liver transplantation.

Lafora disease due to EPM2B mutations: a clinical and genetic study.

OBJECTIVE: To study EPM2B gene mutations and genotype-phenotype correlations in patients with Lafora disease. METHODS: The authors performed a clinical and mutational analysis of 25 patients, from 23 families, diagnosed with Lafora disease who had not shown mutations in the EPM2A gene. RESULTS: The authors identified 18 mutations in EPM2B, including 12 novel mutations: 4 nonsense mutations (R265X, C26X, W219X, and E67X), a 6-base pair (bp) microdeletion resulting in a two amino acid deletion (V294_K295del), a 4-bp insertion resulting in a frameshift mutation (S339fs12), and 6 missense mutations (D308A, I198N, C68Y, E67Q, P264H, and D233A). In our data set of 77 families with Lafora disease, 54 (70.1%) tested probands have mutations in EPM2A, 21 (27.3%) in EPM2B, and 2 (2.6%) have no mutations in either gene. The course of the disease was longer in patients with EPM2B mutations vs patients with EPM2A mutations. CONCLUSIONS: Genetic allelic heterogeneity is present in Lafora disease associated with mutations in EPM2B. Patients with mutations in EPM2A and EPM2B express similar clinical manifestation, although patients with EPM2B-associated Lafora disease seem to have a slightly milder clinical course. The lack of mutations in EPM2A and EPM2B in two families could be because of the presence of mutations in noncoding, nontested regions or the existence of an additional gene associated with Lafora disease.

Rhythmic teeth grinding induced by temporal lobe seizures.

The authors report the clinical and polygraphic features of rhythmic teeth grinding observed in a patient as the predominant symptom related to temporal lobe seizures during sleep and wakefulness. This observation demonstrates that exceptionally a teeth-grinding event can be not only a parasomnia (sleep bruxism) but also an epileptic-related motor event. Electromyographic and autonomic features of seizure-related teeth grinding support the interpretation of this motor phenomenon as a particular form of masticatory activity.

Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms.

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.

Idiopathic partial epilepsy with auditory features (IPEAF): a clinical and genetic study of 53 sporadic cases.

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.

A wavelet based analysis of energy redistribution in scalp EEG during epileptic seizures.

In this work, wavelet decomposition and multiresolution analysis are used to explore the changes in scalp EEG signals during epileptic seizures. EEG tracings, which include non-epileptic periods, the beginning of seizure and the peak of seizure, have been decomposed in five details using order 10 Daubechies orthonormal wavelets. Energy has then been computed, at each detail, from square wavelet coefficients, in order to unmask the presence of brief episodes of energy relocation among different scales. Results reveal the existence of significant changes in energy distribution at seizure onset; this redistribution, however, exhibits significant differences from one patient to another, and also among different channels in the same patient. Some channels exhibit a significant energy increase at low scales (high frequencies greater than 20 Hz) at seizure onset, whereas energy drops at higher scales. Other channels, however, exhibit energy increase at high scales (frequency less than 15 Hz) revealing a predominance of low-frequency activity. These two patterns may be simultaneously present at seizure onset and may change with different spatial evolution during the subsequent seizure progression. Wavelet analysis appears as a powerful tool for extracting features relative to seizure, and to study their propagation among different regions in the scalp.

Atypical familial motor neuropathy in patients with mutant TTR Ile68Leu.

Two sisters from an Italian family shared progressive motor symptoms, preceding the onset of sensory and autonomic disturbances. The familial occurrence of axonal and slowly progressive polyneuropathy led us to consider these patients as candidates for TTR molecular analysis. We found a missense mutation causing Ile68Leu TTR substitution in both. The aims of this work are to report the possibility of a motor onset of amyloid polyneuropathy and to suggest the search for TTR mutations in familial cases of axonal polyneuropathy. Second, to stress the possible occurrence of amyloid within the spinal canal as the potential pathogenesis and responsible for motor presentation.

Impaired facial emotion recognition in early-onset right mesial temporal lobe epilepsy.

BACKGROUND: Anteromedial temporal lobe regions, particularly the amygdala, participate in the recognition of emotions from facial expressions. The authors studied the ability of facial emotion recognition (ER) in subjects with symptomatic epilepsy, evaluating whether mesial temporal lobe damage is related to an impairment in the recognition of specific emotions and whether the onset of seizures in a critical period of life could prevent the development of ER. METHODS: Groups included patients with temporal lobe epilepsy (TLE) with MRI evidence of mesial temporal sclerosis (MTS) (n = 33); patients with TLE with MRI evidence of temporal lobe lesions other than MTS (n = 30); and patients with extratemporal epilepsy (n = 33). Healthy volunteers (n = 50) served as controls. ER was tested by matching a facial expression with the name of one of the following basic emotions: happiness, sadness, fear, disgust, and anger. A face-matching task was used to control visuoperceptual abilities with face stimuli. RESULTS: No subject showed deficits in the face-matching task. ER was impaired in patients with right MTS, especially for fearful faces. Patients presenting left MTS, right or left temporal lobe lesions other than MTS, or extratemporal seizure foci showed ER performances similar to controls. In all subjects with right TLE, the degree of emotion recognition impairment was related to age at first seizure (febrile or afebrile) and age at epilepsy onset. CONCLUSIONS: Early-onset right-sided mesial temporal lobe epilepsy is the key substrate determining a severe deficit in recognizing emotional facial expressions, especially fear.

Early ictal speech and motor inhibition in fronto-mesial epileptic seizures: a polygraphic study in one patient.

OBJECTIVE: To investigate ictal motor inhibition occurring during seizures in a patient with a tumor located in the left fronto-mesial pre-central cortex. METHODS: Awake and sleep video-polygraphic monitoring, recording scalp EEG and EMG activities from several cranial, trunk and limbs muscles, was performed in a patient with drug-resistant recurrent focal motor seizures before surgical treatment. Speech/motor tasks were repeatedly administered to the patient during the recording sessions in order to evaluate the occurrence of early ictal motor inhibition. RESULTS: Thirty-four seizures were recorded during wakefulness showing a stereotyped pattern of inhibition of speech and voluntary movements followed by sequential activation of upper limb-trunk-lower limb muscles contralateral to the tumor. Polygraphic recordings showed that: (1) initial speech and motor arrest were associated with the EMG evidence of progressive muscle tone suppression in cranial and right distal upper limb muscles; (2) tonic contraction of right deltoid, biceps brachii, intercostalis and paraspinalis muscles appeared after motor inhibition; (3) tonic-clonic activity in the right tibialis anterior muscle occurred at the end of seizures. Eleven subclinical seizures were recorded during sleep showing mild focal tonic EMG activity in right side trunk muscles. CONCLUSIONS: Our findings evidenced early and somatotopically organized inhibition of voluntary movement at the beginning of epileptic seizures with fronto-mesial onset. The demonstration that speech and motor arrest were associated with progressive EMG suppression in cranial and limb muscles supports the hypothesis of motor inhibitory seizures originating in the mesial aspect of pre-motor frontal cortex.

Video games are exciting: a European study of video game-induced seizures and epilepsy.

BACKGROUND: Video game seizures have been reported in photosensitive and non-photosensitive patients with epilepsy. The game Super Mario World, has led to many cases of first seizures. We examined whether this game was indeed more provocative than other programs and whether playing the game added to this effect. METHODS: We prospectively investigated 352 patients in four European cities, using a standard protocol including testing of a variety of visual stimuli. We correlated historical data on provocative factors in daily life with electroencephalographic laboratory findings. RESULTS: The video game, Super Mario World proved more epileptogenic than standard TV programs and as provocative as programs with flashing lights and patterns. Most striking was the fact that video game-viewing and-playing on the 50 and 100 Hz TV was significantly more provocative than viewing the standard program (P < 0.001, P < 0.05 respectively). Playing the video game Mario World on a 50 Hz TV, appeared to be significantly more provocative than playing this game on the 100 Hz TV (P < 0.001). Of 163 patients with a history of TV-, VG- or CG-seizures, 85% of them showed epileptiform discharges in response to photic stimulation, 44% to patterns, 59% to 50 Hz TV and 29% to 100 Hz TV. CONCLUSIONS: Children and adolescents with a history of video game seizures are, in the vast majority, photosensitive and should be investigated with standardised photic stimulation. Games and programs with bright background or flashing images are specifically provocative. Playing a video game on a 100 Hz TV is less provocative [published with videosequences].

Brainstem involvement in Unverricht-Lundborg disease (EPM1): An MRI and (1)H MRS study.

MRI of the brain and proton MRS ((1)H MRS) of the pons and dentate were obtained in 10 patients with genetically confirmed Unverricht-Lundborg disease (EPM1) and 20 control subjects. Patients with EPM1 showed (p < or = 0.01) loss of bulk of the basis pontis, medulla, and cerebellar hemispheres. Cerebral atrophy was present in six patients. The N-acetylaspartate/creatine and choline/creatine ratios were reduced in the pons but not in the dentate (p < or = 0.005). Brainstem involvement could play a role in pathophysiology of EPM1.