Antonella Benvenga

The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy

The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of ‘autoimmune epilepsy’. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy.

Mobile phone emissions modulate brain excitability in patients with focal epilepsy

BACKGROUND Electromagnetic fields (EMFs) emitted by mobile phones had been shown to increase cortical excitability in healthy subjects following 45 min of continuous exposure on the ipsilateral hemisphere. OBJECTIVE Using Transcranial Magnetic Stimulation (TMS), the current study assessed the effects of acute exposure to mobile phone EMFs on the cortical excitability in patients with focal epilepsy. METHODS Ten patients with cryptogenic focal epilepsy originating outside the primary motor area (M1) were studied. Paired-pulse TMS were applied to the M1 of both the hemisphere ipsilateral (IH) and contralateral (CH) to the epileptic focus before and immediately after real/sham exposure to the GSM-EMFs (45 min). The TMS study was carried out in all subjects in three different experimental sessions (IH and CH exposure, sham), 1 week apart, according to a crossover, double-blind and counter-balanced paradigm. RESULTS The present study clearly demonstrated that an acute and relatively prolonged exposure to GSM-EMFs modulates cortical excitability in patients affected by focal epilepsy; however, in contrast to healthy subjects, these effects were evident only after EMFs exposure over the hemisphere contralateral to the epileptic focus (CH). They were characterized by a significant cortical excitability increase in the exposed hemisphere paired with slight excitability decrease in the other one (IH). Both sham and real EMFs exposure of the IH did not affect brain excitability. CONCLUSION Present results suggest a significant interaction between the brain excitability changes induced by EMFs and the epileptic focus, which eliminated the excitability enhancing effects of EMFs evident only in the CH.

A novel c132‐134del mutation in Unverricht‐Lundborg disease and the review of literature of heterozygous compound patients

Unverricht‐Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disease caused by mutation of the cystatin B gene (CSTB), located on chromosome 21q22.3. The most common mutation is an expansion of unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations are rare. Among these, heterozygous compound mutations are described to induce a more severe phenotype than that of homozygous dodecameric repetition. We report two siblings affected by heterozygous compound mutations carrying a novel mutation of the deletion of three nucleotides in exon 2 of the gene in position 132–134 of the coding sequence (c.132‐134del) in the allele not including the dodecamer repetition. This mutation results in the loss of two amino acid residues and insertion of an asparagine in position 44 (p.Lys44_Ser45delinsAsn). Our patients presented a very different clinical picture. The male patient had a severe myoclonus, drug‐resistant epilepsy and psychiatric comorbidity, while his affected sister had only very rare seizures and sporadic myoclonic jerks at awakening. The revision of literature about heterozygous compound EPM1 patients confirms this gender phenotypic expressivity, with female patients carrying less severe symptoms than male patients. These data lead to the hypothesis of complex gender‐specific factors interacting with CSTB expressivity in EPM1 patients.

Hyperventilation induces sympathetic overactivation in mesial temporal epilepsy

OBJECTIVE Hyperventilation (HV) during electroencephalography (EEG) is a standard clinical procedure to trigger seizures in patients affected by mesial temporal lobe epilepsy (MTLE). Despite the pathophysiology of this susceptibility to HV is not definitively understood, it may be hypothesized to be related to ictal and interictal sympathetic nervous system abnormalities, the presence of which is well known in MTLE patients. In order to test this hypothesis we investigated the HV effect on heart rate variability (HRV) in a group of MTLE patients, compared to a matched group of healthy controls. MATERIAL AND METHODS Forty patients affected by MTLE and 40 age- and sex-matched controls were enrolled in the study. In those subjects, a standard electroencephalographic recording has been acquired and the high and the low frequency components (HF, LF) of heart rate variability (HRV) and their ratio (LF/HF) have been analyzed at rest and during the HV. Indeed, LF/HF is a reliable index of sympathetic tone modulation. RESULTS HRV did not differ between MTLE and healthy subjects at rest, whereas HV induced a significant LF/HF increase only in MTLE. Within the MTLE group, males showed higher LF/HF increase during HV respect to females, while no differences related to the side of the epileptic focus were found. DISCUSSION MTLE patients showed an increased sympathetic response to HV compared to healthy subjects. HRV analysis points towards an autonomic overactivation as a pathophysiological pathway subtending seizure triggered by hyperventilation in MTLE. Autonomic susceptibility in MTLE may help to explain the increased prevalence of arrhythmic events in these patients, potentially predisposing to Sudden Unexpected Death in Epilepsy (SUDEP).

Osteomalacic myopathy: An uncommon side effect of antiepileptic drugs

366:2294–2304. 2. Rosen BA. Guillain-Barr e syndrome. Pediatr Rev 2012;33:164–170. 3. Antoine JC, Mosnier JF, Absi L, Convers P, Honnorat J, Michel D. Carcinoma associated paraneoplastic peripheral neuropathies in patients with and without anti-onconeural antibodies. J Neurol Neurosurg Psychiatry 1999;67:7–14. 4. Lagrange E, Veran O, Besson G. Pure motor relapsing Guillain-Barr e syndrome associated with anti-GM1 antibodies revealing urinary bladder cancer. Eur J Neurol 2007;14:e7. 5. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135–1140. 6. Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, et al. Antibodies to Kv1 potassium channel-complex proteins leucinerich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 2010;133:2734–2748. 7. Irani SR, Pettingill P, Kleopa KA, Schiza N, Waters P, Mazia C, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012;72:241–255. 8. Hart IK, Waters C, Vincent A, Newland C, Beeson D, Pongs O, et al. Autoantibodies detected to expressed K1 channels are implicated in neuromyotonia. Ann Neurol 1997;41:238–246. 9. Lancaster E, Huijbers MG, Bar V, Boronat A, Wong A, MartinezHernandez E, et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 2011;69:303–311. 10. T€ uz€ un E, K€ urt€ unc€ u M, Lang B, Ic€ oz S, Akman-Demir G, Eraksoy M, et al. Bickerstaff’s encephalitis and Miller Fisher syndrome associated with voltage-gated potassium channel and novel anti-neuronal antibodies. Eur J Neurol 2010;17:1304–1307.

Calcium metabolism serum markers in adult patients with epilepsy and the effect of vitamin D supplementation on seizure control

PURPOSE To evaluate serum markers of calcium metabolism in adult patients with epilepsy (PWE) treated with antiepileptic drugs (AEDs) and the effect of vitamin D supplementation on seizure frequency. METHODS Serum levels of calcium, phosphate, intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D (25[OH]D) were compared in 160 PWE on chronic therapy with AEDs and 42 matched controls. Blood concentrations were analyzed taking into account the different features of epilepsy and treatment. Finally, the effect of vitamin D supplementation on seizure control was assessed in a subgroup of 48 drug resistant epileptic patients. RESULTS PWE showed lower serum levels of 25[OH]D compared to control subjects (p < .001). Only 25% PWE showed normal 25[OH]D levels, whereas 41,9% had a vitamin D failure and 33,1% a vitamin D deficiency (p < .001). 25[OH]D serum levels depended on treatment duration, number of medications and enzyme-inducing AEDs (p < .001, p < .001, p = .013, respectively). Polytherapy and enzyme-inducing AEDs showed more detrimental effects on the 25[OH]D and calcium serum levels. The administration of vitamin D failed to significantly improve seizure control. CONCLUSIONS PWE show deficiency of vitamin D. The serum levels of 25[OH]D depend on the features and duration of AEDs treatment. Vitamin D administration in drug resistant epilepsy patients does not result in a reduction of seizure frequency.

P2.12 Mobile phone emissions modulate brain excitability in patients affected by focal epilepsy

Introduction: It has been shown in healthy subjects that electromagnetic fields (EMF) emitted by mobile phones increase cortical excitability. Objective: The aim of our study is to assess via Transcranial Magnetic Stimulation (TMS) the effects of the acute exposition to electromagnetic fields of a mobile phone operating in the Global System for Mobile Communication (GSM-EMFs) on the cortical excitability in patients affected by focal epilepsy. Methods: Ten patients affected by focal epilepsy originating outside the primary motor area (M1) were studied using a double-blind, cross-over, counter-balanced design. Single and paired-pulse TMS were applied to the M1 of the hemisphere ipsilateral (IPSIH) to the epileptic focus and the contralateral one (CONTRAH) before and immediately after real/sham exposure to the GSM-EMFs (45 minutes). Interstimulus intervals (ISIs) of 1 and 3 ms were selected to test short-interval intracortical inhibition (SICI), ISIs of 7, 9, 11, 13 ms were used to test intracortical facilitation (ICF). Results: The real exposure over the CONTRAH side induced an increase of brain excitability in the same exposed hemisphere paired with an excitability decrease in the other one (IPSIH). Focusing on the EMF effect across ISIs, we observed in the same condition a clear increase of ICF in the CONTRAH (exposed), and concurrently an increase of SICI in the other one. These results could be due to interhemispheric inhibition mechanisms. There were no significant changes of the brain excitability in the sham and the real IPSIH exposure conditions. No significant changes of rest motor threshold were found in all conditions. Conclusions: Our findings suggest that in patients with focal epilepsy GSM-EMFs acute exposure of the CONTRAH but not the IPSIH significantly modulates cortical excitability.

P16-6 Effects of mobile phone emissions on the motor cortex excitability in focal epilepsy

Methods: Sixteen patients with refractory focal epilepsy were studied with TMS prior to and three months following epilepsy surgery. AED use in each patient did not change between the pre and post-operative TMS studies. Motor threshold (MT) at rest and recovery curve analysis using paired pulse stimulation at a number of short (2, 5, 10 and 15 ms) and long (50 300 ms) interstimulus intervals (ISIs) were measured. The patients were divided at the end of a one year follow-up period into seizure free (10/16) and ongoing seizure groups. Findings: A decrease in cortical excitability (p < 0.05), maximum at the long ISIs 250 and 300 ms was observed in both hemispheres postoperatively in the seizure free patients. This was not seen in patients who continued to have seizures. Conclusion: Successful surgical removal of the epileptic focus and postoperative seizure freedom is associated with bilateral decreased cortical excitability. This suggests that changes in cortical excitability associated with refractory epilepsy are not permanent and can be reversed if seizures are controlled.

P6-24 Mobile phone emission modulates inter-hemispheric functional coupling of EEG alpha rhythms in epileptic patients

EEG changes. He did not lose consciousness during seizures. Interictal EEG showed normal background and paroxysmal fast activities. There were no special findings in magnetic resonance imaging, magnetoencephalogram, and single photon emission computed tomography. His IQ was 37 on the Tanaka-Binet intelligence test. Conclusions: Fast waves which were seen in myoclonic status are characteristic in this case. We will discuss this atypical EEG pattern and consider the diagnosis.