Melania Guida

A Clinical-EEG Study of Sleepiness and Psychological Symptoms in Pharmacoresistant Epilepsy Patients Treated with Lacosamide

Our aim was to evaluate the EEG and clinical modifications induced by the new antiepileptic drug lacosamide (LCM) in patients with epilepsy. We evaluated 10 patients affected by focal pharmacoresistant epilepsy in which LCM (mean 250 mg/day) was added to the preexisting antiepileptic therapy, which was left unmodified. Morning waking EEG recording was performed before (t0) and at 6 months (t1) after starting LCM. At t0 and t1, patients were also administered questionnaires evaluating mood, anxiety, sleep, sleepiness, and fatigue (Beck Depression Inventory; State-Trait Anxiety Inventory Y1 and Y2; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Fatigue Severity Scale). We performed a quantitative analysis of EEG interictal abnormalities and background EEG power spectrum analysis. LCM as an add-on did not significantly affect anxiety, depression, sleepiness, sleep quality, and fatigue scales. Similarly, adding LCM to preexisting therapy did not modify significantly patient EEGs in terms of absolute power, relative power, mean frequency, and interictal abnormalities occurrence. In conclusion, in this small cohort of patients, we confirmed that LCM as an add-on does not affect subjective parameters which play a role, among others, in therapy tolerability, and our clinical impression was further supported by evaluation of EEG spectral analysis.

What is the role for EEG after sleep deprivation in the diagnosis of epilepsy? Issues, controversies, and future directions.

In patients with a first seizure, the identification of early sensitive and specific biomarkers for formulating a diagnosis of epilepsy is fundamental. Sleep deprivation (SD) has long been used as a means of enhancing EEG sensitivity in the diagnostic process. However, huge methodological differences among the studies addressing this topic have led to highly variable results and often confusing assumptions. Here, we provide a detailed description of the correlations between SD and epilepsy, along with their putative mechanistic explanations derived from experimental studies in animals and humans. We also outline the clinical studies evaluating the role of SD EEG and discuss them critically in terms of: (a) study design and SD EEG methodology; (b) EEG sensitivity and specificity; (c) the role of drug-induced sleep EEG and EEG during spontaneously occurring sleep; and (d) the relevance of patient features, syndromes, and subsyndromes, as well as their correlations with neuroimaging details. Finally, we propose specific studies that might increase the role of SD EEG in the diagnosis and prognosis of epilepsy.

Controversial Issues on EEG after Sleep Deprivation for the Diagnosis of Epilepsy

EEG after sleep deprivation (SD-EEG) is widely used in many epilepsy centers as an important tool in the epilepsy diagnosis process. However, after more than 40 years of use, there are a number of issues which still need to be clarified concerning its features and role. In particular, the many scientific papers addressing its role in epilepsy diagnosis often differ remarkably from each other in terms of the type of patients assessed, their description and study design. Furthermore, also the length and the type of EEG performed after SD, as well as the length of SD itself, vary dramatically from one study to another. In this paper we shortly underscore the abovementioned differences among the different reports, as well as some interpretations of the findings obtained in the different studies. This analysis emphasizes, if needed, how SD-EEG still represents a crucial step in epilepsy diagnosis, and how additional, controlled studies might further shape its precise diagnostic/prognostic role.

Treatment of epilepsy in patients with Alzheimer’s disease

ABSTRACT Introduction: Epilepsy is significantly more frequent in AD patients than in age-matched controls, even though the true extent of the phenomenon is not clear yet. Areas covered: In this review, we describe in detail the available data on the pharmacological treatment of epilepsy in patients with AD. We also briefly describe general principles of AEDs use in elderly, as well as the potential cognitive profile of AEDs and safety of concomitant psychotropic drugs in patients with epilepsy and AD. Expert commentary: As some preclinical data suggest a role of epileptiform discharges in cognitive decline in AD, a prompt diagnosis and treatment of seizures in these patients should be pursued. The few data on the use of AEDs in AD patients suggest that newer AEDs (in particular lamotrigine and levetiracetam) might be good choices. Experimental data even support a potential role of some AEDs in modifying the disease course of AD.

Susceptibility-weighted imaging in parenchymal neurosyphilis: identification of a new MRI finding.

Background General paresis (GP) is a late form of parenchymal neurosyphilis causing dementia and neuropsychiatric disorders. The diagnosis is often difficult since the clinical signs are protean. So far, neuroimaging has played a minor role as radiological findings are not specific. Methods We studied three immunocompetent patients, admitted to hospital for cognitive impairment. The diagnosis of neurosyphilis was formulated on the basis of serological texts and cerebrospinal fluid analysis. The patients underwent a 3 T MR examination including susceptibility-weighted imaging (SWI) sequence before and after the initiation of penicillin therapy. Results In all patients, SWI revealed cortical hypointensity, mostly distributed in frontal and temporal lobes. In drug-naive patients, the hypointensity extended over the whole cortical thickness, from the cortical/subcortical junction to the pial surface. After starting the penicillin therapy, the cortical hypointensity partially reversed, involving only the deep cortical layers. Conclusions The MRI pattern at SWI observed in patients with GP was not reported in other infectious or inflammatory disease of the central nervous system, thus we suggest it could be a peculiar radiological finding of the disease. On the basis of previous pathological data, we hypothesise that cortical SWI hypointensity could be expression of iron deposits within activated microglia.

Effects of antiepileptic drugs on interictal epileptiform discharges in focal epilepsies: an update on current evidence

Interictal epileptiform discharges (IEDs), occurring in the electroencephalograms (EEG) of patients with focal epilepsy, are crucial for diagnosis, while their relationship with seizure severity and recurrence is controversial. The effects of antiepileptic drugs (AEDs) on IEDs are even more debated. In general, it is currently believed by experts in the field that most of the classical AEDs do not significantly affect IEDs occurrence in these patients, and that monitoring their EEG effects during treatment is useless. In this review, we update the existing literature on the effects of classical and newer AEDs on focal IEDs, emphasizing the scarcity of data concerning the latter. We also discuss potential limits of available clinical and experimental data and future perspectives.

Social cognition in Juvenile Myoclonic Epilepsy

OBJECTIVE Juvenile Myoclonic Epilepsy (JME) is a common genetic generalized epilepsy syndrome. Several studies have detailed cognitive and imaging abnormalities pointing to frontal lobe dysfunction, as well as disadvantageous behavioral traits and poor social outcome, challenging the commonly held view of JME being a benign disorder. Social cognition is the ability to elaborate mental representations of social interactions and to use them correctly in social contexts, and includes Theory of Mind (ToM), which pertains to the attribution of cognitive and affective mental states to self and others and seems to rely on complex fronto-temporal interactions. ToM has been recently assessed in focal epilepsy syndromes, but little is available for generalized epilepsies. We performed a cross-sectional study to assess social cognition, with an emphasis on ToM, as well as standard cognitive functions in patients with JME. METHOD We recruited twenty JME patients and twenty matched controls. Tests used to assess social cognition and ToM included the Emotion Attribution Task, Strange Stories Task (SST), Faux Pas Task (FPT), Reading the Mind in the Eyes Task and Social Situation Task. Subjects were also assessed via an extensive neuropsychological battery. RESULTS Patients exhibited worse performance in the SST and in several scores of the FPT. They also showed widespread cognitive impairment, involving executive functions, psychomotor speed, verbal and visuo-spatial memory. CONCLUSIONS In addition to cognitive impairment for fronto-temporal tasks, some features of social cognition are also altered in JME. The latter deficit may underlie the poor social outcome previously described for these patients, and might also relate to imaging findings of frontal lobe dysfunction.

F43. Electrophysiological tests in patients with anti-MuSK myasthenia gravis: A retrospective study

Introduction Myasthenia gravis (MG) with autoantibodies to muscle-specific tyrosine kinase (MuSK) represents a distinct type of disease, as compared MG with antibodies against acetylcholine receptor (AchR-Abs). MuSK-MG patients have peculiar clinical features characterized by predominant oculo-bulbar symptoms and a lack of response to conventional MG treatments. Since the role of electrophysiological tests in MuSK patients is still argued, our aim was to investigate their electrophysiological profile in order to arise a light over this darkness. Methods We retrospectively evaluated repetitive nerve stimulation (RNS) and single-fibre electromyography (SF-EMG) reports of 63 MuSK patients, at the time of MG diagnosis, and we compared them with 35 non-timomatous AChR-Abs positive patients matched with MuSK group according to gender, age at onset of MG, age at MG diagnosis and severity of the disease. Disease severity was graded according to Myasthenia Gravis Foundation of America (MGFA) classification. Seronegative patients and thymoma-associated MG patients were excluded from the study. Results Sixty-three MuSK patients (11 males; 52 females; mean age at MG onset: 37 ± 2.0; mean age at diagnosis: 38.7 ± 2.0) and 35 AChR-Abs positive patients (9 males; 26 females; mean age at MG onset: 31.2 ± 2.7: mean age at diagnosis: 33.1 ± 2.5) were enrolled in the study. Fifty-nine MuSK patients (93.6%) and 31 AChR-Abs positive patients (88.5%) underwent RNS, whereas SF-EMG was tested in 17 MuSK patients and in 7 AChR-Abs patients. RNS showed a significant decrement in a higher percentage of AChR-Abs positive patients than the MuSK group (p  Conclusion While SR-EMG positivity was significantly higher in AChR-Abs group, there was no difference regarding SF-EMG. In MusK group, the decrement of RNS was more evident in proximal muscles while RNS in distal muscles can be negative. Although neurophysiological evaluation is still important for MG diagnosis, it plays a secondary role after anti-MuSK titration.

S61. Electroencephalography patterns in patients with thymoma and limbic autoimmune encephalitis: Report of three cases

Introduction Although Myasthenia gravis (MG) is the most common autoimmune disease associated with thymoma, a small proportion of thymomatous patients can suffer from limbic autoimmune encephalitis (LE). LE is usually characterized by rapid progressive short-term memory deficits, psychiatric symptoms, and seizures. Patients can present antibodies against cell surface antigens, including contactin-associated protein-like 2 (CASPR2) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Our aim was to analyze the EEG findings of these patients to find possible EEG homologies among their patterns. Methods Clinical information was obtained from a retrospective review of medical records and EEG recordings of three patients with thymoma and LE: two with seropositivity for AMPAR antibodies and one for CASPR2 antibodies. Results The first case was a 37 years-old man with a subacute onset of memory loss, confusion, anxiety and behavioral disorders in the setting of an invasive thymoma (type B2-B3). Brain MRI and dosage of acetylcholine receptor antibodies (AChR-Abs) were normal. EEG showed bilateral fronto-temporal spikes together with slow theta and delta activity. Clinical suspicion of a paraneoplastic neurological syndrome associated with thymoma was confirmed by the serological presence of AMPAR-Abs. The second case was a 47 years-old female patient with Myasthenia Gravis (MG) and seropositivity for AChR-Abs, treated for recurrent thymoma (type B2). She presented three episodes of generalized seizures, together with mental disorientation, impairment of recent memory and insomnia. Brain MRI was normal. EEG showed a peculiar pattern, comprising lateralized right fronto-temporal spikes and generalized sharp waves. Serological tests detected the presence of antibodies to CASPR2. The third case was a 52 years-old female patient with thymoma (type B2-B3) who developed confusion, short-term memory loss and psychomotor agitation after thymectomy. Cerebrospinal fluid (CSF) examination showed a mild blood-CSF barrier damage and brain MRI revealed increased T2 signal involving mesio-temporal cortical areas. EEG showed electrical abnormalities in the fronto-temporal regions. Antibodies to the glutamate receptor 1 (GluR1) and GluR3 subunits of AMPAR were detected both in serum and CSF. Conclusion Limbic autoimmune encephalitis should be suspected in patients with invasive thymoma and subacute onset of confusion, memory loss and seizures. In all these three cases EEG showed epileptiform activity, especially in the fronto-temporal regions, together with slow theta and delta activity, without a pathognomonic pattern. Our results strongly emphasize the importance of testing biological samples when a possible autoimmune CNS involvement is suspected. Even if antibody testing remains the cornerstone in the diagnostic pathway, EEG is paramount in the differential diagnosis with similar disorders, in orienting toward limbic encephalopathy, especially when MRI is inconclusive.

Cyclic alternating pattern and interictal epileptiform discharges during morning sleep after sleep deprivation in temporal lobe epilepsy.

PURPOSE Sleep deprivation (SD) increases the occurrence of interictal epileptiform discharges (IED) compared to basal EEG in temporal lobe epilepsy (TLE). In adults, EEG after SD is usually performed in the morning after SD. We aimed to evaluate whether morning sleep after SD bears additional IED-inducing effects compared with nocturnal physiological sleep, and whether changes in sleep stability (described by the cyclic alternating pattern-CAP) play a significant role. METHODS Adult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7days from n-PSG, they underwent also a morning EEG after night SD (SD-EEG). We included only TLE patients in which both recordings showed IED. SD-EEG consisted of waking up patients at 2:00 AM and performing video EEG at 8:00 AM. For both recordings, we obtained the following markers for the first sleep cycle: IED/h (Spike Index, SI), sleep macrostructure, microstructure (NREM CAP rate; A1, A2 and A3 Indices), and SI association with CAP variables. RESULTS The macrostructure of the first sleep cycle was similar in n-PSG and morning SD-EEG, whereas CAP rate and SI were significantly higher in SD-EEG. SI increase was selectively associated with CAP phases. CONCLUSIONS SD increases the instability of morning recovery sleep compared with n-PSG, and particularly enhances CAP A1 phases, which are associated with the majority of IED. Thus, higher instability of morning recovery sleep may account at least in part for the increased IED yield in SD-EEG in TLE patients.