Anna Serafini

Are Early Seizures Predictive of Epilepsy after a Stroke? Results of a Population-Based Study

Background: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures. Methods: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study. Results: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS. Conclusions: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation.

Neurophysiology of juvenile myoclonic epilepsy

Juvenile myclonic epilepsy (JME) can be firmly diagnosed by a careful interview of the patient focusing on the seizures and by the EEG with the help, if necessary, of long-term video-EEG monitoring using sleep and/or sleep deprivation. Background activity is normal. The interictal EEG shows diffuse or generalized spike-wave (SW) and polyspike-wave (PSW) discharges. In some patients, non-specific changes or misleading features such as focal changes are found. Changes are mostly seen at sleep onset and at awakening. Provoked awakenings are more likely to activate interictal paroxysmal abnormalities than spontaneous awakenings. The presence of a photoparoxysmal response with or without myoclonic jerks (MJ) is common (30% of the cases). Myoclonic jerks are associated with a discharge of fast, irregular, generalized PSWs that predominate anteriorly. Myoclonic jerks appear to be associated with rhythmic EEG (spike) potentials at around 20Hz. These frequencies are in the range of movement-related fast sensorimotor cortex physiological rhythms. The application of jerk-locked averaging technique has provided findings consistent with a cortical origin of MJ. Paired TMS (transcranial magnetic stimulation) studies showed a defective intracortical inhibition, due to impaired GABA-A mediated mechanisms. In this review, we present the EEG characteristics of JME with particular emphasis on the pathophysiology of MJ and on the role of sleep deprivation on interictal and ictal changes.

Sleep before and after temporal lobe epilepsy surgery

PURPOSE Patients with epilepsy often complain of non-restorative sleep. This is the consequence of the acute effect of seizures and the chronic effect of epilepsy responsible for disrupting sleep architecture. Other factors such as antiepileptic drugs (AEDs), also play a role in the alteration of sleep organization. The aim of this study was to evaluate the specific effect of seizures and interictal epileptiform abnormalities (IEAs) on sleep, in particular to see whether reducing seizure frequency by epilepsy surgery might improve sleep organization in these patients. METHODS Eleven patients with refractory mesial temporal lobe epilepsy, who underwent surgical treatment and who were seizure free at the follow-up, were included in the study. Treatment with AEDs was not significantly modified before the second year of follow-up. Patients were evaluated before surgery, at 1-year and 2-year follow-up visits with a videoEEG monitoring (24h/24). At each follow-up visit, interictal epileptiform abnormalities and sleep macrostructure parameters were assessed. RESULTS All patients showed a reduction of their IEAs. At 1-year follow-up, total sleep time and REM sleep increased significantly (p=0.032 and p=0.006, respectively). At 2-year follow-up, an important increase of REM sleep was observed (p=0.028). Most significant variations were noted 1 year after surgery. No significant variations were observed between the first and the second year after surgery. CONCLUSIONS Surgical treatment of temporal lobe epilepsy may improve sleep macrostructure by reducing the number of seizures and of IEAs. These results indirectly confirm the role of epilepsy in disrupting sleep organization chronically.

Cardiac asystole during a cluster of right temporo-parietal seizures

Ictal bradycardia and asystole can appear during an epileptic seizure. They must be promptly recognized and treated due to their potential life threatening consequences. Indeed, they have been implicated in the pathogenesis of sudden unexpected death in epilepsy (SUDEP). We report the case of a 33 year-old woman with a right temporo-parietal lobe epilepsy who presented a 19 s asystole during a cluster of seizures. Careful interview revealed appearance of numerous episodes of fall in the previous years. The patient underwent cardiological investigations including echocardiography and His bundle electrography that resulted to be normal. A pacemaker was immediately implanted and, although she continued presenting seizures, no more episodes of falls occurred. In order to better preview ictal asystole several risk factors need to be searched. Attention should be paid to an accurate medical history (ask for episodes of falls) and a simultaneous ECG/EEG recording. The occurrence of bradycardia during a seizure should lead to further cardiological investigations. This could help preventing the occurrence of dramatic consequences such as traumatic falls or SUDEP.

Worsening of negative myoclonus by lamotrigine in a case of idiopathic focal epilepsy of children with long-term follow-up

We report the case of a 5-year-old boy, first referred in 1995, with benign epilepsy with centro-temporal spikes (BECTS) with proximal negative myoclonus as the only seizure type who experienced severe aggravation of seizures when lamotrigine (25 mg/d) was prescribed in association to valproate (400 mg/d). Lamotrigine was stopped and progressively the drops of the legs disappeared within 6 months but valproate was continued. The overall prognosis was benign, confirmed by long-term follow-up until age 20, inkeeping with the diagnosis of BECTS. There was a clear relationship between introduction of lamotrigine and the detrimental effect and the condition improved dramatically when lamotrigine was stopped. Thus lamotrigine may aggravate BECTS in certain conditions and should be used with proper care in this indication.

Temporal intermittent delta activity: A marker of juvenile absence epilepsy?

PURPOSE To report three cases of juvenile absence epilepsy (JAE) with temporal intermittent, asynchronous delta activity over the temporal regions. METHODS Long term video-EEG using the international 10/20 system and supplementary anterior-inferior temporal electrodes. Cohort of 1123 patients included in our active file seen at least one time over one year. RESULTS Among 23 patients with JAE (2% of our active file), temporal intermittent rhythmic delta activity (TIRDA) was observed in 3 (13%). Moreover, this activity was never observed in 80 patients with juvenile myoclonic epilepsy. None of the three patients had inadequate antiepileptic drug for idiopathic generalized epilepsy. Case 1 had no antiepileptic drug. Case 2 was treated with valproate (1000 mg/day) and case 3 with levetiracetam (1500 mg/day). These delta activities were activated by hyperventilation and drowsiness. They decreased in NREM sleep and reappeared in REM sleep. The frequency was around 3 Hz. These changes were not frequently recorded in any given patient. CONCLUSION The presence of TIRDA in the clinical and EEG context is very suggestive of JAE as posterior delta waves are of childhood absence epilepsy but with a more anterior location over the temporal lobe. This pattern was not described before probably because in this easily diagnosed and treated type of IGE, few patients have long-term video-EEG and also because a wrong diagnosis of focal epilepsy can be made. This pattern must be known to avoid the risk of treating this epilepsy by inappropriate antiepileptic drugs.

Transcranial magnetic stimulation in sleep fragmentation: a model to better understand sleep disorders

OBJECTIVE To investigate practice-dependent plasticity and cortical inhibition/excitability in good sleepers after a night of sleep fragmentation (SF), by means of transcranial magnetic stimulation (TMS). METHODS In basal condition (BC), after a full night of spontaneous sleep, and in fragmented condition (FC), after a fragmented night of sleep, motor evoked potential (MEP) amplitude, motor threshold (MT), silent period (SP), and intracortical inhibition were assessed. In both conditions subjects performed, also, a bimanual motor task: MEPs were recorded before and after exercise, and after rest. We evaluated the presence of post-exercise facilitation and delayed facilitation. Subjects reported their alertness level (Stanford Sleepiness Scale-SSS). RESULTS MT and SSS were significantly increased in SF. Instead, no significant differences for MEP amplitude or SP or intracortical inhibition were found. In both conditions post-exercise facilitation and delayed facilitation were present. CONCLUSION SF produces disruption of nocturnal sleep and increases daytime sleepiness. Confirmatory features of this clinical behaviour could be that in FC we observed a significant increase in SSS and in MT. SF was unable to modify cortical inhibition\excitability and\or to influence plasticity-related parameters. These results seem inconsistent with some of TMS alterations observed in sleep deprivation (SD) and restless legs syndrome (RLS). We suggest that SD and SF represent different phenomena that can depend on various networks acting on motor cortex. We speculate that alterations in cortical excitability found in RLS are intrinsically related to the underlying disease itself and are not instead directly associated with the SF present in RLS.

Zonisamide for refractory juvenile absence epilepsy

PURPOSE To examine the clinical effect of zonisamide (ZNS) in patients with drug-resistant juvenile absence epilepsy (JAE). METHODS Between 2006 and 2010, 13 JAE patients were successively treated with add-on ZNS. Safety and efficacy were assessed according to the patient and caregiver reports at visits every 3 months. Response rate was defined as a 50% or greater reduction in seizure frequency. RESULTS Mean age was 42 years. No patient had been seizure free for a period ≥12 months before ZNS. The mean follow-up was 34 months. The mean dosage of ZNS was 388 mg. ZNS was effective for absence seizures (AS) in all patients (more than 50% AS reduction). Four patients reached seizure reduction on 550-600 mg/day. Three (23%) had a reduction in AS frequency >75% and five (38.5%) between 50% and 75%. Seizure freedom was achieved in five patients (38.5%) (three patients with AS only and two with AS plus generalized tonic-clonic seizures (GTCS)). Before ZNS, four patients had AS evolving to absence status. After ZNS, three of them were in the seizure-free group, the later never experienced this type of complication. Among seven patients with AS plus GTCS, two of them did not report any improvement in the frequency of GTCS (29%). CONCLUSION This observational post-marketing study confirms the broad-spectrum activity of ZNS that includes GTCS, myoclonic seizures and now AS. This study provides evidence that add-on ZNS is efficient and well tolerated in adult patients with refractory JAE, even at high doses.

Focal epilepsy as first symptom in CADASIL

Recurrent transient ischemic attacks, migraine and dementia represent the principal symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). During the course of the disease, about 10% of patients may experience epileptic seizures, mainly related to the presence of an ischemic stroke. We present a 30-year-old woman with new-onset focal epilepsy leading to the diagnosis of CADASIL. The neuropsychological testing revealed no cognitive impairment. Interictal EEG demonstrated spikes and polyspikes with low amplitude over the right occipital region during NREM sleep. MRI showed white-matter hyperintensities on both hemispheres with confluent lesions at the right parieto-occipital junction, with juxtacortical components. Like in multiple sclerosis, we can suppose that this type of white matter lesions, close to the cortex, may be causative of seizures.

Sleep Disturbances Among Dialysis Patients

Sleep disturbances are extremely common among dialysis patients. Subjective sleep complaints are reported in up to 80% of patients and are characterized by difficulty in initiating and maintaining sleep, problems with restlessness, jerking legs, snoring, choking sensations and/or daytime sleepiness (Holley et al., 1992; Walker et al., 1995; Veiga et al., 1997). Epidemiological studies have found how sleep apnea syndrome (SAS), restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are much more prevalent than in the general population. These sleep problems appear to have significant negative effects on the quality of life as they are often cited as major sources of stress. Indeed, interviews of patients on hemodialysis and on peritoneal dialysis have found that sleep disturbances are one of the seven most distressing symptoms experienced (Eichel et al., 1986; Bass et al., 1999). Half of patients complaining of sleep disturbances feel that these problems affect their daily living and activity, and 21% consider that relief of this symptom would improve significantly their subjective quality of life (Parfrey et al., 1988; Iliescu et al., 2003). In the following sections two major sleep disturbances associated with Insomnia, Restless Legs Syndrome and Sleep Apnea Syndrome, will be reviewed in detail.