Epilepsy related to focal neuronal lipofuscinosis: extra-frontal localization, EEG signatures and GABA involvement.

Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.

Are auras a reliable clinical indicator in medial temporal lobe epilepsy with hippocampal sclerosis?

BACKGROUND AND PURPOSE: Medial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS) is the most frequent form of surgical temporal lobe epilepsy. In this study, it was aimed to determine whether different types of aura represent a cardinal and characteristic feature of MTLE-HS and might provide a diagnostic complement to help identify patients who will be seizure-free after surgery. METHODS: All types of auras and associations of auras reported by 400 MTLE-HS patients referred for surgery were retrospectively collected and their statistical correlation with the postoperative outcome was examined in a subgroup of 305 patients who underwent surgery. RESULTS: A total of 876 auras were collected, classified into 12 categories. Globally, MTLE-HS patients reported widely variable auras and groupings of auras. Most common were autonomic and abdominal visceral auras, followed by psychoaffective and experiential auras; less common, but seen in 10%-15% of patients, were non-specific auras, somatosensory auras and visual auras, and least common, reported by less than 10% of patients, were auditory, gustatory, vestibular, olfactory and intellectual auras. No auras were reported in 10% of patients. 65% of patients experienced more than one type of aura (two to seven). No specific groupings of aura type were apparent. No evidence was found for correlation between postoperative outcome and (i) any category of aura, (ii) the number of categories of aura per patient and (iii) any association of categories of auras. CONCLUSION: Auras and association of auras vary widely in MTLE-HS and provide no useful insight into surgical outcome.

Lateralizing value of semiology in medial temporal lobe epilepsy.

OBJECTIVES: Analysing the clinical characteristics of seizures constitutes a fundamental aspect of the presurgical evaluation of patients with medial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE-HS), the most frequent form of focal epilepsy accessible to surgery. We sought to retrospectively determine whether objective manifestations could have a reliable lateralizing value in a large population of MTLE-HS patients and if their presence could help to identify those patients who would be seizure free after surgery. MATERIAL AND METHODS: We analysed the frequency and predictive lateralizing value of objective ictal and postictal signs in 391 patients with MTLE-HS (183 left/208 right). Data were derived from chart review and not from blinded videoEEG analysis. Correlation between the presence of reliable lateralizing signs and postoperative outcome was performed in a subgroup of 302 patients who underwent surgery. RESULTS: Contralateral dystonic posturing was the most frequent and reliable lateralizing sign that correctly lateralized the focus in 96% of patients. Unilateral head/eye deviation was noted in 42% of the patients and predicted unilateral focus in 67%. Ipsilateral postictal nose wiping, contralateral clonus and hypokinesia correctly lateralized the focus in 75%, 81%, respectively, and 100 of patients but were less frequently depicted. Postictal aphasia was a strong lateralizing sign for left MLE-HS. The presence of reliable lateralizing signs was not a predictor of seizure freedom. CONCLUSION: Seizure semiology is a simple tool that may permit reliable lateralization of the seizure focus in MTLE-HS. The presence of reliable lateralizing signs is not associated with a better postoperative outcome.

[Obstructive sleep apnea syndrome: a cause of cognitive disorders in the elderly?]. / Le syndrome d'apnées obstructives du sommeil : une cause de troubles cognitifs chez les personnes âgées ?

Obstructive sleep apnea syndrome is a chronic disease characterized by repeated upper airway obstructions during sleep, resulting in fragmented sleep with arousals, nocturnal intermittent hypoxemia and diurnal dysfunctions. Despite its high prevalence in elderly, sleep apnea syndrome seems to be underestimated and difficult to be recognized because of the lack of clinical symptoms specificity in this population. Among the numerous consequences of the obstructive sleep apnea syndrome, cognitive impairment prevails on the attention, executive functions and memory. Neuroimaging studies in human and experimental models allowed to highlight neural correlates of these cognitive dysfunctions in obstructive sleep apnea syndrome. The obstructive sleep apnea syndrome with cognitive impairment shares some features with Alzheimer's disease, involving genetic predisposition ApoE4, hippocampus and synaptic plasticity abnormalities. In this context, the question arises whether obstructive sleep apnea syndrome is a possible etiological or aggravating factor of cognitive decline in elderly with mild cognitive impairment or Alzheimer's disease. Although there are conflicting results in studies evaluating therapeutic efficiency of continuous positive air pressure, obstructive sleep apnea syndrome seems nevertheless as a correctable factor, at least for its impact on some cognitive consequences. Looking for sleep apnea syndrome in elderly with cognitive decline should be considered in a global, diagnosis and therapeutic management.

The yield of routine EEG in geriatric patients: A prospective hospital-based study.

STUDY AIM: To study the yield of routine EEG in geriatric patients. PATIENTS AND METHODS: We examined standard EEG recordings of 701 patients aged 84.6±6.4 years. These were performed over a 15 month-period in a geriatric hospital. The majority of patients were hospitalized and 46.5% suffered from multiple medical problems. RESULTS: We found EEG abnormalities in 392/701 (56%) patients. These consisted of permanent diffuse slowing, either isolated (17.1%) or with intermixed epileptiform abnormalities (2.4%), focal slowing (15.4%), intermittent diffuse slowing (8.9%), triphasic waves (1.14%), periodic epileptiform discharges (0.57%), flat and inactive tracing (0.14%), status epilepticus (0.99%), seizures (0.42%), interictal epileptiform abnormalities (8.7%). Epileptiform abnormalities (both ictal and interictal) were observed in 92/701 (13.1%) patients. These were focal in the majority of cases (85.9%), most frequent in temporal regions (42%), followed by centroparietal (20.2%) and temporo-parieto-occipital carrefour regions (17.2%), but less frequent in frontal (6.3%) and occipital regions (3.8%). We found sleep activity without other EEG abnormalities in 13.7% of patients and subclinical rhythmic electrographic discharge in adult (SREDA) in 1% of cases. CONCLUSIONS: In this study, EEG abnormalities were very common, which reflects the high frequency of cerebral dysfunction in geriatric patients. These abnormalities are of various types, often suggestive of different aetiologies, and may be helpful in clinical management.

[Idiopathic generalised epilepsies in the elderly: the viewpoint of a geriatrician]. / Epilepsies généralisées idiopathiques chez le sujet âgé : le point de vue du gériatre.

INTRODUCTION: Long-term follow-up studies indicate a low remission rate in idiopathic generalised epilepsies (IGE) (Martinez-Juarez et al., 2006), suggesting they may persist to an advanced age. However there are few estimates of IGE frequency in the elderly. METHODS: EEGs of 700 patients aged over 70 years, recorded between January 2006 and March 2007, were reviewed for anomalies consistent with IGE. We then examined the clinical history of patients with these anomalies. RESULTS: A persistent IGE was identified in four female patients (mean age: 79 years); in two cases it was a juvenile myoclonic epilepsy (JME) and in two an epilepsy with grand mal seizures. Seizures in three patients had begun in childhood or adolescence and in one at 40 years. Before hospitalization, few or no seizures were reported and IGE had not been diagnosed. IGE was revealed in each patient by a relatively severe event: an absence status (AS), subcontinuous myoclonic seizures or repeated convulsive generalised seizures (CGS). These events were not situation-related but in one patient the relapse of simple convulsive seizures, may have been related to the withdrawal of anti-epileptic drugs (AED) several months previously. EEG records showed generalised spikes or polyspikes and waves organised in a status epilepticus or in interictal rhythmic discharges. In one case they were evident only from a 24 hours recording. Clonazepam injection was used to suppress the AS episode and the subintrant myoclonia. After the AS, interictal generalised epileptic discharges persisted. Two of the four patients had familial history of epilepsy or febrile seizures but in no case was an epileptogenic lesion evident in brain CT scan or MRI. Clinical exams and biologic parameters were normal. All of the patients had worked and were married with children. Appropriate therapies were followed after the diagnosis of IGE. One patient with JME had been treated by Valproate which was discontinued by the general practitioner because of lethargy and replaced by Carbamazepine; seizures were aggravated under both Carbamazepine and then Lamotrigine and until the patient became seizure-free on Levetiracetam. The antiepiletic treatment was also modified in a second patient, while the two others responded well to Valproate. CONCLUSIONS: IGE can exacerbate in the elderly, as different types of seizures including AS, subintrant myoclonia or repeated CGS. Our data suggest persistent IGE are quite frequent in an aged population and may be underestimated due to difficulties in diagnosis. Correctly diagnosed, adjustment of AED may offer substantial clinical improvements in IGE of the elderly.