Tobias Loddenkemper

Deep brain stimulation in epilepsy

Summary Since the pioneering studies of Cooper et al. to influence epilepsy by cerebellar stimulation, numerous attempts have been made to reduce seizure frequency by stimulation of deep brain structures. Evidence from experimental animal studies suggests the existence of a nigral control of the epilepsy system. It is hypothesized that the dorsal midbrain anticonvulsant zone in the superior colliculi is under inhibitory control of efferents from the substantia nigra pars reticulata. Inhibition of the subthalamic nucleus (STN) could release the inhibitory effect of the substantia nigra pars reticulata on the dorsal midbrain anticonvulsant zone and thus activate the latter, raising the seizure threshold. Modulation of the seizure threshold by stimulation of deep brain structures—in particular, of the STN—is a promising future treatment option for patients with pharmacologically intractable epilepsy. Experimental studies supporting the existence of the nigral control of epilepsy system and preliminary results of STN stimulation in animals and humans are reviewed, and alternative mechanisms of seizure suppression by STN stimulation are discussed.

Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy.

Developmental Outcome After Epilepsy Surgery in Infancy

OBJECTIVES. Our goals were to determine the effect of epilepsy surgery in infants (<3 years of age) on development and describe factors associated with postoperative developmental outcome. METHODS. We identified 50 infants among 251 consecutive pediatric patients (<18 years old) undergoing epilepsy surgery. Charts were reviewed for clinical data and neurodevelopmental testing with the Bayley Scales of Infant Development. A developmental quotient was calculated to compare scores of children at different ages. RESULTS. Complete data were available on 24 of 50 infants. Surgeries included 14 hemispherectomies and 10 focal resections. Seventeen patients became seizure free; 5 patients had >90% seizure reduction, 1 had >50% seizure reduction, and 1 had no change. The developmental quotient indicated modest postoperative improvement of mental age. The preoperative and postoperative development quotients correlated well. Younger infants had a higher increase in developmental quotient after surgery. Patients with epileptic spasms were younger and had a lower developmental quotient at presentation, but increase in developmental quotient was higher in this subgroup. CONCLUSIONS. After surgery, seizure frequency and developmental quotient improved. Developmental status before surgery predicted developmental function after surgery. Patients who were operated on at younger age and with epileptic spasms showed the largest increase in developmental quotient after surgery.

Neurological manifestations of the oculodentodigital dysplasia syndrome

Oculodentodigital dysplasia (ODDD) (MIM 164200) is a rare autosomal dominant inherited disorder affecting the development of the face, eyes, limbs and dentition. Neurological complications are thought to be occasional manifestations of the disorder. This report illustrates the neurological manifestations by a pedigree of two ODDD patients with spastic paraparesis, cerebral white matter hyperintensity and basal ganglia hypointensity. A systematic review of the English, French, German and Italian literature on ODDD is also provided to summarize the neurological manifestations of the disorder. 243 previously described ODDD cases presented a spectrum of neurological manifestation including spasticity (25), subcortical white matter lesions (9) and basal ganglia changes (6) on MRI. Additional findings consisted of gaze palsy and squinting (28), bladder and bowel disturbances (21), visual loss (20) and blindness (4), hearing loss (15), ataxia (11), nystagmus (9), muscle weakness (5) and paresthesias (3). Neurological manifestations, including spasticity associated with MRI changes, are an underrecognized feature in the ODDD phenotype. A clinical guide to the neurological manifestations of ODDD may assist in the assessment of patients with this condition.

Lateralizing signs during seizures in focal epilepsy

This article reviews lateralizing semiological signs during epileptic seizures with respect to prediction of the side of the epileptogenic zone and, therefore, presurgical diagnostic value. The lateralizing significance of semiological signs and symptoms can frequently be concluded from knowledge of the cortical representation. Visual, auditory, painful, and autonomic auras, as well as ictal motor manifestations, e.g., version, clonic and tonic activity, unilateral epileptic spasms, dystonic posturing and unilateral automatisms, automatisms with preserved responsiveness, ictal spitting and vomiting, emotional facial asymmetry, unilateral eye blinking, ictal nystagmus, and akinesia, have been shown to have lateralizing value. Furthermore, ictal language manifestations and postictal features, such as Todds palsy, postictal aphasia, postictal nosewiping, postictal memory dysfunction, as well as peri-ictal water drinking, peri-ictal headache, and ipsilateral tongue biting, are reviewed. Knowledge and recognition of semiological lateralizing signs during seizures is an important component of the presurgical evaluation of epilepsy surgery candidates and adds further information to video/EEG monitoring, neuroimaging, functional mapping, and neuropsychological evaluation.

Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy

PURPOSE To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. RESULTS Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3-17.9) and median duration of epilepsy 8.0 (1.9-16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. CONCLUSIONS In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group.

Can Semiology Predict Psychogenic Nonepileptic Seizures? A Prospective Study

Reducing health and economic burdens from diagnostic delay of psychogenic nonepileptic seizures (PNES) requires prompt referral for video electroencephalography (VEEG) monitoring, the diagnostic gold standard. Practitioners make VEEG referrals when semiology suggests PNES, although few semiological signs are supported by well‐designed studies, and most VEEG studies neglect to concurrently measure how accurately seizure witnesses can ascertain semiology. In this study, we estimate the value of eyewitness‐reported and video‐documented semiology for predicting PNES, and we measure accuracy of eyewitness reports.

Intravenous ketamine for the treatment of refractory status epilepticus: A retrospective multicenter study

To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE).

Autonomic changes with seizures correlate with postictal EEG suppression

Objective: Sudden unexpected death in epilepsy (SUDEP) poses a poorly understood but considerable risk to people with uncontrolled epilepsy. There is controversy regarding the significance of postictal generalized EEG suppression as a biomarker for SUDEP risk, and it remains unknown whether postictal EEG suppression has a neurologic correlate. Here, we examined the profile of autonomic alterations accompanying seizures with a wrist-worn biosensor and explored the relationship between autonomic dysregulation and postictal EEG suppression. Methods: We used custom-built wrist-worn sensors to continuously record the sympathetically mediated electrodermal activity (EDA) of patients with refractory epilepsy admitted to the long-term video-EEG monitoring unit. Parasympathetic-modulated high-frequency (HF) power of heart rate variability was measured from concurrent EKG recordings. Results: A total of 34 seizures comprising 22 complex partial and 12 tonic-clonic seizures from 11 patients were analyzed. The postictal period was characterized by a surge in EDA and heightened heart rate coinciding with persistent suppression of HF power. An increase in the EDA response amplitude correlated with an increase in the duration of EEG suppression (r = 0.81, p = 0.003). Decreased HF power correlated with an increase in the duration of EEG suppression (r = −0.87, p = 0.002). Conclusion: The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures. These results provide autonomic correlates of postictal EEG suppression and highlight a critical window of postictal autonomic dysregulation that may be relevant in the pathogenesis of SUDEP.

Convulsive seizure detection using a wrist-worn electrodermal activity and accelerometry biosensor

The special requirements for a seizure detector suitable for everyday use in terms of cost, comfort, and social acceptance call for alternatives to electroencephalography (EEG)–based methods. Therefore, we developed an algorithm for automatic detection of generalized tonic–clonic (GTC) seizures based on sympathetically mediated electrodermal activity (EDA) and accelerometry measured using a novel wrist‐worn biosensor. The problem of GTC seizure detection was posed as a supervised learning task in which the goal was to classify 10‐s epochs as a seizure or nonseizure event based on 19 extracted features from EDA and accelerometry recordings using a Support Vector Machine. Performance was evaluated using a double cross‐validation method. The new seizure detection algorithm was tested on >4,213 h of recordings from 80 patients and detected 15 (94%) of 16 of the GTC seizures from seven patients with 130 false alarms (0.74 per 24 h). This algorithm can potentially provide a convulsive seizure alarm system for caregivers and objective quantification of seizure frequency.