Jörg Wellmer

Focal cortical dysplasia type IIb: completeness of cortical, not subcortical, resection is necessary for seizure freedom.

Purpose:u2002 Focal cortical dysplasia type IIb (FCD IIb) lesions are highly epileptogenic and frequently cause pharmacoresistant epilepsy. Complete surgical resection leads to seizure freedom in most cases. However, the term “complete” resection is controversial with regard to the necessity of performing resections of the subcortical zone, which is frequently seen in these lesions on magnetic resonance imaging (MRI).

A systematic review of suggestive seizure induction for the diagnosis of psychogenic nonepileptic seizures

Suggestive seizure induction is a widely used method for diagnosing psychogenic nonepileptic seizures (PNES). Despite seven decades of multidisciplinary research, however, there is still no unified protocol, no definitive agreement on the ethical framework and no consensus on diagnostic utility. This systematic review surveys the evidence at hand and addresses clinically relevant aspects of suggestive seizure induction. In addition to its use for facilitating the diagnostic process, its mechanism of action and utility in elucidating the psychopathology of PNES will be discussed.

Hyperventilation and photic stimulation are useful additions to a placebo-based suggestive seizure induction protocol in patients with psychogenic nonepileptic seizures

The early and definitive diagnosis of psychogenic nonepileptic seizures is a common challenge in epileptology practice. Suggestive seizure induction is a valuable tool to aid the differentiation between epileptic and psychogenic nonepileptic seizures, especially when long-term video-EEG monitoring is inconclusive or unavailable. In this retrospective analysis, we compared the diagnostic yield of a classical, placebo-based induction protocol with that of an extended protocol that includes hyperventilation and photic stimulation as means of suggestion while also implementing more open, standardized patient information. We investigated whether the diversification of suggestive seizure induction has an effect on diagnostic yield and whether it preempts the administration of placebo. Data from 52 patients with confirmed psychogenic nonepileptic seizures were analyzed. While suggestive seizure induction using only placebo-based suggestion provoked a typical event in 13 of 20 patients (65%), the extended protocol was positive in 27 of 34 cases (84%); this improvement was not significant (p=0.11). Noninvasive suggestion techniques accounted for 78% of inductions, avoiding placebo administration in a majority of patients. Still, placebo remains an important part of suggestive seizure induction, responsible for 22% (6 out of 27) of successful inductions using our extended protocol. Our study demonstrates that the diversification of suggestive seizure induction is feasible and beneficial for both patients and diagnosticians.

Diagnosing psychogenic nonepileptic seizures: Video-EEG monitoring, suggestive seizure induction and diagnostic certainty

Psychogenic nonepileptic seizures (PNES) can remain undiagnosed for many years, leading to unnecessary medication and delayed treatment. A recent report by the International League Against Epilepsy Nonepileptic Seizures Task Force recommends a staged approach to the diagnosis of PNES (LaFrance, et al., 2013). We aimed to investigate its practical utility, and to apply the proposed classification to evaluate the role of long-term video-EEG monitoring (VEEG) and suggestive seizure induction (SSI) in PNES workup. Using electronic medical records, 122 inpatients (mean age 36.0±12.9years; 68% women) who received the diagnosis of PNES at our epilepsy center during a 4.3-year time period were included. There was an 82.8% agreement between diagnostic certainty documented at discharge and that assigned retroactively using the Task Force recommendations. In a minority of cases, having used the Task Force criteria could have encouraged the clinicians to give more certain diagnoses, exemplifying the Task Force reports utility. Both VEEG and SSI were effective at supporting high level diagnostic certainty. Interestingly, about one in four patients (26.2%) had a non-diagnostic (negative) VEEG but a positive SSI. On average, this subgroup did not have significantly shorter mean VEEG recording times than VEEG-positive patients. However, VEEG-negative/SSI-positive patients had a significantly lower habitual seizure frequency than their counterparts. This finding emphasizes the utility of SSI in ascertaining the diagnosis of PNES in patients who do not have a spontaneous habitual event during VEEG due to, for example, low seizure frequency.

Rho-associated protein kinase 2 (ROCK2): a new target of autoimmunity in paraneoplastic encephalitis

Onconeural antibodies are associated with cancer and paraneoplastic encephalitis. While their pathogenic role is still largely unknown, their high diagnostic value is undisputed. In this study we describe the discovery of a novel target of autoimmunity in an index case of paraneoplastic encephalitis associated with urogenital cancer.A 75-year-old man with a history of invasive bladder carcinoma 6 years ago with multiple recurrences and a newly discovered renal cell carcinoma presented with seizures and progressive cognitive decline followed by super-refractory status epilepticus. Clinical and ancillary findings including brain biopsy suggested paraneoplastic encephalitis. Immunohistochemistry of the brain biopsy was used to characterize the inflammatory response. Indirect immunofluorescence assay (IFA) was used for autoantibody screening. The autoantigen was identified by histo-immunoprecipitation and mass spectrometry and was validated by expressing the recombinant antigen in HEK293 cells and neutralization tests. Sera from 125 control patients were screened using IFA to test for the novel autoantibodies.IFA analysis of serum revealed a novel autoantibody against brain tissue. An intracellular enzyme, Rho-associated protein kinase 2 (ROCK2), was identified as target-antigen. ROCK2 was expressed in affected brain tissue and archival bladder tumor samples of this patient. Brain histopathology revealed appositions of cytotoxic CD8+ T cells on ROCK2-positive neurons. ROCK2 antibodies were not found in the sera of 20 patients with bladder cancer and 17 with renal cancer, both without neurological symptoms, 49 healthy controls, and 39 patients with other antineuronal autoantibodies. In conclusion, novel onconeural antibodies targeting ROCK2 are associated with paraneoplastic encephalitis and should be screened for when paraneoplastic neurological syndromes, especially in patients with urogenital cancers, occur.

Recurrent loss of consciousness despite DDD pacing: psychogenic pseudosyncope in a 19-year-old man.

Unexplained recurrent syncope requires interdisciplinary assessment. Paroxysmal bradyand tachycardias can mimic psychiatric conditions [1, 2] and, on the other hand, epileptic seizures, panic attacks and psychogenic phenomena can be mistaken for dysrhythmias. While the former misdiagnosis can be avoided by structured cardiological workup, the latter requires neurological assessment considering the differential diagnosis psychogenic pseudosyncope [3]. A 19-year-old man with recurrent syncope of unknown origin was referred to our epilepsy center for neurological assessment. Attacks with transient loss of consciousness first occurred 2 years previously. A typical event would often be preceded by a rising sensation of pressure and pulsation in the neck and head, followed by a (usually backwards) fall. The ensuing unconsciousness usually lasted 4–5 min with reorientation afterwards lasting several minutes. No motor activity, tongue bite or enuresis during the events was reported. Within 3 months prior to neurological assessment, 1–2 events per week were noted. Previous medical history included autonomic dysfunction, arterial hypertension, nicotine addiction, obesity (135 kg) and obstructive sleep apnea; he was diagnosed in other institutions as having ‘‘Tourette’s syndrome, social phobia, Asperger syndrome’’ and ‘‘attention deficit disorder’’. Multiple cardiological investigations had led to implantation of an event recorder, which registered eventcorrelated narrow complex tachycardias of up to 187 bpm as well as bradycardias of 40 bpm. An electrophysiological study revealed no sign of habitual arrhythmia and no inducible tachycardias. ‘‘Sick sinus syndrome’’ was diagnosed and a DDD pacemaker was implanted. However, the attacks persisted with unaltered frequency. On repeated cardiological assessment, pacemaker function was intact and no signs of autonomic dysfunction or dysrhythmia were found. A neurological investigation was recommended. During 2 days of continuous electroencephalography(EEG-)video monitoring, no interictal epileptic discharges were recorded and no transient loss of consciousness occurred. Tilt-table test was impossible due to weight restrictions of the equipment; Schellong testing was normal with no sign of autonomic dysfunction. The patient was then subjected to suggestive ‘‘seizure’’ provocation through postural maneuvers (sitting down and standing up swiftly) and intravenous administration of saline (mixed with Vitamin B12 for pink coloring); he was informed that these techniques induced fits in some patients. Mattresses were placed on the floor to avoid injury. Rapid postural changes akin to Schellong testing did not elicit loss of consciousness or any significant changes in blood pressure. After three consecutive injections, however, the patient suddenly fell to the ground and was unresponsive for 92 s. Before, during and after the event Electronic supplementary material The online version of this article (doi:10.1007/s00392-014-0711-5) contains supplementary material, which is available to authorized users.

Coregistrating magnetic source and magnetic resonance imaging for epilepsy surgery in focal cortical dysplasia

Background Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals. Methods We here present data from 21 adult FCD II patients, investigated during a 10u202fyear period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes. Results FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3u202f±u202f8,1u202fmm to the MRI-lesion. After a mean follow up of >3u202fyears, we saw >80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033). Conclusion We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy.

Latent autoimmune diabetes and limbic encephalitis with antibodies against glutamic acid decarboxylase

Antibodies against glutamic acid decarboxylase (GAD) are a hallmark of type 1 diabetes and its late-onset variant, latent autoimmune diabetes of the adult (LADA).1 While cerebrovascular disease and dementia are common causes of cognitive dysfunction and neurological deficits in diabetic patients,2,3 rare autoimmune disorders of the central nervous system such as stiff-person syndrom or limbic encephalits can also occur on the basis of shared GAD autoimmunity.4,5

Research on dissociative seizures: A bibliometric analysis and visualization of the scientific landscape

Dissociative seizures are a common and often elusive differential diagnosis in epilepsy centers. Considering their high prevalence, long diagnostic delays, and disappointing rates of treatment response, scientific research dedicated to dissociative seizures is surprisingly scarce. In order to chart the scientific landscape of dissociative seizures and to visualize thematic clusters and trends in research, a comprehensive bibliometric analysis was performed. The Web of Science database was examined to identify relevant English language documents from the last half-century. A total of 1751 documents with titles referring to dissociative seizures were identified. Automated textual analysis of all titles and abstracts revealed that research clusters around three major topics: differential diagnosis in epilepsy centers, management and treatment, and psychopathology. Time analysis of term networks revealed that the focus of clinical research has moved from diagnostic procedures to treatment approaches. Furthermore, interest within etiological research is shifting from an emphasis on early life trauma and personality traits to the role of anxiety and emotion regulation. With respect to individual contributing authors, a relatively small network of prolific scientists with a remarkable degree of collaboration emerges. By mapping relevant publications, it becomes evident that dissociative seizures still represent a subject mostly within the realm of neurology and epileptology, with a tendency to settle in the latter domain. This analysis sheds light on an important niche subject and highlights trends in research focus and output.

P90. Super selective amytal injection (Wada-Test) in a 14 year old with left sided parieto-insular epilepsy due to Focal cortical dysplasia

Introduction The classical Wada-test is performed by injecting a narcotic (usually amobarbital) into the left internal carotid artery (ICA) in order to establish language dominance. In the presurgical workup of epilepsy, it has largely been replaced by less invasive methods such as functional MRI and functional Transcranial Doppler Ultrasound. In exceptional cases, the Wada-test can be performed superselectively: the narcotic is injected into a branch of the middle cerebral artery (MCA). This allows proving or excluding language function in a small brain volume. We document the utility of a superselective Wada test in a 14-year-old girl with a dysplastic lesion in the left supramarginal cortex and dorsal insula. Methods A 14u202fyear old girl presented with pharmacoresistant epilepsy. 3u202fT MRI revealed a left dorsal insular/supramaginal gyrus FLAIR hyperintensity suspicious of focal cortical dysplasia as the likely epileptogenic lesion. Multimodal presurgical work-up confirmed this. Yet, it was questionable if an extended lesionectomy would harm language function. Left ACI Wada-Test was inconclusive. Therefore, a superselective Wada-Test of an M3 branch of the left MCA/perirolandic artery was performed. Results Following the application of 70u202fmg Amobarbital, both EEG-slowing in electrodes C3, P3, and T5 and repeat angiography confirmed the correct localization of barbiturate action. During the superselective Wada-test, the patient was able to complete a comprehensive test battery of language functions (counting, naming, reading, calculating, spontaneous speech) without evident dysfunction. Neuronavigation and intraoperative electrophysiological monitoring supported an extended lesionectomy, preserving the white matter adjacent to the pyramidal tract. Early after surgery, the patient suffered from a Gerstmann’s syndrome and slight amnestic aphasia. However, this resolved within the first postoperative weeks. Histopathology confirmed focal cortical dysplasia type IIb. Following surgery, the patient is now seizure free for 18u202fmonths under reduced antiepileptic drugs. Her academic performance has improved compared to the preoperative status. Conclusion The Wada-test simulates the effect of resective or disconnective surgery on language functions by temporarily inactivating brain areas. Technical advances in catheter angiography allow injecting the narcotic into single MCA-branches or other arteries of similar diameter, thus simulating the effect of small cortical resections. In selected patients, this method can be a valuable supplement of multimodal presurgical workup, and may obviate the need for intra- or extraoperative cortical mapping.