Christoph Kellinghaus

Electro-clinical and imaging characteristics of focal cortical dysplasia: correlation with pathological subtypes.

INTRODUCTION Focal cortical dysplasia (CD) is a common cause of pharmaco-resistant epilepsy. CD is due to abnormalities in neuronal migration, proliferation, and/or differentiation that result in four distinct pathological subtypes: 1A, 1B, 2A, and 2B. In order to provide clinical correlation to these pathological subtypes, we reviewed the electro-clinical and imaging characteristics and surgical outcomes of the four pathological subtypes of CD. METHODS We retrospectively reviewed patient data from epilepsy surgeries at the Cleveland Clinic Foundation between 1990 and 2002. Only those patients with the definite pathological diagnosis of isolated cortical dysplasia were included in the study (n = 145). RESULTS Pathological subtypes 2A and 2B were predominantly frontal in location, and had a more severe epilepsy syndrome with lower intelligence quotient scores than subtypes 1A and 1B. Patients with subtype 1A FCD had less severe, later onset epilepsy that was predominantly located in the temporal lobe. Risk factors for epilepsy included febrile seizures for type 1A, head trauma for types 1A and 1B, and perinatal adverse events for type 2B. Type 2B demonstrated significantly more FLAIR signal abnormalities than the other groups. Sixty-three percent of patients overall had an Engel I outcome at 6 months follow-up. The best outcomes were in the 2B subtype, and in those who did not require an invasive EEG evaluation. CONCLUSIONS Clinically important differences exist between the pathological subtypes of CD, which may assist in their management, and provide further insight into their underlying pathophysiology.

Intravenous lacosamide for treatment of status epilepticus.

Kellinghaus C, Berning S, Immisch I, Larch J, Rosenow F, Rossetti AO, Tilz C, Trinka E. Intravenous lacosamide for treatment of status epilepticus.
Acta Neurol Scand: 2011: 123: 137–141.
© 2010 John Wiley & Sons A/S.

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy

Background: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. Objective: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. Methods: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor “group,” covariate “age”). Results: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. Conclusions: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI. CPE = cryptogenic partial epilepsy; DTI = diffusion tensor imaging; EPI = echoplanar imaging; FA = fractional anisotropy; GMC = gray matter concentration; GTCS = generalized tonic-clonic seizures; IGE = idiopathic generalized epilepsy; JME = juvenile myoclonic epilepsy; MNI = Montreal Neurological Institute; ROI = region of interest; VBM = voxel based morphometry; WM = white matter.

Focal Semiologic and Electroencephalographic Features in Patients with Juvenile Myoclonic Epilepsy

Summary:  Purpose: A few reports have described focal electroencephalographic or clinical features or both of juvenile myoclonic epilepsy (JME), but without video‐EEG documentation. We examined focal clinical and EEG features in patients with JME who underwent video‐EEG monitoring.

Intravenous lacosamide as successful treatment for nonconvulsive status epilepticus after failure of first-line therapy

Treatment of status epilepticus usually requires intravenous anticonvulsant therapy. Lacosamide is a novel anticonvulsant drug that is available as infusion solution. We describe a patient with nonconvulsive status epilepticus who was successfully treated with intravenous lacosamide.

Frequency of seizures and epilepsy in neurological HIV-infected patients

BACKGROUND Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. METHODS The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. RESULTS Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse. CONCLUSIONS Seizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group.

Severity of histopathologic abnormalities and in vivo epileptogenicity in the in utero radiation model of rats is dose dependent.

Summary:  Purpose: Malformations of cortical development (MCDs) are a frequent cause of refractory epilepsy in humans. The in utero radiation model in rats shares many clinical and histopathologic characteristics with human MCDs. Previous studies reported the presence of clinical seizures in radiated rats, but also suggested a dose‐dependent differential effect.

Effects of eyelid closure, blinks, and eye movements on the electroencephalogram

OBJECTIVE To characterize the effects of the eyeball and eyelid positions during eyeblinks on electroencephalographic (EEG) potentials. METHODS Movements of the upper eyelids and eyes were measured in two healthy subjects using the magnetic search coil technique during horizontal and vertical eye rotations, eyeblinks, and lid closure. Corresponding signal changes were recorded simultaneously on the electroencephalogram (EEG). RESULTS Spontaneous blinks produced small eye movements directed down and inward, whereas slow or forced blinks were associated with delayed upward eye rotations (i.e. Bells phenomenon); both types of blinks caused positive EEG potentials with bifrontal distribution maximum at Fp1 and Fp2. CONCLUSIONS In prior reports, these positive EEG artifacts have been attributed to upward eyeball rotation during blinks-Bells phenomenon. By contrast, our findings indicate that movements of the eyelid contribute to a greater extent to these EEG potentials than do upward eyeball rotations. SIGNIFICANCE Care is required in attributing EEG artifacts to movements of either eyeball or eyelid, since our findings suggest that they both contribute to these potentials.

Atrioventricular block following lacosamide intoxication

Lacosamide (LCM) is a novel anticonvulsant that modulates voltage-dependent sodium channels. Although it is known to cause a slight, dose-dependent prolongation of the PR interval on the ECG, third-degree atrioventricular (AV) block has been described as an adverse event in only a few patients participating in diabetic neuropathic pain studies and in no patient with epilepsy. We describe an 89-year old patient with decreased renal function and taking two other negative dromotropic agents who accidentally received two intravenous boli of 400 mg LCM within 6 hours. She had a normal PQ interval before and after the first dose of LCM and developed a reversible complete AV block approximately 30 minutes after the second bolus. We conclude that particular caution must be exercised when using very high doses of LCM in patients with significant cardial and renal risk factors.

Incidence of seizures in patients with multiple sclerosis treated with intrathecal baclofen

Oral and intrathecal baclofen (ITB) have been associated with epileptic seizures. The authors observed a higher incidence of epileptic seizures in 99 patients with multiple sclerosis (MS) treated with ITB vs a matched control group (7% vs 1%, p < 0.05). Three patients with MS on ITB developed status epilepticus. Seizures were often associated with additional triggering factors.