Fritz Leutmezer

Electrocardiographic changes at the onset of Epileptic seizures

Summary:  Purpose: We studied heart‐rate (HR) changes at the transition from the preictal to the ictal state in patients with focal epilepsies to gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function.

Ictal Scalp EEG in Unilateral Mesial Temporal Lobe Epilepsy

Summary: Purpose: We wished to determine the predictive significance of unilateral hippocampal atrophy and interictal spikes on localization of ictal scalp EEG changes and assess whether ictal EEG provides information that might change treatment or influence prognosis in patients with such characteristics of epilepsy.

Postictal Psychosis in Temporal Lobe Epilepsy

Summary:  Purpose: Postictal psychosis is a well‐known complication, occurring especially in patients with temporal lobe epilepsy. It usually runs a benign course. The literature on this topic is sparse, and the underlying pathogenic mechanisms are not known.

Idiopathic generalized epilepsy phenotypes associated with different EFHC1 mutations

We sequenced 61 patients with various idiopathic generalized epilepsy (IGE) syndromes for mutations in the EFHC1 gene. We detected three novel heterozygous missense mutations (I174V, C259Y, A394S) and one possibly pathogenic variant in the 3′ UTR (2014t>c). The mutation I174V was also detected in 1 of 372 screened patients with temporal lobe epilepsy. We conclude that mutations in the EFHC1 gene may underlie different types of epilepsy syndromes.

Clinical seizure lateralization in mesial temporal lobe epilepsy: Differences between patients with unitemporal and bitemporal interictal spikes

Objective: To compare the reliability of clinical seizure lateralization in temporal lobe epilepsy patients with unitemporal and bitemporal independent interictal spikes and unilateral hippocampal atrophy or sclerosis (HA/HS) on MRI scan. Patients and methods: We studied 11 patients with unitemporal and 10 patients with bitemporal interictal spikes. We calculated a spike ratio by dividing the number of spikes ipsilateral to the side of HA/HS by those occurring contralaterally. Results: Clinical seizure lateralization was correct, i.e., ipsilateral to the side of HA/HS, significantly more often in the unitemporal group. Spike ratios were significantly higher in seizures that were lateralized correctly as compared with both incorrectly and nonlateralized seizures. Within the individual patients, a significant positive correlation between spike ratios and the proportion of correctly lateralized seizures was found. We identified three categories of symptoms according to lateralization accuracy. Category 1 symptoms (version, postictal paresis, and early ictal vomiting/retching) lateralized to the side of HA/HS in 100% of patients in the uni- and bitemporal groups. Category 2 symptoms (dystonic posturing, mouth deviation, postictal dysnomia/dysphasia, and ictal speech) provided a 100% correct lateralization in the unitemporal but not in the bitemporal patients. Category 3 symptoms (nonversive early head turning and unilateral upper extremity automatisms) yielded erroneous lateralization in both patient groups. Conclusions: We conclude that reliable clinical seizure lateralization in mesial temporal lobe epilepsy can only be achieved in patients with unitemporal interictal spikes, whereas clinical lateralization in patients with bitemporal spikes must be viewed cautiously.

Disruption of nigrostriatal and cerebellothalamic pathways in dopamine responsive Holmes’ tremor

Holmes’ tremor is an unusual combination of rest, postural and kinetic tremor of the extremities. Medical treatment of this condition still remains unsatisfactory. The case of a 20-year-old female patient is reported who developed right-sided Holmes’ tremor 9 months after a left-sided, cavernoma induced midbrain/pontine haemorrhage at the age of 16 years. Beta-CIT single photon emission computed tomography revealed abolished dopamine transporter activity in the left basal ganglia and striatum, in accordance with missing ipsilateral tegmento-frontal connectivity (medial forebrain bundle), demonstrated by diffusion tensor MRI. Tractography showed reduced fibre connectivity of the superior and middle cerebellar peduncles on the lesioned side. Administration of pramipexole and L-DOPA led to a clinically significant reduction in tremor severity. In conclusion, our results support the notion that Holmes’ tremor was a result of diminished striatal dopaminergic input in our patient.

Exploratory investigation of eight circulating plasma markers in brain tumor patients

Several blood biomarkers have been established for the early diagnosis, screening and follow-up of non central nervous system cancers. However, there is lack of knowledge on biochemical blood alterations in brain tumor patients. In this study, we prospectively collected blood plasma samples of 105 adult brain tumor patients with diffuse low-grade glioma (World Health Organization (WHO) II, n = 7), anaplastic glioma (WHO III, n = 10), glioblastoma multiforme (WHO IV, glioblastoma multiforme (GBM)) (n = 34), meningioma (WHO I, n = 8), atypical meningioma (WHO II, n = 5), and intracerebral metastasis (ICM; n = 41). In each case, we measured plasma concentrations of neuropeptide Y, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, placental growth factor (PlGF), S100B, secretagogin, interleukin 8, and glial fibrillary acidic protein (GFAP) using enzyme-linked immunosorbent assay. Plasma marker concentrations were correlated to patient parameters including neuropathological diagnosis and neuroradiological features. Most of the markers were detectable in all diagnostic categories in variable concentrations. GFAP plasma detectability was strongly associated with a diagnosis of GBM (p < 0.001). Plasma GFAP and plasma placental growth factor showed promising moderate potential in the differential diagnosis of unifocal GBM versus unifocal supratentorial ICM (area under the curve = 0.73, p < 0.05). To summarize, our data show that none of the investigated markers is suitable to substitute histological diagnosis. However, measurement of circulating GFAP and PlGF may support neuroradiological differential diagnosis of GBM versus ICM.

Highly encephalitogenic aquaporin 4-specific T cells and NMO-IgG jointly orchestrate lesion location and tissue damage in the CNS.

In neuromyelitis optica (NMO), astrocytes become targets for pathogenic aquaporin 4 (AQP4)-specific antibodies which gain access to the central nervous system (CNS) in the course of inflammatory processes. Since these antibodies belong to a T cell-dependent subgroup of immunoglobulins, and since NMO lesions contain activated CD4+ T cells, the question arose whether AQP4-specific T cells might not only provide T cell help for antibody production, but also play an important role in the induction of NMO lesions. We show here that highly pathogenic, AQP4-peptide-specific T cells exist in Lewis rats, which recognize AQP4268–285 as their specific antigen and cause severe panencephalitis. These T cells are re-activated behind the blood–brain barrier and deeply infiltrate the CNS parenchyma of the optic nerves, the brain, and the spinal cord, while T cells with other AQP4-peptide specificities are essentially confined to the meninges. Although AQP4268–285-specific T cells are found throughout the entire neuraxis, they have NMO-typical “hotspots” for infiltration, i.e. periventricular and periaqueductal regions, hypothalamus, medulla, the dorsal horns of spinal cord, and the optic nerves. Most remarkably, together with NMO-IgG, they initiate large astrocyte-destructive lesions which are located predominantly in spinal cord gray matter. We conclude that the processing of AQP4 by antigen presenting cells in Lewis rats produces a highly encephalitogenic AQP4 epitope (AQP4268–285), that T cells specific for this epitope are found in the immune repertoire of normal Lewis rats and can be readily expanded, and that AQP4268–285-specific T cells produce NMO-like lesions in the presence of NMO-IgG.

Genital automatisms in complex partial seizures

Objective: To determine which brain region is responsible for the generation of sexual automatisms. Methods: Ninety consecutive patients with medically refractory focal epilepsy (74 with temporal lobe and 16 with frontal lobe epilepsy) referred to an epilepsy monitoring unit were studied. The occurrence of the following sexual automatisms was assessed during prolonged video-EEG monitoring: 1) repeatedly grabbing or fondling the genitals and 2) pelvic or truncal thrusting or similar movements. Results: Five patients repeatedly fondled or grabbed their genitals during or immediately after some of their seizures. All five had temporal lobe epilepsy, as evidenced from prolonged video-EEG monitoring, high-resolution MRI, and good to excellent outcome after epilepsy surgery. Sexual automatisms did not occur with frontal lobe epilepsy. Conclusion: Sexual automatisms cannot be related exclusively to frontal lobe seizures. As previously proposed, apparently sexual hypermotoric pelvic or truncal movements are common in frontal lobe seizures, but this study suggests that discrete genital automatisms, like fondling and grabbing the genitals, are more common in seizures evolving from the temporal lobe.

A novel mutation in the MFSD8 gene in late infantile neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinoses (NCL) are lysosomal storage disorders and constitute the most common group of progressive neurodegenerative diseases in childhood. Most NCLs are inherited in a recessive manner and are clinically characterised by a variable age at onset, epileptic seizures, psychomotor decline, visual impairment and premature death. To date, eight causative genes have been identified to underlie various clinical forms of NCL. We performed a genome-wide linkage analysis followed by sequencing the recently described NCL gene MFSD8 in three affected and three unaffected members of a consanguineous Egyptian family with an autosomal recessively inherited progressive neurodegenerative disorder. The clinical picture of the patients was compatible with a late infantile NCL (LINCL); however, impairment of the visual system was not a cardinal symptom in the respective family. By linkage analysis, we identified two putative loci on chromosome 1p36.11-p35.1 and 4q28.1-q28.2. The latter locus (4q28.1-q28.2) contained the MFSD8 gene, comprising a novel homozygous missense mutation in exon 5 (c.362a>g /p.Tyr121Cys), which segregated with the disease in the three affected sibs. We describe a novel mutation in the previously identified MFSD8 gene in a family with a common phenotype of LINCL, but no clinical report of vision loss. Our results enlarge the mutational and perhaps the nosological spectrum of one of the recently identified subtypes of NCL, called CLN7.