Arterial thromboembolism in a cat with transient myocardial thickening.

Feline arterial thromboembolism has been reported to be secondary to various feline cardiomyopathies; however, it has not been described in cats with transient myocardial thickening. A previously healthy, one-year-old, castrated male cat presented with acute paraparesis and congestive heart failure. Echocardiography revealed asymmetric left ventricular free wall thickening and left atrial enlargement. Antithrombotic treatment and cardiac medication resulted in reperfusion and mobility on day seven in one limb and on day 10 in the other. Different complications were managed successfully, including worsening acute kidney injury, inflammation, pleural effusion, and anemia. After three weeks, the cat was discharged and prescribed oral antithrombotic drugs (clopidogrel and rivaroxaban) and cardiac medication. Within five months, echocardiographic findings normalized, and medical treatment was gradually discontinued. To date, the cat remains healthy at 1735 days after the initial diagnosis and 1494 days after the last antithrombotic medication. To the best of our knowledge, this is the first case report on feline arterial thromboembolism combined with transient myocardial thickening, with favorable long-term survival.

Irish wolfhounds with subclinical atrial fibrillation: progression of disease and causes of death.

INTRODUCTION: To evaluate the frequency of dilated cardiomyopathy (DCM) and cardiac death (CD) in Irish wolfhounds (IW) with subclinical atrial fibrillation (AF) and to compare cardiac and all-cause mortality to those of a contemporaneous control group of apparently healthy IW with sinus rhythm. ANIMALS: Fifty-two IW with AF, but without echocardiographic evidence of DCM or other cardiac disease, and an age- and gender-matched control cohort of 52 apparently healthy IW. METHODS: Data from 1552 IW were retrospectively evaluated. Fifty-two dogs with subclinical AF were compared with 52 IW controls. Time from initial diagnosis to development of DCM was recorded, and survival data were analyzed using cumulative incidence functions. RESULTS: 26/52 AF dogs developed DCM. At study end, in the AF and control group each, 49/52 AF dogs had died, three remained alive. Death in the AF cohort was attributed to CD in 22/49 dogs (12 congestive heart failure [CHF], 10 sudden cardiac deaths [SCD]), while 27 dogs died from non-CD. In the control group, significantly fewer dogs developed DCM (11/52 dogs, p=0.004), even fewer died from CD (5/49; three CHF, two SCD; p=0.001). The odd ratios (95% confidence interval) for dogs with AF vs. controls to develop DCM was 3.7 (1.6-8.8) and to die from CD was 7.2 (2.4-21.2). Median all-cause survival for AF IWs (CD, 36.3 months; non-CD, 33.2 months) did not differ significantly from the control group (CD, 28.6 months, p=0.377; non-CD, 45.3 months, p=0.631). CONCLUSION: IW with subclinical AF commonly develop DCM and die from cardiac death.

Impact of withdrawal of antiepileptic medication on the duration of focal onset seizures.

PURPOSE: To systematically evaluate the duration of focal onset seizures under medication withdrawal as a function of drug half-life. METHODS: Adults with drug resistant focal epilepsy and invasive electroencephalographic (iEEG) recording between 01/2006 and 06/2016 (n = 128) were identified. Patients with multifocal or unknown epileptic foci were excluded, as well as subclinical seizures, isolated auras, or status epileptic. Antiepileptic drugs (AEDs) were withdrawn upon admission. The seizure duration was determined based on the invasive EEG data, and the latency since start of the monitoring was noted in hours. A negative binomial mixed model was used to compare the seizure durations before and after a cut-off, which was set at 2.5 half-lives of the individual anticonvulsive medication as this is thought to separate therapeutic and ineffective drug levels. RESULTS: In total, 70 patients were included in the study and the duration of 672 seizures analyzed. On average, the patients were treated with 2.36 ± 0.78 AEDs. The individual cut-off of 2.5 half-lives was on average reached after 95.02 ± 80.18 h. The seizure frequency (321 vs. 351) and the rate of generalization (15.6% vs. 16.8%) was comparable before and after the individual cut-off point. The mean seizure duration was not statistically significantly prolonged after 2.5 half-lives by a factor of 1.168 for focal onset seizures (p = 0.090) and a factor of 1.091 for secondary generalized seizures (p = 0.545). CONCLUSIONS: Although AED withdrawal increases the likelihood for epileptic seizures, it did not prolong the seizure duration, nor did it increase the rate of secondary generalization in our study.

Dilated cardiomyopathy in 151 Irish Wolfhounds: Characteristic clinical findings, life expectancy and causes of death.

Dilated cardiomyopathy (DCM) is an important cause of morbidity in Irish Wolfhounds (IW), a breed also predisposed to neoplastic and orthopedic diseases that shorten life expectancy. The objective of this study was to investigate survival and causes of death in IW with DCM and to characterise the clinical findings of DCM over time. Data from cardiovascular examinations performed in 1591 IW, including echocardiography and electrocardiography, were retrospectively evaluated. IW with DCM on medical therapy with long term longitudinal follow-up were included in this study (n=151; 95 males, 56 females). Based on their clinical status at initial diagnosis, IW were classified into one of three groups: preclinical DCM with sinus rhythm (PC-DCM-SR, n=35), preclinical DCM with atrial fibrillation (PC-DCM-AF, n=87), and congestive heart failure with DCM and AF (CHF-DCM-AF, n=29). Survival data were analyzed using cumulative incidence functions, Kaplan-Meier and Cox regression. CHF was predominantly characterized by chylous pleural and mild pericardial effusions. Causes of death were cardiac (CD) in 73/151 and non-cardiac (non-CD) in 62/151; 16 dogs remained alive at study end. The majority of deaths in both preclinical DCM groups were non-CD (PC-DCM-AF=51.9% non-CD, 48.1% CD; PC-DCM-SR, 65.5% non-CD, 34.5% CD). In the CHF-DCM-AF group most dogs (89.6%) experienced a CD. Median survival of the CHF-DCM-AF group (7.3 months) was significantly shorter than in the PC-DCM-AF group (21.9 months) or PC-DCM-SR group (29.1 months, P=0.001). CHF-DCM-AF in IW was associated with reduced life expectancy and CD, while most IW with preclinical DCM died from non-cardiac causes.

Quantitative and qualitative analysis of ictal vocalization in focal epilepsy syndromes.

PURPOSE: To investigate the frequency, localizing significance, and intensity characteristics of ictal vocalization in different focal epilepsy syndromes. METHODS: Up to four consecutive focal seizures were evaluated in 277 patients with lesional focal epilepsy, excluding isolated auras and subclinical EEG seizure patterns. Vocalization was considered to be present if observed in at least one of the analyzed seizures and not being of speech quality. Intensity features of ictal vocalization were analyzed in a subsample of 17 patients with temporal and 19 with extratemporal epilepsy syndrome. RESULTS: Ictal vocalization was observed in 37% of the patients (102/277) with similar frequency amongst different focal epilepsy syndromes. Localizing significance was found for its co-occurrence with ictal automatisms, which identified patients with temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative analysis of vocalization intensity allowed to distinguish seizures of frontal from temporal lobe origin based on the intensity range (p = 0.0003), intensity variation (p < 0.0001), as well as the intensity increase rate at the beginning of the vocalization (p = 0.003), which were significantly higher in frontal lobe seizures. No significant difference was found for mean intensity and mean vocalization duration. CONCLUSIONS: Although ictal vocalization is similarly common in different focal epilepsies, it shows localizing significance when taken into account the co-occurring seizure semiology. It especially increases the localizing value of automatisms, predicting a temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative parameters of the intensity dynamic objectively distinguished frontal lobe seizures, establishing an observer independent tool for semiological seizure evaluation.

[Importance of imaging diagnostics and EEG for differential diagnosis of epileptic seizures]. / Bildgebende Diagnostik und EEG in der Differenzialdiagnose epileptischer Anfälle.

Electroencephalography (EEG) and neuroimaging are the two most crucial diagnostic methods for epilepsy. The EEG represents the only specific method to detect epileptogenicity of a brain lesion. The EEG shows some syndrome-specific alterations, helps to make therapeutic decisions and allows prognosis about the disease. Neuroimaging in epilepsy includes magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Neuroimaging is crucial to clarify the underlying etiology and to localize the epileptogenic zone and has contributed to expanding the spectrum of patients where epilepsy surgery can be provided. Both EEG and neuroimaging are valuable methods in the hands of experienced epileptologists but both can also be misdiagnosed and lead to a wrong diagnosis and treatment decisions. This review discusses the contribution of both methods, their potential role and limitations and shows typical examples of wrong interpretation.

Structural changes in the temporal lobe and piriform cortex in frontal lobe epilepsy.

BACKGROUND: Neuronal networks involved in seizure generation, maintenance and spread of epileptic activity comprise cortico-subcortical circuits. Although epileptic foci vary in location across focal epilepsy syndromes, there is evidence for common structures in the epileptogenic networks. We recently reported evidence from functional neuroimaging for a unique area in the piriform cortex, common to focal epilepsies in humans, which might play a role in modulating seizure activity. In this study, we aimed to identify common areas of structural abnormalities in patients with frontal lobe epilepsy (FLE). METHODS: T1-weighted MRI scans of 43 FLE patients and 25 healthy controls were analysed using voxel based morphometry. Differences in regional grey matter volume were examined across the whole brain, and correlated with age at epilepsy onset, duration and frequency of seizures. RESULTS: We detected areas of increased grey matter volume in the piriform cortex, amygdala and parahippocampal gyrus bilaterally, as well as left mid temporal gyrus of patients relative to controls, which did not correlate with any of the clinical variables tested. No common areas of atrophy were detected across the FLE group. CONCLUSIONS: Structural abnormalities within the piriform cortex and adjacent structures of patients with FLE provide further evidence for the involvement of this area in the epileptogenic network of focal epilepsies. Lack of correlation with duration or age of onset of epilepsy suggests that this area of abnormality is not a consequence of seizure activity.

Postmortem 3-D reconstruction of skull gunshot injuries.

BACKGROUND: In cases of severe decomposition or skeletonization of a corpse after cerebral gun shot injury it is difficult to exactly reconstruct the bullet path in the brain. However, in case of murder or homicide this might become necessary to answer forensic questions such as the ability to move or other actions of the victim. MATERIALS AND METHODS: Therefore a method in terms of three dimensional reconstruction technique was developed by fusing computed tomography scans (CT) of the original skull and magnetic resonance images (MRI) of a normal brain of adequate size. Hereby five cases were investigated. RESULTS: In three cases an excellent concordance between the reconstructed bullet trajectory and the autopsy reports was achieved. In one case the original brain was not available for CT-scanning due to previous autopsy. However, the findings were in line with the pathology report. In one case there was a difference of about 1-2 cm between the original autopsy description and the reconstructed bullet path. This was due to only a part of the skull being available for image reconstruction. CONCLUSION: The findings suggest that this method can successfully be applied to adequately reconstruct bullet paths in cases of completely skeletonized skulls, but should carefully be used in cases of incomplete skulls.

Disrupted segregation of working memory networks in temporal lobe epilepsy.

Working memory is a critical building block for almost all cognitive tasks, and impairment can cause significant disruption to daily life routines. We investigated the functional connectivity (FC) of the visuo-spatial working memory network in temporal lobe epilepsy and its relationship to the underlying white matter tracts emanating from the hippocampus. Fifty-two patients with unilateral hippocampal sclerosis (HS) (30 left) and 30 healthy controls underwent working memory functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). Six seed regions were identified for FC analysis; 4 within a task-positive network (left and right middle frontal gyri and superior parietal lobes), and 2 within a task-negative network (left and right hippocampi). FC maps were created by extracting the time-series of the fMRI signal in each region in each subject and were used as regressors of interest for additional GLM fMRI analyses. Structural connectivity (SC) corresponding to areas to which the left and right hippocampi were connected was determined using tractography, and a mean FA for each hippocampal SC map was calculated. Both left and right HS groups showed atypical FC between task-positive and task-negative networks compared to controls. This was characterised by co-activation of the task-positive superior parietal lobe ipsilateral to the typically task-negative sclerosed hippocampus. Correlational analysis revealed stronger FC between superior parietal lobe and ipsilateral hippocampus, was associated with worse performance in each patient group. The SC of the hippocampus was associated with the intra-hemispheric FC of the superior parietal lobe, in that greater SC was associated with weaker parieto-frontal FC. The findings suggest that the segregation of the task-positive and task-negative FC networks supporting working memory in TLE is disrupted, and is associated with abnormal structural connectivity of the sclerosed hippocampus. Co-activation of parieto-temporal regions was associated with poorer working memory and this may be associated with working memory dysfunction in TLE.

Altered microstructural connectivity in juvenile myoclonic epilepsy: the missing link.

OBJECTIVES: Juvenile myoclonic epilepsy (JME) is characterized by myoclonic jerks of the upper limbs, often triggered by cognitive stressors. Here we aim to reconcile this particular seizure phenotype with the known frontal lobe type neuropsychological profile, photosensitivity, hyperexcitable motor cortex, and recent advanced imaging studies that identified abnormal functional connectivity of the motor cortex and supplementary motor area (SMA). METHODS: We acquired fMRI and diffusion tensor imaging (DTI) in a cohort of 29 patients with JME and 28 healthy control subjects. We used fMRI to determine functional connectivity and DTI-based region parcellation and voxel-wise comparison of probabilistic tractography data to assess the structural connectivity profiles of the mesial frontal lobe. RESULTS: Patients with JME showed alterations of mesial frontal connectivity with increased structural connectivity between the prefrontal cognitive cortex and motor cortex. We found a positive correlation between DTI and fMRI-based measures of structural and functional connectivity: the greater the structural connectivity between these 2 regions, the greater the observed functional connectivity of corresponding areas. Furthermore, connectivity was reduced between prefrontal and frontopolar regions and increased between the occipital cortex and the SMA. CONCLUSION: The observed alterations in microstructural connectivity of the mesial frontal region may represent the anatomic basis for cognitive triggering of motor seizures in JME. Changes in the mesial frontal connectivity profile provide an explanatory framework for several other clinical observations in JME and may be the link between seizure semiology, neurophysiology, neuropsychology, and imaging findings in JME.

[Neuroimaging of epilepsies]. / Bildgebende Diagnostik der Epilepsien.

Neuroimaging is crucial for the diagnosis of epilepsy, in particular for syndromic diagnosis of focal epilepsies and for presurgical evaluation. We give recommendations on the optimized acquisition of MRI and discuss the principle and role of additional neuroimaging methods including nuclear medicine and image processing.

Neural correlates of working memory in Temporal Lobe Epilepsy--an fMRI study.

It has traditionally been held that the hippocampus is not part of the neural substrate of working memory (WM), and that WM is preserved in Temporal Lobe Epilepsy (TLE). Recent imaging and neuropsychological data suggest this view may need revision. The aim of this study was to investigate the neural correlates of WM in TLE using functional MRI (fMRI). We used a visuo-spatial 'n-back' paradigm to compare WM network activity in 38 unilateral hippocampal sclerosis (HS) patients (19 left) and 15 healthy controls. WM performance was impaired in both left and right HS groups compared to controls. The TLE groups showed reduced right superior parietal lobe activity during single- and multiple-item WM. No significant hippocampal activation was found during the active task in any group, but the hippocampi progressively deactivated as the task demand increased. This effect was bilateral for controls, whereas the TLE patients showed progressive unilateral deactivation only contralateral to the side of the hippocampal sclerosis and seizure focus. Progressive deactivation of the posterior medial temporal lobe was associated with better performance in all groups. Our results suggest that WM is impaired in unilateral HS and the underlying neural correlates of WM are disrupted. Our findings suggest that hippocampal activity is progressively suppressed as the WM load increases, with maintenance of good performance. Implications for understanding the role of the hippocampus in WM are discussed.

Congruence and discrepancy of interictal and ictal EEG with MRI lesions in focal epilepsies.

OBJECTIVE: To compare the occurrence and localization of interictal epileptiform discharges (IEDs) and epileptic seizure patterns (ESPs) with the localization of MRI lesions. METHODS: We retrospectively analyzed the EEG and MRI data of a series of patients with focal epilepsies that had been studied from 1991 to 2009. RESULTS: In patients with temporal lesions, the localization of IEDs was most congruent (58.6% with IEDs exclusively over the lesional lobe and 29.7% with a majority of temporal IEDs). This differed (p < 0.001) from frontal lesions (27.5% with exclusively frontal IEDs, 24.6% with a majority of frontal IEDs). In parieto-occipital lobe lesions, only 12.1% had IEDs exclusively over the lesional lobe compared to 48.5% with no parieto-occipital IEDs at all. Patients with central lesions often lacked any IEDs (54.5%, p < 0.001). The occurrence and localization of ESPs also differed between the regions. They were most congruent in temporal lesions (63.5% of patient had ESPs only over the lesional lobe, 23.4% had the majority of ESPs over the lesional lobe), which differed from frontal and parieto-occipital lesions (37.7% and 30.3% of patients with ESPs only over the lesional lobe). Patients with central lesions had ESPs very frequently only outside the lesional lobe (63.6%). Surgery outcome did not differ between the regions. CONCLUSIONS: The occurrence and localization of interictal and ictal EEG findings differs vastly for lesions in different brain regions. These findings should be used to carefully weigh the results from EEG studies particularly in patients with extratemporal epilepsies considered for epilepsy surgery.

Dysprosody during epileptic seizures lateralizes to the nondominant hemisphere.

OBJECTIVE: In human speech, the changes in intonation, rhythm, or stress reflect emotions or intentions and are called prosody. Dysprosody is the impairment of prosody and has been described in stroke and neurodegenerative disorders. Reports in epilepsy patients are limited to case reports. METHODS: We assessed prosody qualitatively and quantitatively in 967 focal epilepsy patients. The qualitative assessment was performed by 2 native German speakers, and the quantitative frequency analysis used linguistic software tools. For the quantitative analysis, the formant F0 (a frequency peak, which is an approximation of pitch) and the further spectral frequency peaks of our patients' voices were analyzed. RESULTS: We found 26 patients with ictal dysprosody through qualitative analysis (2.7% of all focal epilepsies). The qualitative changes affected mostly the pitch and the loss of melody. The seizure patterns at the time of ictal dysprosody were always in the nondominant hemisphere (100%) and were mostly right temporal (n = 22; 84.6%). Quantitative analysis of 15 audio samples (11 patients) showed a change in the frequency of formant F0 of several patients and a reduction of frequency variation during ictal speech, expressed as the SD of formant F0 (ictal 14.1 vs interictal 27.2). CONCLUSIONS: Ictal dysprosody localizes seizure onset or propagation to the nondominant temporal lobe. This information can be used in the evaluation of patients considered for resective epilepsy surgery.

Converging PET and fMRI evidence for a common area involved in human focal epilepsies.

OBJECTIVES: Experiments in animal models have identified specific subcortical anatomic circuits, which are critically involved in the pathogenesis and control of seizure activity. However, whether such anatomic substrates also exist in human epilepsy is not known. METHODS: We studied 2 separate groups of patients with focal epilepsies arising from any cortical location using either simultaneous EEG-fMRI (n = 19 patients) or [¹¹C]flumazenil PET (n = 18). RESULTS: Time-locked with the interictal epileptiform discharges, we found significant hemodynamic increases common to all patients near the frontal piriform cortex ipsilateral to the presumed cortical focus. GABA(A) receptor binding in the same area was reduced in patients with more frequent seizures. CONCLUSIONS: Our findings of cerebral blood flow and GABAergic changes, irrespective of where interictal or ictal activity occurs in the cortex, suggest that this area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery.

Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy.

OBJECTIVE: The aim of this study was to determine if there were focal cortical abnormalities in juvenile myoclonic epilepsy (JME) using neuropsychological investigations and MRI. METHODS: Twenty-eight patients with JME and a large sample of healthy controls were assessed using a series of neuropsychological tests as well as structural and diffusion tensor MRI (DTI). DTI measures assessed fractional anisotropy (FA) within a white matter skeleton. RESULTS: Neuropsychological testing indicated subtle dysfunctions in verbal fluency, comprehension, and expression, as well as nonverbal memory and mental flexibility. Utilizing whole-brain voxel-based morphometry for gray matter MRI data and tract-based spatial statistics for white matter diffusion MRI data, we found reductions in gray matter volume (GMV) in the supplementary motor area and posterior cingulate cortex and reductions in FA in underlying white matter of the corpus callosum. Supplementary motor area FA predicted scores in word naming tasks and expression scores. Posterior cingulate cortex GMV and FA predicted cognitive inhibition scores on the mental flexibility task. CONCLUSIONS: The neuropsychological, structural, and tractography results implicate mesial frontal cortex, especially the supplementary motor area, and posterior cingulate cortex in JME.

[Combined Scanners (PET/CT, SPECT/CT) Versus Multimodality Imaging with Separated Systems]. / Kombinierte Hybridsysteme (PET/CT, SPECT/CT) versus multimodale Bildgebung mit getrennten Systemen.

With increasing use of combined PET/CT scanners in the last few years, multimodality imaging (Nuclear Medicine/Radiology) found its way into clinical routine diagnostics. In this overview, necessary components for multimodality imaging, strategies for image analysis and image presentation, and diagnostic goals of combined imaging are demonstrated and discussed. A special focus is on the question, whether combined scanners can be replaced by a software approach with separated modalities. Advantages and limitations of multimodality imaging with combined or separated scanners are shown.

No evidence of cerebral oedema in severe acute mountain sickness.

In a randomized, double-blind cross-over study 10 subjects were exposed to a simulated altitude of 4500 m for 10 h after administration of placebo, acetozolamide (250 mg bid) or theophylline (250 mg bid). T2-weighted magnetic resonances images (MRI) and diffusion weighted MRI were obtained directly after exposure to altitude under hypoxic conditions. Although eight of 10 subjects had moderate to severe acute mountain sickness (AMS), we found no evidence of cerebral oedema, irrespective of the medication taken. Almost all subjects showed a decrease in inner cerebrospinal fluid (iCSF) volumes (placebo - 10.3%, P= 0.02; acetazolamide - 13.2%, P= 0.008, theophylline -12.2%, n.s.). There was no correlation between AMS symptoms and fluid shift. However, we found a significantly positive correlation of large (>10 ml) iCSF volume and more severe AMS after administration of placebo (r = 0.76, P= 0.01). Moderate to severe AMS after high altitude exposure for 10 h is associated with a decreased iCSF-volume independent of AMS severity or medication without signs of cerebral oedema.