Acute DWI Reductions In Patients After Single Epileptic Seizures - More Common Than Assumed

Background: Changes of cerebral diffusivity detected by magnetic resonance imaging (MRI) have been reported in epilepsy. Diffusion weighted imaging (DWI) detects changes in the distribution of water molecules by measuring the apparent diffusion coefficient (ADC) and is mainly used in the diagnosis of ischemic stroke. DWI changes in epilepsy were reported in status epilepticus (SE) or series of seizures. It remains unclear whether this phenomenon also occurs after single seizures. Accordingly, possible pathomechanisms have only been discussed on the presumed basis of ongoing epileptic brain activity.Methods: In this retrospective study, we systematically analyzed DWI alterations related to epileptic seizures in 454 patients who received MRI scanning within the first 24 h after seizure onset.Results: DWI restrictions not classified as ischemic stroke were observed in 18 patients (4%). We found DWI restrictions in 19% of patients with SE/seizure series and in 3% of patients after single focal and 2.5% after single generalized seizures. 17 patients with DWI alterations were diagnosed with a structural epilepsy. DWI signal decreased in the majority of patients within the first days and could not be detected in follow-up imaging >3 months. In all patients except one, DWI alterations were detected in the same hemisphere as the lesion. In the case of seizure series or SE, DWI restrictions mostly presented with a typical “garland-like” pattern alongside the cortical band or on the border of a defined lesion, while in isolated seizures, the restrictions were often rather subtle and small.Discussion: We show that DWI restrictions can be observed in patients after single epileptic seizures. As the vast majority of these patients was diagnosed with an epilepsy due to structural cerebral pathology, DWI restriction may reflect a higher vulnerability in these regions. This might also explain the fact that diffusivity changes were observed after single focal seizures as well as after multiple seizures or SE. The occurence itself on one side as well as the spatial pattern of this phenomenon on the other may thus not only be related to the duration of ictal activity, but to structural pathology

Diagnostic value of video-oculography in progressive supranuclear palsy: a controlled study in 100 patients

Background!#!The eponymous feature of progressive supranuclear palsy (PSP) is oculomotor impairment which is one of the relevant domains in the Movement Disorder Society diagnostic criteria.!##!Objective!#!We aimed to investigate the value of specific video-oculographic parameters for the use as diagnostic markers in PSP.!##!Methods!#!An analysis of video-oculography recordings of 100 PSP patients and 49 age-matched healthy control subjects was performed. Gain of smooth pursuit eye movement and latency, gain, peak eye velocity, asymmetry of downward and upward velocities of saccades as well as rate of saccadic intrusions were analyzed.!##!Results!#!Vertical saccade velocity and saccadic intrusions allowed for the classification of about 70% and 56% of the patients, respectively. By combining both parameters, almost 80% of the PSP patients were covered, while vertical velocity asymmetry was observed in approximately 34%. All parameters had a specificity of above 95%. The sensitivities were lower with around 50-60% for the velocity and saccadic intrusions and only 27% for vertical asymmetry.!##!Conclusions!#!In accordance with oculomotor features in the current PSP diagnostic criteria, video-oculographic assessment of vertical saccade velocity and saccadic intrusions resulted in very high specificity. Asymmetry of vertical saccade velocities, in the opposite, did not prove to be useful for diagnostic purposes

Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis.

The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be traced as a four-stage progression scheme of sequential corticofugal axonal spread. The examination of eye movement control gains deep insights into brain network pathology and provides the opportunity to detect both disturbance of the brainstem oculomotor circuitry as well as executive deficits of oculomotor function associated with higher brain networks.To study systematically oculomotor characteristics in ALS and its underlying network pathology in order to determine whether eye movement deterioration can be categorized within a staging system of oculomotor decline that corresponds to the neuropathological model.Sixty-eight ALS patients and 31 controls underwent video-oculographic, clinical and neuropsychological assessments.Oculomotor examinations revealed increased anti- and delayed saccades' errors, gaze-palsy and a cerebellary type of smooth pursuit disturbance. The oculomotor disturbances occurred in a sequential manner: Stage 1, only executive control of eye movements was affected. Stage 2 indicates disturbed executive control plus 'genuine' oculomotor dysfunctions such as gaze-paly. We found high correlations (p<0.001) between the oculomotor stages and both, the clinical presentation as assessed by the ALS Functional Rating Scale (ALSFRS) score, and cognitive scores from the Edinburgh Cognitive and Behavioral ALS Screen (ECAS).Dysfunction of eye movement control in ALS can be characterized by a two-staged sequential pattern comprising executive deficits in Stage 1 and additional impaired infratentorial oculomotor control pathways in Stage 2. This pattern parallels the neuropathological staging of ALS and may serve as a technical marker of the neuropathological spreading

Eye movement alterations in presymptomatic C9orf72 expansion gene carriers

Objective: The clinical manifestation of amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration, whereas frontotemporal dementia (FTD) patients show alterations of behavior and cognition. Both share repeat expansions in C9orf72 as the most prevalent genetic cause. Before disease-defining symptoms onset, structural and functional changes at cortical level may emerge in C9orf72 carriers. Here, we characterized oculomotor parameters and their association to neuropsychological domains in apparently asymptomatic individuals with mutations in ALS/FTD genes. Patients and methods: Forty-eight carriers of ALS genes, without any clinical symptoms underwent video-oculographic examination, including 22 subjects with C9orf72 mutation, 17 with SOD1, and 9 with other ALS associated gene mutations (n = 3 KIF5A; n = 3 FUS/FUS + TBK1; n = 1 NEK1; n = 1 SETX; n = 1 TDP43). A total of 17 subjects underwent a follow-up measurement. Data were compared to 54 age- and gender-matched healthy controls. Additionally, mutation carriers performed a neuropsychological assessment. Results: In comparison to controls, the presymptomatic subjects performed significantly worse in executive oculomotor tasks such as the ability to perform correct anti-saccades. A gene mutation subgroup analysis showed that dysfunctions in C9orf72 carriers were much more pronounced than in SOD1 carriers. The anti-saccade error rate of ALS mutation carriers was associated with cognitive deficits: this correlation was increased in subjects with C9orf72 mutation, whereas SOD1 carriers showed no associations. Conclusion: In C9orf72 carriers, executive eye movement dysfunctions, especially the increased anti-saccade error rate, were associated with cognitive impairment and unrelated to time. These oculomotor impairments are in support of developmental deficits in these mutations, especially in prefrontal areas