Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Good Outcome of Resective Epilepsy Surgery in a 1-Year-Old Child with Drug-Resistant Focal Epilepsy with a Novel Pathogenic COL4A1 Mutation.

Pathogenic variants in COL4A1, encoding the α chain of type IV collagen, have been associated with cerebrovascular pathology as well as malformations of cortical development, thereby causing structural epilepsy. This case illustrates successful resective epilepsy surgery in a 12-month-old girl with left occipital focal cortical dysplasia (FCD) associated with a heterozygous splice-donor variant in COL4A1. She presented with drug-resistant focal epilepsy with daily seizures from the age of 2 months, refractory to several combinations of antiseizure medications, as well as mild right-sided hemiparesis and developmental delay. All presurgical diagnostic modalities, including ictal and interictal electroencephalography, magnetic resonance imaging, and ictal fluorodeoxyglucose positron emission tomography, showed congruent findings, pointing toward one single left occipital epileptogenic zone (EZ). We performed a left occipital lobectomy, using intraoperative electrocorticography to confirm the boundaries of the EZ. After surgery, the patient has remained seizure free, and both cognitive and motor developments have improved. Histopathology of the resected brain tissue showed FCD type Ia. Resective epilepsy surgery can have a very good outcome, also in patients with genetic mutations in COL4A1, constituting a less invasive option than the previously used more radical surgical procedures such as hemispherectomy.

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

OBJECTIVE: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. METHODS: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. RESULTS: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. SIGNIFICANCE: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

Uncrossed corticospinal tract in health and genetic disorders: Review, case report, and clinical implications.

BACKGROUND AND PURPOSE: Crossing pathologies of the corticospinal tract (CST) are rare and often associated with genetic disorders. However, they can be present in healthy humans and lead to ipsilateral motor deficits when a lesion to motor areas occurs. Here, we review historical and current literature of CST crossing pathologies and present a rare case of asymmetric crossing of the CST. METHODS: Description of the case and systematic review of the literature were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed database was searched for peer-reviewed articles in English since 1950. All articles on ipsilateral stroke, uncrossed CST, and associated neurologic disorders were screened. Furthermore, a literature review between the years 1850 and 1980 including articles in other languages, books, opinions, and case studies was conducted. RESULTS: Only a few descriptions of CST crossing pathologies exist in healthy humans, whereas they seem to be more common in genetic disorders such as horizontal gaze palsy with progressive scoliosis or congenital mirror movements. Our patient presented with aphasia and left-sided hemiparesis. Computed tomographic (CT) scan revealed a perfusion deficit in the left middle cerebral artery territory, which was confirmed by diffusion-weighted magnetic resonance imaging (MRI), so that thrombolysis was administered. Diffusion tensor imaging with fibre tracking revealed an asymmetric CST crossing. CONCLUSIONS: The knowledge of CST crossing pathologies is essential if a motor deficit occurs ipsilateral to the lesion side. An ipsilateral deficit should not lead to exclusion or delay of therapeutic options in patients with suspected stroke. Here, a combined evaluation of CT perfusion imaging and MRI diffusion imaging may be of advantage.

Hemispheric differences in the duration of focal onset seizures.

OBJECTIVE: To assess hemispheric differences in the duration of focal onset seizures and its association with clinical and demographic factors. METHODS: A retrospective analysis was performed on adult patients with drug-resistant unifocal epilepsy, who underwent intracranial EEG recording between 01/2006 and 06/2016. Seizure duration was determined based on the subdural and/or stereo-EEG (sEEG) recordings. Hemispheric differences in seizure duration were statistically evaluated with regard to clinical and demographic data. RESULTS: In total, 69 patients and 654 focal onset seizures were included. The duration of seizures with left-hemispheric onset (n = 297) was by trend longer (91.88 ± 93.92 s) than of right-hemispheric seizures (n = 357; 71.03 ± 68.53 s; p = .193). Significant hemispheric differences in seizures duration were found in temporal lobe seizures (n = 225; p = .013), especially those with automotor manifestation (n = 156; p = .045). A prolonged duration was also found for left-hemispheric onset seizures with secondary generalized commencing during waking state (n = 225; p = .034), but not during sleep. A similar hemispheric difference in seizure duration was found in female patients (p = .040), but not in men. CONCLUSIONS: Hemispheric differences in seizure duration were revealed with significantly longer durations in case of left-hemispheric seizure onset. The observed differences in seizure duration might result from brain asymmetry and add new aspects to the understanding of seizure propagation and termination.

Living with global amnesia: self-established compensation strategies of a patient with severe memory impairment - a narrative report.

We report the case of C.H., a 48-year-old patient with global amnesia caused by herpes simplex encephalitis at the age of 20 and subsequent extensive bilateral temporal lobe lesions. Neuropsychological examinations performed at various intervals found persistent dense explicit memory impairment and limited vocabulary, yet intact procedural memory. Despite these limitations, C.H. self-developed and acquired a variety of effective strategies. As a result, C.H. achieved a high level of autonomy in everyday life. Her remarkable case is an encouraging and helpful example for successful implementation of creative methods and procedures to compensate and alleviate cognitive limitation, even if extensive.

Unilateral Blinking: Insights from Stereo-EEG and Tractography.

To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.

Who seizes longest? Impact of clinical and demographic factors.

OBJECTIVE: To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from intracranial electroencephalographic (iEEG) recordings. METHODS: Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006-2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports. RESULTS: In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic-clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS-BTCs; 556/654, P < .001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P = .003) and was significantly shortened (P < .001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P = .015) and sign of four (P = .043) were associated with longer bilateral tonic-clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P < .001) and disease duration (P = .028) were essential for prediction of FS-BTC duration, whereas the vigilance state (P = .085) was the main prediction factor for the duration of FBTCSs. SIGNIFICANCE: The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures.

Motor hyperactivation during cognitive tasks: An endophenotype of juvenile myoclonic epilepsy.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. METHODS: This prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. RESULTS: During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005). SIGNIFICANCE: Motor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.

Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings.

Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.

Unilateral temporal interictal epileptiform discharges correctly predict the epileptogenic zone in lesional temporal lobe epilepsy.

OBJECTIVE: To evaluate the necessity of recording ictal electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE) considered for resective surgery who have unilateral temporal interictal epileptiform discharges (IEDs) and concordant ipsitemporal magnetic resonance imaging (MRI) pathology. To calculate the necessary number of recorded EEG seizure patterns (ESPs) to achieve adequate lateralization probability. METHODS: In a retrospective analysis, the localization and lateralization of interictal and ictal EEG of 304 patients with lesional TLE were analyzed. The probability of further contralateral ESPs was calculated based on a total of 1967 recorded ESPs, using Bayes' theorem. RESULTS: Two hundred seventy-one patients had unilateral TLE, and in 98% of them (265 of 271), IEDs were recorded during video-EEG monitoring. Purely unilateral temporal IEDs were present in 61% (166 of 271 patients). Ipsilateral temporal MRI pathology was found in 83% (138 of 166). Ictal EEG was concordant with the clinical side of TLE in 99% (136 of 138) of these patients. Two patients had discordant ictal EEG with both ipsilateral and contralateral ESPs. Epilepsy surgery with resection in the lesioned temporal lobe was still performed, and both patients remain seizure-free. Probability calculations demonstrate that at least 6 recorded unilateral ESPs result in a >95% probability for a concordance of >0.9 of any further ESPs. SIGNIFICANCE: The combination of purely unilateral temporal IED with ipsitemporal MRI pathology is sufficient to identify the epileptogenic zone, and the recording of ictal ESP did not add any surgically relevant information in these 138 patients. Rarely, discordant ESPs might be recorded, but the surgical outcome remains excellent after surgery on the lesioned side.

Effects of carbamazepine and lamotrigine on functional magnetic resonance imaging cognitive networks.

OBJECTIVE: To investigate the effects of sodium channel-blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy. METHODS: In a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel-blocking AED. We propensity-matched 42 patients taking levetiracetam (LEV) as "patient-controls" and included further 42 age- and gender-matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out-of-scanner psychometric measures of verbal fluency. RESULTS: Patients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV-treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out-of-scanner fluency scores correlated positively with left putamen activation. SIGNIFICANCE: Our study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well-tolerated sodium channel-blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task-negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks.

A diffusion-based connectivity map of the GPi for optimised stereotactic targeting in DBS.

BACKGROUND: The GPi (globus pallidus internus) is an important target nucleus for Deep Brain Stimulation (DBS) in medically refractory movement disorders, in particular dystonia and Parkinson's disease. Beneficial clinical outcome critically depends on precise electrode localization. Recent evidence indicates that not only neurons, but also axonal fibre tracts contribute to promoting the clinical effect. Thus, stereotactic planning should, in the future, also take the individual course of fibre tracts into account. OBJECTIVE: The aim of this project is to explore the GPi connectivity profile and provide a connectivity-based parcellation of the GPi. METHODS: Diffusion MRI sequences were performed in sixteen healthy, right-handed subjects. Connectivity-based parcellation of the GPi was performed applying two independent methods: 1) a hypothesis-driven, seed-to-target approach based on anatomic priors set as connectivity targets and 2) a purely data-driven approach based on k-means clustering of the GPi. RESULTS: Applying the hypothesis-driven approach, we obtained five major parcellation clusters, displaying connectivity to the prefrontal cortex, the brainstem, the GPe (globus pallidus externus), the putamen and the thalamus. Parcellation clusters obtained by both methods were similar in their connectivity profile. With the data-driven approach, we obtained three major parcellation clusters. Inter-individual variability was comparable with results obtained in thalamic parcellation. CONCLUSION: The three parcellation clusters obtained by the purely data-driven method might reflect GPi subdivision into a sensorimotor, associative and limbic portion. Clinical and physiological studies indicate greatest clinical DBS benefit for electrodes placed in the postero-ventro-lateral GPi, the region displaying connectivity to the thalamus in our study and generally attributed to the sensorimotor system. Clinical studies relating DBS electrode positions to our GPi connectivity map would be needed to complement our findings.

The role of the pallidothalamic fibre tracts in deep brain stimulation for dystonia: A diffusion MRI tractography study.

BACKGROUND: Deep Brain Stimulation (DBS) of the Globus pallidus internus (GPi) is gold standard treatment in medically refractory dystonia. Recent evidence indicates that stimulation effects are also due to axonal modulation and affection of a fibre network. For the GPi, the pallidothalamic tracts are known to be the major motor efferent pathways. The aim of this study is to explore the anatomic vicinity of these tracts and DBS electrodes in dystonia applying diffusion tractography. METHODS: Diffusion MRI was acquired in ten patients presenting for DBS for dystonia. We applied both a conventionally used probabilistic tractography algorithm (FSL) as well as a probabilistic streamline tracking approach, based on constrained spherical deconvolution and particle filtering with anatomic priors, to the datasets. DBS electrodes were coregistered to the diffusion datasets. RESULTS: We were able to delineate the pallidothalamic tracts in all patients. Using the streamline approach, we were able to distinguish between the two sub-components of the tracts, the ansa lenticularis and the fasciculus lenticularis. Clinically efficient DBS electrodes displayed a close anatomic vicinity pathway of the pallidothalamic tracts, and their course was consistent with previous tracer labelling studies. Although we present only anatomic data, we interpret these findings as evidence of the possible involvement of fibre tracts to the clinical effect in DBS. Electrophysiological intraoperative recordings would be needed to complement our findings. In the future, a clear and individual delineation of the pallidothalamic tracts could optimize the stereotactic process of optimal electrode localization. Hum Brain Mapp 38:1224-1232, 2017. © 2016 Wiley Periodicals, Inc.

Seizure-associated aphasia has good lateralizing but poor localizing significance.

OBJECTIVE: To investigate the occurrence of ictal and postictal aphasia in different focal epilepsy syndromes. METHODS: We retrospectively analyzed the video-electroencephalographic monitoring data of 1,118 patients with focal epilepsy for seizure-associated aphasia (SAA). Statistical analysis included chi-square analysis and Fisher's exact test. RESULTS: We identified 102 of 1,118 patients (9.1%) in whom ictal or postictal aphasia (SAA) was part of their recorded seizures (n = 59 of 102; 57.8%) or who reported aphasia by history (n = 43; 42.2% only reported aphasia by history). Postictal aphasia was present in 18 patients (30.5%). Six of the 59 patients had both ictal and postictal aphasia (10.2%). SAA occurred either with left hemisphere seizure onset or with seizures spreading from the right to the left hemisphere. SAA was most common in patients with parieto-occipital epilepsy (10.9%; five of 46 patients), followed by patients with temporal (6.7%; 28 of 420 patients), focal (not further localized; 4.8%; 22 of 462 patients), and frontal epilepsy (2.1%; four of 190 patients; p = 0.04). SAA was more common in parieto-occipital epilepsy than in frontal epilepsy (p = 0.02). In contrast, there was no significant difference in SAA between temporal and parieto-occipital epilepsy (p = 0.36). SIGNIFICANCE: SAA has a high lateralizing but limited localizing value, as it often reflects spread of epileptic activity into speech-harboring brain regions.

Temporal-pattern similarity analysis reveals the beneficial and detrimental effects of context reinstatement on human memory.

A powerful force in human memory is the context in which memories are encoded (Tulving and Thomson, 1973). Several studies suggest that the reinstatement of neural encoding patterns is beneficial for memory retrieval (Manning et al., 2011; Staresina et al., 2012; Jafarpour et al., 2014). However, reinstatement of the original encoding context is not always helpful, for instance, when retrieving a memory in a different contextual situation (Smith and Vela, 2001). It is an open question whether such context-dependent memory effects can be captured by the reinstatement of neural patterns. We investigated this question by applying temporal and spatial pattern similarity analysis in MEG and intracranial EEG in a context-match paradigm. Items (words) were tagged by individual dynamic context stimuli (movies). The results show that beta oscillatory phase in visual regions and the parahippocampal cortex tracks the incidental reinstatement of individual context trajectories on a single-trial level. Crucially, memory benefitted from reinstatement when the encoding and retrieval contexts matched but suffered from reinstatement when the contexts did not match.

Applied multimodal diagnostics in a case of presenile dementia.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The possibility of disease-modifying strategies has evoked a need for early and accurate diagnosis. To improve the accuracy of the clinical diagnosis of AD, biomarkers like cerebrospinal fluid (CSF) and neuroimaging techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) have been incorporated into the diagnostic guidelines of AD. CASE PRESENTATION: In this case report we outline in reference to one of our patients with presenile dementia the current approaches to the diagnosis of AD. The patient was a 59-year old woman presenting with progressive memory decline. CSF-Aß42 was normal while P-tau was slightly increased. FDG-PET indicated a pattern typical for AD, amyloid-PET showed an extensive global amyloid load, and tau-PET depicted a pronounced hippocampal tracer accumulation. The MRI scan was rated as normal at routine diagnostics, however quantitative volumetric analysis revealed significant atrophy especially of the parietal lobe. The combination of biomarkers and neuroimaging techniques was therefore suggestive of an underlying AD pathology. CONCLUSIONS: To enable early and accurate diagnosis of AD and thereby also patient recruitment for anti-tau or anti-ß-amyloid therapeutic trials, a combination of biomarkers and neuroimaging techniques seems useful.

Ruptured basilar artery perforator aneurysms--treatment regimen and long-term follow-up in eight cases.

INTRODUCTION: Basilar artery (BA) perforator aneurysms may lead to severe subarachnoid hemorrhage (SAH). The acute management is uncertain. The anatomic approach is challenging both for coiling and clipping, and flow diverter stenting may be dangerous due to the required antiplatelet therapy. We report on our experiences in eight patients. METHODS: We retrospectively analyzed eight patients with ruptured BA perforator aneurysm, including clinical characteristics, imaging data, treatment regimen, clinical course, and long-term outcome. RESULTS: Patients presented with major SAH and World Federation of Neurosurgical Societies (WFNS) scores of I in three, II in two, and V in three cases. In four patients, the aneurysm was detected in the initial angiography, in four only in follow-up angiography. Five patients were treated conservatively and three patients had endovascular therapy. In the conservative group, the aneurysm spontaneously thrombosed in three cases. One patient suffered from a re-SAH and stayed permanently dependent due to an associated perforator stroke (modified Rankin Scale (mRS) 5). The remaining four patients recovered well (mRS 0 and 1 in two cases, each) including three patients also exhibiting perforator strokes. Regarding the endovascular group, one parent vessel was an angioma feeder and embolized with Onyx. The second aneurysm spontaneously thrombosed periinterventionally. The third patient underwent coiling. Two parent vessels were occluded postinterventionally, resulting in perforator strokes. Final mRS scores were 0, 2, and 2, respectively. CONCLUSION: Conservative management of ruptured BA aneurysms might be a first-line treatment option with common spontaneous aneurysm occlusion, low rate of re-SAH, and promising clinical outcome.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18-65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22-54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23-46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy.

Connectivity patterns of pallidal DBS electrodes in focal dystonia: a diffusion tensor tractography study.

Deep brain stimulation (DBS) of the internal pallidal segment (GPi: globus pallidus internus) is gold standard treatment for medically intractable dystonia, but detailed knowledge of mechanisms of action is still not available. There is evidence that stimulation of ventral and dorsal GPi produces opposite motor effects. The aim of this study was to analyse connectivity profiles of ventral and dorsal GPi. Probabilistic tractography was initiated from DBS electrode contacts in 8 patients with focal dystonia and connectivity patterns compared. We found a considerable difference in anterior-posterior distribution of fibres along the mesial cortical sensorimotor areas between the ventral and dorsal GPi connectivity. This finding of distinct GPi connectivity profiles further confirms the clinical evidence that the ventral and dorsal GPi belong to different functional and anatomic motor subsystems. Their involvement could play an important role in promoting clinical DBS effects in dystonia.