Search

Objective: Cognitive dysfunction is a core symptom of anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis, but detailed studies on prevalence, characteristics of cognitive deficits, and the potential for recovery are missing. Here, we performed a prospective longitudinal study to assess cognitive long‐term outcome and identify clinical predictors. Methods: Standardized comprehensive neuropsychological assessments were performed in 43 patients with NMDAR encephalitis 2.3 years and 4.9 years (median) after disease onset. Cognitive assessments covered executive function, working memory, verbal/visual episodic memory, attention, subjective complaints, and depression and anxiety levels. Cognitive performance of patients was compared to that of 30 healthy participants matched for age, sex, and education. Results: All patients had persistent cognitive deficits 2.3 years after onset, with moderate or severe impairment in >80% of patients. Core deficits included memory and executive function. After 4.9 years, significant improvement of cognitive function was observed, but moderate to severe deficits persisted in two thirds of patients, despite favorable functional neurological outcomes (median modified Rankin Scale = 1). Delayed treatment, higher disease severity, and longer duration of the acute phase were predictors for impaired cognitive outcome. The recovery process was time dependent, with greater gains earlier after the acute phase, although improvements were possible for several years after disease onset. Interpretation: Cognitive deficits are the main contributor to long‐term morbidity in NMDAR encephalitis and persist beyond functional neurological recovery. Nonetheless, cognitive improvement is possible for several years after the acute phase and should be supported by continued cognitive rehabilitation. Cognition should be included as an outcome measure in future clinical studies. ANN NEUROL 2021;90:949–961 [ABSTRACT FROM AUTHOR]

Objectives: Genetic variant classification is a challenge in rare adult‐onset disorders as in SCA‐PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA‐PRKCG a comprehensive phenotype description from a German multi‐center cohort, including standardized 3D MR imaging. Methods: This cross‐sectional study prospectively obtained neurological, neuropsychological, and brain imaging data in 33 PRKCG variant carriers. Protein modeling was added as a classification criterion in variants of uncertain significance (VUS). Results: Our sample included 25 cases confirmed as SCA‐PRKCG (14 variants, thereof seven novel variants) and eight carriers of variants assigned as VUS (four variants) or benign/likely benign (two variants). Phenotype in SCA‐PRKCG included slowly progressive ataxia (onset at 4–50 years), preceded in some by early‐onset nonprogressive symptoms. Ataxia was often combined with action myoclonus, dystonia, or mild cognitive‐affective disturbance. Inspection of brain MRI revealed nonprogressive cerebellar atrophy. As a novel finding, a previously not described T2 hyperintense dentate nucleus was seen in all SCA‐PRKCG cases but in none of the controls. Interpretation: In this largest cohort to date, SCA‐PRKCG was characterized as a slowly progressive cerebellar syndrome with some clinical and imaging features suggestive of a developmental disorder. The observed non‐ataxia movement disorders and cognitive‐affective disturbance may well be attributed to cerebellar pathology. Protein modeling emerged as a valuable diagnostic tool for variant classification and the newly described T2 hyperintense dentate sign could serve as a supportive diagnostic marker of SCA‐PRKCG. [ABSTRACT FROM AUTHOR]

Objective Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis. Methods Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry. Results Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls. Interpretation Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis. Ann Neurol 2013;74:257-265 [ABSTRACT FROM AUTHOR]

MRI Results of the MACPAF Study. Background: Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF). Objective: Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function. Methods: Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure. Results: There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS2 score had no impact. Lesion volumes varied from 5 to 150 mm3 and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation. Conclusions: According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure. (J Cardiovasc Electrophysiol, Vol. 24, pp. 14-21, January 2013) [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus-dystonia (MD). We investigated short- and long-term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi- and VIM-DBS in MD. Ten MD-patients (nine ε-sarcoglycan-mutation-positive) were evaluated pre- and post-surgically following continuous bilateral GPi- and VIM-DBS at four time points: presurgical, 6, 12, and as a last follow-up at a mean of 62.3 months postsurgically, and in OFF-, GPi-, VIM-, and GPi-VIM-DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke-Fahn-Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL-scores. MD-symptoms significantly improved at 6 months post-surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long-term evaluation post-surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long-lasting stimulation-related adverse events (AEs) were observed. Both GPi- and VIM-DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation-induced events of GPi-DBS in comparison with VIM-DBS, GPi-DBS seems to be preferable. Combined GPi-VIM-DBS can be useful in cases of incapaciting myoclonus, refractory to GPi-DBS alone. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Successful prospective remembering (PR) comprises at least two components: one retrospective component that refers to the encoding and retrieval of the content of the intention and a second prospective component that involves the retrieval of the intended action at the appropriate moment. Whereas the retrospective component is very similar to memory skills like learning and retention of new information, the prospective component is thought to rely mainly on executive function. Head injuries can disturb PR during both of these stages. To disentangle the relative impact of executive functions and retrospective memory processes on PR we embedded a PR task in a 2-back verbal working memory paradigm. Fifty-six neurological patients with brain damage of various aetiologies were divided pre-experimentally into tour groups on the basis of their delayed recall Index in the Wechsler Memory Scale-Revised (WMS-R, indicating absence or presence of deficits in retrospective memory functions) and their age-corrected score in the Behavioural Assessment of the Dysexecutive Syndrome (BADS, indicating absence or presence of deficits in executive functions). Additionally, 19 controls matched for age and education were examined. We found that patients with deficits in executive functions detected fewer cues than any other group irrespective of their retrospective memory performance. However, eight patients with severe anterograde memory deficits could retain neither the intention nor its content. Thus, intactness of the retrospective component seems to be a necessary but not sufficient prerequisite for successful prospective remembering. For the execution of the intended action itself executive functions play a critical role. [ABSTRACT FROM AUTHOR]