Josephine Heine1,2, Ute A Kopp1, Johanna Klag1, Christoph J Ploner1, Harald Prüss1,3, Carsten Finke1,4,5. 1. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 2. Department of Psychology, Humboldt Universität zu Berlin, Berlin, Germany. 3. German Center for Neurodegenerative Diseases, Berlin, Germany. 4. Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany. 5. Berlin School of Mind and Brain, Humboldt Universität zu Berlin, Berlin, Germany.
Abstract
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.
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.
Authors: Anusha Yeshokumar; Eliza Gordon-Lipkin; Ana Arenivas; Mark Rosenfeld; Kristina Patterson; Raia Blum; Brenda Banwell; Arun Venkatesan; Eric Lancaster; Jessica Panzer; John Probasco Journal: Neurol Neuroimmunol Neuroinflamm Date: 2022-07-06
Authors: Adam Al-Diwani; Jakob Theorell; Valentina Damato; Joshua Bull; Nicholas McGlashan; Edward Green; Anne Kathrin Kienzler; Ruby Harrison; Tasneem Hassanali; Leticia Campo; Molly Browne; Alistair Easton; Hooman Soleymani Majd; Keiko Tenaka; Raffaele Iorio; Russell C Dale; Paul Harrison; John Geddes; Digby Quested; David Sharp; Soon Tae Lee; David W Nauen; Mateusz Makuch; Belinda Lennox; Darren Fowler; Fintan Sheerin; Patrick Waters; M Isabel Leite; Adam E Handel; Sarosh R Irani Journal: Brain Date: 2022-08-27 Impact factor: 15.255