PMC8239148_01
Time course of diagnostic and therapeutic approach. AB, antibody testing; BDI, Beck Depressions Inventory; CE, clinical examination; CSF, cerebrospinal fluid; m, month; MRI, magnetic resonance imaging; NP, neuropsychology; y, year. The black arrow and the arrows after the blue arrows placed after the squares with symptoms indicate an improvement of symptoms. The dotted lines before the square "depressive syndrome" indicate its repeated occurrence.
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F1
MRI at first presentation (Figure 1) revealed enlarged lateral ventricles, but no clear frontotemporal atrophy. CSF analysis at second presentation (Figure 1, 4 months after initial presentation) showed no pleocytosis, but elevated levels of phosphorylated tau protein 181 as a neuroaxonal destruction marker [ptau181: 65 pg/ml (pathological >61 pg/ml)]. We assumed an anti-flotillin 1/2-associated dementia 6 months after her first presentation (Figure 1) based on the neuropsychologically-confirmed dementia syndrome affecting several cognitive subdomains, proof of pathological tau and elevated phosphorylated tau protein in CSF, and clinical features of dementia entailing a slowly progressing onset in conjunction with obvious, subjective speech difficulties and a depressive syndrome fulfilling the criteria for autoimmune dementia according to Banks et al. and Sechi and Flanagan. We therefore assumed that her dementia probably has an autoimmune-based origin, in line with recent guidelines from Banks et al., which is why she was given corticosteroids starting 6 months after first presentation (Figure 1). However, as she failed to tolerate the intravenous route 3 months after diagnosis and 6 months after first presentation, two cycles were administered as a high-dosage oral therapy of 1 g prednisone per day over 3 days repeated monthly (Figure 1), planned to proceed for four further applications. In the clinical follow-up 10 months after initial presentation (Figure 1) and after four cycles of oral steroids, she presented objectively with less cognitive decline as assessed by mini-mental status examination (MMSE) (actual MMSE 29/30, prior MMSE 9 months earlier 27/30). At this second follow up, serum anti-flotilin 1/2 antibodies (1:10) were again detected in an autoantibody test in blood samples (Figure 1).
Cognitive profile at baseline. Illustration of neuropsychological test results at baseline presented as z-scores. Blue-shaded fields denote the normal range. Normative values of the RCFT Copy test only allows a distinction between a pathological and normal performance (in this case normal performance expressed as z-score between -1 and 1). The area between dotted lines indicates normal range. CERAD, Consortium to Establish a Registry for Alzheimer's Disease; WAIS-IV, Wechsler Adult Intelligence Scale:Fourth Edition; WMS-IV, Wechsler Memory Scale:Fourth Edition; RCFT, Rey Osterrieth Complex Figure Test.
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F2
Neuropsychological testing at first presentation (Figure 1) revealed impairment in verbal fluency, processing speed, cognitive flexibility, working memory span, and verbal memory (Figure 2, first presentation).
PMC8239148_02
Time course of diagnostic and therapeutic approach. AB, antibody testing; BDI, Beck Depressions Inventory; CE, clinical examination; CSF, cerebrospinal fluid; m, month; MRI, magnetic resonance imaging; NP, neuropsychology; y, year. The black arrow and the arrows after the blue arrows placed after the squares with symptoms indicate an improvement of symptoms. The dotted lines before the square "depressive syndrome" indicate its repeated occurrence.
fpsyt-12-626121-g0001.jpg
PMC8239148_02_fpsyt-12-626121-g0001.jpg
F1
MRI at first presentation (Figure 1) revealed enlarged lateral ventricles, but no clear frontotemporal atrophy. CSF analysis at second presentation (Figure 1, 4 months after initial presentation) showed no pleocytosis, but elevated levels of phosphorylated tau protein 181 as a neuroaxonal destruction marker [ptau181: 65 pg/ml (pathological >61 pg/ml)]. We assumed an anti-flotillin 1/2-associated dementia 6 months after her first presentation (Figure 1) based on the neuropsychologically-confirmed dementia syndrome affecting several cognitive subdomains, proof of pathological tau and elevated phosphorylated tau protein in CSF, and clinical features of dementia entailing a slowly progressing onset in conjunction with obvious, subjective speech difficulties and a depressive syndrome fulfilling the criteria for autoimmune dementia according to Banks et al. and Sechi and Flanagan. We therefore assumed that her dementia probably has an autoimmune-based origin, in line with recent guidelines from Banks et al., which is why she was given corticosteroids starting 6 months after first presentation (Figure 1). However, as she failed to tolerate the intravenous route 3 months after diagnosis and 6 months after first presentation, two cycles were administered as a high-dosage oral therapy of 1 g prednisone per day over 3 days repeated monthly (Figure 1), planned to proceed for four further applications. In the clinical follow-up 10 months after initial presentation (Figure 1) and after four cycles of oral steroids, she presented objectively with less cognitive decline as assessed by mini-mental status examination (MMSE) (actual MMSE 29/30, prior MMSE 9 months earlier 27/30). At this second follow up, serum anti-flotilin 1/2 antibodies (1:10) were again detected in an autoantibody test in blood samples (Figure 1).