MRI abnormalities in Creutzfeldt-Jakob disease and other rapidly progressive dementia.

OBJECTIVE: To investigate brain MRI abnormalities in a cohort of patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt-Jakob disease (CJD). METHODS: One hundred and seven patients with diagnosis of prion disease (60 with definite sCJD, 33 with probable sCJD and 14 with genetic prion disease) and 40 non-prion related RPD patients (npRPD) underwent brain MRI including DWI and FLAIR. MRIs were evaluated with a semiquantitative rating score, which separately considered abnormal signal extent and intensity in 22 brain regions. Clinical findings at onset, disease duration, cerebrospinal-fluid 14-3-3 and t-tau protein levels, and EEG data were recorded. RESULTS: Among patients with definite/probable diagnosis of CJD or genetic prion disease, 2/107 had normal DWI-MRI: in one patient a 2-months follow-up DWI-MRI showed CJD-related changes while the other had autopsy-proven CJD despite no DWI abnormalities 282 days after clinical onset. CJD-related cortical changes were detected in all lobes and involvement of thalamus was common. In the npRPD groups, 6/40 patients showed DWI alterations that clustered in three different patterns: (1) minimal/doubtful signal alterations (limbic encephalitis, dementia with Lewy bodies); (2) clearly suggestive of alternative diagnoses (status epilepticus, Wernicke or metabolic encephalopathy); (3) highly suggestive of CJD (mitochondrial disease), though cortical swelling let exclude CJD. CONCLUSIONS: In the diagnostic work-up of RPD, negative/doubtful DWI makes CJD diagnosis rather unlikely, while specific DWI patterns help differentiating CJD from alternative diagnoses. The pulvinar sign is not exclusive of the variant form.

Spontaneous intracranial hypotension: a case series and literature review.

Spontaneous intracranial hypotension (SIH) is a condition of negative intracranial pressure resulting from cerebrospinal fluid (CSF) leakage from the dural sac and is a well-known cause of orthostatic headache. Diagnosis and management can be difficult, often requiring coordination between multiple disciplines. Low CSF pressure and diffuse meningeal enhancement on brain MRI are the major instrumental features of the classic syndrome. Neuroimaging plays a key role in diagnosing SIH, particularly in atypical clinical presentations, by recognizing the specific findings of brain sagging on MRI and detecting the level of CSF leak on spinal imaging, thus guiding therapy accordingly. Since SIH could present with such a heterogeneous clinical picture, careful history taking and increased awareness of atypical presentations are of utmost importance. We review the existing SIH literature, illustrate management, clinical and neuroimaging findings of four consecutive patients with atypical SIH, who were recently referred to our hospital for evaluation to simplify and streamline the management of SIH.

Disorders of arousal in 4 older men: evidence from clinical practice.

STUDY OBJECTIVES: To describe clinical and video-polysomnographic features of disorders of arousal (DoA) in older adults. METHODS: Four consecutive male patients with nocturnal motor behaviors underwent a clinical interview, neurologic examination, laboratory tests, brain magnetic resonance imaging, and nocturnal in-laboratory or 24- to 48-hour home video polysomnography. The patients repeated an evaluation after 6 months of follow-up, including a 48-hour home video polysomnography in 2 patients. RESULTS: The patients were aged 65-72 years, and 1 patient has Parkinson disease. Sleep-related behavioral episodes had begun from 12-55 years before our observation. Three patients presented with a positive family history for DoA. Sleep motor episodes were described as suddenly raising the head or trunk, sitting in bed, screaming, speaking, gesturing, and sleepwalking (in 1 patient). When questioned, all patients seemed confused, rarely reporting any dream-like content. We recorded 25 DoA episodes of different intensity and complexity arising from nonrapid eye movement sleep. The semiology of the episodes was similar to that described in younger patients, consisting of sleep terrors and confusional arousals. All patients presented with physiological rapid eye movement sleep muscle atonia. Medication therapy reduced the frequency of the episodes in 2/4 patients. CONCLUSIONS: DoA may begin in adulthood and persist or arise in older adults, sometimes causing sleep-related injuries. Motor patterns of DoA in older adults are similar to those of younger patients. A combined clinical examination and video polysomnography recording are crucial in establishing a definitive diagnosis of nocturnal motor behavior in all older adults and especially in those affected by neurodegenerative diseases. CITATION: Loddo G, Fragiacomo F, Mainieri G, et al. Disorders of arousal in 4 older men: evidence from clinical practice. J Clin Sleep Med. 2022;18(1):129-136.

Cognitive correlates and baseline predictors of future development of visual hallucinations in dementia with Lewy bodies.

Visual hallucinations (VH) are common in dementia with Lewy bodies (DLB), and are among the core symptoms for its clinical diagnosis. VH have been associated with cognitive alterations, although research findings in this area are still limited. The present study aimed at investigating the cognitive correlates of VH in DLB, and the baseline neuropsychological features predicting the future development of VH. A cross sectional study compared the cognitive profile of 18 DLB patients with VH with that of 32 DLB without VH. A longitudinal study involved 34 DLB patients with no VH at baseline, among whom 17 developed VH and 17 remained without VH at follow-up. Logistic regression analyses were carried out to investigate what baseline cognitive variables independently predicted the development of VH at follow-up. DLB patients with VH had worse performance on the copy of the Rey complex figure, assessing visual construction/perception, than those without VH in the cross-sectional study (p = .001). Significant impairments in attention and visual memory delayed recall were also present. Baseline performance on the immediate prose memory was the only significant predictor of VH development in the longitudinal study (p = .03). DLB patients are more at risk of developing VH if presenting more severe immediate verbal memory impairment, and this might be related to a combination of (a) DMN-related dysfunctions, (b) impairment in medial temporal lobe-related functions, and (c) frontal abilities including long-term encoding of information and working memory. Differences between hallucinating and non-hallucinating patients in visual construction/perception, typical of DLB symptomatology, may be essential for VH to emerge in individuals with an at risk cognitive profile.

Psychiatric Phenocopy Syndrome of Behavioral Frontotemporal Dementia: Behavioral and Cognitive Fingerprint.

Behavioral and cognitive variables predicting behavioral frontotemporal dementia (bvFTD) versus primary psychiatric disorders mimicking bvFTD (phenocopy syndrome: bvFTD-PS) were studied. Forty-one probable/definite bvFTD and 16 bvFTD-PS patients were evaluated with cognitive battery, Neuropsychiatric Inventory, and Stereotypic and Ritualistic Behavior-revised questionnaires. Twenty-seven healthy subjects served as control. Severity of cognitive impairment/behavioral symptoms and profile of cognitive deficits were similar, with bvFTD-PS showing impaired executive abilities and memory. However, phonemic fluency was impaired only in bvFTD (p < 0.001). Depression was worse in bvFTD-PS, while apathy, disinhibition, and dietary changes characterized bvFTD. Phonemic fluency and depression accounted for the best predictive diagnostic model. A structured psychiatric screening of bvFTD mimickers may often yield a psychiatric diagnosis with predominant depressive symptoms and therefore a potentially treatable condition.

Testing Hippocampal Memory in Prodromal Dementia with Lewy Bodies.

The Free and Cued Selective Reminding test (FCSRT) was used to assess memory in 19 patients with prodromal dementia with Lewy bodies (DLB) and 25 Alzheimer's disease (AD) patients. DLB scored better than AD in selective measures of the FCSRT: immediate total recall (p = 0.01) and index of sensitivity of cueing (p = 0.001), while free delayed and total memory scores were similarly impaired. The index of sensitivity of cueing held a sensitivity of 76% and specificity of 79% in distinguishing DLB. FCSRT could help in disentangling hippocampal memory deficits from memory impairment due to ineffective recall strategies.

Specific Verbal Memory Measures May Distinguish Alzheimer's Disease from Dementia with Lewy Bodies.

BACKGROUND: Standard measures of commonly used memory tests may not be appropriate to distinguish different neurodegenerative diseases affecting memory. OBJECTIVE: To study whether specific measures of verbal memory obtained with the Rey Auditory Verbal Learning test (RAVLT) could help distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). METHODS: Twenty-nine DLB and 32 AD patients participated in the study and were followed longitudinally for 3 years until the diagnosis was confirmed according to standard clinical criteria. Twenty-eight healthy elderly subjects served as controls. The following verbal memory measures were evaluated: verbal learning (VL), verbal forgetting (VF), percentage of verbal forgetting (VF%), and serial position effects of the immediate recall performance. RESULTS: DLB and AD groups have comparable performances at the RAVLT immediate and delayed recall tasks. However, VL was higher in DLB than AD while VF% was greater in AD. With a VF% cut-off ≥75%, AD and DLB patients were differently distributed, with 58% of AD versus 21% of DLB above this cut-off. The recency effect was significant higher in AD than DLB. DISCUSSION: DLB patients had a better performance in VL than AD, but worse VF and recency effect. These specific measures of verbal memory could be used as cognitive markers in the differential diagnosis between these two conditions.

Sleep-Wake Profile in Dementia with Lewy Bodies, Alzheimer's Disease, and Normal Aging.

BACKGROUND: Alterations of the sleep-wake cycle are common features of neurodegenerative dementia. OBJECTIVES: To study differences in sleep-wake profiles in dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and healthy controls. METHODS: 30 DLB and 32 AD patients, and 33 healthy elderly participants were studied. Patients were evaluated for global cognitive impairment, extrapyramidal signs, fluctuations of attention, and behavioral disorders. A comprehensive sleep-wake profile was obtained including a set of questionnaires [Pittsburgh Sleep Quality Index (PSQI), REM Sleep Behavior Disorder Single-Question screen (RBD1Q), Epworth Sleepiness Scale (ESS)] and 12-day sleep diaries. RESULTS: Patients were matched for age, gender, and disease severity. DLB patients showed more severe daytime somnolence/dysfunction due to somnolence, and a higher proportion of RBD-like symptoms (70%) compared to AD and controls (p < 0.001), regardless of the presence of psychoactive drug treatment. As for sleep timing, DLB patients had a greater number of daytime naps and longer night sleep, with the latter being associated with use of clonazepam. The severity of fluctuations was associated with the presence of RBD (Clinician Assessment of Fluctuation score = RBD+: 5.2±3.7; RBD-: 2.1±3.2, p = 0.04). AD patients reported the best sleep-wake profile, while healthy controls declared the poorest sleep quality, although sleep timing and the quality of wakefulness were comparable between AD and controls. DISCUSSION: RBD and daytime fluctuations of attention may coexist in DLB and even reciprocally potentiate each other. Self-reports of sleep quality may lead to an underestimation of sleep disturbances in AD, possibly influenced by anosognosia, compared to normal elderly individuals who complain mainly of insomnia.