Rapidly Progressive Dementia

Geschwind, Michael D.

doi:10.1212/con.0000000000000319

Cited by 91 publications

(143 citation statements)

References 53 publications

(90 reference statements)

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“…These phenotypes encompass a constellation of cognitive, behavioural, language, motor and movement impairments. When a rapidly progressive course is encountered, some of these phenotypes may be encompassed under the umbrella term of 'rapidly progressive dementias' [19]. Prion disease, notably Creutzfeldt-Jakob disease, is a potential underlying diagnosis in rapidly progressive dementias [19].…”

Section: Introductionmentioning

confidence: 99%

Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates

et al. 2020

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Corticobasal degeneration typically progresses gradually over 5-7 years from onset till death. Fulminant corticobasal degeneration cases with a rapidly progressive course were rarely reported (RP-CBD). This study aimed to investigate their neuropathological characteristics. Of the 124 autopsy-confirmed corticobasal degeneration cases collected from 14 centres, we identified 6 RP-CBD cases (4.8%) who died of advanced disease within 3 years of onset. These RP-CBD cases had different clinical phenotypes including rapid global cognitive decline (N = 2), corticobasal syndrome (N = 2) and Richardson's syndrome (N = 2). We also studied four corticobasal degeneration cases with an average disease duration of 3 years or less, who died of another unrelated illness (Intermediate-CBD). Finally, we selected 12 age-matched corticobasal degeneration cases out of a cohort of 110, who had a typical gradually progressive course and reached advanced clinical stage (Endstage-CBD). Quantitative analysis showed high overall tau burden (p = 0.2) and severe nigral cell loss (p = 0.47) in both the RP-CBD and End-stage-CBD groups consistent with advanced pathological changes, while the Intermediate-CBD group (mean disease duration = 3 years) had milder changes than End-stage-CBD (p < 0.05). These findings indicated that RP-CBD cases had already developed advanced pathological changes as those observed in End-stage-CBD cases (mean disease duration = 6.7 years), but within a significantly shorter duration (2.5 years; p < 0.001). Subgroup analysis was performed to investigate the cellular patterns of tau aggregates in the anterior frontal cortex and caudate by comparing neuronal-toastrocytic plaque ratios between six RP-CBD cases, four Intermediate-CBD and 12 age-matched End-stage-CBD. Neuronalto-astrocytic plaque ratios of Intermediate-CBD and End-stage-CBD, but not RP-CBD, positively correlated with disease duration in both the anterior frontal cortex and caudate (p = 0.02). In contrast to the predominance of astrocytic plaques we previously reported in preclinical asymptomatic corticobasal degeneration cases, neuronal tau aggregates predominated in RP-CBD exceeding those in Intermediate-CBD (anterior frontal cortex: p < 0.001, caudate: p = 0.001) and End-stage-CBD (anterior frontal cortex: p = 0.03, caudate: p = 0.01) as demonstrated by its higher neuronal-to-astrocytic plaque ratios in both anterior frontal cortex and caudate. We did not identify any difference in age at onset, any pathogenic tau mutation or concomitant pathologies that could have contributed to the rapid progression of these RP-CBD cases. Mild TDP-43 pathology was observed in three RP-CBD cases. All RP-CBD cases were men. The MAPT H2 haplotype, known to be protective, was identified in one RP-CBD case (17%) and 8 of the matched End-stage-CBD cases (67%). We conclude that RP-CBD is a distinct aggressive variant of corticobasal degeneration with characteristic neuropathological substrates resulting in a fulminant disease process as evident both clinically and pathological...

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Section: Introductionmentioning

confidence: 99%

Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates

et al. 2020

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“…There are some excellent and comprehensive reviews, [1][2][3] including by Murray,4 in this journal. The archetypal diagnosis is Creutzfeldt-Jakob disease (CJD), and most experiences have been reported from specialist prion disease referral centres and from a small number of specialist cognitive clinics.…”

Section: Introductionmentioning

confidence: 99%

CJD mimics and chameleons

Mead

Rudge

2017

Pract Neurol

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Rapidly progressive dementia mimicking Creutzfeldt–Jakob disease (CJD) is a relatively rare presentation but a rewarding one to become familiar with, as the potential diagnoses range from the universally fatal to the completely reversible. Patients require urgent decisions about assessment and investigation and have quickly evolving needs for treatments and support, through symptom management and end-of-life care in most cases. We have based this pragmatic review on the experiences of a specialist prion referral centre in the UK, which, unsurprisingly, is strongly biased towards seeing patients with CJD. Cases eventually proven not to have prion disease might be described as ‘CJD-mimics’; being referred from UK neurologists, these are the most challenging cases. CJD in its classical presentation is very rarely mimicked; however, it is highly heterogeneous, and atypical forms can mimic virtually all common neurodegenerative syndromes. Warning features of a mimic include generalised seizures, hyponatraemia, fever, a facial movement disorder, a normal neurological examination and a modestly rapid presentation. Contrast-enhancing lesions or MRI signal hyperintensity outside the striatum, thalamus or cortex and a cerebrospinal fluid pleocytosis are key investigation pointers to a CJD mimic.

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“…This is a case of RPD induced by CJD which exhibited unusual clinical and EEG manifestations, yet typical MRI findings, which may be relevant to physicians to consider the CJD etiology in similar clinical pictures. RPD refers to a condition characterized by a quick decline in more than one cognitive domain with functional disability in a short time (Geschwind, 2016). The differential diagnosis of RPD includes many treatable conditions that our patient multimodal work-up allowed to rule out.…”

Section: Discussionmentioning

confidence: 99%

“…The differential diagnosis of RPD includes many treatable conditions that our patient multimodal work-up allowed to rule out. Among these, paraneoplastic autoimmune encephalopathies, infections, toxic or metabolic conditions, neoplasms, and other conditions such as dural arteriovenous fistula (DAVF) that sometimes manifest as RPD (Geschwind, 2016).…”

Section: Discussionmentioning

confidence: 99%

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation

Prodi

Rossi

Bertaina

et al. 2020

Front. Behav. Neurosci.

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We describe the clinical features, neuropsychological tests, laboratory, electroencephalography (EEG), magnetic resonance imaging (MRI) and positron emission tomography (PET) findings of a 59-year-old woman who presented to our Centre for cognitive impairment since few months, with language disturbances, particularly anomia, dyscalculia, and memory loss. The clinical and neuropsychological features were non-specific and overlapping with those of other rapidly progressing neurodegenerative disorders. However, brain MRI played a pivotal role in the diagnosis, showing cortical diffusion restriction, particularly in the parietal lobes and posterior cingulum, with sparing of the perirolandic cortex, typical of Creutzfeldt-Jakob disease (CJD). Brain MRI abnormalities were visible since the first evaluation and remained stable at 2 and 6 weeks follow up. Basal ganglia and thalami were never involved. PET showed left lateralized reduced glucose metabolism, with partial overlap with MRI signal abnormalities. Despite MRI were strongly indicative of CJD, clinical, laboratory and EEG findings did not fulfill the diagnostic criteria for CJD which applied at the time of clinical assessment. Indeed, neither myoclonus, visual or cerebellar signs or akinetic mutism were present. Also, the characteristic periodic sharp wave complexes were absent at baseline EEG, and the CSF assay for 14-3-3 was negative. We, therefore, performed a real-time quaking-induced conversion (RT-QuIC) assay on a frozen sample of corticospinal fluid (CSF), which showed a positive result. RT-QuIC is a prion protein conversion assay that has shown high diagnostic sensitivity and specificity for the diagnosis of CJD. RT-QuIC has been recently incorporated in the National CJD Research and Surveillance Unit and Center for Disease Control and Prevention (CDC) diagnostic criteria for CJD. The fatal evolution of the disease brought the patient to death 13 months after symptoms onset. Pathology proved the diagnosis of sporadic CJD, subtype MM/MV 2C.

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Rapidly Progressive Dementia

Cited by 91 publications

References 53 publications

Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates

Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates

CJD mimics and chameleons

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation

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