Rapidly Progressive Dementia

Abstract

Purpose of review: This article presents a practical approach to the evaluation of patients with rapidly progressive dementia.

Recent findings: The approach presented in this article builds upon the standard dementia evaluation, leveraging widely available tests and emergent specific markers of disease to narrow the differential diagnosis and determine the cause(s) of rapid progressive decline. The discovery of treatment-responsive causes of rapidly progressive dementia underscores the need to determine the cause early in the symptomatic course when treatments are most likely to halt or reverse cognitive decline.

Summary: A pragmatic and organized approach to patients with rapidly progressive dementia is essential to mitigate diagnostic and therapeutic challenges and optimize patient outcomes.

FIGURE 13-1

Imaging and histopathology of the patient in CASE 13-1. Axial diffusion-weighted MRI slices show restricted diffusion within the cortical ribbon (A) and caudate heads (B). Hematoxylin and eosin (H&E)–stained section (C) shows spongiform changes.

FIGURE 13-2

Common causes of rapidly progressive dementia stratified by rate of progression and potential reversibility. Causes in the top right quadrant (shaded area) typically associate with the most rapidly progressive presentations and the greatest potential for response to appropriate treatments; practical approaches to rapidly progressive dementia should prioritize their detection.

FIGURE 13-3

Still image of the patient in CASE 13-2 experiencing a left faciobrachial-crural seizure (A), with continuous EEG monitoring. Typical EEG findings (frontal infraslow activity) are obscured by motor artifact associated with the seizure (shaded red area). B, Results of indirect immunofluorescent assay of murine cerebellum section showing prominent synaptic staining within the molecular layer in a pattern typical of leucine-rich glioma inactivated protein 1 (LGI1) antibody encephalitis (subsequently confirmed with cell-based assay [not shown]).

FIGURE 13-4

Neuroimaging findings associated with specific causes of rapidly progressive dementia. Creutzfeldt-Jakob disease: Axial fluid-attenuated inversion recovery (FLAIR) images show striatal thalamus (A) and cortical (B) hyperintensities. Autoimmune/inflammatory encephalitis: Coronal FLAIR image (C) shows bilateral limbic/hippocampal hyperintensities. Infectious encephalitis: Axial noncontrast FLAIR images (D, E) show right anteromedial temporal lobe hyperintensities in a patient with herpes simplex encephalitis. Metabolic/nutritional deficiency: Axial FLAIR image (F) shows dorsomedial thalamic hyperintensities in a patient with Wernicke-Korsakoff syndrome due to thiamine (vitamin B₁) deficiency; sagittal noncontrast T1-weighted image (G) shows diencephalon hyperintensity indicating metabolic encephalopathy in a patient with hepatic dysfunction. Vascular disease: Axial FLAIR image (H) shows strokes and diffuse ischemic white matter changes; axial gradient recalled echo (GRE) image (I) shows bilateral anterior and dorsomedial thalamic hemorrhage causing acute-onset amnesia; axial postcontrast T1-weighted image (J) shows enhancement of vessels in the right hemisphere (arrows), suggesting central nervous system vasculitis. Reprinted with permission from Day GS, Tang-Wai DF, Neurodegener Dis Manag. © 2014 Future Medicine Ltd.

FIGURE 13-5

Imaging of the patient in CASE 13-3. A, Fludeoxyglucose positron emission tomography (FDG-PET) imaging shows increased metabolism within mediastinal, thyroid (inset), and myocardial tissues. B, Hematoxylin and eosin (H&E)–stained needle core biopsy of the thyroid shows non-necrotizing granulomatous inflammation with giant cells (arrows).

FIGURE 13-6

Imaging of the patient in CASE 13-4. Axial fluid-attenuated inversion recovery (FLAIR) images show bilateral temporal lobe and corpus callosal lesions (insets) at presentation (A) and 10 days later following empiric immunosuppressant treatment (B).

FIGURE 13-7

Common EEG findings in patients with rapidly progressive dementia (RPD). A, Generalized diffuse slowing in a patient with RPD due to Alzheimer disease. B, Triphasic waves in a patient with RPD associated with metabolic encephalopathy. C, Lateralized (left) periodic discharges in a patient with RPD associated with a left occipital glioma and frequent complex partial seizures. D, Frontal intermittent rhythmic delta activity in a patient with hydrocephalus associated with cryptococcal meningitis. E, Frontal infraslow activity (red shaded area) preceding a faciobrachial dystonic seizure in a patient with RPD associated with leucine-rich glioma inactivated protein 1 (LGI1) autoantibodies. F, Extreme delta brush in a patient with autoimmune RPD associated with N-methyl-d-aspartate (NMDA) receptor autoantibodies, red shaded area highlighting segment with beta rhythm superimposed on the crests of delta waves. All images displayed in traditional 10–20 placement; distance between green vertical bars = 1 second.

FIGURE 13-8

Imaging of the patient in CASE 13-5. Axial fluid-attenuated inversion recovery (FLAIR) (A) and diffusion-weighted image (B) show increased signal within the cortical ribbon, most prominent in left frontal, parietal, and temporal areas.