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Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in
Two non-exclusive mechanisms have been postulated. Firstly, in the context of aging and neurodegeneration, the integrity of the blood-brain barrier (BBB) can become compromised, resulting in increased permeability. Notably, amyloid plaques have been hypothesized to counteract this BBB leakage. However, upon the administration of antibodies, these plaques are targeted and subsequently eliminated, potentially uncovering the occurrence of micro-hemorrhage
Secondly, an alternate perspective posits that the introduction of antibodies into the bloodstream triggers an immune-inflammatory response as part of the treatment regimen. This orchestrated immune reaction might inadvertently precipitate micro-hemorrhages.
magnetic resonance imaging of the brain
Magnetic resonance imaging of the brain uses magnetic resonance imaging (MRI) to produce high-quality two- or three-dimensional images of the brain, brainstem, and cerebellum without ionizing radiation (X-rays) or radioactive tracers.
History
T ...
in patients with Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
. ARIA is associated with anti-amyloid drugs, particularly human monoclonal antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Mon ...
such as aducanumab. There are two types of ARIA: ARIA-E and ARIA-H. The phenomenon was first seen in trials of bapineuzumab
Bapineuzumab (nicknamed "bapi") is a humanized monoclonal antibody that acts on the nervous system and may have potential therapeutic value for the treatment of Alzheimer's disease and possibly glaucoma. However, in 2012 it failed to produce sig ...
.
ARIA-E
ARIA-E refers tocerebral edema
Cerebral edema is excess accumulation of fluid ( edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compres ...
, involving the breakdown of the tight endothelial junctions of the blood-brain barrier and subsequent accumulation of fluid. In a double-blind
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...
trial of the humanised monoclonal antibody solanezumab
Solanezumab (proposed INN, LY2062430) is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector for patients with Alzheimer's disease. The drug originally attracted extensive media coverage proclaiming it a breakthrough, but ...
(n = 2042), sixteen patients (11 taking the drug, 5 taking a placebo), or 0.78% developed ARIA-E. A further 7 patients developed ARIA-E during an open-label extension of the trial.
The effect of ARIA-E depends on the severity and location of the edema. Symptoms may include headache
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
, changes in mental state, confusion
In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"
, vomiting, nausea, tremor and gait disturbances.
ARIA-H
ARIA-H refers to cerebral microhaemorrhages (mH), small haemorrhages on the brain, often accompanied by hemosiderosis. mH are usually seen as small, round and low intensitylesion
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals.
Types
There is no de ...
s and are small haemosiderin deposits. Some studies define mH as being less than or equal to 10mm, while others define the cut-off as ≤ 5mm. The prevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
of mH in healthy elderly people is approximately 6%, but this value increases to between 50% and 80% in elderly people with cerebrovascular disease
Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. Th ...
.
Mechanism of action
Two non-exclusive mechanisms have been postulated. Firstly, in the context of aging and neurodegeneration, the integrity of the blood-brain barrier (BBB) can become compromised, resulting in increased permeability. Notably, amyloid plaques have been hypothesized to counteract this BBB leakage. However, upon the administration of antibodies, these plaques are targeted and subsequently eliminated, potentially uncovering the occurrence of micro-hemorrhage
Secondly, an alternate perspective posits that the introduction of antibodies into the bloodstream triggers an immune-inflammatory response as part of the treatment regimen. This orchestrated immune reaction might inadvertently precipitate micro-hemorrhages.ARIA MRI Classification Criteria
References
External links
{{Medical resources , ICD10 = , ICD9 = , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = Anti-amyloid monoclonal antibodies Neuroimaging Magnetic resonance imaging