Cerebral Amyloidosis - Symptoms and Treatment

Introduction

Cerebral amyloidosis is characterized by abnormal protein deposition in the brain's blood vessels. This can lead to bleeding into the brain and dementia. Bleeding usually occurs in the cortical, subcortical, and leptomeningeal vessels of the brain, and not the deep areas. The most prevalent risk factor is increasing age. It is more commonly seen in individuals above fifty-five years. It may also have a hereditary pattern which is common amongst young individuals. If bleeding is more than expected, symptoms may occur immediately and resemble a stroke.

What Is An Amyloid Deposit?

Amyloid consists of self-assembled, pink-colored, extracellular, low-molecular-weight amorphous protein in the form of fibrils. The main components of amyloid are a fibrillar protein and an amyloid P component. The fibrillar protein is characteristic of each type of disease. The deposits can build up in any body part.

• Normal protein deposited in excess.

• Defective protein is being deposited.

On spectroscopy, these pink-colored amorphous deposits appear as non-branching fibrils, whereas beta-pleated sheet configuration can be well appreciated on X-ray crystallography.

It can be of various types:

• Generalized.

• Localized.

• Familial.

Among all these types, the most common type of amyloidosis is localized to the central nervous system (CNS). These fibrillar deposits may cause progressive cognitive deficits, dementia, stroke, cerebellar and extrapyramidal signs, or a combination of all these.

These deposits can be in the form of

• Parenchymal pre-amyloid deposits give negative under congo-red or thioflavin S staining.

• Parenchymal amyloid deposits are usually present in compact plaques, which gives extensive congo-red or thioflavin S staining.

• Cerebral amyloid angiopathy exhibits congo-red or thioflavin S staining, where the fibrillar deposits will affect the small and medium-sized capillaries.

What Are the Symptoms of Cerebral Amyloidosis?

The symptoms of cerebral amyloidosis include

• Drowsiness.

• Headache.

• Seizure.

• Stupor or rarely coma.

• Vomiting.

• Confusion.

• Delirium.

• Double vision or decreased vision.

• Speech problem.

• Weakness and fatigue.

• Paralysis.

If the bleeding is not severe, then the symptoms are

• Episodes of confusion.

• Loss of mental function or dementia.

• Headaches.

• Seizure.

What Is the Pathophysiology of Cerebral Amyloidosis?

The A-beta form tends to deposit in the blood vessels of the brain. These deposits, in turn, cause a series of events, including the release of inflammatory mediators, the activation of the complement pathway, oxidative stress, and altered permeability of the blood-brain barrier and cell toxicity.

The A-beta form typically deposits in the tunica media, surrounding smooth muscle cells and tunicaitia. As the severity increases, these deposits involve all layers of the vessels showing loss of smooth muscle cells. Hence the normal vascular architecture is lost, and double barreling and micro-aneurysm can be seen. These deposits can also obliterate the vessel lumen, causing ischemia and infarction.

What Are the Laboratory Investigations to Be Carried Out?

The investigations that can be carried out are

• Computed Tomography (CT) Scan: It is the imaging of choice to detect any bleeding in the brain. It may be used to evaluate cortical hemorrhage along with subdural, subarachnoid, and intraventricular hemorrhage.

• Magnetic Resonance Imaging (MRI): It is used to detect small or chronic cortical hemorrhage and rule out any other probable causes of acute cortical-subcortical bleeding. It also helps in assessing the progression of the disease.

• Positron Emission Tomography (PET) Scan: To detect amyloid deposits in the brain.

Accurate recognition of the imaging findings is crucial in clinical decisions in patients with cerebral amyloidosis. Histological confirmation is required by post-mortem autopsy, and it is considered the standard gold method to reach a definitive diagnosis. Congo-red stains are used as a standard method, but as it has low sensitivity, Daylon stain is used more commonly.

As it is more sensitive, it can detect even smaller amounts of amyloid deposition. Fluorescent microscopy is also useful in detecting amyloid deposits as per the modified Boston's criteria, which develop multiple lobar cortical or cortico-subcortical hemorrhages like cerebral microbleeds and intracerebral brain hemorrhage (ICH), or single lobar hemorrhage along with focal or disseminated cortical superficial hemosiderosis could be easily diagnosed after eliminating all the other probable causes of hemorrhage.

What Is the Treatment for Cerebral Amyloidosis?

There is no specific treatment protocol for managing cerebral amyloidosis. Surgical interventions increase the risk of mortality. Immunosuppressive drugs have shown beneficial effects.

Anti-platelet and anticoagulant drugs should be avoided in elderly patients as it increases the risk of bleeding. In addition, rehabilitation is often required in cases of weakness or clumsiness involving speech, physical or occupational therapy. Sometimes, drugs for Alzheimer's disease, which can improve memory, are also used.

What Are the Differential Diagnosis for Cerebral Amyloidosis?

Differential diagnosis includes

• Hemorrhagic tumor.

• Hemorrhagic transformation of an ischemic stroke.

• Lobar extension of a hypertensive putaminal hemorrhage.

• Arteriovenous malformation (AVM).

Other imaging differential diagnosis includes

• Hypertensive microangiopathy.

• Hemorrhagic metastases.

• Multiple cavernoma syndromes.

• Diffuse axonal injury.

• Radiation-induced vasculopathy.

• Neurocysticercosis.

What Are the Complications of Cerebral Amyloidosis?

The complications of cerebral amyloidosis are

• Stroke (if the amyloid deposits are limited to cerebral vessels only).

• Dementia (if the amyloid deposits show widespread distribution throughout the brain parenchyma).

• Hydrocephalus.

• Seizures.

• Recurrent episodes of hemorrhage in the brain.

Conclusion

Cerebral amyloidosis can be present in sporadic and hereditary forms. While the hereditary form is rare and only affects young individuals, the sporadic form is more common in elderly individuals, and its severity increases with age. The beta-amyloid forms deposits in the cerebral cortex's small and mid-sized blood vessels and leptomeninges. Localized amyloidosis is more common in the brain and can cause dementia, cognitive reduction, and stroke. The advancements in clinical and imaging tools allow reliable, definitive diagnoses.