Hereditary cerebral hemorrhage with amyloidosis

Hereditary cerebral hemorrhage with amyloidosis (HCHWA) is a neurological condition in which an abnormal protein (amyloid) builds up in the walls of the arteries of the brain (and less frequently, veins). This process is known as amyloid deposition, which can lead to strokes, seizures, neurological deficits, cognitive decline, and dementia. Symptoms usually present before the 5th decade of life.^[1] There are many different ways of classifying the types of HCHWA based on the underlying genetic changes, proteins involved, signs and symptoms, and the regions in which they were first described. Based on the region in which they were first described, the subtypes include:^[1][2]

• The Dutch, Arctic, Piedmont, Iowa, Flemish, Italian types are caused by mutations in the APP gene
• The British and Danish types are caused by mutations in the ITM2B gene
• The Icelandic type is caused by mutations in the CST3 gene 

All types of HCHWA currently described are inherited in an autosomal dominant manner.^[2] There is no cure for HCHWA, however, antihypertensive therapy is typically recommended.^[3][1]

Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is the most common type of hereditary cerebral hemorrhage with amyloidosis (HCHWA). It is named for the families in two coastal villages in the Netherlands who were first documented with the condition.^[4] HCHWA-D typically presents with stroke between 39 and 76 years of age. It is caused by mutations in the APP gene and is inherited in an autosomal dominant manner.^[5][2]

Approximately 87% of individuals with hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) have intracranial hemorrhage (bleeding in the brain) and 13% have infarcts (stroke).^[3] The first stroke usually occurs between the ages of 45 and 65 years, and is not caused by hypertension or hemorrhagic diathesis (bleeding tendency).^[6] 

Signs and symptoms of HCHWA-D may include: seizures/epilepsy, nausea, vomiting, progressive headache, focal neurological signs (double or decreased vision, speech difficulties, confusion, delirium, weakness or paralysis, sensation changes or loss of sensation, progressive intellectual deterioration and memory disturbance), and impairment of consciousness.^[5][6][7][8] Psychiatric abnormalities, including dementia are also common, with some patients developing dementia without intracranial hemorrhage.^[3][8]

hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is caused by mutations in the APP gene. The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). The function of the amyloid precursor protein is still being studied; however, researchers suspect that it is involved in the binding of other proteins on the surface of cells and that it might play a role in the development and maintenance of nerve cells (neurons).^[2]

Mutations in the APP gene lead to the production of proteins that are less stable than normal and that tend to cluster together. These aggregated proteins form protein clumps called amyloid deposits that build-up in certain areas of the brain and its blood vessels. The amyloid deposits, known as plaques, damage brain cells, eventually causing cell death and impairing various parts of the brain, leading to the symptoms of HCHWA-D.^[2]

There is no known effective treatment for hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D). Treatment is supportive and based on the control of symptoms. In some cases, rehabilitation is needed for weakness or clumsiness. This can include physical, occupational, or speech therapy. Occasionally, some patients are good candidates for medications that can help improve memory. Seizures may be treated with anticonvulsants such as phenytoin and carbamazepine.^[7] 

The management of intracranial hemorrhage (ICH) related to HCHWA-D is identical to the standard management of ICH. The main objectives include discontinuing use of anticoagulation agents (for example, warfarin), managing intracranial pressure, and preventing complications.^[3]