Year : 2006 | Volume
: 16 | Issue : 4 | Page : 745--747
Cerebral amyloid angiopathy
BKD Prasad, GS Kejriwal, SN Sahu
Maharajah's Institute Of Medical Sciences, Nellimarla-535217, A.P, India
Mims Medical College Hospital, Nellimarla-535217 , A.P.
Cerebral amyloid angiopathy (CAA) is a very rare entity. This is an age related disease and is not a manifestation of systemic amyloidosis in any of its forms. Sporadic cases are most common, though hereditary cases do exist. Alzheimer«SQ»s disease predispose to CAA. This condition is to be borne in mind when a spontaneous intracerebral haemorrhage with lobar pattern or one situated very superficial location in the cortical region is presented.
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Prasad B, Kejriwal G S, Sahu S N. Cerebral amyloid angiopathy.Indian J Radiol Imaging 2006;16:745-747
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Prasad B, Kejriwal G S, Sahu S N. Cerebral amyloid angiopathy. Indian J Radiol Imaging [serial online] 2006 [cited 2020 May 29 ];16:745-747
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Cerebral amyloid angiopathy is a condition in which a protein (AB peptide) or amyloid is deposited in the arteriolar walls of the brain. The protein deposits weaken the blood vessels and make them more fragile and prone to bleed. These pathological changes lead to repeated massive spontaneous intracerebral haemorrhages in the elderly normotensive subjects. ,
A normotensive female aged 55 yrs, presented with left hemiparesis. Sensorium was normal. Plain CT showed an irregular hyperdense lesion over right parietal lobe with surrounding edema located superficially in the high parietal region. Bilateral basal ganglia are spared. [Figure 1],[Figure 2]
A female-aged 78 yrs, normotensive, presented with right hemiparesis and altered sensorium. Plain CT scan showed inhomogenous hyperdensities suggestive of bleed of different ages in left temporoparietal region with perilesional edema. The left lateral ventricle is compressed with dilatation of right lateral ventricle. There is midline shift to the right [Figure 4].
Cerebral amyloid angiopathy is a very common cause of intracerebral haemorrhage only second in frequency to hypertensive intracerebral haemorrhage . They are usually seen in normotensive adults over 60 years of age . They are almost always superficially located and have a distribution distinctly different from those resulting from hypertensive bleeds. It is responsible for about 10 to 20% of all cases of spontaneous intracerebral haemorrhages . The disease process particularly affects the arterioles of the cortex only. It is not found in the white matter, basal ganglia, brainstem or cerebellum. Hence the intracerebral haemorrhages in CAA are particularly in the cortex and sub cortical region of parietal and occipital lobes and never seen in deep white matter, basal ganglia, brainstem and cerebellum as is the case in the hypertensive intracerebral hemorrhage . In autopsy studies it is found that in normotensive persons over the age of 70, more than 40% of brains demonstrated amyloid changes in arterioles whereas, it is 30% between the age groups of 60 to 70 . These amyloid proteins replace the contractile elements of arteriolar muscle layer leading to increased fragility and haemorrhages . This amyloid protein intensively stain red with congored and hence this disease is also known as congophilic angiopathy .
Most common form of CAA is the sporadic form associated with aging. Frontal and parietal lobes are more often affected than the temporal and occipital lobes. 10 - 50% of sporadic CAA involves more than one lobe. CAA is sporadic but it may also be hereditary and transmitted as autosomal dominant trait. It presents in two hereditary forms 1) Icelandic form and 2) Dutch form. In hereditary CAA, genetic defects are typically on chromosome 21, which allow accumulation of amyloid in the arterioles.
A) Icelandic form (hereditary cystatin C amyloid angiopathy) has a single nucletide substitution at codon 68 of cystatin C - gamma trace leading to replacement of glutamine by leucine. Patients have also abnormally low cystine in the CSF. Symptoms often begin at the age of 30 to 40 years with multiple brain haemorrhages, dementia, paralysis and death with in 10 to 20 years due to repeated haemorrhages .
B) Dutch form (hereditary cerebral haemorrhage with amyloidosis - Dutch) has mutation at codon 692 and 693 of APP. . Here the onset is at age 40 - 60 years with headache and massive hemorrhages often in parietal lobe. More than half of the patients die from their first hemorrhage.
Other hereditary forms are also seen.
a) Flemish type with mutation involving the amyloid precursor. Symptoms include dementia.
b) Familial Alzheimer's disease where CAA is more common than in general population and occurs in more than 60% of patients over the age of 60 years.
c) British type with unknown gene defect associated with progressive dementia, ataxia and spasticity.
d) Familial oculo-leptomeningeal amyloidosis with unknown gene defect, described in Japanese, Italian and North American families. Amyloid deposits occur in blood vessels of eye and meninges. Brain haemorrhages are rare.
Approximately 50% of haemorrhages in sporadic CAA involve more than one lobe. Persons usually present with headache, dementia or Alzheimer's disease. Then symptoms of lobar haemorrhage supervene with neuralgic symptoms, sensory loss, weakness, visual changes, speech problem, and decreased level of consciousness, nausea and vomiting depending on which lobe is affected.
Diagnosis is made most often from patient's history, inquiry into familial occurrence, onset and pattern of symptoms as well as neurologic examination. Brain CT and MRI are required to identify lobar haemorrhage and to exclude bleed due to aneurysm, arteriovenous malformation and hypertension. Angiography is not helpful and brain biopsy is rarely performed, as the risk is not justifiable in the absence of effective treatment. Since CAA is an age related disorder and not a manifestation of systemic amyloidosis, biopsy of liver, spleen and peripheral vessels will not be of helpful in its diagnosis . In familial forms genetic analysis may be helpful.
Radiologically CAA haemorrhage typically occurs in lobar pattern, or situated superficially, as the disease affects the smaller caliber vessels situated at peripheral location . The haemorrhages may be multiple in number and are of different stages of resorption. In contrast, hypertensive haemorrhages are situated deep in the brain, thalamus and midbrain .
Although there is no effective treatment for the underlying disease process, measures can be taken to prevent further haemorrhage, and symptomatic treatment for seizures and allied symptoms.
Prognosis is usually poor. Each episode of haemorrhage carries the risk of death or permanent brain damage with disability and dependence on others.
CAA is a cause of spontaneous lobar intracerebral haemorrhage in normotensive elderly. It may be sporadic or hereditary. There is amyloid deposition in the arterioles of cerebral cortex with fragility and increased incidence of intracerebral haemorrhage. The major risk factor is age above 60 and Alzheimer's disease.
Acknowledgements - we gratefully acknowledge the Princpal and Medical Superintendent of Maharajah's Institute of Medical Sciences ,Vizianagaram to allow us to work on the cases and to permit to publish the paper.
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