Cerebral calcification

Osteopetrosis (marble bone disease), characterized by increased bone density, is due to inability to resorb bone. One form occurs along with renal tubular acidosis and cerebral calcification. It is due to mutations in the gene (located on chromosome 8q22) encoding carbonic anhydrase II (CAII), one of four isozymes of carbonic anhydrase present in human tissues. The reaction catalyzed by carbonic anhydrase is shown below ... 

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

Sly WS, Hewett-Emmett D, Whyte MP, Yu YS, Tashian RE (1983) Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci USA 80 2752-2756... 

Other infections clearly associated with increased risk of terata include toxoplasmosis, cytomegalovirus, and herpes simplex. Microphthalma, blindness, hydrocephalus, and cerebral calcification can occur after infection with these organisms. 

Mueller, S., Bell, W. and Seit rt, J. (1976) Cerebral calcifications associated with intrathecal therapy in acute lymphocytic leukaemia. J. Pediat., 88, 650. 

Atherosclerosis is main cause of cardiovascular deaths. It is characterized by a localised plaque in the intima and is composed of cholesterol esters, deposition of fibrous proteins and calcification. These plaques may narrow the arterial lumen and can cause distalischemia. The coronary and cerebral circulation are main sites of atherosclerosis. Raised levels of VLDL, LDL... 

The heart may be enlarged with left ventricular hypertrophy, particularly in cases which have exhibited hypertension during life. Metastatic calcification of the valves and of the myocardium may be present, explaining no doubt the cardiac murmurs which may have been detected clinically in such cases. Occasionally, medullary proliferation of large arteries and, in the smaller arteries, fragmentation of the intimal elastic lamina has been reported, in one case with impregnation with calcium salts. Local calcification of the media of the middle cerebral artery has been described. 

A CT scan or MRI of the brain following a strokelike episode reveals a lucency (an area of luminosity) that is consistent with infarction. Later, cerebral atrophy and calcifications may be observed on brain imaging studies. The vascular territories of focal brain lesions and the prior medical history of these patients differ substantially from those of typical patients with stroke. Serial MRI studies often demonstrate lesion resolution, differentiating these lesions from typical ischemic strokes. An electroencephalogram is often performed when seizures are a concern. This is especially necessary in MELAS since patients occasionally have intractable status epilepticus as a terminal condition. Mental deterioration usually progresses after repeated episodic attacks. Psychiatric abnormalities (e.g., altered mental status, schizophrenia) may accompany the strokelike episodes. The encephalopathy may progress to... 

Q13 Arterial emboli, which can block blood vessels and cause ischaemia or infarction in the tissues they affect, tend to originate in the left heart and are associated with valvular disease and dysrhythmias. Mitral stenosis is associated with abnormal atrial rhythm, particularly atrial fibrillation. Fibrillation and other rhythm abnormalities in the atria favour blood coagulation, resulting in production of thromboemboli which can move to distant parts of the circulation, such as the cerebral circulation. Thrombi could also form on surfaces of valves distorted by calcification and other abnormalities. In view of the risks of thromboembolism, it is usual to provide anticoagulant therapy to patients with mitral valve problems and atrial fibrillation. 

Cerebral computed tomography (CT) scanning in patients with EC was reported to show basal ganglia calcification in 30% (15 of 50 cases) and mild cerebral atrophy in 8% (4 of 50 cases) (Halpern et al., 1991). AH three children in our study of infant-onset hypothyroidism who exhibited... 

V9. Varma, R., Allen, W. S., and Wardi, A. H., The arabinose content of cerebral and vitreous humour hyaluronate-peptide. J. Neurochem. 20, 241—244 (1973). VIO. Vejlens, L., Glycosaminoglycans human bone tissue. I. Pattern of compact bone in relation to age. Calcif. Tissue Res. 7,175-190 (1971). 

At postmortem examination there were no gross abnormalities, except for mild atrophy of the brainstem, and microscopy showed only mild gliosis in the medial reticular formation of the medulla oblongata. There was slight myelin pallor in the cerebral hemispheres and brainstem. There was bilateral focal necrosis and calcification in the brain stem nuclei. The distribution of the lesions extended into the tegmentum of the pons and medulla oblongata, with involvement of the nuclei of cranial nerves VI, VII, X, and XII, where there was moderate to severe neuronal loss and free... 

Biological Applications Calcium indicatois zinc indicators treating acute cell death, cerebral infarction, myocardial infarction, hepatonecrosis, kidney ischemic necrosis, necrotizing pancreatitis, amyloidosis, atherosclerosis, diseases characterized by calcification and/or plaque formation, osteoporosis, Paget s disease, heterotropic ossification, hypercalce-mia, cancer, inflammation, diabetes mellitus, epilepsy, epithelial disorders, glaucoma, HIV-associated conditions, respiratory disorders, streptococcal infection, viral diseases ... 

The atheromatous plaque develops plate-like areas of calcium which have a characteristic roentgenographic appearance clearly distinguishable from non-atherosclerotic calcification which occurs in peripheral, carotid, and cerebral vessels. In the coronary artery visualization of calcification is pathognomonic for atherosclerosis no other forms of vascular calcification occur (6). 

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