Central Nervous System- Basic Neuropathology
Question No. 19. The Answer is: (B). The followings are true:
1. Infantile onset of manifestations.
3. Leukodystrophy.
Discussion: The three entities are all leukodystrophies. Alexander disease and Canavan disease are featured by macroencephaly. In contrast, Aicardi-Goutières syndrome has microencephaly.
Canavan disease (Spongy degeneration of the brain; Aspartoacylase deficiency) is an inherited disorder of aspartic acid metabolism due to aspartoacylase deficiency resulting in the accumulation of N-acetylaspartic acid in the brain. It is characterized by degeneration of the white matter of the brain (leukodystrophy) with macrocephaly. Canavan disease is inherited as an autosomal recessive trait. It is more common among Ashkenazi Jews than in the general population. Typically, symptoms begin in the first year of life. Parents tend to notice when a child is not reaching particular developmental milestones, including poor muscle tone and lack of head control. Eventually, the child can develop feeding problems, seizures, and loss of vision. Although death often occurs before 18 months of age, some live until they are teenagers or, rarely, young adults.
Alexander disease is a rare, genetically determined leukodystrophy of the central nervous system. It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP). The majority of cases are sporadic (not inherited), but there are families in which more than one child will have the disorder. Alexander disease primarily affects males and usually begins at about 6 months of age. The destruction of white matter in the brain is accompanied by the formation of fibrous protein deposits called Rosenthal fibers. The astrocytes can show a mild to moderate degree of cytologic atypia and also contain cytoplasmic eosinophilic globules. Symptoms may include mental and physical retardation, dementia, enlargement of the brain and head, spasticity (stiffness of arms and/or legs), and seizures. There is no cure for Alexander disease, nor is there a standard course of treatment. Treatment of Alexander disease is symptomatic and supportive. The prognosis for individuals with Alexander disease is generally poor. The infantile form is the most severe form and most patients do not survive after 6 years of age. The juvenile and adult onset forms have later onset and more protracted course of disease.
Aicardi-Goutières syndrome is an early-onset (in the first year of life) progressive encephalopathy that shows an autosomal recessive pattern of inheritance and is characterized by acquired microcephaly, basal ganglia calcifications, white matter alterations, chronic cerebrospinal fluid (CSF) lymphocytosis and raised levels of interferon-a in the CSF. Following a normal pregnancy and neonatal period, onset usually occurs in the first year of life, between the ages of 3 and 6 months. The gene responsible for the syndrome has still not been identified. There is, to date, no cure for AGS, and the therapeutic interventions that have been tried in isolated cases have not been substantiated scientifically.