neurologic disorders
Cerebellar Disorders
Etiology of Cerebellar Disorders
The most common cause of cerebellar disorders is Alcoholic cerebellar degeneration Such malformations are almost always sporadic, often occurring as part of complex malformation syndromes (eg, Etiology ) that affect other parts of the central nervous system (CNS). Malformations manifest early in life and are nonprogressive. Manifestations vary markedly depending on the structures involved; ataxia is usually present. Hereditary ataxias may be autosomal recessive or autosomal dominant. Autosomal recessive ataxias include Friedreich ataxia (the most prevalent), ataxia-telangiectasia, abetalipoproteinemia, ataxia with isolatedvitamin Edeficiency, and cerebrotendinous xanthomatosis. gene in people who do not have Friedreich ataxia; however, in people with Friedreich ataxia, the GAA sequence may be repeated 70 to > 1000 times ( Etiology references , In Friedreich ataxia, gait unsteadiness begins between ages 5 and 15; it is followed by upper-extremity ataxia, dysarthria, and paresis, particularly of the lower extremities. Mental function often declines. Tremor, if present, is slight. Reflexes and vibration and position senses are lost. Talipes equinovarus (clubfoot), scoliosis, and progressive cardiomyopathy are common. By their late 20s, patients may be confined to a wheelchair. Death, often due to arrhythmia or heart failure, usually occurs by middle age. Spinocerebellar ataxias(SCAs) are the main autosomal dominant ataxias. Classification of these ataxias has been revised many times recently as knowledge about genetics increases. Currently, at least 44 different gene loci are recognized; about 10 involve expanded DNA sequence repeats. Some involve a repetition of the DNA sequence CAG that codes for the amino acid glutamine, similar to that in Huntington disease. Manifestations of SCAs vary. Some of the most common SCAs affect multiple areas in the central and peripheral nervous systems; neuropathy, pyramidal signs, and Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS) , as well as ataxia, are common. Some SCAs usually cause only cerebellar ataxia. SCA type 3, formerly known as Machado-Joseph disease, may be the most common dominantly inherited SCA worldwide. Symptoms include ataxia, Secondary and Atypical Parkinsonism , and possibly Acquired ataxias may result from nonhereditary neurodegenerative disorders (eg, Multiple System Atrophy (MSA) ), systemic disorders, Toxins that can cause cerebellar dysfunction include Carbon Monoxide Poisoning , heavy metals, Rarely, Neurologic paraneoplastic syndromes occurs as a paraneoplastic syndrome in patients with breast cancer, ovarian cancer, small cell carcinoma of the lung, or other solid tumors. Cerebellar degeneration may precede the discovery of the cancer by weeks to years. Anti-Yo, now called PCA-1 (Purkinje cell cytoplasmic antibody type 1) is a circulating autoantibody that occurs in the serum or cerebrospinal fluid (CSF) of some patients, especially women with breast or ovarian cancer. In children, primary brain tumors (medulloblastoma, cystic astrocytoma) may be the cause; the midline cerebellum is the most common site of such tumors. Rarely, in children, reversible diffuse cerebellar dysfunction follows viral infections. 1.Pandolfo M:Friedreich ataxia.Arch Neurol. 65 (10):1296–1303, 2008. doi:10.1001/archneur.65.10.1296 2.Cook A, Giunti P: Friedreich's ataxia: clinical features, pathogenesis and management.Br Med Bull124 (1):19–30, 2017. doi: 10.1093/bmb/ldx034 