Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum

Abstract

Ethanol consumption remains a major concern at a world scale in terms of transient or irreversible neurological consequences, with motor, cognitive, or social consequences. Cerebellum is particularly vulnerable to ethanol, both during development and at the adult stage. In adults, chronic alcoholism elicits, in particular, cerebellar vermis atrophy, the anterior lobe of the cerebellum being highly vulnerable. Alcohol-dependent patients develop gait ataxia and lower limb postural tremor. Prenatal exposure to ethanol causes fetal alcohol spectrum disorder (FASD), characterized by permanent congenital disabilities in both motor and cognitive domains, including deficits in general intelligence, attention, executive function, language, memory, visual perception, and communication/social skills. Children with FASD show volume deficits in the anterior lobules related to sensorimotor functions (Lobules I, II, IV, V, and VI), and lobules related to cognitive functions (Crus II and Lobule VIIB). Various mechanisms underlie ethanol-induced cell death, with oxidative stress and endoplasmic reticulum (ER) stress being the main pro-apoptotic mechanisms in alcohol abuse and FASD. Oxidative and ER stresses are induced by thiamine deficiency, especially in alcohol abuse, and are exacerbated by neuroinflammation, particularly in fetal ethanol exposure. Furthermore, exposure to ethanol during the prenatal period interferes with neurotransmission, neurotrophic factors and retinoic acid-mediated signaling, and reduces the number of microglia, which diminishes expected cerebellar development. We highlight the spectrum of cerebellar damage induced by ethanol, emphasizing physiological-based clinical profiles and biological mechanisms leading to cell death and disorganized development.

Clinical Application of Microsurgery Using the Cerebellar Medulla Fissure Approach in Severe Ventricular Hemorrhage with Casting of the Fourth Ventricle and Its Influence on Neurological Recovery

“…The incidence of other postoperative complications is high, which is not conducive to the recovery of patients. Even when patients' lives can be saved, these complications may lead to lifelong disability [ 23 ]. With the development of medical technology, microsurgery has been applied to various cardiovascular and cerebrovascular diseases.…”

Ataxias: Hereditary, Acquired, and Reversible Etiologies

“…It has been proposed that alcohol-induced cerebellar degeneration requires a large amount of daily alcohol drinking (>140 g or 50 ounces of wine per day, approximately 10 times of a standard drink) for more than 10 years. 23 24 A study found that this amount of alcohol is associated with cerebellar vermis atrophy identified by a computed tomography imaging study in 41 cases attributed to alcohol use. 23 On the other hand, a small amount of daily alcohol ingestion with 5 g for a similar length of time can also lead to ataxia.…”

Systemic effects of excessive alcohol consumption

“…Bowel, bladder, and sexual dysfunction may occur with peripheral nerve involvement 7-9. The central nervous system effects include a deficit in cognitive ability, severe impairment in memory, and degradation of the cerebellum, causing cerebellar ataxia–difficulty with muscle movement, coordination, postural stability, and balance–from a deficiency in B vitamins, particularly thiamine 6-9,17,18,24…”