I. What is ataxia? Ataxia refers to clumsiness of movement or imbalance that is not caused by muscle weakness. The word “ataxia” can also be simply thought of as poor coordination, or it can be used to qualify a specific neurodegenerative disorder. Ataxia can affect the fingers, arms or legs, trunk, speech or eye movements. Patients may feel unsteady in standing and walking, shaky in holding objects, slurred speech, stiffness and weakness in the lower extremities, drunkenness, double vision, choking and coughing at food, etc. This progressive loss of balance can lead to a number of medical problems. Therefore, individuals suffering from ataxia should seek medical help in time to find the underlying causes of the symptoms and receive appropriate treatment. Why does ataxia occur? In most cases, ataxia is caused by a decline in the function of a specific part of the brain, the cerebellum, and is often referred to as “microcephaly. The right hemisphere of the cerebellum controls coordination of the right side of the body, the left hemisphere controls coordination of the left side of the body, the middle part of the cerebellum controls more complex movements such as walking posture, gait, head and trunk stability and eye movements, and the rest of the cerebellum helps coordinate eye movements, speech and swallowing. Ataxia can also be caused by dysfunction of the pathways to and from the cerebellum, which receives information from the spinal cord, inner ear and other parts of the brain, and outputs signals from the cerebellum to the spinal cord and brain, which explains why the severity of ataxia in some patients does not match the degree of cerebellar atrophy shown on MRI. The cerebellum does not directly control movement and sensation, but with the involvement of the cerebellum and the afferent and efferent nerves and corresponding nuclei, the body is able to perform fine and precise movements and maintain correct posture. At the same time, the body’s motor-sensory pathways also input information to the cerebellum, so a person with weak limbs may also feel poorly coordinated. Third, how to diagnose ataxia? A neurologist specializes in diagnosing ataxia by taking a detailed history and the patient’s conscious symptoms, performing a neurological physical examination and a series of ancillary tests, including the site of the lesion (localization diagnosis) and the cause of the lesion (qualitative diagnosis). (1) Detailed history taking can provide clues for etiological diagnosis, such as acute onset, subacute onset, and insidious onset, the etiology of which is often different, and the presence of infection, trauma, and poisoning before the onset can also suggest the etiology. Patients should provide as detailed a history as possible and describe self-perceptions, which can assist the physician in making a faster and more accurate diagnosis. (2) For patients with ataxia, neurological physical examination needs to be targeted, such as eye movements, limb coordination, trunk posture and gait, etc. (3) Routine ancillary examinations: cranial MRI is crucial in the diagnostic process and can indicate the presence of tumors, stroke, and neurodegenerative changes in the patient’s brain. Some other tests are also necessary, such as routine blood tests, folic acid, B12, VE, lipids, thyroid and parathyroid function tests, and for some patients, tumor markers, cerebrospinal fluid cytology and biochemistry. (4) Genetic testing: Genetic testing is required for cases with a family history, or for sporadic cases that start before the age of 50, have no clear cause, and get progressively worse. The main purpose of this test is to clarify the cause of the genetic disease in the family. Although the majority of genetic diseases currently lack targeted treatments, as science develops, the pathogenesis of genetic diseases will gradually be revealed and targeted treatments will be explored. Genetic testing is also important for the life planning of the patient’s offspring, but for genetic disorders with adult onset, genetic testing is not recommended for minor offspring to avoid an “informed burden”. Acute onset ataxia can be caused by head trauma, stroke, brain hemorrhage, brain tumors, severe viral infections, exposure to certain drugs or toxins (heavy metals, certain antiepileptic drugs, heavy alcohol consumption), etc. Gradual onset of ataxia can be caused by genetic disorders; grain allergies (wheat, rye and barley); hypothyroidism; specific vitamin deficiencies (vitamin E and vitamin B12); small exposures to specific drugs or toxins (heavy metals, antiepileptic drugs, chronic alcohol abuse); certain antineoplastic drugs; structural disorders – prenatal cerebellar hypoplasia; multiple sclerosis other immune system disorders or underlying cancer affecting the immune system (paraneoplastic syndrome), etc. Classification of ataxia Classification of rare neurological disorders such as ataxia is difficult, and many classifications have been tried in the past, thus it is not difficult to explain why different types of ataxia have such complicated names. As research into the etiology and pathogenesis of the disease has advanced, as well as the development of neuroimaging and molecular diagnostic techniques, the classification of ataxia has become clearer and closer to its etiology. From the etiological point of view, the main types are as follows: 1. Primary ataxia: monogenic inherited ataxia, including multiple genetic types: autosomal dominant, autosomal recessive, sex-linked, mitochondrial maternal Multifactorial diseases, including disseminated late-onset ataxia, multi-systemic atrophic cerebellar type 2. Secondary ataxia: trauma, brain tumor, poisoning by toxic or specific drugs Ataxia caused by stroke, immune diseases, endocrine diseases, etc. V. What is autosomal dominant/recessive ataxia? Chromosome is the material in the nucleus of a cell that contains genetic information (genes) and is easily dyed dark by alkaline dyes, so it is called chromosome (chromatin). The number of chromosomes in a normal human body cell is 23, consisting of 22 pairs of autosomes and one pair of sex chromosomes, 46XY in males and 46XX in females. autosomal dominant disorders have the causative gene located on the autosome, and a single allele mutation can cause the disease, and the offspring of a patient have a 50% chance of inheriting the causative allele. In autosomal recessive disorders, the causative gene is located on the autosome, but a single allele mutation does not cause the disease, i.e., the trait is recessive, and only a pair of alleles are mutated to reveal the disease. Autosomal dominant ataxia: generally referred to as spinocerebellar ataxia (SCA), with the development of genetic research, the number of disease types named according to the causative gene has gradually increased, SCA12, SCA17 and DRPLA. These types have similar forms of mutations, all of which are dynamic mutations in nucleotide repeat sequences and are easy to carry out genetic testing, and are clinically manifested by early genetic presentation, i.e., the offspring have an earlier age of onset than the previous generation. Autosomal recessive ataxia: Generally early onset ataxia, mostly before the age of 15 years, with various neurological abnormalities such as skeletal deformities, cognitive impairment, epilepsy, vision loss, cardiomyopathy, diabetes mellitus, dyslipidemia, etc., requiring relevant tests to provide clues for etiological diagnosis. The relatively common types of ataxia include Friedreich ataxia (FA), ataxia with vitamin E deficiency (AVED), ataxia-telangiectasia (AT), and ataxia with oculomotor dilation (OCD). Ataxia with oculomotor apraxia (AOA), beta lipoprotein deficiency (ABL), etc.