OVERVIEW

What is spinocerebellar ataxia?

Spinocerebellar ataxia (SCA), previously known as autosomal dominant cerebellar ataxia, is a neurodegenerative disorder with genetic involvement.

It typically manifests during adolescence or middle age, primarily characterized by degeneration of the cerebellum, spinal cord, and brainstem. In addition to ataxia, symptoms may include uncontrolled body movements and pyramidal or extrapyramidal signs.

Is spinocerebellar ataxia common?

SCA is relatively rare, with a prevalence of approximately 8 to 12 per 100,000 individuals.

Are spinocerebellar ataxia and Friedreich ataxia the same disease?

No, they are distinct conditions. Although both are hereditary ataxias, Friedreich ataxia is an autosomal recessive disorder that begins in childhood. It primarily affects the dorsal columns, lateral columns of the spinal cord, and the heart, leading to progressive gait and postural ataxia, dysarthria, and loss of deep sensation. Non-neurological manifestations often include cardiac damage, diabetes, and skeletal deformities.

What are the types of spinocerebellar ataxia?

Historically, Harding classified SCA into autosomal dominant cerebellar ataxia types I, II, and III based on the presence of ophthalmoplegia/extrapyramidal symptoms and retinal degeneration:

• Type I: Ataxia accompanied by ophthalmoplegia, optic atrophy, dementia, and extrapyramidal symptoms;

• Type II: Associated with macular degeneration, with or without ophthalmoplegia or extrapyramidal symptoms;

• Type III: Presents as a pure ataxia syndrome.

Currently, SCA is more commonly classified genetically based on its loci. These loci are sequentially numbered from SCA1 to SCA40 (and beyond) in the order of their discovery.

SYMPTOMS

What are the common manifestations of spinocerebellar ataxia?

The symptoms of various SCA subtypes are similar, overlapping, yet each has its own characteristics. The common clinical manifestations include:

• Onset typically occurs between 30–40 years of age, often insidious and difficult to detect, with slow progression. However, cases with childhood onset or onset at 70 years have also been reported.

• The main feature is cerebellar ataxia. Most patients initially experience lower limb ataxia, manifesting as unsteady walking and sudden falls, followed by clumsiness in the hands, intention tremor, nystagmus, cognitive dysfunction, dementia, and atrophy of distal limb muscles (hands and feet).

• Genetic anticipation is observed, meaning that within the same SCA family, the age of onset tends to become earlier and symptoms more severe in successive generations.

Among the many types of spinocerebellar ataxia, which are the most common? What are their clinical manifestations?

The most common subtypes are SCA1, SCA2, SCA3, and SCA6. Their characteristics are as follows:

• SCA1 is characterized by ophthalmoplegia, particularly the inability to look upward.

• SCA2 patients exhibit prominent slow saccadic eye movements. Physical examination may reveal weakened or absent upper limb tendon reflexes (involuntary muscle contractions upon rapid tendon stretching).

• SCA3, also known as Machado-Joseph disease (MJD), is the most common autosomal dominant SCA. In addition to ataxia, it presents with:

• Slow saccadic and pursuit eye movements, eyelid retraction causing bulging eyes (resembling a fixed stare);

• Brainstem dysfunction, such as dysarthria (speech disorders including imprecise articulation, uneven tone, slow speech rate, and irregular rhythm), dysphagia, weak cough, and tongue fasciculations;

• Extrapyramidal symptoms, including muscle rigidity and dystonia. Patients may also experience muscle spasms and fasciculations;

• Cognitive dysfunction or even dementia, as well as autonomic dysfunction symptoms such as cold intolerance, nocturia, and orthostatic dizziness.

• SCA6 patients may experience early symptoms like thigh muscle spasms, nystagmus when looking downward, diplopia, and positional vertigo (a spinning sensation of the surroundings or oneself in specific positions).

How does spinocerebellar ataxia progress?

SCA has an insidious onset, progresses slowly, and worsens persistently—like descending a long slope, gradual but relentless.

What severe consequences can spinocerebellar ataxia cause?

• SCA patients with ataxia are prone to falls and injuries;

• In advanced stages, limb paralysis may confine patients to bed; severe cognitive decline or dementia can lead to loss of self-care ability;

• Patients with choking on water or dysphagia often suffer from poor nutrition and recurrent lung infections;

• Vision deterioration or even blindness significantly impacts quality of life;

• Recurrent epileptic seizures may result in death.

CAUSES

What are the causes of spinocerebellar ataxia?

SCA is a genetic disorder caused by gene mutations. Some subtypes of SCA (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) are associated with the expansion of CAG repeat sequences in the polyglutamine tract region of encoded protein products. CAG repeat expansion can produce toxic "gain-of-function" variants, where the mutant protein acquires new pathogenic functions.

Is spinocerebellar ataxia contagious?

SCA is a genetic disease and is not contagious.

What are the genetic characteristics of spinocerebellar ataxia?

Most SCAs are autosomal dominant genetic disorders with the following characteristics:

• The disease manifests as long as one pathogenic gene is present in the body.

• The disease is unrelated to gender, with equal chances of occurrence in males and females.

• In a patient's family, the disease may appear in multiple consecutive generations. However, due to changes in internal or external environments, the effect of the pathogenic gene may not always be expressed (incomplete penetrance). Some individuals who should develop the disease may remain phenotypically normal carriers, while their children still have a 1/2 chance of inheriting the disease, resulting in skipped-generation inheritance.

• Unaffected offspring (aa) who marry normal individuals (aa) generally will not pass on the disease to their descendants.

In SCA patients, due to the instability of CAG repeat sequences in both somatic and germ cells, affected families experience genetic anticipation across successive generations. This means the age of onset becomes progressively earlier and symptoms worsen in later generations.

DIAGNOSIS

How is spinocerebellar ataxia diagnosed?

When diagnosing SCA, doctors primarily rely on the patient's cerebellar ataxia symptoms and typical signs of various subtypes, combined with family genetic history and imaging tests such as MRI. Genetic testing is required for confirmation.

What tests are needed for suspected spinocerebellar ataxia?

Generally, neurological examinations, CT scans, MRI, brainstem evoked potentials, electromyography (EMG), electroencephalography (EEG), and cerebrospinal fluid analysis are required. Genetic testing may be necessary for definitive diagnosis.

• Neurological examination: A detailed assessment can reveal signs of neurological damage, aiding in diagnosis.

• CT or MRI: These scans may show cerebellar and brainstem atrophy in SCA patients, helping rule out other causes of ataxia, such as infections, tumors, or demyelinating diseases.

• Brainstem evoked potentials: This test can detect early brainstem damage, even in asymptomatic patients.

• Electromyography (EMG): SCA often involves peripheral neuropathy, and EMG can identify such damage.

• Electroencephalography (EEG): Patients with seizures may require EEG to assess the cause and treatment efficacy.

• Lumbar puncture (cerebrospinal fluid analysis): While SCA patients typically have normal cerebrospinal fluid, this test helps exclude infections, multiple sclerosis, or other ataxia causes.

• Genetic testing: Used to confirm SCA and determine the subtype.

Are there any precautions for spinocerebellar ataxia tests?

• MRI: The procedure is noisy; earplugs may help. It is lengthy, so patient cooperation is essential.

• Brainstem evoked potentials, EMG, EEG: Wash hair before the test. Some discomfort or pain may occur.

• Lumbar puncture: Check vital signs beforehand. Blood tests may be required for comparison. Empty the bladder and bowels before the test and wear loose clothing. During the procedure, leg pain or numbness may occur—report discomfort immediately. Post-test, lie flat for at least 6 hours without a pillow, drink fluids, and keep the puncture site dry.

Is lumbar puncture invasive? Is genetic testing expensive? Are these tests mandatory?

Although cerebrospinal fluid results are normal in SCA, lumbar puncture helps differentiate it from infections or other ataxia causes. The procedure is minimally invasive with few complications. Follow your doctor's advice on whether to proceed.

SCA is genetic, so genetic testing is the definitive diagnostic method. If SCA is strongly suspected, genetic testing is recommended under medical guidance.

Which diseases are easily confused with spinocerebellar ataxia? How to differentiate them?

Many conditions present with ataxia, including toxin/drug exposure, infections, ischemic/hemorrhagic stroke, progressive multifocal leukoencephalopathy, prion diseases, Whipple’s disease, autoimmune disorders, tumors, paraneoplastic cerebellar degeneration, and other hereditary ataxias. Distinguishing SCA from Friedreich’s ataxia is particularly important (see "Introduction" for details).

Doctors differentiate these conditions using family history, neurological exams, imaging (CT/MRI), evoked potentials, EMG/EEG, cerebrospinal fluid analysis, and genetic testing if needed.

TREATMENT

Which department should I visit for spinocerebellar ataxia?

It is recommended to see a neurologist.

Can spinocerebellar ataxia heal on its own?

SCA is a genetic disease and cannot heal on its own.

How is spinocerebellar ataxia treated?

There is currently no specific treatment for SCA, but symptomatic treatment can alleviate symptoms.

• Medication:

• Levodopa can improve extrapyramidal symptoms such as muscle rigidity;

• Baclofen can reduce spasms;

• Amantadine can improve ataxia, while clonazepam is recommended for patients with ataxia accompanied by myoclonus;

• Neurotrophic drugs such as coenzyme A, inosine, and B vitamins may be tried, though their efficacy is uncertain.

• Epileptic seizures require antiepileptic treatment under a doctor's guidance.

• Surgery: Thalamotomy may be performed.

• Other treatments: Umbilical cord mesenchymal stem cell therapy may be effective for ataxia; physical therapy, functional rehabilitation, and psychotherapy are also options.

What are the common side effects of medications for spinocerebellar ataxia?

• Levodopa: Common adverse reactions include nausea, vomiting, orthostatic hypotension, abnormal involuntary movements in the head, face, tongue, upper limbs, and upper body, depression, and difficulty urinating. Long-term use may lead to poor drug response or dyskinesia (e.g., involuntary limb movements), requiring prompt medical attention if they occur.

• Baclofen: Common adverse reactions include daytime drowsiness and nausea.

• Amantadine: Persistent adverse reactions include difficulty concentrating, dizziness, irritability, loss of appetite, nausea, nervousness, skin purplish-red net-like spots or livedo reticularis, and sleep disturbances or nightmares. Other common side effects include hallucinations and confusion, especially in elderly patients.

• Clonazepam: The most common adverse reactions are drowsiness, ataxia, and behavioral disturbances. Long-term use may lead to weight gain.

Can spinocerebellar ataxia be cured?

SCA is a genetic disease and currently has no cure.

DIET & LIFESTYLE

What should patients with spinocerebellar ataxia pay attention to in their diet?

A diet rich in high-quality protein and fiber, adequate water intake, and balanced nutrition with reasonable combinations of protein, calcium, vitamin D, minerals, and fruits.

In the late stages of the disease, difficulty swallowing and choking on water may occur, which can lead to aspiration pneumonia. Under medical guidance, a nasogastric tube or gastrostomy feeding should be used.

What should patients with spinocerebellar ataxia pay attention to in daily life?

• Patients are advised to engage in about 30 minutes of daily exercise under family supervision, combining aerobic and strength training with moderate intensity and avoiding overexertion.

• Ensure sufficient sleep every day.

• Learn self-regulation when experiencing high stress or emotional tension.

• Avoid falls, injuries, and strenuous exercise.

Does spinocerebellar ataxia affect fertility?

Generally, SCA does not involve the reproductive system and therefore does not affect fertility.

Since SCA is mostly a dominant genetic disorder, offspring are at risk of inheriting the disease. Patients planning to have children should seek pre-pregnancy counseling and prenatal diagnosis.

How should family members care for a patient with spinocerebellar ataxia?

• Patients often experience dizziness and unsteady walking, so precautions should be taken to prevent falls and injuries.

• For bedridden patients unable to move independently, limb massages and passive movements should be provided to prevent disuse atrophy. Rehabilitation exercises should be conducted under the guidance of a therapist.

• Position the patient in a side-lying posture with support cushions and turn them at least every two hours to prevent pressure sores.

• Children with intellectual disabilities or learning difficulties should receive academic support. Adolescents and others facing self-esteem or psychosocial challenges due to the disease may require specialized counseling and emotional support.

• For patients with swallowing difficulties or choking on water, which may lead to aspiration pneumonia, nasogastric tube feeding or gastrostomy should be administered under medical supervision.

PREVENTION

Can Spinocerebellar Ataxia Be Prevented? How to Prevent It?

SCA is a genetic disorder and cannot be prevented. However, patients should seek genetic counseling before pregnancy, and prenatal diagnosis is necessary if already pregnant.

How Can Patients with Spinocerebellar Ataxia Prevent Complications?

• Patients may experience falls and injuries due to unsteady walking or dizziness, so fall prevention measures should be taken.

• For patients with difficulty swallowing or choking while drinking, which may lead to aspiration pneumonia, a nasogastric tube or gastrostomy feeding should be used under medical guidance to avoid aspiration pneumonia.

• Patients with seizures must take medication as prescribed by a doctor and should not stop or reduce the dosage on their own to prevent symptom recurrence, worsening, or even life-threatening status epilepticus.