Purkinje Cells and Ataxia

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Questions and Answers

What is a primary reason for the classification of hereditary ataxias into spinocerebellar ataxias (SCAs)?

They are purely cerebellar disorders.

They exhibit significant involvement of both the cerebellum and central nervous system. (correct)

They result exclusively in peripheral nerve damage.

They are limited to upper motor neuron involvement.

Which of the following clinical manifestations is associated with upper motor neuron involvement in SCA?

Spasticity (correct)

Tongue atrophy

Generalized dystonia

Sensory loss

What genetic analysis method is commonly used to identify specific mutations related to SCAs?

Exome sequencing

Immunoblotting techniques

Polymerase chain reaction (PCR) of nucleotide repeats (correct)

Next-generation sequencing

In what scenario is genetic testing most definitively used among family members?

When a specific mutated gene is recognized Signup and view all the answers

Which testing type is NOT typically included in genetic testing scenarios for SCAs?

Immunological testing Signup and view all the answers

What percentage of known SCA genes is covered by current commercially available genetic test panels?

75% Signup and view all the answers

Which type of SCA commonly involves basal ganglionic involvement resulting in bradykinesia?

Earlier-onset forms Signup and view all the answers

Which neurological symptom is indicative of peripheral nerve involvement in some SCAs?

Sensory disturbances Signup and view all the answers

Which statement about the degeneration of Purkinje cells is true?

It is highly associated with ataxia. Signup and view all the answers

What is the primary cause of Purkinje cell degeneration linked to mitochondrial dysfunction?

Insufficient energy supply. Signup and view all the answers

Which neurodegeneration mechanism involves calcium release and is linked to channelopathies?

Increased calcium release from endoplasmic reticulum. Signup and view all the answers

How can family history impact the clinical manifestation of spinocerebellar ataxia?

Severity and onset of symptoms may vary even among relatives. Signup and view all the answers

What role do triplet repeat expansions play in spinocerebellar ataxia?

They predict an earlier onset and more severe symptoms. Signup and view all the answers

Which feature is commonly seen in pediatric and adolescent phenotypes of spinocerebellar ataxia?

Earlier onset and more severe symptoms. Signup and view all the answers

Which of the following describes a crucial aspect of the pathophysiology of Purkinje cells?

Mitochondrial dysfunction is linked to their degeneration. Signup and view all the answers

What is a common misconception about the symptoms of spinocerebellar ataxia?

Variation in symptoms is notable among individuals. Signup and view all the answers

What does a negative gene test panel for SCA indicate?

It does not exclude hereditary ataxia. Signup and view all the answers

In which subtype of SCA is gross cerebellar atrophy most pronounced?

SCA2 Signup and view all the answers

What treatment is primarily used to manage seizures in spinocerebellar ataxia?

Antiepileptic drugs Signup and view all the answers

Which point is most accurate regarding CAG repeat expansion in spinocerebellar ataxia?

Longer CAG repeats are linked to a worse prognosis. Signup and view all the answers

What type of atrophy is specifically observed in SCA3?

Pontocerebellar atrophy with enlargement of the fourth ventricle Signup and view all the answers

Which statement regarding the irreversible nature of spinocerebellar ataxia is correct?

Symptoms become almost irreversible once evident. Signup and view all the answers

Which option is a potential long-term consequence of spinocerebellar ataxia?

Most patients will need wheelchair support within 10 to 15 years. Signup and view all the answers

Upon assessment, what does neuroimaging primarily reveal in patients with SCA?

Gross cerebellar atrophy and brain ventricle enlargement Signup and view all the answers

Ataxia is classified as a disease rather than a clinical finding.

False Signup and view all the answers

Cerebellar ataxia is the only type of ataxia based on the location of dysfunction.

False Signup and view all the answers

Nystagmus is a symptom associated with ataxia due to brain dysfunction.

True Signup and view all the answers

The cerebellum is primarily responsible for the coordination of movements in the body.

True Signup and view all the answers

Ataxia does not affect speech or gait and only presents as visual disturbances.

False Signup and view all the answers

All spinocerebellar ataxias (SCAs) are classified as autosomal recessive disorders.

False Signup and view all the answers

The mutation in KCNA1 is associated with episodic ataxias (EAs).

True Signup and view all the answers

Normal CAG repeat alleles typically contain between 50 to 71 repeats.

False Signup and view all the answers

Spinocerebellar ataxia (SCA) primarily affects the spine and not the cerebellum.

False Signup and view all the answers

Pathogenic CAG repeat alleles in ataxias can expand to as many as 1,300 repeats.

True Signup and view all the answers

SCA2 and SCA3 are among the rarest forms of spinocerebellar ataxia.

False Signup and view all the answers

Anticipation in spinocerebellar ataxia refers to a decrease in the number of CAG repeats across generations.

False Signup and view all the answers

Episodic ataxias are classified as autosomal recessive conditions.

False Signup and view all the answers

SCA 10 is caused by the expansion of ATTCT, a hexanucleotide.

False Signup and view all the answers

The global prevalence of spinocerebellar ataxia ranges from 1 to 5 per 1,000,000.

False Signup and view all the answers

Autosomal inheritance patterns characterize all forms of SCA involving CAG repeat amplification.

True Signup and view all the answers

Ataxia can be categorized into three main types: Sporadic, Genetic, and Environmental.

False Signup and view all the answers

Friedreich’s Ataxia follows an autosomal dominant inheritance pattern.

False Signup and view all the answers

Purkinje cells are the only cells involved in degeneration related to spinocerebellar ataxia.

False Signup and view all the answers

Ataxia manifests with symptoms such as dizziness and poor balance.

True Signup and view all the answers

The degeneration of Purkinje cells affects muscle coordination and fine movement.

True Signup and view all the answers

Six forms of SCA involving CAG repeat amplification encode alanine rather than glutamine.

False Signup and view all the answers

Hereditary ataxias usually manifest in adulthood.

False Signup and view all the answers

Acquired ataxia can result from exposure to high levels of alcohol.

True Signup and view all the answers

Toxic RNA gain of function is one of the common mechanisms of SCA pathogenesis.

True Signup and view all the answers

SCA3 has the highest prevalence among the various types of spinocerebellar ataxia.

True Signup and view all the answers

Multiple System Atrophy (MSA) is a genetic condition causing ataxia.

False Signup and view all the answers

Visual impairment can accompany vestibular symptoms in ataxia.

True Signup and view all the answers

Structural or demyelinating conditions cannot cause acquired ataxia.

False Signup and view all the answers

The degeneration of Purkinje cells is not associated with ataxia.

False Signup and view all the answers

Mitochondrial dysfunction contributes to the survival and conduction of active Purkinje cells.

False Signup and view all the answers

Channelopathies linked to certain SCAs involve mutations in voltage-gated calcium channels.

True Signup and view all the answers

Loss of autophagy is unrelated to neurodegeneration in Purkinje cells.

False Signup and view all the answers

The onset and severity of symptoms in spinocerebellar ataxia can vary significantly, even among family members.

True Signup and view all the answers

Larger triplet repeat expansions in spinocerebellar ataxia suggest a later onset and less severe presentation.

False Signup and view all the answers

Mitochondrial calcium influx is linked to SCA28 and contributes to enzyme activation in Purkinje cells.

True Signup and view all the answers

The clinical manifestation of spinocerebellar ataxia shows no phenotypic overlap among its various subtypes.

False Signup and view all the answers

Study Notes

Purkinje Cells and Ataxia

Degeneration of Purkinje cells correlates strongly with ataxia.
Purkinje cells are notably vulnerable due to their large cell bodies with abundant cytoplasm.

Mitochondrial Dysfunction

Proper mitochondrial function is crucial for the survival and conduction of Purkinje cells.
Impaired mitochondrial performance leads to the degeneration of these cells.

Channelopathies

Mutations in voltage-gated calcium channels result in excessive calcium release from stores, leading to degeneration in spinocerebellar ataxias (SCA) 15, 16, and 29.
Increased mitochondrial calcium influx is implicated in SCA28, promoting apoptosis of Purkinje cells.

Autophagy and Proteostasis

Loss of autophagy and accumulation of misfolded long polyglutamine peptide contribute to neurodegeneration.

Family and Patient History

Family history is critical; onset and progression of symptoms can vary, often gradually manifesting over years.
The size of triplet repeat expansions has a direct relationship with the severity and pace of disease onset.

Clinical Features

There is a significant phenotypic overlap among various SCA subtypes, even within families.
Pediatric cases tend to present more severely and at an earlier age.

Central Nervous System Involvement

Most hereditary ataxias affect not only the cerebellum but also the brainstem and spinal cord.
Symptoms may include tongue atrophy, fasciculations, spasticity, and hyperreflexia.

Genetic Testing in Diagnosis

Definition of SCA subtypes requires clinical manifestations followed by genetic analysis as the gold standard.
Advances in molecular genetic testing enable earlier classification and diagnosis of SCAs.

Scenarios for Genetic Testing

Multiple testing types include diagnostic, predictive, prenatal, carrier tests, and risk factor assessments.
Genetic testing in families with positive histories is crucial for identifying specific SCA subtypes.

Neuroimaging Findings

Neuroimaging reveals cerebellar atrophy, notably prominent in SCA2; other SCAs may show regional differences.
Specific atrophies are seen in different SCAs, such as pontocerebellar atrophy in SCA3.

Management of Spinocerebellar Ataxia

Spinocerebellar ataxia is a genetic disorder with no definitive cure; treatment focuses on symptom relief.
Common treatments include antiepileptic drugs, botulinum toxin for dystonia, beta-blockers, and antidepressants.

Prognosis of Spinocerebellar Ataxia

Full symptoms often take years to develop and are typically irreversible once evident.
Most patients may require wheelchair support within 10 to 15 years; physical therapy can help delay this need.

Inherited Neurological Disorders

Ataxia is a neurological sign indicating lack of coordination in muscle movements, often presenting with abnormal gait, speech changes, and eye movement disorders.
Three main types of ataxia: cerebellar, sensory, and vestibular, each affecting different coordination systems.
Ataxia can be classified as sporadic (without family history), genetic (hereditary), or acquired (due to environmental factors).

Types of Ataxia

Sporadic Ataxia: Develops in adulthood due to factors like head trauma, tumors, or toxin exposure.
Genetic Ataxia: Inherited, showing clear patterns such as autosomal dominant, autosomal recessive, or X-linked inheritance.
Acquired Ataxia: Resulting from structural conditions, inflammation, or toxicity, usually not inherited.

Genetic Ataxia Examples

Friedreich’s Ataxia (FRDA): Autosomal recessive; onset typically before age 20, requiring abnormal genes from both parents.
Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS): X-linked inheritance, risk increases with age.

Spinocerebellar Ataxia (SCA)

SCA is a hereditary, progressive neurodegenerative disorder primarily affecting the cerebellum, with over 40 distinct genetic subtypes known.
Major types include SCA1, SCA2, SCA3, and SCA6, accounting for most cases.
CAG repeat expansions are common mechanisms in several types of SCA, leading to neurodegeneration.

Etiology and Epidemiology

SCA has a global prevalence of 1 to 5 per 100,000 people.
SCA3 is most prevalent (25-50%), followed by SCA2 (13-18%), SCA6 (13-15%), and SCA7.
Genetic anticipation observed with increasing CAG repeats in successive generations.

Pathophysiology

Pathogenesis involves genetic mutations leading to abnormal proteins that cause neurodegeneration through mechanisms like transcriptional dysregulation and mitochondrial dysfunction.
Purkinje cells are primarily affected; their degeneration correlates with the symptoms of ataxia.
Mitochondrial dysfunction and channelopathies contribute to the progression of SCA.

Family and Patient History

Family history is crucial for diagnosis; gradual onset and slow progression are typical.
Clinical manifestations vary among family members, with early onset often observed in pediatric cases.
The severity of the disease may correlate with the size of triplet repeat expansions.

Management and Prognosis

Management of ataxia usually focuses on symptomatic relief and support, as many genetic ataxias are progressive and lack curative treatments.
Prognosis varies widely depending on the type of ataxia and individual patient factors, including genetic background and family history.

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Description

Explore the critical relationship between Purkinje cell degeneration and ataxia. This quiz covers mitochondrial dysfunction, channelopathies, and the role of autophagy in neurodegeneration, along with the importance of family history in symptom progression.