About azorean neurologic disease

What is azorean neurologic disease?

Machado-Joseph Disease (MJD-III), also called spinocerebellar ataxia type III, is a rare, inherited, ataxia (lack of muscular control) affecting the central nervous system and characterized by the slow degeneration of particular areas of the brain called the hindbrain. Patients with MJD may eventually become crippled and/or paralyzed but their intellect remains intact. The onset of symptoms of MJD varies from early teens to late adulthood.

Three forms of Machado-Joseph Disease are recognized: Types MJD-I, MJD-II, and MJD-III. The differences in the types of MJD relate to the age of onset and severity. Earlier onset usually produces more severe symptoms.

What are the symptoms for azorean neurologic disease?

Weakness in the arms or legs symptom was found in the azorean neurologic disease condition

Spinocerebellar Ataxia 3 (SCA3) is a rare, inherited form of ataxia. Signs and symptoms may begin between childhood and late adulthood and vary greatly. Symptoms may include slowly progressive clumsiness in the arms and legs; a manner of walking (gait) that may be mistaken for drunkenness; Difficulty speaking and swallowing; impaired eye movements or vision; and lower limb spasticity. Some people with SCA3 develop dystonia or symptoms similar to those of Parkinson’s disease; twitching of the face or tongue; nerve damage (neuropathy); or problems with urination and the autonomic nervous system.

What are the treatments for azorean neurologic disease?

Azorean neurologic disease is one of the 40 types of spinocerebellar ataxia (SCA). It is the third type and is called type 3 SCA. Mutations in the gene that codes for the protein ataxin-3 cause the disease. Particularly, the gradual expansion of the CAG repeats is the cause. Normal ataxin-3 is involved in protein homeostasis and cytoskeleton regulation in the central nervous system. The abnormal ataxin protein leads to the loss of neurons in the CNS, especially Purkinje fibers in the cerebellum. It primarily affects walking, speech, and movements of the eyes.

Treatment
SCA has no definitive treatment yet. But the existing treatment is mainly symptomatic and supportive.
1. Symptomatic therapies are:
2. Antiepileptic drugs for seizures
3. Botulinum toxin injections for dystonia
4. Beta-blockers and primidone for tremors
5. Antidepressants for depression
6. Levodopa for symptoms of parkinsonism.
7. Citalopram decreases the level of ataxin-3 and improves the behavioral status of patients.
8. Dantrolene inhibits the release of calcium from its stores and preserves the functioning of Purkinje cells.
9. Chlorzoxazone is the FDA-approved activator of calcium-activated potassium channels, and it normalizes the electrophysiology and action potential firing of Purkinje cells.
10. Varenicline has shown improvement in cerebellar dysfunction in some SCA type-3 patients.
11. Rapamycin, an mTOR inhibitor, upregulates autophagy, one of the pathways to remove aggregated misfolded protein.
12. Neurorehabilitation and physical therapy play a crucial role in the management of motor functions. Speech therapy may assist in regaining the ability to talk.

Symptoms
Weakness in the arms or legs,Involuntary jerking,Cramping in hands and feet,Twitching of the facial muscles,Double vision,Bulging eyes, difficulty looking upward and opening eyes, and involuntary lateral movements of eye
Conditions
Ataxia,Intranuclear inclusions of ataxin-3
Drugs
Antiepileptic drugs for seizures,Botulinum toxin injections for dystonia,Beta-blockers and primidone for tremors,Antidepressants for depression,Levodopa for symptoms of parkinsonism,Citalopram, Dantrolene, Chlorzoxazone, Varenicline, Rapamycin

What are the risk factors for azorean neurologic disease?

Azorean neurologic disease, also known as Joseph's disease, is spinocerebellar ataxia. It is a genetic disorder caused by a CAG sequence duplicated multiple times within the gene on the long arm of chromosome 14. The gene in normal shape codes for the protein ataxin-3. The mutation leads to misfolded protein production and aggregation in the nucleus of neurons, especially Purkinje cells in the cerebellum. The clinical manifestations include loss of control and coordination of muscles leading to disordered eye movement, locomotion, and speech.

Risk factors for Azorean disease are:
1. Familial history of the disease: persons with a first-line family member with ataxia are likely to develop the disease. The familial occurrence should be considered an alarm for early intervention.
2. Viral infections that target the immune and nervous systems. The viruses include chickenpox, Epstein-Barr, and coxsackie virus.
3. Bacterial infections such as Lyme disease
4. Exposure to toxins such as mercury, lead, thallium, alcohol, and insecticides.
5. History of chemotherapy for cancers
6. Bleeding, blood clots, abscess, or blockage in the cerebellum
8. Paraneoplastic disorders: diseases triggered by an immune response in response to cancers
9. Other conditions such as migraine, alcoholism, vertigo, and stroke raise the risk of severity.
10. Genetic counseling is the most effective way to address the risks of developing the disease and thus, the severity can be reduced.

Symptoms
Weakness in the arms or legs,Involuntary jerking,Cramping in hands and feet,Twitching of the facial muscles,Double vision,Bulging eyes, difficulty looking upward and opening eyes, and involuntary lateral movements of eye
Conditions
Ataxia,Intranuclear inclusions of ataxin-3
Drugs
Antiepileptic drugs for seizures,Botulinum toxin injections for dystonia,Beta-blockers and primidone for tremors,Antidepressants for depression,Levodopa for symptoms of parkinsonism,Citalopram, Dantrolene, Chlorzoxazone, Varenicline, Rapamycin

Is there a cure/medications for azorean neurologic disease?

Azorean neurologic disease, also known as type 3 spinocerebellar ataxia, is a neurodegenerative disease. The neurons degrade due to the aggregation of misfolded protein ataxin-3. The cerebellum is the principal part of the brain affected due to the disease. It results in the loss of control and coordination of muscles in various parts, such as the legs, mouth, and eyes. The disease commonly occurs in the 40s.
Cure/medications
There is no definitive cure for Azorean disease yet. However, there are treatment modalities to alleviate the symptoms and retain the quality of life of the patients.
1. Symptomatic therapies are:

  • Anticonvulsants can decrease episodes of seizures.
  • botulinum toxin injections can reduce dystonia
  • Antidepressants for depression
  • Levodopa can reduce parkinsonism-like symptoms.
  • Tremors can be addressed with beta-blockers and primidone
2. Citalopram decreases the level of ataxin-3 and improves the behavioral status of patients.
3. Dantrolene inhibits the release of calcium from its stores and protects the Purkinje fibers.
4. Chlorzoxazone is an activator of calcium-activated potassium channels, which normalizes the electrophysiology and action potential firing of Purkinje cells.
5. Varenicline has shown improvement in cerebellar dysfunction in some SCA type-3 patients.
6. Rapamycin, an mTOR inhibitor, upregulates autophagy, one of the pathways that remove aggregated misfolded protein.
7. Neurorehabilitation and physical therapy are important to retain normal motor functions, including gait, postural balance, and physical strength. Occupational therapies help patients carry out daily chores easily and reduce their dependency.

Symptoms
Weakness in the arms or legs,Involuntary jerking,Cramping in hands and feet,Twitching of the facial muscles,Double vision,Bulging eyes, difficulty looking upward and opening eyes, and involuntary lateral movements of eye
Conditions
Ataxia,Intranuclear inclusions of ataxin-3
Drugs
Antiepileptic drugs for seizures,Botulinum toxin injections for dystonia,Beta-blockers and primidone for tremors,Antidepressants for depression,Levodopa for symptoms of parkinsonism,Citalopram, Dantrolene, Chlorzoxazone, Varenicline, Rapamycin

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