Treatable Ataxia

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• Treatable Ataxia

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INTRODUCTION
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• The term ataxia denotes inability to make smooth,
  accurate and coordinated movements usually due to
  a disorder of the cerebellum and / or sensory
  pathways in the posterior column of the spinal
  cord . The main cause of ataxia is failure of the
  cerebellum to modify muscle tone and contractions
  to achieve coordination.

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• Examples of treatable ataxias include those due
  to deficiencies of vitamin E or coenzyme Q10 and
  Episodic Ataxia Type 2 (EA2), in which episodes
  of cerebellar dysfunction are reduced by
  acetazolamide treatment

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• Gluten ataxia responds to a strict gluten-free
  diet even in the absence of an enteropathy. The
  diagnosis of gluten ataxia is vital as it is one
  of the very few treatable causes of sporadic
  ataxia.
• Ataxia with isolated Vit E deficiency (AVED)
  responds to high dose of Vitamin E and is one of
  the important causes of treatable ataxia.

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• Cerebrotendinous xanthomatosis is one of the very
  few treatable causes of progressive ataxia.
• The involvement of mitochondrial and respiratory
  chain dysfunction and oxidative stress in
  Friedreich ataxia (FRDA) pathogenesis suggests
  that FRDA may be amenable to treatment with
  combined antioxidant and bioenergetic therapy.

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• The term ataxia denotes inability to make smooth,
  accurate and coordinated movements. The main
  cause of ataxia is failure of the cerebellum to
  modify muscle tone and contractions to achieve
  coordination. This failure may occur due to
  cerebellar dysfunction or due to damage of the
  structures and pathways that feed information to
  the cerebellum regarding coordination (sensory
  pathways in the posterior column of the spinal
  cord). .

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Causes of Acute Ataxia
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• 1) Drug ingestion and toxicity (toxic ataxia).
• 2) Post-infectious
• Acute cerebellar ataxia (Acute postinfectios
  cerebellitis).
• Miller-Fisher syndrome.
• 3) Infectious
• Cerebellar abscess.
• Viral encephalitis (brain stem).
• Labyrinthitis.

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• II- ELECTRICAL
• Long QT syndrome
• Short QT syndrome
• Brugada syndrome
• Catecholaminergic ventricular tachycardia
• Idiopathic ventricular tachycardia
• Progressive cardiac conduction defect
• Wolff-Parkinson-White syndrome
• Congenital heart block

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• 4) Head trauma
• Hematoma.
• Postconcussion syndrome.
• Vertebrobasilar occlusion.
• 5) Myoclonic encephalopathy/Neuroblastoma
  syndrome.
• 6) Vascular disorders
• Cerebellar hemorrhage.
• Posterior fossa subdural hematoma.
• Kawasaki disease.
• 7) Conversion hysteria.

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• Risk factors for SCD in children include children
  with LVEDP gt25mmHg, children presenting gt2 years
  of age, decreased tissue Doppler-imaging
  velocities and ventricular tachyarrhythmias
  (VTs).

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Causes of Recurrent Ataxia
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• A Migraine
• Basilar.
• Benign paroxysmal vertigo.
• B Multiple sclerosis.
• C Pseudoataxia Epileptic Ataxia.

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• D Genetic/Metabolic disorders
• Dominant recurrent ataxia.
• Episodic ataxia type 1 paroxysmal ataxia and
  myokymia.
• Episodic ataxia type 2 Acetazolamide-Responsive
  Ataxia .
• pyruvate decarboxylase deficiency.
• Hartnup disease.
• Maple syrup urine disease, juvenile form

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• Causes of Chronic Ataxia.

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• Nonprogressive
• 1) Head trauma.
• 2) Ataxic cerebral palsy
• Kernicterus , Asphixia , Metabolic
  hypoglycemia, hypernatremia.
• 3) Congenital malformations
• Cerebellar aplasias.
• Cerebellar hemisphere aplasia/hypoplasia.
• Cerebellar vermis aplasia/hypoplasia.
• Arnold-Chiari malformation.
• Basilar impression.

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• Progressive
• 1) Brain tumor
• Cerebellar astrocytoma
• Cerebellar hemangioblastoma Von Hippel-Lindau
  disease
• Medulloblastoma
• Ependymoma
• Pontine glioma
• Frontal lobe

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• 2) Genetic
• Autosomal dominant
• Spinocerebellar degenerations
• Autosomal recessive
• Abetalipoproteinemia
• Ataxia telangiectasia
• Friedreichs ataxia
• Ataxia with episodic dystonia
• Ataxia with Isolated Vitamin E Deficiency
• Cerebellar ataxia due to Coenzyme Q10 deficiency

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• Cerebrotendinous Xanthomatosis
• Ataxia without oculomotor apraxia
• Maple syrup urine disease
• Ramsy Hunt syndrome
• Liposomal storage disease

• Juvenile GM2 gangliosidosis
• Juvenile sulfatide lipidosis
• Marinesco-Sjorgen syndrome
• Nieman Pick variant
• Refsum disease
• Mitochondrial disorders
• Hartnup disease

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• X-linked inheritance
• Adrenoleukodystrophy
• Leber optic neuropathy
• With adult onset dementia
• With deafness
• With deafness and loss of vision.

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• Classification of treatable ataxia

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A) Treatable Causes of Non-Genetic Ataxia I

• Congenital.
• Infectious/Post-infectious
• Ebstein-Barr.
• HIV/Syphillis.
• Measles, Rubella, Varicella.
• Enterovirus.
• HTLV1.

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B) Treatable Causes of Non-Genetic Ataxia II.

• Metabolic Acute thiamin (B1) deficiency,
• chronic vitamin B12 and E deficiencies, and
• autoimmune thyroiditis.
• Toxic (drug induced)

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C) Treatable Causes of Non-Genetic Ataxia III.

• Paraneoplastic.
• Other autoantibodies e.g. Anti-gliadin
  antibodies ( the most common, treated with
  gluten-free diet and anti-immune therapy)
• Anti-immune therapy steroids, plasmapheresis,
  IVIG, Methotrexate, and others.

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Treatable Genetic Ataxia

• Recurrent
• Dominant recurrent ataxia.
• Episodic ataxia type 1 paroxysmal ataxia and
  myokymia
• Episodic ataxia type 2 Acetazolamide-Responsive
  Ataxia
• Pyruvate decarboxylase deficiency. Hartnup
  disease.
• Maple syrup urine disease, juvenile form.

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• Chronic
• Abetalipoproteinemia. (
• Friedreichs ataxia.
• Ataxia with Isolated Vitamin E Deficiency.
  Cerebellar ataxia due to Coenzyme Q10
  deficiencyCerebrotendinous Xanthomatosis.
• Hartnup disease.
• Maple syrup urine disease. Ramsy Hunt syndrome.

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• Diagnosis

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A diagnostic approach to ataxia includes

• Neurological and medical history, including drug
  and toxin exposures
• Family history of neurological problems.
• Neurological and medical examinations .
• Blood tests to rule out specific deficiencies and
  toxins.
• Urine screen for mercury exposure .

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• Brain Imaging Magnetic Resonance Image (MRI) or
  Computed Tomogram (CT)
• Possible neuroimaging of the spinal cord.
• Electrophysiologic testing Electromyography(EMG)
  and nerve conduction velocity testing if there
  are signs or symptoms of peripheral nerve
  dysfunction.

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• Treatment of ataxia

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• First of all, search for treatable causes of
  ataxia. Since there is no universal treatment for
  ataxia, treatment of the underlying cause in
  those instances in which there is a treatable
  etiology is obligatory.

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TREATMENT GOALS

• Treat known causes, diet, replacement therapies,
  and
• detoxification therapy.
• Improve performance using symptom-specific drugs
  and retraining of nerve pathways.
• Improve activities of daily living and quality of
  life.
• Slow up disease progression using anti-oxidants
  and neuroprotective drugs.
• Gene therapy and stem cell therapy.

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• We advise patients with ataxia to work toward
  remaining in good general health by engaging in
  regular physical and mental exercise, eating and
  sleeping well, and avoiding injury from taking
  too much medicine, falling, or developing
  aspiration pneumonia. A primary care physician is
  essential for coordination of health care
  available for patients, encouragement of
  preventative health management, education of
  patients about avoidance of risks, and to guide
  the use of medications

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• Examples of treatable ataxias include those due
  to deficiencies of vitamin E or coenzyme Q10 and
  Episodic Ataxia Type 2 (EA2), in which episodes
  of cerebellar dysfunction are reduced by
  acetazolamide treatment.

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• Baclofen in low doses may reduce leg spasticity.
  GABAergic agents such as clonazepam,
  beta-blockers such as propranolol, or Primidone
  may reduce the prominence of some cerebellar
  tremors.

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• THANK YOU