Issues with movement

Question 1

What is Friedreich Ataxia?

Answer 1

Neurodegenerative disorder

• due to deficiency in frataxin resulting in increased oxidative stress
• resulting in axonal degeneration
• accumulation of iron in mitochondria

Genetics

• triple repeat 9q13
• autosomal recessive

Clinical features:
Frequent falls
Recessive (autosomal)
Inc (upping plantars)
Eye signs (nystagmus)
Dorsal column changes - loss of vibration / proprioception
Reflexes absent
Explosive speech
I
Cerebella involvement - ataxia, dysarthria
Hypertrophic cardiomyopathy (most common cause of death)
Scoliosis and skeletal abN (pes cavus, hammer toes)

Ix

• nerve conduction studies abN
• sural nerve sensory loss

Management

• genetic counselling
• screen for cardiomyopathy / scoliosis / diabetes
• antioxidants
• iron chelators

Question 2

What is ataxia telangiectasia?

Answer 2

Neurodegenerative condition due to defect in the ATM gene which has an important role in cell cycle control, intracellular protein transport, and DNA damage response

Affects multiple systems:

• onset of ataxia with loss of ambulation by adolescence
• oculomotor apraxia and horizontal nystagmus
• Telangiectasis appears in mid childhood (bulbar conjunctivae, bridge of nose, ears, extremities, loss of skin elasticity)
• 50% have reduced Ig A, G, E with recurrent sinopulmonary infections
• Marked increase risk of lymphoma, leukaemia and Hodgkin’s disease / brain tumours

Question 3

What are neurodegenerative causes of ataxia?

Answer 3

Ataxia telangiectasia
Friedrich’s ataxia
Batten’s disease
Rett’s syndrome

Question 4

What are causes of ataxia?

Answer 4

Congenital anomalies of posterior fossa

• dandy walker malformation
• chiari malformation
• encephalocele
• agenesis of cerebellar vermis

Infectious cause

• cerebellar abscess
• acute vestibular neuritis (a/w viral AOM or URTI) and presents with nystagmus toward unaffected ear, vertigo and vomiting
• acute cerebellar ataxia: s/in 1-3yo two to three weeks post viral infection, presents with sudden onset, truncal ataxia and horizontal nystagmus

Toxin

• alcohol
• anticonvulsants (especially phenytoin at high dose)

Brain tumours

• medulloblastomas (post fossa by definition)
• any other tumours in the posterior fossa

Metabolic disorders
- Abetalipoproteinaemia

Question 5

What is the most common class of neurodegenerative disease in children?

Answer 5

Neuronal ceroid lipofuscinoses
(Collectively known as Batten Disease)

Aetiology

• metabolic disorder
• caused by lysosomal dysfunction affecting lipid breakdown resulting in accumulation of lipofusin

Genetics
- Autosomal recessive

Infantile type (CLN1) 
Late infantile type (CLN2) 
- most common 
- myoclonic seizures between 2-4 yo in a previously normal child 
Juvenile type (CLN3)
- onset 5-10 yo

At least 20 genes have been identified in association with Batten disease now…

Clinical features

• Cerebella ataxia (initially clumsy / unsteady)
• Visual deterioration: Optic atrophy and blindness, examines w brownish discolouration of macula
• Myoclonic seizures
• Regression of skills / intellectual deterioration

Question 6

What is metachromatic leukodystrophy?

Answer 6

An autosomal recessive white matter disease.
Multiple forms
- Most common is late infantile form
- Presents between 12 and 18 mo of age as irritability, inability to walk, and hyperextension of the knee, causing genu recurvatum. Deep tendon reflexes are diminished or absent. Gradual muscle wasting, weakness, and hypotonia become evident and lead to a debilitated state.
- MRI is characterised by bilateral symmetrical confluent areas of signal change in periventricular white matter with sparing of subcortical U fibres, as seen in this scan.