Ataxia in Childhood

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Ataxia in Childhood a collection of clinical
cases
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Childhood Ataxia

• 4 Clinical Case descriptions
• Cerebellum Structure Function
• Ataxia Clinical Features
• Classification of Childhood Ataxia
• Discussion of selected Ataxic disorders

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Clinical case 1

• History
• Miss M.K. a 13 year old female, previously well
• Normal milestones, coping well at school
• Preceding history of vesicular rash, fever and
  malaise
• Rash erupted 10 days prior to admission
• Acute onset of unsteady gait, confusion, refusing
  to speak
• No history of immunocompromise

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Clinical case 1

• Examination
• Thriving child, not dysmorphic
• Crops of vesicles over trunk and limbs
• Florid cerebellar signs ataxia, DDK,
• intention tremor, truncal hypotonia,
• dysarthric speech, no nystagmus,
• mildly encephalopathic
• Investigations
• LP - normal pressures, chemistry, cell counts
• CT Brain - NAD

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Diagnosis

• Post varicella cerebellitis with encephalitis

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Clinical case 2

• History
• Master S.K. 11 year old boy, previously well,
  referred from
• Leratong hospital
• c/o 5 months fatigue, loss of weight, dizziness,
  poor balance
• Mother reported slurred speech, drunken gait,
  poor handwriting
• He was previously right-handed but was now using
  his left hand only

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Clinical case 2

• Examination
• Normal growth including head circumference
• Not dysmorphic, no skin lesions of neurocutaneous
  syndromes
• Systemic exam normal
• CNS alert and responsive. Nil meningism.
  Cranial nerves intact.
• Tone truncal hypotonia, Power full, Reflexes
  ? pendular
• Sensation intact, Proprioception intact
• Cerebellum
• titubation, dysarthric speech, DDK (marked on
  right), dysmetria, intention tremor, heelshin
  test on right, horizontal nystagmus present.
• Gait broad-based ataxic gait.

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Clinical case 2

• Investigations
• CT Brain posterior fossa lesion, highly
  calcified vermal and right cerebellar
  hemisphere mass

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Diagnosis

• Cerebellar medulloblastoma

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Clinical case 3

• History
• Miss B.M. aged 6 yrs from Ladysmith referred to
  Neuro Clinic
• with her 8 yr old similarly affected brother
• 2 year history of red eyes, poor balance,
  frequent falls,
• shaking of head, now becoming progressively
  worse
• Milestones normal, intellectually normal
• No family history of note

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Clinical case 3

• Examination
• marked gait ataxia
• DDK
• Dysmetria
• cerebellar speech
• pendular reflexes
• some dystonic posturing of trunk and arms
• apraxic movement of eyes
• conjunctival telangiectasia

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Clinical case 3

• Investigations
• CT Brain marked cerebellar atrophy
• Immunoglobulins (no result)
• Chromosomes

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Diagnosis

Ataxia Telangiectasia
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Clinical case 4

• History
• Master D.H. 9 year old male
• Presented at 7 years of age with poor balance
• Bumping into things falling over regularly
• Mom had noticed deformity of feet and assumed
  this was the cause of the problem
• Taken to physiotherapist who referred him to
  paediatrician for investigation of ataxia
• Family history maternal grandmother had 3
  cousins with weakness, who became
  wheelchair-bound and died in their mid 30s

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Clinical case 4

• Examination
• Thriving child. Normal head circumference.
• No dysmorphic features. Systemic exam NAD.
• CNS Distal muscle wasting.
• Significant pes cavus bilaterally with hammer
  toes.
• Tone globally reduced with rounded back but no
  kyphoscoliosis.
• Power proximally 5/5 , distally 3/5
• Reflexes globally absent, plantars equivocal
• Sensation glove and stocking sensory loss
• Proprioception intact

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Clinical case 4

• Examination (continued)
• Cerebellum dysarthric speech
• DDK
• dysmetria
• Mild intention tremor
• No nystagmus
• Gait high-stepping broad-based ataxic gait
• Unable to stand on one leg
• Investigations
• CT Brain MRI normal
• Cardiac assessment normal
• Nerve conduction axonal sensory peripheral
  neuropathy
• Blood investigation.

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Diagnosis

• ..homozygous expansion in frataxin gene
• Friedreichs Ataxia

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Cerebellum Structure Function

• The cerebellum is a vast coordinator of
  information receiving approximately 40 times
  more afferent than efferent fibres.
• This vast afferent input gives the cerebellum
  a total picture of the bodys position in space,
  motion, head position and limb position as well
  as the state of contraction of different
  muscles.
• The cerebellum sythesises this information,
  allowing one to adjust the speed, force and
  direction of a particular movement.

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Cerebellum Structure Function

• Organ of learned, skilled motor movements
• Stores movement patterns which are available for
  instant retrieval, enabling one to perform
  previously learned, difficult combinations of
  movements effortlessly
• Postnatally maturing organ so in assessing
  clinical signs of cerebellar disease, one has to
  consider the childs stage of development.

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Cerebellum Structure Function

• Three main anatomical subdivisions
• Central vermis
• Two lateral hemispheres
• Hemispheric lesions may present
• with ipsilateral cerebellar signs
• Vermal lesions may present with
• central hypotonia and bilateral signs

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Cerebellum Structure Function
Three main functional subdivisions Archicerebell
um (Vestibular) Paleocerebellum (Spinal)
Neocerebellum (Cortical)

• Archicerebellum - spatial position movement of
  head
• Paleocerebellum - proprioceptive regulation of
  muscle tone, posture and gait
• Neocerebellum - coordinates skilled motor
  movements

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Cerebellar disease Clinical Features

• Ataxia - incoordination of postural control and
  gait
• - incoordination of skilled fine
  movements speech
• Vertigo (uncommon in children)
• Vomiting (postural, projectile, positional)
• Ataxia
• Nystagmus
• Intention tremor
• Speech (slow, slurred, staccato)
• Hypotonia
• Dysmetria
• Dysdiadochokinesia
• Titubation

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Classification of Childhood Ataxia
Acute Chronic non-progressive Chronic progressive
Infections Toxins / Metabolic Posterior fossa tumours Trauma Migraine/Vascular Hydrocephalus Perinatal Congenital Malformations Cerebellar-Kidney associations Post-natally acquired Brain tumours Metabolic disorders Spino-cerebellar degenerations
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Acute Childhood Ataxias

• Infections
• Cerebellar abscess
• Viral cerebellitis (varicella, coxsackie, mumps,
  EBV, polio)
• Bacterial (diphtheria, pertussis, typhoid)
• Toxins / Metabolic
• alcohol / antiepileptic drugs
• heavy metal poisoning
• Hartnup / MSUD
• organic aminoacidurias
• Posterior fossa tumours
• Trauma - cerebellar haemorrhage
• Migraine - basilar
• Vascular - embolism / thrombosis / AVM (rare)
• Hydrocephalus

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Chronic Non-Progressive Childhood Ataxias

• Perinatal
• Birth asphyxia Cerebral palsy (hypotonic with
  or without ataxia)
• Hydrocephalus
• Metabolic (hypoglycaemia /kernicterus)
• Congenital Malformations
• Primary cerebellar hypoplasia
• Dandy-Walker
• Arnold-Chiari
• Cerebellar-Kidney associations
• Meckel Gruber syndrome
• Zellweger syndrome
• Von Hippel Lindau
• Postnatally acquired
• Hypoxic insults Cerebral Palsy
• Trauma
• Deficiency thiamine, hypothyroidism

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Chronic Progressive Childhood Ataxias 1

• Brain tumours
• - Cerebellar astrocytoma
• - Von Hippel-Lindau (cerebellar
  haemangioblastoma hypernephroid tumours)
  
• - Ependymoma
• - Medulloblastoma
• - Neuroblastoma (opsomyoclonus)

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Chronic Progressive Childhood Ataxias 2

• Metabolic disorders
• Sphingolipidoses (Metachromatic Leukodystropy,
  Krabbes, Niemann-Pick, Gauchers)
• Ceroid-lipofuscinosis
• Abnormalities of DNA repair (Ataxia
  Telangiectasia, Cockayne syn.)
• Energy metabolism (Leigh syndrome, pyruvate
  dehydrogenase deficiency)
• Fatty acid metabolism (Adrenoleukodystrophy,
  Refsums)
• - Other metabolic disorders (Abetalipoprotein
  aemia, Hartnups, MSUD)

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Chronic Progressive Childhood Ataxias 3

• Spino-cerebellar degenerations
• Hereditary Spinocerebellar degeneration
• - Autosomal recessive (Friedreichs ataxia,
  Cockayne, Behr syn.)
• - Autosomal dominant (SCA types 5 7, episodic
  ataxias)
• - X-linked
• Spinocerebellar Leukodystrophies
• Progressive myoclonic epilepsy

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Friedreichs Ataxia

• Chronic progressive childhood ataxia
• Hereditary spinocerebellar ataxia
• Autosomal recessive chromosome 9q13-q21
• Mutant gene (frataxin) contains expanded
• GAA triplet repeats
• Dying back neuropathy of the long ascending
• descending tracts of the spinal cord
• Diagnostic Criteria
• - onset before 20 years
• - autosomal recessive inheritance
• - combined involvement peripheral nerves
• cerebellar tracts
• pyramidal tracts
• posterior columns

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Friedreichs Ataxia

• CNS Clinical Features (variable)
• Cerebellar
• Progressive Ataxia (2-16years, more marked in
  legs, wide based gait)
• Progressive cerebellar speech
• Titubation
• Nystagmus
• Corticospinal
• Weakness distal wasting calf and hand muscles
• Positive Babinski reflex
• Absent knee ankle reflexes (may be present
  initially)
• Posterior column
• Vibratory proprioception loss
• Positive Romberg test
• Peripheral nerves
• Distal sensory loss

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Friedreichs Ataxia

• Associated Clinical Features
• Talipes-equino-varus
• Pes cavus (early onset/birth)
• Claw hand deformity
• Spastic bladder
• Cranial nerve involvement
• Kyphoscoliosis
• Cardiomyopathies common, HOCM, progression to
  intractable CCF
• Arrhythmias
• Diabetes (abnormal glucose tolerance and insulin
  resistance)
• Prognosis (variable)
• Most wheelchair bound by mid-twenties
• Disease may become static and survival into
  sixties is possible
• Mortality from CMO and respiratory problems 2 to
  severe scoliosis

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Ataxia Telangiectasia

• Chronic progressive childhood ataxia
• Autosomal recessive - Chromosome 11q22-q23
• Defect of DNA repair
• Pathology degeneration of cerebellar cortex,
  demyelination of posterior columns,
  spinocerebellar tracts peripheral nerves,
  degeneration of posterior roots, sympathetic
  ganglia AHC and loss of pigmentary cells
  substantia nigra, locus cereus, oculomotor
  complex, hypothalamus.

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Ataxia Telangiectasia

• Clinical features
• - Progressive ataxia- Abnormal eye movements
• - Dystonic posturing hands feet
• - Facial grimacing / slow spreading smile
• - Choreoathetosis- Cerebellar speech
• - Oculocutaneous telangiectasia- Intellectual
  fall off- Immune abnormalities
• - Increased incidence of malignancies

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Ataxia Telangiectasia

• Ataxia - Onset at 2-4 years, progresssive
• - Awkwardness - Initially truncal
• Oculomotor apraxia - Impaired upward gaze -
  Concomitant eye blinking - Poor saccadic
  eye movements - Jerking head movements
• Telangiectasia - Onset 2-6 years
• - Bulbar conjunctivae - Ears,
  neck, antecubital popliteal fossae
• Skin - Café-au-lait spots, vitiligo
• - Sclerodermoid changes

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Ataxia Telangiectasia

• Immune deficiency
• - Cellular (thymic hypoplasia, ? tonsils,
  adenoids, spleen,
• lymph nodes, lymphopaenia)
• - Humoral (? synthesis immunoglobulins with
  recurrent sinopulmonary infections with
  bronchiectasis)
• ? IgG, IgA, IgE ? IgM
• Other clinical features
• - Mild polyneuropathy
• - Hypotonia, reduced reflexes
• - ? Muscle bulk weakness
• - Intellectual fall off
• - Defect in DNA repair, sensitivity to ionising
  radiation,
• increased risk of malignancy especially
  ALL/gliomas.

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Ataxia Telangiectasia

• Associations - Mental handicap in 1/3 cases
• - Hypogonadism
• - Hepatic dysfunction
• - Insulin resistance
• Management - No specific treatment
• - Prompt Rx sinopulmonary infections to avoid
  bronchiectasis
• - Avoid exposure to radiation
• Investigations - Chromosomes
• - Immunoglobulins (? IgG, IgA, IgE ? IgM)
• Other increased AFP, CEA
• Prognosis - Wheelchair bound by 10 -15 years of
  age
• - 60 mortality by 3rd decade
• (infections, lymphoreticular malignancy)