Ataxia

The word ataxia derives from ataktos, a Greek word meaning ‘lack of order’; it has been defined
variously as a failure of coordination of the muscles; irregularity of muscle action; difficulty with
walking/gait; the problem with movement orientation because of abnormal agonist-antagonist muscle
coordination; or motor incoordination most notable when walking or sitting.

There is a spectrum of unsteadiness in walking, from ‘clumsy’ to profound ataxias.

Ataxia can be divided into three groups:

 Acute.
 Recurrent (also called episodic or intermittent).
 Chronic/progressive.

Acute ataxia (meaning evolution of symptoms within 3 days) has a few common causes which account
for 80% of children with this:

1. intoxications; 2. infectious causes (varicella); and 3. post-infectious causes (Guillain-Barré syndrome).

Recurrent ataxia can be due to mitochondrial disorders or other metabolic disorders (aminoacidurias
[e.g., Hartnup disease], organic acidaemias [e.g., Maple Syrup Urine Disease (MSUD)], or lysosomal
storage diseases [e.g., Niemann-Pick type C]).

Progressive ataxia has a wide differential including hereditary ataxias, metabolic disorders, brain
tumors, and neurodegenerative conditions such as leucodystrophies (adrenoleukodystrophy,
metachromatic, Pelizaeus–Merzbacher disease). Although acute ataxia usually has a benign cause,
recurrent and progressive ataxia generally indicates more serious pathology.

Mnemonics

Causes of ataxia are acute, episodic, and progressive (FLAMING SPINNER):

F=FRDA (Friedreich ataxia)

L=Labyrinthitis (vertigo causing ataxia)/Lysosomal storage diseases
A=
 AT (ataxia-telangiectasia),
 Abetalipoproteinaemia,
 Argininosuccinic aciduria
M=
 Medulloblastoma,
 Metabolic: MSUD (maple syrup urine disease),
 MLD (metachromatic leucodystrophy, also called arylsulfatase A [ARSA] deficiency),
 Metal disease: Wilson Disease,
 Migraine: basilar artery,
 Mitochondrial disorders (Kearns-Sayre, MERRF (myoclonic epilepsy with ragged red fibers),
NARP (neuropathy, ataxia, and retinitis pigmentosa),
 Multiple sclerosis,
 Myxedema (hypothyroidism)
 I=
 Infection (e.g., cerebellitis, meningitis, mastoiditis),
 IEMs (Inborn errors of metabolism, e.g., OTC [ornithine transcarbamylase deficiency]
N=Neuroblastoma (occult)
G=GBS (Guillain-Barré syndrome)/Genetic (hereditary) ataxias (many)
S=
 SCAs (spinocerebellar ataxias, autosomal dominant),
 SCARs (spinocerebellar ataxias, autosomal recessive),
 SPAX (spinocerebellar ataxias with prominent spasticity),
 Supratentorial tumours
P=
 Post-infectious cerebellitis,
 Posterior fossa tumors,
 Paroxysmal vertigo,
 Pellagra (niacin deficiency; can cause the four Ds: dermatitis (photosensitive), diarrhea,
dementia, and death),
 Pellagra-like dermatosis (Hartnup disorder [HND]),
 Pyruvate Carboxylase deficiency,
 Psychogenic (not real ataxia, but impersonating this)
I=Intoxication/Ingestion (drugs)/Inner ear pathology (e.g. labyrinthitis)
N=Nutritional deficiencies: deficiencies of vitamin B1 (thiamine), B3 (niacin/nicotinic acid), B6
(pyridoxine), B12 (cobalamin), E
N=Neurodegenerative disorders
E=Ependymoma/EA (episodic ataxias)
R=Refsum disease, Rett syndrome

Examination

 Start by introducing yourself to the parent and the child.

 Note the child’s level of consciousness,
o alertness (medications [toxins] or encephalopathies—e.g., acute disseminated
encephalomyelitis [ADEM] can alter these),
o quality of movement (e.g., choreoathetosis with AT)
o any obvious asymmetry, such as head tilt (ataxia plus head tilt equals posterior fossa
tumor until proved otherwise),
o scoliosis (can occur in ataxic cerebral palsy or FRDA),
o asymmetrical ataxia (which can mean brain tumor, stroke, or demyelinating disease).
 If the child is sitting or lying down when first seen, look around for any nearby peripheral aides
such as a wheelchair.
 If the child’s feet are uncovered, note any pes cavus (FRDA).
 Stand back and look for
o any rash, such as telangiectasia over the eyes and ears and bridge of the nose in AT,
o resolving varicella (acute cerebellitis, post-infectious cerebellar ataxia);
 o pellagra-like rash, with hyperpigmented, crusted, and fissured well-defined plaques on
sun-exposed areas of the face,
o dorsum of hands and legs (Hartnup disease; ‘pellagrous glove and boot’);
o urticaria (Kawasaki) or
o purpura (Henoch–Schönlein); or (rarely)
o ichthyosis with Refsum disease.
 Ask the child a few age-appropriate questions (e.g., their age, school, grade, teacher’s name,
favorite subjects, and in older children, specifically ask their full name, current location, and day
of the week), to get an impression of their orientation in time, place and person (for
intoxications or encephalopathies) and the quality of their speech (e.g., slurring with AT).
 If the child is sitting or lying down initially, ask the child, parent, or examiners whether the child
can walk. If the child can walk, then perform a gait examination. Focus on heel-toe (tandem)
walking in particular to check cerebellar vermis function.
You can check the gait examination
 Also, note any scoliosis during the gait examination, which can occur with any more progressive
neurodegenerative disorders, or with FRDA, Rett disorder, or ataxic cerebral palsy.
 When the child is walking on their heel and toes, any pes cavus should be easily seen (FRDA).
 In the lower limbs, focus on cerebellar and proprioceptive function and muscle strength;
 examine the upper limbs. Take note of the muscle bulk in the hands (for peripheral neuropathy),
and take the pulse for any arrhythmia (embolic cause of cerebellar stroke, mitochondrial disease
with pre-excitation, cardiomyopathy with mitochondrial disease or FRDA).
 During the cranial nerve examination,
o thoroughly check the third, fourth and sixth nerve function,
o look for nystagmus (many hereditary ataxias) or opsoclonus (neuroblastoma),
o checking the hearing (acute middle and inner ear pathology, FRDA, Refsum).
o Check the eyes carefully for visual acuity, visual fields, and then ask to examine the fundi
(for evidence of papilloedema, retinitis, or optic atrophy).
 The other findings sought on the head and neck examination including
o checking the head circumference (for hydrocephalus, such as from aqueduct stenosis or
tumors),
o looking for scars of shunts or other neurosurgery, feeling the head for shunts,
reservoirs.
o Feel the hair (abnormal in argininosuccinic acid and AT),
o look at the eyes (bulbar conjunctivae), nose and ears, for telangiectasia (AT).
o Next, check the ears, nose, throat, and mastoids for infection (labyrinthitis) and,
o if relevant, perform the Dix-Hallpike maneuver (only suggest this if you think the patient
could have benign paroxysmal vertigo).
o Then check for any other site of infection (for infectious or post-infectious ataxia
causes), including checking for signs of meningitis if the child is febrile.
 A full cardiorespiratory examination is appropriate.
o The BP is checked for hypertension (neuroblastoma, or hypertension as cause of stroke).
o The heart is examined for murmurs or arrhythmias (embolic stroke).
  The chest is examined for two reasons: first to check for involvement in any neurological process
that can affect respiratory reserve, as with GBS (get the child to count out loud; how far can they
count?), and second to check for signs of chest infection, such as Mycoplasma which may
present with crackles and wheezes.
 The abdomen should be examined for hepatosplenomegaly (EBV) or any masses
(neuroblastoma).
 After your examination, present a relevant differential diagnosis and suggest the investigations
most appropriate to confirm your diagnosis. This is a vast area. Suggesting brain (+/– spinal cord)
imaging and gene tests are often appropriate.

Ataxia-telangiectasia (AT) (ATAXIA CASE):

 ATM (ataxia-telangiectasia mutated) gene codes for serine-protein kinase ATM; only known
cause/Age: ataxia/cerebellar dysfunction (onset 1–4 years) antedates telangiectasia/IgA
(Immunoglobulin A) decreased

 Telangiectasia of exposed areas (bulbar conjunctivae, nose [bridge], ears, neck, antecubital
fossa): age 3 to 10 years/Ten years of age often require wheelchair/Truncal ataxia/Tone
decreased/Three out of ten develop malignancy (usually [85%] leukemia or lymphoma)

 Apraxia of eye movement (cannot follow object across field; vertical and horizontal saccadic
movements affected) and nystagmus

 X-ray of the chest (CXR) for sinopulmonary infection (increased susceptibility)

 Immune deficiency (cell-mediated immunity decreased)/Ionising radiation sensitivity

 Absent reflexes

 Choreoathetosis

 Cancer risk 40–100 times normal; especially ALL, AML, lymphoma, brain tumors,
adenocarcinoma of the stomach, basal cell carcinoma, ovarian dysgerminoma

 Alpha-fetoprotein (AFP) increased/Ageing appears premature (grey hair)

 Speech slurred (dysarthria)/Susceptibility to sinobronchopulmonary infections and serious

neoplasia (as above)

 Elevated carcinoembryonic antigen/Endocrine: insulin-resistant diabetes/Elasticity of skin is

lost/Eleven = chromosome locus (11q22.3)

Friedreich ataxia (FRDA) (FRIEDREICHS):

 FXN gene (at 9q13) codes for frataxin, a mitochondrial protein; only known cause/Five–fifteen
age group/Feet: pes cavus

 Reduced sense of vibration, position/Romberg test positive/Recessive

  Impaired sense of vision

 Eyes: optic atrophy/nystagmus

 Dysarthria

 Deafness

 Reflexes in lower limb absent, but …

 Extensor plantar/Equinovarus feet (plantar flexors, inverters affected)

 Insulin requirement (T1DM)

 Iron misdistribution in mitochondria allows oxidative damage, decreased ATP production

 Cardiac disease; hypertrophic non-obstructive cardiomyopathy

 Hyperglycaemia (diabetes in up to 30%)

 Spastic lower limbs (pyramidal weakness)/Scoliosis

Mitochondrial disorders (MITOCHONDRIAL):

 Myopathy (proximal)

 Myoclonus

 Migraine

 Inheritance recessive

 Tubular (renal) defects

 Optic atrophy

 Cataract/Chorea

 Heart: cardiomyopathy/pre-excitation syndromes

 Ophthalmoplegia

 Neuropathy

 Neurogenic weakness

 Neurologic: encephalopathy

 Deafness (sensorineural)/Diabetes/Dementia

 Retinopathy (pigmentary)

 Increased lactate: blood (fasting > 3.0 mmol/L); CSF > 1.5 mmol/L
  Ataxia

 Lid: ptosis

 Seizure

 Stroke-like episodes

 Spasticity

Multiple sclerosis signs and symptoms may differ greatly from person to person and over the course of
the disease depending on the location of affected nerve fibers. Symptoms often affect movement, such
as:

 Numbness or weakness in one or more limbs that typically occurs on one side of your body at a
time, or your legs and trunk
 Electric-shock sensations that occur with certain neck movements, especially bending the neck
forward (Lhermitte sign)
 Tremor, lack of coordination or unsteady gait
 Vision problems are also common, including:
 Partial or complete loss of vision, usually in one eye at a time, often with pain during eye
movement
 Prolonged double vision
 Blurry vision

Multiple sclerosis symptoms may also include:

 Slurred speech
 Fatigue
 Dizziness
 Tingling or pain in parts of your body
 Problems with sexual, bowel and bladder function