Ataxia in children

1. Ataxia in children

5. • ARCHICEREBELLUM/ FLOCCULO
NODULAR/VESTIBULO CERELLUM
• - Eye movements, gross balance and orientation
• - Inferior cerebellar pudencle
• PALLEOCEREBELLUM/ SPINOCEREBELLUM/ VERMIS
& PAR VERMIAN REGION
• - Posture, Muscle tone, Axial muscle
• control, Locomotion
• - Inferior/ middle/ superior pudencle
• NEOCEREBELLUM/ CELEBELLAR
HEMISPHERES/PONTO CEREBELLUM
• - Coordinating movements, Fine motor control
• - middle/ superior pudencle

6. Ataxia
1. Sensory Ataxia: results from the loss
of sensory input from the lower
extremities due to diseases of
peripheral nerves, dorsal roots, dorsal
columns of the spinal cord or medial
lemnisci.
2. Cerebellar Ataxia: results from a lesion
or degeneration focused in the body’s
gait and balance center: the vermis of
the cerebellum

7. Characteristic Sensory Ataxia Cerebellar Ataxia
Location of
lesion
Peripheral nerve or posterior
column disease
Cerebellar vermis
Gait Wide based gait
High stepping gait
Lurching, staggering
On Exam Can look normal while sitting
Loss of peripheral position and
vibration sense
+ve Romberg
Unable to stay balanced
sitting
-worse if legs crossed,
-worse with running /
standing

8. Characteristic Sensory Ataxia Cerebellar Ataxia
Associated Findings Loss of position and vibration
sense extremities
Intention tremor
Scanning speech
Hypotonia
Ocular and limb dysmetria
Speech Normal Often slurred
Hints Patient often looks to feet to
know their position in space
Patient looks like acute
alcohol intoxication

9. Approach to child with ataxia

10. Approach to child with ataxia
• HISTORY
Ensure that your patient is stable and comfortable and then proceed
further. In addition to a thorough history, include the following pertinent
questions:
• 1. HPI: timing, onset, progression (congenital vs insidious vs acute), nature of
ataxia, associated symptoms: fever, nausea, vomiting, lethargy, headache,
head tilting?
• a. Any previous episodes of ataxia?
• b. Onset: any recent viral infection or cough?
• c. Any medications, drugs or poisons possibly ingested?
• d. Any alcohol or other illegal drugs?
• e. Any trauma?
• f. Is there the possibility of a suicide attempt?
• g. Any change in mental status?

11. • 2. PMH:
Birth Hx: exposures
, TORCHES (congenital infections including
toxoplasmosis, rubella, CMV, Herpes, Syphillis),
congenital anomalies (ataxia can be congenital or
hereditary, but not appear until later).
• 3. Family History: sickle cell, metabolic disease,
epilepsy, migraines or Friedrich’s ataxia

12. • PHYSICAL EXAM
• full physical exam including vital signs and growth
parameters.
• General: awake, alert, acute distress, dysmorphic features
• Skin: scars, crusted varicella lesions
• fluid in middle ear, cervical adenopathy, papilledema,
hemorrhages
• Chest: chest rales, arrhythmias, murmurs
• Abdomen: hepatosplenomagaly, masses
• MSK: decreased strength

14. • Neuro: full neuro exam: cranial nerves, tone, power, reflexes,
sensation (pain, vibration, light touch, temperature and
proprioception),focal neurological findings
Assessment of Ataxia (Testing Cerebellar Function):
• truncal control.
• ask the child to walk several steps with natural gait,
then assess tandem gait (walk heel toe).
ask the child to walk several times around an object (ie. chair).
fall or lean towards the side of the lesion.
• tremor
• dysmetria
• dysdiadochokinesia

15. • PROCEDURES FOR INVESTIGATION
• 1. Bloodwork:
CBC and differential (infection)
Electrolytes with bicarbonate (imbalances),
Monospot
Toxicology screen (for anticonvulsants, hypnotics and phenothiazines, for
alcohol and drugs of abuse; for heavy metals)
Consider metabolic screen and IgA (for ataxia telangiectasia)
• 2. Urine: toxicology screen
• 3. Lumbar Puncture: if differential includes meningitis and fundi are
normal ;
look for CSF protein if demyelinating disease is suspected.
• 4. Imaging: Consider CT/ MRI if there are focal neurological findings.
• 5. Consults: Neurology.

16. Cerebellar Dysfunction
• Cerebellar lesions or dysfunction disturb
regulation of muscle tone, motor control, and
coordination of movement.
• Hypotonia -
typically seen with acute hemispheric lesions
with hyporeflexia.
usually a transient phenomenon after an acute
lesion but can be seen in chronic lesions as well

17. • Ataxia is a broad term that refers to a disturbance in the
smooth performance of voluntary motor acts.
• abasia(inability to walk due to spasticity, chorea, or tremor),
• asynergia (lack of coordination between parts that normally
act in unison),
• dysmetria(inaccuracy in judging distance or scale, resulting
in undershoot or overshoot of intended position of limb or
eye),
.

18. • dysdiadochokinesia
• impaired check/excessive rebound responses.
• Cerebellar dysarthria produces abnormalities in articulation
(slurring and inaccuracy in range, force and timing; patients
sound as if inebriated)
• phonation (vocal quality can be harsh or uneven),
• resonation (a nasal quality is common),
• prosody (patients tend to place equal and excessive emphasis
on each syllable)

19. • Intention tremor .
• Postural tremor is a rare manifestation
• Eye movement abnormalities -pathologic
nystagmus (smooth pursuit in one direction
alternating with saccadic pursuit in the other).
• Ocular dysmetria (conjugate overshoot or
undershoot of a visual target accompanied by
voluntary saccades)

20. • Nonmotor manifestations like cerebellar
cognitive affective syndrome has been
described in patients with isolated cerebellar
lesions of various etiologies, which can all
produce alterations in executive functions,
spatial cognition, personality, and language
use.

21. Nonhereditary Causes of Ataxia
The most prevalent causes of acute cerebellar
ataxia are viruses (e.g., coxsackievirus,
rubeola, varicella), traumatic insults, and
toxins (e.g., alcohol, barbiturates, antiepileptic
drugs).

22. Selected Causes of Ataxia in Childhood
• Congenital
• Agenesis of vermis of the cerebellum
• Aplasia or dysplasia of the cerebellum
• Basilar impression
• Chiari malformation
• Cerebellar dysplasia with microgyria,
macrogyria, or agyria

23. Congenital
• Cervical spinal bifida with herniation of the
cerebellum (Chiari malformation, type 3)
• Dandy-Walker syndrome
• Encephalocele
• Hydrocephalus (progressive)
• Hypoplasia of the cerebellum

24. Degenerative and/or Genetic
• Acute intermittent cerebellar ataxia
• Ataxia, retinitis pigmentosa, deafness, vestibular abnormality, and
intellectual deterioration
• Ataxia-telangiectasia
• Biemond posterior column ataxia
• Cerebellar ataxia with deafness, anosmia, absent caloric responses,
nonreactive pupils, and hyporeflexia
• Cockayne syndrome
• Dentate cerebellar ataxia (dyssynergia cerebellaris progressiva)
• Familial ataxia with macular degeneration
• Friedreich ataxia
• Hereditary cerebellar ataxia, intellectual retardation,
choreoathetosis, and eunuchoidism
• Hereditary cerebellar ataxia with myotonia and cataracts

25. Degenerative and/or Genetic
• Hypertrophic interstitial neuritis
• Marie’s ataxia
• Marinesco-Sjögren syndrome
• Pelizaeus-Merzbacher disease
• Periodic attacks of vertigo, diplopia, and ataxia—autosomal
dominant inheritance
• Posterior and lateral column difficulties, nystagmus, and
muscle atrophy
• Progressive cerebellar ataxia and epilepsy
• Ramsay Hunt syndrome (myoclonic seizures and ataxia)
• Roussy-Lévy syndrome
• Spinocerebellar ataxia (SCAs); olivopontocerebellar ataxias

26. • Endocrinologic
• Cretinism
• Hypothyroidism
• Infectious or Postinfectious
• Acute cerebellar ataxia
• Acute disseminated encephalomyelitis
• Cerebellar abscess
• Coxsackievirus,Diphtheria,Echovirus,Infectious mononucleosis (Epstein-
Barr virus infection)
• Infectious polyneuropathy,Japanese B encephalitis,Mumps
encephalitis,Mycoplasma pneumoniae,Pertussis,Polio,Postbacterial
meningitis,Rubeola,Tuberculosis,Typhoid,Varicella

27. • Metabolic
• Abetalipoproteinemia
• Argininosuccinic aciduria
• Ataxia with vitamin E deficiency (AVED)
• GM2 gangliosidosis (late)
• Hartnup disease
• Hyperalaninemia
• Hyperammonemia I and II
• Hypoglycemia
• Kearns-Sayre syndrome
• Leigh disease
• Maple syrup urine disease (intermittent)

28. Metabolic
• MERRF (Myoclonic epilepsy with ragged red fibers)
• Metachromatic leukodystrophy
• Mitochondrial complex defects (I, III, IV)
• Multiple carboxylase deficiency (biotinidase deficiency)
• Neuronal ceroid-lipofuscinosis
• Neuropathy, ataxia, retinitis pigmentosa (NARP)
• Niemann-Pick disease (late infantile)
• 5-Oxoprolinuria
• Pyruvate decarboxylase deficiency
• Refsum disease
• Sialidosis
• Triose-phosphate isomerase deficiency
• Tryptophanuria
• Wernicke encephalopathy (thiamine or B1 deficiency

29. • Neoplastic
• Frontal lobe tumors
• Hemispheric cerebellar tumors
• Midline cerebellar tumors
• Neuroblastoma
• Pontine tumors (primarily gliomas)
• Spinal cord tumors
• Primary Psychogenic
• Conversion reaction

30. • Toxic
• Alcohol
• Benzodiazepines
• Carbamazepine
• Clonazepam
• Lead encephalopathy
• Phenobarbital
• Phenytoin
• Primidone
• Tick paralysis poisoning

31. • Traumatic
• Acute cerebellar edema
• Acute frontal lobe edema
• Vascular
• Angioblastoma of cerebellum
• Basilar migraine
• Cerebellar embolism
• Cerebellar hemorrhage
• Cerebellar thrombosis
• Posterior cerebellar artery disease
• Vasculitis
• von Hippel-Lindau disease

32. Hereditary Ataxias
• Group1-
caused by enzymatic
defects,
autosomal recessive
manner and
typically present in
childhood; fortunately,
many of these are now
treatable
• Group 2-
progressive degenerative
ataxias
AR-Friedreich ataxia
autosomal dominant
spinocerebellar ataxias,
episodic
ataxias,dentatorubropallidol
uysian atrophy [DRPLA])
the very rare X-linked
ataxias.

33. Treatable Causes of Inherited Ataxia
Disorder Metabolic Abnormality
Distinguishing
ClinicalFeatures
Treatment
Ataxia with
vitamin E
deficiency
Mutation in alpha-
tocopherol transfer protein
Ataxia, areflexia,
retinopathy
Vitamin E
Bassen-
Kornzweig
syndrome
Abetalipoproteinemia
Acanthocytosis,
retinitis
pigmentosa, fat
malabsorption
Vitamin E
Hartnup
disease
Tryptophan malabsorption
Pellagra rash,
intermittent ataxia
Niacin
Familial
episodic ataxia
type 1 and type
2
Mutations in potassium
channel (KCNA1) and
a1Avoltage-gated calcium
channel, respectively
Episodic attacks,
worse with
pregnancy or birth
control pills
Acetazolamid
e

34. Mitochondrial
complex defects
Complexes I, III, IV
Encephalomyelopat
hy
Possibly riboflavin,
CoQ10,
dichloroacetate
Multiple
carboxylase
deficiency
Biotinidase
deficiency
Alopecia, recurrent
infections, variable
organic aciduria
Biotin
Pyruvate
dehydrogenase
deficiency
Block in E-M and
Krebs cycle
interface
Lactic acidosis,
ataxia
Ketogenic diet,
possibly
dichloroacetate
Refsum disease
Phytanic acid,
alpha-hydroxylase
Retinitis
pigmentosa,
cardiomyopathy,
hypertrophic
neuropathy,
ichthyosis
Dietary restriction
of phytanic acid
Urea cycle
defects
Urea cycle
enzymes
Hyperammonemia
Protein restriction,
arginine,
benzoate, alpha-
ketoacids

35. Friedreich Ataxia
• one of the most
common hereditary
ataxias
• Progressive gait ataxia
around puberty wild,
with a reeling or
lurching quality

36. Friedreich Ataxia
Clinical Manifestations
• Bladder dysfunction (spastic bladder )
• upper extremities affected only late in the
disease course.
• typically require a wheelchair within fifteen
years of symptom onset.

37. • facial weakness, with cerebellar dysarthria and
dysphagia.
• Lateral or horizontal nystagmus
• Impairment of pupillary responsivity and limited
extraocular movements ,cataracts, retinitis
pigmentosa, and optic atrophy.
• Auditory dysfunction
• higher cortical function appears intact

38. Friedreich Ataxia
• DTR(Lower limb ) lost
• Late-onset disease can be spastic with hyperreflexia..
Cremasteric and abdominal reflexes may be lost. The
masseter reflex remains intact
• Virtually all facets of cerebellar function are involved, and
both gross and fine coordination are affected.
• Position sense, vibration sense,impaired.
• Axonal sensory neuropathy
• Hypertrophic cardiomyopathy is the leading cause of death in
Friedreich ataxia patients.

39. • MRI studies document atrophy of the upper
cervical spinal cord and cerebellum.
• Diagnosis is suggested by the clinical
manifestations and sometimes by family history.
The presence of an abnormal 5-hour glucose
tolerance curve is corroborative. Spinal fluid
findings may include elevated protein content
and mild pleocytosis

41. • Friedreich ataxia is caused by an unstable GAA
trinucleotide repeat in the first intron
of X25, which decreases expression of the
mitochondrial protein, frataxin

42. • Treatment
• Idebenone, a short-chain analog of coenzyme Q10.16 at
5 or 10 mg/kg/day
• Therapy with Vit E other antioxidants, iron chelators,
and/or glutathione peroxidase mimetics has been
suggested
• interferon gamma (IFNγ)
• Symptomatic treatment in the form of antispasticity
agents can be helpful to relieve painful muscle spasms,
and surgical correction of scoliosis is palliative.

43. Ataxia telangiectasia
• Ataxia telangiectasia (A-T) is an autosomal
recessive disorder primarily characterized by
cerebellar degeneration, telangiectasia,
immunodeficiency, cancer susceptibility and
radiation sensitivity.

44. • Mutation in DNA repair factor-ATM (Ataxia
telangiectasia Mutated)
• The neuropathological hallmark of A-T is
diffuse degeneration or atrophy of the
cerebellar vermis and hemispheres,

45. • Progressive cerebellar ataxia
• Oculomotar apraxia
• Choreoathetosis
• oculocutaneous telangiectasia
• chronic sinupulmonary infections
• Ataxia begins soon after child begins to walk

46. • Immunological manifestations
-low levels of one or more classes of
immunoglobulin(IgG, IgA, IgM or IgG subclasses),
failure to make antibodies in response to vaccines or
infections,
and lymphopenia, especially affecting T-lymphocytes
• Cancer
-People with A-T have a highly increased incidence of
cancers.(Lymphomas and leukemias)
• Radiation sensitivity
• Feeding, swallowing, and nutrition

47. • Poor growth
• Insulin-resistant diabetes
• early aging such as premature graying of the
hair
• Delayed pubertal development/gonadal
dysgenesis
• Acquired deformity of the feet ,Scoliosis

49. Classic Form Mild Form
Neurological
Manifestations
during
the toddler years resulting in
wheelchair
dependency around the age of 10.
- mild neurological deficits in
childhood with slower age-related
neurodegeneration.
The predominant neurological
symptoms or symptoms
to present first may be myoclonus,
dystonia,choreoathetosis or tremor
with ataxia appearing
later.
Immunodeficiencie suffer from some type of
immunodeficiency
and/or lymphopenia
Immunodeficiencies do occur, but
are less common

50. Classic Form Mild Form
Pulmonary Disease Relatively common. Less common.
Cancer Although malignancies in these
individuals tend
to occur at a younger age and
are often lymphoid
in nature, cancers in older
individuals do occur
and include both hematopoietic
and
non-hematopoietic malignancies
Malignancies tend to
appear later in life and
include a
higher proportion of non-
hematopoietic cancers.
The diagnosis of cancer can
precede the diagnosis
of A-T.

51. • Laboratory Abnormalities in A-T
• Elevated and slowly increasing serum alpha-fetoprotein
levels after two years of age
• Low serum levels of immunoglobulins (IgA, IgG, IgG
subclasses, IgE) and lymphopenia (particularly affecting
T-lymphocytes)
• Spontaneous and X-ray induced chromosomal breaks
and rearrangements in cultured lymphocytes and
fibroblasts
• Reduced survival of cultured lymphocytes and
fibroblasts after exposure to ionizing radiation [209]
• Cerebellar atrophy detected by MRI

52. • Management
• The management and treatment of A-T is
symptomatic and supportive
• anti-Parkinson and anti-epileptic drugs may be
useful in the management of symptoms
• gamma globulin therapy and childhood
immunizations
• Chest physiotherapy and insufflator-exsufflator
device

53. • gastrostomy tube (G-tube or feeding tube)
• standard cancer treatment regimens need to
be modified to avoid the use of radiation
therapy and radiomimetic drugs
• L-DOPA, anticholingeric drugs-improve basal
ganglia
• Loss of balance,impaired speech-
amantadine,fluxetine
• Tremors-gabapentin,clonazepam

54. Spinocerebellar Ataxia
• The dominantly inherited ataxias, now called
spinocerebellar ataxias (SCAs), are progressive
disorders in which the cerebellum slowly
degenerates, often accompanied by
degenerative changes in the brainstem and
other parts of the central nervous system (and
less commonly the peripheral nervous system)

55. • There are three major genetic categories of
SCAs :
1) expanded CAG/polyQ ataxias;
2) nonprotein coding repeat expansion
ataxias; and
3) ataxias caused by conventional mutations
(missense, deletion, insertion, duplication).

56. • A second feature of SCAs is the remarkably wide range in
phenotype.
This heterogeneity stems primarily from the fact that DNA
repeat expansions, which cause the most common SCAs,
can vary greatly in size. The tendency for expansions to
change size is why these mutations are described as
“dynamic.”
• Larger expansions typically cause more severe, earlier-
onset disease.
• Smaller expansions cause later-onset disease with a more
circumscribed pattern of degeneration.

57. SCA1
• SCA1 begins as a gait disorder, evolving to severe four
limb ataxia with dysarthria and leaving most patients
wheelchair-bound within 15-20 years.
• SCA1 is caused by polyQ-encoding CAG repeat
expansions.
• SCA1 manifest signs of widespread cerebellar and
brainstem dysfunction with relatively little
supratentorial involvement.
• Neuropathologic findings include neuronal loss in the
cerebellum and brainstem, and degeneration of
spinocerebellar tracts.

58. SCA2
• characterized by ataxia, dysarthria, slow
saccades, and peripheral neuropathy.
• Extremely slow saccades are very common but
not pathognomonic.
• The expanded CAG repeat in SCA2 encodes
polyQ in the disease gene product, ataxin-2.

59. SCA3(Machado-Joseph Disease (MJD)
• most often begins as a progressive ataxia accompanied by lid retraction and
infrequent blinking (creating “staring eyes”), ophthalmoparesis, and impaired
speech and swallowing.
• Neuropathological findings include widespread degeneration of cerebellar afferent
and efferent pathways, pontine and dentate nuclei,cell bodies of the substantia
nigra, subthalamiC nucleus, globus pallidus, cranial motor nerve nuclei and anterior
horns.
• The mutation in SCA3 is an expanded CAG repeat that encodes polyQ in the disease
gene product ataxin-3.
• MJD varies widely depending on repeat length: early onset rigidity and dystonia for
the largest expansions, adult onset ataxia for the medium sized expansions), and
late-onset ataxia
• The most variable feature of SCA3 is the degree of peripheral nervous system
involvement

60. SCA5
• This rare and relatively pure form of slowly
progressive dominant cerebellar ataxia is
sometimes reported as the “Lincoln family
ataxia”.
• defective gene was recently discovered to be
the SPTBN2 gene encoding ß-III spectrin

61. SCA6
• “milder” disease, most often manifesting as a “pure”
cerebellar ataxia accompanied by dysarthria and gaze-
evoked nystagmus.
• decreased vibration and position sense, impaired
upward gaze, and, late in the disease, spasticity and
hyperreflexia.
Eye movements are among the key findings in SCA6,
ranging from difficulty fixating on moving objects to
diplopia without marked ductional deficits.
• The disease progresses more slowly than in other SCAs

62. • Episodic Ataxias
• There are currently eight described episodic
ataxias, all of which are rare dominant disorders
characterized by intermittent ataxia.
•
EA1, EA2, and EA5 are caused by
channelopathies;
• EA6 is caused by mutation of a glutamate
receptor; and
• the causes of EA3, EA4, EA7, and EA8 are
unknown.

63. Hereditary Spastic Ataxia
• a heterogeneous group of disorders that
combine the features of hereditary spastic
paralysis and spinocerebellar ataxia.
• present first with lower limb spasticity followed
by ataxia, dysarthria, impaired ocular
movements, and gait disturbance.
• Autosomal dominant, recessive, and X-linked
forms

64. Acute Ataxia
• Acute cerebellar ataxia typically presents with
rapidly progressive symptoms evolving over a few
hours but at most over 1 to 2 days.
• In cases associated with a prodromal illness, the
onset of ataxia is usually within 1 to 3 weeks after
the onset of the prodromal illness.

65. Causes of Acute Cerebellar Ataxia
• Inflammatory
• Infectious cerebellitis
Postinfectious cerebellitis
Brainstem encephalitis
Acute disseminated encephalomyelitis
Multiple sclerosis
Vasculitis
Paraneoplastic disorders
Miller Fisher variant of Guillain–Barré syndrome
• Intoxication
Alcohol
Drugs

66. • •Brain Space Occupying/Mass Lesions
Tumors
Abscesses
Vascular
Vertebrobasilar dissection
Thromboembolism,CNS Trauma
• Postconcussion syndrome
Miscellaneous
Labyrinthitis
Basilar migraine
Benign paroxysmal vertigo
Epilepsy (nonconvulsive status, minor motor status)

67. Causes of Acute Episodic
Cerebellar Ataxia
Metabolic Disorders Genetic Disorders
Mitochondrial disorders
Urea cycle defects
Aminoacidopathies
Ataxia telangiectasia
Episodic ataxias
Organic acidopathies
Spinocerebellar ataxias

68. Investigations in Acute Ataxia
• Computed Tomography and Magnetic Resonance Imaging
• Cerebrospinal Fluid
• Electromyography andElectroencephalography
• Toxicology
• Urinary Catecholamines/Metaiodobenzylguanidine
Scintigraphy
• Antibody levels

69. • Treatment and Prognosis
• Acute postinfectious cerebellitis is usually a self-limited condition
with most children showing a spontaneous recovery within the first
week.
After an active infection is ruled out, a trial of immunosuppression
is usually warranted.
Corticosteroids, such as solumedrol in a daily dose of 20 to
30 mg/kg up to 1000 mg a day, are usually pulsed for 3 to 5 days.
If there is no improvement =plasmapheresis or intravenous
immunoglobulin
the use of rituximab 375 mg/m2 weekly for 4 weeks has been
reported to show benefit

70. • OMAS frequently require prolonged treatment with IVIg
and corticosteroids to prevent relapses.
• Children with the Miller Fisher variant of GBS should be
admitted to the hospital for careful monitoring of
respiratory and autonomic function.. The recommended
dose of immunoglobulin is 2 g/kg over 2 to 5 days.
The decision for active treatment depends on status of
ambulation and respiratory and bulbar involvement.
• Systemic infections and brainstem encephalitis should be
treated with standard antibiotic/antiviral protocols,
although outcome in brainstem encephalitis is uncertain.

71. • Treatment of toxic ingestion-
no specific treatment is available.
administration of an antidote, chelation, dialysis,
• Ataxia related to postconcussion syndrome usually clears by 6
monthsataxia.
• EA1 may respond to antiepileptic medication. Both EA1 and
EA2 respond to daily acetazolamide.
• Daily nicotinamide administration (50–300 mg) - neurologic
complication in Hartnup disease.
• Acetazolamide has been shown to abort acute attacks of
ataxia in pyruvate dehydrogenase deficiency.
• Nonmetastatic neuroblastoma should be removed surgically.