Ataxia

clinical approach to a pt of ataxia

1. APPROACH TO ATAXIA
Dr. Deep Chandh Raja.S

2. SYNOPSIS
Important concepts in Ataxia
ATAXIA MIMICKERS
Tests of Cerebellar dysfunction
Step-wise approach to Cerebellar Ataxias
Summary
ALGORITHM for cerebellar ataxias

3. ‘In Simple Terms…”
•ATAXIA- “Absence of ORDER” (Greek Word)
•In Neurological Terms-
“Incoordination of movement”
•A major feature of a disease or just one of the
various clinical features of a disease

4. Definition
•Ataxia is the inability to make smooth,
accurate and coordinated movements
•Arises from disorders of:
––Cerebellum
––Sensory pathways (Sensory Ataxia)
––Posterior columns, dorsal root ganglia,
peripheral nerves
––Frontal lobe lesions
––Extra pyramidal system
––Vestibular system

5. Tests to differentiate Various systems
in Ataxia- “The Ataxia Mimickers”

6. Cerebellar Ataxia
Cortical Ataxia
Myopathy
Labrynthine Ataxia
Sensory Ataxia
(Posterior Column)
Thalamic Ataxia
Sensory Ataxia
(Peripheral
Neuropahy))

7. SENSORY ATAXIA
“Disturbances in the sensory input to the cerebellum”
•Tests of proprioception- Joint sense, passive
movement
“The corrective effects of the Visual system”
•Classical Sensory Ataxic Gait
•Romberg’s sign
•Loss of tendon reflexes
•Features of Peripheral neuropathy

9. •Caveats
Friederick’s ataxia, Multiple sclerosis…
•Overlap of clinical features to be expected in
clinical practice

10. Muscle weakness
•In the Miller-Fisher syndrome, which is
considered to be a variant of acute Guillain-Barré
polyneuropathy
•The severe ataxia and intention tremor are
presumably a result of a highly selective
peripheral disorder of spinocerebellar nerve
fibers
•Simple “tests of muscle power” can help detect
muscle weakness in various muscle groups
•CAVEAT- lead poisoning

11. Labrynthine Disorders
•Input to cerebellum
•Dizziness, light headedness, perception of
“movement”, rotatory nystagmus
•Infections, neoplasms, vascular causes
CAVEAT: involvement of flocculonodular lobe of
cerebellum, paraneoplastic and lateral
medullary syndromes (lateral medulla and
inferior lobe of cerebellum)

12. Cortical Ataxias
FRONTAL LOBE ATAXIA refers to disturbed coordination due to
dysfunction of the contralateral frontal lobe;
-Results from disease involving the frontopontocerebellar fibers
en route to synapse in the pontine nuclei.
•hyperreflexia, increased tone and Release reflexes
A lesion of the “SUPERIOR PARIETAL LOBULE” (areas 5 and 7 of
Brodmann) may rarely result in ataxia of the contralateral
limbs

13. Thalamic Ataxias
-transient ataxia affecting contralateral limbs
after lesion of anterior thalamus
-may see associated motor (pyramidal tract)
signs from involvement of internal capsule
- also can result in asterixis in contralateral
limbs (hemiasterixis)

14. BEWARE OF EXTREMELY ANXIOUS PATIENTS!!!

15. CEREBELLAR
ATAXIAS
“ATAXIA IS THE MOST IMPORTANT FEATURE
AMIDST OTHER CLINICAL SIGNS OF CEREBELLAR
DYSFUNCTION”

16. NEO CEREBELLUM
FLOCCULONODULAR
LOBE
SPINO CEREBELLUM

20. TESTS OF CEREBELLAR DYSFUNCTION

21. ATAXIA
“errors in the RATE, RANGE, FORCE & DIRECTION
of movement”
•GAIT ATAXIA
•TRUNCAL ATAXIA
•LIMB ATAXIA

22. CLASSIC FEATURES AND TESTS
Dyssynergia: results in jerky decomposed
movements (heel-knee-shin test)
Dysmetria: due to delayed activation of
antagonists
•- often correction to target by series of jerky
corrections (finger nose test)
•- may lead to intention tremor in limbs with
finger-to-nose or foot-to-target testing as
rhythmic oscillation emerges close to target
Dysdiadochokinesis: irregularities of force,
speed, and rhythm

23. Other features
Hypotonia: decrease in resistance to passive movement of
muscles related to depression of gamma motor neuron
activity (usually seen transiently in acute phase of
cerebellar lesions), pendullar knee jerk
Rebound phenomenon: related to poor tone and weak
check response, so when tap or displace limb, wider range
of movement in return to static position, incl. Holmes
phenomenon when suddenly release flexed arm held
against resistance - unable to stop flexion and arm strike
self (delay in activation of antagonist triceps muscle)
Dysarthria: often scanning type with irregularities in tone,
with words broken into syllables; often slow with
occasional rapid portions ("explosive speech")

24. Other features
Ocular Motor Abnormalities:
- usually if vestibular connections or flocculonodular lobe
affected
- pursuit movements no longer smooth, but saccadic
- may over- or under-shoot target with attempts at fixation
(ocular dysmetria)
- in primary position may see saccadic intrusions (such
as macro square-wave jerks) or primary nystagmus (incl.
vertical, esp up-beat nystagmus) or periodic alternating
nystagmus
-rebound nystagmus can occur with contralateral-beating
nystagmus on return of eyes to primary position after
eccentric gaze evoked nystagmus to one side
Writing abnormalities
Positional projectile vomiting (posterior fossa lesions)

25. APPROACH TO CEREBELLAR ATAXIA
IN ADULTS

26. THE “FOUR” QUESTIONS????
•Mode of ONSET ?
•PROGRESSION ?
•Focal /Symmetric involvement ?
•Localisation of the cerebellar lesion ?
HISTORY
EXAMINATION

27. MODE OF ONSET
•ACUTE- hours to days
•SUB ACUTE- days to weeks
•CHRONIC- months to years

28. ACUTE ONSET ATAXIA
•INTOXICATION: alcohol , lithium , phenytoin ,
barbiturates
•POST INFECTIOUS: Acute Viral Cerebellitis,
VZV
•VASCULAR: Infarction (AICA, PICA syndromes),
Haemorrhage, Subdural hematoma

29. SUB ACUTE ATAXIA
•INTOXICATION: Mercury, Solvents, Glue
•NUTRITIONAL: B1 and B12 deficiency
•INFECTION: HIV
•DEMYELINATING: Multiple Sclerosis
•NEOPLASTIC: Glioma, Metastases

30. CHRONIC ATAXIA
•AUTOIMMUNE CAUSES : Paraneoplastic
syndromes, Gluten hypersensitivity, Anti GAD
abs.
•HYPOTHYROIDISM
•INFECTIONS: Syphilis (Tabes Dorasalis)
•CONGENITAL LESIONS: Arnold-Chiari and Dandy
Walker Syndromes
•INHERITED ATAXIAS: AD,AR,XR,XD,Mitochondrial

31. PROGRESSION
•Progressive
•Static
•Intermittent symptoms
•Reversible Ataxias

32. PROGRESSIVE ATAXIA
CLASSIFICATIONS OF GREENFIELD AND OF
HARDING
into three main groups:
(1) the spinocerebellar ataxias, with unmistakable
involvement of the spinal cord (Romberg sign, sensory
loss, diminished tendon reflexes, Babinski signs);
(2) the pure cerebellar ataxias, with no other
associated neurologic disorders; and
(3) the complicated cerebellar ataxias, with a variety
of pyramidal, extrapyramidal, retinal, optic nerve,
oculomotor, auditory, peripheral nerve, and
cerebrocortical accompaniments including what is
now referred to as multiple system atrophy

33. STATIC ATAXIAS
•Vascular causes
REVERSIBLE ATAXIAS
•Infectious causes – post viral
•Thyroid
•Drugs
•Toxins
INTERMITTENT SYMPTOMS
•Episodic Ataxias (Inherited etiology)

34. FOCAL / SYMMETRIC ATAXIAS
•Cerebellar symptoms on same side of lesion, or
•Bilateral symptoms
FOCAL ATAXIAS
Vascular causes, Multiple Sclerosis, Cerebellar
abscess, cerebellar glioma, PML (HIV), Congenital
causes
SYMMETRIC ATAXIAS
Intoxication, Nutritional, Post inhectious,
Hypothyroid, Autoimmune causes

35. LOCATION OF LESION
•CEREBELLAR HEMISPHERIC SYNDROME
Ipsilateral head & Body cerebellar signs Infarct,
Neoplasm, Abscess, Demyelination
•ROSTRAL VERMIS SYNDROMEgait and Trunk
Ataxia Alcoholism, B1 deficiency
•CAUDAL VERMIS SYNDROME Disequilibrium,
Trunk ataxiaMedullobalstomas
•PANCEREBELLAR SYNDROME Bilateral signs
Toxins, metabolic, Infections, Autoimmune,
Inherited
•CEREBELLAR PEDUNCLES Dramatic cerebellar
symptoms

37. PICA
(Lateral medullary-Wallenberg Syndrome)

38. AICA
(Lateral Inferior Pontine Syndrome)
•Vestibular N. i/l vertigo, nystagmus
•Cochear n.  i/l deafness
•7
th
Cranial Nerve i/l facial palsy
•Cerebellum  i/l Ataxia
•5
th
cranial nerve i/l hemisensory loss of face
•Spinothalamic Tract C/L hemisensory loss

39. THE NEXT STEP …RULE OUT
ACQUIRED ATAXIAS
INHERITED ATAXIAS
SPORADIC or
IDIOPATHIC
ATAXIAS

40. ACQUIRED ATAXIAS
•First rule out the Structural causes (MRI Brain/
CT head)
-CVJ anomalies
-Posterior fossa tumors
-Demyelinating diseases
-Hypoxic encephalopathies
-Vascular causes- infarct, haemorrhage

41. Acquired Causes
•HYPOTHYROIDISM- Mild gait ataxia PLUS
Systems of hypothyroidism

42. ALCOHOLISM
•Vermian Atrophy

43. TOXINS
•Cancer chemotherapeutics 5 FU, Cytarabine
•Metals Bismuth, Mercury (parasthesiass,
restricted visual defects), Lead
•SolventsPaint thinners , toluene (Cognitive
defects PLUS pyramidal tract signs)
•AnticonvulsantsPhenytoin (purkinje cell
loss)avoid in epileptics with ataxia

44. INFECTIONS
•VZV in children
•EBV in children
•Bickerstaff’s encephalitis (brain
stemophthalmoplegia,ataxia,lower c.n
palsies)
•HIV ( Lymphomas, PML, Infections,
Toxoplasmosis)
•CJD (17% classic CJD, Ataxic variant of CJD)
•Syphilis (Tabes Dorsalis)
•Whipple’s disease

45. AUTOIMMUNE CAUSES
PARANEOPLASTIC SYNDROMES
•ANTI Hu abs. Small Cell Cancer Lung
(extrapyramidal signs)
•ANTI Yo abs. Ovarian cancer
•ANTI Ri abs. Breast cancer (opsoclonus –
saccadomania, Trunk ataxia)
•ANTI Tr abs. Hodgkin’s lymphoma (hearing
loss)

46. •GLUTEN SENSITIVITY - Anti Gliadin abs.
(ataxia, brisk reflexes, peripheral neuropathies)
•ANTI GAD abs. – Diabetes, hypothyroidism,
peripheral neuropathySTIFF PERSON
syndrome
AUTOIMMUNE CAUSES

47. NUTRITIONAL CAUSES
•FAT MALABSORPTION- Vit. E deficiency
•Vit. B12 , B1 deficiencies

48. INHERITED ATAXIAS
•AD
•AR
•MITOCHONDRIAL DISTURBANCES
•X LINKED RECESSIVE
•X LINKED DOMINANT

49. INHERITED ATAXIAS

50. INHERITED ATAXIAS

51. AUTOSOMAL DOMINANT

52. •SPINO CEREBELLAR ATAXIAS (Types131)-
previously olivopontocerebellar atrophies
•DentatoRubroPallidoLuysian Atrophy
•EPISODIC ATAXIAS (Types 17)
AUTOSOMAL DOMINANT

53. SCA SALIENT FEATURES
•3-5th decade of life ONSET, loss of ambulation
over 10-15 yrs. from onset
•Phenomena called ANTICIPATION and
PENETRANCE differs from each
SCAresponsible for various ages of
presentation and variable phenotypic
expression
•CAG repeat expansion in most of them

54. •UMN SIGNS SCA 1, SCA7, SCA 8
•OLDER AGESCA 6
•MENTAL RETARDATIONSCA 13
•VISUAL LOSSSCA 7
•CHOREA, MYOCLONUSDRPLA
•SEIZURES SCA 10
•AREFLEXIASCA 2
•INTEREPISODIC NYSTAGMUSEA 2
•INTEREPISODIC MYOKYMIA EA1
•NO FAMILY h/o SCA 6
AD ATAXIAS’ SALIENT FEATURES

55. SCA 5
SCA 2MJD
SCA 7

56. AUTOSOMAL RECESSIVE ATAXIAS

57. •FRIEDERICK’S ATAXIA
•ATAXIA TELANGIECTASIA
•ATAXIA WITH ISOLATED VIT.E DEFICIENCY
•ABETALIPOPROTEINEMIA
•ENZYME DEFICIENCIES (Maple Syrup urine
disease, Urea cycle defects, Sialidosis,
Adrenoleucodystrophy,Organic aciduria,
Pyruvate dehydogenase def.)
AUTOSOMAL RECESSIVE ATAXIAS

58. Friederick’s ataxia
•Unstable expansion of GAA repeatsFRATAXIN
proteiniron accumulation in
mitochondrianito.injuryneuronal injury
•DORSAL GANGLION CELLS- absent reflexes
•DORSAL COLUMN DEGENERATION-
dec.post.column senses
•SPINOCEREBELLAR TRACT-gait atxia, dysarthria
•CORTICOSPINAL TRACT- Babinski Positive
•OTHER SIGNS- dysphagia,optic atrophy, spinal and
foot deformities, diabetes (10%), cardiac defects
(50%)

59. Friederick’s ataxia

60. •NATURAL HISTORY:
-onset <25 yrs. At ADOLESCENCE
-loss of ambulation 15 yrs. Since onset
-Death usualyy due to cardiac complications
•VARIANTS:
-FA with Retained reflexes
-Late onset FA
Friederick’s ataxia

61. ATAXIA TELANGIECTASIA
•OCULOMOTOR APRAXIA , TELANGIECATSIAS
IN EYES, SKIN
•Hematological malignancies (defective DNA
repairs)
•Infections (Ig deficiencies)
•Other features-peripheral neuropathy,
choreoathetosis

62. ATAXIA TELANGIECTASIA

63. Mitochondrial Inheritance
•MERRF
•MELAS
•NARP
•RP degeneration
•Short stature, Endocrine deficiencies,

64. X linked ATAXIAS
•X linked Dominant- Fragile X syndrome
•CGG repeats’ expansion

65. •X linked Recessive Ataxias- Sideroblastic
anemia with ataxia
X linked ATAXIAS

66. SPORADIC or IDIOPATHIC ATAXIAS
•Unknown genetic defects after ruling out
acquired causes
•Old age of onset
•Presents with Dysautonomia –Orthostatic
hypotension, erectile dysfunction, Urinary
incontinence

67. Investigations
•MRI Brain and Upper cervical cord
•CT Head
•Vit. E, B12 levels
•Total cholesterol levels, Thyroid hormones
•NCV and EMG studies (to rule out other systems’
involvement)
•Toxicology screen (includes phenytoin levels)
•Serology screen (for autoantibodies)
•CSF analysis
•Genetic Analyses (GAA, CGG, CAG repeat
analyses)

68. TREATMENT
•Reversible causes to be identified and treated
•Structural lesions to be considered for surgery
•Dietary modifications
•IDEBENONE- in Friederick’s Ataxia
•RILUZOLE- in Friederick’s Ataxia
•ACETAZOLAMIDE- in Episodc Ataxia
•GENETIC COUNSELLING

69. HISTORY SUMMARY
1. Duration: acute, subacute vs chronic
2. Rate of Progression: static vs progressive
3. Constant vs Paroxysmal
4. Associated features:
- headache & vomiting suggesting mass lesion with raised ICP
- previous neurological events (similar with ataxia - as in
episodic ataxias, or other as in multiple sclerosis or
vertebrobasilar TIAs)
5. Medical History:
- recent infection, Hx of malignancy or weight loss, breast
mass / tenderness, cough / hemoptysis
- drug use / intoxication, medications, alcohol, smoking,
environmental exposures
6. Family History positive or negative (in siblings or cousins
but not parents suggesting autosomal recessive or parents
and/or sibs suggesting autosomal dominant inheritance

70. EXAMINATION SUMMARY
General examination:
- signs of primary neoplasm (with paraneoplastic or metastatic
ataxia), vascular disease (stroke), cardiac abnormality (
Friedreick's) or Kayser-Fleischer rings (Wilson's)
-short stature and cataracts with mitochondrial disease

Higher Mental Functions:
- confusion associated with ataxia in Wernicke's, drug or
environmental toxicity, prion diseases or any condition
obstructing 4th ventricle leading to hydrocephalus with raised
ICP

71. Cranial Nerves:
- ophthalmoplegia seen in Wernicke's, brainstem infarcts,
demyelinating lesions, and Miller-Fisher syndrome (MFS)
- nystagmus common in most vestibulocerebellar (or
pancerebellar) disorders but prominent if drug toxicity (eg.
phenytoin), Wernicke's and multiple sclerosis (also episodic
ataxia-2)
- associated brainstem (cranial nerve) dysfunction if
concomitant involvement of brainstem or compression of it
by mass effect from cerebellum
- hearing loss or tinnitus with lesions of the cerebellopontine
angle (eg. vestibular schwannoma or meningioma)
EXAMINATION SUMMARY

72. EXAMINATION SUMMARY
Motor:
- weakness associated with ataxia is uncommon but can be
seen ipsilaterally with infarcts (or other lesions) of the basis
pontis or internal capsule (ataxic hemiparesis syndrome)
- also seen in MFS (with concomitant demyelinating
polyneuropathy), cord dysfunction (in paraneoplastic
syndromes or demyelinating multifocal disease)
- tremor associated either as intention tremor of cerebellar
origin or postural tremor in FXTAS (Fragile X), multiple
sclerosis, Wilson's disease
- myoclonus in prion disorders with cerebellar involvement
- parkinsonism with ataxia in multiple systems atrophy (also
dystonia and chorea if DRPLA)

73. SUMMARY
•RULE OUT “ATAXIA MIMICKERS”
•CONFIRM PREDOMINANT CEREBELLAR
INVOLVEMENT WITH RESPECTIVE TESTS
•ANSWER THE “FOUR” QUESTIONS
(Onset, progression, Symmetry, Localisation of
lesion)
•RULE OUT ACQUIRED CAUSES
•LARGE PEDIGREE CHART
•GENETIC ANALYSES

74. ALGORITHM
PEDIGREE CHART
ACQUIRED
CAUSES
AD
IMAGING
(MRI,CT)
SCA1,2
MJD
SCA6,7
SCA10,12
DRPLA
SCA17
FA
AT
AVED
ABETALIPOPROTEINEMIA