Approach to a patient

with ataxia

Dr Rakesh Shukla
Professor Of Neurology

Definition
Ataxia (Gk. Taxis = Order; means lack of order)
Ataxia denotes a syndrome of imbalance and
incoordination involving gait, limbs, and speech
and
usually results from the disorder of the
cerebellum or its
connections
It is characterized by dyssynergia, dysmetria,
dysdiadochokinesia (Joseph Babinski).
It is a disorder of rate, range, direction and force
of
movements (Gordon Holmes).

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Clinical scenario
RK, 22 years young man presented with
C/O headache, double vision, difficulty in walking 2025 days
P/H RTA 3 mths back, tractor on which he was
travelling
overturned, No loss of consciousness, had a local
penetrating
injury in the nape of neck from a bolt in the tractor
received
local wound dressing, Eptoin (100g) 3HS
No H/o fever

Clinical scenario
O/E Afebrile vitals-normal, wt 43 kg GCS 15, fundus
NAD
No sign of meningeal irritation, broad based gait
ataxia,
tandem walking impaired, Gaze evoked nystagmus
+nt,
broken smooth pursuit
Speech NAD, Rombergs sign negative, no motor
weakness,
DTR normal, planters bilateral flexor
Diag Acute onset cerebellar syndrome presenting as
gait

Investigation
HB 11 gm%, TLC 8,400 cells/cmm, DLC P58 L41E1,
Platelet count 1.8 lac/cmm
Blood sugar-R 122mg/dl, S urea 15 mg/dl
S creatinine 0.8 mg/dl
Serum electrolytes, LFT normal
HIV, HbsAg, HCV-non reactive
PT/PC/ INR normal

Imaging: CECT scan brain

Imaging: MRI scan brain

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

 Cerebellum has been recognised as a distinct division of the

brain since Herophilus (335-280 BC) and Galen (131-200 AD)
Angevine et al., (1961) listed 24 different nomenclatures,
terminology used by Larsell (1972) is used commonly at
present.
It has a volume of about 144 cm3 and weighs 150g (~10% of
brain weight), but its surface area is about 40% that of the
cerebellar cortex.

Dorsal view of the cerebellum

Development of cerebellum
Vestibular proprioceptors provide information about the
movement of head and its position. Having no limbs,
primitive animals have only the flocculonodular lobe which
coordinates the axial muscles that position the eyes, head
and trunk
All higher animals having limbs have the anterior lobe to
coordinate proprioceptive input from limbs and trunk.
Emergence of vertical bipedal from the quadripedal posture
places particular demands on gait coordination
The third and newest cerebral lobe (posterior lobe) expands
in equal measure with the cerebrum, motor cortex,
pyramidal tract, basis pontis and inferior olivary nuclei

Cerebro-cerebello-cerebral circuit

Generalisations about cerebellar

disease
Lesions

Manifestations

Lateralized
Ipsilateral signs and symptoms
Generalised
Bilateral symmetrical symtomatology
Acute
Severe abnormalities at onset,
remarkable recovery with time
Chronic
Gradual progressive decline
Vestibulo cerebellar
Disequilibrium and an ataxic gait
Vermis
Truncal and gait ataxia
Cerebellar hemispheres Appendicular ataxia

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Differentiation of sensory and

cerebellar ataxia
Sensory ataxia is due to severe sensory neuropathy,
ganglinopathy or lesions of the posterior column of the
spinal
cord. e.g. Sjogrens syndrome, cisplatin, CCNU, Paraneoplastic
disorders,
SACD, Tabes dorsalis.
Cerebellar
ataxia
Sensory ataxia
Scanning speech

Normal speech

Nystagmus and other ocular signs

Absent

Sensory exam normal, Romberg

test negative

Sensory loss, Rombergs test

postive

Pendular reflexes

Hypo to aeflexia

Reeling, ataxic gait

Stamping gait

Differentiation of vestibular and

cerebellar ataxia
Vestibular ataxia is due to lesion of vestibular pathways
resulting
in impairment & imbalance of vestibular inputs. e.g.
vestibular,
Cerebellar ataxia
Vestibular disorders
neuronitis, streptomycin toxicity.
Sense of imbalance

Vertigo and associated tinnitus and

hearing loss

Past pointing is in the ipsilateral limb

and in the direction of the lesion

Present in both the limbs and in the

direction of the lesion

Gaze evoked rystagmus

Direction of the rystagmus in away from

the lesion

Scanning speech, intention tremors,

dysdiadochokinesia, rebound
phenomena, hypotonia and pendular
reflexes

Absent

Differentiation between cerebellar

and frontal lobe disorder
Frontal lobe ataxia (Bruns ataxia) is due to involvement
of
subcortical small vessels, Binswangers disease, multi
infarct
Cerebellar

Frontal Lobes

Base of support

Wide based

Wide based

Velocity

Variable

Very slow

Stride

Irregular, lurching

Short, shuffling

Heal to shin

Abnormal

Normal

Initiation

Normal

Hesitant

Turns

Unsteady

Hesitant, Multistep

state or NPH.

Postural instability *

****

Falls

Frequent

Late events

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Important points in history

Age at onset
Mode of onset
Precipitating factors
Rate of progression
Symptoms of raised ICP
Presence of systemic symptoms
Drug history and toxin exposure
Family history

Examination
Neck tilt and titubation
Nystagmus and other ocular movement
abnormalities
Dysarthria
Intention tremor
Hypotonia
Past pointing
Rebound phenomenon
Macrographia
Stance
Ataxic Gait
Pendular knee jerk

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Individual with
progressive
ataxia
Autosomal
recessive or
uncertain
inheritance

Negative
FH
<25
years
old

Exclude
secondary
causes

ARCAs, X-linked and

mitochondrial inherited
Test for:
FRDA (GAA); AT (fetoprotein);
AVED (vit. E level);
Refsums
(phytanic acid); Wilsons
Negativ
e

Test for
other
recessive
ataxias

ADCA I
(ataxia + CNS
signs)
SCA 1, 2, 3, 4,
8, 12,
17, and FGF 14

Autosomal
dominant
inheritance
>25
years
old
Consid
er
ADCAs
Hardings
classification

ADCA II
(cerebellar
syndrome +
pigmentary
maculopathy)
SCA 7

ADCA III
(pure
cerebellar
syndrome)
SCA 5, 6, 10,
11,
14, 15, and 22

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Diagnosis of hereditary ataxia

Insidious onset, symmetrical, and progressive
Age at onset
Early onset ataxia (age at onset below 25 years) is more
likely to be consistent with autosomal recessive inheritance
Exceptions Friedreichs ataxia, Tay Sachs disease
Late onset ataxia (age at onset over 25 years) is usual for
those ataxias with dominant inheritance.
Exceptions, SCA7, DRPLA, EA-1, EA-2
Family history:
- Direct questioning of patient and relatives.
- H/o consanguinity
- Pedigree charting
- Negative family history does not exclude the diagnosis

Causes Of negative F/H

May be seen in
- Adoption
- Genetic non paternity
- Anticipation
- De novo mutation
- Small family size
- In X-linked inheritance only males are
affected.
- In mitochondrial disorders matrilineal mode
of
inheritance may be apparent although
penetrance is
variable

Clinical features of Friedreichs

Ataxia
Autosomal recessive inheritance
Onset before 25 years
Progressive limb and gait ataxia
Absent DTR in legs
Electrophysiological evidence of axonal
sensory neuropathy
Dysarthria*
Areflexia in all four limbs*
Distal loss of position and vibration sense*
Extensor plantar responses*
Pyramidal weakness of the legs*
*Develop within 5 years of onset of disease

Autosomal dominant ataxias

Heterogenous group of disorders with onset after
25 years
25 different genetic loci have been identified
(SCA1 to SCA2)
Have diverse associated neurological features
(retinopathy, optic atrophy, extra pyramidal or
pyramidal signs, peripheral neuropathy, cognitive
impairment, or epilepsy)
Most common forms-SCA1, SCA2 and SCA.

Bedside differentiation of SCAs

Large study n=526 patients (17 centres) with SCA 1,2,
3 or 6:
- Pyramidal signs (67%) and brainstem oculomotor
sign (74%) were most frequent in SCA 1
- PN involvement was most frequent in SCA 2 (68%)
- 24% of patients with SCA3 had dystonia
A decrease in visual (83%) and auditory (24%) acuity
was
the predominant sign in SCA7
No clinician can accurately distinguish between
different
David G,polyglutamine
et al., Human Med expansion
Genet 1998; 7:SCAs;
165-70 but this form
Maschke
et al.,
Mov Disord 2005;
20: 1405-12
of SCA
canM,be
distinguished
from
other SCA types
Schmitz-Hubsch T, et al., Neurology 2008; 71: 982-9

Clues to the SCAs

Clinical Features

Age at onset

Genetic Forms

Young adult: SCA 1, 2, 3, 21

Older adult: SCA 6
Childhood onset: SCA 7, 13, DRPLA
Upper motor neuron
SCA 1, 3, 7, 12
signs
Some in SCA 6, 8
Rare in SCA 2
Slow saccades
Early, prominent: SCA 2, 7, 12
Late: SCA 1, 3
Rare: SCA 6
Extra-pyramidal signs
Early chorea: DRPLA
Akinetic-rigid, Parkinson: SCA 2, 3, 21
Generalized areflexia
SCA 2, 4, 19, 21
Late: SCA 3
Rare: SCA 1
Visual loss
SCA 7
Dementia
Prominent: SCA 17, DRPLA
Early: SCA 2, 7
Otherwise: rare
Myoclonus
SCA 2, 14
Tremor
SCA 12, 16, 19
Seizures
SCA 10

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Classification of acquired
cerebellar ataxias
Ataxias due to toxic reasons
Alcoholic cerebellar degeneration (ACD)
Ataxias due to other toxic reasons
Immune-mediated ataxias
Paraneoplastic cerebellar degeneration (PCD)
Other immune-mediated ataxias
Ataxias due to vitamin deficiency
Ataxias due to other rare causes

Symmetrical acquired ataxias

Acute
- Drugs: phenytoin, phenobarbitone, lithium,
Chemotherapeutic agents
- Alcohol
- Infectious: Acute viral cerebellitis, Post-infectious
- Toxins: Toulene, glue, gasoline, methyl mercury
Subacute
- Alcohol, or Nutritional (B1, B12)
- Paraneoplastic
- Antigliadin or anti GAD antibody
- Prion diseases
Chronic
- MSA-C
- Hypothyroidism
- Phenytoin toxicity

Asymmetrical acquired ataxias

Acute
- Vascular: Cerebellar infarction or hemorrhage,
Subdural
Haemotoma
- Infectious: Abscess
Subacute
- Neoplastic : Glioma, metastates, lymphoma
- Demyelination : MS
- HIV related : Progressive multi-focal leucoencephalopathy
Chronic
- Congenital lesions: Arnold Chiari malformation, Dandy
Walker syndrome

Tumors that produce ataxia

Medulloblastoma
Astrocytoma
Ependymoma
Hemangioblastoma
Metastatic tumor
Meningioma
Cerebellopontine angle
schwannoma

Sporadic ataxia
All acquired causes have been ruled out and
there is no family history
A genetic explanation for sporadic ataxia is
obtained in 4-22%
SCA6 is the most common dominant mutation
detected in between 6% and 13% of patients
The frequency of the Freiedreichs GAA expansion
among cases of adult-onset is between 4 and 8%.

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Treatment
Identify treatable causes of ataxia
No proven therapy for SCAs
Some patients with parameoplastic cerebellar
syndrome improve following removal of tumour
and immunotherapy
Preliminary evidence suggests that idebenone, a
free radical scavenger improves myocardial
hypertrophy
Genetic counselling can reduce risk in future

Treatable causes of ataxia

Hypothyroidism
AVED
Vitamin B12 deficiency
Wilsons Disease
Ataxia with anti-gliadin antibodies and gluten
senstive enteropathy
Ataxia due to malabsorption syndromes
Lymes disease
Mitochondrial encephalomyopathies,
aminoacidopathies, Leukodystrophies and urea
cycle abnormalities

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

Conclusion
Thorough history and examination is required
Age at onset and family history are most
important
Hereditary ataixas can be divided into early onset
(<25 years) or late onset (> 25 years)
Early onset ataxias are usually recessive, while
late onset ataxias are usually dominant
Friedreichs ataxia is the most common recessive
disorder while SCA2 is the most common
dominant disorder.
Contd

Conclusion contd

No single physical sign is specific for a single

disorder
Investigations should be performed in a logical order
Treatable causes should be excluded

Outline of todays lecture

Clinical Scenario
Anatomy and Physiology
Is it Cerebellar Ataxia
History and Examination
Classification
Hereditary Ataxias
Acquired Ataxias
Treatment
Conclusion
MCQs

1. A horizontal gaze evoked nystagmus in which the

direction of the fast phase reverses with sustained
lateral gaze or beats transiently in the opposite
direction when the eyes return to primary position is
called
A. Periodic alternating nystagmus
B. Seesaw nystagmus
C. Rebound nystagmus
D. Dysconjugate nystagmus

1. A horizontal gaze evoked nystagmus in which the

direction of the fast phase reverses with sustained
lateral gaze or beats transiently in the opposite
direction when the eyes return to primary position is
called
A. Periodic alternating nystagmus
B. Seesaw nystagmus
C. Rebound nystagmus
D. Dysconjugate nystagmus

2. The typical signs of cerebellar herniation include the

following
EXCEPT
A. Stiff neck
B. Alteration of consciousness
C. Ptosis and pupillary abnormality
D. Cardiac and respiratory abnormalities

2. The typical signs of cerebellar herniation include the

following
EXCEPT
A. Stiff neck
B. Alteration of consciousness
C. Ptosis and pupillary abnormality
D. Cardiac and respiratory abnormalities

3. Rombergs sign is positive in which type of lesion :

A. Cerebellar
B. Posterior column
C. Hysterical
D. Vestibular

3. Rombergs sign is positive in which type of lesion :

A. Cerebellar
B. Posterior column
C. Hysterical
D. Vestibular

4. Hardings classification of cerebellar ataxia is

based upon :
A. Mode of inheritance
B. Site of involvement
C. Chromosomal abnormality
D. Metabolic abnormality

4. Hardings classification of cerebellar ataxia is

based upon :
A. Mode of inheritance
B. Site of involvement
C. Chromosomal abnormality
D. Metabolic abnormality

5. Which statement is not true of Friedreichs

ataxia?
A. Recessive inheritance
B.Dysarthria
C. Flexor plantar response
D. Absent ankle jerk

5. Which statement is not true of Friedreichs

ataxia?
A. Recessive inheritance
B.Dysarthria
C. Flexor plantar response
D. Absent ankle jerk

6. Alcoholic cerebellar degeneration is

characterized by :
A. Gaze evoked nystagmus
B. Limb ataxia
C. Gait ataxia
D. Action myoclonus

6. Alcoholic cerebellar degeneration is

characterized by :
A. Gaze evoked nystagmus
B. Limb ataxia
C. Gait ataxia
D. Action myoclonus

7. Cerebellar ataxia can result from intoxication

with :
A. Lead
B. Mercury
C. Manganese
D. Gold

7. Cerebellar ataxia can result from intoxication

with :
A. Lead
B. Mercury
C. Manganese
D. Gold

8. Wadias type of spinocerebellar degeneration is

characterized by
A. Limitation of downgaze
B. Limitation of upgaze
C. Slowing of saccadic movements
D. Broken smooth pursuit

8. Wadias type of spinocerebellar degeneration is

characterized by
A. Limitation of downgaze
B. Limitation of upgaze
C. Slowing of saccadic movements
D. Broken smooth pursuit

9. Which of the following spinocerebellar ataxias (SCAs)

has a similar
ion channel, genetic and chromosomal abnormality
as familial
hemiplegic migraine
A. SCA type 2
B. SCA type 4
C. SCA type 6
D. SCA type 8

9. Which of the following spinocerebellar ataxias (SCAs)

has a similar
ion channel, genetic and chromosomal abnormality
as familial
hemiplegic migraine
A. SCA type 2
B. SCA type 4
C. SCA type 6
D. SCA type 8

10. A combination of ipsilateral oculomotor palsy and

ipsilateral
cerebellar ataxia is seen in which of the brainstem
syndromes
A. Claude
B. Nothnagel
C. Weber
D. Benedikt

10. A combination of ipsilateral oculomotor palsy and

ipsilateral
cerebellar ataxia is seen in which of the brainstem
syndromes
A. Claude
B. Nothnagel
C. Weber
D. Benedikt