Approach to a patient with ataxia - PowerPoint Presentation

Slide1

Approach to a patient with ataxia

Dr Rakesh Shukla

Professor Of NeurologySlide2

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).

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Slide4
Slide5

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide6

Clinical scenario

RK, 22 years young man presented with

C/O headache, double vision, difficulty in walking 20-25 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 feverSlide7

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, Romberg’s sign negative, no motor weakness,

DTR normal, planter’s bilateral flexor

Diag Acute onset cerebellar syndrome presenting as gait

ataxia

D/D chronic subdural haematoma, phenytoin intoxication

Clinical scenarioSlide8

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 normalSlide9

Imaging: CECT scan brainSlide10

Imaging: MRI scan brainSlide11

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide12

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 cm

3

and weighs 150g (

~10% of brain weight), but its surface area is about 40% that of the cerebellar cortex.Slide13

Dorsal view of the cerebellum Slide14

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

Slide15

Cerebro-cerebello-cerebral circuit

Slide16

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 ataxiaSlide17

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide18

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. Sjogren’s syndrome, cisplatin, CCNU, Para-neoplastic

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, Romberg’s test

postive

Pendular

reflexes

Hypo to aeflexia

Reeling, ataxic gait

Stamping gaitSlide19

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,

neuronitis, streptomycin toxicity.

Cerebellar

ataxia

Vestibular disorders

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

AbsentSlide20

Differentiation between cerebellar and frontal lobe disorder

Frontal lobe ataxia (Brun’s ataxia) is due to involvement of

subcortical small vessels, Binswanger’s disease, multi infarct

state or NPH.

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

Postural instability

*

****

Falls

Late events

FrequentSlide21

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide22

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 historySlide23

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 jerkSlide24
Slide25

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide26

Individual with progressive ataxia

Negative FH

Autosomal recessive or uncertain inheritance

Autosomal dominant inheritance

Exclude secondary causes

>25 years old

<25 years old

ARCAs, X-linked and

mitochondrial inherited

Consider ADCAs

Test for:

FRDA (GAA); AT (

α

-fetoprotein);

AVED (vit. E level); Refsum’s

(phytanic acid); Wilson’s

Harding’s classification

Negative

ADCA I

(ataxia + CNS signs)

SCA 1, 2, 3, 4, 8, 12,

17, and FGF 14

ADCA II

(cerebellar syndrome + pigmentary maculopathy)

SCA 7

ADCA III

(“pure” cerebellar syndrome)

SCA 5, 6, 10, 11,

14, 15, and 22

Test for other

recessive

ataxiasSlide27

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide28

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 Friedreich’s 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 diagnosisSlide29

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

Slide30

Clinical features of

Friedreich’s

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 diseaseSlide31

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.Slide32

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 polyglutamine expansion SCAs; but this form of SCA can be distinguished from other SCA types

David G, et al., Human Med Genet 1998; 7: 165-70

Maschke M, et al., Mov Disord 2005; 20: 1405-12

Schmitz-Hubsch T, et al., Neurology 2008; 71: 982-9Slide33

Clues to the SCAs

Clinical Features Genetic Forms

Age at onset

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 10Slide34

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide35

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 causesSlide36

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 toxicitySlide37

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 leuco-encephalopathy

Chronic

- Congenital lesions: Arnold Chiari malformation, Dandy Walker syndrome

Slide38

Tumors that produce ataxia

Medulloblastoma

Astrocytoma

Ependymoma

Hemangioblastoma

Metastatic tumor

Meningioma

Cerebellopontine

angle

schwannomaSlide39

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 Freiedreich’s GAA expansion among cases of adult-onset is between 4 and 8%. Slide40

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide41

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 generationsSlide42

Treatable causes of ataxia

Hypothyroidism

AVED

Vitamin B12 deficiency

Wilson’s Disease

Ataxia with anti-gliadin antibodies and gluten senstive enteropathy

Ataxia due to malabsorption syndromes

Lyme’s disease

Mitochondrial encephalomyopathies, aminoacidopathies, Leukodystrophies and urea cycle abnormalitiesSlide43

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide44

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

Friedreich’s

ataxia is the most common recessive disorder while SCA2 is the most common dominant disorder.

Contd…Slide45

No single physical sign is specific for a single disorder

Investigations should be performed in a logical order

Treatable causes should be excluded

Conclusion

contd

…Slide46

Outline of today’s lecture

Clinical Scenario

Anatomy and Physiology

Is it Cerebellar Ataxia

History and Examination

Classification

Hereditary Ataxias

Acquired Ataxias

Treatment

Conclusion

MCQsSlide47

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

nystagmusSlide48

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

nystagmusSlide49

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 abnormalitiesSlide50

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 abnormalitiesSlide51

3. Romberg’s sign is positive in which type of lesion :

A. Cerebellar

B. Posterior column

C. Hysterical

D. VestibularSlide52

3. Romberg’s sign is positive in which type of lesion :

A. Cerebellar

B. Posterior column

C. Hysterical

D. VestibularSlide53

4. Harding’s classification of cerebellar ataxia is based upon :

A. Mode of inheritance

B. Site of involvement

C. Chromosomal abnormality

D. Metabolic abnormalitySlide54

4. Harding’s classification of cerebellar ataxia is based upon :

A. Mode of inheritance

B. Site of involvement

C. Chromosomal abnormality

D. Metabolic abnormalitySlide55

5. Which statement is not true of

Friedreich’s

ataxia?

A. Recessive inheritance

B.Dysarthria

C. Flexor plantar response

D. Absent ankle jerkSlide56

5. Which statement is not true of

Friedreich’s

ataxia?

A. Recessive inheritance

B.Dysarthria

C. Flexor plantar response

D. Absent ankle jerkSlide57

6. Alcoholic cerebellar degeneration is characterized by :

A. Gaze evoked

nystagmus

B. Limb ataxia

C. Gait ataxia

D. Action

myoclonusSlide58

6. Alcoholic cerebellar degeneration is characterized by :

A. Gaze evoked

nystagmus

B. Limb ataxia

C. Gait ataxia

D. Action

myoclonusSlide59

7. Cerebellar ataxia can result from intoxication with :

A. Lead

B. Mercury

C. Manganese

D. GoldSlide60

7. Cerebellar ataxia can result from intoxication with :

A. Lead

B. Mercury

C. Manganese

D. GoldSlide61

8.

Wadia’s

type of

spinocerebellar

degeneration is characterized by

A. Limitation of

downgaze

B. Limitation of

upgaze

C. Slowing of saccadic movements

D. Broken smooth pursuit Slide62

8.

Wadia’s

type of

spinocerebellar

degeneration is characterized by

A. Limitation of

downgaze

B. Limitation of

upgaze

C. Slowing of saccadic movements

D. Broken smooth pursuit Slide63

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 8Slide64

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 8Slide65

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.

BenediktSlide66

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