Transcript Approach to a patient with ataxia

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 today’s 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 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 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, 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
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 today’s 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
 Lateralized
 Generalised
 Acute




Chronic
Vestibulo cerebellar
Vermis
Cerebellar hemispheres
Manifestations
Ipsilateral signs and symptoms
Bilateral symmetrical symtomatology
Severe abnormalities at onset,
remarkable recovery with time
Gradual progressive decline
Disequilibrium and an ataxic gait
Truncal and gait ataxia
Appendicular ataxia
Outline of today’s 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. 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 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,
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
Absent
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
Frequent
Late events
Outline of today’s 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 today’s 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
Negative FH
Autosomal recessive or
uncertain inheritance
<25 years
old
Exclude secondary
causes
ARCAs, X-linked and
mitochondrial inherited
Test for other
recessive
ataxias
>25 years
old
Consider
ADCAs
Test for:
FRDA (GAA); AT (α-fetoprotein);
AVED (vit. E level); Refsum’s
(phytanic acid); Wilson’s
Negative
Autosomal dominant
inheritance
ADCA I
(ataxia + CNS signs)
SCA 1, 2, 3, 4, 8, 12,
17, and FGF 14
Harding’s 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 today’s 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 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 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 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 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
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: 982-9
Clues to the SCAs
Clinical Features
Age at onset
Upper motor neuron
signs
Slow saccades
Extra-pyramidal signs
Generalized areflexia
Visual loss
Dementia
Myoclonus
Tremor
Seizures
Genetic Forms
Young adult: SCA 1, 2, 3, 21
Older adult: SCA 6
Childhood onset: SCA 7, 13, DRPLA
SCA 1, 3, 7, 12
Some in SCA 6, 8
Rare in SCA 2
Early, prominent: SCA 2, 7, 12
Late: SCA 1, 3
Rare: SCA 6
Early chorea: DRPLA
Akinetic-rigid, Parkinson: SCA 2, 3, 21
SCA 2, 4, 19, 21
Late: SCA 3
Rare: SCA 1
SCA 7
Prominent: SCA 17, DRPLA
Early: SCA 2, 7
Otherwise: rare
SCA 2, 14
SCA 12, 16, 19
SCA 10
Outline of today’s 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 leuco-encephalopathy
 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 422%
 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%.
Outline of today’s 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 generations
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 abnormalities
Outline of today’s 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
 Friedreich’s 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 today’s 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. Romberg’s sign is positive in which type of lesion :
A. Cerebellar
B. Posterior column
C. Hysterical
D. Vestibular
3. Romberg’s sign is positive in which type of lesion :
A. Cerebellar
B. Posterior column
C. Hysterical
D. Vestibular
4. Harding’s classification of cerebellar ataxia is based upon :
A. Mode of inheritance
B. Site of involvement
C. Chromosomal abnormality
D. Metabolic abnormality
4. Harding’s 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 Friedreich’s ataxia?
A. Recessive inheritance
B.Dysarthria
C. Flexor plantar response
D. Absent ankle jerk
5. Which statement is not true of Friedreich’s 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. 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
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
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