2. INTRODUCTION
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
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
10. 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
11.
12. 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)
17. ATAXIA
“errors in the RATE, RANGE, FORCE & DIRECTION
of movement”
•GAIT ATAXIA
•TRUNCAL ATAXIA
•LIMB ATAXIA
18. 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
19. 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")
20. 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)
36. TOXINS
• Cancer chemotherapeutics 5 FU, Cytarabine
• Metals Bismuth, Mercury (parasthesiass,
restricted visual defects), Lead
• SolventsPaint thinners , toluene (Cognitive
defects PLUS pyramidal tract signs)
• AnticonvulsantsPhenytoin (purkinje cell
loss)avoid in epileptics with ataxia
37. INFECTIONS
• VZV in children
• EBV in children
• Bickerstaff’s encephalitis (brain
stemophthalmoplegia,ataxia,lower c.n
palsies)
• HIV ( Lymphomas, PML, Infections,
Toxoplasmosis)
• CJD (17% classic CJD, Ataxic variant of CJD)
• Syphilis (Tabes Dorsalis)
• Whipple’s disease
38. 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)
39. • GLUTEN SENSITIVITY - Anti Gliadin abs.
(ataxia, brisk reflexes, peripheral neuropathies)
• ANTI GAD abs. – Diabetes, hypothyroidism,
peripheral neuropathySTIFF PERSON
syndrome
AUTOIMMUNE CAUSES
45. 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
SCAresponsible for various ages of
presentation and variable phenotypic
expression
• CAG repeat expansion in most of them
46. Spinocerebellar Ataxia (SCA)
Dominant SCA syndromes have many overlapping signs: Difficult to
distinguish on clinical grounds
Common features to all: Gait ataxia; Dysarthria
Features in some ataxias: Ocular D; Extrapyramidal; Peripheral nerve;
Intellectual D; Seizures
Features with some predictive value for specific gene defects
47. SCA: Clinical Syndromes
•SCA 1: Hypermetric saccades; ++Tendon reflexes; Evoked motor
potentials Long conduction times
•SCA 2 Slowing saccads; Myoclonus or action tremor
•SCA 3/Machado-Joseph: Gaze-evoked nystagmus; Prominent
spasticity or neuropathy
•SCA 4: Cerebellar syndrome; Sensory neuropathy
•SCA 5: Pure cerebellar syndrome
•SCA 6: Pure cerebellar syndrome; -ve family history; Late onset > 50
•SCA 7: Retinal degeneration; Hearing loss; Onset in 1st decade
•SCA 8: Pure cerebellar syndrome
•SCA 10: Pure cerebellar syndrome ± Seizures
•SCA 11: Pure cerebellar syndrome
•SCA 12: Early arm tremor; Late dementia
•SCA 13: Early childhood onset; Mental retardation
•SCA 14: Ataxia; Myoclonus (with early onset)
48. Relationship between ADCAs and SCAs
ADCA type SCA type
I -Cerebellar plus
(Pyramidal, Extra-pyramidal,
Ophthalmoplegia, & Dementia) 1,2,3,4,12,16,17, DRPLA
II Cerebellar + pigmentary
maculopathy 7
III pure cerebellar ± Mild
pyramidal signs 5,6,8,11,14,15,22
Ataxia and epilepsy 10
Early onset with mental retardation 13
55. • TYPE 3-ATAXIC AMYYOTROPHIC
• CEREBELLAR SYMPTOMS
• DISITAL SENSORY LOSS
• DISITAL ATROPY
• DEPRESSED OR ABSENT DTR
• NO PYRAMIDAL OR EXTRA PYRAMIDAL
SYMPTOMS
56. DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; DRPLA
MYOCLONIC EPILEPSY WITH CHOREOATHETOSIS
NAITO-OYANAGI DISEASE; NOD
ATROPHIN 1, INCLUDED
CLINICAL SYNOPSIS
Neurological:
Miscellaneous:
Labs:
Gene Map Locus: 12p13.31 CAG 49-75
(N<24)
Myoclonus
epilepsy ( longer repeats)
Dementia
Ataxia
Choreoathetosis
Onset usually in the 20s and death in the
40s
commaon in Japan
Combined degeneration of dentatorubral
and pallidoluysian systems
DRPLA protein , neuronal cytoplasm
57. EPISODIC ATAXIA, TYPE 1; EA1
PAROXYSMAL ATAXIA WITH NEUROMYOTONIA, HEREDITARY
EPISODIC ATAXIA WITH MYOKYMIA; EAM
ATAXIA, EPISODIC, WITH MYOKYMIA; AEM; AEMK
MYOKYMIA WITH PERIODIC ATAXIA
CLINICAL SYNOPSIS
Neurological
Miscellaneous
Labs
Treatment
Gene Map Locus: 12p13
Myokymia
Continuous muscle movement
Periodic ataxia
Continuous muscle movement
Periodic ataxia
Ataxic attacks provoked by abrupt postural
change, emotional stimulus, and caloric-vestibular
stimulation, startle
Onset in second decade
Hand posture resembling carpopedal spasm
Potassium voltage-gated channel gene mutation
Continuous spontaneous activity on EMG at rest
Muscle biopsy consistent with denervation, with
enlargement of muscle fiber
Phenytoin, not Acetazolamide
58. EPISODIC ATAXIA, TYPE 2; EA2
PERIODIC VESTIBULOCEREBELLAR CEREBELLOPATHY,
HEREDITARY PAROXYSMAL ATAXIA,
FAMILIAL PAROXYSMAL ATAXIA
ACETAZOLAMIDE-RESPONSIVE PAROXYSMAL CEREBELLARATAXIA; APCA
EPISODIC ATAXIA, NYSTAGMUS-ASSOCIATED CEREBELLAR ATAXIA
CLINICAL SYNOPSIS
Neurological
Miscellaneous
Labs
Treatment
Gene Map Locus: 19p13
Episodic ataxia
Cerebellar ataxia
Vertigo
Diplopia
Downbeat nystagmus
Ataxia precipitated by stress or
excitement, not by startle
attacks last 1/2 to 6 hrs.
point mutation alpha 1A calcium
voltage dependant channel
allelic with SCA6 & familial
hemiplegic migraine
Response to oral acetazolamide
63. • 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
64. ATAXIA TELANGIECTASIA
• OCULOMOTOR APRAXIA , TELANGIECATSIAS
IN EYES, SKIN
• Hematological malignancies (defective DNA
repairs)
• Infections (Ig deficiencies)
• Other features-peripheral neuropathy,
choreoathetosis
67. X linked ATAXIAS
• X linked Dominant- Fragile X syndrome
• CGG repeats’ expansion
68. • X linked Recessive Ataxias- Sideroblastic
anemia with ataxia
X linked ATAXIAS
69. 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
70. 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)
71. 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
72. 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
73. 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
74. 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
75. 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)
76. 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
Atxaia can be a component of any of these systems involvement….
BUT THEN HOW ARE WE GOING TO SAY THAT THE ATAXIA OF THE PT IS BECAUSE ONLY BCOS OF CEREBELLAR INVOLVEMENT…BY TESTING THE CELEBELLAR FUNCTIONS….WE MUST KNOW WHAT TESTS ARE TO BE DONE TO ELICIT THIS DYSFXN….THATS EASY TO UNDERSATND IF WE KNOW THE CLINICAL ASPECTS OF ANATOMY, PHYSIO AND VASCULAR SUPPLY IF CERE….
LOCALOSATION OF SYMP AND SIGNS…
IN ADDITION TO ATAXIA………OTHER…..trouble coordinating complex movements including contraction of agonist and antagonist muscle pairs;
inaccuracy in reaching target due to premature arrest of movement (hypometria) or overshoot the target (hypermetria)
trouble with rapid alternating movements such as pronation-supination of arm, with
Abnormalitites in breathing and its integration with speech
We are looking at the variuos causes and salient features of each will be discussed shortly……