This document discusses different types of ataxia, including their causes and clinical features. It begins by defining ataxia as a lack of muscle coordination during voluntary movements. It then covers various forms of ataxia such as cerebellar ataxia (the most common type), sensory ataxia affecting proprioception, cortical ataxia involving the frontal lobe, and thalamic ataxia. The document also discusses the classification of cerebellar ataxias into hereditary forms like autosomal dominant and recessive types, as well as the clinical assessment and diagnostic approach for ataxia.

1. Presenter-Dr Satya Prasad Mahapatra
Moderator- Dr Dhiraj Kishor
Approach To Ataxia

2. Ataxia
 Ataxia- from Greek- a- [lack of]+ taxia [order]
 Lack of order
 Of rate, rhythm and force of contraction of
voluntary movements.
 Disorganised, poorly co-ordinated or clumsy
movements
 Traditionally used specifically for lesions
involving;
 Cerebellum or it's pathways
 Proprioceptive sensory pathways

3. Neural-Localization
 Cerebellum (Most common)
 Sensory pathways (Sensory Ataxia)
 Posterior columns
 Dorsal root ganglia
 Peripheral nerve
 Frontal lobe lesions-fronto-cerebellar fibers

4. Sensory Ataxia
 Sensory neuropathy and posterior column
disease of the spinal cord (sensory ataxia )
 Loss of distal joint, position sense
 Absence of cerebellar signs such as dysarthria
or nystagmus
 Loss of tendon reflexes
 Corrective effects of vision on sensory ataxia
 Romberg sign

6. Cortical Ataxia
 FRONTAL LOBE ATAXIA refers to disturbed
coordination due to dysfunction of the
contralateral frontal lobe
 Results from disease involving
frontopontocerebellar fibers en route to synapse
in the pontine nuclei.
 Hyper-reflexia, 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

7. Vestibular Dysfunction
 Vertigo is prominent
 Consistent fall to one side
 Nystagmus
 Limb ataxia is absent
 Speech is normal
 Joint position sense is normal
 Patient complains of vertigo rather than
imbalance

8. Thalamic Ataxia
 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)

11. Clinical features of cerebellar
disease
 Ataxia(appendicular
or axial)
 Dysmetria
 Dyssynergia
 Dysdiadochokinesia
 Rebound
Phenomenon
 Dysarthria
 Tremor
 Titubation
 Increased Postural
Sway
 Hypotonia
 Asthenia
 Nystagmus

14. Cerebellar Ataxia: Classification
 Acquired or Congenital
 Acute or Sub-acute or Chronic
 Familial or Non familial
 AD or AR or Sporadic
 Ipsilateral signs or Bilateral signs
 Symmetrical or Asymmetrical
 Progressive , Static or Improving, Recurrent/
Episodic
 a/w Higher function, Cranial nerve,Extra-
pyramidal,Peripheral Neuropathy features.

15. Classification
 Hereditary Group:
 Autosomal Dominant cerebellar Ataxias
 Spinocerebellar ataxia type 1-31, SCA36, Episodic ataxias
 Autosomal Recessive cerebellar Ataxias
 Friedreich's ataxia, Ataxia Telengiectasia, Spastic ataxia
 X-linked cerebellar ataxias
 Fragile X tremor ataxia syndrome
 Mitochondrial
 Myoclonus Epilepsy with Ragged Red Fibers(MERRF)
 Kearns Syre Syndrome (KSS)
Contd...

16. Cerebellar Ataxia: Classification
(Contd..)
 Non hereditary Group (Sporadic)
 Degenerative progressive
o MSA-C, Idiopathic late onset cerebellar ataxia (IOCA)
 Non-progressive developmental disorders
o Cayman ataxia, Joubert syndrome
 Toxins induced cerebellar degeneration
o Alcohol, Anticonvulsants, Anticancer drugs etc
 Autoimmunity associated
o Multiple sclerosis, Gluten ataxia, Ataxia with anti-GAD Ab
 Paraneoplastic cerebellar degeneration
 Infection mediated
o Post viral infection cerebellitis, Enteric fever,
Adeno/retroviral, malaria, Prions

17. Cerebellar Ataxia:
Classification (Contd..)
 Developmental malformation(congenital)
o Dandy-Walker Malformation
o Chiari Malformation
o Vermial Agenesis

18. Diagnostic Approach
 Meticulous evaluation of History
 Age at Onset
 Course of disease
 Drug intake
 Family History
 Personal Social & Occupational information
 Distribution of ataxia
 History of other system illness
 Neurological evaluation
 Ancillary tests

19. History
 Age at onset
 Childhood
 (congenital, metabolic, infectious, posterior fossa tumors,
hereditary ataxias -more common)
 Adult
 (sporadic ataxias, hereditary ataxias)
 Course of illness(progression)
 Acute
 (metabolic/toxic, infectious, inflammatory, traumatic)
 Subacute
 (metabolic/toxic, infectious, inflammatory,
paraneoplastic, tumor)
 Chronic
 (more likely genetic, degenerative, tumour,
paraneoplastic)

20. History
 Drug intake:
o Phenytoin, Barbiturates, Lithium, Immunosuppressants(Methotrexate,
Cyclosporine), Chemotherapy(Fluorouracil, Cytarabine )
 Family history:
o Study at least 3 generations
o Consanguinity
o Ethnicity
 Social/Occupational History:
o Alcohol and drug use
o Toxins (Heavy metals, Solvents, Thallium)
o Smoking (Vascular)

21. History
 Distribution of ataxia:
 Symmetric- Acquired, Hereditary, Degenerative
ataxias
 Asymmetric- Vascular, Tumours, Congenital causes
 Other system illness
 Gastrointestinal symptoms- Gluten ataxia
 Mass lesion- Paraneoplastic ataxias

22. Harrison 20th

24. Examination
 Neurological Examination
 Other System Evaluation
 Breast Lump, mass per-abdomen etc.
 Rating Scales
 International Cooperative Ataxia Rating Scale
(ICARS)
 Scale for the assessment and rating of
ataxia(SARA)
 Unified MSA Rating Score (UMSARS)

25. Ancillary Tests
 Neuro imaging
MRI of brain and spine
 Electro-diagnostic tests
EMG/NCV, EEG, evoked potentials, ERG
 Tests of autonomic dysfunction
Tilt-table tests, sympathetic skin responses and
other tests
 Ophthalmologic examination
Pigmentary retinopathy, Macular degeneration,
Cataracts, Kayser-Fleischer rings

26. Ancillary Tests
 Genetic tests (available in India)
 AD: SCA 1, 2, 3, 6, 7, 8, 10, 11,12, 14, 17,23 and 28
 AR: FRDA, AOA1 and 2, AT, ARSACS
 X-linked: FXTAS
 Mitochondrial —entire genome sequencing
 Laboratory studies
 Metabolic
 Thyroid function, Vitamins B12, E, and B1, Serum
Cholesterol & Plasma lipoprotein profile, Serum
cholesterol & Urine bile alcohol, phytanic acid, toxicology
screen
 Immune function
 Immunoglobulin levels, Antigliadin antibodies, GAD antibodies,
paraneoplastic antibodies

27. Ancillary Tests
 Laboratory studies:
 Mitochondrial
 Serum lactate and pyruvate
 Other
 Heavy metals, Peripheral blood smear for acanthocytes, Very
long chain fatty acids, Hexosarninidase A/13, Alpha
fetoprotein & Immunoglobulins, Serum ceruloplasmin & 24
hour urinary copper
 Tissue Studies:
 Muscle, skin and nerve biopsies
 CSF Studies:
 Cell count, glucose and protein, oligoclonal bands, 14-3-3
protein, GAD antibodies, paraneoplastic antibodies, Lactate/
Pyruvate

28. Hereditary Group:
 Autosomal Dominant cerebellar Ataxias
 Spinocerebellar ataxia type 1-31, SCA36, Episodic ataxias
 Autosomal Recessive cerebellar Ataxias
 Friedreich's ataxia, Ataxia Telengiectasia, Spastic ataxia
 X-linked cerebellar ataxias
 Fragile X tremor ataxia syndrome
 Mitochondrial
 Myoclonus Epilepsy with Ragged Red Fibers(MERRF)
 Kearns Syre Syndrome (KSS)

29. INTRODUCTION:
 Autosomal Dominant Cerebellar Ataxias
 Clinically and Genetically heterogeneous group of
neurodegenerative disorders.
 Characterised by progressive cerebellar and spinal cord
dysfunction.
 Clinical Features:
 Gait Ataxia, Limb Incoordination, Dysarthria
 Pyramidal and Extrapyramidal involvement
 Occulomotor incordination
 Peripheral Neuropathy
 Retinal degeneration

32. Clinical Behavior of Common
SCA subtypes:
 Late onset 3rd to 4th decade.
 Diffuse Neuro degeneration
 Predominantly OPCA.
 Variable rates of progression
 Rapid progression: ADCA-I, ADCA-II and ADCA-IV
 Repeat expansion SCA progresses rapidly (except SCA6)
 Higher repeats leads to increase severity of the disease
 Slow progression: ADCA-III (Pure cerebellar forms)
 Variable age at onset
 Anticipation

36. Hereditary Group:
 Autosomal Dominant cerebellar Ataxias
 Spinocerebellar ataxia type 1-31, SCA36, Episodic ataxias
 Autosomal Recessive cerebellar Ataxias
 Friedreich's ataxia, Ataxia Telengiectasia, Spastic ataxia
 X-linked cerebellar ataxias
 Fragile X tremor ataxia syndrome
 Mitochondrial
 Myoclonus Epilepsy with Ragged Red Fibers(MERRF)
 Kearns Syre Syndrome (KSS)

37. Autosomal Recessive cerebellar
ataxias
 Introduction:
 Autosomal recessive cerebellar ataxia (ARCAs) are group
of neurodegenerative disorders
 More than 20 genes are known to cause ARCAs
 Infantile-adult onset (generally <25 yrs)
 Cerebellar ataxias with predominant peripheral
neuropathy
 Other features: Cardiac involvement, Muscular
involvement, immunodeficiency, metabolic derangements
etc
 FRDA accounts for the major prevalent ARCA

38. Friedreich ataxia
 One of the most common hereditary ataxias
 Prevalence: 2 - 4/100,000
 1 in 40,000 in Caucasians populations
 Carrier frequency:1/60-1/100
 Slowly progressive ataxia
 Initial presentation b/w 5-15yrs
 Most are wheelchair bound by late teens- Early 20s
 Scoliosis and pes cavus in 10%
 Heart abnormalities cause premature death in 60% to 80%
 Intronic GAA repeat expansions in the FXN gene
 About 25% of FXN mutation carriers have an atypical
phenotype, such as late onset, for example up to 64 years
 FA with retained tendon reflex The Cochrane Library 2012, Issue 4

45. Hereditary Group:
 Autosomal Dominant cerebellar Ataxias
 Spinocerebellar ataxia type 1-31, SCA36, Episodic ataxias
 Autosomal Recessive cerebellar Ataxias
 Friedreich's ataxia, Ataxia Telengiectasia, Spastic ataxia
 X-linked cerebellar ataxias
 Fragile X tremor ataxia syndrome
 Mitochondrial
 Myoclonus Epilepsy with Ragged Red Fibers(MERRF)
 Kearns Syre Syndrome (KSS)

46. X-linked ataxia
 Fragile X associated Tremor-Ataxia syndrome
(FXTAS)
 Major Diagnostic criteria:
 Onset >50 years, M>F
 Neurologic: Gait ataxia, tremor,
 parkinsonism, cognitive decline,
 polyneuropathy, autonomic dysfunction
 Systemic: Premature ovarian failure
 Brain MRI: cerebral/cerebellar atrophy,
T2 signal in middle cerebellar peduncles
 Neuropathology: intranuclear inclusions
in brain and spinal cord

47. FXTAS Genetic features
 Expanded CGG repeat
 FMR gene
 Chromosome Xq27.3
 Premutation repeat length
 55-200
 Elevated levels FMR1 mRNA
 Toxic gain of function?
 Decreased FMR1 mRNA translational efficiency

48. Sporadic ataxias
 Multiple system atrophy (MSA)
 Toxins/metabolic
 Paraneoplastic cerebellar degeneration
 Immune-mediated ataxias (gluten, anti-GAD)
 Infectious etiology

49. Beware of MSA C
 Clinical features:
 Parkinsonism
 Asymmetric, posture/action
tremor, early gait pro lems, +
dopy responsive
 Cerebellar
 Gait and limb ataxia, nystagmus,
dysarthria
 Autonomic
 Orthostatic hypotension, bladder
dysfunction, impotence
 Other
 Hyperreflexia, antecollis,
inspiratory trill r, RBD, dystonia
 Pathology:
 Neuronal cell loss and gliosis
 Glial cytoplasmic inclusions
 No Lewy bodies

51. Toxins-
Alcohoic Cerebellar
Degeneration(ACD)
• Features:
• Central Ataxia, Lower-limb tremor, Psychosis, Dementia
 Patho-phsyiology:
 Damage to GABA-A receptor, Impaired Glucose metabolism, Vit
B1 deficiency
 MRI:
 Superior cerebellar and cerebral atrophy
 Treatment:
 Alcohol abstinence, Vit B1 replacement

52. Toxins-
Drug Induced Ataxia-
 Metals – Bismuth, Mercury( paresthesias, resticted visual
defects), Lead
 Solvents- Paint thinners, Toluene( Cognitive defects +
Pyramidal tract signs)

53. Immune mediated-
Gluten Ataxia:
 Etiology- IgA/IgG Anti-Gliadin Ab, Anti-endomysial Ab and
Ab against Tissue Trans-glutaminase
 Clinical features- 50-60 years onset, Gait Ataxia,
Peripheral neuropathy and gluten sensitivity
 Patho-physiology- Ab targets PC due to share
antigenicity of gluten
 Investigation- Serum-IgA, IgG-antigliadin, anti
endomyseium,TTG, MRI-Cerebellar atrophy and WMH,
Intestinal Biopsy
 Rx- Gluten-free diet, I.V.I.G
Brain(2003),126,685-691

54. Immune mediated- GAD
ataxia
 Clinical phenotype:
 Onset 20-75 years
 F > M
 Neurologic: Ataxia, nystagmus, dysarthria
 Systemic: Autoimmune disease
 Studies: Anti-GAD Antibodies in serum, CSF
 Brain MRI: cerebellar atrophy in some
 Treatment:
 Steroids, IVIG?
Arch Neurol. 2001;58:22

55. Paraneoplastic cerebellar
degeneration
 Clinical features:
 Onset precedes neoplasm
 Pancerebellar syndrome: Gait and limb ataxia, dysarthria,
nystagmus, oculomotor dysfunction
 Evolution: Rapid over weeks to months, then stabilize
 Loss of Purkinje cells in the cerebellar cortex, deep
cerebellar nuclei & inferior olivary nuclei
 ? T cell mediated
 PCD can be associated with any cancer, but most common:
o Lung cancer (small-cell)
o Ovarian/Breast carcinoma
o Hodgkins lymphoma
Brain (2003) :126 ; 1409-1418

56. Paraneoplastic ataxia associated
antibodies:
Brain (2003) :126 ; 1409-1418

57. When to suspect?
 Age :Late (60 -70 yrs)
 Onset: Sub acute
 Progression: weeks to months then stabilize
 Compatible clinical history
 CSF : Pleocytosis, oligoclonal bands
 MRI: Normal in initial stage, cerebellar atrophy develops
in subsequent months
 FDG-PET Scan: Hypermetabolism
 If initial screening is negative , repeat screening is
advisable

58. Vitamin deficiency induced Ataxias

59. INFECTIONS
 VZV in children
 EBV in children
 Bickerstaff's encephalitis(Brainstem-
Opthalmoplegia, ataxia, lower cranial nerve
palsies)
 HIV ( Lymphomas, PML, Infections,
Toxoplasmosis)
 OD (17% classic OD, Ataxic variant of CJD)
 Syphilis (Tabes Dorsalis)
 Whipple's disease

61. Diagnostic approach to sporadic
adult-onset ataxia

62. Diagnostic approach to
sporadic adult-onset ataxia

64. Ataxia with seizures Ataxia with Dementia
 Anti GAD ataxia
 Anti gliadin ataxia
 Mitochondrial
ataxia
 Episodic ataxia
 DRPLA
 SCA 10, SCA 7
 CJD
 Anti gliadin ataxia
 FXTAS syndrme
 SCA 17, 19, 21, 2, 1, 6
 HIV/AIDS
 Mitochondrial disease
 Amyloid ataxia

65. Ataxia with Neuropathy
 Friedreich ataxia
 AOA2
 Fragile X syndrome
 Vit E deficiency ataxia
 Anti gliadin ataxia
 SCA 12, 18,25,27,8,3,4
 ARSACS
 Refsum disease
 Ataxic sensory neuronopathy of Sjogren
syndrome

68. APPROACH

69. CASE
HISTORY
• 40 year old female, right handed
individual, school teacher by occupation from
kGF came with complaints of

70. CASE
CHIEF COMPLAINTS
• SWAYING forwards and sideways while
getting up from supine posture — 2 yrs

71. CASE
HOPI
• Apparently normal 2 yrs ago
• She noticed swaying forwards and side ways while
getting up from supine posture and while walking in
narrow passages. gradual onset, slowly progressive
• She started appreciating worsening of swaying
whenever she stood in attention posture with hands
held behind during morning school prayer hours.
• Clumpsiness of hands present in the form of illegible
handwriting but not small in size.

72. CASE
• No involuntary movements like tremors.
• She is able to sit up and stand without support.
• No change in speech
• She did not complain of tightness or loosening of
limbs
• No h/o dizziness/light headedness/or perception
of movement.
• No h/o tinnitus

73. CASE
• No back pain or radiating pain
• No difficulty in walking /gripping slippers
• No difficulty in mixing food /reaching out
objects
• Able to differentiate hot /cold water
• Able to feel the floor
• Washbasin sign - negative

74. CASE
• No h/o altered sensorium,
• No h/o disorientation.
• She was able to precieve the smell normally
• She was able to read the news paper
• No h/o double vision
• No h/o reduced sensations over face and she
was able to chew the food.

75. CASE
• She was able to close the eyes and no h/o
deviation of ankle of mouth or drooling of
saliva.
• No h/o hard of hearing,no vertigo
• No h/o dysphagia,nasal regurgitation
• No h/o dysarthria

76. CASE
• She was able to feel the sensation of the
bladder,initiate and control
micturiation,completely evacuate the bladder.
• No h/o bowel incontinence constipation.
• No h/o any altered sweating pattern

77. CASE
• No h/o fever, headace,seizures
• No h/o loss of appetite / weight loss
• No h/o skin rashes
• No h/o trauma
• No h/o any drug intake/exposure to toxins
• No h/o recent vaccination

78. Swaying gait
How to utilize history in localization?

81. How to approach a
patient with sub-acute
unilateral/focal ataxia

83. How to approach a patient
with chronic unilateral/focal
ataxia

85. How will you approach a
patient with chronic
symmetrical ataxia?

87. How will you approach a
patient with symmetrical
sub-acute ataxia

89. How will you approach a
patient with acute
symmetrical ataxia

91. Acquired Vs genetic causes of
ataxia

92. ACQUIRED CAUSES OFATAXIA
Vascular: ischemic stroke, hemonliagic stroke. AV malformations
Infectious: Acute cerebellitis, postinfectious encephalomyelitis"
cerebellar abscess, HIV
Toxic: Alcohol. anticonvulsants, mercury, 5-FU. crtosine arabinoside.
Neoplasticicompressive: Gliomas. ependymomas. meningiomas. basal meningeal
carcinomatosis, craniovertebral junction abnonnalities
Immune: Multiple sclerosis. paraneoplastic syndromes, anti-GAD.. gluten ataxia
Deficiency: Hypothyroidism.. vitamin B1 and B125 vitamin F
GENETIC CAUSES OFATAXIA
Autosomal recessive: FA. AT. AVED, AOA 1. AOA 2, other inborn errors of
metabolism
Autosomal dominant: SCA types 1 through 28, episodic ataxias (types 1. 2)

93. Ataxias based on age of onset

97. Ataxia due to drugs and toxins
What to remember during history?

98. Drugs
• Anti-epileptics
Phenytion, carbamazepine,
Barbiturates,gabapentin,
topiramate
• Chemotherapeutic agents
5-FU, cisplatin, paclitaxel,
Cyclosporin,methotrexate
• Anti psychotics
lithum
• cardiac amiodarone
• Antibiotics metronidazole

99. Toxin induced ataxia
• Cocaine and heroin
• Metals: mercury, lead
• Toluene and benzene derivatives: glue paint
• Shell fish
• Eucalyptus oil
• Insecticides: chlordecone,phosphine,carbondi-
sulphide( cellophane
manufacture)