![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](https://image.slidesharecdn.com/satyaataxiafinal-200811075219/85/Approach-to-a-case-of-ataxia-2-320.jpg)
Approach to a case of 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)