Approach to ataxia

approach to ataxia- Dr pallav jain

1. 1 PRESENTER- DR.PALLAV JAIN DM RESIDENT(NEUROLOGY) GMC,KOTA Approach to Ataxia

2. Introduction Ataxia = from Greek- a- [lack of]+ taxia [order ] R ate , rhythm and force of contraction of voluntary movements Disorganized , poorly coordinated, or clumsy movements Traditionally used specifically for lesions involving Cerebellum or it’s pathways Proprioceptive sensory pathways

3. Localisation Cerebellum (most common ) Sensory pathways (Sensory Ataxia)-posterior columns, dorsal root ganglia, peripheral nerves Vestibular dysfunction

4. 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

5. Vestibular Dysfunction Vertigo is prominent Consistent fall to one side Nystagmus Limb ataxia is absent Speech is normal Joint position sense is normal

6. Approach to ataxic patient 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 6

7. 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, tumor , paraneoplastic ) 7

8. Drug intake Phenytoin , barbiturates, lithium, immunosuppressants ( methotrexate , cyclosporine), chemotherapy (fluorouracil, cytarabine ) Family history Study at least 3 generations Consanguinity Ethnicity Social/Occupational History Alcohol and drug use, toxins (heavy metals, solvents, thallium), smoking (Vascular) History 8

9. Distribution of ataxia Symmetric - Acquired, Hereditary, degenerative ataxias Asymmetric- Vascular, Tumors , congenital causes Other system illness Gastrointestinal symptoms- gluten ataxia Mass lesion- paraneoplastic ataxias History 9

10. Children Refusal to walk or with a wide-based, "drunken" gait. Vertigo, dizziness and vomiting Personality and behavioral changes . Abnormal mental status A history of head trauma ,neck trauma Patients with a recent infection or vaccination Previous similar episodes of acute ataxia . Children with family members with ataxia 10

11. Examination Neurological examination Ataxia (appendicular or axial) Dysmetria Dysdiadochokinesia Rebound Phenomenon Dysarthria Tremor Titubation and increased postural sway Hypotonia Nystagmus Other system evaluation Breast Lump, mass per-abdomen etc. 11

12. Neuro-ophthalmologic evaluation in ataxia Retinal pigmentosa Refsum disease,mitochondrial disorders Retinal/Macular degeneration SCA 7,aceruloplasminemia Optic atrophy/visual loss MS,FA Square wave jerks FA Occulomotor apraxia AT,AOA1,AOA2 Slow saccades Downbeat Nystagmus SCA2,SCA 7 SCA 6,EA2,anti GAD ataxia 12

13. Other Non cerebellar signs Focal and lateralized brainstem deficits( hemiparesis,facial palsy) Posterior circulation stroke,tumour,MS Paplidema , headache Posterior fossa tumours INO Posterior circulation stroke,MS Spasticity, UMN signs SCA 1,3,7,8 , Strokes,tumour compressing brainstem Basal ganglia deficits SCA 1,2,12,17, MJD,MSA,Wilson Tremor SCA 12,115/16, FAXTS 13

14. 14 Deafness Mitochondrial,superficial himosiderosis Myoclonus Mitochondrial ,ceroid lipofuschinosis,SCA 7(early onset),SCA 14 Palatal myoclonus Alexander disease,SCA20 Cognitive decline Alcohol,MS,CJD,HIV,DRPLA,SCA12,13, superficial siderosis Psychiatric features SCA 12,17,27 Autonomic failure MSA,FXTAS

15. Ataxia with Neuropathy Friedreich ataxia AOA2 Fragile X syndrome Vit E deficiency ataxia Anti gliadin ataxia SCA 2,3,4,12 , 18,25,27 Refsum disease 16

16. Ataxia with Dementia Anti gliadin ataxia FXTAS syndrme SREAT SCA 17, 19, 21, 2, 1, 6 HIV/AIDS Mitochondrial disease Amylodosis 17

17. Ataxia with seizures Anti GAD Anti gliadin Mitochondrial ataxia Episodic ataxia DRPLA SCA 10, SCA 17 CJD SREAT 18

18. Investigations Neuro imaging Electro diagnostic tests Ophthalmologic examination- Pigmentary retinopathy, macular degeneration, cataracts , Kayser -Fleischer rings

19. Genetic tests Metabolic – Thyroid function, vitamins B12, E, and B1, serum cholesterol & plasma lipoprotein profile, phytanic acid, toxicology screen Immune function - Immunoglobulin levels, Antigliadin antibodies, GAD antibodies , paraneoplastic antibodies

20. Laboratory studies Mitochondrial( Serum lactate and pyruvate) Heavy metals,PBF for acanthocytes , VLCF, hexosaminidase A/B, 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

21. Signs that Distinguishes SCA subtypes Benign course SCA 6 UMN signs SCA 1,7 ,8 and 3 Akinetic rigid syndrome SCA 3,2,17 & 12,21 Chorea SCA 2,1,3 Action tremor SCA 12,16 Slow saccades SCA 2 & 7 may be in 1,3 Downbeat nystagmus SCA 6 Hyporeflexia / Areflexia SCA 2,4,3 & 19,21 Vision loss SCA 7 Seizure SCA 10 Myoclonus SCA14 or SCA19 Cognitive impairment SCA 2,14,19,21,23 23

22. Genetic Testing Protocol of ataxias Spinocerebellar Ataxia Aut.Dominant Aut.Recessive Sporadic LOCA (>25) EOCA (<25) SCA 1 SCA 2 SAC 3 SCA 7 SCA 12 FRDA NO YES YES NO SCA 6 SCA 8 SCA 17 DRPLA YES NO Rare types of SCAs (ADCA) screening Investigation for other ARCA genes Level 2 Level 1 Level 3 features suggestive of SCA LOCA-Late onset cerebellar ataxia EOCA-Early onset cerebellar ataxia SCA27 SCA28 Age at Onset (Yrs) 10-30 >30 Variable SCA11 SCA14 SCA23 SCA5 SCA13 SCA14 SCA15 SCA28 24

23. Disease Additional features over Cerebellar Ataxia Distinguishable features Laboratory findings Sensory Axonal neuropathy MRI-spinal atrophy FA Pes cavus , Amyotrpohy , Extensor Plantar, Nystagmus Cardiomyopathy , DM GAA expansion in FXN Ataxia Vit E Def. Pes Cavus , Extensor Plantar, Head Tremor Retinitis Pigmentosa , Cardiomyopathy Low VitE MRI-Cerebellar Atrophy Infantile onset SCA Pes cavus, Amyotorphy, Ophthalmoplegia,Cognitive Impairment, Chorea Seizures,Hearing loss , Hypogonadism - MRI-Normal Abetalipoprotenemia Pes cavus, Amyotrophy Retinitis Pigmentosa , Lipid Malabsorption , Cardiomyopathy Low VitE , low lipoprotein , acanthocytes Clinical approach to ARCA MRI findings and Nerve conduction studies 25

24. Disease Additional features over Cerebellar Ataxia Distinguishable features Laboratory findings Ataxia with sensorimotor Axonal neuropathy MRI- Cerebellar Atrophy Late onset Tay sachs Amyotrophy , tremor, Myoclonus Prominent Extrapyramidal , Seizures,Psychiatric Impairment Hexoseaminidase levels- Ataxia telengiectasia Occulomotor Apraxia , Amyotrophy,Tremor Myoclonus , Extrapyramidal , Babinski Sign Telengiectasia,Lymphoid cancer , Radiosensitivity,Immunodeficiency,DM High alpha-fetoprotein and low immunoglobin AT like disorders Occulomotor Apraxia , Extrapyramidal Radiosensitivity,Immunodeficiency low immunoglobin Ataxia with OA1 Occulomotor apraxia,Pes cavus , Amyotrophy , tremor, Extrapyramidal , cognitive impairment Scoliosis Low albumin, High Cholesterol Aprataxin gene Ataxia with OA2 Occulomotor Apraxia , Pes Cavus , amyotrophyTremors , Extrapyramidal , cognition Impairment Scoliosis High alpha-fetoprotein, High cholesterol Senataxin gene 26

25. Disease Additional features over Cerebellar Ataxia Distinguishable features Laboratory findings MRI-Spinal +Cerebellar Atrophy AR ataxia Charlevoix- Saguenay Pes Cavus , Amyotrophy , Spasticity, extensor Plantar, cogitive Impairment Chromosome 13 MRI-Cerebellar Atrophy + WMH Cerebrotendinous xanthomatosis Pes Caus Amyotrophy , Spasticity, myoclonus , Parkinsonism Psychiatric Impairment,Tendon Xanthomas,Seizures,Cataract,Liver failure CYP27A1 27

26. Sporadic ataxias Multiple system atrophy (MSA ) Toxins/metabolic Paraneoplastic cerebellar degeneration Immune-mediated ataxias (gluten, anti-GAD ) Infectious etiology 28

27. Diagnostic approach to sporadic adult-onset ataxia 29

28. Antibody Condition Anti- Yo (Purkinje cell antobody type1) Breast and ovarian Ca Anti- Hu (Anti neuronal nuclear antibody type1) Small cell lung Ca (SCLC) Anti- Tr Hodgkin Lymphoma Anti-mGluR1 (metabotrpin glutamate receptor) Hodgkin Lymphoma Anti-CRMP5 ( Collapsin receptor mediated protein)/Anti-CV2 SCLC Anti-ZIC4 (zinc finger protein) SCLC Paraneoplastic ataxia associated antibodies

29. Causes of sensory ataxia Polyneuropathy Paraneoplastic sensory neuronopathy Sjogren’s syndome Miller Fisher Syndrome Dysproteinemia Cisplatin Pyridoxine excess Acute sensory neuronopathy Chronic ataxic neuropathy Myelopathy Multiple sclerosis Tumour or cord compression Vascular malformation Vacuolar myelopathy Myeloneuropathy Freidriech’s Ataxia Vitamin B12 deficiency Vitamin E deficiency Tabes dorsalis Nitrous oxide 31

30. 32 Cerebral Sensory frontal Base of support Wide base Looks down Wide base Velocity Variable Slow Very slow Initiation Normal Normal Hesitant Turns Unsteady Unstaedy Hesitant,multiple steps Postural instability + + +++++ Falls Late event More in night Frequent Heel shin Abnormal Abnormal,difficulty in point of initiation Normal

31. Question & Answers 34

32. Differential diagnosis Non cerebellar causes of acute ataxia Acute ataxic variant of GBS Miller Fischer Syndrome Acute vestibulitis / labyrinthitis 35

33. Autosomal recessive ataxia MRI- Cervical cord atrophy without cerebellar atrophy FA Ataxia with Vitamin E deficiency 36

34. Patient p/w Autosomal dominant anticipation ataxic gait With vision loss SCA-7 37

35. Identify the sign 38

36. Hot cross bun Seen in Axial T2 W images Seen in Multiple System Atrophy (MSA-C) Crucifrom hyperintensities in Pons Due to selective loss of myelinated transverse pontocerebellar fibers and neurons in the pontine raphe with preservation of the pontinetegmentum and corticospinal tracts . 39

37. May also be seen in SCA 2 SCA 3 Vcjd HIV related PML 40

38. A 9-year-old girl p/w gait instability. O/E, she has reduced sensation to light-touch and pinprick, reduced vibratory sensation , and impaired proprioception.DTR - are absent. She also have truncal and limb ataxia and choreoathetosis . Correct ? a. AD in inheritance b. Results from a trinucleotide repeat expansion c. R esults in impaired DNA repair d. Patients with this disorder have hypergammaglobulinemia e.Reduced risk of malignancy is seen with this disorder 41

39. A 19-year-old woman is brought to the clinic for progressive gait disorder. She had a history remarkable for bilateral cataracts, cognitive decline, and personality changes that are of unclear etiology and under investigation . On examination, she has dysmetria , a widebased gait , and evidence of neuropathy . Which of the following tests would help? a. Thyroid-stimulating hormone b. Analysis of CAG repeat number on chromosome 14 c. Serum cholesterol levels d. Serum cholestanol levels e. Serum copper and ceruloplasmin 42

40. A 63-year-old , h/o of alcoholism>30 years’ p/w walking difficulties. O/E- wide based , lurching gait,minimal dysmetria on FN or HS testing.No eye movement abnormalities,no nystagmus.MRI -cerebellar atrophy, particularly in the midline.Which of the following statements is correct? a)His history of alcoholism is unlikely to be related as only acute alcohol intoxication leads to gait ataxia b) Chronic alcohol exposure leads to significant cerebellar hemisphere atrophy with relative sparing of midline structures c) Chronic alcohol exposure predominantly leads to atrophy of midline cerebellar structures, such as the vermis d)Thiamine deficiency leads to memory loss and eye movement abnormalities, but not ataxia 43

41. 44

42. Localization of cerebellar lesions Gait ataxia Limb ataxia Dysarthria Titubation Action tremor 45 Anterior vermis Lateral hemispheres Posterior left hemisphere & vermis Ant . Vermis & associated deep nuclei Dentate nuclei, or cerebellar outflow to ventral thalamus

43. Localization of cerebellar lesions Palatal tremor Saccadic dysmetria Square wave jerks Gaze evoked nystagmus Higher cognitive changes 46 Dentate nucleus, Guillain Mollaret triangle Dorsal vermis Cerebellar outflow Flocculus & paraflocculus Lateral hemispheres