Sixth Annual Intensive Update in Neurology - PDF document

Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 1 THE WOBBLY PATIENT: ADULT ONSET ATAXIA Rosalind Chuang, M.D. Movement Disorders Swedish Neuroscience Institute September 15, 2016 Disclosure: none Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 2 Objectives • Review algorithm for work up of patients with ataxia • Review common forms of g

enetic ataxia • Understand which genetic tests to obtain and rationale for genetic testing Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 3 What is ataxia? • Dysfunction of the cerebellum or cerebellar pathways • Core symptoms: • Balance & gait • Hand incoordination • Dysarthria • Oculo - motor abnormality Sixth Annual Intensive Update i

n Neurology 9/15 - 16/2016 4 APPROACH TO THE ATAXIC PATIENT A detailed history and exam are always free! Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 5 Question to self: “Is it ataxia?” Other causes of imbalance  Visual: blindness  Vestibular: BPPV, Ménière syndrome  Cortical: dementia, medications  Musculoskeletal: muscle weakness,

hip/knee joint problems  Proprioception/Sensory: sensory ataxia Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 6 Drugs & Dementia are common cause of falls in elderly Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 7 Cerebellar Exam: S cale for the a ssessment and r ating of a taxia (SARA) 1. Gait 2. Stance 3. Sitting 4. Speech 5. Finge

r chase 6. Nose - finger 7. Fast alternating hand movements 8. Heel shin slide Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 8 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 9 Questions to ask 1. Age of onset 2. Rate of disease progression 3. Family history 4. Systemic clues Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 10 Approa

ch to the ataxic patient • Family history • Not limited to ataxia • Consider: • Dementia • Other movement disorders: Tremors, parkinsonism, chorea, dystonia • Epilepsy • Mental retardation, learning disability, autism • Psychiatric disease, history of suicide or alcoholism • History of institutionalization • “Cerebral palsy” • Vision lo

ss • Premature ovarian failure • Autonomic dysfunction • Other medical diseases: DM II , deafness Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 11 The detailed family pedigree • Don’t accept “old age” as cause of death • Did parent remain ambulatory throughout? • Aunts, uncles, first cousins • Why was someone “institutionalized?â€

 • “Really alcoholics?” • Children: any difficulty learning to walk? Learning disability? • Ethnicity • Ashkenazi Jewish ancestry? • French Canadians? • Possibility of consanguinity? Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 12 Approach to the ataxic patient • Cerebellar ataxia confirmed • Always do MRI brain to exclude stru

ctural causes • Additional clues for another cause of ataxia • Labs: ( Fogel et al 2007) • Basic screen: Comprehensive metabolic panel, Vit B1, B12, E, CBC with smear, thyroid studies, ESR, CRP, ANA, immunofixation , RPR • Secondary screening labs: anti - GAD, cholesterol • If systemic clues are present: • paraneoplastic panel (with CT imaging), c

eliac, copper/ ceruloplasmin • Imaging: MRI brain/C spine • Consults: neuro - ophtho , neuro - muscular Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 13 CASE PRESENTATION 65 year old male with progressive ataxia… Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 14 Case Presentation • 65 year old gentleman with ataxia • PMH: DM II, HTN

• His wife noticed at breakfast that his speech was slightly slurred • Difficulty holding utensil at breakfast • Stumbled while walking • Stable for past 3 months • Walking/stumbling has improved • Occasionally drops cups • Slurred speech resolved Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 15 Questions to ask 1. Age of onset • Lateâ

€¦ 2. Rate of disease progression • Acute onset, no progression 3. Family history • None 4. Systemic clues • Stroke risk factors Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 16 Acute onset cerebellar ataxia • Vascular (stroke) • Wernicke’s encephalopathy • Infections • More common in children • Trauma • Autoimmune: MS, ADEM, Mille

r - Fisher Syndrome) • Vestibular • Functional (psychogenic) Cerebellar and Afferent Ataxias. Pandolfo , Massimo; Manto , Mario; MD, PhD. CONTINUUM:, October 2013. Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 17 Case Presentation • 65 year old male with progressive ataxia • Onset 4 months prior • Saw 2 prior physicians 2 months after onse

t of “dizziness” • Extensive work up… • No family history, no risk factors (no tobacco, illicit drugs or alcohol history) • On initial exam: • SARA score of ~10 • Dysarthria • Abnormal saccades • Review of past work up: • CT chest with nodule: scar tissue • FDG - PET scan: “possible cerebellitis ” • CSF: +EBV IgG Referred for possi

ble infectious cerebellitis Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 18 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Sub - acute, progressive with SARA of 10 over 4 month period 3. Family history • None 4. Systemic clues • None: no h/o fevers, chills, cough, malaise Sixth Annual Intensive Update in Neurology

9/15 - 16/2016 19 Case presentation #2: conclusion • Referred to pulmonary consult for lung biopsy • Whole body PET scan positive • Biopsy: neuro - endocrine tumor Paraneoplastic cerebellar ataxia • Ataxia stable with chemotherapy/XRT • Had 3 rounds of IVIg with slight improvement with first round, no additional improvement with subsequent IVIg Sixth

Annual Intensive Update in Neurology 9/15 - 16/2016 20 Paraneoplastic ataxia • Most common malignancies: • SCLC • Breast, ovarian • Hodgkin’s • Usually sub - acute • Ataxia can precede identification of underlying tumor by 4 years • Should everyone with ataxia have routine screening for paraneoplastic syndrome? • If rapid progression over months

, yes. Also include CT Chest/abdomen/pelvis with contrast and whole body PET. • If negative initially, some still recommend Q6 month paraneoplastic panel Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 21 Case presentation: Patient #3 • 65 year old computer engineer with no PMH until September 2015 • A woke in middle of night with chest pains an

d sensory symptoms described as “electrical impulses” • New onset headaches causing insomnia from 10/2015 - 12/2015 • Spontaneously resolved December 2015 • Hyperacusis • Cognitive decline - not noticeable to colleagues or family but it “hurt” to think • His wife started to notice short term memory changes in February 2016 • Handwriting chang

es: messy, clumsy Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 22 Case # 3 Physical exam February 2016 • Halting speech, repeating same stories, frequent word finding difficulties • CN: impaired smooth pursuit. But vertical gaze intact. No hypermetric saccades • Reflexes: areflexic • Sensation: Normal • Movement disorders: Excessive st

artle to facial stimuli No myoclonus UPDRS: slight neck rigidity, slight bradykinesia of all limbs, no tremors SARA 11.5 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 23 Case # 3 • Labs: • RA , CRP, ESR , Hashimoto's Ab negative • Paraneoplastic Panel (serum) #1: negative • RPR non reactive • CSF November 2015: • Glucose 53, Protein 25,

WBC 2, RBC 6, CSF ACE 1.7 (normal), IgG Index 0.5 (normal), Lyme negative, Oligoclonal Bands negative, VDRL non - reactive • EMG/NCS: negative • DaT scan: February 2016 • “ Scintigraphic findings indicate nigrostriatal degeneration indicating Parkinsonian syndrome” Referred to Movement Disorders for atypical parkinsonism Sixth Annual Intensive Upd

ate in Neurology 9/15 - 16/2016 24 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Acute/Sub - acute, rapidly progressive with SARA of 11.5 3. Family history • None 4. Systemic clues • Sensory symptoms • Significant Cognitive changes Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 25 Case # 3: Conclusion Additional l

abs • Whole body PET scan: negative • CSF March 17, 2016 • Paraneoplastic (Mayo Clinic) negative • Voltage gated K channel requested, not done • CSF Tau total 6169 pg /ml • 14 - 3 - 3 to Prion Disease Center (Available April 2016) • Positive • RT - quic positive • Progressive cognitive decline with agitation • Family consented for Brain d

onation to Prion Center • Passed away May 11, 2016 • Autopsy confirmed prion protein in brain tissue Sporadic CJD Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 26 Sporadic CJD • Peak age ~55 - 75 years old • Survival 1 year • 300 cases in USA/year • First symptom: • Dementia (37 %) • Cerebellar (34 %) • Visual (15 %) • P sychi

atric disturbances (14 %) • Extrapyramidal 4% ( Krasniaski 2014) • Prodromal symptoms Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 27 Sub - acute ataxia • Paraneoplastic • Potentially treatable! • Infection: • Prion disease • Infection precautions with brain biopsy/lumbar puncture • Send 14 - 3 - 3 to Case Western (Prion Surveillanc

e Center) for RT - quic • Auto - immune • Anti - GAD • SREAT • Gluten Ataxia Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 28 Gluten Ataxia: brief word… • Controversial • Celiac related antibodies • Anti - gliadin (not recommended, high false positive) • Anti - TTG (tissue transglutaminase ) • Anti - TG6 ( transglutaminase 6) â€

¢ Antibodies can also be present in ataxias with confirmed genetic cause • Gold standard: gut biopsy • Treatment: gluten free diet • European Consensus Statement on ataxia does NOT recommend routine testing for gluten antibodies • It is potentially treatable, so if sub - acute onset, I send labs after 3 - 4 weeks of high carbohydrate diet • Or, just ha

ve patient go on gluten free diet for a few weeks and repeat exam Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 29 SLOWLY PROGRESSIVE ATAXIA Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 30 Slowly progressive ataxia • Acquired • Toxin • Alcohol • Drugs: Lithium, phenytoin , carbamazepine , amiodarone • Structural: • NPH • Tu

mors • Vitamin Deficiencies: • Vit B1, B12, E, CoQ10 • Neuro - degenerative • Genetic Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 31 Case # 4 • 65 year old male Onset of symptoms 1.5 years ago with gait changes • Had problems walking on the beach on vacation in Hawaii • Speech was slower • On exam, SARA score was 8 • On further ques

tioning: • REM behavior disorder • Mild difficulty swallowing • Erectile dysfunction for 2 years • Orthostatic BPs: decrease of 20mmHg systolic Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 32 “ILOCA” • Idiopathic late onset cerebellar ataxia • Coined by Anita Harding in 1981 • Many cases have been reclassified since: • Spinocerebe

llar ataxias (SCAs) • Fragile X - Ataxia syndrome (FXTAS) • Friedreich’s ataxia (FA) • Multiple system atrophy (MSA) Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 33 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Slowly progressive over 1.5 years 3. Family history • None 4. Systemic clues • Urinary dysfuncti

on • Orthostatic hypotension • REM behavior disorder Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 34 Truly negative family history…now what? • MSA, MSA, MSA (multiple system atrophy) • Consider this early and continue to evaluate at every clinic visit. • More rapid progression of SARA score • Check orthostatic BPs ( supine and standing)

at each visit • Review of systems every visit: Autonomic dysfunction, REM behavior • Findings of parkinsonism Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 35 “24 - 36 % OF LATE ONSET ATAXIA PATIENTS TRANSITION TO MSA - C IN 5 - 10 YEARS” DR. H. PAULSON, AAN 2008 • 29% per Abele et al. The aetiology of sporadic adult onset ataxia,

Brain 2002 • 33% per Gilman et al. Evolution of sporadic OPCA into MSA. Neurology 2000 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 36 Fig. 1 Prevalence of MSA, FRDA, SCA2, SCA3 and SCA6. M. Abele et al. Brain 2002;125:961 - 968 Fig. 1 Prevalence of MSA, FRDA, SCA2, SCA3 and SCA6. ( A ) Whole study population ( n = 112). ( B ) Subgroup of pat

ients with a disease duration of ≥4 years ( n = 81). Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 37 Second consensus statement on the diagnosis of MSA (Gilman et al. Neurology 2008) Probable MSA  Autonomic failure involving urinary incontinence OR an orthostatic decrease of blood pressure within 3 minutes of standing by �30mmHg systol

ic or �15mmHg diastolic AND  Poorly levodopa responsive parkinsonism OR  Cerebellar syndrome Possible MSA  Parkinsonism OR cerebellar syndrome AND  At least one feature suggesting autonomic dysfunction that does not meet criteria AND At least one criteria of the following: o Babinski o Stridor o Rapidly progressive parkinsonism o Poorly resp

onsive to levodopa o Postural instability within 3 years of motor onset o Ataxia, dysarthria, oculomotor dysfunction o Dysphagia years of motor onset o Atrophy on MRI of putamen, MCP, pons, or cerebellum Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 38 GENETIC ATAXIAS ~25% of ataxia patients with family history have positive genetic test ~10% of spor

adic ataxia patients have positive genetic test Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 39 Approach to the ataxia patient: The “negative” family history • Early death of parents • Incomplete penetrance • Family estrangement or geography • Cultural barriers to discussing medical history • Adoption • Possibility of non - paternity

Consider genetic testing Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 40 Brusse et al . Clin Genet 2007 SCA 8 Have patient ask other relatives Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 41 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 42 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 43 Case Presentation • 61 y

ear old gentleman with ~3 - 5 years of cognitive changes and imbalance • Paranoia/delusions started ~5 years ago • Forgetting conversations ~3 years ago • Balance changes ~1 - 2 years ago with 1 - 2 falls/week • Family history: • Parents: Mother: healthy. Father: died in war • Siblings: 1 brother with balance changes • Children: 1 daughter, healthy

• Grandson: learning disability Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 44 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Slowly progressive over 3 - 5 years 3. Family history • Yes! Brother with ataxia • Also, grandson with learning disability 4. Systemic clues • Cognitive changes • Psychiatric changes

Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 45 FXTAS (Fragile X Ataxia Syndrome) Clinical symptoms: • Late onset (�45 years old) • Action tremor (similar to ET with postural � intention) • Ataxia (axial and appendicular) • Parkinsonism • Peripheral neuropathy • Autonomic (orthostatic, impotence, urinary dysfunction) • Cogni

tive changes ( fronto - executive) Imaging on MRI: MCP sign and hyper - intensities within corpus callosum Prevalence within sporadic ataxias: 1.5% in men, 0.2% in women Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 46 FXTAS • X chromosome • Pre - mutations with 55 - 200 CGG repeats in FMR1 gene • Carriers: • Males 1:813, Females 1:259 â

€¢ Females: • Premature ovarian failure with menopause 40 years old Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 47 FXTAS case conclusion • Fragile X genetic testing April 2016 • 77 CGG repeats • Asymptomatic daughter: 69 CGG repeats • Grandson: �500 expansions Genetic testing has implications for the entire family Sixth Annual Inten

sive Update in Neurology 9/15 - 16/2016 48 IF YOU HAVE A MALE WITH LATE ONSET TREMOR AND ATAXIA… Think Fragile X ataxia pre - mutation carriers Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 49 Case presentation • 58 year old Caucasian gentleman • First symptom: Clumsy hands, dropping tools • Two years later, developed gait imbalance then fal

ls. + dysarthria . • Reflexes normal • As part of work up, diagnosed with DM II • No clear neuropathy, mildly decreased vibratory sensation in toes • EMG/NCS normal Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 50 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Very slowly progressive 2+ years 3. Family history

• None 4. Systemic clues • Possible neuropathy, DM II Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 51 Classic Friedreich’s ataxia (FRDA) • Most common form of inherited ataxia in Caucasians • 1/29,000 • 1:85 are carriers • Classic neurologic phenotype: • Ataxia • Dysarthria • Neuropathy (impaired vibration/proprioception) • Pyra

midal weakness • Non - neuro symptoms: scoliosis, diabetes, cardiomyopathy Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 52 Adult onset Friedreich’s ataxia • Reflexes preserved or hyperreflexic • Generally don’t have cardiomyopathy • Generally die of cachexia or pneumonia Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 53 AUTOSOM

AL DOMINANT ATAXIAS Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 54 Case presentation • 65 year old gentleman with mild imbalance • Started to notice clumsiness ~8 years ago, attributed to ‘aging’ • Stopped drinking alcohol because more easily affected • When fatigued, speech is more slurred • Handwriting “messy” • No cognitive c

hanges, no lightheadedness, urinary problems • Family History: no problems with balance • Exam: • Vibratory sensation: slightly reduced, normal pinprick • SARA score 6 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 55 Clinical pearls for autosomal dominant ataxias • SCA 3 most common ~21% cases worldwide • SCA 2 is the second most common w

ith quite variable phenotype • SCA 6 • “Pure” late onset cerebellar ataxia • “Sporadic” mutations occur more commonly than the other SCAs • SCA 10 is associated with Hispanic population • But SCA 2 is still more common • SCA 31 and 36 in Japanese ancestry Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 56 SCA 2 (ATXN2): great mimicker

! • CAG repeat expansion • Normal 31 • Intermediate 32 - 33 repeats • Full mutation �40 • Variable age of onset • Not dependent on number of CAG repeats • Anticipation phenomenon - • Earlier disease onset, more severe symptoms • Variable phenotype • ALS (~32/33 CAG) • Parkinsonism (34 - 39 CAG) • Dystonia or chorea (34 - 39 CAG) •

Ataxia �(40 CAG) Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 57 © 2013 American Academy of Neurology. Published by American Academy of Neurology. 2 Cerebellar and Afferent Ataxias. Pandolfo , Massimo; Manto , Mario; MD, PhD CONTINUUM: Lifelong Learning in Neurology. 19(5, Movement Disorders):1312 - 1343, October 2013. DOI: 10.1212/01.CON.00

00436158.39285.22 Table 7 - 4 Non - Ataxia Signs and Symptoms Suggesting Specific Genetic Subtypes of Autosomal Dominant Spinocerebellar Ataxia Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 58 Distinguishing features of autosomal dominant ataxias available by commercial testing Disease Distinguishing clinical features in addition to ataxia SCA1 Pyra

midal signs, neuropathy SCA2 Slow saccades, neuropathy, hyporeflexia, dementia SCA3 Pyramidal signs, parkinsonism, lid retraction, nystagmus, neuropathy SCA5 Slowly progressive SCA 6 Pure cerebellar, slowly progressive, downbeat nystagmus , mild neuropathy, late onset spasticity, “sporadic” SCA 7 Visual loss SCA 8 Pure cerebellar, sometimes episodic SCA 10 M

exican families, seizures SCA 12 Slowly progressive, postural hand tremor, subtle parkinsonism (bradykinesia) SCA 13 Mild mental retardation, delayed motor development SCA 14 Can be pure cerebellar, myoclonus, myokymia , dystonia, vibratory loss SCA 17 Dementia, parkinsonism, dystonia, psychiatric, chorea, HD - like. Seizures. SCA 28 Slowly progressive, hyperref

lexia , nystagmus , and ophthalmoparesis Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 59 © 2013 American Academy of Neurology. Published by American Academy of Neurology. 2 Cerebellar and Afferent Ataxias. Pandolfo , Massimo; Manto , Mario; MD, PhD CONTINUUM: Lifelong Learning in Neurology. 19(5, Movement Disorders):1312 - 1343, October 2013. DOI:

10.1212/01.CON.0000436158.39285.22 Table 7 - 2 Geographical Distribution of the Most Common Autosomal Dominant Spinocerebellar Ataxias Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 60 SCA 3 (Machado - Joseph Disease) • ATXN3 gene, CAGs • Clinical phenotype: • Ataxia • Dystonia - rigid • Parkinsonian • Amyotrophy • Different subtypes:

• Type I disease (13% of individuals ) young onset • Spasticity, rigidity, bradykinesia • Minimal ataxia • Type II: disease (57 %), • Ataxia, UMN signs (spastic paraplegia) • Type III disease (30%) • L ater age ataxia and peripheral polyneuropathy. • Type IV disease • Dopa - responsive parkinsonism • Ask about Portuguese Azorean ances

try Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 61 Back to Case: • 65 year old gentleman with mild imbalance • Started to notice clumsiness ~8 years ago , attributed to ‘aging’ • Stopped drinking alcohol because more easily affected • When fatigued, speech is more slurred • Handwriting “messy” • No cognitive changes, no lighthea

dedness, urinary problems • Family History: no problems with balance • Exam: • Vibratory sensation: slightly reduced, normal pinprick • SARA score 6 Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 62 Case continued • On further questioning of family history: Still no family history of imbalance • Sister is undergoing speech therapy for “sl

urred speech” • But no problems with balance • …except she uses a cane because of “knee problems” Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 63 Questions to ask 1. Age of onset • Late… 2. Rate of disease progression • Very slow progression 3. Family history • Possible! S ister with dysarthria and possible imbalance 4. Systemic c

lues • Possible Sensory symptoms vs age related Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 64 What genetic tests to perform for the sporadic ataxia? • Most common in European population: SCA 6, SCA 2, 3 and Friedreich’s . • Common autosomal dominant SCAs: SCA 1, 2, 3, 6, 7 available through genetic panel (relatively inexpensive but not al

ways covered by insurance) • Fragile X: very inexpensive, usually covered by insurance • Friedreich’s : very inexpensive, usually covered by insurance • In Asia: SCA 6, 3, 2, DRPLA, SCA 1 • DRPLA not so common in the USA Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 65 Case conclusion “Additional diagnostic test was performed” SCA 6 posi

tive! Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 66 Ataxia labs • University of Washington: • SCA 1, 2, 3, 6, 7 ($$) • Separate testing for Autosomal recessive: Friedreich’s and Fragile X ($) • Athena: • Full panel is $$$$ • University of Chicago Ataxia exome panel • $4800 (no insurance!) • Does not cover common autosomal domin

ant SCAs • See website for Excel spread sheet of genes tested: http://dnatesting.uchicago.edu/tests/ataxia - exome - panel • UCLA Ataxia Exome panel • Commercial labs: Invitae , Fulgent for whole exome sequencing (does not cover common autosomal dominant SCAs) Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 67 ALL TESTS STILL NEGATIVE? ~40% o

f patients with sporadic, late onset cerebellar ataxia remain diagnostic mysteries… Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 68 Resources • Clin Gen https ://www.clinicalgenome.org / • “Gene Reviews” • Gene Tests: https://www.genetests.org/ Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 69 REMEMBER! Absence of limb ataxia d

oes not mean the patient is not cerebellar dysfunction! Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 70 REMEMBER! Always look at MRI brain…don’t trust radiology reports for cerebellar atrophy or diffusion abnormality Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 71 REMEMBER! • Rarely does genetic test result change outcome or manag

ement. • Rarely should genetic testing be the sent on first clinic visit. • Paraneoplastic panel and genetic test should never be sent on the same day. Sixth Annual Intensive Update in Neurology 9/15 - 16/2016 72 Resources 1. OMIM 2. Van de Warrenburg et al. “EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood” Euro J

Neuro 2014 3. Corben et al. “Consensus clinical management guidelines for Friedreich’s ataxia” Orphanet 201 4 4. Pandolfo and Manto “Cerebellar and Afferent Ataxias” Continuum AAN October 2013 5. Van Gaalen & van de Warrenburg “Practical approach to late onset cerebellar ataxia: putting the disorder with lack of order into order.” Pract Neuro

2012 6. Brusse E. et al . (2007). Diagnosis and management of early and late onset cerebellar ataxia. Clin Genet 71: 12 - 24, 2007 7. Fogel and Perlman (2007) “An approach to the patient with late onset cerebellar ataxia” Nat Clin Pract Neurol 2: 629 - 635. 8. Durr , E. et al. “Clinical and genetic abnormalities in patients with Friedreich’s Ataxia”