APPROACH TO ATAXIA

Dr. Deep Chandh Raja.S

SYNOPSISImportant concepts in AtaxiaATAXIA MIMICKERSTests of Cerebellar dysfunctionStep-wise approach to Cerebellar AtaxiasSummaryALGORITHM for cerebellar ataxias

‘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

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

Tests to differentiate Various systems in Ataxia- “The Ataxia Mimickers”

Cerebellar Ataxia Cortical Ataxia

Myopathy

Labrynthine Ataxia

Sensory Ataxia (Posterior Column) Thalamic Ataxia

Sensory Ataxia(Peripheral

Neuropahy))

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

• CaveatsFriederick’s ataxia, Multiple sclerosis…• Overlap of clinical features to be expected in

clinical practice

Muscle weakness

• In the Miller-Fisher syndrome, which is considered to be a variant of acute Guillain-Barré polyneuropathy

• The severe ataxia and intention tremor are presumably a result of a highly selective peripheral disorder of spinocerebellar nerve fibers

• Simple “tests of muscle power” can help detect muscle weakness in various muscle groups

• CAVEAT- lead poisoning

Labrynthine Disorders

• Input to cerebellum• Dizziness, light headedness, perception of

“movement”, rotatory nystagmus• Infections, neoplasms, vascular causesCAVEAT: involvement of flocculonodular lobe of

cerebellum, paraneoplastic and lateral medullary syndromes (lateral medulla and inferior lobe of cerebellum)

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

A lesion of the “SUPERIOR PARIETAL LOBULE” (areas 5 and 7 of Brodmann) may rarely result in ataxia of the contralateral limbs

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)

BEWARE OF EXTREMELY ANXIOUS PATIENTS!!!

CEREBELLAR ATAXIAS

“ATAXIA IS THE MOST IMPORTANT FEATURE AMIDST OTHER CLINICAL SIGNS OF CEREBELLAR DYSFUNCTION”

NEO CEREBELLUM

FLOCCULONODULAR LOBE

SPINO CEREBELLUM

TESTS OF CEREBELLAR DYSFUNCTION

ATAXIA

“errors in the RATE, RANGE, FORCE & DIRECTION of movement”•GAIT ATAXIA•TRUNCAL ATAXIA•LIMB ATAXIA

CLASSIC FEATURES AND TESTSDyssynergia: 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 targetDysdiadochokinesis: irregularities of force, speed, and rhythm

Other featuresHypotonia: 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 jerkRebound 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")

Other featuresOcular 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 sideWriting abnormalitiesPositional projectile vomiting (posterior fossa lesions)

APPROACH TO CEREBELLAR ATAXIAIN ADULTS

THE “FOUR” QUESTIONS????

• Mode of ONSET ?• PROGRESSION ?

• Focal /Symmetric involvement ?• Localisation of the cerebellar lesion ?

HISTORY

EXAMINATION

MODE OF ONSET

• ACUTE- hours to days

• SUB ACUTE- days to weeks

• CHRONIC- months to years

ACUTE ONSET ATAXIA

• INTOXICATION: alcohol , lithium , phenytoin , barbiturates

• POST INFECTIOUS: Acute Viral Cerebellitis, VZV

• VASCULAR: Infarction (AICA, PICA syndromes), Haemorrhage, Subdural hematoma

SUB ACUTE ATAXIA

• INTOXICATION: Mercury, Solvents, Glue

• NUTRITIONAL: B1 and B12 deficiency

• INFECTION: HIV

• DEMYELINATING: Multiple Sclerosis

• NEOPLASTIC: Glioma, Metastases

CHRONIC ATAXIA• AUTOIMMUNE CAUSES : Paraneoplastic

syndromes, Gluten hypersensitivity, Anti GAD abs.

• HYPOTHYROIDISM

• INFECTIONS: Syphilis (Tabes Dorasalis)

• CONGENITAL LESIONS: Arnold-Chiari and Dandy Walker Syndromes

• INHERITED ATAXIAS: AD,AR,XR,XD,Mitochondrial

PROGRESSION

• Progressive

• Static

• Intermittent symptoms

• Reversible Ataxias

PROGRESSIVE ATAXIA CLASSIFICATIONS OF GREENFIELD AND OF HARDING into three main groups: (1) the spinocerebellar ataxias, with unmistakable involvement of the spinal cord (Romberg sign, sensory loss, diminished tendon reflexes, Babinski signs); (2) the pure cerebellar ataxias, with no other associated neurologic disorders; and (3) the complicated cerebellar ataxias, with a variety of pyramidal, extrapyramidal, retinal, optic nerve, oculomotor, auditory, peripheral nerve, and cerebrocortical accompaniments including what is now referred to as multiple system atrophy

STATIC ATAXIAS• Vascular causes

REVERSIBLE ATAXIAS• Infectious causes – post viral• Thyroid• Drugs• Toxins

INTERMITTENT SYMPTOMS• Episodic Ataxias (Inherited etiology)

FOCAL / SYMMETRIC ATAXIAS• Cerebellar symptoms on same side of lesion, or• Bilateral symptomsFOCAL ATAXIASVascular causes, Multiple Sclerosis, Cerebellar

abscess, cerebellar glioma, PML (HIV), Congenital causes

SYMMETRIC ATAXIASIntoxication, Nutritional, Post inhectious,

Hypothyroid, Autoimmune causes

LOCATION OF LESION• CEREBELLAR HEMISPHERIC SYNDROME

Ipsilateral head & Body cerebellar signs Infarct, Neoplasm, Abscess, Demyelination

• ROSTRAL VERMIS SYNDROMEgait and Trunk Ataxia Alcoholism, B1 deficiency

• CAUDAL VERMIS SYNDROME Disequilibrium, Trunk ataxiaMedullobalstomas

• PANCEREBELLAR SYNDROME Bilateral signs Toxins, metabolic, Infections, Autoimmune, Inherited

• CEREBELLAR PEDUNCLES Dramatic cerebellar symptoms

PICA (Lateral medullary-Wallenberg Syndrome)

AICA (Lateral Inferior Pontine Syndrome)

• Vestibular N. i/l vertigo, nystagmus• Cochear n. i/l deafness• 7th Cranial Nerve i/l facial palsy• Cerebellum i/l Ataxia• 5th cranial nerve i/l hemisensory loss of face• Spinothalamic Tract C/L hemisensory loss

THE NEXT STEP …RULE OUT

ACQUIRED ATAXIAS

INHERITED ATAXIAS

SPORADIC or IDIOPATHIC

ATAXIAS

ACQUIRED ATAXIAS

• First rule out the Structural causes (MRI Brain/ CT head)

-CVJ anomalies-Posterior fossa tumors-Demyelinating diseases-Hypoxic encephalopathies-Vascular causes- infarct, haemorrhage

Acquired Causes

• HYPOTHYROIDISM- Mild gait ataxia PLUS Systems of hypothyroidism

ALCOHOLISM

• Vermian Atrophy

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

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

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)

• GLUTEN SENSITIVITY - Anti Gliadin abs.(ataxia, brisk reflexes, peripheral neuropathies)

• ANTI GAD abs. – Diabetes, hypothyroidism, peripheral neuropathySTIFF PERSON syndrome

AUTOIMMUNE CAUSES

NUTRITIONAL CAUSES

• FAT MALABSORPTION- Vit. E deficiency

• Vit. B12 , B1 deficiencies

INHERITED ATAXIAS

• AD• AR• MITOCHONDRIAL DISTURBANCES• X LINKED RECESSIVE• X LINKED DOMINANT

INHERITED ATAXIAS

INHERITED ATAXIAS

AUTOSOMAL DOMINANT

• SPINO CEREBELLAR ATAXIAS (Types131)-previously olivopontocerebellar atrophies

• DentatoRubroPallidoLuysian Atrophy

• EPISODIC ATAXIAS (Types 17)

AUTOSOMAL DOMINANT

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

• UMN SIGNS SCA 1, SCA7, SCA 8• OLDER AGESCA 6• MENTAL RETARDATIONSCA 13• VISUAL LOSSSCA 7• CHOREA, MYOCLONUSDRPLA• SEIZURES SCA 10• AREFLEXIASCA 2• INTEREPISODIC NYSTAGMUSEA 2• INTEREPISODIC MYOKYMIA EA1• NO FAMILY h/o SCA 6

AD ATAXIAS’ SALIENT FEATURES

SCA 5

SCA 2MJD

SCA 7

AUTOSOMAL RECESSIVE ATAXIAS

• FRIEDERICK’S ATAXIA• ATAXIA TELANGIECTASIA• ATAXIA WITH ISOLATED VIT.E DEFICIENCY• ABETALIPOPROTEINEMIA• ENZYME DEFICIENCIES (Maple Syrup urine

disease, Urea cycle defects, Sialidosis, Adrenoleucodystrophy,Organic aciduria, Pyruvate dehydogenase def.)

AUTOSOMAL RECESSIVE ATAXIAS

Friederick’s ataxia• Unstable expansion of GAA repeatsFRATAXIN

proteiniron accumulation in mitochondrianito.injuryneuronal injury

• DORSAL GANGLION CELLS- absent reflexes• DORSAL COLUMN DEGENERATION-

dec.post.column senses• SPINOCEREBELLAR TRACT-gait atxia, dysarthria• CORTICOSPINAL TRACT- Babinski Positive• OTHER SIGNS- dysphagia,optic atrophy, spinal and

foot deformities, diabetes (10%), cardiac defects (50%)

Friederick’s ataxia

• 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

ATAXIA TELANGIECTASIA

• OCULOMOTOR APRAXIA , TELANGIECATSIAS IN EYES, SKIN

• Hematological malignancies (defective DNA repairs)

• Infections (Ig deficiencies)• Other features-peripheral neuropathy,

choreoathetosis

ATAXIA TELANGIECTASIA

Mitochondrial Inheritance

• MERRF• MELAS• NARP

• RP degeneration• Short stature, Endocrine deficiencies,

X linked ATAXIAS

• X linked Dominant- Fragile X syndrome• CGG repeats’ expansion

• X linked Recessive Ataxias- Sideroblastic anemia with ataxia

X linked ATAXIAS

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

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)

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

HISTORY SUMMARY1. Duration: acute, subacute vs chronic2. Rate of Progression: static vs progressive3. Constant vs Paroxysmal4. 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 exposures6. Family History positive or negative (in siblings or cousins but not parents suggesting autosomal recessive or parents and/or sibs suggesting autosomal dominant inheritance

EXAMINATION SUMMARYGeneral 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

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

EXAMINATION SUMMARYMotor:- 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)

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

ALGORITHM

PEDIGREE CHART

ACQUIRED CAUSES

AD

IMAGING (MRI,CT)

SCA1,2MJD

SCA6,7SCA10,12

DRPLASCA17

FAAT

AVEDABETALIPOPROTEINEMIA