Childhood Ataxia

Childhood AtaxiaChildhood AtaxiaJennifer Jennifer BergquistBergquist, M.D., M.D.

September 12, 2005September 12, 2005

DefinitionsDefinitionsAtaxiaAtaxia is the inability to make smooth, accurate and is the inability to make smooth, accurate and coordinated movementscoordinated movementsAtaxia can arise from disorders of:Ataxia can arise from disorders of:–– Cerebellum (most common)Cerebellum (most common)–– Sensory pathways (Sensory Ataxia)Sensory pathways (Sensory Ataxia)

posterior columns, dorsal root ganglia, peripheral nervesposterior columns, dorsal root ganglia, peripheral nerves–– Motor pathways (Paretic Ataxia)Motor pathways (Paretic Ataxia)

CorticospinalCorticospinal tractstracts–– Frontal lobe lesionsFrontal lobe lesions

via via frontofronto--cerebellarcerebellar associative fibersassociative fibers

CerebellarCerebellar ataxiaataxia is defined as the lack of coordination of is defined as the lack of coordination of movement that is movement that is not not due to paresis, alternation in tone, due to paresis, alternation in tone, sensory loss, or presence of involuntary movementssensory loss, or presence of involuntary movements

ClassificationsClassifications::

CongenitalCongenital–– Usually from CNS malformationsUsually from CNS malformationsAcquiredAcquired–– AcuteAcute

Defined as unsteadiness of walking or of fine Defined as unsteadiness of walking or of fine motor movement of less than 72hrs duration in a motor movement of less than 72hrs duration in a previously well childpreviously well child

–– Episodic and/or chronicEpisodic and/or chronicRare in children; usually secondary to genetic or Rare in children; usually secondary to genetic or metabolic disordermetabolic disorder

Differential DiagnosisDifferential DiagnosisCongenitalCongenital–– CNS MalformationsCNS Malformations

CerebellarCerebellar hypoplasiahypoplasiaVermianVermian aplasiaaplasiaDandyDandy--walker walker ChiariChiari malformationmalformation

–– JoubertJoubert’’ss syndromesyndrome

HereditaryHereditary–– AutosomalAutosomal recessiverecessive

FriedreichFriedreich’’ss ataxiaataxiaAtaxiaAtaxia--TelagiectasiaTelagiectasiaAbetalipoproteinemiaAbetalipoproteinemiaVitamin E deficiencyVitamin E deficiency

–– AutosomalAutosomal DominantDominantSpinocerebellarSpinocerebellar AtaxiasAtaxias

Acute/SubAcute/Sub--acuteacute–– Infectious/ImmuneInfectious/Immune--

mediatedmediatedAcute Acute CerebellarCerebellarAtaxia*Ataxia*Acute disseminated Acute disseminated encephalomyelitis*encephalomyelitis*MeningoencephalitisMeningoencephalitisAcute Acute labyrinthitislabyrinthitisMultiple sclerosisMultiple sclerosis

–– Drug/ToxinDrug/Toxin--related*related*Alcohol, Alcohol, BZDsBZDs, , anticonvulsants, heavy anticonvulsants, heavy metals, carbon metals, carbon monoxidemonoxide

Differential DiagnosisDifferential DiagnosisAcute/SubAcute/Sub--acuteacute (cont.)(cont.)–– Mass lesionsMass lesions

TumorTumorVascular lesions (AVM)Vascular lesions (AVM)AbscessAbscess

–– TraumaTraumaHemorrhageHemorrhagePostPost--concussion concussion Vertebral artery Vertebral artery dissectiondissection

–– ParaPara--neoplasticneoplasticOpsoclonusOpsoclonus--myoclonusmyoclonus((neuroblastomaneuroblastoma))

–– Sensory ataxiaSensory ataxiaGuillanGuillan--BarreBarreMultiple sclerosisMultiple sclerosis

–– PareiticPareitic ataxiaataxiaFrontal lobe lesionFrontal lobe lesion

–– OtherOtherBasilar migraine Basilar migraine Benign paroxysmal Benign paroxysmal vertigovertigoNonNon--convulsive seizuresconvulsive seizuresInborn errors of Inborn errors of metabolismmetabolismHysterical gait disorderHysterical gait disorderCogan syndromeCogan syndrome

Clinical HistoryClinical History

Chief complaint is usually refusal to walk, Chief complaint is usually refusal to walk, ““staggeringstaggering”” gait, or clumsinessgait, or clumsinessInitial evaluation should focus on Initial evaluation should focus on excluding excluding serious causes of acute ataxiaserious causes of acute ataxia–– R/O Mass lesions, CNS infection, hydrocephalusR/O Mass lesions, CNS infection, hydrocephalus

Age at disease onset, progression rate, Age at disease onset, progression rate, accompanying symptoms, exposure to toxins accompanying symptoms, exposure to toxins and mode of inheritance should always be and mode of inheritance should always be consideredconsidered

Clinical HistoryClinical History

History should include:History should include:–– Antecedent or current symptoms of infectionAntecedent or current symptoms of infection–– Recent immunizationsRecent immunizations–– Recurrent or persistent headache, vomiting or Recurrent or persistent headache, vomiting or

diplopiadiplopia (signs of increased intracranial (signs of increased intracranial pressure)pressure)

–– Drug ingestionDrug ingestion–– Recent head or neck traumaRecent head or neck trauma–– h/oh/o previous similar episodes or + family previous similar episodes or + family

historyhistory

Physical ExamPhysical ExamMental statusMental status–– Helps differentiate between ACA and more serous conditions Helps differentiate between ACA and more serous conditions

(ingestion, ADEM, +/(ingestion, ADEM, +/--mass lesions)mass lesions)–– Ophthalmologic examOphthalmologic exam–– NystagmusNystagmus: common in : common in cerebellarcerebellar disorderdisorder–– PapilledemaPapilledema or cranial nerve palsies: intracranial focus lesion or or cranial nerve palsies: intracranial focus lesion or

hydrocephalushydrocephalus–– PupillaryPupillary abnormalities: mass lesion, stroke, intoxicationabnormalities: mass lesion, stroke, intoxication

Tone/strengthTone/strength–– Asymmetry uncommon in acute Asymmetry uncommon in acute cerebellarcerebellar ataxiaataxia–– Must differentiate poor coordination from weaknessMust differentiate poor coordination from weakness–– Muscle tone usually preserved in Muscle tone usually preserved in cerebellarcerebellar disordersdisorders–– Evaluate Evaluate DTRsDTRs

Hyperreflexia/areflexiaHyperreflexia/areflexia-- suggest causes other than suggest causes other than cerebellarcerebellar ataxiaataxia

Physical ExamPhysical Exam::CerebellarCerebellar SignsSigns

GaitGait-- wide based gait, staggeringwide based gait, staggeringPosturePosture-- truncaltruncal, head , head titubationtitubationDysarthriaDysarthria-- fluctuations in rhythm, tone, volume, clarity fluctuations in rhythm, tone, volume, clarity (scanning speech, slurring, (scanning speech, slurring, dysprosodydysprosody))DysmetriaDysmetria-- poor coordination of voluntary movementspoor coordination of voluntary movements–– fingerfinger--toto--nose (upper extremity) or healnose (upper extremity) or heal--toto--shin (lower shin (lower

extremity), extremity), dysdiadochokinesiadysdiadochokinesia, intention or kinetic tremor, intention or kinetic tremor

OculomotorOculomotor-- gazegaze--evoked evoked nystagmusnystagmus, impairment of , impairment of smooth pursuit smooth pursuit

FindingsFindings remain unchanged with eyes open or shut with remain unchanged with eyes open or shut with cerebellarcerebellar ataxia! ataxia! (i.e. negative (i.e. negative rombergromberg))

Localization of Localization of CerebellarCerebellar LesionsLesions

VermalVermal (midline) lesions(midline) lesions::–– TruncalTruncal and gait and gait

abnormalities, abnormalities, oculomotoroculomotordisturbances disturbances

–– speech is sparedspeech is sparedHemispheric lesionsHemispheric lesions::–– IpsilateralIpsilateral limb limb hypotoniahypotonia, ,

dysmetriadysmetria, and tremor, and tremorPatients veer to the Patients veer to the affected side when affected side when walkingwalking

–– DysarthriaDysarthriaDeep Deep cerebellarcerebellar nucleinuclei–– Resting tremor, Resting tremor, myoclonusmyoclonus, ,

opsoclonusopsoclonus

Evaluation of the Ataxic ChildEvaluation of the Ataxic ChildPrimary aim of laboratory and Primary aim of laboratory and radiologicradiologic investigations is investigations is to identify serious conditions mimicking postto identify serious conditions mimicking post--viral ataxiaviral ataxia–– PostPost--viral (ACA) is a diagnosis of exclusionviral (ACA) is a diagnosis of exclusion

Urine and/or serum toxin screenUrine and/or serum toxin screen–– Recommended in all children with acute or episodic ataxiaRecommended in all children with acute or episodic ataxia

NeuroimagingNeuroimaging with CT or MRIwith CT or MRI–– Recommended in all children with acute or subRecommended in all children with acute or sub--acute onset of acute onset of

ataxia (controversial) ataxia (controversial) –– Others recommend imaging only with atypical presentation or no Others recommend imaging only with atypical presentation or no

spontaneous improvement after 1spontaneous improvement after 1--2 weeks2 weeks–– low yield in the absence of altered MS, focal low yield in the absence of altered MS, focal neurologicneurologic findingsfindings

CSF examinationCSF examination–– Indicated when inflammatory or infectious disorders are Indicated when inflammatory or infectious disorders are

suspected suspected –– PleocytosisPleocytosis and elevated protein can be seen in ACAand elevated protein can be seen in ACA

Evaluation of the Ataxic ChildEvaluation of the Ataxic ChildFurther diagnostic testing should be guided by considering the mFurther diagnostic testing should be guided by considering the mode ode of inheritance, age at disease onset, progression rate, and of inheritance, age at disease onset, progression rate, and accompanying symptomsaccompanying symptomsElectrophysiology testingElectrophysiology testing–– NerveNerve--conduction studiesconduction studies-- peripheral neuropathiesperipheral neuropathies–– VEP, SEP, VEP, SEP, AEPsAEPs –– demyelinatingdemyelinating diseasedisease

Genetic testingGenetic testing–– FriedreichFriedreich’’ss ataxia, Ataxiaataxia, Ataxia--TelangiectasiaTelangiectasia, , SCAsSCAs

Metabolic workMetabolic work--upup–– PyruvatePyruvate, lactate, , lactate, ketonesketones, , LFTsLFTs, urine organic and serum amino , urine organic and serum amino

acids (inborn error of metabolism)acids (inborn error of metabolism)–– Urinary Urinary catecholaminescatecholamines, abdominal imaging (, abdominal imaging (neuroblastomaneuroblastoma))–– Vitamin E, lipids (Vitamin E, lipids (abetalipoproteinemiaabetalipoproteinemia))–– AlphaAlpha--fetofeto protein (ataxiaprotein (ataxia--telagiectasiatelagiectasia))

Acute Acute CerebellarCerebellar AtaxiaAtaxia

Most common cause of childhood ataxia Most common cause of childhood ataxia accounting for 40% of all casesaccounting for 40% of all casesMost common in children 2Most common in children 2--4 yrs (almost always 4 yrs (almost always <6 yrs) <6 yrs) Onset is sudden with predominant symptom of Onset is sudden with predominant symptom of truncaltruncal ataxiaataxia, uncoordinated gate, mental , uncoordinated gate, mental status is status is normalnormal““purepure”” acute acute cerebellarcerebellar ataxia is ataxia is notnot associated associated with fever, seizures, or other systemic signs with fever, seizures, or other systemic signs (consider acute disseminated encephalomyelitis)(consider acute disseminated encephalomyelitis)


PostPost--infectious infectious cerebellarcerebellar demyelinationdemyelination–– Autoimmune phenomenon incited by infection w/ Autoimmune phenomenon incited by infection w/

crosscross--reaction of Abs against reaction of Abs against cerebellarcerebellar epitopesepitopes–– History of antecedent illness 5History of antecedent illness 5--21 days prior to onset 21 days prior to onset

is obtained in ~70% of patientsis obtained in ~70% of patients–– ~1/4 of cases are preceded by ~1/4 of cases are preceded by VaricellaVaricella infection, but infection, but

numerous agents have been implicated numerous agents have been implicated (EBV, (EBV, CoxsackievirusCoxsackievirus, Echovirus, , Echovirus, EnterovirusEnterovirus))

–– Vaccinations have been implicated (Vaccinations have been implicated (espesp measles) but measles) but causal relationship has not been proven causal relationship has not been proven


NeuroimagingNeuroimaging is usually normalis usually normal–– rare cases demonstrate focal rare cases demonstrate focal cerebellarcerebellar lesions on lesions on

MRIMRIDiagnosis of exclusionDiagnosis of exclusionSupportive treatment Supportive treatment (although steroids and IVIG have (although steroids and IVIG have been beneficial in select cases)been beneficial in select cases)

Ataxia improves in a few weeks but may last up Ataxia improves in a few weeks but may last up to 2 monthsto 2 monthsPrognosis for complete recovery is excellent Prognosis for complete recovery is excellent (>90%); however, a small number have long(>90%); however, a small number have long--term term sequelaesequelae

Acute Disseminated Acute Disseminated EncephalomyelitisEncephalomyelitis

MultiMulti--focal immunefocal immune--mediated mediated demyelinatingdemyelinating disease disease following a viral illnessfollowing a viral illnessMean age 6Mean age 6--8 years old8 years oldDistinguished from ACA by alteration of mental status Distinguished from ACA by alteration of mental status and/or presence of focal neurological deficits (seizures, and/or presence of focal neurological deficits (seizures, hemiparesishemiparesis, cranial neuropathies) and systemic , cranial neuropathies) and systemic symptomssymptomsMRI reveals multiMRI reveals multi--focal focal demyelinatingdemyelinating lesions in lesions in white/gray matter, cerebellumwhite/gray matter, cerebellum–– MRI findings are similar to those seen in multiple sclerosisMRI findings are similar to those seen in multiple sclerosis

Treatment: steroids or IVIGTreatment: steroids or IVIGPrognosis: recovery occurs over 4Prognosis: recovery occurs over 4--6 weeks; 606 weeks; 60--80% 80% have normal neurological outcomeshave normal neurological outcomes

Toxic Toxic CerebellarCerebellar SyndromesSyndromes

Drug ingestion accounts for ~1/3 of all cases of Drug ingestion accounts for ~1/3 of all cases of acute ataxia in childrenacute ataxia in childrenAnticonvulsants (Anticonvulsants (dilantindilantin, , tegretoltegretol), lithium, ), lithium, BZDsBZDs, alcohol and antihistamines are common , alcohol and antihistamines are common offenders offenders (also heavy metals, solvents)(also heavy metals, solvents)

Bimodal age distributionBimodal age distribution–– Young children < 6 with accidental ingestionsYoung children < 6 with accidental ingestions–– Adolescents as a result of substance abuseAdolescents as a result of substance abuse

Mental status changes w/ lethargy, confusion, Mental status changes w/ lethargy, confusion, inappropriate speech are commoninappropriate speech are commonDiagnosed via urinary and/or serum toxin screenDiagnosed via urinary and/or serum toxin screen

Mass LesionsMass Lesions

4545--60% of all childhood brain tumors arise in the brain 60% of all childhood brain tumors arise in the brain stem or cerebellumstem or cerebellumPosterior Posterior fossafossa tumors usually present with slowly tumors usually present with slowly progressive ataxia and symptoms of increased ICPprogressive ataxia and symptoms of increased ICPFocal Focal neurologicneurologic findings are common (findings are common (papilledemapapilledema, , cranial nerve palsies, cranial nerve palsies, hemiparesishemiparesis))Common InfraCommon Infra--tentorialtentorial tumors:tumors:–– AstrocytomasAstrocytomas: account for >50% of all primary CNS : account for >50% of all primary CNS

malignancies; most common brain tumor of childhoodmalignancies; most common brain tumor of childhood–– MedulloblastomaMedulloblastoma: arises from the cerebellum; most common : arises from the cerebellum; most common

malignant malignant brain tumor in children; 40% of all posterior brain tumor in children; 40% of all posterior fossafossatumorstumors

MRI allows better visualization of cerebellum and is the MRI allows better visualization of cerebellum and is the recommended study (lack of bone artifact, high recommended study (lack of bone artifact, high resolution and capability of imaging different planes)resolution and capability of imaging different planes)

PatientPatient’’s MRIs MRI

AtaxiaAtaxia--TelangiectasiaTelangiectasiaAutosomalAutosomal recessiverecessiveMost common degenerative ataxiaMost common degenerative ataxiaAge of ataxia onset is ~15moAge of ataxia onset is ~15mo--2yrs with progression to 2yrs with progression to loss of ambulation by adolescence loss of ambulation by adolescence Clinical manifestations include progressive ataxia, Clinical manifestations include progressive ataxia, oculomotoroculomotor dysfunction, dysfunction, oculocutaneousoculocutaneous telangiectasiastelangiectasias(present around age 5)(present around age 5)Combined B and T cell immunodeficiency Combined B and T cell immunodeficiency (decreased (decreased IgAIgA, , IgG2, CD4 T cells);IgG2, CD4 T cells); presents with recurrent presents with recurrent sinopulmonarysinopulmonaryinfectionsinfectionsIncreased risk of malignancy (lymphoma, leukemia, HD, Increased risk of malignancy (lymphoma, leukemia, HD, brain tumors)brain tumors)Laboratory investigation reveals increased alphaLaboratory investigation reveals increased alpha--fetoprotein and decreased fetoprotein and decreased immunoglobulinsimmunoglobulins, CD4 cells, CD4 cells

TelangiectasiasTelangiectasias

Telangiectasia presents after the diagnosis should already have been confirmed by the presence of ataxia and infections

PINNA BULBAR CONJUNCTIVA

FriedreichFriedreich’’ss AtaxiaAtaxiaAutosomalAutosomal recessive recessive Age of onset between 10Age of onset between 10--15 years 15 years (before 25)(before 25)

Mutation in gene encoding a Mutation in gene encoding a mitochodrialmitochodrial protein protein fraxatinfraxatin which leads to iron overload and increased which leads to iron overload and increased production of free radicalsproduction of free radicalsClinical features: progressive Clinical features: progressive sensorysensory ataxia, impaired ataxia, impaired vibration and position sense, vibration and position sense, areflexiaareflexia of lower of lower extremities, progressive weakness of extremities, progressive weakness of LEsLEs, , oculomotoroculomotordisturbances, disturbances, dysarthriadysarthria, hearing impairment, reduced , hearing impairment, reduced visual acuityvisual acuityNonNon--neurologicneurologic features: skeletal deformities (scoliosis), features: skeletal deformities (scoliosis), hypertrophichypertrophic cardiomyopathycardiomyopathy, diabetes mellitus, diabetes mellitusCognition is normal Cognition is normal Prognosis: wheelPrognosis: wheel--chair bound by 10chair bound by 10--12 yrs. Median 12 yrs. Median survival after disease onset is ~35yrssurvival after disease onset is ~35yrs

Documents

Childhood Ataxia