Ataxia in Childhood – a collection of clinical cases

Ataxia in Ataxia in Childhood – Childhood –

a collection of clinical a collection of clinical casescases

Childhood AtaxiaChildhood Ataxia

4 Clinical Case descriptions 4 Clinical Case descriptions Cerebellum: Structure & FunctionCerebellum: Structure & Function Ataxia: Clinical FeaturesAtaxia: Clinical Features Classification of Childhood AtaxiaClassification of Childhood Ataxia Discussion of selected Ataxic disordersDiscussion of selected Ataxic disorders

Clinical case # 1Clinical case # 1History :History :

Miss M.K. a 13 year old female, previously wellMiss M.K. a 13 year old female, previously well

Normal milestones, coping well at schoolNormal milestones, coping well at school

Preceding history of vesicular rash, fever and Preceding history of vesicular rash, fever and malaisemalaise

Rash erupted 10 days prior to admissionRash erupted 10 days prior to admission

Acute onset of unsteady gait, confusion, refusing to Acute onset of unsteady gait, confusion, refusing to speakspeak

No history of immunocompromise No history of immunocompromise

Clinical case # 1Clinical case # 1Examination :Examination :

Thriving child, not dysmorphicThriving child, not dysmorphic Crops of vesicles over trunk and limbsCrops of vesicles over trunk and limbs Florid cerebellar signs: ataxia, DDK, Florid cerebellar signs: ataxia, DDK,

intention tremor, truncal hypotonia, intention tremor, truncal hypotonia, dysarthric speech, no nystagmus, dysarthric speech, no nystagmus, mildly encephalopathicmildly encephalopathic

Investigations :Investigations : LP - normal pressures, chemistry, cell LP - normal pressures, chemistry, cell

countscounts CT Brain - NADCT Brain - NAD

Diagnosis Diagnosis

Post varicella cerebellitis with Post varicella cerebellitis with encephalitisencephalitis

Clinical case # 2Clinical case # 2

History : History :

Master S.K. 11Master S.K. 11 year old boy, previously well, referred year old boy, previously well, referred from from Leratong hospitalLeratong hospital

c/o 5 months fatigue, loss of weight, dizziness, poor c/o 5 months fatigue, loss of weight, dizziness, poor balancebalance

Mother reported slurred speech, “drunken” gait, poor Mother reported slurred speech, “drunken” gait, poor handwriting handwriting

He was previously right-handed but was now using his He was previously right-handed but was now using his left hand onlyleft hand only

Clinical case # 2Clinical case # 2Examination :Examination :

Normal growth including head circumferenceNormal growth including head circumference Not dysmorphic, no skin lesions of neurocutaneous Not dysmorphic, no skin lesions of neurocutaneous

syndromessyndromes Systemic exam normalSystemic exam normal CNS:CNS: alert and responsive. Nil meningism. Cranial alert and responsive. Nil meningism. Cranial

nerves intact.nerves intact. Tone : truncal hypotonia, Power : full, Reflexes : ? Tone : truncal hypotonia, Power : full, Reflexes : ?

pendularpendular Sensation : intact, Proprioception : intactSensation : intact, Proprioception : intact

Cerebellum : Cerebellum : titubation, dysarthric speech, +DDK (marked on titubation, dysarthric speech, +DDK (marked on right), +dysmetria, +intention tremor, + heelshin right), +dysmetria, +intention tremor, + heelshin test on right, horizontal nystagmus present. test on right, horizontal nystagmus present.

Gait : broad-based ataxic gait. Gait : broad-based ataxic gait.


Investigations :Investigations :

CT Brain : CT Brain : posterior fossa lesion, posterior fossa lesion, highly highly calcified vermal and calcified vermal and right cerebellar right cerebellar hemisphere masshemisphere mass

Diagnosis Diagnosis

Cerebellar medulloblastomaCerebellar medulloblastoma


History :History :

Miss B.M. aged 6 yrs from Ladysmith referred to Miss B.M. aged 6 yrs from Ladysmith referred to Neuro Clinic Neuro Clinic with her 8 yr old similarly affected brotherwith her 8 yr old similarly affected brother

2 year history of red eyes, poor balance, frequent 2 year history of red eyes, poor balance, frequent falls, falls, shaking of head, now becoming progressively worseshaking of head, now becoming progressively worse

Milestones normal, intellectually normalMilestones normal, intellectually normal

No family history of noteNo family history of note


Examination :Examination :

marked gait ataxiamarked gait ataxia DDKDDK DysmetriaDysmetria cerebellar speechcerebellar speech pendular reflexespendular reflexes some dystonic posturing of trunk and armssome dystonic posturing of trunk and arms apraxic movement of eyesapraxic movement of eyes conjunctival telangiectasiaconjunctival telangiectasia


Investigations : Investigations :

CT Brain: marked cerebellar atrophyCT Brain: marked cerebellar atrophy Immunoglobulins (no result)Immunoglobulins (no result) Chromosomes………Chromosomes………

Diagnosis Diagnosis

Ataxia Ataxia TelangiectasiaTelangiectasia


History : History :

Master D.H. 9 year old maleMaster D.H. 9 year old male Presented at 7 years of age with poor balancePresented at 7 years of age with poor balance Bumping into things & falling over regularlyBumping into things & falling over regularly Mom had noticed deformity of feet and assumed Mom had noticed deformity of feet and assumed

this was the cause of the problemthis was the cause of the problem Taken to physiotherapist who referred him to Taken to physiotherapist who referred him to

paediatrician for investigation of ataxiapaediatrician for investigation of ataxia Family history: maternal grandmother had 3 Family history: maternal grandmother had 3

cousins with weakness, who became wheelchair-cousins with weakness, who became wheelchair-bound and died in their mid 30’sbound and died in their mid 30’s

Clinical case # 4Clinical case # 4Examination : Examination :

Thriving child. Normal head circumference. Thriving child. Normal head circumference. No dysmorphic features. Systemic exam NAD. No dysmorphic features. Systemic exam NAD.

CNS:CNS: Distal muscle wasting. Distal muscle wasting. Significant pes cavus bilaterally with hammer toes. Significant pes cavus bilaterally with hammer toes. Tone : globally reduced with rounded back but no Tone : globally reduced with rounded back but no

kyphoscoliosis.kyphoscoliosis. Power : proximally 5/5 , distally 3/5Power : proximally 5/5 , distally 3/5 Reflexes : globally absent, plantars equivocalReflexes : globally absent, plantars equivocal Sensation : glove and stocking sensory lossSensation : glove and stocking sensory loss Proprioception : intactProprioception : intact

Clinical case # 4Clinical case # 4Examination (continued): Examination (continued):

Cerebellum : dysarthric speechCerebellum : dysarthric speech +DDK+DDK +dysmetria +dysmetria Mild intention tremorMild intention tremor No nystagmusNo nystagmus Gait : high-stepping broad-based ataxic gaitGait : high-stepping broad-based ataxic gait Unable to stand on one legUnable to stand on one leg

Investigations : Investigations :

CT Brain & MRI normalCT Brain & MRI normal Cardiac assessment normal Cardiac assessment normal Nerve conduction – axonal sensory peripheral Nerve conduction – axonal sensory peripheral

neuropathyneuropathy Blood investigation….Blood investigation….

DiagnosisDiagnosis

…… ……..homozygous expansion in frataxin ..homozygous expansion in frataxin genegene

= Friedreich’s Ataxia= Friedreich’s Ataxia

Cerebellum: Structure & FunctionCerebellum: Structure & Function

The cerebellum is a vast coordinator of information receiving approximately 40 times more afferent than efferent fibres.

This vast afferent input gives the cerebellum a total picture of the body’s position in space, motion, head position and limb position as well as the state of contraction of different muscles.

The cerebellum sythesises this information, allowing one to adjust the speed, force and direction of a particular movement.


Organ of learned, skilled motor movementsOrgan of learned, skilled motor movements

Stores movement patterns which are Stores movement patterns which are available for instant retrieval, enabling one available for instant retrieval, enabling one to perform previously learned, difficult to perform previously learned, difficult combinations of movements effortlessly combinations of movements effortlessly

Postnatally maturing organ & so in Postnatally maturing organ & so in assessing clinical signs of cerebellar assessing clinical signs of cerebellar disease, one has to consider the child’s disease, one has to consider the child’s stage of development.stage of development.


Three main anatomical subdivisions:Three main anatomical subdivisions:

Central vermis Central vermis

Two lateral hemispheresTwo lateral hemispheres

Hemispheric lesionsHemispheric lesions may present may present with with ipsilateral cerebellar signsipsilateral cerebellar signs

Vermal lesionsVermal lesions may present with may present with central hypotonia and central hypotonia and bilateral signsbilateral signs


Archicerebellum - spatial position & movement of head Archicerebellum - spatial position & movement of head

Paleocerebellum - proprioceptive & regulation of muscle Paleocerebellum - proprioceptive & regulation of muscle tone, posture and gaittone, posture and gait

Neocerebellum - coordinates skilled motor movementsNeocerebellum - coordinates skilled motor movements

Three main functional Three main functional subdivisions:subdivisions:

Archicerebellum Archicerebellum (Vestibular)(Vestibular)Paleocerebellum Paleocerebellum (Spinal) (Spinal) Neocerebellum Neocerebellum (Cortical) (Cortical)

Cerebellar disease : Clinical Cerebellar disease : Clinical FeaturesFeatures

Ataxia: Ataxia: - incoordination of postural control and - incoordination of postural control and gaitgait

- incoordination of skilled fine - incoordination of skilled fine movements & speechmovements & speech

Vertigo (uncommon in children)Vertigo (uncommon in children) Vomiting (postural, projectile, positional)Vomiting (postural, projectile, positional) AtaxiaAtaxia NystagmusNystagmus Intention tremorIntention tremor Speech (slow, slurred, staccato)Speech (slow, slurred, staccato) HypotoniaHypotonia DysmetriaDysmetria DysdiadochokinesiaDysdiadochokinesia TitubationTitubation

Classification of Childhood Classification of Childhood AtaxiaAtaxia

AcuteAcute Chronic non-Chronic non-progressiveprogressive

Chronic Chronic progressiveprogressive

InfectionsInfections

Toxins / Toxins / MetabolicMetabolic

Posterior fossa Posterior fossa tumourstumours

TraumaTrauma

Migraine/Migraine/VascularVascular

HydrocephalusHydrocephalus

PerinatalPerinatal

Congenital Congenital MalformationsMalformations

Cerebellar-Kidney Cerebellar-Kidney associationsassociations

Post-natally acquiredPost-natally acquired

Brain tumours Brain tumours

Metabolic Metabolic disordersdisorders

Spino-cerebellar Spino-cerebellar degenerationsdegenerations

Acute Childhood AtaxiasAcute Childhood Ataxias

InfectionsInfections- Cerebellar abscessCerebellar abscess- Viral cerebellitis Viral cerebellitis (varicella, coxsackie, mumps, EBV, (varicella, coxsackie, mumps, EBV,

polio)polio)- Bacterial Bacterial (diphtheria, pertussis, typhoid)(diphtheria, pertussis, typhoid)

Toxins / MetabolicToxins / Metabolic- alcohol / antiepileptic drugsalcohol / antiepileptic drugs- heavy metal poisoningheavy metal poisoning- Hartnup / MSUDHartnup / MSUD- organic & aminoaciduriasorganic & aminoacidurias

Posterior fossa tumoursPosterior fossa tumours Trauma - Trauma - cerebellar haemorrhagecerebellar haemorrhage Migraine - Migraine - basilarbasilar Vascular -Vascular - embolism / thrombosis / AVM (rare) embolism / thrombosis / AVM (rare) HydrocephalusHydrocephalus

Chronic Non-Progressive Chronic Non-Progressive Childhood AtaxiasChildhood Ataxias

PerinatalPerinatal- Birth asphyxia – Cerebral palsy (hypotonic with or without Birth asphyxia – Cerebral palsy (hypotonic with or without

ataxia)ataxia)- HydrocephalusHydrocephalus- Metabolic (hypoglycaemia /kernicterus)Metabolic (hypoglycaemia /kernicterus)

Congenital MalformationsCongenital Malformations- Primary cerebellar hypoplasiaPrimary cerebellar hypoplasia- Dandy-WalkerDandy-Walker- Arnold-ChiariArnold-Chiari

Cerebellar-Kidney associationsCerebellar-Kidney associations- Meckel Gruber syndromeMeckel Gruber syndrome- Zellweger syndromeZellweger syndrome- Von Hippel LindauVon Hippel Lindau

Postnatally acquiredPostnatally acquired- Hypoxic insults – Cerebral Palsy Hypoxic insults – Cerebral Palsy - TraumaTrauma- Deficiency – thiamine, hypothyroidismDeficiency – thiamine, hypothyroidism

Chronic Progressive Childhood Chronic Progressive Childhood Ataxias 1Ataxias 1

Brain tumoursBrain tumours

- Cerebellar astrocytoma - Cerebellar astrocytoma - Von Hippel-Lindau - Von Hippel-Lindau (cerebellar (cerebellar

haemangioblastoma & haemangioblastoma & hypernephroid tumours) hypernephroid tumours)

- Ependymoma- Ependymoma - Medulloblastoma- Medulloblastoma - Neuroblastoma - Neuroblastoma (opsomyoclonus)(opsomyoclonus)


Metabolic disordersMetabolic disorders

- Sphingolipidoses Sphingolipidoses (Metachromatic Leukodystropy, (Metachromatic Leukodystropy, Krabbes, Niemann-Pick, Krabbes, Niemann-Pick,

Gauchers) Gauchers)

- Ceroid-lipofuscinosisCeroid-lipofuscinosis

- Abnormalities of DNA repair Abnormalities of DNA repair ((Ataxia Telangiectasia,Ataxia Telangiectasia, Cockayne syn.)Cockayne syn.)

- Energy metabolism Energy metabolism (Leigh syndrome, pyruvate (Leigh syndrome, pyruvate dehydrogenase dehydrogenase

deficiency)deficiency)

- Fatty acid metabolism Fatty acid metabolism (Adrenoleukodystrophy, Refsums)(Adrenoleukodystrophy, Refsums)

- - Other metabolic disorders Other metabolic disorders (Abetalipoproteinaemia, (Abetalipoproteinaemia, Hartnups, Hartnups, MSUD)MSUD)


Spino-cerebellar degenerationsSpino-cerebellar degenerations

Hereditary Spinocerebellar degeneration Hereditary Spinocerebellar degeneration

- Autosomal recessive (- Autosomal recessive (Friedreichs ataxia, Friedreichs ataxia, Cockayne, Cockayne, Behr syn.) Behr syn.)

- Autosomal dominant (SCA types 5 & 7, episodic - Autosomal dominant (SCA types 5 & 7, episodic ataxias) ataxias)

- X-linked- X-linked

Spinocerebellar LeukodystrophiesSpinocerebellar Leukodystrophies

Progressive myoclonic epilepsyProgressive myoclonic epilepsy

Friedreich’s AtaxiaFriedreich’s Ataxia

• Chronic progressive childhood ataxia• Hereditary spinocerebellar ataxia• Autosomal recessive : chromosome 9q13-q21• Mutant gene (frataxin) contains expanded GAA triplet repeats• Dying back neuropathy of the long ascending & descending tracts of the spinal cord • Diagnostic Criteria - onset before 20 years - autosomal recessive inheritance - combined involvement : peripheral nerves

cerebellar tractspyramidal tractsposterior columns

Friedreich’s AtaxiaFriedreich’s AtaxiaCNS Clinical Features : CNS Clinical Features : (variable)(variable)

CerebellarCerebellar• Progressive Ataxia (2-16years, more marked in legs,

wide based gait)• Progressive cerebellar speech• Titubation• Nystagmus

Corticospinal• Weakness & distal wasting calf and hand muscles• Positive Babinski reflex• Absent knee & ankle reflexes (may be present initially)

Posterior column• Vibratory & proprioception loss• Positive Romberg test

Peripheral nerves• Distal sensory loss

Friedreich’s AtaxiaFriedreich’s Ataxia

Associated Clinical Features :

Talipes-equino-varus Pes cavus (early onset/birth) Claw hand deformity Spastic bladder Cranial nerve involvement Kyphoscoliosis Cardiomyopathies – common, HOCM, progression to

intractable CCF Arrhythmias Diabetes (abnormal glucose tolerance and insulin

resistance)

Prognosis: (variable) Most wheelchair bound by mid-twenties Disease may become static and survival into sixties is

possible Mortality from CMO and respiratory problems 2° to severe

scoliosis

Ataxia TelangiectasiaAtaxia Telangiectasia

• Chronic progressive childhood ataxia

• Autosomal recessive - Chromosome 11q22-q23

• Defect of DNA repair

• Pathology = degeneration of cerebellar cortex, demyelination of posterior columns, spinocerebellar tracts & peripheral nerves, degeneration of posterior roots, sympathetic ganglia & AHC and loss of pigmentary cells substantia nigra, locus cereus, oculomotor complex, hypothalamus.

Ataxia TelangiectasiaAtaxia Telangiectasia

Clinical features:

- Progressive ataxia- Abnormal eye movements- Dystonic posturing hands & feet- Facial grimacing / slow spreading smile- Choreoathetosis- Cerebellar speech - Oculocutaneous telangiectasia- Intellectual fall off- Immune abnormalities- Increased incidence of malignancies

Ataxia TelangiectasiaAtaxia Telangiectasia Ataxia - Onset at 2-4 years, progresssive

- Awkwardness- Initially truncal

Oculomotor apraxia - Impaired upward gaze- Concomitant eye blinking

- Poor saccadic eye movements- Jerking head movements

Telangiectasia - Onset 2-6 years

- Bulbar conjunctivae - Ears, neck, antecubital &

popliteal fossae

Skin - Café-au-lait spots, vitiligo

- Sclerodermoid changes

Ataxia TelangiectasiaAtaxia Telangiectasia Immune deficiency:

- Cellular (thymic hypoplasia, tonsils, adenoids, spleen,

lymph nodes, lymphopaenia)- Humoral ( synthesis immunoglobulins with

recurrent sinopulmonary infections with bronchiectasis)

IgG, IgA, IgE IgM

Other clinical features

- Mild polyneuropathy- Hypotonia, reduced reflexes- Muscle bulk & weakness- Intellectual fall off - Defect in DNA repair, sensitivity to ionising radiation, increased risk of malignancy especially ALL/gliomas.

Ataxia TelangiectasiaAtaxia TelangiectasiaAssociations: - Mental handicap in 1/3 cases

- Hypogonadism- Hepatic dysfunction- Insulin resistance

Management: - No specific treatment- Prompt Rx sinopulmonary infections to

avoid bronchiectasis- Avoid exposure to radiation

Investigations: - Chromosomes- Immunoglobulins ( IgG, IgA, IgE IgM)- Other – increased AFP, CEA

Prognosis: - Wheelchair bound by 10 -15 years of age- 60% mortality by 3rd decade (infections, lymphoreticular malignancy)

Documents

Ataxia in Childhood – a collection of clinical cases