Ataxia in Childhood – a collection of clinical cases.
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Transcript of 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.
Clinical case # 2Clinical case # 2
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
Clinical case # 3Clinical case # 3
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
Clinical case # 3Clinical case # 3
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
Clinical case # 3Clinical case # 3
Investigations : Investigations :
CT Brain: marked cerebellar atrophyCT Brain: marked cerebellar atrophy Immunoglobulins (no result)Immunoglobulins (no result) Chromosomes………Chromosomes………
Diagnosis Diagnosis
Ataxia Ataxia TelangiectasiaTelangiectasia
Clinical case # 4Clinical case # 4
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.
Cerebellum: Structure & FunctionCerebellum: Structure & Function
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.
Cerebellum: Structure & FunctionCerebellum: Structure & Function
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
Cerebellum: Structure & FunctionCerebellum: Structure & Function
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)
Chronic Progressive Childhood Chronic Progressive Childhood Ataxias 2Ataxias 2
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)
Chronic Progressive Childhood Chronic Progressive Childhood Ataxias 3Ataxias 3
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)