Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Paediatric Neuromuscular Disease

What is old in neuromuscular disease

(and should be remembered)

Recent Advances in Neuromuscular Disease

VS

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Insist on accurate terminology

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Changing DiagnosisPatient RT

1

2

3

4

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Muscle weaknessMuscle wastingHypotoniaHyporeflexiaSensory disturbance

Traditional symptoms and signs

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseaseMuscle weakness is not a complaint of childhood

My deltoids are about MRC 4/5

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Trouble walking and runningPoor at sportsCannot keep up with peersPoor coordinationTires easilyFalls frequently

Parental concerns20 ambulant children with weakness

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Behaviour disorder (dermatomyositis) Delayed intellectual or language development (DMD) Dysmorphic features : high palate, micrognathia,UDT, Arthrogryposis (foetal akinesia deformation syndrome) Feeding difficulty, pharyngeal incoordination Leucodystrophy (congenital musc dystrophy) Vocal cord palsy at birth (SMA) Constipation (myotonic dystrophy) Elevated aminotransaminases (dystrophies)

Some atypical presentations

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Read between the lines

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

22/12 5 year old male - prep grade

“Cannot run as fast as classmates”

“Always falling over”

“Teacher has recommended a check to see why he cannot run fast”

O/E: Gait - prominent lumbar lordosis - broad based

Imp: No serious abnormality - seems to be an awkward clumsy child

Patient JF - medical record notesVisit - 1

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseasePatient JF - medical record notesVisit - 2

2/2 “Noticed by teachers to be not running properly”

O/E: “Pleasant boy with rolling gait with pelvis tending to drop to right”

“Right quads slightly wasted”

“Tone, power, reflexes normal”

Plan: “X-ray hips. Refer to Orthopaedic clinic”

19/2 Orthopaedic and Neurology Clinics

Classical Duchenne

Can barely walk up steps or rise from floor

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Duchenne Muscular Dystrophy

Known family history

Delayed motor milestones

Gait disturbance

Delayed mental development

Delayed language development

Presentation

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Duchenne Muscular Dystrophy

Age at walking - 111 patients

months

num

ber

of p

atie

nts

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Duchenne Muscular Dystrophy

Known or suspected family history Unexplained delay in motor development

Especially male not walking by 18 months Unexplained gait disturbance - esp. toe walking Unexplained intellectual impairment Unexplained language delay

Indications for CK(In relation to muscular dystrophy)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Do not expect classic adult features

in

children

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular Atrophy

Commences in lower extremities Hands and forearms attacked early Disease is one of childhood Heredity is a marked feature Fibrillar or fascicular tremors are frequent Degenerative electrical changes often seen early Disease of peripheral nerves

Hallmarks of peroneal muscular atrophyTooth (1886)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular Atrophy

Harding / Thomas Brain 103:259 1980

Age at onset

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular Atrophy

0

5

10

15

20

25

30

number

0--3 3--6 6--9 9--11years

Age at onset of symptomsRCH - 42 children

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular AtrophyChampagne bottle legs

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular Atrophy

7

52

14

36

50

63

55

93

2

9

36

45

68

0 20 40 60 80 100

Hypotonia

Sensory

DTR's normal

DTR's absent

DTR's depressed

Foot deformity

Frequent falls

Abnormal walk/run

Weakness

% patients

Signs Symptoms

Symptoms / signs at presentationRCH - 44 patients (types 1 & 2)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular AtrophyBrothers with PMA type 1

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Affected parents may be asymptomatic

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular Atrophy

34 years. Asymptomatic5 years age. Poor coordination, frequent falls, no foot deformity

Patient HR (1)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular Atrophy

34 years. Asymptomatic5 years age. Poor coordination, frequent falls, no foot deformity

Patient HR (2)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Peroneal Muscular AtrophyAsymptomatic parents

11 affected parents 4 definite symptoms 2 minimal deficit on examination 5 asymptomatic / normal examination

Vanasse et al 1981

RCH Series 7 out of 40 affected parents asymptomatic

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Congenital Myotonic Dystrophy

54 mothers of CMyoD children

asymptomatic at time of diagnosis 20

symptomatic - no medical attention 14

Harper 1975

Asymptomatic parents

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Ask for old photographs

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Congenital Myotonic DystrophyPatient JS (centre)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Review old biopsies and postmortems

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseaseReview old material / ask for photographs

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Review undiagnosed patients

changing signs

improved knowledge

new diagnostic tests

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Emery Dreifuss DystrophyPatient AB

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Do not always accept what parents tell you

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseasePatient CNFather of BN

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseasePatient BNDaughter of CN

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

If you think you are onto a good thing

stick to it

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Tomaculous Neuropathy (HNPP)

Acute onset brachial palsy while swimming

Patient SW 12y

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Tomaculous Neuropathy (HNPP)

32

4

1

Family of SW

1 Transient foot drop

2 Four focal neuropathies

3 Ulnar palsy

4 Brachial plexus palsy

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Tomaculous Neuropathy (HNPP)Pathology

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Tomaculous Neuropathy (HNPP)

Recurrent mononeuropathies or plexopathies NCS abnormalities in clinically unaffected nerves Characteristic pathology - myelin thickenings Autosomal dominant inheritance DNA deletion 17p 11.2 (PMP-22 gene)

Cardinal Features

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Tomaculous Neuropathy (HNPP)

Incidence: 16 / 100,000 population (?higher) Onset: 50% in second decade (birth - old age) Problem: Initial mononeuropathy (or plexopathy) Deficit: Motor > sensory. Painless Recover: Days to weeks

Note: Clinical heterogeneity. Many asymptomaticSome: tingling, cramps, myalgia, pes cavus

Clinical

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Tomaculous Neuropathy (HNPP)

Nerves subject to compression, stretch, friction

Usually associated with trivial trauma Commonest sites

• peroneal at fibula head• ulnar at elbow• radial at spiral groove of humerus• median at carpal tunnel• brachial plexus, sciatic, cranial

ClinicalSites involved

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Remember :

You may be dealing with an iceberg

The most dangerous bit is not obvious

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseaseFamily H (1)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseaseFamily H (2)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseaseFamily H (3)

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

Name Year AgeRH 1921 17SH 1926 24WB 1928 11AR 1935 39JB 1940 27MR 1940 16DB 1941 19GH 1948 24WR 1952 29DH 1952 12

Family H (4)

15 others positive for MH by CK or biopsy (2000)

Anaesthetic related deaths

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

5m Delayed development, hypotoniaDysmorphic features - ptosis, abnormal ears, small

- antimongoloid slant to eyes

4y Muscle biopsy (needle) - non specific / neurogenic

12y Scoliosis. CK 2243 (rr<240). Review of biopsy

16y Scoliosis surgery. Subtle MH reaction

In vitro testing for MH - positive

Patient MB (female)

Diagnosis: King-Denborough syndrome

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseasePatient MB

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

King-Denborough Syndrome

Small build Cryptorchidism Pectus carinatum Kyphosis / lordosis Hypoplastic mandible Crowded lower teeth Antimongoloid slant to eyes Ptosis Low attachment of ears Webbed neck

J Pediatrics 83:37 1973

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

King-Denborough Syndrome

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular DiseaseCentral core myopathy

MH susceptible

M.O.

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Central Core Myopathy

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Neuromuscular Disease

DNA might be the gold standard

but

it is not always infallible

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Myotonic Dystrophy

K.M.

S.M.M.M.

From 7 yrs: fatigue, poor concentration, poor writing, feet turning in

“Known to be affected” - DNA studies 1993 age 3 years

“A double check on the original studies will not go astray”

Patient MM - 9 yrs

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Myotonic Dystrophy

K.M.

S.M.M.M.

Allele 1 - 5 Allele 2 - 13 ie WNL. Repeated with same result

Patient MM - 9 yrs

Children’s Neuroscience CentreRoyal Children’s Hospital, Melbourne

Paediatric Neuromuscular Disease

Clinical Clues and Pitfalls

a series of anecdotes, experiences, facts and figures

Lloyd Shield