Children

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Paediatric Neuromuscular Disease
Recent Advances in Neuromuscular Disease
VS
What is old in neuromuscular disease (and
should be remembered)
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Neuromuscular Disease
Insist on accurate terminology
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Changing Diagnosis
Patient RT
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2
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Neuromuscular Disease
Traditional symptoms and signs

• Muscle weakness
• Muscle wasting
• Hypotonia
• Hyporeflexia
• Sensory disturbance

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Neuromuscular Disease
Muscle weakness is not a complaint of childhood
My deltoids are about MRC 4/5
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Neuromuscular Disease
Parental concerns
20 ambulant children with weakness

• Trouble walking and running
• Poor at sports
• Cannot keep up with peers
• Poor coordination
• Tires easily
• Falls frequently

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Neuromuscular Disease
Some atypical presentations

• 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)

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Neuromuscular Disease
Read between the lines
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Neuromuscular Disease
Patient JF - medical record notes
Visit - 1
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
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Neuromuscular Disease
Patient JF - medical record notes
Visit - 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
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Duchenne Muscular Dystrophy
Presentation

• Known family history
• Delayed motor milestones
• Gait disturbance
• Delayed mental development
• Delayed language development

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Duchenne Muscular Dystrophy
Age at walking - 111 patients
number of patients
months
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Duchenne Muscular Dystrophy
Indications for CK
(In relation to 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

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Neuromuscular Disease
Do not expect classic adult features in children
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Peroneal Muscular Atrophy
Hallmarks of peroneal muscular atrophy
Tooth (1886)

• 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

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Peroneal Muscular Atrophy
Age at onset
Harding / Thomas Brain 103259 1980
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Peroneal Muscular Atrophy
Age at onset of symptoms
RCH - 42 children
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Peroneal Muscular Atrophy
Champagne bottle legs
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Peroneal Muscular Atrophy
Symptoms / signs at presentation
RCH - 44 patients (types 1 2)
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Peroneal Muscular Atrophy
Brothers with PMA type 1
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Neuromuscular Disease
Affected parents may be asymptomatic
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Peroneal Muscular Atrophy
Patient HR (1)
34 years. Asymptomatic
5 years age. Poor coordination, frequent falls,
no foot deformity
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Peroneal Muscular Atrophy
Patient HR (2)
34 years. Asymptomatic
5 years age. Poor coordination, frequent falls,
no foot deformity
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Peroneal Muscular Atrophy
Asymptomatic parents
Vanasse et al 1981

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

• RCH Series
• 7 out of 40 affected parents asymptomatic

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Congenital Myotonic Dystrophy
Asymptomatic parents
Harper 1975

• 54 mothers of CMyoD children
• asymptomatic at time of diagnosis 20
• symptomatic - no medical attention 14

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Neuromuscular Disease
Ask for old photographs
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Congenital Myotonic Dystrophy
Patient JS (centre)
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Neuromuscular Disease
Review old biopsies and postmortems
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Neuromuscular Disease
Review old material / ask for photographs
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Neuromuscular Disease
Review undiagnosed patients changing
signs improved knowledge new diagnostic tests
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Emery Dreifuss Dystrophy
Patient AB
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Neuromuscular Disease
Do not always accept what parents tell you
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Neuromuscular Disease
Patient CN
Father of BN
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Neuromuscular Disease
Patient BN
Daughter of CN
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Neuromuscular Disease
If you think you are onto a good thing stick to
it
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Tomaculous Neuropathy (HNPP)
Patient SW 12y
Acute onset brachial palsy while swimming
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Tomaculous Neuropathy (HNPP)
Family of SW
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3
2
4 Brachial plexus palsy
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3 Ulnar palsy
2 Four focal neuropathies
1 Transient foot drop
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Tomaculous Neuropathy (HNPP)
Pathology
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Tomaculous Neuropathy (HNPP)
Cardinal Features

• 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)

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Tomaculous Neuropathy (HNPP)
Clinical

• Incidence 16 / 100,000 population (?higher)
• Onset 50 in second decade (birth - old age)
• Problem Initial mononeuropathy (or plexopathy)
• Deficit Motor gt sensory. Painless
• Recover Days to weeks
• Note Clinical heterogeneity. Many
  asymptomatic Some tingling, cramps,
  myalgia, pes cavus

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Tomaculous Neuropathy (HNPP)
Clinical
Sites involved

• 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

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Neuromuscular Disease
Remember You may be dealing with an iceberg
The most dangerous bit is not obvious
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Neuromuscular Disease
Family H (1)
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Neuromuscular Disease
Family H (2)
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Neuromuscular Disease
Family H (3)
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Neuromuscular Disease
Family H (4)
Anaesthetic related deaths
15 others positive for MH by CK or biopsy (2000)
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Neuromuscular Disease
Patient MB (female)
5m Delayed development, hypotonia Dysmorphic
features - ptosis, abnormal ears, small -
antimongoloid slant to eyes 4y Muscle biopsy
(needle) - non specific / neurogenic 12y Scoliosis
. CK 2243 (rrlt240). Review of
biopsy 16y Scoliosis surgery. Subtle MH
reaction In vitro testing for MH - positive
Diagnosis King-Denborough syndrome
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Neuromuscular Disease
Patient MB
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King-Denborough Syndrome
J Pediatrics 8337 1973

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

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King-Denborough Syndrome
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Neuromuscular Disease
Central core myopathy
MH susceptible
M.O.
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Central Core Myopathy
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Neuromuscular Disease
DNA might be the gold standard but it is not
always infallible
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Myotonic Dystrophy
Patient MM - 9 yrs
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
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Myotonic Dystrophy
Patient MM - 9 yrs
K.M.
S.M.
M.M.
Allele 1 - 5 Allele 2 - 13 ie WNL. Repeated
with same result
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Paediatric Neuromuscular Disease

• Clinical Clues and Pitfalls
• a series of anecdotes, experiences, facts and
  figures

Lloyd Shield