Acute Flaccid Paralysis - Malaysian Paediatric Association
Acute Flaccid Paralysis - Malaysian Paediatric Association
Acute Flaccid Paralysis - Malaysian Paediatric Association
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<strong>Acute</strong> <strong>Flaccid</strong> <strong>Paralysis</strong><br />
Terrence Thomas<br />
Pediatric Neurologist<br />
Pediatric Neurology<br />
Update 2010<br />
Sabah Women<br />
& Children’s Hospital<br />
Hospital Likas
Agenda<br />
●<br />
●<br />
●<br />
●<br />
Overview of AFP<br />
Update on Guillain Barré syndrome<br />
Viruses and anterior horn cell disease<br />
Review clinical / diagnostic approach to AFP
<strong>Acute</strong> <strong>Flaccid</strong> <strong>Paralysis</strong> (AFP) Definition<br />
●<br />
●<br />
Rapid evolution of motor weakness (< than 4 days)<br />
Loss of tone in paralysed limb<br />
Excludes weakness due to trauma, spastic<br />
paralysis.
AFP Surveillance - Why do it?<br />
Wild Poliovirus<br />
Only endemic in 4 countries: India, Pakistan, Afghanistan, Nigeria<br />
Malaysia:<br />
●<br />
●<br />
●<br />
good vaccine coverage<br />
last outbreak 1986<br />
2 sporadic cases (parents refused vaccine) in 1992 ¹<br />
Neighbours:<br />
●<br />
imported cases into Indonesia in 2005<br />
¹ Hussain. J Paed Child Health 04
∗<br />
Confirmed Polio<br />
WHO Protocol for AFP Surveillance<br />
Residual paralysis<br />
Death<br />
Lost to follow up<br />
Polio Compatible<br />
Inadequate stools<br />
AFP<br />
Wild Poliovirus No wild Poliovirus<br />
No residual paralysis<br />
2 adequate stools<br />
∗ ∗ ∗<br />
∗<br />
Discarded (Non-polio AFP)<br />
Expert<br />
Committee<br />
Review<br />
WHO. GPEI
Confirmed Polio<br />
3<br />
∗<br />
AFP Surveillance: Areas of Shortfall<br />
2<br />
Residual paralysis<br />
Death<br />
Lost to follow up<br />
Polio Compatible<br />
1<br />
Inadequate stools<br />
AFP<br />
Wild Poliovirus No wild Poliovirus<br />
No residual paralysis<br />
2 adequate stools<br />
∗ ∗ ∗<br />
∗<br />
Discarded (Non-polio AFP)<br />
Expert<br />
Committee<br />
Review<br />
WHO. GPEI
1<br />
2<br />
3<br />
AFP Surveillance: Areas of Shortfall<br />
AFP<br />
●<br />
●<br />
Inadequate stools<br />
●<br />
●<br />
●<br />
Lost to follow up<br />
●<br />
under recognition<br />
under-reporting (“too much work, let’s avoid it”)<br />
not taken (patient is constipated)<br />
missed (patient moves ward care areas, staff changes)<br />
specimen handling (wrong lab, test label error (AFB))<br />
missed 60 day follow up for Residual <strong>Paralysis</strong><br />
WHO. GPEI
AFP in Malaysia, 1997 - 2001: main aetiology<br />
Guillain Barré syndrome<br />
CNS infection<br />
Transverse myelitis<br />
Non-polio enterovirus<br />
Hypokalemic paralysis<br />
Viral myalgia / myositis<br />
total n = 517<br />
156<br />
84<br />
55<br />
32<br />
27<br />
13<br />
%<br />
30<br />
16<br />
11<br />
Hussain. J Paed Child Health 04<br />
6<br />
5<br />
3
Exposed myelin<br />
epitopes on<br />
nodes of Ranvier<br />
Guillain Barré Syndrome: Site of injury
Normal<br />
nerve<br />
GBS<br />
nerve<br />
Guillain Barré Syndrome: Pathophysiology<br />
Node of Ranvier<br />
Open Na<br />
channels t<br />
Anti-ganglioside<br />
Abs block<br />
Na t channels<br />
Conduction<br />
block<br />
Vucic. J Clin Neurosc 09
<strong>Paralysis</strong><br />
Guillain Barré Syndrome: Disease course<br />
Full Motor<br />
Power Clinical course of GBS<br />
Prodromal<br />
infection<br />
Anti-Ganglioside antibodies<br />
0 2 4 6 8<br />
Time from onset of weakness (weeks)
Guillain Barré Syndrome: Symptoms in children<br />
n=49, age < 18 yrs<br />
Mean age<br />
Weakness<br />
Pain<br />
Ataxia<br />
Paraesthesia<br />
Dysautonomia<br />
Cranial neuropathy<br />
Shortness of breath<br />
7.1 yrs<br />
73 %<br />
55 %<br />
44 %<br />
18 %<br />
18 %<br />
15 %<br />
4 %<br />
Sladky J Child Neurol 04
GBS Scale: Hughes Functional Scale<br />
Grade 0<br />
Grade 1<br />
Grade 2<br />
Grade 3<br />
Grade 4<br />
Grade 5<br />
Grade 6<br />
healthy<br />
minor symptoms, able to run<br />
walks 5m without support but unable to run<br />
walks 5m needing support<br />
bed or chair bound<br />
requiring assisted ventilation<br />
death<br />
Hughes. Lancet 1978
GBS in children: Investigations<br />
●<br />
●<br />
Nerve conduction studies<br />
- demonstrates conduction block<br />
- differentiates demyelinating and axonal forms<br />
CSF analysis<br />
- high protein, normal cells<br />
Note: NCS and CSF may be normal in 1st week of illness !
Guillain Barré Syndrome: clinical variants<br />
AIDP<br />
AMAN<br />
AMSAN<br />
PCB variant<br />
Miller Fisher syndrome<br />
Sensory GBS<br />
Autonomic GBS<br />
acute immune demyelinating polyradiculopathy<br />
acute motor axonal neuropathy<br />
acute motor-sensory axonal neuropathy<br />
pharyngo-cervical-branchial variant
Clinical features amongst GBS subtypes<br />
Age, yrs<br />
Prodromal illness<br />
Weakness<br />
Paraesthesia<br />
Cranial nerve<br />
involvement<br />
Autonomic symptoms<br />
Respiratory failure 1<br />
* p
Clinical features, Outcome amongst GBS subtypes<br />
max GBS score<br />
onset to IVIG, days<br />
ventilation days<br />
PICU stay, days<br />
hospital stay, days<br />
GBS score at 6 mths<br />
* p
AntiGanglioside antibodies in Guillain Barré Syndrome<br />
GM 1<br />
GD1a<br />
GalNac-GD1a<br />
GD1b<br />
GT1a<br />
GQ1b<br />
Children n=63 Adults n=39<br />
n<br />
4<br />
0<br />
1<br />
2<br />
1<br />
0<br />
% n %<br />
6.5<br />
-<br />
1.6<br />
3.2<br />
1.6<br />
-<br />
5<br />
1<br />
1<br />
3<br />
0<br />
0<br />
13.0<br />
2.6<br />
2.6<br />
7.7<br />
-<br />
-<br />
NS<br />
NS<br />
Schessl. Arch Dis Child 07
GQ1b antibody syndrome<br />
SWACH<br />
●<br />
●<br />
●<br />
●<br />
●<br />
Hospital Likas<br />
internal & external ophthalmoplegia<br />
ataxia<br />
areflexia<br />
85 % patients positive for GQ1b antibodies<br />
Overlap with Bickerstaff’s encephalitis:<br />
●<br />
encephalopathy<br />
seizures
GBS: Treatment options<br />
Efficacious<br />
Plasma exchange<br />
up to 5 exchanges in 2 weeks<br />
IV Immunoglobulins<br />
GBS scale Grade 4 within 2 weeks of onset<br />
Not Recommended:<br />
Plasma exchange + IVIG<br />
IV Methylprednisolone<br />
IVIG + IV Methylprednisolone<br />
²<br />
¹<br />
¹<br />
Raphael.<br />
Cochrane Library 02<br />
Hughes.<br />
Cochrane Library 02<br />
¹ not better ² no benefit<br />
PE/Sandoglobulin GBS<br />
Trial Group. Lancet 97<br />
Hughes.<br />
Cochrane Library 02<br />
Dutch GBS Study<br />
Group. Lancet 04
AFP Case vignette 1<br />
●<br />
●<br />
●<br />
●<br />
●<br />
●<br />
SWACH<br />
Hospital Likas<br />
2.5 yrs. boy<br />
2 weeks ago had cough, coryza<br />
presented with refusal to walk<br />
later noted limited excursion in upper limbs<br />
no fever, diarrhoea<br />
no change in sensorium, seizures
AFP Case vignette 1<br />
SWACH<br />
Hospital Likas<br />
Examination:<br />
●<br />
●<br />
●<br />
●<br />
●<br />
●<br />
●<br />
Irritable; strong cry<br />
refused to stand but able to kick out<br />
resists upper limb exam by pushing away examiners hands<br />
refuses to reach out for objects<br />
normal tone; repeated taps to elicit reflexes; flexor plantars<br />
no ataxia<br />
no muscle / bone / joint tenderness
AFP Case vignette 1<br />
SWACH<br />
Hospital Likas<br />
Differential Diagnosis<br />
●<br />
●<br />
Viral myalgia (normal CK levels - not myositis)<br />
Transient synovitis
AFP Case vignette 1<br />
SWACH<br />
Hospital Likas<br />
Day 2-3 admission<br />
●<br />
●<br />
●<br />
●<br />
●<br />
still whingy, irritable<br />
tone now reduced - upper and lower limbs<br />
knee jerks difficult to elicit<br />
upper limbs - still reduced movements<br />
lower limbs - beginning to stand by day 3
AFP Case vignette 1<br />
SWACH<br />
Hospital Likas<br />
Day 4-5 admission<br />
●<br />
standing by day 4; upper limbs still hypotonic, weak<br />
Is this mild GBS ??<br />
Nerve conduction studies, day 5 illness
AFP Case vignette 1<br />
SWACH<br />
Hospital Likas<br />
2nd week of illness<br />
●<br />
●<br />
●<br />
●<br />
no longer fretful<br />
walking day 6-7 illlness<br />
upper limbs - distal function good,<br />
limited proximal movements<br />
repeat NCS day 14 - still completely normal study<br />
Impression:<br />
● ? spinal cord disorder<br />
● ? brachial neuritis
AFP Case vignette 1<br />
T2 Sagittal spine<br />
SWACH<br />
Hospital Likas<br />
T2 axial<br />
sections
AFP Case vignette 1<br />
SWACH<br />
Hospital Likas<br />
Treatment<br />
●<br />
IV Methylprednisolone 20 mg/kg/day for 5 days<br />
6 weeks oral steroid taper<br />
● outcome: - good manual dexterity<br />
No viral studies were done<br />
(family not keen)<br />
- bilateral deltoid wasting<br />
- rotate and elevates scapula<br />
to reach objects at shoulder level
AFP in Malaysia, 1997 - 2001: main aetiology<br />
Guillain Barré syndrome<br />
CNS infection<br />
Transverse myelitis<br />
Non-polio enterovirus<br />
Hypokalemic paralysis<br />
Viral myalgia / myositis<br />
total n = 517<br />
156<br />
84<br />
55<br />
32<br />
27<br />
13<br />
%<br />
30<br />
16<br />
11<br />
Hussain. J Paed Child Health 04<br />
6<br />
5<br />
3
Viral myelitis<br />
Enteroviruses<br />
polio virus<br />
Flaviviruses<br />
enterovirus 71<br />
coxsackie A, B<br />
West Nile virus<br />
Japanese encephalitis<br />
Kincaid. Curr Neurol Neurosc Rep 06
Poliovirus<br />
Baker AB.<br />
Neurology 57<br />
Viral myelitis<br />
acute flaccid paralysis<br />
aseptic meningitis<br />
undifferentiated fever<br />
brainstem<br />
encephalitis<br />
acute flaccid paralysis<br />
brainstem encephalitis<br />
aseptic meningitis<br />
EV71<br />
undifferentiated fever
Mouse model of human EV71 infection<br />
Jane Cardosa, Wong Kum Thong<br />
anterior horn cells, lumbar spine trigeminal nucleus, brainstem<br />
Ong KC. J Neuropathol Exp Neurol 08
West Nile Virus<br />
genus<br />
range<br />
vector<br />
reservoir<br />
clinical infection<br />
flaviviridae<br />
Africa, Europe<br />
now North America, Asia (India, China), Australia<br />
Culex spp<br />
birds<br />
encephalitis<br />
acute flaccid paralysis<br />
(anterior horn cell injury)
West Nile Virus<br />
Phylogenetic Tree<br />
LINEAGE 1<br />
LINEAGE 2<br />
LINEAGE 3<br />
LINEAGE 4<br />
Czech Rep 1997<br />
Asn<br />
Russia 1998 Thr<br />
Russia<br />
Pro<br />
1999<br />
New York 1999 Pro<br />
New Jersey 1999 Pro<br />
New York 1999 Pro<br />
Mexico 2003 Pro<br />
Israel 1998 Pro<br />
Tunisia 1997 Thr<br />
Italy 1998 Thr<br />
France 2000 Thr<br />
Romania 1996 Pro<br />
Russia<br />
Pro<br />
1999<br />
Kenya 1998 Thr<br />
China 2001 Thr<br />
Egypt 1951 Pro<br />
Ethiopia 1976 Thr<br />
Australia 1960 Ala<br />
Uganda 1937 His<br />
South Africa 1989 His
AFP Case vignette 2<br />
●<br />
●<br />
●<br />
●<br />
●<br />
●<br />
SWACH<br />
Hospital Likas<br />
1 yr. 3 mths boy<br />
normal neurodevelopment<br />
5 days of fever, with rash: - oral ulcers<br />
- macular and vesicular rash<br />
over the palms and soles<br />
awoke in the morning with flaccid weakness Left leg<br />
constipation on day before<br />
associated urinary retention
AFP Case vignette 2<br />
SWACH<br />
Hospital Likas<br />
Examination:<br />
●<br />
●<br />
alert, well oriented; fretful<br />
no cranial nerve deficits<br />
● Left lower limb: - weak hip flexion<br />
●<br />
●<br />
other limbs normal<br />
- flaccid muscles about the knee, ankle<br />
- absent knee, ankle reflexes<br />
lax anal tone, distended bladder
AFP Case vignette 2<br />
SWACH<br />
Hospital Likas<br />
Differential Diagnosis:<br />
●<br />
●<br />
●<br />
HFMD - enteroviral infection<br />
Transverse myelitis<br />
other Spinal cord lesions<br />
Investigations<br />
●<br />
stool, throat, rectal samples: no viruses cultured; PCR neg
T2 Sag<br />
Spine<br />
T2 Ax<br />
Spine
AFP Case vignette 2<br />
SWACH<br />
Hospital Likas<br />
Final Diagnosis:<br />
●<br />
HFMD - enteroviral infection<br />
VS<br />
Transverse myelitis<br />
Treatment<br />
●<br />
IV Methylprednisolone, later IV Immunoglobulins<br />
Outcome<br />
●<br />
Residual flaccid paralysis below the Left knee
AFP: Diagnostic flowchart<br />
Pediatric Protocols for<br />
<strong>Malaysian</strong> Hospitals, 2nd ed
LETM<br />
anterior horn<br />
cells<br />
complete cord<br />
central cord
TM differential diagnoses<br />
diffuse leptomeningeal<br />
carcinomatosis<br />
spinal cord AV<br />
malformation<br />
neuroblastoma<br />
vertebral body<br />
disease
vignette 1<br />
anterior<br />
cord lesion
Botulism: Clinical<br />
presentation<br />
History<br />
●<br />
●<br />
●<br />
constipation<br />
swallowing difficulty<br />
limb and respiratory muscle weakness<br />
● later drowsiness, encephalopathy<br />
Examination<br />
●<br />
●<br />
●<br />
ptosis, ophthalmoplegia (dilated pupils)<br />
weak gag reflex<br />
hypotonia, muscle weakness, areflexia
Botulism: Risk factors<br />
Utah study, n = 39<br />
Father with outdoor occupation<br />
wild, unprocessed honey<br />
Thompson. Neurol 05<br />
Living near residential construction 34<br />
Breast fed + other foods<br />
Breast fed only<br />
Living near highway construction<br />
Specific food risk factors<br />
corn syrup<br />
n<br />
22<br />
16<br />
11<br />
10<br />
%<br />
87<br />
56<br />
41<br />
28<br />
5
Botulism: Nerve conduction study<br />
Repetitive stimulation at 30 Hz for 1 second<br />
L ulnar nerve<br />
L tibial nerve<br />
POSITIVE incremental response<br />
suggestive of a pre-synaptic<br />
defect in neuromuscular<br />
transmission
Botulism: Clinical presentation<br />
Management<br />
●<br />
●<br />
●<br />
Rule out differential diagnoses<br />
Supportive measures, ICU care<br />
(Clostridium Botulinum Immune Globulin)
AFP: Concluding remarks<br />
Careful approach<br />
●<br />
●<br />
●<br />
history and examination<br />
recognise emergencies: - respiratory compromise<br />
- treatable spinal cord lesions<br />
Diligently complete the AFP surveillance workup !
The end
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