Introduction
Methods
Author | Inclusion period | Country/region | No pts | EV-D68 pos | Gender (% male) | Age (mean or median with range) | Prodrome (%) | Limb weakness (%) | Asymmetry (%) | Sensory involvement (%) | Hyporeflexia (%) | Cranial nerve dysfunction (%) | Ventilatory support (%) | Bowel/bladder dysfunction (%) | CSF pleocytosis (%) | Protein raised in CSF (%) | MRI spine: T2 hyperintensity (%) | Nerve root enhancement (%) | Brainstem lesions | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Andersen | 2001–2014 | Australia | 8 | 0% (13% EV-A71) | 25 | Med 5 | 100 | 100 | 100 | 0 | NS | 25 | NS | 0 | 85 | 71 | 100 | 38 | 25 |
2 | Messacar | 2012–2015 | USA | 159a | 20–45% | 56–91 | Med 7.1 (0.4–73) | 64–100 | 83–100 | 47–70 | 21–44 | 80–81 | 18–83 | 9–34 | 18–51 | 64–91 | 45–58 | 90–100 | 20–40 | 35–75 |
3 | Elrick | 2012–2016 | USA | 34 | 13% | 65 | Med 5 (< 1–15) | 100 | 100 | 97 | 0 | 67 | > 24 | 24 | 6 | 97 | 45 | 100 | 38 | 62 |
4 | Yea | 2014 | Canada | 25 | 28% | 64 | Med 7.8 (0.8-15.0) | 88 | 100 | NS | 12 | 88 | > 20 | 28 | 36 | 72 | 28 | 100 | 72 | 32 |
5 | Gordon-Lipkin | 2014–2017 | USA | 16 | 23% | 69 | Med 4 (3–6) | 100 | 100 | NS | 6 | 63 | 50 | 31 | NS | 100 | NS (Med 6.3 g/L) | 100 | 13 | 42 |
6 | Chong | 2015 | Japan | 59 | 15% | 59 | Med 4.4 (2.6–77) | 97 | 100 | 68 | 20 | 90 | 17 | 8 | 27 | 85 | 46 | 100 | 51 | 42 |
7 | Knoester | 2015–2016 | Europe | 29 | 100%b | 52 | Med 4 (1.6–55) | 92 | 100 | NS (usual) | 7 | 87 | 60 | 66 | 7 | 91 | NS (Med 3.8 g/L) | 92 | 16 | 68 |
8 | Bonwitt | 2016 | USA | 10 | 20% (10% EV-A71) | 70 | Med 6 (3–14) | 80 | 100 | NS | NS | NS | 30 | 10 | 50 | 78 | NS (Med 5.8 g/L) | 100 | 0 | 30 |
9 | Iverson | 2016 | USA | 5 | 60% | 20 | Mean 7.7 (3.5–12) | 100 | 100 | NS | NS | NS | 80 | NS | NS | 100 | NS | 80 | NS | NS |
10 | Hübner | 2016 | Germany | 16 (7)c | 6% | 50 | Mean 4.6 (1.7-14.3) | 100 | 100 | 86 | NS | NS | NS | 14 | NS | 43 | NS | 86 | NS | NS |
11 | Ruggieri | 2016 | Argentina | 11 | 36% | 54 | Mean 3.2 (0.3–6) | 100 | 100 | 81 | 0 | 100 | 45 | 36 | 0 | 63 | 18 | 100 | NS | 45 |
12 | Sarmast | 2017 | India | 9 | 0% | 56 | Med 5.5 (2–7) | 100 | 100 | 100 | 0 | 100 | 11 | NS | 0 | 89 | 22 | 100 | NS | 11 |
13 | McKay | 2018 | USA | 80 | 37% (29% EV-A71) | 59 | Med 4 (0.7–32) | 99 | 100 | NS | NS | NS | NS | NS | NS | 83 | NS (Med 4.7 g/L) | 100 | NS | NS |
14 | Ramsay | 2018 | UK | 40 (16)d | 36% | 53 | 55% under 5 yo | 55 | 98 | NS | NS | NS | NS | 55 | NS | 18 | NS | 43 | NS | NS |
Epidemiology
Clinical features
Differential diagnosis
Acute flaccid myelitis (with EV-D68) | Guillain-Barré syndrome | Acute transverse myelitis | |
---|---|---|---|
Prodrome | |||
Type | Febrile illness often with respiratory and/or gastrointestinal symptoms | Febrile illness often with gastrointestinal symptoms and or respiratory symptoms | Commonly a preceding febrile illness |
Time until onset of weakness | Usually within 1 week | Several weeks | Days to weeks |
Clinical details | |||
Neurologic deficits | Asymmetric flaccid weakness, with upper limbs often more affected, proximal > distal | Ascending weakness, lower limbs > upper limbs | Symmetric weakness, may be asymmetric initially |
Reflexes | Typically low or absent | Low or absent | Usually high, can be low initially |
Sensory symptoms | Typically no sensory deficits | Paresthesia and slight distal sensory symptoms (except in AMAN) | Common, often with a sensory level |
Cranial nerve deficits | Bulbar weakness and asymmetric facial palsy common; sometimes oculomotor deficits | Symmetric facial weakness; oculomotor deficits in MFS | None |
Other symptoms | Pain, autonomic dysfunction | Pain, autonomic dysfunction | Bowel and bladder dysfunction |
Time course | Progressive over hours to days | Progressive symptoms over several days | Progressive over 4 h to 21 days |
Findings | |||
CSF | Slight pleocytosis, raised protein. May be completely normal | Raised protein after several days, without pleocytosis (“dissociation cytoalbuminique”) | Slight pleocytosis, raised protein. May be completely normal |
Microbiology | EV-D68 in respiratory specimen | Campylobacter jejuni in feces; EBV, CMV, HEV, Zika virus in blood | Usually none |
MRI brain | Typical T2-hyperintense region in the dorsal pons, sometimes also in caudate nuclei. Cranial nerve enhancement possible | Normal | Normal |
MRI spine | Longitudinally extensive diffuse slightly hyperintense central cord lesion, usually most pronounced in the cervical region. Sometimes cauda equina root enhancement | Cauda equina root enhancement may be found | Central cord focal hyperintense lesion over multiple levels affecting white and gray matter |
EMG | Findings of motor axonopathy with low CMAPs, normal NCV. Normal sensory findings | Decreased NCV with blocks are typical. Normal sensory findings in AMAN | Normal |
Treatment/prognosis | |||
Treatment | No effective treatment, potential positive effect of IVIG | IVIG and/or plasmapheresis effective | High-dose steroids, sometimes IVIG and/or plasmapheresis |
Prognosis | Improvement over several months, but often significant residual weakness and muscle atrophy | Often complete recovery over the course of weeks until months | Partial recovery over the course of months until years |
Investigations
Blood | Routine investigations (blood count, inflammatory parameters, creatine kinase, liver and renal function tests) |
Auto-antibodies (anti-MOG IgG, anti-AQP4, anti-GM1, anti-GQ1b) | |
Oligoclonal bands (both serum and CSF) | |
Microbiology: testing for enterovirus (including poliovirus), EBV, CMV, VZV, HEV, Zika virus* | |
CSF | Routine investigations (cell count, protein, glucose) |
Oligoclonal bands (both CSF and serum) | |
Microbiology: testing for enterovirus, parechovirus, HSV, VZV, EBV | |
Further microbiologic testing | Nasopharyngeal swab for enterovirus testing Stool sample for enterovirus and C. jejuni testing |
Imaging | Contrast-enhanced MRI of the brain and spine |
Neurophysiologic testing | EMG with motor and sensory investigation of an affected limb |