Friday, June 2, 2023
| Specimen source | No. of patients with specimens available(% of 238) | No. (%) positive | EV/RV type results (no.) |
|---|---|---|---|
| Any source* | 219 (92) | 107 (49) | EV-D68 (34) |
| EV-A71 (12) | |||
| Coxsackievirus A2 (1) | |||
| Coxsackievirus A4 (1) | |||
| Coxsackievirus A9 (1) | |||
| Coxsackievirus A16 (1) | |||
| Coxsackievirus B3 (1) | |||
| Echovirus 11 (1) | |||
| RV-A101 (2) | |||
| RV-A24 (1) | |||
| RV-A38 (1) | |||
| RV-A54 (1) | |||
| RV-A81 (1) | |||
| RV-A85 (1) | |||
| RV-B4 (1) | |||
| RV-C54 (1) | |||
| Other/Untyped EV/RV (46) | |||
| Respiratory | 190 (80) | 92 (48) | EV-D68 (33) |
| EV-A71 (10) | |||
| RV-A101 (2) | |||
| RV-A24 (1) | |||
| RV-A38 (1) | |||
| RV-A54 (1) | |||
| RV-A81 (1) | |||
| RV-A85 (1) | |||
| RV-B4 (1) | |||
| RV-C54 (1) | |||
| Other/Untyped EV/RV (40) | |||
| Stool | 119 (50) | 24 (20) | EV-D68 (3) |
| EV-A71 (2) | |||
| Coxsackievirus A2 (1) | |||
| Coxsackievirus A4 (1) | |||
| Coxsackievirus A9 (1) | |||
| Coxsackievirus A16 (1) | |||
| Coxsackievirus B3 (1) | |||
| Echovirus 11 (1) | |||
| Other/Untyped EV/RV (13) | |||
| CSF | 187 (79) | 9 (5) | EV-D68 (2) |
| EV-A71 (1) | |||
| Other/Untyped EV/RV (6) | |||
| Serum | 90 (38) | 3 (3) | EV-D68 (1) |
| Echovirus 11 (1) | |||
| Other/Untyped EV/RV (1) |
Table 1. Enterovirus/rhinovirus (EV/RV) polymerase chain reaction test results from respiratory, stool, cerebrospinal fluid (CSF), and serum specimens collected from patients with onset of confirmed acute flaccid myelitis (N = 238) — United States, 2018
*Some patients had multiple positive specimens.
| Characteristic | No. (%) | |||
|---|---|---|---|---|
| EV-D68 (n = 34) | EV-A71 (n = 12) | Other (n = 192)* | Total (N = 238) | |
| Demographic | ||||
| Median age, yrs | 5.9 | 1.6 | 5.3 | 5.3 |
| Range | 1.4–56.9 | 0.9–32.7 | 0.5–81.8 | 0.5–81.8 |
| IQR | 3.7–7.9 | 1.1–2.1 | 3.4–8.3 | 3.3–8.2 |
| Male sex | 20 (59) | 11 (92) | 107 (56) | 138 (58) |
| Geographic region | ||||
| South | 16 (47) | 0 (0) | 64 (33) | 80 (34) |
| Midwest | 6 (18) | 1 (8) | 54 (28) | 61 (26) |
| West | 6 (18) | 11 (92) | 39 (20) | 56 (24) |
| Northeast | 6 (18) | 0 (0) | 35 (18) | 41 (17) |
| Race/Ethnicity | ||||
| White | 23 (68) | 10 (83) | 92 (48) | 125 (53) |
| Hispanic | 5 (15) | 1 (8) | 41 (21) | 47 (20) |
| Black | 2 (6) | 0 (0) | 19 (10) | 21 (9) |
| Asian | 1 (3) | 0 (0) | 7 (4) | 8 (3) |
| Multiracial | 0 (0) | 0 (0) | 4 (2) | 4 (2) |
| Native Hawaiian/Pacific Islander | 0 (0) | 0 (0) | 1 (1) | 1 (0) |
| Unknown | 3 (9) | 1 (8) | 28 (15) | 32 (13) |
| Prodromal signs/symptoms in the 4 weeks before onset of limb weakness | ||||
| Any illness, no. (% of total) | 34 (100) | 12 (100) | 184 (96) | 230 (97) |
| Days before weakness onset (IQR)† | 5 (4–7) | 3 (2.5–6.5) | 6 (3–9) | 6 (3–9) |
| Any respiratory illness or fever, no. (% of total) | 34 (100) | 12 (100) | 174 (91) | 220 (92) |
| Days before weakness onset (IQR)† | 5 (4–7) | 3 (2–5) | 6 (3–9) | 6 (3–8) |
| Any respiratory illness, no. (% of total) | 33 (97) | 7 (58) | 151 (79) | 191 (80) |
| Days before weakness onset (IQR)† | 5 (4–7) | 3 (1–5) | 6 (4–9) | 6 (4–9) |
| Any fever, no. (% of total) | 28 (82) | 12 (100) | 144 (75) | 184 (77) |
| Days before weakness onset (IQR)† | 3 (2–6) | 3 (2–5) | 3 (2–6) | 3 (2–6) |
| Neck/back pain, no. (% of total) | 18 (53) | 4 (33) | 88 (46) | 110 (46) |
| Days before weakness onset (IQR)† | 2 (1–3) | 1.5 (0.5–4) | 1 (1–3) | 1.5 (1–3) |
| Headache, no. (% of total) | 12 (35) | 2 (17) | 73 (38) | 87 (37) |
| Days before weakness onset (IQR)† | 3 (2–3) | 2 (2–2) | 2 (1–6) | 2 (1–5.5) |
| Any gastrointestinal illness, no. (% of total) | 9 (26) | 6 (50) | 38 (20) | 53 (22) |
| Days before weakness onset (IQR)† | 2 (1–4) | 2.5 (2–3) | 3 (2–4) | 2 (2–4) |
| Rash, no. (% of total) | 3 (9) | 7 (58) | 13 (7) | 23 (10) |
| Days before weakness onset (IQR)† | 4.5 (2–7) | 4 (3–6) | 9.5 (3–18.5) | 4 (3–7) |
| Signs/Symptoms at evaluation | ||||
| Gait difficulty | 19 (56) | 6 (50) | 99 (52) | 124 (52) |
| Pain in neck or back | 20 (59) | 4 (33) | 87 (45) | 111 (47) |
| Fever | 16 (47) | 8 (67) | 59 (31) | 83 (35) |
| Pain in affected limb(s) | 10 (29) | 3 (25) | 69 (36) | 82 (34) |
| Headache | 13 (38) | 2 (17) | 51 (27) | 66 (28) |
| Neck weakness | 7 (21) | 1 (8) | 31 (16) | 39 (16) |
| Ataxia/Discoordination | 6 (18) | 8 (67) | 24 (13) | 38 (16) |
| Facial weakness | 9 (26) | 0 (0) | 28 (15) | 37 (16) |
| Dysphagia | 6 (18) | 2 (17) | 23 (12) | 31 (13) |
| Bladder retention/incontinence | 2 (6) | 3 (25) | 23 (12) | 28 (12) |
| Altered consciousness | 2 (6) | 6 (50) | 18 (9) | 26 (11) |
| Dysarthria | 6 (18) | 1 (8) | 17 (9) | 24 (10) |
| Numbness in affected limb(s) | 2 (6) | 1 (8) | 13 (7) | 16 (7) |
| Paresthesia in affected limb(s) | 0 (0) | 0 (0) | 16 (8) | 16 (7) |
| Bowel retention/incontinence | 1 (3) | 3 (25) | 10 (5) | 14 (6) |
| Diplopia | 2 (6) | 1 (8) | 9 (5) | 12 (5) |
| Ptosis | 3 (9) | 0 (0) | 6 (3) | 9 (4) |
| Seizures | 2 (6) | 1 (8) | 3 (2) | 6 (3) |
| Initial neurologic exam findings | ||||
| Decreased strength in upper limb(s) | 22 (65) | 4 (33) | 127 (66) | 153 (64) |
| Decreased strength in lower limb(s) | 16 (47) | 2 (17) | 67 (35) | 85 (36) |
| Any sensory abnormalities | 5 (15) | 0 (0) | 25 (13) | 30 (13) |
| Any cranial nerve abnormalities | 12 (35) | 2 (17) | 37 (19) | 51 (21) |
| Abnormal mental status | 1 (3) | 5 (42) | 6 (3) | 12 (5) |
| CSF microscopic examination§ | ||||
| CSF pleocytosis | 31/32 (97) | 12/12 (100) | 140/166 (84) | 183/210 (87) |
| Median cells/mm3 | 95 | 125 | 91.5 | 94 |
| Range | 9–499 | 17–685 | 6–814 | 6–814 |
| IQR | 36–170 | 67–480 | 42.5–157.5 | 43–163 |
| MRI findings¶ | ||||
| Supratentorial lesions | 3/33 (9) | 3/12 (25) | 23/182 (13) | 29/227 (13) |
| Brainstem lesions | 15/33 (45) | 11/12 (92) | 74/182 (41) | 100/227 (44) |
| Cerebellar lesions | 1/33 (9) | 9/12 (75) | 38/182 (21) | 50/227 (22) |
| Cervical cord lesions | 33/34 (97) | 12/12 (100) | 174/187 (80) | 219/233 (94) |
| Thoracic cord lesions | 28/31 (90) | 6/11 (55) | 142/163 (87) | 176/205 (86) |
| Conus lesions | 16/25 (64) | 2/5 (40) | 2/5 (36) | 71/177 (40) |
| Nerve root enhancement | 5/33 (15) | 6/12 (50) | 38/182 (21) | 49/227 (22) |
Table 2. Demographic and clinical characteristics of patients with onset of confirmed acute flaccid myelitis (N = 238), by virus type — United States, 2018
Abbreviations: CSF = cerebrospinal fluid; EV = enterovirus; IQR = interquartile range; MRI = magnetic resonance imaging.
*Other category includes all patients who did not have a positive EV-D68 or EV-A71 test, including those who were never tested, those who had negative test results, and those who had positive test results for other viruses.
†Timing calculated among cases with the prodromal illness/symptom and documented dates of onset.
§Among 210 cases with CSF results available. Median cells/mm3 calculated among cases with CSF pleocytosis (>5 white blood cells per mm3).
¶Supratentorial, brainstem, and cerebellar lesions among 227 cases with brain MRI reports available. Cervical cord lesions among 233 cases with cervical spine reports available, thoracic cord lesions among 205 cases with thoracic spine reports available, and conus lesions among 177 cases with lumbosacral spine reports available. Nerve root enhancement among 227 cases with a contrast MRI of the spine.
| Characteristic | No. (%) | |||
|---|---|---|---|---|
| EV-D68 (N = 34) | EV-A71 (N = 12) | Other (N = 192)* | Total (N = 238) | |
| Hospitalization | ||||
| Hospitalized | 34 (100) | 12 (100) | 187 (97) | 233 (98) |
| Hospitalized ≥1 day before onset of limb weakness | 7 (21) | 4 (33) | 14 (7) | 25 (11) |
| Hospitalized on same day or after onset of limb weakness | 27 (79) | 8 (67) | 171 (89) | 206 (87) |
| Hospitalized, unknown timing | 0 (—) | 0 (—) | 2 (1) | 2 (1) |
| Timing from onset of weakness to hospitalization,† days | ||||
| Median interval from onset of weakness to hospitalization | 1 | 0.5 | 1 | 1 |
| Range | 0–5 | 0–5 | 0–54 | 0–54 |
| IQR | 0–2 | 0–2.5 | 0–2 | 0–2 |
| 0–1 | 20/27 (74) | 5/8 (63) | 109/171 (64) | 134/206 (65) |
| 2–3 | 6/27 (22) | 2/8 (25) | 44/171 (26) | 52/206 (25) |
| 4–7 | 1/27 (4) | 1/8 (13) | 8/171 (5) | 10/206 (5) |
| >7 | 0/27 (—) | 0/8 (—) | 10/171 (6) | 10/206 (5) |
| Treatment received | ||||
| Steroids, no IVIG | 8 (24) | 1 (8) | 46 (24) | 55 (23) |
| IVIG, no steroids | 9 (26) | 8 (67) | 37 (19) | 54 (23) |
| Both steroids and IVIG | 12 (35) | 2 (17) | 67 (35) | 81 (34) |
| Plasma exchange | 5 (15) | 1 (8) | 26 (14) | 32 (13) |
| Admitted to ICU | 25 (74) | 5 (42) | 99 (52) | 129 (54) |
| Respiratory support | 19 (56) | 3 (25) | 43 (22) | 65 (27) |
| Mechanical ventilation | 15 (44) | 1 (8) | 39 (20) | 55 (23) |
| Location of first medical encounter after onset of weakness§ | ||||
| Emergency department | 17/27 (63) | 2/8 (25) | 115/176 (65) | 134/211 (64) |
| Primary care provider | 5/27 (19) | 4/8 (50) | 40/176 (23) | 49/211 (23) |
| Urgent care provider | 4/27 (15) | 0/8 (—) | 12/176 (7) | 16/211 (8) |
| Unknown/missing/other | 1/27 (4) | 2/8 (25) | 9/176 (5) | 12/211 (6) |
| Timing from onset of limb weakness to first medical encounter,§ days | ||||
| Median interval from onset of weakness to first medical encounter¶ | 0 | 0 | 1 | 0 |
| Range | 0–3 | 0–1 | 0–15 | 0–15 |
| IQR | 0–1 | 0–0.5 | 0–1 | 0–1 |
| 0–1 | 19/27 (70) | 8/8 (100) | 133/176 (76) | 160/211 (76) |
| 2–3 | 5/27 (19) | 0/8 (—) | 29/176 (16) | 34/211 (16) |
| 4–7 | 0/27 (—) | 0/8 (—) | 4/176 (2) | 4/211 (2) |
| >7 | 0/27 (—) | 0/8 (—) | 2/176 (1) | 2/211 (1) |
| Unknown/Missing | 3/27 (11) | 0/8 (—) | 8/176 (5) | 11/211 (5) |
Table 3. Characteristics of hospitalization, treatment, and first medical encounter after onset of limb weakness among patients with confirmed acute flaccid myelitis (N = 238), by virus type — United States, 2018
Abbreviations: EV = enterovirus; ICU = intensive care unit; IQR = interquartile range; IVIG = intravenous immunoglobulin.
*Other category includes all patients who did not have positive EV-D68 or EV-A71 test results, including those who were never tested, those who had negative test results, and those who had positive test results for other viruses.
†Among the 206 patients (EV-D68 = 27; EV-A71 = 8; other = 171) who were hospitalized on or after the date of onset of limb weakness;
§Among the 211 patients who had onset of limb weakness as an outpatient (206 patients who were hospitalized on or after the date of onset of limb weakness and five patients who were never hospitalized).
¶Among 200 patients who had onset of limb weakness as an outpatient and known timing of onset of limb weakness and first medical encounter (211 patients minus the 11 with timing unknown).
This activity is intended for public health officials, pediatricians, emergency department physicians, internists, and other clinicians caring for children with presumed or confirmed acute flaccid myelitis (AFM).
The goal of this activity is to describe findings of medical record review of 238 patients with confirmed AFM in 2018, including cases associated with enterovirus (EV)-D68 and EV-A71, considering clinical characteristics of patients and settings and timing of seeking medical care for limb weakness.
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Background: Acute flaccid myelitis (AFM) is a serious neurologic syndrome that affects mostly children and is characterized by the acute onset of limb weakness or paralysis. Since U.S. surveillance for AFM began in 2014, reported cases have peaked biennially. This report describes the clinical characteristics of AFM patients during 2018, the most recent peak year.
Methods: Medical records from persons meeting AFM clinical criterion (acute onset of flaccid limb weakness) were submitted to CDC. Patients with confirmed AFM met the clinical criterion and had magnetic resonance imaging indicating spinal cord lesions largely restricted to gray matter and spanning one or more vertebral segments. Symptoms, physical findings, test and imaging results, and hospitalization data were abstracted and described.
Results: Among 238 patients with confirmed AFM during 2018, median age was 5.3 years. Among the 238 patients, 205 (86%) had onset during August–November. Most (92%) had prodromal fever, respiratory illness, or both beginning a median of 6 days before weakness onset. In addition to weakness, common symptoms at clinical evaluation were gait difficulty (52%), neck or back pain (47%), fever (35%), and limb pain (34%). Among 211 who were outpatients when weakness began, most (76%) sought medical care within 1 day, and 64% first sought treatment at an emergency department. Overall, 98% of patients were hospitalized, 54% were admitted to an intensive care unit, and 23% required endotracheal intubation and mechanical ventilation.
Conclusion: Clinicians should suspect AFM in children with acute flaccid limb weakness, especially during August–November and when accompanied by neck or back pain and a recent history of febrile respiratory illness. Increasing awareness in frontline settings such as emergency departments should aid rapid recognition and hospitalization for AFM.
Acute flaccid myelitis (AFM) is a serious neurologic syndrome that can cause paralysis, predominantly in previously healthy children. Similar to poliomyelitis-associated acute flaccid paralysis caused by poliovirus infection, AFM is a syndrome characterized by the acute onset of flaccid limb weakness accompanied by predominantly gray matter lesions in the spinal cord. AFM can progress rapidly over the course of hours or days, leading to permanent paralysis and the life-threatening complication of respiratory failure.[1]
National surveillance for AFM was initiated in 2014, after California and Colorado reported clusters of AFM or acute limb weakness among previously healthy children, none of whom had laboratory or epidemiologic evidence of poliovirus infection.[2,3] Since 2014, reported AFM cases have peaked in the late summer to early fall every 2 years in the United States.[4] Although national case reporting for AFM did not begin until 2014, retrospective case investigations have documented sporadic cases before 2014 and increased numbers of cases during 2014, 2016, and 2018.[5,6] Together, these data suggest that the epidemiology of AFM shifted during or shortly before 2014, and likely reflect a new or emerging etiology.
Multiple viruses, including West Nile virus, adenovirus, and nonpolio enteroviruses, are known to cause AFM in a small percentage of infected persons.[7–10] Pathogens are rarely recovered from the cerebrospinal fluid (CSF) of AFM patients, but enteroviruses are the most common pathogens detected in nonsterile site specimens, such as respiratory and stool specimens.[4,11] Enterovirus D68 (EV-D68) is the most common enterovirus type identified among AFM patients; poliovirus has not been detected in any cases.[4,11,12] In addition, recent data, including animal model studies and studies of enterovirus-binding antibodies in CSF, indicate that nonpolio enteroviruses, and EV-D68 in particular, are likely a primary cause of AFM in the United States since 2014.[13–17] However, other viruses that cause AFM might be contributing to the biennial peaks. A cluster of 11 AFM cases in Colorado associated with enterovirus A71 (EV-A71) contributed to the number of cases reported in 2018.[18,19]
Based on the observed biennial pattern, another increase in AFM cases is anticipated to occur in the United States in late summer/early fall 2020 (https://www.cdc.gov/grand-rounds/pp/2020/20200703-acute-flaccid-myelitis.html). This report summarizes findings from review of medical records from patients with confirmed AFM in 2018, including cases known to be associated with EV-D68 and EV-A71, and describes the clinical characteristics of patients and settings and timing of seeking medical care for limb weakness. These data might facilitate rapid case recognition of AFM and prompt referral to care.
