Wednesday, December 6, 2023
| Characteristic | Patient | ||||||
|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| Age,y/sex | 28/F | 37/F | 55/F | 20/F | 57/M | 31/F | 27/F |
| Days from illness onset | 3 | 2 | 10 | 5 | 3 | 4 | 3 |
| Medical history | Uncontrolled hyperthyroidism | Unremarkable | Influenza A(H3N2) virus encephalitis in 2012 | Treated for Russell−Silver syndrome | Unremarkable | Recent breast implants | Unremarkable |
| Leukocyte count, cells/mm3 | 2 | 2 | 10 | 5 | 2 | 3 | 13 |
| CSF | |||||||
| Protein, g/L | 0.143 | 0.270 | 2.305 | 0.251 | 0.313 | 0.162 | 7.156 |
| Glucose, g/L | 0.61 | 0.50 | 0.74 | 1.07 | 0.55 | 0.71 | 1.22 |
| Chloride, g/L | ND | ND | 7.60 | 6.78 | 7.10 | 6.80 | 7.02 |
| Virus type | B seq EPI_ISL_179707 | B seq EPI_ISL_179711 | B | B | B seq EPI_ISL_182519 | B | B seq EPI_ISL_182518 |
| Cerebral imaging result | MRI, abnormal† | CT, normal | MRI, abnormal‡ | MRI, normal | MRI, normal | NA | MRI, abnormal§ |
| Diagnosis | Confirmed encephalitis | Possible encephalitis | Confirmed encephalitis | Confirmed encephalitis | Possible encephalitis | Cerebellar ataxia | Confirmed encephalitis |
| Length of hospitalization, d | 7 | 9 | 18 | 17 | 10 | 5 | 3 |
| Outcome | Died | Complete resolution | Complete resolution | Complete resolution | Complete resolution | Complete resolution | Died |
| Clinical findings | Fever, headache, sleepiness, left upper limb motor deficit, coma, GCS score 3–4 | Fever, headache, sleepiness, photophobia, vertigo, stiff neck, positive Romberg sign | Fever, confusion, photophobia, dizziness, right facial paralysis, aphasia, stiff neck, coma, GCS score 8 | Fever, agitation, nystagmus, stiff neck, coma, GCS score 9–10 | Fever, headache, dysarthria, right side motor deficit, vomiting | Fever, headache, vomiting, vertigo, photophobia, ataxia, positive Romberg sign, movement and balance disorder | Fever, headache, vomiting, lethargy, aphasia, upward deviation of eyes, seizures, coma, GCS score 3 |
Table. Characteristics of 7 patients with neurologic complications of influenza B virus infection, Romania*
*All patients showed negative RT-PCR results for influenza B virus in CSF. CSF, cerebrospinal fluid; CT, computed tomography; GCS, Glasgow coma scale; MRI, magnetic resonance imaging; NA, not available; ND, not determined.
†MRI on day 3. See Figure 1 for a detailed description.
‡MRI on day 8. See Figure 2 for a detailed description.
§MRI on day 2 showed multiple areas of hyperintensities.
This activity is intended for infectious disease clinicians, neurologists, internists, intensivists, and other clinicians caring for patients with influenza B-related neurologic manifestations.
The goal of this activity is to describe neurologic complications of influenza B virus infection in adults, based on a case series from a tertiary facility in Romania.
Upon completion of this activity, participants will be able to:
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This study was approved by the ethics committee of the Stefan S. Nicolau Institute of Virology (Bucharest, Romania). Although this was a retrospective study, informed consent was obtained from each patient included in the study, as part of routine hospital activity.
We conducted a retrospective study of 7 patients given a diagnosis of influenza in whom neurologic complications developed. These patients were hospitalized in a tertiary care facility (Dr. Victor Babes Clinical Hospital of Infectious and Tropical Diseases, Bucharest, Romania) during the 2014–15 influenza season.
We used the case definition for encephalitis from the 2013 Consensus Statement of the International Encephalitis Consortium. Major criterion was altered mental status (defined as decreased or altered level of consciousness, lethargy, or personality change) lasting ≥24 hours with no alternative cause identified. Minor criteria were fever (temperature ≥38°C), generalized or partial seizures, new onset of focal neurologic findings, CSF leukocyte count ≥5 cells/mm3, and abnormality of brain parenchyma on neuroimaging suggestive of encephalitis.[13]
We collected nasopharyngeal swab specimens from all patients with ILI and sent these specimens to the National Reference Center for Influenza (Cantacuzino Institute, Bucharest, Romania) for antigenic and genetic characterization. Specimens were examined by using real-time reverse transcription PCRs (RT-PCRs) with the Superscript III Platinum One-Step Quantitative RT-PCR System (Invitrogen, Carlsbad, CA, USA) for influenza type A and type B viruses. Samples positive for influenza A viruses were tested by using a second real-time RT-PCR that discriminated between influenza A(H1N1)pdm09 and A(H3N2) virus subtypes. For samples positive for influenza B viruses, we used a second real-time RT-PCR and specific minor-groove binder probes to determine lineage.[14]
Positive specimens were inoculated into an MDCK line, and virus isolates were characterized antigenically by using a hemagglutination inhibition assay and turkey/guinea pig erythrocytes. We used the conventional Sanger sequencing technique to monitor influenza virus evolution for the complete hemagglutinin (HA) gene. The PRISM BigDye Terminator v3.1 Ready Reaction Cycle Sequencing Kit (Applied Biosystems, Foster City, CA, USA) was used to sequence DNA templates on a PRISM 3100-Avant Genetic Analyzer (Applied Biosystems). We determined genotypes of all virus sequences from patients by alignment with sequences found in Romania with World Health Organization reference viruses. We performed phylogenic analysis by using maximum-likelihood inference and a generalized time-reversible model of nucleotide substitution and a Γ model of rate heterogeneity with RAxML version 8.00 software.[15]
