Neurological Manifestations of Influenza Infection in Adults and Children: Results of a National British Surveillance Study

Abstract

Introduction In recent years an increasing range of neurological syndromes has been associated with the emergence of novel influenza A:H1N1 (2009), and other influenza viruses. We aimed to describe the features of adults and children with neurological manifestations associated with influenza in the UK. Method A surveillance study was performed in conjunction with the BNSU and BPNSU* over a 24–month period (February 2011 to February 2013). Inclusion criteria specified acute neurological illness within 1 month of proven influenza infection and prospective case definitions were applied. Results Twenty–five cases were identified: 4 adults and 21 children [6 (23%) with pre–existing neurological disorders]. Four (16%) cases (all with encephalopathy syndromes) died. Twenty cases (80%) required admission to intensive care. Seventeen (68%) had Glasgow Outcome Scores of 2–5 indicating poor outcome. Polymerase chain reaction (PCR) of respiratory secretions identified: influenza A in 21 (20 H1N1) and influenza B in 4 cases. Two had co–infection with Streptococcus pneumoniae (one adult with septicaemia; one child with meningitis). Cerebrospinal fluid (CSF) revealed a pleocytosis in 3 out of 18 cases (median 184×106 cells/litre [range 16–900]). Influenza PCR was negative in all 10 CSF samples tested. Cerebral magnetic resonance imaging was performed in 3 cases, computerised tomography in 6, and 14 had both. Recognised acute encephalopathy syndromes were seen in 5, and non–specific changes including cerebral oedema and/or diffusion restriction in 5. For the 4 adults, 2 presented with acute extrapyramidal movement disorders, 1 with Guillain–Barré syndrome and 1 with acute encephalopathy. Of the 21 children, 17 presented with acute encephalopathy, 3 with encephalitis and 1 with acute dyskinesia. Encephalopathy syndromes were documented in 7 cases (6 children, 1 adult). They were characterised by their clinical presentation and neuroimaging and included 4 with Acute Necrotising Encephalopathy (ANE), 1 Acute Infantile Encephalopathy Predominantly Affecting the Frontal Lobes (AIEF), 1 Haemorrhagic Shock & Encephalopathy (HSE) syndrome and 1 Acute Haemorrhagic Leukoencephalopathy (AHL). Treatments included: systemic steroids in 4 cases, 1 had intravenous immunoglobulin, and 3 cases received both. None received plasma exchange. Influenza vaccination was indicated in eight cases, but none had received it. Conclusion This paediatric and adult UK cohort identified a severity of influenza related neurological manifestation not reported previously. Cases were more common in children, particularly those with underlying neurological conditions. Encephalopathy syndromes such as ANE, AIEF, HSE and AHL were seen more frequently in children and were associated with a worse outcome. Acute movement disorders and Guillain–Barré syndrome were identified more commonly in adults. Influenza related encephalopathy may be more common in those with abnormal genetically determined host inflammatory responses, but the virus itself is rarely detected in ...

Severe post-influenza (H1N1) encephalitis involving pulvinar nuclei in an adult patient

“…Moreover, while the treatment of the acute encephalitis/meningitis relies on antiviral and antibacterial agents, in ADEM it consists of immunosuppression and immunomodulation with steroids, intravenous immunoglobulin and plasma exchange, since it appears to be a predominantly inflammatory disease 15. Immunotherapy was ineffective in our patient, with other cases of irreversible encephalitis refractory to treatment already described in children10 16 and, more rarely, in adults 17 18. Several cases of bilateral thalamic lesions related to H1N1 encephalopathies have been described in the literature 12 13 17 19–21.…”

“…We reviewed the PubMed indexed cases of H1N1 encephalopathies in adults (n=8), and all of the three cases identified as ADEM had had a poor outcome;18 27 28 in two other cases identified as ANE, a 20-year-old patient had good recovery and a 42-year-old man died without clear information regarding the interval between respiratory and neurological symptoms, making an ADEM diagnosis uncertain 10 17. Finally, in the remaining three cases, there was also no clear distinction between acute and post-infectious encephalitis, and two of them had a bad outcome 29–31.…”

CNS infections – The challenges ahead

“…A variety of acute encephalopathies have been described including the severe Acute Necrotizing Encephalopathy (ANE) seen mainly in infancy and the Mild Encephalitis / Encephalopathy associated with a Reversible Splenial Lesion (MERS) in older children. It is interesting that many of the affected patients were neurologically impaired prior to the illness (11,13). Genetic susceptibility to IAE may at least partly explain this phenomenon (14,15).…”

“…Emergence of H1N1 since 2009 has focused on IAE from different parts of the globe (11,12,13). A variety of acute encephalopathies have been described including the severe Acute Necrotizing Encephalopathy (ANE) seen mainly in infancy and the Mild Encephalitis / Encephalopathy associated with a Reversible Splenial Lesion (MERS) in older children.…”

Inflammatory damage on respiratory and nervous systems due to hRSV infection

“…Indeed, infection with other respiratory viruses, such as hMPV, Flu and hADV, has been associated with neurological dysfunction [12][13][14][15]. In addition, seizures are a common symptom associated to the neurotropic strain of Flu, hADV and probably hRSV [13,15,16 ,17].…”