Acute Necrotizing Encephalitis in an Adult Patient with Novel Influenza A (H1N1) Infection

Neurologic complications of pandemic (H1N1) 2009 were first reported in children a case series of 4 pediatric patients in the United States in May 2009 in May 2009 [1]. Most subsequent reports were also of cases in children, because those <17 years of age appear most vulnerable [2], we are presenting a case of Encephalopathy in an adult young female with H1N1 influenza infection, with complete recovery, according to our records, this is the only case reported in the middle east .


Introduction
Influenza A (H1N1), which is also called human influenza virus with swine origin, has created a major worldwide health problem within a short time after its emergence [3]. This infection is often self-limited but sometimes can cause severe and fatal complications [4,5]. Involvement of the CNS in influenza virus infection is very rare, but serious manifestations like seizures, encephalitis, myelitis, Reye syndrome, and other neurologic disorders have been described previously in association with respiratory tract infection with seasonal influenza A or B viruses [6]. These findings indicate that, as with seasonal influenza, neurologic complications can occur with ongoing novel influenza A (H1N1) pandemic, but the frequency with which these occur is unknown. Encephalitis has been reported with novel H1N1 infection, mainly in children [7].
Other Neurologic manifestations of influenza are now known to include acute disseminated encephalomyelitis, Guillain-Barre syndrome, transverse myelitis, and acute necrotizing encephalopathy (ANE). Reports of ANE began surfacing from Japan during the influenza epidemics of the mid-and late 1990s [1]. According to studies from Japan, in the most severe cases of influenza-associated ANE, patients develop altered mental status with or without seizures and then rapidly progress to a comatose state within a mean of 24-72 hours from the onset of fever and upper respiratory symptoms [1,8,9]. Seizures are often resistant to antiepileptic medications. Death, which occurs in roughly 30% of cases, results largely from cardiorespiratory compromise or complications from mechanical ventilation [10]. two patients; in three other patients mild to severe neurologic sequelae were noted.

Case Study
To our knowledge, encephalopathy associated with the novel H1N1 influenza strain was first reported in a case series of 4 pediatric patients in the United States in May 2009 [13,14]. All 4 patients had mild seizures and/or altered mental status and all recovered fully without any neurological sequelae at discharge. There has been only few cases reported of encephalopathy in a novel H1N1 infection in adult; we are reporting a similar case in adult previously healthy female.
A 40 years old Indian female previously healthy was admitted with 3 days of medium grade fever, non productive cough, shortness of breath and was diagnosed with Pneumonia, her Neurological examination was within normal, Laboratory studies revealed increased white blood cell count (17.4×10 9 /L), Neutrophilia 85.5%, decreased lymphocytes 6.0, and elevated C-reactive protein of 15.8mg/dL. Serum electrolytes and renal and liver function tests were within normal limits. Her chest x ray shows bilateral scattered pneumonic patches; her H1N1 serology was positive, Tamiflu started on 3rd day of admission, Patient was shifted to intensive care unit and intubated Secondary to respiratory distress &hypoxia. She was sedated by continuous Dormicum infusion & Remifentanil, chest condition was getting better after three days from Tamiflu started.
Neurology service was consulted on day 6 as patient doesn't regain consciousness after discontinuation of sedation. O/E :pt was unconscious, not responding to verbal stimulation, in response to pain there is extension of lower limbs & moving upper limb, reflexes was brisk bilaterally, bilateral extensor planter Response. She had MRI, MRV, MRA done subsequently and showed Right frontal, right posterior parieto-occipital, left Tempro -parieto -occipital, extensive high cerebral and patchy left upper cerebral as well as right thalamic extending to upper right midbrain: hyper intensity suggesting micro bleeds and hemorrhagic components in T 2 with some restriction in DWI, some T 1 hyper intensities serpentine signals are seen filling the related sulci and leptomeninges , likely representing meningeal exudates (Figure 1 A course of IVIG was tried based on the reported cases of autoimmune nature of the disease, 2gm/Kg over 5 days, after which patient shows much improvement & regained consciousness 2 days after last dose of IVIG. Patient was is fully conscious, oriented to time, place & persons, indulges in family conversation, no focal neurological signs, apart from generalized weakness, preserved peripheral reflexes, bilateral equivocal planter responses, with no visual field defects, no signs of cranial nerves affection, preserved gag response, she was on nasogastric tube feeding till she regain consciousness & started oral feeding. She was started on physical Rehab, but she was found to have bilateral drop foot with no back pain, preserved peripheral reflexes; on EMG showed: Generalized extensive axonal damage suggesting critical illness neuropathy, she was discharged after 35 days (Table 1) [15][16][17][18][19][20] .

Discussion
H1N1-associated encephalitis was defined by the Center of Disease Control and Prevention as altered mental status >24h, in patients with laboratory-confirmed H1N1 virus infection, within 5 days of influenza-like illness symptom onset plus two or more of the following: fever, focal neurological signs, CSF pleocytosis, EEG and/or abnormal neuroimaging indicative of encephalitis [1]. Our patient almost fulfilled all of these criteria. However it is noteworthy that neurological signs and symptoms were noted almost 20 days after the initial onset of respiratory illness when sedation was discontinued.
The clinical course of ANE is rapidly progressive; patients present with fever and nonspecific symptoms, such as cough, emesis, and/or diarrhea, and quickly develop neurologic dysfunction. Approximately 18% of cases of ANE in Japan have been associated with influenza A infection [3]. The strain most frequently associated with ANE is influenza A, H3N2 subtype, although cases associated with H1N1 and influenza B has also been described [2,7,[11][12][13]. The disease is associated with significant morbidity and mortality, and survivors usually exhibit at least short-term neurologic sequelae [6]. In addition to antiviral therapies such as Oseltamivir, corticosteroids and intravenous immune globulin have been used to treat selected cases of ANE in Japan, with varying degrees of patient improvement [12]. Currently, there is no definitive treatment for ANE, and management of these patients' centers upon supportive care for neurologic failure and treatment of increased intracranial pressure if present. Then they start monitoring some of Acute necrotizing Encephalitis in H1N1 adult infection.