influenza is an acute , usually self limited , febrile illness caused by infection with influenza type a or b viruses that occur in outbreaks of varying severity almost every winter .
symptoms are primarily related to the respiratory system , but myositis , rhabdomyolysis , myoglobinuria , myocarditis , pericarditis , and central nervous system ( cns ) involvement has been described with influenza virus infection .
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.[25 ] these findings indicate that , as with seasonal influenza , neurologic complications can occur with on going 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 .
there has been only one case report of encephalopathy associated with novel h1n1 infection in adult .
we are describing a case of novel h1n1 infection presenting with multi - system involvement ( bilateral pneumonia , severe rhabdomyolysis leading to renal failure and encephalitis ) in adult patient
a 27-year - old , male , immunocompetent patient presented with 5 days history of fever , running nose , dry cough , and sore throat .
he had generalized tonic - clonic convulsion , altered sensorium and increasing breathlessness requiring ventilatory support after hospitalization . with this brief illness patient
he was intubated and sedated , his limbs were swollen , pulse : 108/min , temperature : 37c , and blood pressure was 138/84 mmhg .
cns examination revealed sedated patient ( receiving iv midazolam ) , pupils were normal size reacting to light , all deep tendon reflexes were absent , and there was generalized hypotonia .
auscultation revealed the presence of crepetitions in right infra scapular and infra - axillary regions of chest .
laboratory investigations on presentation to us showed hemoglobin : 14.42 gm% , total wbc counts : 1730 cells / cu.mm , platelet count : 1.25 lacs / cu.mm , serum bilirubin total : 1.2 mg% , direct : 0.5 mg% , indirect : 0.7 mg% , sgpt : 200 iu / l , sgot : 607 iu / l , alkaline phosphatase : 204 iu / l , ldh : 4491
iu / l , cpk mb : 156 iu / l , urine myoglobin:>1000 ng / ml , total protein : 5.8 gm% , albumin : 3.0 gm% , globulin : 2.8 gm% , serum creatinine : 1.4 mg% , s. na : 139 mmol / l , s.k : 5.0 mmol / l , c - reactive protein : 4.5 mg% ( normal < 1 mg% ) , serum procalcitonin : < 0.5 ng / ml and arterial blood gas analysis was normal ( on control mode ventilation with 100% fio2 ) .
his pharyngeal secretion was positive for h1n1 pcr testing at government referral laboratory for h1n1 testing .
his x - ray chest showed right mid - zone consolidation , while ultrasonography of abdomen and 2d - echocardiography was normal .
he was treated with capsule oseltamivir 75 mg 2 bid through ryles tube , iv fluid , iv cefipime / tazobactum 1.125 gm q8h , iv midazolam , iv levetiracetam 500 mg q8h , other supportive treatment along with ventilatory support .
methyl prednisolone 40 mg q8h , sodium bicarbonate , iv levocarnitine , and iv pantoprazole was added to above regimen from next day . on second day
he developed severe hypercapnia ( pco2 : 146 mmhg ) , hypertension and tachycardia ( no rhythm disturbances on ecg ) and was treated with change in ventilatory settings , along with iv amioderone and nifedipine . from third day evening
he started having continuous fever and worsening of serum creatinine ( 3.42 mg% which continue to worsen further up to 7.9 mg% ) . despite this worsening creatinine level
follow up investigations after 4 days showed hemoglobin : 14.6 gm% , total wbc counts : 14,100 cells / cu.mm , platelet count 2.2l acs / cu.mm , crp : 4.81 mg% , serum procalcitonin : > 10 ng / ml , cpk total : 3710 iu / l , s.k : 5.0 mmol / l , blood culture : sterile and x - ray chest ( pa ) showed right mid and lower zone and left lower zone consolidation , which showed worsening as compare to previous x - ray . his antibiotics were changed to inj meropenem and fluconazole for suspected ventilator associated pneumonia .
his antibiotics were changed to cefoperazone - sulbactum 3 gm iv bid and tygecycline 100 mg iv loading dose followed by 50 mg iv bid .
after 48 hours of change in antibiotics his condition started improving and he was maintaining spo2 100% with fio2 40% on controlled mode ventilation .
he continued to spike fever up to 40 - 40.5c despite improvement in respiratory system .
his fever spikes reduced from third day onward and successfully weaned of in the next 3 days .
his methyl prednisolone was tapered every fifth day ( 40 mg q8h for 5 days , q12h for 5 days , qd for 5 days followed by tab prednisolone 20 mg for 5 days , 10 mg for 5 days and then stopped .
his plain ct scan of brain was performed which was normal and ct thorax showed bilateral interstitial pneumonia with ground - glass opacities in right mid , lower and left lower zones 
 [ figure 1 ] .
hrct thorax : bilateral interstitial pneumonia with ground - glass opacities in right mid , lower , and left lower zone he was subjected for non - contrast mri brain and csf examination once he was off the ventilatory support .
mri brain diffusion weighted images showed areas of restricted diffusion in the region of brain stem , posterior limb of internal capsule , periventricular region on both sides , deep while matter in both parietal region and splenium of corpus callosum and corresponding adc map showed relative hypointense signals , all changes appear to be due to underlying acute demyelinating encephalomyelitis ( adem ) [ figures 2 and 3 ] .
csf examination showed 5 cells / cu.mm , protein : 47.2 mg% , glucose : 93.7 mg% and gram stain results were negative .
emg was normal , while ncv showed generalized predominantly pure motor , mixed axonal , and demyelinating polyneuropathy .
cns examination showed spontaneous eye opening , he try to follow verbal and painful stimuli with eye movement .
he showed flexion movement of upper limb on painful stimuli , localizes pain in lower limb with generalized hypotonia and areflexia .
diffusion - weighted images mri brain : areas of restricted diffusion in the region of the brain stem diffusion - weighted images mri brain : areas of restricted diffusion in the region of posterior limb of internal capsule , periventricular region on both sides , deep while matter in both parietal region and splenium of corpus callosum
neurological complications of seasonal influenza virus infection have been well described in pediatric age group and young adults .
neurological complications usually occur early in the course of disease and include encephalopathy , encephalitis , seizures , reye syndrome , and guillain - barre syndrome ( gbs ) . severity of complication ranging from mild and transient central nervous system alterations to severe forms associated with high mortality .
the pathogenesis of influenza virus encephalitis is unclear . whether the influenza virus invades the brain parenchyma is still a controversial issue .
however , recent reports have indicated that viral rna is not detected in the csf of most patients with influenza - associated encephalitis
. findings of pathologic examination , including the lack of detectable viral antigen in brain tissues , also have suggested that direct viral invasion and inflammation are unlikely to be the causes of this disease .
it has been hypothesized that the respiratory tract infection triggers immune system cytokines that result , in rare instances , in an inflammatory process in the brain , which can lead to neurologic squeal or fatal outcomes .
neurological complications with novel h1n1 pandemic reported so far are seen in the pediatric age group and many patients have recovered from h1n1 and develop neurological complications ( polyneuropathy , transverse myelitis , encephalitis ) .
our adult immunocompetent patient presented with initial symptoms suggestive of influenza - like illness of 5 days duration before he develops encephalitis .
however our patient developed episodes of seizures with loss of consciousness with ongoing acute phase of influenza virus infection , which was suggestive of cns involvement by influenza virus .
our patient developed cns involvement with acute lung injury , these timing of neurological involvement is consistent with available information in literature .
the clinical findings of severe encephalitis were confirmed by evidence of extensive involvement of brain parenchyma on mri brain examination performed after he recovered from acute lung injury .
methyl prednisolone 120 mg / day intravenously was used on presentation in our patient for the acute lung injury associated with viral pneumonia .
emg - ncv examination showed generalized predominantly pure motor , mixed axonal and demyelinating polyneuropathy .
it is difficult to differentiate critical care neuropathy from viral associated neuropathy with available investigations in our patient .
glucocorticoids and plasmapherasis had been used in some patients with success . as patient developed secondary bacterial pulmonary infection glucocorticoids
only one case report of rhabdomyolysis in novel h1n1 patient so far in the literature , though it was well described with seasonal influenza .
our patient also had severe myositis , swollen limbs with rhabdomyolysis and myoglobinuria ( urinary myoglobin > 1000 ng / ml ) leading to renal failure on presentation .
myositis , rhabdomyolysis , and myoglobinuria are well known complication of influenza , although acute tubular necrosis and renal failure are not common.[111519 ] during hospitalization , he also developed tachycardia requiring use of iv amiodarone , for which we were not able to point out any immediate cause , raising suspicion of myocardial involvement by influenza virus .
although the supportive investigations such as cpk mb , 2d echocardiography , and ecg were normal and we had not carried out any myocardial biopsy to confirm diagnosis of myocarditis .
generally , all these supportive investigations are inconclusive in most of the patients requiring myocardial biopsy for diagnosis .
as the myocardial involvement is patchy in nature it may some time be difficult to prove the presence of myocarditis even after doing biopsy .
severe inflammatory response generated by the body in response to influenza virus infection had led to more severe and extensive involvement of lung , muscle and brain . our patient had multisystem involvement ( pneumonia , encephalitis , neuropathy myositis , and possible myocarditis ) from novel h1n1 influenza virus infection .
this is probably first case report with multisystem involvement from novel h1n1 infection with significant post illness debility . in conclusion ,
novel h1n1 infection can present with life - threatening multi - system involvement including encephalitis in adult patients .
 neurological complications of influenza are well known . 
 influenza a is commonly associated with neurological complications . 
 neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel h1n1 infection . 
 we are describing a case of novel h1n1 infection presenting with multi - system involvement ( encephalitis , bilateral pneumonia , severe rhabdomyolysis leading to renal failure and polyneuropathy ) in adult patient . 
INTRODUCTION
CASE REPORT
DISCUSSION