Study: Pediatric Neurological Complications With H1N1

 

 

# 4915

 

 

Despite being relatively mild for the vast majority of those it infected, the novel H1N1 virus – at least in a small percentage of victims – showed unusual, and sometimes severe, symptoms.

 

The most obvious difference between the pandemic virus and seasonal influenzas of the past has been the age shift in infections, hospitalizations, and deaths.

 

Unlike seasonal influenza, novel H1N1 has taken its biggest toll on those under the age of 65.

 

While the total number of flu-related fatalities appears to be less than normally seen with seasonal flu, In terms of years of life lost, novel H1N1 was anything but benign (see Study: Years Of Life Lost Due To 2009 Pandemic).

 

 

But the difference between pandemic H1N1 and seasonal flu go beyond this profound age shift. The symptomology of this virus differed for many people as well.

 

A brief review, before we get to today’s study.

 

Researchers in Hong Kong discovered that the H1N1 virus – unlike seasonal flu – easily infects and replicates in the conjunctival tissues of the eye  (see I Only Have Eyes For Flu).

 

Another difference observed with novel H1N1 has been its unusually high rate of gastro-intestinal symptoms. Diarrhea and vomiting have both been commonly reported with H1N1 pandemic influenza as evidenced by this report from Maggie Fox of Reuters.

 

US flu study confirms H1N1 more serious in youth

Thu Oct 8, 2009 10:41pm BST

* 45 percent of those hospitalized were under 18

* Diarrhea, vomiting in 42 percent of children with H1N1

* Quick drug treatment may save lives

 

 

And in December of last year, we saw a report from the NIH on autopsies performed on H1N1 victims in New York that showed unusual levels of lung damage.

 

 Virus Damages Entire Airway

Monday, Dec. 7, 2009

In fatal cases of 2009 H1N1 influenza, the virus can damage cells throughout the respiratory airway, much like the viruses that caused the 1918 and 1957 influenza pandemics, report researchers from the National Institutes of Health (NIH) and the New York City Office of Chief Medical Examiner.

 

 

Beyond the gastro-intestinal and pulmonary symptoms, we’ve also seen a number of neurological complications, particularly (but not exclusively) in children.

 

The first hint of this came last summer when the CDC’s MMWR (July 23rd issue) reported on 4 pediatric patients with the novel H1N1 virus who presented with neurological symptoms including unexplained seizures and altered mental status.

 

Neurologic Complications Associated with Novel Influenza A (H1N1) Virus Infection in Children --- Dallas, Texas, May 2009

. . .  On May 28, 2009, the Dallas County Department of Health and Human Services (DCHHS) notified CDC of four children with neurologic complications associated with novel influenza A (H1N1) virus infection admitted to hospitals in Dallas County, Texas, during May 18--28.

 

In November, in a blog entitled Japan: Influenza Related Encephalopathy we looked at a report in the Yomiuri Shimbun on 132 flu patients with neurological complications during the opening four months of the pandemic.

 

 

All of which serves as prelude to today’s study by researchers at the University of Utah which is to be published later today in the Annals of Neurology  (link not available yet).  

 

Heightened Neurologic Complications in Children with Pandemic H1N1 Influenza

Jeffrey J. Ekstrand, Amy Herbener, Julia Rawlings, Beth Turney, Krow Ampofo, E. Kent Korgenski, Joshua L. Bonkowsky. Annals of Neurology; Published Online: September 20, 2010 (DOI:10.1002/ana.22184)

 

Since the link has not appeared, what we do have is the press release on this study:

 

 

Higher incidence of seizures seen in children with H1N1 virus compared to seasonal flu

Vaccination important to combat flu-related neurological complications

 

 

This was a retrospective study, where researchers identified 303 children hospitalized with the pandemic H1N1 virus, 18 of which developed neurological symptoms.  

 

They compared these cases to records of 234 children admitted to the hospital in previous years due to seasonal influenza.

 

The most common neurological complications exhibited with novel H1N1 were seizures (12 patients or 67%), with seven exhibiting status epilepticus, a potentially life-threatening condition involving continuous or recurrent seizures that can last for a half hour or longer.

 

The mean age of children admitted with neurological symptoms from H1N1 was more than twice the age (6.5 years) than usually seen with seasonal flu (2.4 years).

 

And abnormal EEG (electroencephalogram) readings were more common in pandemic H1N1 cases than in seasonal influenza.

 

The researchers are unsure why these neurological manifestations appear more common in novel H1N1 influenza, but suggest that it may be part of an autoimmune response.

 

You can find more details of this study in an review published today by Medpage Today:

 

Seizures in Kids Linked to H1N1 Flu

By Nancy Walsh, Staff Writer, MedPage Today

 

 

While it is easy to dismiss the 2009 pandemic virus as overblown based simply on the total number of fatalities, when one looks a little deeper one discovers that the virus played by its own set of rules.

For the demographic group usually hit hardest by the flu – those in their 70s and 80s and most likely to die from the infection - novel H1N1 was almost like a year without influenza.  

But for many children, and younger adults, H1N1 proved to be a serious challenge.

 

This year, we’ve a double threat looming with this fall’s flu season.   The (former) pandemic H1N1 virus is likely to return, along with (potentially) the new Perth H3N2 strain.

 

And H3N2, if it returns, is unlikely to spare the elderly as did the pandemic virus.

 

The good news is both of these are covered (along with an influenza B strain) in this year’s trivalent flu vaccine. 

Three good reasons to get your flu shot early this year.

Neurologic Manifestations of Pandemic (H1N1) 2009 Virus Infection

 

 

# 4324

 

 

Once again we have additional evidence of neurological problems being induced by the novel H1N1 virus.  This time from an expedited letter appearing in the CDC’s Journal of Emerging Infectious Diseases .

 

DOI: 10.3201/eid1603.091699

Suggested citation for this article: Kitcharoen S, Pattapongsin M, Sawanyawisuth K, Angela V, Tiamkao S. Neurologic manifestations of pandemic (H1N1) 2009 virus infection [letter]. Emerg Infect Dis. 2010 Mar; [Epub ahead of print]

Neurologic Manifestations of Pandemic (H1N1) 2009 Virus Infection

 

 

This four page letter describes the presentation, testing, and course of illness of a 34-year-old man, previously healthy, who was admitted to Chaiyaphum Hospital in Chaiyaphum, Thailand, back in August with flu-like symptoms.

 

By day 2 post admission, the patient’s condition had deteriorated, with significant neurological symptomology.   

 

Some excerpts from the report follow:

 

. . .  progressive quadriparesis with bilateral, symmetric paresthesia (glove-and-stocking pattern), and areflexia developed. His motor weakness (grades III/V) began in both legs and then involved both arms and hands. Other neurologic examinations showed limitation of extraocular movement in all directions, normal pupil size and light reflex, and facial diplegia.

 

On Day 3, acute respiratory failure occurred.

From there, the patient’s neurological deficits increased, and testing pretty much ruled out the `usual suspects’ for those types of symptoms.

 

. . . . negative results for syphilis testing and for serologic tests for HIV, hepatitis B virus, hepatitis C virus, Japanese encephalitis virus, herpes simplex virus, and Mycoplasma pneumoniae. A CSF antigen test was negative, and CSF culture was negative for bacteria.

 

Although a diagnosis of GBS (Guillain Barre Syndrome) was considered, testing and some clinical signs did  not support that diagnosis.   The authors conclude:

 

Our report shows neurologic manifestations associated with pandemic (H1N1) 2009 virus infection in an adult. The manifestation of progressive quadriplegia with diffuse sensory loss is compatible with a polyneuropathy. The neurologic signs developed 2 days after the respiratory tract signs.

 

You can read the whole paper here.

 

This, of course, isn’t our first hint of neurological problems stemming from the H1N1 virus.   And in truth, on rare occasions, even seasonal flu can induce neurological problems.

 

But pandemic strains, like novel H1N1 and the H5N1 bird flu virus, seem more adept at producing neurological manifestations.

 

In November, in a blog entitled Japan: Influenza Related Encephalopathy we looked at this report in the Yomiuri Shimbun.

 

 

132 flu patients hit with brain disorders since July

The Yomiuri Shimbun

A total of 132 influenza patients in Tokyo and 27 prefectures have developed encephalopathy, or swelling of the brain, since July, according to the National Institute of Infectious Diseases.

 

Normally, only about 40 to 50 seasonal flu sufferers develop encephalopathy each year, meaning the latest figure has already more than doubled in four months since the new strain of flu began spreading.

 

Earlier in November, Children’s Hospital in Pittsburgh, PA reported several children with H1N1 related encephalitis. 

 

And last summer, CDC’s MMWR  (July 23rd issue) reported on 4 pediatric patients with the novel H1N1 virus who presented with neurological symptoms including unexplained seizures and altered mental status.

 

Neurologic Complications Associated with Novel Influenza A (H1N1) Virus Infection in Children --- Dallas, Texas, May 2009

Neurologic complications, including seizures, encephalitis, encephalopathy, Reye syndrome, and other neurologic disorders, have been described previously in association with respiratory tract infection with seasonal influenza A or B viruses (1--2), but not with novel influenza A (H1N1) virus.

 

On May 28, 2009, the Dallas County Department of Health and Human Services (DCHHS) notified CDC of four children with neurologic complications associated with novel influenza A (H1N1) virus infection admitted to hospitals in Dallas County, Texas, during May 18--28.

 

 

As more reports, studies, and investigations into the impact and sequelae of this pandemic come in, we will get a better idea of how to regard this H1N1 virus.   

 

While not the killer pathogen some feared, it quite obviously differs from seasonal flu on several fronts.

 

The next few years are going to be a time of much study, and hopefully discovery, as we sift through the reams of data accumulated over the past nine months.

Japan: Influenza Related Encephalopathy

 

 

# 4069

 

Encephalopathy isn’t a distinct disease, but rather refers to a syndrome of diffuse brain dysfunctions, which may be associated with a variety of causes.

 

Viral and bacterial infections are among the common culprits, but encephalopathy may also be caused by trauma, prions, toxic chemical exposures, and even a thiamine deficiency (Wernicke’s Encephalopathy).

 

The overriding hallmark of encephalopathy is an altered mental state, although depending and severity of encephalopathy, common neurological symptoms such as progressive memory loss and changes in cognitive ability,  personality changes, inability to concentrate, lethargy, and loss of consciousness may be seen.

 

In recent years Influenza has been seen as a rare cause of encephalopathy.  

 

In an eMedicine article on Influenza by  Robert W Derlet, MD, Professor of Emergency Medicine, University of California at Davis School of Medicine encephalopathy is listed under clinical presentation:

 

Acute encephalopathy has recently been associated with influenza A virus. In a case series of 21 patients, Steininger et al described clinical, CSF, MRI, and EEG findings.4 Clinical features included altered mental status, coma, seizures, and ataxia. Of those who underwent further testing, most had abnormal CSF, MRI, and EEG findings.

 

The CDC’s MMWR (July 23rd issue) reported on 4 pediatric patients with the novel H1N1 virus who presented with neurological symptoms including unexplained seizures and altered mental status.

 

Neurologic Complications Associated with Novel Influenza A (H1N1) Virus Infection in Children --- Dallas, Texas, May 2009

Neurologic complications, including seizures, encephalitis, encephalopathy, Reye syndrome, and other neurologic disorders, have been described previously in association with respiratory tract infection with seasonal influenza A or B viruses (1--2), but not with novel influenza A (H1N1) virus.

 

On May 28, 2009, the Dallas County Department of Health and Human Services (DCHHS) notified CDC of four children with neurologic complications associated with novel influenza A (H1N1) virus infection admitted to hospitals in Dallas County, Texas, during May 18--28.

 

And as previously mentioned, even seasonal influenza has been linked to very rare neurological symptoms.  The editorial note from the MMWR stated that:

 

Considering that clusters of influenza-associated encephalopathy in children have been reported during previous community outbreaks of seasonal influenza (1--2) and that children appear to be infected with novel influenza A (H1N1) virus more frequently than adults (3), additional neurologic complications in children are likely to be reported as the pandemic continues.

 

Clinicians should consider influenza associated encephalopathy in the differential diagnosis of children with ILI and seizures or mental status changes, and remain aware of the potential for severe neurologic sequelae associated with seasonal or novel influenza A (H1N1) virus infection.

 

The incidence of neurological involvement with most influenza viruses appears to be quite low, although obviously not unheard of.

 

Earlier this month, Children's Hospital of Pittsburgh reported 5 kids with encephalitis over the past 6 weeks. 

 

Today we learn via the Daily Yomiuri Online that a surprising number of H1N1 patients in Japan have presented with encephalopathy since July.   

 

In a normal year, Japanese health officials say they might see 40 to 50 such cases – but in the past four months they’ve seen more than twice that many.

 

A hat tip to Treyfish on FluTrackers for posting this link.

 

 

132 flu patients hit with brain disorders since July

 

The Yomiuri Shimbun

A total of 132 influenza patients in Tokyo and 27 prefectures have developed encephalopathy, or swelling of the brain, since July, according to the National Institute of Infectious Diseases.

 

Normally, only about 40 to 50 seasonal flu sufferers develop encephalopathy each year, meaning the latest figure has already more than doubled in four months since the new strain of flu began spreading.

 

Encephalopathy occurs when viruses cause the immune system to overreact, resulting in a swelling of the brain.

 

Though the ages of the 132 people in question range from 1 to 67, most were under 15.

 

By age, 7-year-olds constituted the largest group, with 22 sufferers. This is older than the average age for encephalopathy sufferers, who are most often aged between 1 and 3.

 

Further examination of 60 of the 132 patents revealed consciousness-related malfunctions.

 

The period over which these malfunctions occurred following the initial fever ranged from one day for 12 people, two days for 36 people, and four days for eight people.

 

The examination reconfirmed that in many cases, the serious symptoms occurred in the early stages of the disease.

 

Of 59 patients whose symptom development had ended, three, or 5 percent, died. Seven, or 12 percent, suffered aftereffects such as physical paralysis or mental or nerve disorders.

 

Forty-nine, or 83 percent, fully recovered.

 

Nobuhiko Okabe, chief of the institute's Infectious Disease Surveillance Center, said: "If a patient exhibits such symptoms as slow responses or saying strange things, encephalopathy could be the cause. In such cases, patients should see a doctor immediately."

(Nov. 24, 2009)