Thanks to Dr.C.L.Wong.

 

STUDY ON "ENTEROVIRUS 71" VIA PAST MEDICAL DOCUMENTATION

Shen Mao Zhong (Neuro-radiology specialist)

Head of Department of Radiology

China Medical College Hospital

If a survey were to be carried out to name the hottest media character for May and June 1998 on newspapers and TV, 'Enterovirus 71' is certainly on the list.

Since May there is a continuous influx of young children suffering from hand-foot-mouth disease (HFMD) in various major hospitals and paediatric clinics. A small portion of them were complicated with encephalitis and their condition deteriorated fast. Some even died. Primary investigation found that this was mainly caused by enterovirus 71. Enterovirus 71 had been cultured from the spinal cord and medulla oblongata of the brainstem of one dead child. This doubtlessly confirmed the cause of the surge of HFMD and encephalitis.

What is this enterovirus 71 which almost turns Taiwan upside down? We searched all documents, hoping to find records of its past evils (See table attached for details).

Enterovirus 71 was first found as a new enterovirus in 1969 - 1973 in California, USA from victims of encephalitis and polio-like syndrome. In the same time frame, the same enterovirus was found in the outbreak of non-bacterial encephalitis and HFMD in Australia, Sweden and Japan. The enterovirus 71 was then first known. In a major outbreak in Bulgaria in the year 1975, among the recorded 705 cases, 149 developed polio-like syndrome, 44 dead. This was the first country that recorded high mortality. Another outbreak of HFMD occurred in Japan in 1978, in which 692 young children were infected by enterovirus 71. Among them some developed meningitis and encephalitis but all recovered. A big scale outbreak also occurred in Hungary in the same year mainly with polio-like syndrome without death. Since then reports of cases from all over the world, including our neighboring Hong Kong (1986) had been recorded but all agreed that enterovirus 71 is not deadly. Until 1997 when a severe E71 infection occurred in Malaysia where it was coupled with infection of central nervous system. Postmortem of 4 victims found inflammation of brainstem and spinal cord and E71 had been strained. The clinical symptoms were very similar to that of Taiwan outbreak. Victims first developed symptoms of HFMD, having fever for 3 to 4 days before falling into stupor, restlessness followed by fast breathing, increased heart beat and then dyfunction of heart and lungs, shock and death.

From these past records, outbreak of E71 infection had occurred in various parts of the world in the 70s and 80s that triggered different clinical diseases including HFMD, meningitis, encephalitis, polio-like syndrome. However, except the 44 death in Bulgaria in, generally it was not linked with high mortality. Epidemic was rare in the 90s. However, it seemed to get more savage in the Malaysian outbreak. And it has claimed 50 lives of young children in the short period of one month plus epidemic in Taiwan. Judging from the symptoms which are so similar with that in Malaysia, it should be highly suspected to have been transmitted from Malaysia.

How long it will continue to savage? According to the records of 1973 & 1978 Japan outbreak, the epidemic reached its peak in 3 months. Thus, this epidemic in Taiwan may slow down after July.

Epidemic of Enterovirus 71 in various parts of the world

* Cases in Malaysia cannot be found in official medical magazines. Information is adapted from that provided by Professor Lam of microbiology MU in BBS, American Health Net.

EVIDENCES OF ENTEROVIRUS ATTACKING BRAINSTEM IN LIVE BODY actually also attacking dentatus nucleus of cerebellum

Medical supt Chai Chang Hai, paediatrical neurological specialist

Head of Radiological dept Shan Mao Zhong, neuro-radiological specialist

Pheng Qing Tien, Chan Wei De, Su Bain Hong, Qiu Xiu Hui

China Medical College Hospital

This outbreak of enterovirus besides causing HFMD, a group of young children among those infected were coupled with fast changing conditions which needed ICU care even sudden death. These victims in severe condition showed obvious signs and symptoms of encephalitis. Based on the clinical signs and symptoms, pediatrics suggested the location of encephalitis at brainstem. This was confirmed by the 3 visiting American specialists based on the postmortem of the dead cases during the Malaysian outbreak. But chances to see the lesions in live bodies were rare. MRI was the best device we hoped to see the encephalitis lesion in the brainstem. However, during the outbreak, only a teaching hospital at the central region said that their MRI had seen something. All other major hospitals had not seen clear-cut evidence of enteroviral encephalitis.

Our hospital OPD had diagnosed and treated over 1600 HFMD cases since May this year. Among them 20 cases were with encephalitis, 12 with severe condition and were admitted to infant ICU. MRI were done on 7 of them. One of the first 4 was found slight abnormal signals from the beak of the pons of the brainstem, which we dared not confirm its implication. However, for the last 3, clear signals of abnormality can be seen right at the middle of the midbrain, back of the pons, as well as at the dentatus nucleus of the cerebellum. One of them also had it at the back of medulla oblongata. One most severe case not only had it at the above mentioned brainstem location and dentatus nucleus of the cerebellum, also had it at the cervical spinal cord. The evidence of encephalitis attacking brainstem detected by MRI were in accordance with the clinical signs and symptoms, i.e. stupor, difficulty in breathing, low blood pressure. Attack on the cerebellum also explained tremor of both hands, inability to walk steadily (in the case of one 4 year old boy).

With the prominent finding in 3 from the 7 cases, thus we can primarily conclude that:

• MRI images showed that the enteroviral encephalitis attacked midbrain and the back of the pons of the brainstem and dentatus nuclues of the cerebellum. It also attacked the back of medulla oblongata, even the cervical spinal cord.

As the pediatricians in our hospital had decided that the location of the enteroviral encephalitis lesion is a the brainstem, plus the team work spirit of staff at the emergency and ICU wards, rate of success in treatment had been high. All victims with encephalitis attacking the brainstem, except two still in ICU, had been transferred to ordinary ward or discharged.

ENTEROVIRUS INFECTION

Higher Rate of success with Early Detection and Early Treatment

The outbreak of HFMD suspected to be caused by enterovirus had caused panics among the general public especially parents. What everyone is keen to know are what caused the disease, it's channel of infection and most of all, how it can be cured? Since May, the OPD and A&E of this hospital have seen 2889 patients with HFMD. Among them 82 were admitted due to severity condition. Among the 82, 34 were complicated with central nerves symptoms, such as encephalitis, meningitis or myelitis etc, 17 were in critical condition and were admitted to ICU. 12 of the 17 either recovered completely or regained stability, among them 2 who were in deadly condition of shock, unconsciousness, pulmonary oedema, congestion of the lungs were also saved by efforts of all pediatricians.

The hospital had isolated E71 from some of these victims. And by using MRI on 2 severe had discovered obvious lesions in the midbrain, pons and the cerebellum. Thus, E71 may by the main cause. It attacked midbrain, brainstem and caused unconsciousness and even shock. Early detection and early treatment raise the chance of cure.

(Dr. Qiu Xiu Hui, Paediatric Infection)

 

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MRI FINDINGS OF POLIO-LIKE SYNDROME CAUSED BY E71

Head of Radiology Department, Shen Mao Zhong (neuro-radiologist)

China Medical College Hospital

The recent outbreak of enterovirus infection in Taiwan is estimated to have affected 100,000 children mainly manifested in HFMD and pharyngitis. However, a small number (271 cases up to 10^th July) were admitted to ICU of various major hospitals and 54 young children have lost their lives. Thus, it is roughly estimated that @2.7/1000 develop severe condition with mortality rate at @ 5/10000. Clinical manifestation in those in severe condition is stupor, increased heartbeat, fast breathing, low blood pressure, even shock and death. Up to now, all agreed that the severe cases are mainly due to virus attacking the brainstem. This has also been confirmed by several postmortem as well as MRI by China Medical College Hospital and "Zhang Ji".

In this outbreak of virus infection, besides HFMD, pharyngitis and encephalitis of the brainstem, a bunch of victims also showed polio-like syndrome mainly manifesting in monoplegia either in upper or lower limbs.

Reviewing the past documents, the main signs and symptoms during the 1973 outbreak in Japan were HFMD with 24% of the victims complicated with infection of the central nerves. A small number of them show polio-like monoplegia. In the 1975 outbreak on Bulgaria, of the 705 children infected by E71 throughout the country, 149 (21%) had polio-like syndrome which caused 44 death. Postmortem confirmed viral invasion of spinal cord. In the 1978 Hungarian outbreak, 1550 young children were infected with E71. Majority of them show meningitis and encephalitis but there were still 13 with polio-like syndrome.

In fact, in the entereovirus family, the one, which easily causes polio-like syndrome, is not E71, but E70. E70 normally causes congestive conjunctivitis first, followed by polio-like syndrome few days later. Other than E70, Coxsackie A7, A9, A23 also cause polio-like syndrome. Professor Hong Zhu Pei of Taiwan National University had reported outbreak of congestive conjunctivitis in Taiwan as early as 1975 & '76 which developed a polio-like syndrome, acute cruralis paralysis 3-30 days following the onset of conjunctivitis. But the victims were all adults between the age of 21 to 55 years.

As E70, E71, Coxsackie viruses and poliovirus are all entereovirus family, it is likely for them to cause polio-like syndrome. Generally, the polio-like syndrome caused by E70, E71 and coxsackie viruses are milder than that caused by poliovirus, and victims mostly will recover.

At the China Medical College Hospital in this outbreak, up to now, there were 70 cases with central nerves infection. Among them 3 cases shown monoplegia, 2 of them brachialis paralysis and one cruralis paralysis. The cruralis paralysis case is a 14 month baby boy who started with HFMD. He was admitted to ICU with increased heartbeat, fast breathing rate 5 days later. The MRI confirmed that his brainstem had been attacked. After he successfully gout out of danger with the treatment of the pediatrician, he was again found with monoplegia of lower left limb. MRI discovered lesions at the left side of the poliomyelon at the end part of the myelon of thoracic spine which implied attack of virus (refer to pictures) and is in accordance to the clinical symptoms. In fact the location of attack in this cause is the exact location of attack in infantile poliomyelitis. The difference is it attacked one side of the myelon, thus is manifested by monoplegia. The baby boy made conspicuous daily improvement and was discharged. His monoplegia should recover within one month.

 

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