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Acute neurological syndromes caused by viruses

Involvement of the brain is one of the most serious consequences of a viral infection. Many virus families have the ability to invade and replicate in brain tissue, but fortunately serious brain infections are rare. Clinically, neurological diseases caused by viruses can be divided into acute and chronic syndromes. The pathology may be due either to multiplication of virus in the cells of the brain or, due to the (misdirected) immune response of the host - post-infectious encephalo-myelitis.

Viruses which infect the brain may reach the central nervous system either by the blood stream or by spread along peripheral nerves. Asymptomatic infection of the brain is common.
Where a virus infects the brain directly, it can usually be isolated either from brain tissue or from the cerebrospinal fluid. This is not the case with the post infectious syndromes.

Acute neurological syndromes

There are four main syndromes:

1. Aseptic meningitis
2. Acute flaccid paralysis
3. Encephalitis
4. Post infectious encephalo-myelitis

1. Aseptic meningitis

This is the commonest viral syndrome. The condition is self-limiting and has a good prognosis. Infection is confined to the meninges. The clinical features include fever, headache, neck stiffness, photophobia and vomiting. CSF findings include a pleocytosis consisting of both polymorphs and lymphocytes, but usually with a lymphocyte predominance, normal glucose and no bacterial growth (hence the term aseptic).
Viruses are by far the commonest cause of meningitis. Infections may occur at any age, but are particularly common in children and young adults.
Common viral agents include: enteroviruses and mumps virus (and less commonly HSV-2 and varicella-zoster virus).
Sometimes, the underlying brain tissue may also be involved, giving rise to meningo-encephalitis. The prognosis depends on the extent of damage done to brain parenchyma.

2. Encephalitis (grey matter disease)

Viral replication occurs in the brain tissue itself, causing destructive lesions in the grey matter. The main symptoms include: fever, drowsiness, confusion, depressed level of consciousness, convulsions and focal neurological signs. Morbidity and mortality is very high. Viruses that cause this condition include herpes simplex, rabies and some of the arboviruses.

The arboviruses are a miscellaneous group of enveloped, ssRNA viruses that infect animals. They are transmitted from one vertebrate host to another via blood sucking arthropods. The main reservoirs are wild birds and small mammals. Man may be infected if bitten by the insect vector.
In South Africa, there are no enzootic arboviruses that specifically cause encephalitis. Rarely, however, encephalitis may occur as part of the clinical course of infection with viruses such as, West Nile virus, Rift Valley fever virus and Sinbis virus. These viruses are enzootic in livestock herds in certain parts of the country and farm workers or vets may occasionally be infected.

Rabies virus is an enveloped (bullet shaped) ssRNA virus. It primarily infects warm blooded vertebrates. It is enzootic in most parts of the world. Virus is shed in the saliva of infected animals and humans are occasionally infected if bitten by an infected animal. The behaviour of the infected animal is altered and it is more likely to bite humans or other animals that it comes into contact with (thus ensuring the viruses survival). The most common sources of human infection are dogs and bats.
Virus is introduced into the tissues through a bite. It enters peripheral nerves and travels up the axon to the brain where it replicates. It causes a fatal encephalitis.
Incubation period:
It varies from 9-90 days, depending on the severity and site of the bite. Incubation period is determined by how long the virus takes to reach the brain. (Bites on the foot take longer than bites on the face.)
The disease can be prevented in an exposed person by administration of post exposure prophylaxis in the form of rabies vaccine and rabies immunoglobulin.

3. Acute flaccid Paralysis

This syndrome is due to direct infection of motor neurones (grey matter) in the spinal cord by a virus. Patients present with fever and flaccid paralysis of a group of muscles. Signs of meningitis such as headache and neck stiffness are frequent accompanying features. The most common aetiological agents include the Polioviruses 1, 2 and 3, but with the reduction in prevalence of wild type polio due to successful global vaccination, other (non polio) enteroviruses are responsible for most cases. (see information on enteroviruses and poliomyelitis)

4 (i) Post infectious encephalitis (white matter disease)

This uncommon complication may develop in the convalescent phase, following a number of common viral infections, including: measles, mumps, rubella and primary varicella-zoster virus infection. In addition it may develop following exposure to certain vaccines, such as: vaccinia virus and the older neurotissue rabies vaccines. Widespread demyelinating lesions develop involving the white matter in the brain and spinal cord. Characteristic histological features include: lymphocytic infiltration and perivascular cuffing of adjacent blood vessels. The causative agent cannot be isolated from brain tissue or CSF. The aetiology is somewhat obscure, but it is thought to be a T cell-mediated auto-immune phenomenon, triggered by exposure to foreign antigens which are closely related to host proteins normally present in brain tissue (molecular mimicry).

4 (ii) Gillain Barre syndrome

This syndrome is characterized by poly-neuritis which develops a few days to weeks after the acute phase of a certain bacterial or viral infections. The disease is due to demyelination of peripheral nerves. Patients present with an ascending paralysis, associated with paraesthesia. Like post infectious encephalomyelitis, it is believed to be an immunological phenomenon. Patients usually recover spontaneously over a few weeks or months as affected nerves are re-myelinated.



The enteroviruses are a large family (>100 types so far identified) of small enveloped, ssRNA viruses that gain entry to the body via the gastro-intestinal tract. (Hence the name entero-)
Virus is shed in the faeces and transmission is via the faecal oral route.

Infection is very common. Humans experience repeated infections with different enteroviruses throughout life. Most infections are trivial. Enteroviruses are responsible for a wide range of clinical diseases in humans, including febrile illnesses with a rash, respiratory tract infections, conjunctivitis, myositis, myo-carditis, peri-carditis, hepatitis (hepatitis A virus is an enterovirus), meningitis, meningo-encephalitis and acute flaccid paralysis.

Enteroviruses are the most common cause of aseptic meningitis and acute flaccid paralysis. (See notes on childhood infections for other manifestations of enteroviral infection)


3 related enteroviruses, poliovirus 1, 2 and 3 are responsible for the clinical disease poliomyelitis. This was a dreaded disease before effective vaccines were developed to combat the infection. Global use of vaccine has brought the disease to the point of eradication. Circulation of poliovirus is now limited to certain parts of Africa and the Indian sub-continent. The infection has been targeted for eradication by the world health organization (WHO).


Virus gains access to the body via ingestion. It replicates in gut associated lymphoid tissues. In some individuals this may be followed by a viraemia and haematogenous spread to the CNS. Lytic infection of motor neurons in the anterior horns of the spinal cord leads to a lower motor neuron weakness of muscles supplied by affected motor neurons (Flaccid paralysis).

Incubation period

7-14 days

Clinical outcomes following infection

1. Asymptomatic infection (replication remains confined to the gut)
2. Minor febrile illness which resolves. (viraemia occurs, but virus does not invade the CNS)
3. Minor febrile illness, followed by aseptic meningitis which resolves.
4. Febrile illness followed by meningitis and acute flaccid paralysis.
Note: Most infections are asymptomatic. Less than 1% of infections result in paralysis.

Control through an effective vaccine

Two effective poliovirus vaccines are in wide spread use around the world: the live attenuated (Sabin) and the formalin inactivated (Salk) vaccine. Both contain the 3 strains of virus responsible for paralytic polio, namely polioviruses 1, 2 and 3.

Both vaccines were developed in the 1950s: the live attenuated vaccine was created by serial passage of the virulent virus in cell culture to produce strains of poliovirus which retained the antigenicity, but were unable to cause disease. The inactivated (killed) vaccine contains formalin-inactivated polioviruses. Both vaccines are highly effective at protecting against infection:

Attributes of polio vaccines


Formalin inactivated vaccine (Salk)

Live attenuated vaccine (Sabin)

Route of administration


Oral drops

Immune response

Good, IgG in blood

Good, IgA in gut

Duration of immunity






Stability of vaccine


Not stable, cold chain important

Transmission to vaccine contacts





Reversion to virulence (very rare)
Prolonged shedding in immuno-compromised patients

In South Africa 6 doses of the live attenuated polio vaccine is given routinely to all infants at birth, 6, 10 and 14 weeks, 18 months and 5 years. Multiple doses need to be given as only one strain is likely to "take" each time. (Remember there are three viruses in the vaccine).

Poliomyelitis is a notifiable disease. The department of health needs to be notified of all patients presenting with a polio-like illness. Two stool samples should be taken (on successive days) from patients with acute flaccid paralysis. The stool is sent to the National Institute for Communicable Diseases in Johannesburg for poliovirus testing. The last case of poliomyelitis that occurred in South Africa due to wild type poliovirus was in1987, but periodic outbreaks continue to occur in other parts of Africa. Thus continued vigilance and high vaccine coverage is essential as the virus could be re-introduced into the country.

Many first world countries have abandoned the live attenuated vaccine and now use the killed vaccine due to the rare instances of paralysis that may occur in vaccine recipients of the live vaccine (less than 1 per 10 million doses).

Mumps virus

Mumps virus is an enveloped ssRNA virus belonging to the family Paramyxoviridae. Infection is spread by respiratory droplets. It is responsible for a mild febrile illness in children. The most characteristic feature is painful enlargement of one or both parotid glands. In about 5% of cases the infection may be complicated by aseptic meningitis.

Orchitis develops in about 20% males who contract mumps after puberty.