Viral CNS Infections

Viral infection of the central nervous system is uncommon, but it carries a risk of death and lasting disability out of all proportion to its frequency. The clinical problem is one of triage: to separate the few treatable causes, herpes simplex encephalitis above all, from the many that are self-limited or, like rabies, untreatable, and to act before avoidable damage is done.

The syndrome a patient presents with is the first guide to the cause. Meningitis, the commonest form, is usually benign and self-limited, most often caused by an enterovirus; acute flaccid paralysis points to the enteroviruses too, poliovirus among them.

Encephalitis is the dangerous syndrome: its largest burden worldwide is epidemic arboviral disease, yet the sporadic case that most demands action is herpes simplex encephalitis, which is both treatable and, untreated, usually fatal.

Beyond these acute infections lie two further groups: the chronic and slow infections, in which a virus persists to cause disease over months to years, and the prion diseases, which are not viral infections at all but disorders of a misfolded host protein.

These articles work through the topic.

→ See Viral Diseases of the Central Nervous System for the acute infections: the classification of central nervous system viruses, how they reach and injure the brain, the meningitis, encephalitis and myelitis syndromes, their laboratory diagnosis and differential, the chronic and slow infections, and the principles of treatment.

→ See Prion diseases for the transmissible spongiform encephalopathies: the biology of the prion protein, the spectrum from sporadic Creutzfeldt-Jakob disease to variant disease, their diagnosis, and the biosafety they demand.

Key terms

The vocabulary that recurs across the topic, grouped by theme.

Syndromes by site of inflammation:

Term	Definition
Meningitis	Inflammation of the leptomeninges, usually benign and self-limited when viral.
Encephalitis	Inflammation of the brain parenchyma, marked by altered consciousness and focal signs.
Meningoencephalitis	Inflammation of both the meninges and the parenchyma, the common overlap.
Myelitis	Inflammation of the spinal cord; anterior-horn involvement produces flaccid paralysis.
Radiculitis and neuritis	Inflammation of the dorsal nerve roots and of peripheral nerves.

Patterns and mechanisms:

Term	Definition
Aseptic meningitis	A benign meningitis with a sterile routine bacterial culture; a misnomer, since treatable fungal, tuberculous and other causes produce the same picture.
Primary encephalitis	Encephalitis from direct viral invasion of the brain, with virus demonstrable in the parenchyma.
Post-infectious encephalomyelitis	Also called acute disseminated encephalomyelitis (ADEM): a demyelinating illness following infection or vaccination, immune-mediated, with no virus in the brain.
Slow infection	A persistent infection with a long incubation and slow course, causing disease over months to years.

Neurotropism:

Term	Definition
Neuroinvasiveness	The capacity of a virus to enter the nervous system.
Neurovirulence	The capacity of a virus to cause damage once in the nervous system.
Neurotropism	The product of neuroinvasiveness and neurovirulence: the capacity to infect and harm neural tissue.
Neuronotropic	Able to infect neurons themselves, as distinct from other neural cells such as the oligodendrocytes that JC polyomavirus targets.

References and recommended reading

• Cassady KA, Whitley RJ. Viral Infections of the Central Nervous System. In: Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition, Chapter 3. ASM Press; 2017. The source for the classification of neurological viral disease, the meningitis and encephalitis syndromes, and the clinical approach.
• Burrell CJ, Howard CR, Murphy FA. Viral Syndromes; Prions. In: Fenner and White’s Medical Virology, 5th edition, Chapters 39 and 38. Academic Press / Elsevier; 2017. The source for the syndrome-based classification of central nervous system viral disease and for the transmissible spongiform encephalopathies.