Complete Exploration of Central Nervous System Infections: Causes, Signs, Prognosis, Therapy, and Prevention Methods

Complete Exploration of Central Nervous System Infections: Causes, Signs, Prognosis, Therapy, and Prevention Methods

 

INTRODUCTION

Central nervous system (CNS) infections are sometimes life-threatening

and might have extreme sequelae. These infections trigger inflamma-

tion and edema inside the unyielding skull, leading to dam-

age to mind tissue and lack of operate. The most typical causes

of CNS infections are micro organism and viruses, however fungi, protozoa,

and helminths additionally trigger these infections.

Along with the historical past and bodily examination, scientific

prognosis of CNS infections requires a spinal fluid evaluation

mixed with neuroimaging utilizing both magnetic resonance

imaging (MRI) or computed tomography (CT) scan. Microbio-

logic prognosis of bacterial infections often is made utilizing

Gram stain and tradition of spinal fluid and blood. Polymerase

chain response (PCR) assays and serologic exams are additionally helpful.

Antimicrobial remedy requires that the antibiotics be bactericidal

and that they penetrate the blood–mind barrier. Some CNS infec-

tions, corresponding to a mind abscess, typically require surgical drainage.

CEREBROSPINAL FLUID ANALYSIS

Examination of cerebrospinal fluid (CSF) is vital in making

the prognosis of CNS infections. CSF is obtained by performing

a lumber puncture on the L3–L4 interspace. In the course of the course of,

the CSF stress is measured and fluid obtained for evaluation

of cells (each quantity and cell sort, i.e., neutrophils or lym-

phocytes), protein, and glucose. The outcomes of CSF evaluation in

acute bacterial meningitis, acute viral meningitis, and subacute

meningitis are described in Desk 72–1.

Though CSF evaluation is a vital step within the

prognosis of many CNS infections, a lumbar puncture shouldn’t

be carried out if there are indicators of elevated intracranial stress,

corresponding to papilledema or focal neurologic indicators, as a result of hernia-

tion of the brainstem and demise might happen. A CT scan needs to be

carried out previous to the lumbar puncture to find out whether or not

a mass lesion, corresponding to a mind abscess or most cancers, is current. If a

mass lesion is seen, a lumbar puncture shouldn’t be carried out.

MENINGITIS

Definition

Meningitis is an an infection of the meninges, the membranes that

line the mind and spinal twine (Determine 72–1). Meningitis may be

categorized as acute, subacute, or persistent relying on the velocity

of onset of the preliminary presentation and the speed of development of

the sickness. Acute meningitis is attributable to both pyogenic micro organism,

corresponding to Streptococcus pneumoniae and N. meningitidis, or viruses,

Pathophysiology

Hematogenous unfold (i.e., bacteremia or viremia) is essentially the most

widespread route by which organisms attain the meninges. Direct

unfold through adjoining infections, corresponding to otitis media and sinusitis;

through neurosurgery, corresponding to a shunt to alleviate hydrocephalus; or

through trauma, corresponding to a fracture of the cribriform plate, happens

much less often. The significance of hematogenous unfold is

emphasised by the success of the conjugate vaccines in opposition to

S. pneumoniae, N. meningitidis, and Haemophilus influenzae

sort B that induce circulating IgG antibodies that neutralize the

micro organism within the blood.

Acute bacterial meningitis begins with nasopharygeal colo-

nization adopted by native invasion, entry into the bloodstream,

and invasion of the meninges (Determine 72–2). That is adopted

by an inflammatory response that causes most of the scientific

manifestations, particularly the edema leading to elevated

intracranial stress resulting in headache. Cerebral vasculitis

and infarction can even happen.

Medical Manifestations

Early signs embody the traditional triad of fever, headache,

and stiff neck (nuchal rigidity). Altered psychological standing additionally

generally happens. If untreated, meningitis might progress to

vomiting, seizures, photophobia, and focal neurologic deficits.

Completely different pathogens can current with totally different charges of scientific

development, from acute onset and speedy development (hours to

days) to subacute or persistent onset and sluggish development (days

to weeks). Neisseria meningitidis an infection may be related

with disseminated illness (meningococcemia) and lead to

petechial rash and in the end purpura fulminans (Determine 72–3).

Pathogens

Acute Bacterial Pathogens

The most typical bacterial reason behind acute meningitis total

is S. pneumoniae. Nonetheless, Streptococcus agalactiae (group B

Streptococcus) predominates in neonates, and N. meningitidis is

widespread in youngsters and younger adults (Desk 72–2).

Haemophilus influenzae sort B was an necessary

trigger in younger kids, however the widespread use of the conju-

gate polysaccharide vaccine has vastly decreased its incidence.

Listeria monocytogenes within reason widespread within the very

younger, the very outdated, and immunocompromised sufferers. Much less

widespread pathogens embody Borrelia burgdorferi (Lyme illness)

and Treponema pallidum (syphilis).

Acute Viral Pathogens

The most typical viral causes of acute meningitis are entero-

viruses corresponding to Coxsackie virus and echovirus. Enteroviral

meningitis happens primarily in younger kids, and the height

incidence is in the summertime and fall seasons.

Herpes simplex virus sort 2 (HSV-2) can be a standard trigger

of meningitis. Observe that HSV-2 sometimes causes meningitis,

whereas herpes simplex virus sort 1 (HSV-1) causes encepha-

litis. Main genital infections with HSV-2 usually tend to

lead to meningitis than recurrent HSV-2 infections. Main

and reactivation varicella-zoster virus (VZV) an infection can even

be related to meningitis.

Though arboviruses sometimes trigger encephalitis, arbovi-

ruses corresponding to West Nile virus (WNV) and St. Louis encephalitis

virus can even trigger meningitis. Mumps virus was a com-

mon reason behind meningitis, however widespread use of the mumps

vaccine has vastly decreased its incidence.

Subacute and Power Meningitis

The most typical causes of subacute and persistent men-

ingitis are M. tuberculosis and fungi corresponding to Cryptococcus,

Coccidioides, and Histoplasma. Cryptococcal meningitis happens

mostly in immunocompromised sufferers, corresponding to these

Prognosis

A microbiologic prognosis of acute bacterial meningitis is typi-

cally made by Gram stain and tradition of CSF. Nonetheless, PCR-

primarily based exams are being more and more used as a result of they yield outcomes

quickly and with nice accuracy. For instance, a PCR-based

panel is now out there that exams for the presence in spinal fluid

of six widespread micro organism, seven widespread viruses, and the yeast

Cryptococcus with a turnaround time of 1 hour.

Evaluation of spinal fluid can distinguish between acute bacte-

rial meningitis and viral meningitis (see Desk 72–1). Whereas they

each are likely to have elevated white blood cells (WBCs) and protein

in CSF, bacterial infections are usually neutrophil predominant,

whereas viral infections are lymphocyte predominant. Bacterial

infections are related to low glucose concentrations in

CSF, whereas viral infections have regular glucose ranges.

Subacute and persistent meningitis are usually lymphocyte

predominant with very excessive protein ranges and low glucose.

Viral infections are sometimes identified through the use of PCR assay for

viral DNA or RNA in CSF or by serologic exams for particular

antibody. Gram stain and bacteriologic cultures of CSF

are adverse in viral meningitis. Fungal infections may be

identified by tradition or by serologic exams. Within the case of

Cryptococcus, the India ink take a look at and the cryptococcal antigen

take a look at are additionally helpful.

Therapy

Empiric remedy for acute bacterial meningitis should embody

medication with wonderful penetration into the CSF (capable of cross

the blood–mind barrier), which can be bactericidal, and which can be

lively in opposition to the commonest pathogens. In older kids

and adults, ceftriaxone or cefotaxime plus vancomycin is a

widespread empiric routine. Vancomycin is added to cowl for

Prevention

Prevention methods embody each immunization and che-

moprophylaxis. Vaccines are efficient in stopping bacterial

meningitis, attributable to S. pneumoniae, N. meningitidis, and

H. influenzae sort B. The immunogen within the conjugate vaccines

is the capsular polysaccharide of the organism.

The present conjugate pneumococcal vaccine (Prevnar 13)

protects in opposition to the 13 most typical serotypes. The present

conjugate H. influenzae vaccine protects solely in opposition to the sort B

serotype.

The present conjugate meningococcal vaccine protects

in opposition to 4 widespread serotypes (A, C, Y, and W-135). Observe,

nevertheless, it doesn’t comprise the sort B polysaccharide. The

vaccine in opposition to sort B meningococcus accommodates issue H bind-

ing protein (fHbp) because the immunogen. A second vaccine in opposition to

sort B meningococci containing 4 floor proteins (fHbp,

NadA, NHBA, and PorA) can be out there.

Chemoprophylaxis in opposition to S. agalactiae (group B

Streptococcus) is aimed toward decreasing vaginal carriage within the

mom. If vaginal or rectal cultures are constructive at 35 to 37 weeks

of gestation, then ampicillin needs to be given. Chemoprophylaxis

can be used to scale back nasopharyngeal carriage of N. meningitidis

and H. influenzae sort B. Shut contacts of sufferers with meningi-

tis attributable to these organisms ought to obtain both ciprofloxacin

for Neisseria or rifampin for Haemophilus.

ENCEPHALITIS

Definition

Encephalitis is an an infection of the mind parenchyma predomi-

nantly attributable to viruses. Typically each the mind and the

meninges are concerned, a situation known as meningoencephalitis.

Pathophysiology

The mode of acquisition of the viruses that trigger encephalitis

varies (Desk 72–3). Neonates purchase HSV-2 throughout passage

by means of the start canal. HSV-2 then reaches the mind by

hematogenous unfold. Moms with seen vesicular lesions

are more likely to have newborns with severe HSV-2

infections than moms who’re asymptomatic shedders of

HSV-2 as a result of the quantity of virus current is considerably

higher within the former.

In distinction, HSV-1 most likely reaches the temporal lobe by

journey down sensory neurons following activation of latent

an infection within the trigeminal ganglion (Determine 72–4). Rabies virus

additionally reaches the mind by axonal journey from the positioning of the ani-

mal chew.

Arboviruses, corresponding to WNV, are acquired primarily by mos-

quito chew after which journey to the mind through the bloodstream. The

incidence of arboviral encephalitis peaks in the summertime and

early fall as a result of that’s when mosquitoes are most lively.

VZV may cause encephalitis through the main infec-

tion (varicella is often known as chickenpox) or through the

reactivation an infection (zoster is often known as shingles). VZV

additionally causes a postinfectious encephalomyelitis involving the

mind and spinal twine after decision of the first infec-

tion. Cytomegalovirus (CMV) causes encephalitis primarily in

immunocompromised people corresponding to AIDS sufferers and

these receiving medication to stop transplant rejection. Encepha-

litis attributable to Epstein–Barr virus (EBV) is a uncommon complication

of infectious mononucleosis.

Postinfection encephalitis sometimes follows an an infection or

an immunization by a number of weeks. It’s a demyelinating illness

attributable to an immune assault on neurons, primarily these of the

white matter.

Observe that the lesions in encephalitis are inflammatory

(comprise WBCs, particularly lymphocytes), whereas the lesions of

an encephalopathy present degenerating neurons however no inflam-

mation and don’t comprise WBCs. Encephalopathy is mentioned

later in a separate part.

Medical Manifestations

Probably the most attribute scientific manifestations of encephalitis

embody fever, headache, and altered psychological standing, in addition to

seizures and focal neurologic deficits.

Rabies encephalitis has two scientific manifestations. Most

instances of rabies (80%) current with hyperactivity, agitation,

delirium, hydrophobia, and seizures (known as livid rabies). The

different 20% of instances have paralytic signs through which an ascend-

ing paralysis with out hyperactivity is the predominant characteristic

(known as dumb rabies). Coma and demise are the ultimate widespread

pathway in each kinds.

Pathogens

Viruses are the primary reason behind encephalitis; nevertheless, the trigger

of at the least half of the instances of encephalitis is unknown. Approxi-

mately 15% are attributable to HSV-1. Encephalitis attributable to HSV-1

and HSV-2 is essential as a result of HSV-1 and HSV-2 are the

most typical causes for which antiviral medication can be found,

particularly acyclovir. About 5% are attributable to arboviruses such

as WNV. Rabies virus is a uncommon trigger in the USA however

happens extra often in international locations the place immunization of

canines is just not a standard apply. VZV, CMV, and EBV additionally trigger

encephalitis.

WNV is the commonest arboviral reason behind encephalitis

in the USA. Most WNV infections (80%) are asymp-

tomatic. Many of the remaining 20% develop an acute febrile

“flulike” sickness. Lower than 1% develop CNS illness, of which

half have encephalitis. Different arboviruses that trigger encepha-

litis with some frequency are St. Louis encephalitis virus, the

La Crosse pressure of California encephalitis virus, and Japanese

and Western equine encephalitis viruses (EEE and WEE,

respectively). They’re all transmitted by both Culex or Aedes

mosquitoes.

Postinfection encephalitis follows immunization or an infection

brought about most frequently by VZV, measles, and influenza.

Prognosis

In distinction to meningitis, CSF findings in encephalitis are extra

variable. A gentle elevation in CSF lymphocytes may be seen alongside

with an elevation of protein and a traditional glucose. A standard

CSF sample can be seen in encephalitis.

PCR-based testing of CSF is usually used to find out a

particular etiology, corresponding to with HSV and VZV. WNV encephalitis

is usually identified by discovering WNV-specific IgM within the spinal

fluid.

Rabies may be identified by direct fluorescent antibody stain-

ing of a biopsy of pores and skin from the nape of the neck. A PCR assay

utilizing CSF, saliva, or tissue can be out there. The PCR assay has

the benefit of figuring out the animal reservoir and the geo-

graphic location of the virus as a result of the bottom sequence of the

RNA genome varies in accord with these two options.

Radiographic findings may be helpful as properly. Specifically, in

HSV encephalitis, temporal lobe abnormalities are often seen.

Therapy

Intravenous acyclovir is the remedy of selection for HSV-1,

HSV-2, and VZV encephalitis. There is no such thing as a antiviral remedy for

arboviral or rabies encephalitis.

Prevention

Prevention of rabies contains each preexposure (earlier than the

chew) and postexposure (after the chew) prophylaxis. Preexposure

prophylaxis with the killed vaccine needs to be given to veterinar-

ians and others susceptible to publicity. Postexposure prophylaxis

consists of each the killed vaccine and the hyperimmune

globulins that comprise a excessive titer of anti-rabies virus antibodies.

They’re inoculated at totally different websites so the antibodies don’t

neutralize the virus within the vaccine. This is a vital instance

of passive–lively immunization. There is no such thing as a vaccine for HSV-1,

HSV-2, and WNV.

To cut back the transmission of HSV-2 to the neonate, preg-

nant ladies with lively lesions late in being pregnant ought to obtain

acyclovir and needs to be thought of for cesarean part.

BRAIN ABSCESS

Definition

A mind abscess is a localized, walled-off assortment of pus sur-

rounded by a fibrous capsule inside the mind parenchyma.

Micro organism are the commonest reason behind mind abscesses, however fungi

and protozoa are additionally concerned. Viruses don’t trigger mind abscess.

Pathophysiology

Mind abscess is a acknowledged complication of head and neck

pyogenic infections, corresponding to sinusitis, otitis media, and dental

infections. Sinusitis predisposes to lesions within the frontal lobe,

whereas otitis media predisposes to lesions within the temporal lobe.

Hematogenous unfold from an contaminated website, corresponding to with infective

endocarditis, additionally happens. Desk 72–4 correlates numerous predispos-

ing situations with the organisms prone to trigger mind abscess.

With growing use of immunosuppressive medication, indwell-

ing intravenous catheters, and hyperalimentation, fungal mind

abscesses have turn out to be extra widespread. Immunocompromised

sufferers, particularly these with AIDS, even have mind abscesses

attributable to Toxoplasma gondii.

Medical Manifestations

Headache alone is the commonest symptom of mind abscess,

and thus, when headache alone happens early within the illness, the

prognosis of mind abscess can typically be missed. Because the lesion

progresses, sufferers might develop fever, behavioral adjustments, focal

neurologic deficits, and seizures.

Pathogens

Micro organism

Streptococci, each cardio and anaerobic, are mostly

remoted from bacterial mind abscesses. They’re sometimes of oro-

pharyngeal origin, corresponding to Streptococcus anginosus and viridans

group streptococci. They’re sometimes seen in blended infections

with oral anaerobes corresponding to Prevotella, Fusobacterium, and

Bacteroides. Nocardia asteroides additionally causes mind abscesses.

Monomicrobial infections with Staphylococcus aureus are sometimes

related to infective endocarditis.

Fungi

Fungal abscesses happen primarily in immunocompromised

sufferers. Aspergillus fumigatus can happen in neutropenic

sufferers, rhinocerebral mucormycosis (attributable to Mucor and

Rhizopus species) in diabetic sufferers with ketoacidosis, and

cryptococcal an infection in sufferers with HIV/AIDS. Candida

species are additionally concerned.

Protozoa

Toxoplasma gondii is the primary protozoal reason behind mind abscess.

It is a vital trigger in immunocompromised sufferers, espe-

cially these with AIDS, sufferers receiving most cancers chemotherapy,

or sufferers on immunosuppressive medication used to reinforce

transplant survival. Toxoplasma gondii may be transmitted by

strong organ transplant, particularly coronary heart transplants, in addition to by

the extra widespread modes of transmission, particularly ingestion of

uncooked meat containing cysts or by publicity to cat feces contain-

ing oocytes. Transplacental transmission of T. gondii may cause

intracranial calcifications within the fetus.

Prognosis

MRI is a vital diagnostic modality, typically revealing a

“ring-enhancing” lesion (Determine 72–5). A microbiologic diag-

nosis requires acquiring pus from the abscess and performing a

tradition for cardio and anaerobic micro organism and fungi. In bacte-

rial mind abscesses, the Gram stain often reveals a number of

forms of micro organism indicting a blended an infection. Aspiration of pus

from the lesion is each diagnostic and therapeutic, having the

impact of draining the abscess.

A microbiologic prognosis of Toxoplasma an infection is often

made by figuring out particular radiographic findings in an at-risk

host (e.g., HIV/AIDS) with a constructive Toxoplasma IgG and a

response to particular antiprotozoal remedy. A PCR-based assay

for Toxoplasma nucleic acid can be out there.

Therapy

Empiric antimicrobial remedy for bacterial mind abscesses con-

sists of a third-generation cephalosporin, corresponding to ceftriaxone or

cefotaxime, plus metronidazole. The latter is protection for the

FIGURE 72–5 Mind abscess. Pink arrow factors to a character-

istic ring-enhancing lesion. The blue arrows level to 2 extra

abscesses. (Reproduced with permission from Ropper AH, Samuels MA. Adams

and Victor’s Ideas of Neurology. ninth ed. New York, NY: McGraw-Hill; 2009.)

anaerobic micro organism. Vancomycin needs to be added if the affected person

has undergone a neurosurgical process. Therapy of bacte-

rial and fungal mind abscesses might require aspiration of pus

from the abscess along with antibacterial or antifungal medication.

Mind abscess attributable to Nocardia may be handled with

trimethoprim-sulfamethoxazole. Mind abscess attributable to

Aspergillus may be handled with voriconazole. Therapy of

Toxoplasma mind abscess features a mixture of pyrimeth-

amine and sulfadiazine.

Prevention

There aren’t any vaccines to stop mind abscesses. Early treat-

ment of odontogenic and sinus infections might forestall these

problems. Tight management of blood glucose might forestall

rhinocerebral mucormycosis in diabetics. Therapy of AIDS

sufferers with antiretroviral remedy might forestall Toxoplasma

mind abscess, and when the CD4 rely is <100 cells/μL,

main prophylaxis with trimethoprim-sulfamethoxazole is

really useful in sufferers who’re constructive for Toxoplasma IgG.

SUBDURAL AND EPIDURAL EMPYEMA

Subdural empyema is a group of pus on the internal floor

of the dura mater, whereas epidural empyema is a group of

pus on the outer floor. They will happen adjoining to the dura of

both the mind or spinal twine.

Sinusitis and otitis media are widespread predisposing fac-

tors, and the micro organism inflicting these empyemas are people who

trigger sinusitis and otitis media, particularly, cardio and anaerobic

streptococci, staphylococci, enteric gram-negative rods such

as Escherichia coli, and anaerobic gram-negative rods corresponding to

Prevotella. Combined infections are widespread.

The scientific options embody fever plus signs of elevated

intracranial stress, corresponding to headache, vomiting, focal neuro-

logic deficits, and altered psychological standing. MRI with gadolinium

enhancement reveals a mass adjoining to the dura. Microbiologic

prognosis entails aspirating pus from the lesion and perform-

ing a Gram stain and tradition. Therapy entails surgical drain-

age of the pus mixed with antibiotics applicable for the

micro organism remoted from the aspirated pus.

ENCEPHALOPATHY

Encephalopathy refers to altered mind operate within the absence

of irritation. Generally, sufferers with encephalopathy do

not have fever, headache, seizures, focal neurologic indicators, and

an elevated WBC rely within the blood and spinal fluid, whereas

sufferers with encephalitis typically do. Frequent manifestations of

encephalopathy embody confusion, character adjustments, disori-

entation, aphasia, delirium, and dementia.

There are a number of infection-related causes of encephalopathy

(see later), however most causes are noninfectious (e.g., alcohol,

medication, lead, uremia, or liver failure).

Necessary infection-related causes of encephalopathy

embody the next:

• Progressive multifocal leukoencephalopathy (PML).

PML is attributable to JC virus and happens in immunocom-

promised sufferers, notably AIDS sufferers. An infection with

JC virus happens early in life and stays latent till the

immune system is compromised. PML has occurred in mul-

tiple sclerosis sufferers being handled with natalizumab and

in transplant recipients being handled with mycophenolate.

Microbiologic prognosis is made by detecting JC virus DNA

utilizing PCR assay on mind specimens or spinal fluid. There’s

no antiviral drug remedy and no vaccine. Extra infor-

mation may be present in Chapter 44.

• HIV encephalopathy together with AIDS dementia. One other

CNS illness that’s seen in HIV-infected people is

encephalopathy attributable to HIV itself. It will probably range from

gentle signs corresponding to reminiscence issues and apathy to

extra severe illness corresponding to profound reminiscence loss and

psychosis (AIDS dementia). AIDS dementia is extra possible

to happen when CD4 counts are beneath 200/μL and when the

viral load within the CSF is excessive.

• Creutzfeldt-Jakob illness (CJD) and kuru. CJD is one among

the human transmissible spongiform encephalopathies. The

time period “spongiform” refers back to the spongy, Swiss cheese-like

look of the mind of sufferers with CJD. CJD is brought about

by prions, a misfolded protein through which the conventional alpha-

helical configuration has modified to a beta-pleated sheet,

thereby altering the operate of the protein and resulting in

demise of neurons. Extra data on prions may be

present in Chapter 44.

CJD happens sporadically worldwide at a price of about one

case per million inhabitants. CJD has been transmitted iat-

rogenically by corneal transplant, intracerebral electrodes,

and dura mater grafts. CJD doesn’t have any relationship

to the ingestion of any meals, in contrast to variant CJD, which is

mentioned later.

The primary scientific findings in CJD are dementia and

myoclonus. The development is gradual however inexorable,

leading to coma and demise. Definitive prognosis is made by

observing spongiform adjustments in mind biopsy adopted by

histochemical staining with anti-prion antibodies. There’s

no drug remedy for CJD and no vaccine.

Variant CJD is acquired by the ingestion of prion-

containing beef. It’s declining on account of the ban on the

addition of animal merchandise to cattle feed.

Kuru is a spongiform encephalopathy discovered within the Fore

tribe in New Guinea. It’s now very uncommon as a result of the consuming

rituals that transmitted the agent are not practiced.

• Reye’s syndrome. Reye’s syndrome is a postinfectious

illness consisting of encephalopathy plus liver failure. It

happens primarily following influenza B and varicella infec-

tions in kids and is related to aspirin use. The position

of aspirin in pathogenesis is unsure however a poisonous impact on

mitochondria has been proposed.

After the kid has recovered from the viral an infection,

Reye’s syndrome begins with distinguished vomiting adopted

by encephalopathic adjustments corresponding to lethargy and combative

habits progressing to coma and demise. Cerebral edema

is marked. Fatty degeneration of the liver happens, and liver

enzymes corresponding to transaminases are elevated. Blood ammo-

nia ranges are elevated.

Therapy needs to be instituted promptly. If coma happens,

remedy is much less efficient. Antiviral medication should not efficient.

Supportive measures corresponding to cooling blanket, ventilator to

present respiratory help, management of intracranial pres-

positive, hemodialysis, and fluid and electrolyte steadiness are

used. Vaccines in opposition to varicella and influenza and public

well being campaigns to scale back aspirin use in febrile kids

have vastly decreased the incidence of this illness. Acet-

aminophen needs to be used to scale back fever in kids.