Ali - CNS Infections

8/3/2019 Ali - CNS Infections

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Central Nervous SystemInfections

Clinical Aspects

I m r a n I Al i M .D .

P r o f e s sor of N eu r o l ogyUn i ve rs it

y of T o l edoC o ll ege of M ed i c i ne


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CNS Infections

Objectives Describe the epidemiology/ pathogenesis/

microbiology/ clinical presentation/diagnosis/ basic treatment of common CNS infections


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CNS Infections

Brain Acute Bacterial

Meningitis S. Pneumoniae Subdural Empyema Brain abscess

Viral Meningitis Viral Encephalitis

HSE

HIV

Spinal Cord Epidural Abscess

Viral myelitis


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CNS Anatomy

To understand central nervous systeminfections - pathogenesis, presentations - it isnecessary to recall the basics of CNS anatomy brain and spinal cord are surrounded by the

leptomeninges (pia mater and arachnoid)

pia mater is continuous and tightlyadherent to the brain

arachnoid encloses parenchyma and piamater loosely


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CNS Anatomy

Cerebral spinal fluid (CSF) - located in thespace between the pia mater and thearachnoid mater (a.k.a. - the subarachnoidspace) secretion of CSF mostly by cells in the

choroid plexus (in the lateral, 3rd, 4thventricle)


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CNS Anatomy

CSF Composition: derived from blood plasma

Small amount of protein ( 50% serum), less specific gravity, and

more chloride (n-118-132) than blood plasma Total amount is 140-150 cc on average Opening pressure is approximately 8-16 cm water

(80-160 mm), > 20 cm water is abnormal!


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CNS Anatomy

Dura mater Adherent to the periosteum and skull

except for four rigid septa falx cerebri, falx cerebelli, tentorium

cerebelli, diaphragma selli Brain sits on the cranial fossa

Anterior fossa is actually the roof of thefrontal and ethmoid sinuses


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CNS Anatomy

Blood -Brain barrier Capillaries in the CNS have tight

junctions (no fenestrations in general)

and are surrounded by the foot processesof nearby astrocytes this forms the relatively impermeable

blood brain barrier Blood brain barrier does not generally

allow large molecules to enter CNS by

diffusion


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CNS Infections

CNS is well protected- difficult for organisms to penetrate into brain (also

difficult for

good

things like antibiotics,complement, and antibodies as well)

CNS is a tightly enclosed space and so even

very small amounts of organisms causinginflammation (edema) can have devastatingconsequences


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CNS Infections

CNS infections are grouped by anatomicallocation Encephalitis - infection of brain

parenchyma Meningitis - infection of leptomeninges

Myelitis - infection of spinal cord tissue Neuritis - infection of peripheral nerves Organisms enter CNS via bloodstream,

neuronal pathways, or direct inoculation


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Acute Bacterial Meningitis

Meningitis - inflammation of the meninges if the brain parenchyma is also involved, it is

called meningoencephalitis if brain and spinal cord tissue are also

involved, it is meningoencephalomyelitis

Acute bacterial meningitis infection of meninges due to bacteria with

clinical presentation within 24 - 48 hours

sine qua non is CSF leukocytosis


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Epidemiology and Etiology 3 cases per 100,000 in US rate is over 15x higher in underdeveloped

countries epidemics are also common in addition

to the high endemic rate Common organisms are S. pneumoniae,

N. meningitidis, H. influenzae, L.


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0 - 4 week s : Group B streptococcus ( S.agalactiae ), E. coli, L. monocytogenes

< 18 y / o : H. flu (type b greatly decreased,other strains increasing), N. meningitidis, S

pneumoniae

18 - 50 y / o : N. meningitidis, S pneumoniae >50 y / o : N. meningitidis, S pneumoniae , L.

monocytogenes, GNR


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Epidemiology of ABM


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Risk Factors in the Elderly


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H. influenza Type b vaccine has greatly decreased the rate

of H. flu meningitis but invasive disease due toother encapsulated strains such as type f areincreasing

In patients >5 yo, meningitis may be associatedwith sinusitis, otitis, epiglottitis, pneumonia

Predisposing conditions: DM, alcoholism,

asplenia, CSF leak, hypogammaglobulinemia


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N. meningiditis Serotypes A,B,C, W135, and Y

commonly associated with meningitis Serotype B causes >50% of infections Vaccine is active against A, C, W135,

and Y Terminal complement deficiencies are

associated with increase in attack rate anddecrease in fatality rate


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associated with meningitis


S. pneumoniae # 1 cause of meningitis in 18 - 50 yo often associated with URI/LRTI or

endocarditis predisposing conditions: DM, alcoholism,

asplenia, CSF leak,hypogammaglobulinemia

vaccine covers most common serotypes


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L. monocytogenes Causes 2 - 3% of cases of meningitis but is

seen in neonates, pregnant women, elderly,immunocompromised

Ce ph a losporin s a r e no t ac tiv e a g a ins t L ist e riaa nd v a n c o m y c i n i s not r e li a bl y e ff ec tive

Ampicillin or Trimethoprim-sulfa aretreatments of choice


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ACUTE BACTERIAL MENINGITIS

Consider in patients with fever and any neurologic symptoms/cerebral dysfunctionTypical presentation-headache, fever, lethargy, confusion,vomiting, stiff neck - but presentation may be variable< 80% nuchal rigidity, Kernig

s or Brudzinski

s signsPapilledema:


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Kernigs

s sign patient lies supine with thigh

and knee flexed leg is passively extended and

this is resisted with meningealinflammation

Brudzinski

s sign passive flexion of the neck

causes passive flexion of pelvis/hips


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CID July 2002 :35; 46-52. Thomas, et al. Thediagnostic accuracy of Kernig

s sign, Brudzinski

s sign, and Nuchal Rigidity in Adults with suspected meningitis. Prospective study of meningeal signs prior to LP

Kernig

s sign and Brudzinski

s sign - sensitivity 5%:

positive predictive value - 27% nuchal rigidity - sensitivity 30%: positive predictive

value - 26%


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CSF examination essential Contraindications to lumbar puncture

increased intracranial pressure platelet count


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CSF EXAMINATION Need to order

WBC withdifferential

Glucose Protein

Gram stain andculture Need 4-8 cc Always take more

than you need!

CSF EXAMINATION Special Studies

Cytology Cryptococcal Antigen

and India Ink VDRL AFB & Fungal Smear

& CS Viral Studies ?Latex agglutination


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Bacterial meningitis partially tx WBC >1000 with >60% PMNs Glucose often < 45 Protein may be increased Gram stain and culture positive 60 - 65% Latex agglutination may be helpful here Oral ATB (low dose) usually leaves CSF


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abnormal, especially glucose


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Treatment (begin within 3 0 minu t es ) Needs to cover the most commonly encountered

pathogens: treat for 10 -14 days Ceftriaxone 2 grams iv bid + Vancomycin if >2%

community incidence of high level S.pneumoniaeresistance + Ampicillin 4 grams q6 hours if patient > 50

or immunocompromised Dexamethasone used in children -lactam anaphylaxis - Tmp-smx + chloramphenicol.


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Dexamethasone in adults - 301 patients with bacterial meningitis

157 received Dexamethasone with ATB or 15minutes prior

144 ATB alone mortality and adverse outcome (Glasgow Outcome Scale)

improved with Dexamethasone, especially in the patientsubset with pneumococcal meningitis sensitive to PCN

NEJM 2002: 347: 20 : 1549 - 1556


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Complications

Raised intracranial pressure Seizures Hearing loss Hydrocephalus

Subdural Empyema Cerebral Infarction Cognitive Impairment


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Acute Viral Meningitis

Viral meningitis is often referred to asaseptic meningitis

meningitis without bacterial etiology -generally means viral etiology

Enteroviruses cause 80-85% of cases of

viral meningitis arbovirus, herpes virus, and HIV are also

common causes of aseptic meningitis


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Pathophysiology Mucosal colonization -->viremia -->

BBB crosses by virus (or may travelalong nerve endings) --> viral entry intosubarachnoid space --> spread of virus in

CSF --> inflammatory response specificfor the virus and consisting of lymphocytes begins: T-cell responseneeded to clear CSF


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Clinical manifestations Enterovirus meningitis in kids > 2 weeks old

sudden onset of fever, severe frontal headache, photophobia, nuchal rigidity and myalgias,vomiting, diarrhea, anorexia, cough, sore throat

usually occurs in the summer months

may also be associated with recognizableenteroviral syndromes (eg - classic rash of hand-foot-and-mouth disease, the painful mouth vesiclesof herpangina)


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Clinical manifestations Initial episode of HSV 2 infection often

associated with aseptic meningitis andsigns of genital tract infection

Initial episode of HIV infection may also

be associated with aseptic meningitis


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Diagnosis LP with


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Viral (aseptic) meningitis WBC usually


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Treatment Enterovirus: Consider use of IVIG if

patient is extremely ill Herpes virus: Acyclovir HIV: Consider triple drug therapy


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Chronic Meningitis

Definition Neurologic abnormalities or CSF

abnormalities of > 4 weeks duration

Etiology Infections: TB, Nocardia, Cryptococcus,

Syphilis, Lyme Disease

Noninfectious diseases: Behcet

s,Meningeal Carcinomatosis, Sarcoidosis


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Chronic Meningitis

Clinical Manifestations Often insidious onset of symptoms which

wax and wane over weeks but withgradual neurologic decline

Cranial neuropathies

Focal neurological signs such asweakness, ataxia, sensory loss


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Chronic Meningitis

Diagnosis and Treatment Diagnostic workup is very difficult and is

guided by a thorough history and physicalexam plus lumbar puncture(s)

Treatment is generally not empiric but is

guided by the most likely initial diagnosisif the patient is critically ill or preferably

by a confirmed diagnosis


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Chronic Meningitis

Fungal WBC 60 need special smears

and cultures

Tubercul osi s WBC < 1,000 Glucose > 100 AFB smear and culture

positive more than>85% need to examine10cc centrifuged fluidfor > 1 hour


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Chronic Meningitis

A 36 year old with 3 week history of progressive gait disorder,weakness and multiple cranial neuropathies.


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TB Meningitis

A 12 year old immigrant from South Asia with chronic cough andheadaches. Examination shows bilateral sixth nerve paralysis.


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Intracranial Abscess

Definition: abscess in brain parenchyma May or may not be associated with

meningeal involvement From contiguous foci - 50% From hematogenous dissemination - 25% From direct inoculation - 10% Primary abscess - 15%

I t i l Ab


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Pathogenesis - site of abscess gives a clue to itsorigin Frontal lobe: sinuses, teeth, direct inoculation Temporal lobe: otitis, mastoiditis, sphenoid

sinusitis Cerebellum: otitis, mastoiditis MCA circulation - hematogenous source (eg-

lung abscess, endocarditis) Beneath area of a wound - direct inoculation


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4 stages of abscess formation early cerebritis 1 - 3 days

late cerebritis 4 - 9 days early capsule 10 - 13 days late capsule > 14 days



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Intracranial Abscess Bacteriology

Otitis/mastoiditis - Strep, Bacteroides, GNR Sinusitis - same as otitis + S. aureus Teeth - Fusobacterium, anaerobes, strep

Wound - staph, strep, GNR, Clostridium Endocarditis - staph or strep Lung - actinomyces, anaerobes, strep, fusobacterium,

nocardia Immunocompromised - toxoplasmosis, fungi, GNR,

nocardia



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Clinical manifestations Space occupying lesion --> headache, N/V, seizures, mental status change, focalneurologic deficit deficit depends on location --

cerebellar abscess may have ataxia,temporal lobe may have visual fielddefect, etc

generally < 50% have fever with

presentation


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presentation


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Diagnosis MRI or CT scan with contrast are

diagnostic modalities of choice MRI is very sensitive Avoid LP


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Treatment

Surgical drainage and management of increased ICP almost always required

Search for source Culture abscess for bacteria, fungi,

mycobacteria and obtain immediate gramstain, AFB stain and fungal smears to help

guide therapy Empiric ATB - metronidazole + 3rd gen

ceph+ nafcillin or vancomycin


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Encephalitis

Encephalitis means inflammation of the brain - it is characterized by alterations in

consciousness many non-infectious diseases can be

associated with encephalitis (eg- drug

reactions, vasculitis) in general, infectious encephalitis is due

to viral infection, less commonly


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bacterial, fungal, or tubercular infection


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Encephalitis - Common Viral Causes

Herpesviruses - HSV 1 and 2, VZV (only treatableform of encephalitis)

West Nile HIV Togaviruses - cause EEE (eastern equine encephalitis),

WEE (western EE), and VEE (Venezuelan EE) Flaviviruses - St. Louis encephalitis, West Nile virus Enteroviruses (e.g. poliovirus) Rhabdovirus rabies Paramyxoviruses measles

Encephalitis


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most viruses

Pathophysiology

Encephalitis

Pathogens enter brain parenchyema in severalways Hematogenous - occurs for many viral

infections, rickettsia, bacteria, fungi, and TB Retrograde peripheral transport - rabies,

varicella Exposed olfactory nerves - definitely the route

of entry for Naegleria and Acanthamoeba but inexperimental animals is also route of entry for


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Encephalitis

Clinical Manifestations Classic presentation is altered mental

status and personality changes, decreaseslevel of consciousness, focal neurologicfindings, and seizures


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Encephalitis

Diagnosis EEG often has a characteristic pattern

MRI in HSV encephalitis shows temporallobe involvement

LP often with mild pleocytosis

PCR for HSV is diagnostic


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Encephalitis

Treatment Intravenous Acyclovir is effective

treatment for encephalitis caused byHSV1/2 and VZV.

Ganciclovir and Foscarnet for CMV

HAART for HIV


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West Nile Encephalitis

A 79 year old with headaches, progressive weakness and encephalopathy.


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HIV Encephalitis

A 32 year old with poor memory, weakness and inability to comprehend.

l l l f


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Neurological Complications of

HIV Meningitis- acute or chronic

Encephalopathy Vacuolar myelopathy Peripheral neuropathy

distal symmetric polyneuropathy Mononeuritis multiplex

Myopathy


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Secondary Involvement

Opportunistic infections Toxoplasmosis, Cryptococcus meningitis,

CMV, PML Neoplasms

Lymphoma

Vascular Drug toxicity Nutritional and metabolic


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PML


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PML


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CNS Lymphoma


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M liti I f ti C


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Myelitis- Infectious Causes

Highlights Herpes Virus VZV

Picornavirus Enteroviruses, Polio

Flaviviruses West Nile, Japanese B,

St. Louis Retrovirus

HIV, HTLV-1

Bacterial Lyme, Syphilis

Fungal Aspergillus

Parasitic Schistosomiasis


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Clinical Presentation

Acute to sub acute onset Weakness involving arms and/or legs

Numbness and sensory loss Incontinence (bowel and/or bladder)


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Subdural Empyema

Definition - pyogenic infection of space between the dura and arachnoid

Subdural space is crossed by numeroussmall veins (emissary vessels) and dividedinto several anatomic compartments by the

falx cerebri, tentorium cerebelli, and base of the brain @ 20 % of all intracranial infections


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infection

Subdural Empyema

Organisms reach subdural space throughemissary vessels or direct extension of

osteomyelitis of the skull (as a sequalae of associated epidural abscess) Source of empyema

50 - 80 % frontal or ethmoid sinusitis 10-20% otitis media/mastoiditis 5% hematogenous dissemination of


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Subdural Empyema

Bacteriology aerobic streptococci, staphylococci, S.

pneumoniae, H. influenzae, anaerobes,other gram - negative organisms,

polymicrobic infections are common

Epidemiology 4:1 males to females usually 2nd and 3rd decades of life

Subdural Empyema


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Clinical Manifestations Acts like a rapidly expanding mass lesion Fever, focal headache that later generalizes,

vomiting, altered mental status Focal neurologic signs appear then spread and

expand rapidly to include hemiparesis,seizures

Due to rapid spread < 50% have papilledema Occasionally patients progress neurologically

in weeks, rather than hours


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Subdural Empyema

Diagnosis MRI is diagnostic and very sensitive

CT scan will miss some subduralempyemas

CSF + in 14% of cases but LP is contra-

indicated


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Subdural Empyema

Treatment Neurosurgery for burr holes or

craniotomy Aggressive management of increased ICP

including use of dexamethasone

Culture of empyema fluid May need simultaneous debridement of

sinuses, mastiod, or ear

Subdural Empyema


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Treatment

Antibiotics indicated for a minimum of threeweeks need to cover anaerobes, GNR, GPC

Metronidazole + Ceftriaxone + Nafcillin or Vancomycin would be good empiric therapy

pending culture results

Prognosis 75% mortality if comatose, otherwise @ 15% 42% of survivors develop seizures


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Epidural Abscess

Abscess located between bone and the duramater

Intracranial epidural abscess generallyspills over into the subdural space andforms an associated subdural empyema aswell (81% of the time) etiology/pathogenesis/microbiology/

diagnosis/therapy same as for subduralempyema

Epidural Abscess


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Intracranial epidural abscess

Inflammation of the face or scalp may be present otherwise clinical manifestationsare the same

Spinal epidural abscess is different fromintracranial epidural abscess in spinal canal, dura mater is not adherent

to the vertebra but epidural space is adistinct fat filled anatomic space withoutemissary vessels


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dissemination

Spinal Epidural Abscess

Spinal epidural abscess Spinal canal anatomy allows easy

longitudinal but not subdural spread Ne u ro l og i c a l e m erge n cy!

Etiology

Bacteria enter epidural spinal space bydirect extension from vertebralosteomyelitis or hematogenous


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Less often polymicrobial than intracranialepidural abscess

S aureus 60 -90% and often the sole pathogen followed by streptococci,anaerobes, and gram-negative rods

Abscess at time of diagnosis usually covers4 - 5 vertebra but may extend the wholelength of spine


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Clinical manifestations Focal vertebral pain develops first, followed by

radiculopathy, then motor and/or sensorydeficits (sphincter function if lumbar location),and finally increasing paralysis

Patients may (or may not) have fever and appear quite ill Time course of evolution of clinical features can

be a few hours to days/weeks



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Clinical manifestations Often see nuchal rigidity and severe focal tenderness

Diagnosis MRI is diagnostic modality of choice Myelogram (injection of radio-opaque dye into

arachnoid space) can be used as well to visualize thecord and look for compression (not preferred)

blood cultures are often positive, SED usuallyelevated


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p p Treatment

Immediate surgical drainage traditionalteaching

Case reports of recovery in selected patientswith antibiotics alone

Cover S. aureus, GNR, and anaerobes pending culture results

Vancomycin +3rd gen ceph +metronidazole

Prognosis if treated prior to paralysis/very poor if paralysis present >24 hours


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Recap


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Documents

Ali - CNS Infections