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Flashcards in Neuroinfectious Diseases Deck (47)
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Meningitis general

Defined as inflammation of the meninges

Leptomeninges (arachnoid and pia - these are more common) vs pachymeninges (dural inflammation)

White cells in CSF are always present in meningitis, except in systemic leukopenia

Presentation: HA, neck stiffness, fever if infectious

Many causes: Bacteria, virus, fungi, parasites, chemicals, blood, cancer

Note: Arachnoid and dura are technically not part of CNS (except in optic nerve)


Meningitis CSF profile

Differs by cause

Bacterial: Mainly PMNs, High protein, Low glucose, Positive gram stain 60-70%

Viral: Mainly lymphs, High protein, Normal glucose, Negative gram stain

Fungal and mycobacterial: Mainly lymphs, High protein, Low glucose, Negative gram stain


Complications of meningitis

CN issues (they run in subarachnoid) - CN 8 (deafness) associated with H Flu

Stroke (inflammation of circle of willis)

Death (cerebral edema or sepsis)


Adrenal infarction (N. meningitides)


Approach to meningitis

Things to consider doing:
1) BCx
2) LP - cell count w/diff, protein, gluc, cx
3) ABx**
4) Steroids
5) CT? Not needed if normal neuro exam and not immunosuppressed. Mass effect secondary to cerebral edema is what we worry about before an LP (this would cause herniation). We would see neuro signs though.

Random Note: Papilledema is not a contraindication to LP. Not always a great indication of increased ICP bc it takes a couple of days to develop it.

Give ABx ASAP. Everyone gets Ceftriaxone + vancomycin and maybe ampicillin (older, babies, immunocompromise)


Meningitis signs

Meningeal signs:

1) Neck pain elicited by flexion-extension, not side-to-side movement

2) Kernig sign - neck pain when patients knee is passively extended with the hip flexed at 90 degrees

3) Brudzinski sign - Patient flexes knee and hips when the neck is passively flexed while supine

HA (worsening and persistent)

Many of the signs and symptoms of meningitis are due to the immune response to it so people who are immunocompromised may not have any symptoms

Note: CNS has very poor immune surveillance (We have the BBB so we never really needed good immune surveillance in the CNS). We can have abscess with no fever or signs or anything. Whenever CNS needs help, BBB must break down then it's TOO MUCH HELP.


Encephalitis general

Defined as infection of the brain parenchyma itself

May be diffuse or focal

Presents with fever, HA and personality or mental status changes. Seizures and focal deficits commonly seen too. These personality and seizure features are due to its propensity for the temporal lobe (behavior and memory changes too)

Tends to be fatal

Few days prodrome/behavioral changes

#1 = viral. #1 viral = HSV1

However, 90% of encephalitis is not from HSV1

33% of encephalitis are AI-mediated. #1 = NMDA. #2 = Anti-hu (small cell lung)

Ovarian teratoma with a bit of nervous system tissue - immune system attacks it. This is NMDA

Tx = steroids, Rituxumab, IVIG, remove teratoma/germ cell tumors

Therapy aims to prevent antibodies from entering CNS



Defined as infection of the spinal cord. 3 patterns.

1) Transverse myelitis - disease at one or more segments with dysfunction below that level. #1 cause is demyelinating, AI. Can also be VZV. Everything can be explained by single lesion - inflammation at single segment

2) Slowly progressive spastic paraparesis - diffuse process. No real findings on MRI. Always r/o B12 deficiency. Non-localizing but progressive UMN dysfunction. Can't find 1 single level. #1 is HIV or HTLV1 (caribbean)

3) Acute flaccid paralysis (AHC infection). Asymmetric LMN dysfunction - #1 = polio. Can be west nile, enterovirus D68, colorado, west coast



Defined as infection of the nerve roots as they exit the spinal cord

Presents with shooting radicular pain, usually with weakness in the muscles supplied by the roots as well.

May mimic GBS except CSF is quite different

Consider Lyme or leptomeningeal carcinomatosis

GBS has sensory AND motor involvement. 3-4d feet tingling symmetric ascending paralysis. By 28d patient should be improving. This is a disease of nerve roots that are demyelinating. Chunks of myelin fall into CSF (increased protein). MRI might show enhancement of nerve roots.


How do bacteria gain access to the nervous system?

3 ways

1) Hematogenous spread - bacteremia, embolization of infected tissue

2) Direct extension - ears, sinuses, skull, penetrating trauma

3) Iatrogenic source - ventricular shunts, surgical, LP


Causes of bacterial meningitis

1) GBS
2) E Coli
3) Listeria

Children and Adults
1) Meningococcal meningitis
2) Pneumococcal meningitis

Older adults and immune suppressed
1) Gram negatives
2) Listeria
3) Pneumococcal


Clues for S. pneumo meningitis

Associated with otitis media, sinusitis, skull fx. More frequent in alcoholics


Clues for N. meningidities meningitis

Can occur with meningococcemia, causing a rash and adrenal crisis


Clues for H flu meningitis

Unvaccinated children with nasosinal infections


Clues for Listeria meningitis

Elderly and immunocompromised

Rare listeria rhombencephalitis mimics other brainstem encephalitis (GAM, Bickerstaffs etc)


Treatment of bacterial meningitis - general

Antibiotics should be empiric at first then changed to specific one based on cultures

All patients should get a 3rd generation cephalosporin

Immunocompromised, young (less than 12w) and old (more than 50) should get ampicillin

Vanc in any patient with outside entry to CSF (skull fx, post NSGY), also in immunocompromised and in areas with high resistance of pneumococcus to PCN

Ceftazidime for gram neg coverage in immunocompromised patients


Specific treatment of various bacterial sources of meningitis

1) S.pneumo - PCN sensitive gets PCN-G. PCN resistant gets CTX

2) N.mening - PCNG, ppx close contacts

3) HFlu - PCNG

4) Listeria - Ampicillin and gentamicin

5) Others - should always consult local hospital resistance charts for proper coverage


Bacterial brain abscess general

Aerobes account for 67%. Strep milleri is 50% (sinuses, dental), S.aureus 25% (think trauma/surgery), Gram negative bacilli 25%

Anaerobes account for 33%. Associated with pulmonary and otitic sources. Bacteroides, Fusobacterium, Clostridium.

Not uncommon to find mixed flora

Generally presents as a subacute illness. Fever due to systemic infection but only seen in 50%. HA in 50-70%. Seizures in 30-40%, usually partial. Focal deficits based on location of lesion. Signs and symptoms of high ICP may be there.

May NOT have classic systemic signs and symptoms


Diagnosing an intracranial abscess

Elevated WBC in about half

LP should be avoided as 20-30% will deteriorate and usually only helps with dx with an associated ventriculitis or meningitis

MRI with gad is in the imaging of choice


Intracranial abscess treatment

Combined NRSGY and medical approach

ABx are given for 4-6w. Classic regimen is PCN-G + chloramphenicol. Modern is Cefotaxime + metronidazole. Consider vanc in postop/trauma.

AEDs should be considered. Up to 90% of survivors develop epilepsy.

Steroids reserved for increased ICP


Mycobacterial infections - TB

Caused by myco TB and rarely M. bovis

1% of TB cases involve the CNS. TB meningitis, tuberculoma, Pott's disease.

one third of world's population is infected with TB. 4000 cases of TB meningitis occur in the US every year.

May occur during primary infection or reactivation, spreading to the CNS hematogenously.


Spirochetal infections - neurosyphilis

Caused by T.pallidum

Five CNS syndromes:
1) Acute syphilitic meningitis
2) Cerebrovascular syphilis
3) Tabes Dorsalis
4) General paresis
5) Gummatous neurosyphilis

Tx involves high dose IV PCN-G


Viral meningitis

Most common cause of acute asceptic meningitis

Usually consists of an acute, benign monophasic illness which is self-limited

Usually remits in 7-10d

Similar symptoms as bacterial meningitis but less intense.
- fever, HA, nuchal rigidity
- cranial neuropathies and ICP elevations are not expected in contrast to bacterial**
- Alteration of consciousness, seizures, focal neuro signs suggest coexistent encephalitis


Viral meningitis etiologies

1) Enterovirus - 85-95%. Echovirus, coxsackie
2) Arboviruses - flavivirus, reovirus, bunyavirus
3) Herpesviruses - HSV2 way more common than HSV1
4) HIV - acute seroconversion. HIV can get into CSF at this time. Look for HIV if you also see things like LAD
5) Mumps
6) Lymphocytic choriomeningitis virus (LCM)

Note: HIV doesn't infect neurons. It targets microglia and neuronal damage is caused by cytokine-mediated processes


Viral encephalitis etiologies

Herpes viruses - HSV1, HSV2 in neonates, VZV, EBV, CMV, HHV6, Herpes B

Paramyxoviruses - Measles (SSPE), Rubella, Mumps, Nipah, Hendra

Retroviruses - HIV, HTLV1

Papovaviruses - JC

Arboviruses - Alphaviruses (EEE, WEE, VEE), flavivirus (WNV, St Louis, Japanese), Reovirus (colorado tick), Bunyaviruses (LaCrosse)



HSV1 viral encephalitis

Usually temporal lobe

Can cause encephalitis, meningitis, or myelitis

Most common cause of sporadic, fatal encephalitis in the USA

Accounts for 10% of encephalitis

Causes a focal encephalitis with predilection for inferior frontal and medial temporal lobes

Mortality 70% untreated. 20% with rapid treatment (acyclovir)

Even with treatment, 70% of survivors develop permanent deficits

Most cases are probably due to reactivation of latent infection in trigeminal ganglia


Viral myelitis - polio

Incubation period 7-14d

8% develop meningitis

1% develop acute flaccid paralysis - asymmetric and develops over 3-5d

CSF with early PMNs then lymphocytes, elevated protein

PCR is available

Last WT case in USA 1979

Vaccine: Sabin is live attenuated. Salk is whole killed


Viral ganglionitis - VZV

Herpes zoster begins with radicular pain followed in 3-4d by a painful vesicular rash in a dermatomal distribution. Most common is T5-12.

CN in 15% - zoster ophthalmicus, Ramsay-Hunt

CSF lymphocytic pleocytosis

Rash lasts 10-14d

Pain typically lasts 4-6w

May get post-herpetic neuralgia 1m after shingles

Tx for neuropathic pain: Gabapentin and pregabalin work on presynaptic VGCCs. TCAs (like nortriptyline, anticholinergic side effects). Duloxetine.


HIV related neurologic disease

Caused mainly by HIV - AIDS dementia complex, HIV vascular myelopathy, HIV neuropathy, HIV myopathy

Caused by immunosuppression - progressive multifocal leukoencephalopathy, cryptococcal meningitis, cerebral toxoplasmosis, primary CNS lymphoma

Caused by antiretrovirals - myopathy from AZT and some D drugs, neuropathy


CNS fungal syndromes

1) subacute to chronic meningitis - CSF usually demonstrates elevated opening pressure, lymphocytic pleocytosis, elevated protein and decreased glucose. Eosinophils should suggest C. Immitus and neutrophils should suggest Aspergillus or Mucor (for these 2 hyphae invade the brain).

2) Encephalitis

3) Abscesses

4) Cerebral infarctions


Cryptococcus neoformans (fungal infections)

The most common cause of fungal meningitis

C.neoformans is a ubiquitous organism and enters the body via inhalation. It is a true yeast.

Most common presentation is a subacute meningitis

Can also present with focal deficits and seizures from abscess formation (cryptococcoma), either micro or large

Diagnosis can be rapid with the latex antigen agglutination test

Classically, the dx is made by staining capsule with india ink

Tx with amphotericin B plus flucytosine followed by fluconazole

Send the crypto antigen (quick, sensitive, specific)