Fever with CNS Manifestations

Meningitis:
Bacterial, tubercular, viral, fungal

Encephalitis:
(i) Epidemic
(ii) Sporadic – Herpes, enterovirus, varicella

Others:
Parainfections, autoimmune, ADEM

2
9 month old baby boy

• High fever for last 3 days

• Irritability
• Poor feeding with occasional vomiting
since yesterday
• Has been on oral cephalosporin
• No rash / otorrhea / diarrhea
• Bulging fontanel
• No neck stiffness, meningeal signs absent
• Abdomen soft, hepatomegaly 3cm
Provisional diagnosis

Meningitis

What investigations you will like to do?

LP and CSF examination: Gold standard for diagnosis

• It is should be done in all suspected cases

• CSF to be examined within 30 minutes of LP
• CSF sugar in fluoride vial / bulb
• Collect blood sugar just before LP

CBC, Blood cultures

When should LP be delayed?
• Hypotension, shock
• Severe respiratory distress
• Signs of brainstem herniation such as unequal pupils
• Papilledema
• Decerebrate posturing
What should be done if LP is delayed?
• Send blood cultures and start empirical antibiotics
• CNS imaging if possible (Contrast CT is adequate) or
MRI brain
Tests to be done in CSF
Cytology (5-15/mm3)
Sugar
Protein
Gram stain ( Sensitivity 40-70%, Specificity 97%)
CSF cultures (Sensitivity 70-85% in antibiotic naïve)
PCR and antibody for viral infections
CSF lactate, aminoacids in suspected metabolic diseases
India ink for suspected fungal meningitis
Interpretation of LP when already on antibiotics

• CSF gram stain and culture negative

• Pleocytosis, elevated protein and reduced glucose

persists for several days

• Bacterial antigens have limited role

• PCR may be useful

CSF evaluation
Parameter Pyogenic Aseptic/ Partially Early TBM
(normal) Viral treated pyo
meningitis
Cells (<5/ cumm) 100-10,000 10-1000 5-10,000 10-500, polys
Polymorph Lympho Lymphos> early and
polys then lymphos
Sugar ( > 60% of Low N except Low Low /Normal
BSL) mumps

Protein (20-40 mg%) 100-500 50-200 mg% 100-500 mg% 100-1000

mg%
Gram St & C/S Positive Negative Usually Negative
Negative
ADA, Lactate, LDH High N High High
Other tests
Acute-phase reactants

C-reactive protein (CRP) and serum procalcitonin (PCT):

PCT decreases rapidly (within 24 hours) with appropriate

antibiotic treatment

PCT is not useful in ventriculitis

Petechial fluid

May be utilized for diagnosis meningococcal disease

TB meningitis
CBNAAT or GenXpert MTB/RIF (Sensitivity85.7%)
ADA is not recommended in the diagnosis of TBM
Investigation for TB at other sites
Chest X-ray, Mantoux test ,sputum GA for AFB
USG or CT scan abdomen
CECT or MRI Brain
Imaging
• Contrast MRI has higher sensitivity than CECT for detection of
• Meningeal enhancement
• Infarcts
• Tuberculomas mainly involving the brainstem
• Complications

Slit like Contrast-enhanced

Mild
Plain CT ventricle, low T1w-MRI :
ventriculo
Scan attenuation of leptomeningeal
megaly and
white matter, enhancement
sulcal
obliteration of (arrows) and
effacement
cysterns ventriculomegaly
Investigation results in our patient
Hb11.2 gm/dl, WBC 19600, N75, L21, ESR 55
CRP 46
LP done: Traumatic
Cell count – Plenty of RBC
Protein 124, sugar 34 (blood sugar 96 mg/dl)
Gm stain – Negative, Culture – Pending
Blood culture: Pending
How to Interpret traumatic LP
Normal CSF contains no RBC and their presence indicates
traumatic tap
Progressive clearing of blood between the first and the last
samples is suggestive of traumatic LP
• LP at higher interspaces may produce less hemorrhagic
fluid but may contain RBC
• Leucocytes and protein concentration are altered
• Gram stain, culture and glucose may remain unaltered
Empiric antibiotics

IV Ceftriaxone 100mg/kg
Other supportive measures
72 hrs after treatment started

• Patient’s condition not improved:

Fever persisting
• CSF culture – No growth
• What to do now ?
Emperic Abx following LP (ceftriaxone / cefotaxim)

Poor clinical response - repeat LP Good response

Add vancomycin till sensitivity report

Cont Abx / change according

Review clinical / CSF sensitivity to CSF sensitivity report if
report; change Abx accordingly needed

7 days?

Not improving Improvement

Cont Abx
Re-investigate
Consult neurologist
Repeat LP
• Cell count – 180 (lymho > poly)
• Protein – 220 mg%, Sugar – 24mg%
• Gm stain – Negative

Comment :
Partially treated meningitis and not responding to given
antibiotics
• Suspected Penicillin resistant Pneumococci

• Add Vancomycin (60 mg/kg/day in 4 divided doses)

• Continued for at least 7 days (?)

Contrast imaging done –
Normal study
How long will you treat?

Duration
•Organism not identified – Antibiotics for 10-14 days,
intravenous, no switch to oral
•7 days for meningococcus
•10-14 days for H. influenzae and pneumococcus
Watch for complications
Subdural effusion
Hydrocephalus (HC monitoring)
5 year old boy

Monsoon, rural area

Fever for 2 days
Excessive somnolence
Generalized seizure 1 episode
Altered sensorium since then
What are diagnostic possibilities ?
• Encephalitis
ü Japanese encephalitis
ü Herpes simplex encephalitis
ü Mycoplasma
ü Enterovirus
ü Other viruses –varicella, mumps, measles, rabies,
dengue, chandipura
ü Autoimmune encephalitis -Acute disseminated
encephalomyelitis (ADEM)

• Cerebral malaria
• Encephalopathy (Reye’s syndrome, metabolic
encephalopathy, epileptic encephalopathy)
• Rarely pyogenic meningitis, TBM
Clinical features

• No pallor, icterus, organomegaly

• No skin rash
• No respiratory signs
• Left sided hemiparesis
• No abnormal movements, no meningeal signs
What is the likely diagnosis
Encephalitis
• Infective
• Autoimmune encephalitis
• Vasculitis
• Collagen vascular disease
• Paraneoplastic encephalitis
 Etiology

Infective Non Infective

Epidemic Non epidemic Others

JE virus Enterovirus Bacteria Para neoplastic
Herpes virus Protozoal Autoimmune
Varicella Parasite Intracranial hge
E B virus Toxin Exposure to drugs
Mumps Chemical and toxins
Autoimmune encephalitis
• Antibodies directed against neuronal cell surface protein
and synaptic receptors.

• Not all are uniformly fatal – Some respond to

immunotherapy

• Previously those encephalitis termed “idiopathic” or

“Encephalitis lethargica”
Epidemiological Clues in etiology
Animal contact Person to person transmission
Birds - JE Herpes simplex
Dog - Rabies Varicella
Pigs - JE Enterovirus
Mouse - Rickettsia Influenza
Insect contact Measles, mumps, rubella
Mosquito – JE, P falciparum M pneumoniae
Ticks - Rickettsia
Diagnosis of JE / AES

• Presence of IgM antibody in serum/CSF to JE

• Fourfold rise in IgG antibody in paired sera
• Antigen detection by immunofluroscence
• Nucleic acid detection by PCR
• Virus isolation from brain tissue
• MRI lesions in thalamus, basal ganglia and mid brain
 High signal intensity
lesions in thalamus, basal
ganglia, cerebellum, pons,
mid brain and
occasionally spinal cord.
Involvement of basal
ganglia almost rules out
HSV.

MRI (T2 weighted image) in JE

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HSV Encephalitis: Lab Diagnosis

• DNA PCR from CSF

• Best 3-10 days following symptoms.
• Reduced sensitivity after 2 days of acyclovir
• HSV IgM are notoriously unreliable.
• Four fold rise in IgG between acute and convalescence
sera
• MRI – bilateral temporal lobe involvement is almost
pathognomic
Imaging: Contrast MRI

• Lumber puncture
• MRI especially involves
the temporal lobes,
which may be
associated with
generalized swelling of
the brain parenchyma
• EEG (focal
finding)/PLED
Left temporal hyper intense
lesions diagnosis HSV
encephalitis

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How to distinguish between
encephalitis and cerebral malaria ?
Cerebral malaria

• Epidemiological setting
• Clinical clues – eg. Splenomegaly
• Symmetric CNS findings – UMN lesions
• Ophthalmoscopy – Malarial retinopathy

Patchy retinal whitening

White or orange
discoloration of retinal
vessels
Autoimmune encephalitis

Immune-mediated damage to CNS

Often mimics encephalitis – though actually
they are encephalopathy

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Immune medicated CNS disease
Diverse presentation a follows :
Presentation in infants and toddlers
Ac onset focal neurologic deficits
Presentation with encephalopathy/behavior
disturbance
Seizure as primary manifestation
Movement disorder as primary manifestation.
ADEM

1. Monophasic illness occurring 1-14 days following

vaccine or ≤ 1 week following examthematous fever.
2. Fever usually absent at the onset of neurological
illness.
3. Multifocal neurological signs – Optic nerve, brain and
spinal cord.
4. Disturbed consciousness, stupor and confusion to
coma.
The lesions of ADEM are best
seen in T2 weighted images,
FLAIR sequences. There are
multiple, bilateral, asymmetric
demyelinating lesions of the
subcortical white matter.

Periventricular area is spared.

Sometimes lesions may show
contrast enhancement and
may be in gray matter.

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The MRI shows the following features of
Acute Demyelinating Encephalo Myelitis (ADEM)

T2 cut at the vent. Same in flair image. Supraventricular level,

Level symmetrical
CSF is black,
Patchy hyperintense hyperintensity in
lesion in deep white hyperintense lesion
centrum semi ovale
matter
What are anti NMDAR encephalitis ?
Anti NMDAR encephalitis

• Starts with psychiatric manifestations

• These may be proceeded by a prodrome of headache,
fever and viral like symptoms
• Additional symptoms like  consciousness, seizure,
abnormal movement and autonomic instability.
• MRI and EEG – usually non specific.
• CSF lymphocytic pleocytosis,  protein
• Diagnosis- by NMDAR antibodies in CSF and
serum