Fever with CNS Manifestations · LP and CSF examination: Gold standard for diagnosis • It is...
Transcript of Fever with CNS Manifestations · LP and CSF examination: Gold standard for diagnosis • It is...
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Fever with CNS Manifestations
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Meningitis: Bacterial, tubercular, viral, fungal
Encephalitis: (i) Epidemic(ii) Sporadic – Herpes, enterovirus, varicella
Others: Parainfections, autoimmune, ADEM
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9 month old baby boy
• High fever for last 3 days• Irritability • Poor feeding with occasional vomiting
since yesterday• Has been on oral cephalosporin
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• No rash / otorrhea / diarrhea
• Bulging fontanel
• No neck stiffness, meningeal signs absent
• Abdomen soft, hepatomegaly 3cm
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Provisional diagnosis
Meningitis
What investigations you will like to do?
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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
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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
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Tests to be done in CSF
Cytology (5-15/mm3)SugarProteinGram stain ( Sensitivity 40-70%, Specificity 97%)CSF cultures (Sensitivity 70-85% in antibiotic naïve)PCR and antibody for viral infectionsCSF lactate, aminoacids in suspected metabolic diseasesIndia ink for suspected fungal meningitis
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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
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Parameter (normal)
Pyogenic Aseptic/ Viral
Partially treated pyo meningitis
Early TBM
Cells (<5/ cumm) 100-10,000 Polymorph
10-1000Lympho
5-10,000Lymphos> polys
10-500, polys early and then lymphos
Sugar ( > 60% of BSL)
Low N except mumps
Low Low /Normal
Protein (20-40 mg%) 100-500 mg%
50-200 mg% 100-500 mg% 100-1000
Gram St & C/S Positive Negative Usually Negative
Negative
ADA, Lactate, LDH High N High High
CSF evaluation
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Other testsAcute-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
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TB meningitisCBNAAT 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
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Imaging• Contrast MRI has higher sensitivity than CECT for detection of • Meningeal enhancement• Infarcts • Tuberculomas mainly involving the brainstem• Complications
Mild ventriculo megaly and sulcal effacement
Contrast-enhanced T1w-MRI : leptomeningeal enhancement (arrows) and ventriculomegaly
Slit like ventricle, low attenuation of white matter, obliteration of cysterns
Plain CT Scan
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Investigation results in our patientHb11.2 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
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How to Interpret traumatic LPNormal 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
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Empiric antibiotics
IV Ceftriaxone 100mg/kg
Other supportive measures
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72 hrs after treatment started
• Patient’s condition not improved: Fever persisting
• CSF culture – No growth• What to do now ?
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Emperic Abx following LP (ceftriaxone / cefotaxim)
Poor clinical response - repeat LPAdd vancomycin till sensitivity report
Good response
Review clinical / CSF sensitivityreport; change Abx accordingly
Cont Abx / change accordingto CSF sensitivity report ifneeded
7 days?
Not improving ImprovementCont Abx
Re-investigateConsult neurologist
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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
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• Suspected Penicillin resistant Pneumococci
• Add Vancomycin (60 mg/kg/day in 4 divided doses)
• Continued for at least 7 days (?)
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Contrast imaging done – Normal study
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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)
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5 year old boy
Monsoon, rural areaFever for 2 daysExcessive somnolenceGeneralized seizure 1 episodeAltered sensorium since then
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What are diagnostic possibilities ?• Encephalitis ü Japanese encephalitis ü Herpes simplex encephalitisü Mycoplasmaü Enterovirusü Other viruses –varicella, mumps, measles, rabies,
dengue, chandipuraü Autoimmune encephalitis -Acute disseminated
encephalomyelitis (ADEM)
• Cerebral malaria• Encephalopathy (Reye’s syndrome, metabolic
encephalopathy, epileptic encephalopathy)• Rarely pyogenic meningitis, TBM
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Clinical features
• No pallor, icterus, organomegaly• No skin rash• No respiratory signs• Left sided hemiparesis• No abnormal movements, no meningeal signs
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What is the likely diagnosis
Encephalitis • Infective• Autoimmune encephalitis• Vasculitis• Collagen vascular disease• Paraneoplastic encephalitis
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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
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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”
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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
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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
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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
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• Lumber puncture• MRI especially involves
the temporal lobes, which may be associated with generalized swelling of the brain parenchyma
• EEG (focal finding)/PLED
Imaging: Contrast MRI
Left temporal hyper intense lesions diagnosis HSV
encephalitis
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How to distinguish between encephalitis and cerebral malaria ?
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Cerebral malaria
• Epidemiological setting• Clinical clues – eg. Splenomegaly• Symmetric CNS findings – UMN lesions• Ophthalmoscopy – Malarial retinopathy
Patchy retinal whiteningWhite or orange
discoloration of retinal vessels
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Autoimmune encephalitis
Immune-mediated damage to CNSOften mimics encephalitis – though actually they are encephalopathy
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Immune medicated CNS diseaseDiverse 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.
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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.
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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. LevelPatchy hyperintense lesion in deep white matter
Same in flair image. CSF is black, hyperintense lesion
Supraventricular level, symmetrical hyperintensity in centrum semi ovale
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What are anti NMDAR encephalitis ?
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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