The Great Mimicker

A Case of TB Meningitis
Roxanne Jeen L. Fornolles, M.D.
 GENERAL OBJECTIVE
To present a case of TB Meningitis in a 17-year-old
patient presenting with headache, fever and vomiting.
 SPECIFIC OBJECTIVES
• To identify the differential diagnoses of TB Meningitis.
• To discuss the epidemiology, pathogenesis, clinical
manifestations and current key strategies in the
diagnosis and management of TB Meningitis.
 General Data
CD

17 yr old

Female

Roman Catholic

Bantayan Island Cebu Province

Admitted for the 1st time at UCMed Center

 Chief Complaint

Headache
Fever

Vomiting
 Prenatal, Natal, Postnatal History

Unremarkable

Birth rank: 3/3

 Immunization

BCG 1 dose

OPV 3 doses

DPT 3 doses

Hepatitis B 3 doses

AMV 1 dose

MMR 1 dose
 Past Medical History

Unremarkable

No previous hospitalization or surgical procedure

No history of trauma

Non-asthmatic

Non-hypertensive

No known allergies to food or medications

 Family History

No known heredofamilial diseases

Exposure to Father with PTB (treatment
completed) at the age of 8 years old
 Personal and Social History

She lives with her parents and 2 siblings.

She is a grade 11 student with good academic

performance.

She is a basketball player in their school.

HISTORY OF PRESENT ILLNESS

7 months PTA
• One episode of left sided 2 weeks PTA
headache • Recurrence of Left-sided headache
• Throbbing • Vomiting
• Pain score of 5/10 • Diagnosed with Migraine headache
• numbness at the right • Tramadol plus Paracetamol given
side of the face • CT Scan was advised but unable to
•Paracetamol⇨relief. comply.

4 months PTA
• On and Off headache for 3
days
• Throbbing
• Numbness, right side of the
face.
HISTORY OF PRESENT ILLNESS

1-week PTA
• Generalized tonic seizure lasting
for less than 3 minutes.

3 days PTA
• One episode of fever Tmax of 38 C
• Headache with pain score of 8/10
• Brought to Bantayan Island District
Hospital
• Admitted for 2 days and started
Ceftriaxone; advised to transfer for
further management.
 Physical Examination
General:
• Awake, oriented to person, place and time,
irritable, not in respiratory distress

Vital signs:
• Temp 39.4, PR 77bpm, RR 18cpm, BP 100/62,
Weight 60 kg, Height 157 cm, BMI 24.3 kg/m2
Physical Examination
 Physical Examination
Skin
• Warm, no lesions, good turgor

HEENT:
• Normocephalic, Pink palpebral conjunctivae, pink and moist lips,
no lymphadenopathies

Chest and Lungs:

• Equal Chest Expansion, no retractions, Good air entry, Clear
Breath Sounds, No rales, No wheeze
 Physical Examination
CVS:
• Adynamic precordium, Distinct Heart Sounds, No murmur

Abdomen:
• soft, nontender, Normoactive Bowel Sounds, no organomegaly

Extremities
• warm, strong peripheral pulses, CRT less than 2secs

Tanner Stage
• 5
 Neuro Exam
Mental status
• Awake, conscious, irritable,
oriented to person, place and
time, speech is clear and
fluent with normal
comprehension.

• Combative and disoriented. GCS 15: E4 V5 M6⇨ GCS 14 CN I- not tested CN II- intact, full visual fields

CN III, IV, VI- pupils equally

round and reactive to light and CN V- + corneal reflex on both
CN VII- No facial asymmetry CN VIII- Not tested
accommodation, intact EOM, eyes, facial sensation intact
no ptosis

CN IX, X- (+) gag reflex, palate CN XII- Tongue midline at rest

CN XI- able to shrug shoulder
elevates symmetrically and protrusion
 Neuro Exam
Motor:
Cerebellar • Normal bulk, tone and
strength bilaterally with
Sensory:
• No nystagmus
motor strength of 5/5 on • Intact to light touch
• No tremors
all extremities

Reflexes: Fundoscopic exam: Meningeal signs:

• 2+ and symmetric at
Not done • Absent
biceps, triceps,
brachioradialis knees and
ankles
 Salient Features
17-year-old 

Female

Headache

Nausea and Vomiting

Fever

Seizure

Change in sensorium

Known exposure to Father with PTB (treatment completed) at

the age of 8 yrs old.
 Impression

TO CONSIDER
SPACE OCCUPYING LESION
PROBABLY BRAIN TUMOR
 Differential Diagnoses
BRAIN TUMOR
Age ✔
Headache ✔
Nausea and vomiting ✔
Febrile episodes ✔/-
Seizure ✔
Change in sensorium ✔
Exposure to PTB -
 Differential Diagnoses
CNS INFECTION
Viral Meningoencephalitis Bacterial TB
Meningoencephalitis Meningitis
Age ✔ ✔ ✔
Headache ✔ ✔ ✔
Nausea and ✔ ✔ ✔
Vomiting
Febrile episodes ✔ ✔ ✔
Seizure ✔ ✔ ✔
Change in ✔ ✔ ✔
sensorium
Exposure to TB - - ✔
 Laboratory
Tests done at the ER
CBC TESTS Normal Patient
Normal Patient
Hemoglobin 11-16 12.2 Sodium 137-145 139
Hematocrit 31-46% 35.8%
MCV 80-100 92.3 Potassium 3.5-5.1 4.2
Platelet Count 140-440 387
WBC 5-10 8.56 Creatinine 0.7-1.2 0.6
Differential
count SGPT <35 20.09
Neutrophils 45-65 76
Lymphocytes 20-40 18
Monocytes 2-9 5
Eosinophils 0-6 1
Basophils 0-2 0
 Laboratory
Tests done at the ER

Chest X-ray PAL: Bilateral Interstitial

Pneumonia
 At the ER

Venoclysis started with PLR at maintenance rate

• Ketorolac 30 mg IVTT PRN Q8h FOR headache

• Paracetamol 500mg 1 tab Q4h PRN for fever
• Started on Ceftriaxone 2grms IV drip q12h
Management • Referred to Pedia pulmonologist on call for COVID
clearance
• Vital signs and neuro vital signs monitored q2h
• NPO temporarily except medications
S
Headache with Pain score of
O
VS: T 38.4, PR 64, RR 20s
A
T/C
P
Day 1-2
Transferred to a
9/10. BP 100/60 Meningoencephalitis Regular room
Awake, irritable, oriented to PE findings: Meningeal signs: + nuchal (Bacterial vs TB)
person only rigidity PCAP Ibuprofen 400 mg tab
Neuro exam: q8h every after meals
S- GCS 14
P- 3mm on both eyes, brisk
E- Full visual fields
R- spontaneous respirations
M- 5/5 on all extremities

Hospital Labs:
CBC:
Hgb: 12.8
Hct : 37.6

DAY 1-2 WBC 9.83

Plt 406
Diff count:
Neu 83 H, Lymph 11
Mono 6, Eos 0, Baso 0
Dengue test: ALL NEG
SARS-CoV 2 RT PCR: Neg
UA: Neg
 Cranial MRI (Plain and Contrast)
• Diffuse leptomeningeal enhancement.
• Restricted diffusion is seen in the medial aspect of both temporal lobes, more on the left side with
no corresponding increased signal on the T2 and FLAIR pulse sequences.
• Small foci of T2/FLAIR hyperintensities are noted in the subcortical region of both cerebral
hemispheres.
• Ventricles are normal in size.

Impression:
Diffuse leptomeningeal enhancement compatible with leptomeningitis. Restricted
diffusion in the medial aspect of both temporal lobes, more on the left side which
may be seen in hyperacute infarcts, post-ictal changes in Herpes Simplex
encephalitis
 Lumbar Tap
Normal Patient
CSF Cell count and differential count
Color
Day
Colorless
1-2
Volume 2.5 ml
Transparency Clear
Viscosity Non-viscous
Coagulum W/O Coagulum
WBC 781/cumm H
Segmenters 76%
Lymphocytes 24%
RBC 40/cumm

CSF Protein 12-60 mg/dL 215 H

CSF Glucose 40-80 mg/dL 14 ( 14.5%) L
CSF KOH None seen
CSF CALLAS Negative
CSF Final Report No growth 4 days
CSF Findings
Condition Pressure Leukocytes Protein Glucose
(cmH20) (mg/Dl)

Normal <28 <5, >= 75 % lymph 20-45 >50 (or 75% serum glucose
In neonates: <20

Acute Bacterial meningitis Usually elevated 100-10,000 or more; Usually 100-500 Decreased, usually <40 (or
usually 300-2,000; PMNs <50% of serum glucose)
predominate

Viral meningoencephalitis Normal or slightly Rarely >1,000 cells. PMNs Usually 50-200 Generally normal, may be
elevated early but mononuclear decreased to <40 in some
cells predominate through viral diseases, particularly
most of the course mumps (15-20% of cases)

TB Meningitis Usually elevated 10-500; PMNs early, but 100-3,000; may be higher <50 in most cases;
lymphocytes predominate in the presence of block decreases with time if
through most of the course treatment is not provided

Fungal meningitis Usually elevated 5-500; PMNs early, but 25-500 <50; decreases with time if
lymphocytes predominate treatment is not provided.
through most of the
course. Cryptococcal
meningitis may lack
pleocytosis. Coccidiodal
meningitis may have
eosinophilia
 Meningitis-Encephalitis Panel
Bacteria Viruses
E. Coli K1 Not detected Cytomegalovirus Not detected
H. Influenzae Not detected Enterovirus Not detected
L. monocytogenes Not detected HSV1 Not detected
N. Meningitidis Not detected HSV2 Not detected
S. agalactiae Not detected HHV6 Not detected

Day 1-2
S. pneumonia Not detected Human parechovirus
Varicella Zoster Virus
Not detected
Not detected

Yeast
Cryptococcus neoformans/gratii Not detected

XPERT MTB/RIF
MTB HAS NOT BEEN DETECTED
AFB STAINING: 0
 Hospital
Day 1-2

EEG
Abnormal showing generalized slowing of the background activity suggestive of a nonspecific
encephalopathic process
S
Awake, irritable,
O
VS: T 38.5, PR 70, RR 26 , BP 120/80
A
TB Meningitis
Day 3-4
P
Referred to PIDS
combative, oriented to CN II-Left medial Rectus Palsy PCAP-C Continued on
person only CN II, IV, VI- Right eye: pupil 4mm and reactive to Ceftriaxone
Headache with PS of light, brisk, full EOM Started on:
9/10. Febrile episodes. Left eye: pupil 5mm, sluggish reaction, (+) ptosis Pyrazinamide
Had onset of focal right CN V- Right eye: (+) corneal reflex. Left eye: (-) 400mg+ Rifampicin
sided tonic seizure corneal reflex 150 mg+ INH 75
lasting for 4 seconds. CN VII- No facial asymmetry mg+ Ethambutol
Motor strength: Right sided Hemiparesis 275 mg tab 4 tabs /

Hospital day 2hrs PC BF

Valproic acid
12mkD
Prednisone 1mkD
day 3-4 Labs
Blood Culture: No growth after 4 days of
incubation
Procalcitonin: 0.07
PPD: no induration
CXR of siblings: Negative
CXR of father: Negative
CXR of mother: Not done
S O A P

Febrile episodes still noted.
Generalized tonic Seizure
persisted lasting for 3-4
seconds.
Stuporous; partial eye
opening to pain
Hospital
VS: T 38, PR 78, RR 21, BP 110/80 TB Meningitis
Day 5
Mannitol 0.3 g/k q6H
S-GCS 10 (E2V2M6) PCAP-C Valproic acid
P- Right eye: pupil 2mm and reactive to increased to 17mkD
light, brisk, full EOM. Left eye: pupil 3mm, Started on:
sluggish reaction, (+) ptosis Citicoline 500mg Q8H
E- Full EOM on Right eye, Left medial Esomeprazole 40mg
rectus palsy IVTT OD
R- spontaneous O2 @ 2lpm
M: Right sided Hemiparesis NGT inserted and
Labs:
started on feeding
q3H
FBC inserted

day 5 CBC
Hgb 11.5
Hct 33.7
HGT monitoring
UO and neuro VS
monitored q hourly
WBC 9.46
Plt317
Neu 76, Lymph15, Mono 9, Eos 0 Baso 0
Na: 138 K: 3.4
 Cranial CT Scan:
• Fairly defined foci of hypodensities noted in the medial aspect of both temporal lobes
corresponding to the areas of restricted diffusion seen in the previous MRI study.
• A focus of hypodensity is now appreciated in the genu of the internal capsule.
• The ventricles are normal in size and configuration.

Impression:
• Evolving infarcts to subacute phase, medial aspect of both temporal lobes. New acute
infarct, genu of the left internal capsule.
S O
Febrile episodes still noted.
Generalized tonic Seizure
persisted lasting for 3-4
seconds.
Stuporous; partial eye
opening to pain
Hospital
A P
Day 5
VS: T 38, PR 78, RR 21, BP 110/80 TB Meningitis Mannitol 0.3 g/k q6H
S-GCS 10 (E2V2M6) PCAP-C Valproic acid
P- Right eye: pupil 2mm and reactive to increased to 17mkD
light, brisk, full EOM. Left eye: pupil 3mm, Started on:
sluggish reaction, (+) ptosis Citicoline 500mg Q8H
E- Full EOM on Right eye, Left medial Esomeprazole 40mg
rectus palsy IVTT OD
R- spontaneous O2 @ 2lpm
M: Right sided Hemiparesis NGT inserted and
started on feeding
q3H

day 5 Labs:
CBC
Hgb 11.5
FBC inserted
HGT monitoring
UO and neuro VS
Hct 33.7 monitored q hourly
WBC 9.46
Plt317
Neu 76, Lymph15, Mono 9, Eos 0 Baso 0
Na: 138 K: 3.4
S O A P

Febrile episodes still noted. VS: T 38.1, PR 51, RR 21, BP 120/90 TB Meningitis
Day 6-11
Ceftriaxone day 6
No recurrence of seizures. P/E: HEENT: + Blister on left upper lip PCAP-C completed and shifted to
Lethargic----- awake S-GCS 13 (E4V4M5) Meropenem
P- Right eye: pupil 2mm and reactive Mannitol decreased to
to light, brisk, full EOM. Left eye: pupil 60ml q8h
3mm, sluggish reaction, (+) ptosis Rowagel oral gel applied on
E- Full EOM on Right eye, Left medial lesion QID
rectus palsy O2 inhalation shifted to
R- spontaneous PRN
M: Right sided Hemiparesis Ibuprofen--- Hold
S O A P

Febrile episodes still noted. VS: T 38.1, PR 100/70, RR 20, BP 110/70

Day 12-16
TB Meningitis Mannitol
No recurrence of seizures. P/E: Skin: 1-2 cm grade 1 sacral ulcer on left PCAP-C decreased to
Onset of productive cough. buttock q12h----
Bed sore noted on left S-GCS 13 (E4V4M5) discontinued
buttock. Urine sediments P- Right eye: pupil 2mm and reactive to Dexamethasone
noted on urinary catheter. light, brisk, full EOM. Left eye: pupil 3mm, IV shifted to
sluggish reaction, (+) ptosis Prednisone
E- Full EOM on Right eye, Left medial rectus 10mg/5ml 10ml
palsy TID
R- spontaneous Mebo cream
Motor strength: Right Hemiparesis applied to bed
sore and post
Labs: puncture sites
CBC: q6h
Hgb 13 Referred to
Hct 38 Rehab Medicine
WBC 13.45 for PT
Plt 372 Encouraged to sit-
Neu 79, Lymph 15, Mono 6, Eos 0, Baso 0 up in bed
Serum Na: 139 Serum K: 4.1 CRP: 2.37
 Chest X-Ray:
Bilateral lower lobe pneumonia with interval changes.
 Urinalysis
Color Orange
Slightly cloudy
Ph 8.0
S.G 1.010
Urine Culture and Protein Negative
Sensitivity Glucose Negative
No growth after 48 Ketones Negative
hours Blood +1
Urobilinogen Normal
Nitrite Negative
Leukocyte Esterase +1
Bilirubin Negative
RBC 16-20
WBC 0-2
Epithelial cells Rare
Mucus threads Rare
Bacteria Rare
S O A P

Febrile episodes still noted. VS: T 38.1, PR 100/70, RR 20, BP 110/70

Day 12-16
TB Meningitis Mannitol
No recurrence of seizures. P/E: Skin: 1-2 cm grade 1 sacral ulcer on PCAP-C decreased to
Onset of productive cough. left buttock q12h----
Bed sore noted on left S-GCS 13 (E4V4M5) discontinued
buttock. Urine sediments P- Right eye: pupil 2mm and reactive to Dexamethasone
noted on urinary catheter. light, brisk, full EOM. Left eye: pupil 3mm, IV shifted to
sluggish reaction, (+) ptosis Prednisone

Hospital E- Full EOM on Right eye, Left medial

rectus palsy
R- spontaneous
10mg/5ml 10ml
TID
Mebo cream
Motor strength: Right Hemiparesis applied to bed
Day 12- Labs:
CBC:
sore and post
puncture sites
q6h

16 Hgb 13
Hct 38
WBC 13.45
Referred to
Rehab Medicine
for PT
Plt 372 Encouraged to
Neu 79, Lymph 15, Mono 6, Eos 0, Baso 0 sit-up in bed
Serum Na: 139 Serum K: 4.1 CRP: 2.37
S O
Febrile episodes still noted
With longer intervals
occurring 1-3 x per day.
Productive cough noted.
Hypertensive episodes
Fully awake, follows
commands.
Hospital
Day 17-
21
VS: T 38.2, PR 83bpm, RR
20, BP 140/90-160/90
S-GCS 13 (E4V4M5)
P- Right eye: pupil 2mm
and reactive to light, brisk,
full EOM. Left eye: pupil
3mm, sluggish reaction, (+)
ptosis
E- Full EOM on Right eye,
Left medial rectus palsy
R- spontaneous
Motor strength: Right
Hemiparesis
A P
TB Meningitis
Day 17-21
Meropenem to be
PCAP-C completed for 10 days---
UTI Shifted to Ciprofloxacin
500mg/ tab 1 tab Q12H per
NGT
Started on Captopril
25mg/tab 1 tab Q8H
Prednisone 0.7mg/kg/D
Esomeprazole discontinued
IVF shifted to ISA
S O A P

Febrile episodes occurring VS: T 38.0, PR 80, RR 20, BP 130/80 TB Meningitis

Day 22-25
Ciprofloxacin Day 6
once daily P/E: PCAP-C completed
Occasional productive Skin: good turgor, + healing grade 1 AGE with some Captopril
cough. sacral ulcer Dehydration Valproic acid
LBM x 5 episodes HEENT: moist lips and oral mucosa Prednisone
Fully awake, follows C/L: Clear breath sounds Myrin P Forte 4 tabs OD

Hospital
commands S-GCS 13 (E4V4M5)
P- Right eye: pupil 2mm and reactive to
light, brisk, full EOM. Left eye: pupil
Citicoline 500mg BID
Paracetamol
ORS
3mm, sluggish reaction, (+) ptosis Zinc Sulfate
Day 22- E- Full EOM on Right eye, Left medial
rectus palsy
R- spontaneous

25 Motor strength: Right Hemiparesis

S O A P

Awake, alert and can VS: T 38.0, PR 80, RR 20, BP 130/80

Day of Discharge
TB Meningitis Ciprofloxacin
answer to questions. P/E: PCAP-C Captopril
Skin: good turgor, + healing grade 1 AGE with some Valproic acid
sacral ulcer Dehydration Prednisone
HEENT: moist lips and oral mucosa Myrin P Forte 4 tabs OD
C/L: Clear breath sounds Citicoline 500mg BID
S-GCS 13 (E4V4M5) Paracetamol
P- Right eye: pupil 2mm and reactive to ORS
light, brisk, full EOM. Left eye: pupil Zinc Sulfate
3mm, sluggish reaction, (+) ptosis
E- Full EOM on Right eye, Left medial
rectus palsy
R- spontaneous
Motor strength: Right Hemiparesis
 Final Diagnosis
• TB Meningitis
• Pediatric Community Acquired Pneumonia Moderate
Risk
• Acute Gastroenteritis with Some Dehydration
 Hospital Day 25
Discharged with the following take home medications:
• Ciprofolxacin 500mg/tab 1 tab 2x a day for 4 days more
• Valproic acid 250mg/5ml 10ml q12h per NGT
• Prednisone 10mg/5ml 10ml 2X a day PC BF, PC Dinner
• Myrin P Forte 4 tabs OD PC BF
• Citicoline 500mg BID
• Captopril 25 mg TID
• Paracetamol 500mg/tab 1 tab Q4h for fever
• Chlorhexidine mouth solution swab to oral mucosa TID PC meals
• Feeding with Ensure 6 scoops in 195ml water Q3h
Discussion
 Epidemiology

TB Meningitis
PPS Registry
January 2019-September 2020

2%
Total: 393 cases
18%

81%

Luzon Visayas Mindanao

Release of endorphins
and Reactive O2 Free
radicals
Impaired
neurosignaling and Cell damage
metabolic Cytotoxic Morbidity
pertubations edema
Alteration of
neuronal
microenvironment
Raised ICP

Infarcts
Infiltration cerebral Vascular stenosis,
vessel wall occlusion, spasm Decreased
Cerebral Blood
Flow
Exudate Hydrocephalus Mortality

Leaky BBB Vasogenic edema

Tuberculoma or
Containment of
Tuberculous
Bacilli
abscesses Disease
resolution
Extension of disease Spinal
into spinal canal arachnoiditis,
tuberculomas,
exudate
 Clinical Manifestations
Onset is gradual occurring over a period of
approximately 3 weeks.
SECOND STAGE: signs of
increased ICP and cerebral
FIRST STAGE: personality damage: drowsiness, stiff THIRD STAGE: coma,
changes, listlessness, neck, CN palsies, irregular pulse and
irritability, anorexia and inequality of the pupils, respirations and rising
some fever. vomiting, tache cerebrale, fever.
absence of abdominal
reflexes, and convulsions
 Diagnostic Work-up

Chest radiographs may reveal findings typical of primary TB or less often

with a miliary pattern.

In many cases, by the time meningitis develops, the original focus in the
lungs may no longer be demonstrable by plain radiographic studies.

TST may be of limited value with variable sensitivities

 Diagnostic Work-up

Diagnosis of TBM is difficult and may be based only on clinical

and preliminary CSF findings.

CSF may be clear, usually opalescent and can contain 50-500

WBCs/mm3, with polymorphonuclear leukocytes predominant
very early in the disease and lymphocytes predominating later.
 Diagnostic Work-up
CSF glucose level may be at the lower limits of normal early in the second
stage and very low by the 3rd stage.

Protein content may be normal initially but rises to a very high

concentration, at which pellicles form on standing.

CSF sample should be sent for acid fast smear but a single sample has low
sensitivity, 20-40%.

CSF Culture also has low sensitivity and can take several weeks for the
result.
 Diagnostic Work-up

Neuroimaging can also contribute in the diagnosis of TB Meningitis.

CT Scan or MRI : Hydrocephalus in 80%, basal meningeal enhancement in

75% of young children. Hydrodensities due to cerebral infarcts, cerebral
edema and nodular enhancing lesions may also be seen.

PCR, ELISA latex agglutination

MANAGEMENT
 Anti-TB medications

Rifampicin Isoniazid

Pyrazinamide Ethmabutol
Source: TB (DS and DR) and Latent TB Screening, Diagnoses and Management page 16
Source: TB (DS and DR) and Latent TB Screening, Diagnoses and Management page 17
Source: TB (DS and DR) and Latent TB Screening, Diagnoses and Management page 18
Source: TB (DS and DR) and Latent TB Screening, Diagnoses
and Management page 19
Source: TB (DS and DR) and Latent TB Screening, Diagnoses and
Management page 20
 4 Random Clinical trials
13 prospective cohort studies
1 unpublished ongoing cohort study
 Management

Adjunctive treatment with

corticosteroids improves
survival but does not prevent
severe disability.
 Prognosis

THE MOST IMPORTANT

DETERMINANT OF OUTCOME:
STAGE of ILLNESS at which the
diagnosis is made.
 Prognosis in TB Meningitis
• 100% mortality in 3-4 weeks without treatment.
• 100% survival with treatment started in Stage 1.
• 75% survival with treatment started in Stage 2.
• Stage 3- variable survival; all have neurologic
sequelae.
 Summary
• TB Meningitis remains the leading cause of death
globally.
• Much of the morbidity and mortality caused by
tuberculous meningitis is mediated by a dysregulated
immune response.
• Empirical anti-TB therapy should be started promptly.
Thank You