Cases of TBM / Tuberculomain Pregnancy

Presentor : Dr. Hemamalini

Designation : Consultant Physician

Hospital : Fernandez Hospital, Hyderabad

Date of Presentation : 16.09.2014

Case 1- Tuberculoma

Mrs. S.P.,32 yr old, primi

Admitted on 28.05.14 early hours at 38wks GA

Seizures; GTCS at home&twice after admission

BP- 150/90mmHg, pedal oedema 2+, urine albumin

trace

Preeclampsia profile normal ( CBC with platelets,

CUE, s.bilirubin, SGPT, SGOT, s. Cr, LDH, urine C/S)

Peripartum Management

MgSO4 loading 4gm followed by maintenance 1g/hr

Tab Depin SR 10mg tid

Labour induced for antepartum eclampsia

Vaginal delivery of 2.75 kg boy same day

Postpartum enoxaparin 40mg scly for 5days,

nifedepin SR 10mg bd for 2weeks

Postpartum Period

Headache and left upper limb numbness from 7th pnd

Advised MRI/MRV brain by physician on opd basis

Admitted at another hospital following brain imaging

in view of the findings

3weeks and 6weeks after ATT was started, she came

for follow up with our physician

Brain Imaging was Suggestive of Tuberculoma in Rt.Parietal area

Summary

Primi, normotensive through out pregnancy

presenting at term with GTCS; rightly managed as

eclampsia;

later investigated in view of focal neurological

deficit, found to have intracranial lesion.

Presently on ATT and antiepileptics, doing well

Why we are Presenting this case?

Suspect other differential diagnosis in all cases of

eclampsia if

– focal neurological deficits

– persistent headache/ other neurological

symptoms

– Recurrent seizures despite MgSO4

– Prolonged unconsciousness following seizure

Why we are Presenting this case?

– No features of eclampsia like raised BP/ urine protein

– Late onset seizure ( beyond 1week postpartum)

– Fever with seizures ( not explained by other site

infection)

– Partial seizures with or without secondary

generalisation

– Past history suggestive of recurrent headaches +/-

other neurological symptoms

CASE 2 - TBM

History

Mrs. G., 27yr old, G3A2, 22wks gestation

Previous 2 first trimester losses

Evaluated by rheumatologist 2012- ACL IgG low +ve,

IgM –ve, LAC 1.3, ? APLA- repeated after 3months-

same result

HCQs 200mg, prednisolone 5mg started interval

period

Present Pregnancy

Spontaneous conception

Enoxaparin 40mg scly od since conception inview of APLA;

continued HCQs and prednisolone

Dry cough since two months ( from 4/10 gestation) with low

grade fever in evenings (temperature not documented)

Prednisolone stopped after 2weeks after cough started;

received 2 courses of antibiotcs

Seen by two pulmonologists outside in the previous 1 month

before admission with us. CXR not done

Prescribed inhalers/nebulisations- partial relief

Continued..

Thrombocytopenia 50,000 on routine CBC at

5months gestation

Stopped LMWH

Seen by rheumatologist for low platelets, at this

point as she changed the obstetrician

Platelets dropped to 38,000 but no bleeding

manifestations

Restarted prednisolone at 20mg/day

Continued..

Referred to us 3days later with c/o altered behaviour

since 2days- ? Steroid induced psychosis,? Depressive

illness/other psychiatric problem

History reviewed-Headache since 1week; no vomiting

Cough decreased since one week with cough

suppressants, but drowsy

Lethargic, not speaking, not eating since two days.

Ambulating to toilet

Wt. loss 7kg in pregnancy

At FH

Admitted on 4.08.14 in ICU

Normal built and nourished

Drowsy, lethargic, not willing to ambulate; not talking except

occasional muttering

Other general examination unremarkable

PR: 100/min, BP-90/60mmHg, RR: 20/min, temp 99F

No focal neurological deficit, pupils NSRL, mild neck stiffness,

uncooperative for complete neurological examination, fundus

normal

Lungs clear; other systemic examination normal

Investigations

CBC- 10.5G Hb, 5,000/cmm WBC, 46,000 Plt

CUE- protein 2+, pus cells nil; C/S sterile

TSH- 0.09

Na-127, K-4.3, Cl-92

HIV, HBs Ag –ve

LFT, RFT normal. aPTT- 47.9/28.2

PT- 15.9/13.9

CXR- Miliary TB

MRI Brain- Meningeal EnhancementCSF analysis-

Sugar: 18mg/dl

Protein: 199mg/dl

Total cell count- WBC- 36. RBC 18

Polymorphs 65. lymphocytes 35

ADA- 13 (>10, suspect 10-11)

Grams stain- few pus cells, occasional lymphocytes, no microorg

AFB stain: -ve

Fungal stain- no fungal elements

MTB DNA PCR-ve

Cryptococcal antigen –ve

AFB culture positive ( reported after 6weeks)

At FH

Diagnosis of miliary TB with meningoencephalitis was made

Neurophysician input

ATT started + inj Decadron 8mg IV tid given within 24hrs of

admission, IV ceftriaxone 2G bd, enteral nutrition, inj

optineuron infusion daily

Next 24hrs- pt. deteriorated with worsening level of

consciousness ( E2M2V2), pupils NS, sluggishly reacting,

fundus normal;

Platelets 23,000/cmm, WBC 36,000/cmm

At FH

Fetal scan- intraplacental clot, AEDF

Planned for termination of pregnancy after

repeating brain imaging ( CECT), in view of

worsening maternal condition and poor fetal

prognosis

After multidisciplinary counseling , family wanted

patient to be transferred to a neuro centre, hence

discharged

At the other Hospital

MRI repeated- features s/o TBM with communicating

hydrocephalous and secondary ischemic changes; MRA

normal

EVD ( External Ventricular Drain)was placed on the 2nd

day after transfer in view of acute hydrocephalous

Ventilatory support

ATT, steroids, levetiracetam,supportive care continued

Found to have IUFD;SERPC done. Received RDPs

Outside Hospital

Cardiac arrest- revived- brain dead ( EEG)

CT brain

– mild hydrocephalous

– Intraventricular shunt in situ

– Features s/o cerebal edema also seen ( paucity of CSF

sulcal spaces

– No e/o intracranial herniation

Left against medical advise in view of poor prognosis (

later communication- pt. died on the way home)

Summary

Young lady with 2 previous miscarriages, with

probable APLA syndrome ( though 2 first trimester

miscarriages -not an indication for testing for APLA)

On low dose steroids (? not indicated) for a long

duration

Prolonged cough labeled as allergic bronchitis

without CXR

Low grade fever ignored as not documented

Summary

Steroids hiked in view of thrombocytopenia without

taking into consideration her previous history of fever,

cough and wt.loss

Diagnosed as miliary TB with meningoencephalitis at

22wks gestation after altered level of consciousness

Low sodium secondary to SIADH- indicate severe

disease

Rapid neurological deterioration and later cardiac

arrest and brain death

Lessons to be Learnt APLA investigations and diagnosis according to

guidelines only

Asymptomatic APLA in interval period- no need of

treatment

In pregnancy if APLA confirmed: LDA +/- LMWH only (

no indication for steroids unless secondary APLA)

Evaluate cough beyond 3 weeks with CXR- don’t

hesitate as radiation exposure is very minimal- use

abdominal lead shield

Lessons to be learnt

High degree of suspicion for Koch’s in pregnancy if they

are on steroids

Evaluate for other symptoms before increasing steroid

dose in pregnancy

Evaluate for organic causes of brain disorder before

assuming psychiatric problems

Manage in a centre with

neuroimaging/neurophysician/neurosurgeon support if

TBM is diagnosed

Lessons to be learnt

Thrombocytopenia and neurological symptoms-

always brain imaging is indicated

Do not ignore weight loss in pregnancy – has to be

evaluated; need to consider bone TB too as many of

them may be having low backache or other bone

pains

Evaluation for hyperthyroid, secondary APLA in this

case?

Discussion- Miliary TB

Widespread dissemination of Mycobacterium

tuberculosis via hematogenous spread

Classic miliary TB is defined as milletlike (mean, 2 mm;

range, 1-5 mm) seeding of TB bacilli in the lung, as

evidenced on chest radiography. This pattern is seen in

1-3% of all TB cases

Miliary TB may occur in an individual organ (very rare, <

5%), in several organs, or throughout the entire body

(>90%), including the brain

Characterized by a large amount of TB bacilli

May easily be missed; fatal if left untreated

25% of miliary TB - Meningeal involvement

Miliary TB may mimic many diseases

50% of cases are undiagnosed antemortem;

Therefore, a high index of clinical suspicion is

important to obtain an early diagnosis

Risk Factors for Miliary Tuberculosis

Cancer

Transplantation

HIV infection

Malnutrition

Diabetes

Immunosuppression including, but are not limited to, the following:

Silicosis

End-stage renal disease

Major surgical

procedures -

Occasionally may

trigger dissemination

Progressive Symptoms over days to weeks or occasionally over several months

Weakness, fatigue (90%)

Weight loss (80%)

Headache (10%)

Signs of miliary TB include

the following:

Subtle signs, such as low-

grade fever (20%)

Fever (80%)

Cough (60%)

Generalized

lymphadenopathy (40%)

Hepatomegaly (40%)

Splenomegaly (15%)

Pancreatitis (< 5%)

Multiorgan dysfunction,

adrenal insufficiency

Investigations

High-resolution computed tomography (HRCT) is relatively more

sensitive and shows randomly distributed miliary nodules

In extrapulmonary locations, ultrasonography, CT, and magnetic

resonance imaging are useful

Positron-emission tomographic CT has been investigated as a

promising tool for evaluation of suspected TB.

Fundus examination for choroid tubercles, histopathological

examination of tissue biopsy specimens, and rapid culture

methods for isolation of M. tuberculosis in sputum, body fluids,

and other body tissues aid in confirming the diagnosis

Choroidal Tubercles

Coronal plain computed tomography (A) positron-emission tomography (B) images

showing diffuse increased 18F fluorodeoxyglucose uptake in spleen,multifocal

uptake in liver, mediastinal node (black arrow).

Labs Low sodium levels may correlate with disease severity, and the

syndrome of inappropriate secretion of antidiuretic hormone

(SIADH) or hypoadrenalism

30% of cases, alkaline phosphatase levels are elevated

Elevated levels of transaminases suggest liver involvement or, if

treatment has been initiated, drug toxicity

Leukopenia/leukocytosis may be present; Leukemoid reactions

may occur; patients may have anemia; and thrombocytopenia or,

rarely, thrombocytosis may be present.

ESR elevated in approximately 50%

Cultures for Mycobacteria

Include those of the sputum, blood, urine, or cerebral spinal

fluid.

Sensitivity testing is essential for all positive isolates, and

consider investigation for multidrug-resistant TB (MDR-TB)

in all cases.

Negative sputum smear results (even 3 negatives) do not

exclude the possibility of TB.

Blood cultures are positive in approximately 5% of patients

who do not have HIV infection. 85% positivity rate, if HIV +ve

Lumbar Puncture

Strongly considered, even with normal brain MRI

Leukocytes: Approximately 65% of patients have WBC

counts with 100-500 mononuclear cells/μL.

Lymphocytic predominance (70%)

CSF lactic acid levels are mildly elevated

Elevated protein levels (90%)

Low glucose levels (90%)

RBCs are common

Acid-fast bacilli (≥40% with serial spinal taps)

Nucleic Acid Probes / Other Tests Specificity for smear-negative and culture-negative specimens is

lower than 100% (false-negative results).

False-positive TB cultures are of concern (5%). This may be due to

laboratory contamination

Sputum induction has low sensitivity, and findings are smear-

negative and culture-negative in 80% of patients because of

hematogenous spread

Fiberoptic bronchoscopy is the most effective procedure for obtaining

cultures (bronchoalveolar lavage)

The culture yield for transbronchial biopsies is 90%

Bone marrow biopsy yield is approximately 50%, without serious

adverse effect

Treatment

Miliary TB with meningeal involvement may require

prolonged treatment (up to 12 mo).

Early treatment of patients with suspected miliary

tuberculosis decreases the likelihood of mortality

and improves outcome.

Surgical treatment is rarely necessary. Occasionally,

a ventriculoatrial shunt is indicated for

hydrocephalus

Empirical Treatment

Early empirical therapy for suspected miliary

tuberculosis is prudent

Delay of even 1-8 days contributes to a high

mortality rate

Steroids are warranted for hypotension due to

presumed adrenal insufficiency after an

adrenocorticotropic hormone (ACTH) stimulation

test

For MDR-TB, use a minimum of 1 susceptible

injectable and at least 3 additional susceptible

drugs to prevent the development of additional

resistance

Placenta examination by the pathologist is

imperative.

In a newborn, 3 gastric aspirates of the newborn are

helpful;lumbar puncture is indicated if the newborn

does not thrive

Isolation

Usually removed from isolation when 3 consecutive

sputum smear results are negative and clinical

improvement is shown

Must not be confined with immunosuppressed

patients prior to the establishment of negative

sputum cultures

Negative pressure room or in adequate respiratory

isolation is needed

Prognosis of Miliary TB

If left untreated, the mortality associated is assumed

to be close to 100%

With early and appropriate treatment, mortality is

reduced to less than 10%

The earlier the diagnosis, the better the likelihood of

a positive outcome

Prognosis of Miliary TB

Most deaths occur within the first 2 weeks of

admission to the hospital; may be related to

delayed onset of treatment

Relapse rate is 0-4% with adequate therapy and

directly observed therapy; most relapses occur

during the first 24 months after completion of

therapy

Mortality is strongly associated with

Age

Mycobacterial burden

Delay in initiation of chemotherapy

Laboratory markers such as lymphopenia,

thrombocytopenia, hypoalbuminemia, and elevated

hepatic transaminases

Healing in TB following “successful” treatment

results in fibrosis and consequent anatomical and

physiological alterations of the involved organs

Persistence of physiological, immunological, and

radiological defects in miliary TB in spite of

treatment and the observation of sequelae in

treated cases of pulmonary TB patients point out

that these patients will not regain optimal health

despite achieving a microbiological cure