This document presents the case of a 30-year-old soldier who presented with 1 month of fever and 8 days of progressively worsening sensorium and headache. Examination found neck stiffness and altered sensorium. Investigations showed lymphocytic pleural effusion and CSF with high proteins, low glucose, and AFB positivity. MRI brain showed basal exudates. He was diagnosed with disseminated tuberculosis including tubercular meningitis and pleural effusion. He received ATT and steroids but developed blindness due to optic atrophy. His sensorium and mobility improved with treatment but he remained blind. The case highlights the approach to fever with altered sensorium and complications of tubercular meningitis like hydro

1. Saturday Clinical
Meeting
Presented by Sqn Ldr PK Dixit
Moderated by Col Y S Sirohi
Unit I

2. Patient Particulars
• 30 yrs old serving soldier
• Resident of Kolhapur
• On leave
• Informant: Wife
• Reliability: Fair

3. Presenting Complaints
Fever X 01 month
Headache with altered sensorium X 08 days

4. History of Present Illness
• Fever
– 100-101o
F
– Intermittent
– No chills & rigors
– Evening rise of fever present
– Defervescence with antipyretics

5. History of Present Illness
• Altered sensorium
– Insidious onset, gradually progressive
– Irritability with aggressive behavior
– Confusion with inability to recognize relatives
followed by increased sleepiness with poor
response to verbal commands

6. History of Present Illness
• Headache
– Global
– Associated with 1 episode of non bilious, non
projectile vomiting
• Weight loss
– Unintentional
– 4 Kgs in 01 month

7. Define fever, PUO
• Fever is an elevation of body temperature
that exceeds the normal daily variation and
occurs in conjunction with an increase in the
hypothalamic set point.
• an A.M. temperature of >37.2o
C (>98.9o
F) or a
P.M. temperature of >37.7o
C (>99. 90
F) would
define a fever.

8. PUO
• Fever >38.30
C ( 101 0
F) on at least two
occasions
• Illness duration of >3 weeks
• No known immuno-compromised state
• Diagnosis that remains uncertain after a
thorough history-taking, physical examination
and

9. PUO
• obligatory investigations: determination of erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) level;
platelet count; leukocyte count and differential; hemoglobin
electrolytes, creatinine, total protein, alkaline phosphatase ，
alanine aminotransferase, aspartate aminotransferase ，
lactate dehydrogenase creatine kinase, ferritin, antinuclear
antibodies, and rheumatoid factor; protein electrophoresis;
urinalysis; blood cultures (n = 3); urine culture; chest x-ray;
abdominal ultrasonography; and tuberculin skin test (TST) .

10. Pain sensitive structures in head
• Scalp ，
• Middle meningeal artery ，
• Dural sinuses, falx cerebri
• proximal segments of the large pial arteries.
• The ventricular ependyma, choroid plexus ，
pial veins, and brain parenchyma are not pain-
producing

11. “Red Flags”
• New headache especially in over 50 y.o.
• Abrupt onset, unusually severe
• Change in usual headache pattern
• Associated with focal neurologic findings
• Change in LOC, personality, lethargy
• Fever, neck stiffness
• Systemic signs/symptoms
• Temporal artery tenderness

12. Tumor pain
• The head pain is usually nondescript
• intermittent deep, dull aching of moderate intensity
• worsen with exertion or change in position
• may be associated with nausea and vomiting
• headache of brain tumor disturbs sleep in about 10%
of patients.
• Vomiting that precedes the appearance of headache
by weeks is highly characteristic of posterior fossa
brain tumor.

13. History of Present Illness
No h/o
Seizures, hallucinations, focal weakness of any
limb
Jaundice, abdominal distension
Rash, joint pain, photosensitivity
Cough, hemoptysis

14. History of Present Illness
No h/o
Dysuria, hematuria, increased frequency of
micturition
Substance abuse
Palpitations, dyspnea, ankle edema

15. Past History
• H/o Hansen’s disease (BL) completed 02 years of
MDT, 02 years back
• No past history of TB

16. Personal History
• Mixed diet
• Normal sleep rhythm
• No alcohol/ tobacco consumption
• Denies history of high risk behavior

17. Family History
• No h/o similar illness in the family/ colleagues

18. Summary
• 30 yrs old serving soldier, Old case of Hansen’s
disease, presented with fever of one month duration
along with progressively worsening sensorium with
headache of 8 days duration along with weight loss

19. Causes of Fever with Altered
Sensorium
• Infectious causes
– Encephalitis, Meningitis, cerebral malaria, brain
abscess, sepsis related encephalopathy, sepsis with
DIC/TTP
• Non infectious causes
– Overproduction of heat
– Impaired heat dissipation
– Structural lesions (impaired thermoregulatory
mechanism)
– Misc Causes

20. Infectious causes of fever with altered
sensorium
• Viral
– DNA viruses :- HSV-1, HSV-2, HHV-6, EBV, CMV,
– RNA Viruses :- HIV, Influenza (serotype A), arboviruses (JE)
• Bacterial
– Pyogenic , TBM, legionella, leptospira, Salmonella
• Rickettsial
– Scrub typhus, epidemic typhus
• Fungal
– Cryptococcosis, histoplasmosis
• Parasitic
– Plasmodium, toxoplasma

21. Non infectious causes of fever with
altered sensorium
• Overproduction of heat
– Malignant hyperthermia (NMS, serotonin synd),
Salicylate poisoning, Thyrotoxic encephalopathy,
convulsive status , catatonic schizophrenia
• Impaired heat dissipation
– Heat stroke, anticholinergic toxicity
• Structural lesions
– Hypothalamic lesion, brainstem stroke, SAH
• Misc
– ADEM, cerebral fat embolism, Altered sensorium with
secondary causes of fever

23. Physical signs in suspected meningitis
Kernig’s sign Flexing the hip and extending the knee to elicit
pain in the back
and legs
Brudzinski’s sign Passive flexion of the neck elicits flexion of the
hip
Nuchal rigidity Severe neck stiffness
Jolt
accentuation
Exacerbation of existing headache with rapid
head rotation

24. Causes of Neck rigidity
• Meningitis
• Subarachnoid hemorrhage
• Cerebral abscess
• CNS lymphoma/metastasis
• Posterior fossa tumour
• Raised intracranial tension
• Sarcoidosis (Neurosarcoidosis)

25. Possibilities
• Meningoencephalitis(tubercular, fungal)
• Cerebral abscess
• Sarcoidosis (Neurosarcoidosis)

27. General Examination
• Patient drowsy
• T -101O
F
• Pulse: 58/ min, regular
• BP: 116/70 mm Hg RAS
• RR: 20/ min, regular
• No Pallor, icterus, cyanosis, Clubbing, edema,
lymphadenopathy or Rash

28. General Examination
• Pupils- Normal size, sluggishly reacting to light
• Neck stiffness +
• Fundus examination normal with no evidence of
papilledema
• No cutaneous stigmata of HIV

29. Systemic Examination
• CVS
• S1 S2 heard
• No S3, S4,murmurs heard
• Resp
• Chest movement b/l equal
• No fullness/rib crowding
• No pleural rub, TVF normal
• Absent Breath sounds -left infra scapular region

30. Systemic Examination
• P/A
• Soft, non-tender
• Liver/ spleen: not palpable
• Bowel sounds: present
• No free fluid

31. CNS Examination
• Drowsy but arousable
• Pupils – 3-4 mm B/L reacting to light

32. Motor system
• Bulk : Normal in all four limbs
• Tone : Increased in all four limbs
• Moving all four limbs

33. Power
Joint Movement Right Left
Hip Flexion 4 4
Extension 4 4
Abduction 4- 4-
Adduction 4- 4-
Knee Flexion 4 4
Extension 4- 4-
Ankle Flexion 4 4
Extension 4- 4-

34. CNS Examination
• Reflexes
• Sensory system- localizing deep pain, Rest could not
be assessed
BICEPS TRICEPS SUPINATOR KNEES ANKLE PLANTAR
Right +++ +++ +++ +++ ++ Extensors
Left +++ +++ +++ +++ ++ Extensors

35. Empirical Management
• Parenteral broad spectrum Antibiotics
• Anti malarial
• Antiedema measures
• Anticonvulsants

36. CSF Analysis
30 Dec 16 07 Jan 17
Proteins 115.6 mg/dl(15-45 mg/dl) 52 mg/dl(Globulins-increased)
Glucose 28 mg/dl (98) 15 mg/dl( RBS- 110)
RBC 10/cu mm 10/cu mm
WBC 90 (Neutrophils- 52 %) 450 (Predominantly neutrophils)
Gram/India ink Negative Negative
ZN stain Negative AFB Positive in CSF
HSV 1-2 Negative Negative
CSF Culture and
sensitivity
Negative Negative
ADA 96

37. Neuroimaging

38. NCCT BRAIN – 30 DEC 16

40. MRI BRAIN
31 DEC and 05 JAN 17

43. MRI BRAIN CE
13 JAN 2017

48. Investigations
Parameter 30 Dec 16 06 Jan 17
Hb 11.1 g/dL 11.4 g/dL
TLC 8800/cumm 6200/cumm
DLC P 86 L 10 E 02 M 02 P 83 L 13 E 02 M 02
Platelets 4.33 lakhs/cumm 3.84 lakhs/cumm
PBS Normocytic normochromic smear with Neutrophilia
PBS for MP - Negative
PT/aPTT/INR 19.7/35/1.90 16.7/33/1.50
Urea 11 mg/dl 45 mg/dl
Creatinine 1.42 mg/dl 0.67 mg/dl
Na 135 mEq/dl 139 mEq/dl
K 4.8 mEq/dl 4.0 mEq/dl

49. Investigations
Parameter 30 Dec16 07 Jan17
Bilirubin (Total) 0.65 mg/dL 0.3 mg/dL
Direct Bilirubin 0.20 mg/dl 0.1 mg/dl
AST 15.7 IU/L 24 IU/L
ALT 17.6 IU/L 45 IU/L
TP/Alb/Glo 6.2/3.4/2.8 g/dl 6.1/3.2/2.9 gm/dl
Serum Alk Phosphatase 196 IU/L 188 IU/L
Iron/TIBC 72/280 mg/dl

50. Investigations
Parameter Patient’s value
Urine RE/ME 2-4 pus cells/Hpf
Urine C/S No growth
HbsAg/Anti HCV/HIV Negative
X Ray Chest Pleural effusion Lt

51. Pleural fluid Analysis
Cytology WBC-210 (lymphocytes 95 %), RBC-Plenty
Pleural fluid for malignant cytology Negative
Gram stain/ZN stain- No organism seen/ -ve for AFB
Pleural fluid C/S- No growth
Protein 5.5 g/dl
Glucose 65 mg/dl
ADA 109 U/L (0-40)

52. Tubercular CSF picture
• Protein -100-500mg/dl, <100-25%, >500-10%
• Glu- <45mg/dl (80%)
• Cells- 100-500/mm3
, <100-15%,500-1500-20%
• Incidence of smear positive 1st
sample-37%,
four serial samples-87%

53. Improving AFB detection
• CSF leucocytes- treated with triton prior to
Ziehl–Neelsen staining
• The loop-mediated isothermal amplification
assay (LAMP)

54. How to increase sensitivity of smear?
• Prepare smear from clot
• Use 10ml of last removed CSF sample
• Add 2ml 95% alcohol to CSF if no clot, use
0.02ml for 1cm dia smear
• 200-500 hpf examined by more than one obs

55. Pathogenesis and factors leading to
TBM
• Extremes of age
• Alcoholism
• Drug induced immune suppression
• Malignancy
• AIDS
• Physical trauma

56. CT scan prognostication?
• Normal CECT head- 30% in stage 1
8% in stage 2
• Abnormal CT head in 100% pts stage 3
• Normal CECT in drowsy pt- unlikely to be TBM

57. Phases of tubercular meningitis?
Prodromal
phase
lasting two to three weeks, is characterized by the
insidious onset of malaise, lassitude, headache, low-grade
fever, and personality change.
Meningitic
phase
more pronounced neurologic features, such as
meningismus, protracted headache, vomiting, lethargy,
confusion, and varying degrees of cranial nerve and long-
tract signs.
Paralytic phase illness accelerates rapidly; confusion gives way to stupor
and coma, seizures, and often hemiparesis. For the
majority of untreated patients, death ensues within five to
eight weeks of the onset of illness

58. Stages of tubercular meningitis?
Stage 1 Patients are lucid with no focal neurologic
signs or evidence of hydrocephalus
Stage 2 Patients exhibit lethargy, confusion; they
may have mild focal signs, such as cranial
nerve palsy or hemiparesis
Stage 3 represents advanced illness with delirium,
stupor, coma, seizures, multiple cranial
nerve palsies, and/or dense hemiplegia

59. Pathological processes accounting for
clinical manifestations?
• Proliferative basilar arachnoiditis
• Vasculitis of arteries and veins traversing the
exudates
• Disturbed CSF circulation

60. Categories of CNS tuberculosis
• Tubercular meningitis
• Intracranial tuberculoma
• Spinal tuberculous arachnoiditis

61. Atypical presentations of CNS TB
• Slowly progressing dementia
• Acute meningitic syndrome
• Seizures, focal neurologic deficits, CN palsies
• Hydrocephalus
• TB encephalopathy

62. Final Diagnosis
• Disseminated Tuberculosis : Tubercular meningitis
with vasculitis and pleural effusion(Lt)

63. Course in hospital
He was continued on ATT with iv steroids
Prophylactic anticonvulsants
Anti cerebral edema measures
He showed gradual improvement in sensorium
On 14th Feb 2017 he developed sudden loss of vision
in both eyes

66. Eye Evaluation
• Pupils mid dilated
• Fundoscopy- no papilloedema
• Bilateral optic atrophy

67. Mechanism of visual loss in TBM?
• Optochiasmatic arachnoiditis
• Compression by 3rd
ventricle(hydrocephalus)
• Optic nerve granuloma
• Optic nerve infarction(vasculitis)
• Ethambutol
• INH

68. NCCT BRAIN
14/02/17 and 22/02/17

69. 14/02/17 22/02/17

70. Management
• VP shunt – 14 Feb 17
• Dexamethasone dose modification
• Mannitol
• Iv antibiotics

71. Present Status
• Four score 14
• Well oriented
• Able to walk with support
• Improving vision

72. Aim of Presentation
• To discuss approach to fever with altered sensorium
• Complications of Tubercular meningitis
• Management of Tubercular meningitis

73. THANK YOU