1. Miliary tuberculosis. Tuberculous meningitis. Lecture № 5 The Department of Tuberculosis of KSMA Doc. Fydorova S.V.

2. Miliary TB is consequence of hematogenous dissemination, which usually occurs during the early phase of tuberculous infection. Miliary TB is more frequent in infants, but may develop in any age. Milium (lat.) – «millet», because tuberculous nodi look like millet-grains.

3. Pathogenesis and pathomorphology of miliary TB Source of hematogenous spreading of TB- infection is usually tuberculous lymph node. Caseous necrosis can rupture into blood stream, so MBT spread and enter into different organs and tissues. MBT cause allergycal changes of blood capillaries’ wall. It loss it’s smoothness, becomes rough and penetrative, so MBT sit down on the capillaries’ wall, and than they enter into interstitial space through the vessel’s wall.

4. Pathogenesis and pathomorphology of miliary TB MBT cause allergic changes of blood capillaries’ wall. It loss it’s smoothness, becomes rough and penetrative, so MBT sit down on the capillaries’ wall, and than they enter into interstitial space through the vessel’s wall. Tuberculous granulomas form in the capillaries’ wall and in the interstitial tissue.

5. Pathogenesis and pathomorphology of miliary TB They look like millet- grains. They have mainly productive reaction, so their borders are clear, they don’t fuse together and cavitations don’t form. Miliary foci are located in subpleural areas, where is the highest number of blood capillaries.

6. The main clinical forms of miliary TB acute tuberculous sepsis pulmonary form typhoidal form meningitic form or tuberculous meningitis

7. Clinical picture of acute tuberculous sepsis It is the most severe generalized form of miliary TB. It usually develops in infants or immunosuppressive patients (especially HIV/AIDS). The disease usually begins suddenly with strong dry cough, chest pain, high fever (to 40ºC and more), cyanosis, severe symptoms of general intoxication. Breathlessness and intoxication increase. Outcome may be fatal after some days.

8. Clinical picture of acute tuberculous sepsis Diagnose is usually confirmed by pathomorphological examination. Miliary foci are usually found in many different organs: lung, pleura, brain, liver, spleen, kidneys etc.

9. Clinical picture of pulmonary form There are chest pain, dry cough or a little of sputum, breathlessness, cyanosis, high fever, weakness, sweetness, symptoms of lung affection predominate. Percussion: tympanitis. Auscultation: bronchial timbre of breathing, sometimes a little of fine moist rales or wheezes may be listened.

10. Clinical picture of typhoidal form Severe intoxication is similar to typhus, so this form is called typhoidal. Patient has got pulmonary symptoms, but severe symptoms of intoxication predominate. Lever dysfunction, consciousness abnormalities: delirium, hallucinations, infection psychosis, cramps, collapse, and even toxic shock with fatal outcome.

11. Clinic of meningitic form is clinic of tuberculous meningitis.

12. X-ray picture of miliary TB Diffuse bilateral interstitial changes of lung picture occur during the first days. Then diffuse small miliary foci appear in the X-ray film after 10- 14 days. Mediastinal enlarged lymph nodes may be also detected, especially by computed scan.

13. Differential diagnosis typhus disseminated carcinoma lymphogranulomatosis sarcoidosis connective tissue diseases etc.

14. Differential diagnosis In difficult diagnostic cases diagnostic thoracotomy with lung tissue biopsy may be necessary to confirm diagnose.

15. Tuberculous meningitis is inflammation of the soft membrane of brain caused by MBT. May develop in all ageing groups.

16. TB meningitis occurs rarely in BCG-employment period. When early detection of TB meningitis takes place, it usually finishes with recovery in 93- 96% of cases.

17. Often TB meningitis is complication of other forms of TB primary tuberculous complex, tuberculosis of intrathoracic lymphatic nodes in children tuberculosis of intrathoracic lymphatic nodes, disseminated tuberculosis in adolescence disseminated TB, infiltrative TB, fibrous- cavernous TB in adults are frequently complicated with TB meningitis

18. Pathogenesis of TB meningitis Three conditions are necessary for the development of TB meningitis: common nonspecific sensibilization specific sensibilization caused by MBT hematogenous spreading of tuberculous infection

19. TB meningitis may develop by three different ways Hematogenous way of pathogenesis: The first period: TB infection general hypersensibilization hematogenous spreading of TB-infection rupture of TB-infection through the hematoencephalitic barrier TB-infection enters into the vessel’s net of the soft membrane of brain

20. TB meningitis may develop by three different ways Hematogenous way of pathogenesis: The second period: TB-infection runs through the blood vessel’s wall and enters into the subarachnoid space MBT sits down on the soft membrane of the brain’s basis miliary lesions form on the membrane of brain’s basis.

21. Liquorogenous way of pathogenesis Small dense caseous foci may form in the brain tissue or soft membrane during initial TB-infection period. Such persons don’t have any clinical symptoms, because TB- infection is latent (semidormant). These focal lesions are called Rich’s foci.

22. Liquorogenous way of pathogenesis But if immune response decreases, MBT leave from Rich’s focus to subarachnoid and liquorogenous spreading occurs. Then areas of specific tuberculous inflammation may form in the soft membrane or brain tissue. Sometimes spinal TB may be source of liquorogenous spreading of TB-infection.

23. Neurogenous way of pathogenesis When tuberculoma of brain takes place MBT can spread along the nervous and cause tuberculous lesions in distant sites of the brain tissue.

24. Pathomorphology of TB meningitis specific inflammation appears in the brain basis. Specific changes may spread from hiazma opticus and frontales lobes to the medulla oblongata. Tuberculous granulomas and foci form in blood vessels’ walls and brain tissue. Necrosis of vessels’ wall, thrombosis and hemorrhages develop. Brain ’ s membrane and tissue of the spinal cord involve.

25. There are three periods of TB meningitis prodromal period (it’s duration is from 2 to 6 weeks) clinical period (it’s duration is usually 4 weeks) terminal period with fatal outcome

26. Prodromal period It’s onset is gradual: weakness, loss of appetite, headache, subfebrile fever, constipation, apathy. During this period children may visit a doctor until 20 times. And clinical diagnose may be: acute viral respiratory infection, allergy, poisoning, biliary dyskinesia, gastrointestinal infection etc. At the end of prodromal period hypersensitiveness to the light, noise, touch appears, dysfunction of vegetative nervous system, diffuse red dermographism develop, sometimes Trusso’s spots appear.

27. Main clinical forms of tuberculous meningitis serous meningitis basilar meningitis menigoencephalitis spinal form

28. Serous meningitis Corresponds to the second week of clinical period: All symptoms of prodromal period strongly increase fever is high headache becomes severe, continuous, there is not effect of medicines vomiting appears, it doesn’t relate with meal and it doesn’t relief patient’s condition

29. Basilar meningitis corresponds to the second week of clinical period: forced position of the patient, positive meningeal symptoms (Brudzinsky upper, medium, lower; Kernig) affection of cranial nervous: nn. oculomotorius, abducence, trochlearis, hypoglossus, glossopharingeus

30. Basilar meningitis eye’s fundus affection – ophthalmologist may detect miliary lesions (granulomas) along vessels of eye’s bottom. This symptom is very rare, but it is confirmation of diagnose of TB meningitis.

31. Menigoencephalitis Corresponds to the third week of clinical period. «Focal» symptoms of brain ’ s tissue affection – paralysis, convulsions, loss of speech, loss of memory, violations of intellect, affection of respiratory and cardiovascular centers with fatal outcome may develop.

32. Spinal meningitis usually corresponds to the fourth week of clinical period. Peripheral paralysis, impairment of pelvic organs function.

33. Cerebrospinal fluid (CSF) in TB meningitis The fluid is clear, transparent, colourless. Intracranial pressure is high, so fluid flows out as stream. Thin film appears on the surface of fluid after 24-36-48 hours. Cells increase until some hundreds per mm³ with predomination of lymphocytes. Protein level is high (more than 0.3 g/l). The level of glucose is low (lower than 2. 96 mmol/l), chlorides level decreases too (lower than 115mmol/l). MBT may be detected in 6 – 20% of cases.

34. Diagnosis of TB meningitis analysis of CSF changes of eye’s fundus chest X-ray computerized tomography of brain Computerized tomography of the skull in young adult patient with cerebral TB, with hydrocephaly, hypodense central areas, and atrophic lesions.

35. Differential diagnose viral meningitis fungal meningitis syphilitic meningitis oncological diseases of central nervous system HIV-infection trauma brain stroke etc.

36. The mortality of untreated TB meningitis is 100% so treatment should be started immediately

37. Prognosis Treatment started during prodromal period or serous meningitis – recovery without complications occurs in nearly 100% of cases Treatment started during basilar meningitis – recovery in nearly 100% of cases, but complications (paralysis, blindness, deafness, hydrocephaly etc.) develop in nearly 50% of cases

38. Prognosis Treatment started during menigoencephalitis – nearly 50% of patients die, in 50% of patients complications develop and residual changes stay, which may cause disablement Treatment started during spinal meningitis – usually 100% of patients die

39. Thank you for your attention!