1. Cerebral TuberculosisBy
د. ياسر عبدالله – دكتوراة علم الأحياء الدقيقة الطبية والطفيليات.
رئيس قسم الأحياء الدقيقة الطبية والطفيليات.
Dr. Yasir Hakim, MD Pathology& Microbiology .Assist Professor and Consultant of Pathology & Microbiology
Head Department of Medical Microbiology.
School of Medicine
Dar Uloom –University – KSA

2. Objectives 1) Differentiate between clinical presentation of acute and chronic cerebral and meningitis infection. 2) Differentiate between the cerebrospinal fluid findings in acute and chronic meningitis. 3) Know generally the different microbiological causes of chronic cerebral infection and meningitis. 4) Know the details of the different bacterial causes of chronic meningitis specially tuberculosis and brucellosis. 5) Differentiate between the clinical presentation and laboratory findings of tuberculous and Brucella meningitis. 6) Know the basis of treatment of T.B and Brucella meningitis.

3. Background
Tuberculosis (TB) is an infectious disease that typically affects the lungs. TB is caused by a bacterium called Mycobacterium tuberculosis. If the infection is not treated quickly, the bacteria can travel through the bloodstream to infect other organs and tissues.
Sometimes, the bacteria will travel to the meninges, which are the membranes surrounding the brain and spinal cord.
Infected meninges can result in a life-threatening condition known as meningeal tuberculosis.

4. Background
Meningeal tuberculosis is also known as tubercular meningitis or TB meningitis .
Central nervous system (CNS) tuberculosis (TB) is a serious form of TB, due to haematogenous spread of Mycobacterium tuberculosis (MT).
Manifesting as meningitis, cerebritis and tuberculous abscesses or tuberculomas, it occurs in approximately 1% of all patients with TB, affecting disproportionately children and immunosuppressed patients.

5. CONT:
Tuberculosis (TB) of the central nervous system (CNS) is a granulomatous infection caused by Mycobacterium tuberculosis.
The disease predominantly involves the brain and meninges, but occasionally, it affects the spinal cord. Clinical diagnosis can be difficult; therefore, imaging has an important role in establishing the diagnosis.

6. Pathophsiolgy
Many of the symptoms, signs, and sequelae of tuberculous meningitis (TBM) are the result of an immunologically directed inflammatory reaction to the infection ---- Granuloma.
TBM develops in 2 steps. Mycobacterium tuberculosis bacilli enter the host by droplet inhalation, the initial point of infection being the alveolar macrophages.
Localized infection escalates within the lungs, with dissemination to the regional lymph nodes to produce the primary complex.
During this stage, a short but significant bacterimia is present that can seed tubercle bacilli to other organs.
In persons who develop TBM, bacilli seed to the meninges or brain parenchyma, resulting in the formation of small subpial or subependymal foci of metastatic caseous lesions. These are termed Rich foci. Dissemination to the central nervous system (CNS) .

7. CONT:
The second step in the development of TBM is an increase in size of a Rich focus until it ruptures into the subarachnoid space. Tubercles rupturing into the subarachnoid space cause meningitis. Those deeper in the brain or spinal cord parenchyma cause tuberculomas or abscesses.
A thick gelatinous exudate infiltrates the cortical or meningeal blood vessels, producing inflammation, obstruction, or infarction. Basal meningitis accounts for the frequent dysfunction of cranial nerves (CNs) III, VI, and VII, eventually leading to obstructive hydrocephalus from obstruction of basilar cisterns

8. Risk factors
TB and TB meningitis can develop in children and adults of all ages. However, people with specific health problems are at greater risk of developing these conditions.
Risk factors for TB meningitis include having a history of:
HIV/AIDS.
excessive alcohol use
weakened immune system
diabetes mellitus.
In low-income countries, children between birth and 4 years of age are most likely to develop this condition.
Other risk factors include malnutrition and malignancies.

9. Symptoms
At first, symptoms of TB meningitis typically appear slowly. They become more severe over a period of weeks. During the early stages of the infection, symptoms can include:
Fatigue
Malaise
Low-grade fever
Classic symptoms of meningitis, such as stiff neck, headache, and light sensitivity, are not always present in meningeal tuberculosis

10. CONT: May experience the following symptoms: Fever Confusion
Nausea and vomiting
Lethargy
Irritability
Unconsciousness

11. Complications
The complications of TB meningitis are significant, and in some cases life-threatening. They include:
Seizures
Hearing loss
Increased pressure in the brain
Brain damage
Stroke
Death

12. Epidemiology Sex distribution for TBM
Among persons younger than 20 years, TB infection rates are similar for both sexes.
2) Age distribution
In general, however, TBM is more common in children than in adults, especially in the first 5 years of life. In fact, children aged 0-5 years are affected more commonly with TBM than any other age group.
3) International statics
TBM complicates approximately 1 of every 300 untreated primary TB infections
4 ) Prevalence of TBM by race
Case rates in Asians and Pacific Islanders are the highest, particularly among adults.
Rates among Hispanics, and Native Americans/Alaskan Natives are intermediate.

13. Diagnosis A lumbar puncture, also known as a spinal tap.
Biopsy of the meninges.
Culture(Lowenstein-Jensen medium).
Chest X-ray
CT scan &MRI

14. Treatment Weight-based oral anti-TB drug daily dosing in adults ≥30 kg
The treatment of TB meningitis is isoniazid, rifampicin , pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months.
Steroids can be used in the first six weeks of treatment A few people may require immunomodulatory agents such as thalidomide.

15. Weight-based injectable anti-TB daily dosing in adults ≥30 kg
DRUGS
DAILY DOSE
30–35 KG
36–45 KG
46–55 KG
56–70 KG
>70 KG
Isoniazid
4–6 mg/kg once daily
150 mg
200 mg
300 mg
Rifampicin
8–12 mg/kg once daily
450 mg
600 mg
Pyrazinamide
20–30 mg/kg once daily
800 mg
1000 mg
1200 mg
1600 mg
2000 mg
Ethambutol
15–25 mg/kg once daily
Rifabutin
5–10 mg/kg once daily
Levofloxacin
750–1000 mg once daily
750 mg
Moxifloxacin
400 mg once daily
400 mg
Ethionamide
500–750 mg/day in 2 divided doses
500 mg
Prothionamide

16. 500–750 mg/day in 2 divided doses 500 mg 750 mg
Cycloserine
500–750 mg/day in 2 divided doses
500 mg
750 mg
p-aminosalicylic acida
8 g/day in 2 divided doses
8 g
8–12 g
Bedaquiline
400 mg once daily for 2 weeks then 200 mg 3 times per week
Clofazimine
200–300 mg (2 first months) then 100 mg
Linezolid
600 mg once daily
600 mg
Amoxicillin/clavulanic acidb 7/1
80 mg/kg/day in 2 divided doses
2600 mg
Amoxicillin/clavulanic acidb 8/1
3000 mg
High-dose isoniazid
16–20 mg/kg once daily
600–1000 mg
1000–1500 mg
1500 mg
Imipenem/cilastatin
1000 imipenem/1000 mg cilastatin twice daily
Meropenem
1000 mg three times daily (alternative dosing is 2000 mg twice daily)

17. Weight-based injectable anti-TB daily dosing in adults ≥30 kg
DRUGS
30–33 KG
34–40 KG
41–45 KG
46–50 KG
51–70 KG
>70 KG
Streptomycin
12–18 mg/kg once daily
500 mg
600 mg
700 mg
800 mg
900 mg
1000 mg
Kanamycin
15–20 mg/kg once daily
625 mg
750 mg
875 mg
Amikacin
Capreomycin

18. Resources
Sherris, Medical Microbiology, Introduction to infectious diseases. Latest version

19. مع امنياتى لكم بالتوفيق