Meningitis UPLOAD
Content
MENINGITIS
The following issues will be discussed in this essay: what is meningitis and how it is caused, how the blood brain barrier is related to this disease, specific diagnosis as well as the treatment options available for Jack’s meningitis and the epidemiology on meningitis.
Epidemiology Meningitis affects people of all ages and ethnicities. However, certain regions in the world have a higher epidemic of meningitis than others and these places are termed ‘meningitis belt’. This includes Africa where in 1996 over 250,000 meningitis patients were seen. Meningitis is most commonly caused in Europe by the Neisseria meningitides bacteria. Bacterial meningits is very rare yet it is most fatal. In the early 19th century almost everyone with bacterial meningitis died, now with early detection of the warning signs the risk of mortality is only 5–15%. For people of Jack’s age group, risk factors of contracting the bacteria include by smoking and kissing. The three most common are Neisseria meningitides, mainly serogroup C, Haemophilus influenzae type B, to which the Hib vaccine is given, and Streptococcus pneumoniae. The table below shows details of these and other bacteria. (1)(2)(3)(4)
Fig 1: Organisms that cause bacterial meningitis (5)
Meningitis Meningitis is caused by the inflammation to the meninges of the central nervous system (brain and spinal cord). Meninges are the protective coverings of the brain
1
and spinal cord and consist of the dura mater (outer part), the arachnoid mater and pia mater (inner part) as can be seen below:
Fig 2: Meninges
(6)
The area between the arachnoid and pia mater is called the subarachnoid space. Cerebrospinal fluid (CSF) is found within this space and its main functions are in providing protection to the brain as well as decreasing the brain’s mass. (4) There are many ways in which meningitis can be caused, the main ones being infections by viruses, bacteria and fungi. Other less likely causes include trauma, specific drugs and cancer. The common symptoms presented by most meningitis patients are fever, nausea, headache and vomiting. These symptoms are common with many other diseases therefore meningitis is often not picked up easily using symptoms alone. However there are also key signs that are indicative of the disease and these are sensitivity to light, stiffness in neck and rash. The famous glass test is used to test whether the red rash spots, which is caused by capillary damage, disappears when under pressure by the glass. A positive sign is not seen with this test in meningitis patients and this calls for immediate attention. Another test very often used to help identify meningitis cases is the Kernig’s test. In this the patient is asked to lie on their back and flex their thigh at an angle of 90°. While at this position, the knee is extended. In patients with meningitis, this movement is often very difficult and painful (pain present in the lower thing – hamstrings muscles). (4)(7)(8)
Blood Brain Barrier The brain is protected by harmful substances in the blood by the presence of the blood brain barrier (BBB). The BBB is composed of tight junctions, a continuous basement membrane and astrocytic end feet as can be seen in the following diagram:
2
Fig 3: Blood Brain Barrier (6)
The meninges become inflamed due to the substances released as products by the bacteria and also from the release of lipids and oligosaccharides when the bacteria die. The inflammation causes a disruption in the blood brain barrier as a result of increased permeability. The bacterial cell wall also cause the production of inflammatory mediators, such as interleukin-1 by local macrophages, astrocytes and microglial cells. These induce further permeability in the BBB which causes proteins, mainly albumin, to diffuse in. This can cause a very serious problem of raised intracranial pressure and cerebral oedema. (10)(11) There are two ways in which bacteria can cause meningitis. Firstly, it is thought that bacteria which are present and have caused an infection in the nasopharynx are able to gain access into the choroid plexus (area in brain where CSF is made) directly. But the most common route for bacteria is via the bloodstream. They are able to survive well in the brain due to the low number of immune cells present in the CSF. (10)(11)
Diagnosis
3
As the CSF present in the subarachnoid space is low in immune cells, bacteria are able to multiply in numbers without any resistance by the body’s immune system. Glucose levels fall in the CSF as it is used up by the bacteria. As the blood brain barrier is broken fluid and proteins, in particular albumin, diffuse into the CSF from the blood and there is the risk of cerebral oedema. (4) It was an important for Jack to have a CT scan prior to a lumbar puncture as this is required to make sure there is no raised intracranial pressure and rule out any other causes of Jack’s symptoms. A raised intracranial pressure means that a lumbar puncture, the technique used to withdraw cerebrospinal fluid from levels L3-L4 of spinal cord, could risk in herniation of the brainstem. Upon finding that Jack is clear of raised intracranial pressure in the brain, a sample of cerebrospinal fluid can be taken to be analysed in the lab. Cerebrospinal fluid in a healthy individual is low in protein, low in immune cells and has about 60% glucose as of that of serum. (1)(4)(12) After infection, these states change and the following table can be used with the results of the CSF scan to identify the type of meningitis Jack has:
CSF finding in different conditions[5] Condition Acute viral meningitis Tuberculous meningitis Fungal meningitis Malignant meningitis Subarachnoid hemorrhage Glucose Normal Low Low Low Normal Protein high Cells high, often > 300/mm³ pleocytosis, mixed < 300/mm³ < 300/mm³ usually mononuclear Erythrocytes Acute bacterial meningitis Low
normal or high mononuclear, < 300/mm³ high high high normal, or high
Fig 4: Analysis of cerebrospinal fluid (1)
From Jack’s CSF laboratory results, we can identify that he has acute bacterial meningitis since the results showed that the CSF was low in glucose and high in protein. As explained before, these results can be explained by the fact that
4
glucose is required for the metabolic processes of the bacteria and high protein would be due to leakage from blood through the broken blood-brain barrier.
Treatment Bacterial meningitis is very serious and there is a high mortality rate. For this reason, as soon as meningitis is suspected by signs and symptoms, antibiotics are given even before the results of any specific tests are back. The most widely administered antibiotic given at the first sings of meningitis is benzylpenizillin. This can only be given through an injection or infusion (parenteral route) as the drug can not withstand the acid produced by the stomach. The CSF can be examined to identify which bacteria is present. The most common bacteria for people of Jack’s age group are Neisseria meningitides, Streptococcus pneumonia and Haemophilus influenza which are gram negative diplococci, gram positive cocci and gram negative rods respectively. Cephalosporin is an antibiotic that is effective for all three of the named bacteria and is given as soon as the cause is confirmed to be bacterial. Both benzylpenicillin and cephalosporin are classed as a B-lactam antibiotic which work by inhibiting the formation of the peptidoglycan cell wall of bacteria and thereby destruct bacteria. Vancomycin is another antibiotic that works in similar ways to beta -lactams and shows high effectiveness when used against gram-positive bacteria. It is rarely used, only required when patient is allergic to penicillin or in incidences where other antibiotics are ineffective because of bacterial resistance eg Neisseria meningitides. (11)(13)(14)(15)
It is important to understand from this essay that the signs and symptoms of meningitis need to be recognised instantly in order to carry out treatment. For instance, in acute bacterial meningitis, every second counts so the sooner treatment is started the better the chances of living. Therefore, we can conclude that Jack was very lucky in this case to have received treatment fairly instantly although not having recognised any of the signs and symptoms.
5
References
1. Wikipedia. Meningitis [online] 2008. Available from:
http://en.wikipedia.org/wiki/Meningitis [accessed 25/4/2008].
2. Quagliarello V. Epidemiology and pathogenesis of bacterial meningitis
[online] 2007. Available from: http://www.uptodate.com/patients/content/topic.do? topicKey=cns_infe/6161 [accessed 25/4/2008].
3. Barclay L, Lie D. Intimate Kissing May Be a Risk Factor for Meningococcal
Meningitis [online] 2006. Available from: http://www.medscape.com/viewarticle/523610 [accessed 28/4/2008].
4. Michael-Titus A, Revest P, Shortland P. The Nervous System.
Philadelphia, USA : Churchill Livingstone, 2007.
5. UpToDate Online. Characteristics of causes of bacterial meningitis [online]
2008. Available from: http://www.uptodate.com/online/content/image.do? imageKey=id_pix/bact_men.htm [accessed 26/4/2008]. 6. Wikipedia. Image:Illu meninges.jpg [online] 2006. Available from: http://en.wikipedia.org/wiki/Image:Illu_meninges.jpg [accessed 29/4/2008]. 7. National Institute of Neurological Disorders and Stroke. Meningitis and Encephalitis Fact Sheet [online] 2004 . Available from: http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_enceph alitis_meningitis.htm [accessed 28/4/2008].
8. Medinfo. Meningitis [online] 2005. Available from:
http://www.medinfo.co.uk/conditions/meningitis.html [accessed 26/4/2008].
9. MedicaLook. Blood brain barrier [online] 2007. Available from:
http://www.medicalook.com/human_anatomy/organs/Blood_brain_barrier .html [accessed 26/4/2008].
10. Agamanolis DP. Infections of the nervous system [online] 2007. Available
from: http://www.neuropathologyweb.org/chapter5/chapter5aSuppurative.html [accessed 27/4/2008].
11. Fowler TJ, Scadding JW, ed.. Clinical Neurology. 3rd ed. London, GB :
Arnold, 2003.
12. Joffe AR. Lumbar Puncture and Brain Herniation in Acute Bacterial
Meningitis: A Review. Journal of Intensive Care Medicine. 2007;22(4):194-207.
13. Kumar P, Clark M, ed.. Clinical Medicine. 6th ed. London, GB : Elsevier
Saunders, 2005.
6
14. Wikipedia. Penicillin [online] 2008. Available from: http://en.wikipedia.org/wiki/Penicillin [accessed 28/4/2008]. 15. Wikipedia. Beta-Lactam [online] 2008. Available from: http://en.wikipedia.org/wiki/Beta-lactam [accessed 28/4/2008].
7
The following issues will be discussed in this essay: what is meningitis and how it is caused, how the blood brain barrier is related to this disease, specific diagnosis as well as the treatment options available for Jack’s meningitis and the epidemiology on meningitis.
Epidemiology Meningitis affects people of all ages and ethnicities. However, certain regions in the world have a higher epidemic of meningitis than others and these places are termed ‘meningitis belt’. This includes Africa where in 1996 over 250,000 meningitis patients were seen. Meningitis is most commonly caused in Europe by the Neisseria meningitides bacteria. Bacterial meningits is very rare yet it is most fatal. In the early 19th century almost everyone with bacterial meningitis died, now with early detection of the warning signs the risk of mortality is only 5–15%. For people of Jack’s age group, risk factors of contracting the bacteria include by smoking and kissing. The three most common are Neisseria meningitides, mainly serogroup C, Haemophilus influenzae type B, to which the Hib vaccine is given, and Streptococcus pneumoniae. The table below shows details of these and other bacteria. (1)(2)(3)(4)
Fig 1: Organisms that cause bacterial meningitis (5)
Meningitis Meningitis is caused by the inflammation to the meninges of the central nervous system (brain and spinal cord). Meninges are the protective coverings of the brain
1
and spinal cord and consist of the dura mater (outer part), the arachnoid mater and pia mater (inner part) as can be seen below:
Fig 2: Meninges
(6)
The area between the arachnoid and pia mater is called the subarachnoid space. Cerebrospinal fluid (CSF) is found within this space and its main functions are in providing protection to the brain as well as decreasing the brain’s mass. (4) There are many ways in which meningitis can be caused, the main ones being infections by viruses, bacteria and fungi. Other less likely causes include trauma, specific drugs and cancer. The common symptoms presented by most meningitis patients are fever, nausea, headache and vomiting. These symptoms are common with many other diseases therefore meningitis is often not picked up easily using symptoms alone. However there are also key signs that are indicative of the disease and these are sensitivity to light, stiffness in neck and rash. The famous glass test is used to test whether the red rash spots, which is caused by capillary damage, disappears when under pressure by the glass. A positive sign is not seen with this test in meningitis patients and this calls for immediate attention. Another test very often used to help identify meningitis cases is the Kernig’s test. In this the patient is asked to lie on their back and flex their thigh at an angle of 90°. While at this position, the knee is extended. In patients with meningitis, this movement is often very difficult and painful (pain present in the lower thing – hamstrings muscles). (4)(7)(8)
Blood Brain Barrier The brain is protected by harmful substances in the blood by the presence of the blood brain barrier (BBB). The BBB is composed of tight junctions, a continuous basement membrane and astrocytic end feet as can be seen in the following diagram:
2
Fig 3: Blood Brain Barrier (6)
The meninges become inflamed due to the substances released as products by the bacteria and also from the release of lipids and oligosaccharides when the bacteria die. The inflammation causes a disruption in the blood brain barrier as a result of increased permeability. The bacterial cell wall also cause the production of inflammatory mediators, such as interleukin-1 by local macrophages, astrocytes and microglial cells. These induce further permeability in the BBB which causes proteins, mainly albumin, to diffuse in. This can cause a very serious problem of raised intracranial pressure and cerebral oedema. (10)(11) There are two ways in which bacteria can cause meningitis. Firstly, it is thought that bacteria which are present and have caused an infection in the nasopharynx are able to gain access into the choroid plexus (area in brain where CSF is made) directly. But the most common route for bacteria is via the bloodstream. They are able to survive well in the brain due to the low number of immune cells present in the CSF. (10)(11)
Diagnosis
3
As the CSF present in the subarachnoid space is low in immune cells, bacteria are able to multiply in numbers without any resistance by the body’s immune system. Glucose levels fall in the CSF as it is used up by the bacteria. As the blood brain barrier is broken fluid and proteins, in particular albumin, diffuse into the CSF from the blood and there is the risk of cerebral oedema. (4) It was an important for Jack to have a CT scan prior to a lumbar puncture as this is required to make sure there is no raised intracranial pressure and rule out any other causes of Jack’s symptoms. A raised intracranial pressure means that a lumbar puncture, the technique used to withdraw cerebrospinal fluid from levels L3-L4 of spinal cord, could risk in herniation of the brainstem. Upon finding that Jack is clear of raised intracranial pressure in the brain, a sample of cerebrospinal fluid can be taken to be analysed in the lab. Cerebrospinal fluid in a healthy individual is low in protein, low in immune cells and has about 60% glucose as of that of serum. (1)(4)(12) After infection, these states change and the following table can be used with the results of the CSF scan to identify the type of meningitis Jack has:
CSF finding in different conditions[5] Condition Acute viral meningitis Tuberculous meningitis Fungal meningitis Malignant meningitis Subarachnoid hemorrhage Glucose Normal Low Low Low Normal Protein high Cells high, often > 300/mm³ pleocytosis, mixed < 300/mm³ < 300/mm³ usually mononuclear Erythrocytes Acute bacterial meningitis Low
normal or high mononuclear, < 300/mm³ high high high normal, or high
Fig 4: Analysis of cerebrospinal fluid (1)
From Jack’s CSF laboratory results, we can identify that he has acute bacterial meningitis since the results showed that the CSF was low in glucose and high in protein. As explained before, these results can be explained by the fact that
4
glucose is required for the metabolic processes of the bacteria and high protein would be due to leakage from blood through the broken blood-brain barrier.
Treatment Bacterial meningitis is very serious and there is a high mortality rate. For this reason, as soon as meningitis is suspected by signs and symptoms, antibiotics are given even before the results of any specific tests are back. The most widely administered antibiotic given at the first sings of meningitis is benzylpenizillin. This can only be given through an injection or infusion (parenteral route) as the drug can not withstand the acid produced by the stomach. The CSF can be examined to identify which bacteria is present. The most common bacteria for people of Jack’s age group are Neisseria meningitides, Streptococcus pneumonia and Haemophilus influenza which are gram negative diplococci, gram positive cocci and gram negative rods respectively. Cephalosporin is an antibiotic that is effective for all three of the named bacteria and is given as soon as the cause is confirmed to be bacterial. Both benzylpenicillin and cephalosporin are classed as a B-lactam antibiotic which work by inhibiting the formation of the peptidoglycan cell wall of bacteria and thereby destruct bacteria. Vancomycin is another antibiotic that works in similar ways to beta -lactams and shows high effectiveness when used against gram-positive bacteria. It is rarely used, only required when patient is allergic to penicillin or in incidences where other antibiotics are ineffective because of bacterial resistance eg Neisseria meningitides. (11)(13)(14)(15)
It is important to understand from this essay that the signs and symptoms of meningitis need to be recognised instantly in order to carry out treatment. For instance, in acute bacterial meningitis, every second counts so the sooner treatment is started the better the chances of living. Therefore, we can conclude that Jack was very lucky in this case to have received treatment fairly instantly although not having recognised any of the signs and symptoms.
5
References
1. Wikipedia. Meningitis [online] 2008. Available from:
http://en.wikipedia.org/wiki/Meningitis [accessed 25/4/2008].
2. Quagliarello V. Epidemiology and pathogenesis of bacterial meningitis
[online] 2007. Available from: http://www.uptodate.com/patients/content/topic.do? topicKey=cns_infe/6161 [accessed 25/4/2008].
3. Barclay L, Lie D. Intimate Kissing May Be a Risk Factor for Meningococcal
Meningitis [online] 2006. Available from: http://www.medscape.com/viewarticle/523610 [accessed 28/4/2008].
4. Michael-Titus A, Revest P, Shortland P. The Nervous System.
Philadelphia, USA : Churchill Livingstone, 2007.
5. UpToDate Online. Characteristics of causes of bacterial meningitis [online]
2008. Available from: http://www.uptodate.com/online/content/image.do? imageKey=id_pix/bact_men.htm [accessed 26/4/2008]. 6. Wikipedia. Image:Illu meninges.jpg [online] 2006. Available from: http://en.wikipedia.org/wiki/Image:Illu_meninges.jpg [accessed 29/4/2008]. 7. National Institute of Neurological Disorders and Stroke. Meningitis and Encephalitis Fact Sheet [online] 2004 . Available from: http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_enceph alitis_meningitis.htm [accessed 28/4/2008].
8. Medinfo. Meningitis [online] 2005. Available from:
http://www.medinfo.co.uk/conditions/meningitis.html [accessed 26/4/2008].
9. MedicaLook. Blood brain barrier [online] 2007. Available from:
http://www.medicalook.com/human_anatomy/organs/Blood_brain_barrier .html [accessed 26/4/2008].
10. Agamanolis DP. Infections of the nervous system [online] 2007. Available
from: http://www.neuropathologyweb.org/chapter5/chapter5aSuppurative.html [accessed 27/4/2008].
11. Fowler TJ, Scadding JW, ed.. Clinical Neurology. 3rd ed. London, GB :
Arnold, 2003.
12. Joffe AR. Lumbar Puncture and Brain Herniation in Acute Bacterial
Meningitis: A Review. Journal of Intensive Care Medicine. 2007;22(4):194-207.
13. Kumar P, Clark M, ed.. Clinical Medicine. 6th ed. London, GB : Elsevier
Saunders, 2005.
6
14. Wikipedia. Penicillin [online] 2008. Available from: http://en.wikipedia.org/wiki/Penicillin [accessed 28/4/2008]. 15. Wikipedia. Beta-Lactam [online] 2008. Available from: http://en.wikipedia.org/wiki/Beta-lactam [accessed 28/4/2008].
7
