Meningitis

Neurosurgery

Clinicals - History

Fact Explanation
Duration of the symptoms Meninges are the lining that covers the brain and spinal cord. Meningitis is inflammation of the meninges around the brain and spinal cord. It is usually caused by an infectious pathogens such as bacteria, virus, fungi and parasites. Depending on he duration of the symptoms, it can be subdivided into acute and chronic form. Bacterial meningitis is a medical emergency requiring immediate treatment. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are the most common causative pathogens. Organisms may deffer according to the age of the patient. Eg:- During neonatal period-E.coli, gram negative bacilli, Listeria monocytogens and Group B streptococci, children older than 3 months-Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae, children between 1-3 months with the organisms from both above mentioned groups. Chronic meningitis is different from acute meningitis as it is an uncommon disease with a gradual onset over 2 weeks or more. Fungal infections are the common cause for chronic meningitis. Cryptococcal meningitis is one of the commonest fungal form of the disease.Cryptococcus neoformans is an encapsulated yeast causingopportunistic life-threatening infections, particularly in immuno-compromised patients. Duration of the symptoms
Meninges are the lining that covers the brain and spinal cord. Meningitis is inflammation of the meninges around the brain and spinal cord. It is usually caused by an infectious pathogens such as bacteria, virus, fungi and parasites. Depending on he duration of the symptoms, it can be subdivided into acute and chronic form. Bacterial meningitis is a medical emergency requiring immediate treatment. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are the most common causative pathogens. Organisms may deffer according to the age of the patient. Eg:- During neonatal period-E.coli, gram negative bacilli, Listeria monocytogens and Group B streptococci, children older than 3 months-Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae, children between 1-3 months with the organisms from both above mentioned groups. Chronic meningitis is different from acute meningitis as it is an uncommon disease with a gradual onset over 2 weeks or more. Fungal infections are the common cause for chronic meningitis. Cryptococcal meningitis is one of the commonest fungal form of the disease.Cryptococcus neoformans is an encapsulated yeast causingopportunistic life-threatening infections, particularly in immuno-compromised patients.
Headache Pathogens may cross the BBB transcellularly (through human brain microvascular endothelial cells), paracellularly(penetration between barrier cells with and/or without disruption of tight junctions) and “Trojan horse” mechanism(penetration of the barrier cells using transmigration within infected phagocyte) . High-grade bacteremia may precede the meningitis. Once the organism entered through the blood brain barrier, immune system of the body gets activated to release various cytokines and chemikines. Further it releases reactive oxygen radicals to cause more endothelial and nearby tissue damage. These can cause meningeal irritation, increased intracranial damage and cerebral edema. Headache
Pathogens may cross the BBB transcellularly (through human brain microvascular endothelial cells), paracellularly(penetration between barrier cells with and/or without disruption of tight junctions) and “Trojan horse” mechanism(penetration of the barrier cells using transmigration within infected phagocyte) . High-grade bacteremia may precede the meningitis. Once the organism entered through the blood brain barrier, immune system of the body gets activated to release various cytokines and chemikines. Further it releases reactive oxygen radicals to cause more endothelial and nearby tissue damage. These can cause meningeal irritation, increased intracranial damage and cerebral edema.
Fever Inflammation of the meninges and endothelium releases pyrogens causing fever. Fever
Inflammation of the meninges and endothelium releases pyrogens causing fever.
Vomiting Vomiting is a common finding in the meningitis. Vomiting
Vomiting is a common finding in the meningitis.
Sensitivity to light (photophobia) Inability to tolerate light is due to the meningism that indicates inflammatory activation of the trigeminal sensory nerve fibers in the meninges. Sensitivity to light (photophobia)
Inability to tolerate light is due to the meningism that indicates inflammatory activation of the trigeminal sensory nerve fibers in the meninges.
Pain during retraction of the neck Due to the meningeal irritation. Pain during retraction of the neck
Due to the meningeal irritation.
Seizures Altered cerebral perfusion pressure can cause reduction of the cerebral blood flow and ischaemia. Seizures
Altered cerebral perfusion pressure can cause reduction of the cerebral blood flow and ischaemia.
Decreased alertness and drowsiness There can be increased intracranial pressure which may be due to the increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways etc. Neuronal cell death and cerebral edema may also contribute to the drowsiness. Decreased alertness and drowsiness
There can be increased intracranial pressure which may be due to the increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways etc. Neuronal cell death and cerebral edema may also contribute to the drowsiness.
Excessive crying, refusing the feeds Infants and young children present with nonspecific features. Excessive crying, refusing the feeds
Infants and young children present with nonspecific features.
Hearing loss Inflammation can extends to the cranial nerves, when the 8th nerve is involved that causes sensorineural type hearing loss. Hearing loss
Inflammation can extends to the cranial nerves, when the 8th nerve is involved that causes sensorineural type hearing loss.
Visual problems Visual problems Involvement of the optic and other cranial nerves related to the vision can be the cause. Visual problems
Visual problems Involvement of the optic and other cranial nerves related to the vision can be the cause.
History of immunodeficiency People with immune deficiency like malignancy, chemotherapy, long term steroid use, organ transplant and HIV AIDS are particularly vulnerable for the disease. History of immunodeficiency
People with immune deficiency like malignancy, chemotherapy, long term steroid use, organ transplant and HIV AIDS are particularly vulnerable for the disease.
Long term history of ear pain Chronic otitis media can be a source for the meningitis. Long term history of ear pain
Chronic otitis media can be a source for the meningitis.
Involvement of the other organs Cryptococcus like fungi can lodge in the lungs and disseminate hematogenously causing systemic infection when host immunity is compromised. Cryptococcus can infect and spread to the any part of the body, including the skin, eyes, myocardium, bones, joints, lungs, prostate gland, or urinary tract. Involvement of the other organs
Cryptococcus like fungi can lodge in the lungs and disseminate hematogenously causing systemic infection when host immunity is compromised. Cryptococcus can infect and spread to the any part of the body, including the skin, eyes, myocardium, bones, joints, lungs, prostate gland, or urinary tract.

Clinicals - Examination

Fact Explanation
Febrile Fever is one of the most common presenting features. Febrile
Fever is one of the most common presenting features.
Stiff neck Due to the meningeal irritation. Stiff neck
Due to the meningeal irritation.
Kernig sign This is a bedside diagnostic sign used to evaluate suspected cases of meningitis. Patient is kept in supine position, hip and knee are flexed, the knee is slowly extended by the examiner. It is positive if there is a resistance or pain during extension. Kernig sign
This is a bedside diagnostic sign used to evaluate suspected cases of meningitis. Patient is kept in supine position, hip and knee are flexed, the knee is slowly extended by the examiner. It is positive if there is a resistance or pain during extension.
Brudzinki sign Another sign of meningeal irritation. First one hand is kept behind the patient's head and the other on chest in order to prevent the patient from rising, passive flexion of the neck produces reflex flexion of the patient's hips and knees in a positive Brudzinski's sign. Brudzinki sign
Another sign of meningeal irritation. First one hand is kept behind the patient's head and the other on chest in order to prevent the patient from rising, passive flexion of the neck produces reflex flexion of the patient's hips and knees in a positive Brudzinski's sign.
Tachycardia and hypotension Fast heart rate is observed in hypotensive, confused patients. There is increased mortality with meningococcal septicaemia. Tachycardia and hypotension
Fast heart rate is observed in hypotensive, confused patients. There is increased mortality with meningococcal septicaemia.
Mental status changes Alteration in mental status is a poor prognostic indicator. Mental status changes
Alteration in mental status is a poor prognostic indicator.
Focal neurological signs Subdural effusion or cerebral-space-occupying lesions such as abscess formation can cause these symptoms. Focal neurological signs
Subdural effusion or cerebral-space-occupying lesions such as abscess formation can cause these symptoms.
Buldging of fontanelle Due to the increased intracranial pressure. Buldging of fontanelle
Due to the increased intracranial pressure.
Growth retardation and cognitive impairment Ischaemia can cause neuronal cell death and tissue damage, if the developing brain is affected child may ends up with poor growth. Cognitive impairment is most prominent after pneumococcal meningitis. Growth retardation and cognitive impairment
Ischaemia can cause neuronal cell death and tissue damage, if the developing brain is affected child may ends up with poor growth. Cognitive impairment is most prominent after pneumococcal meningitis.
Sensorineural hearing loss Cranial nerve palsies specially VIII the nerve palsy is the cause for this hearing loss. Sensorineural hearing loss
Cranial nerve palsies specially VIII the nerve palsy is the cause for this hearing loss.
Hydrocephalus There can be involvement of the ventricles causing ventriculitis. Inflamed areas are gradually fibrosed with creating an obstruction to the cerebrospinal fluid outflow, leading to hydrocephalus. Hydrocephalus
There can be involvement of the ventricles causing ventriculitis. Inflamed areas are gradually fibrosed with creating an obstruction to the cerebrospinal fluid outflow, leading to hydrocephalus.
Papilloedema This is due to the increased intracranial pressure. Increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways as in hydrocephalus are the possible causes for the raised intracranial pressure. Papilloedema
This is due to the increased intracranial pressure. Increased blood brain barrier permeability, swelling of the cellular elements of the brain, interstitial edema results from obstruction of flow in normal CSF pathways as in hydrocephalus are the possible causes for the raised intracranial pressure.

Investigations - Diagnosis

Fact Explanation
Lumbar puncture Opening pressure will be elevated in meningitis. Regarding the protein content in the CSF, in bacterial meningitis there is markedly elevated protein (< 1 g/l), where as in other types that may be less prominent. Cell count elevation will be vary according to the organism, elevated white blood cell count (<500 cells/μl) with predominant neutrophils is seen in bacterial meningitis. Predominantly mononuclear pleocytosis with elevated lymphocytes, is seen in viral and fungal aetiologies. Mixed pleocytosis is seen in L. monocytogenes, tuberculous, fungal meningitis and partially or incompletely treated meningitis. Lumbar puncture
Opening pressure will be elevated in meningitis. Regarding the protein content in the CSF, in bacterial meningitis there is markedly elevated protein (< 1 g/l), where as in other types that may be less prominent. Cell count elevation will be vary according to the organism, elevated white blood cell count (<500 cells/μl) with predominant neutrophils is seen in bacterial meningitis. Predominantly mononuclear pleocytosis with elevated lymphocytes, is seen in viral and fungal aetiologies. Mixed pleocytosis is seen in L. monocytogenes, tuberculous, fungal meningitis and partially or incompletely treated meningitis.
Blood culture Is done if the patient seems to be septic or lumbar puncture can not be done safely due to the possibility of increased intracranial pressure before the antibiotics. Blood culture
Is done if the patient seems to be septic or lumbar puncture can not be done safely due to the possibility of increased intracranial pressure before the antibiotics.
Computer tomography(CT) scan of the head and Magnetic Resonance Imaging(MRI) CT scan will be even better as the first investigation specially to rule out the possibility of increased intracranial pressure before doing lumbar puncture. MRI will demonstrate the inflammatory dural meningeal process with enhanced uptake over the affected areas. This also show the intracranial complications such as brain edema, hydrocephalus and infarcts. Computer tomography(CT) scan of the head and Magnetic Resonance Imaging(MRI)
CT scan will be even better as the first investigation specially to rule out the possibility of increased intracranial pressure before doing lumbar puncture. MRI will demonstrate the inflammatory dural meningeal process with enhanced uptake over the affected areas. This also show the intracranial complications such as brain edema, hydrocephalus and infarcts.
PCR Important in identification of meningococcal disease. PCR
Important in identification of meningococcal disease.
Zeihl Neelson Staining for Acid fast bacilli Tuberculosis can be a cause for the chronic meningitis. Zeihl Neelson Staining for Acid fast bacilli
Tuberculosis can be a cause for the chronic meningitis.
Full blood count There can be elevated lymphocytes/leucocytes depending on the causative organism. It is also important to exclude the other causes for the fever such as low platelets in viral infections, high white blood cells (leucocytosis) in bacterial infections. Full blood count
There can be elevated lymphocytes/leucocytes depending on the causative organism. It is also important to exclude the other causes for the fever such as low platelets in viral infections, high white blood cells (leucocytosis) in bacterial infections.

Investigations - Management

Fact Explanation
Lumbar puncture Lumbar puncture Is done during the follow up and when the response is poor to the current treatment within 48 hours of treatment. Lumbar puncture
Lumbar puncture Is done during the follow up and when the response is poor to the current treatment within 48 hours of treatment.
CT imaging CT imaging is performed if there is poor response within 48 hours of antibiotic treatment. This may be due to the potential complications of the disease such as CT imaging
CT imaging is performed if there is poor response within 48 hours of antibiotic treatment. This may be due to the potential complications of the disease such as
Erythrocyte sedimentation rate(ESR) and C Reactive protein(CRP) Is elevated due to the inflammation. Erythrocyte sedimentation rate(ESR) and C Reactive protein(CRP)
Is elevated due to the inflammation.
Renal functions and serum electrolytes Syndrome of inappropriate Antidiuretic Hormone secretion is a complication of meningitis. This can cause hyponatraemia. Reduced intake of fluids can cause electrolyte imbalances. Medications may alter the renal functions and therefore baseline value is also needed. Renal functions and serum electrolytes
Syndrome of inappropriate Antidiuretic Hormone secretion is a complication of meningitis. This can cause hyponatraemia. Reduced intake of fluids can cause electrolyte imbalances. Medications may alter the renal functions and therefore baseline value is also needed.
Liver function tests Medications may alter the liver functions and therefore baseline value is needed before the treatment. Liver function tests
Medications may alter the liver functions and therefore baseline value is needed before the treatment.
Random blood sugar Should be done immediately especially if the patient is drowsy, to rule out the hypoglycaemia as cause for drowsiness.
References
Random blood sugar
Should be done immediately especially if the patient is drowsy, to rule out the hypoglycaemia as cause for drowsiness.
References
HIV screening Those who accept HIV screening should have the antibody check up as these infections are common in people infected with HIV. HIV screening
Those who accept HIV screening should have the antibody check up as these infections are common in people infected with HIV.
MRI/CT brain Increased intracranial pressure is evident on MRI by severe sulcal effacement and midline shift on brain imaging. Therefore cranial CT should be done lumbar puncture, specially in those present with focal neurological deficits or seizures and those who have a disturbed consciousness due to the possible risk of cerebral herniation due to raised intracranial pressure. MRI/CT brain
Increased intracranial pressure is evident on MRI by severe sulcal effacement and midline shift on brain imaging. Therefore cranial CT should be done lumbar puncture, specially in those present with focal neurological deficits or seizures and those who have a disturbed consciousness due to the possible risk of cerebral herniation due to raised intracranial pressure.

Management - Supportive

Fact Explanation
Immediate management This is particularly important if the patient presents with confusion and drowsiness. Airway, breathing, circulation, disability and environment need to be attended. Random blood sugar is done to exclude hypoglycaemia. Lumbar puncture needs to be done before the antibiotics started ( if the possibility of increased intracranial pressure can be rule out) If it is not safe to do the LP blood culture is done and antibiotics are started as soon as possible without delay. Immediate management
This is particularly important if the patient presents with confusion and drowsiness. Airway, breathing, circulation, disability and environment need to be attended. Random blood sugar is done to exclude hypoglycaemia. Lumbar puncture needs to be done before the antibiotics started ( if the possibility of increased intracranial pressure can be rule out) If it is not safe to do the LP blood culture is done and antibiotics are started as soon as possible without delay.
Supportive management Antipyretics (i.e. acetaminophen), and antiemetics, (i.e. promethazine), may be given. Hydration should be checked and due to the possibility of syndrome of inappropriate Antidiuretic hormone, 2/3 of maintenance is preferable. Monitoring of the vital parameters should be done during the initial period. Supportive management
Antipyretics (i.e. acetaminophen), and antiemetics, (i.e. promethazine), may be given. Hydration should be checked and due to the possibility of syndrome of inappropriate Antidiuretic hormone, 2/3 of maintenance is preferable. Monitoring of the vital parameters should be done during the initial period.
Management of the complications Ventriculoperitoneal (VP) shunt is placed for the symptomatic improvement in hydrocephalus. If there are seizures, anticonvulsants should be continued and close follow-up should be done. If there is of rapidly increasing intracranial pressure with clinical deterioration where medical treatment failed, surgical decompression has to be considered as a life saving measure. Extracranial complications such as sepsis, disseminated coagulopathy, multiorgan failure, arthritis and electrolyte imbalance, can occur due to the usually syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Management of the complications
Ventriculoperitoneal (VP) shunt is placed for the symptomatic improvement in hydrocephalus. If there are seizures, anticonvulsants should be continued and close follow-up should be done. If there is of rapidly increasing intracranial pressure with clinical deterioration where medical treatment failed, surgical decompression has to be considered as a life saving measure. Extracranial complications such as sepsis, disseminated coagulopathy, multiorgan failure, arthritis and electrolyte imbalance, can occur due to the usually syndrome of inappropriate antidiuretic hormone (SIADH) secretion.
Patient isolation Is needed for the meningococcal disease during the first 24 h of treatment. Patient isolation
Is needed for the meningococcal disease during the first 24 h of treatment.
Follow up As they are vulnerable for complications such as hearing loss, vision problems, growth retardation, learning disability they need to be followed up with hearing, vision and growth assessment. Follow up
As they are vulnerable for complications such as hearing loss, vision problems, growth retardation, learning disability they need to be followed up with hearing, vision and growth assessment.
Chemoprophylaxis Is recommended for close contacts in meningococcal disease. Rifampicin is used. Chemoprophylaxis
Is recommended for close contacts in meningococcal disease. Rifampicin is used.

Management - Specific

Fact Explanation
Antibiotic therapy Aims of the therapy would be to treat the infection and prevention of long-term central nervous system sequelae.
Diagnostic delays should not be a cause fro delaying the immediate antibiotic therapy. Emperical treatment is started for the most likely pathogens and then changed according to the cultural results. Ampicillin 100 mg/kg plus cefotaxime 50 mg/kg 6h or
Ampicillin 100 mg/kg plus an aminoglycoside 8h is used in the neonates. Vancomycin plus cefotaxime or ceftriaxone is used for the patients older than 3 months. Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus vancomycin is used in the age group beyond 50. Ampicillin is added if Listeria is suspected. Usual treatment duration is 10–14 days, 5–7 days will be sufficient for uncomplicated meningococcal disease, and 3–4 weeks of treatment are needed for L. monocytogenes and Enterobacteriacae.
Antibiotic therapy
Aims of the therapy would be to treat the infection and prevention of long-term central nervous system sequelae.
Diagnostic delays should not be a cause fro delaying the immediate antibiotic therapy. Emperical treatment is started for the most likely pathogens and then changed according to the cultural results. Ampicillin 100 mg/kg plus cefotaxime 50 mg/kg 6h or
Ampicillin 100 mg/kg plus an aminoglycoside 8h is used in the neonates. Vancomycin plus cefotaxime or ceftriaxone is used for the patients older than 3 months. Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus vancomycin is used in the age group beyond 50. Ampicillin is added if Listeria is suspected. Usual treatment duration is 10–14 days, 5–7 days will be sufficient for uncomplicated meningococcal disease, and 3–4 weeks of treatment are needed for L. monocytogenes and Enterobacteriacae.
Acyclovir If there are features of meningoencephalitis, acyclovir, 10 mg/kg three times daily,is added as soon as possible and once the diagnosis is confirmed acyclovir is continued for 14 days. Acyclovir
If there are features of meningoencephalitis, acyclovir, 10 mg/kg three times daily,is added as soon as possible and once the diagnosis is confirmed acyclovir is continued for 14 days.
Antifungal therapy Treatment for the cryptococccus is with amphotericin B(0.7-1.0 mg/kg daily), with or without flucytosine(100 mg/kg in four divided doses daily) for 14 days, followed by maintenance therapy with fluconazole 400 mg daily for eight weeks or until the cerebro spinal fluid (CSF) is sterile. If there is a renal dysfunction, a lipid formulation of amphotericin B (AmBisome 4 mg/kg daily)is used. If the person is not tolerating the amphotericin B fluconazole 400-800 mg daily is used. There is no standard therapy for aspergillus meningitis. Intravenous amphotericin B desoxycholateor combination therapy :intravenous amphotericin B with flucytosine and rifampin is used. Combination therapy is to overcome the difficulty in achieving high drug levels in CSF. Amphotericin B-induced myelopathy is an uncommon side effect of treatment.Itraconazole Is used to treat the patients with Aspergillus brain abscesses, Voriconazole is a new antifungal azole that penetrates into the CSF and used for the treatment of brain abscess due to Aspergillus. Antifungal therapy
Treatment for the cryptococccus is with amphotericin B(0.7-1.0 mg/kg daily), with or without flucytosine(100 mg/kg in four divided doses daily) for 14 days, followed by maintenance therapy with fluconazole 400 mg daily for eight weeks or until the cerebro spinal fluid (CSF) is sterile. If there is a renal dysfunction, a lipid formulation of amphotericin B (AmBisome 4 mg/kg daily)is used. If the person is not tolerating the amphotericin B fluconazole 400-800 mg daily is used. There is no standard therapy for aspergillus meningitis. Intravenous amphotericin B desoxycholateor combination therapy :intravenous amphotericin B with flucytosine and rifampin is used. Combination therapy is to overcome the difficulty in achieving high drug levels in CSF. Amphotericin B-induced myelopathy is an uncommon side effect of treatment.Itraconazole Is used to treat the patients with Aspergillus brain abscesses, Voriconazole is a new antifungal azole that penetrates into the CSF and used for the treatment of brain abscess due to Aspergillus.
Anti tuberculosis treatment When chronic meningitis is suspected, empirically treated with isoniazid, rifabutin, ethambutol, pyrazinamide, streptomycin. Anti tuberculosis treatment
When chronic meningitis is suspected, empirically treated with isoniazid, rifabutin, ethambutol, pyrazinamide, streptomycin.
Steroids Dexamethasone (4 mg every six hours)is given to reduce the inflammatory response occur during the anti microbial treatment. Steroids
Dexamethasone (4 mg every six hours)is given to reduce the inflammatory response occur during the anti microbial treatment.

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