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Brain Abscess

Brain Abscesses

A brain abscess or cerebral abscess is formed as a result of an inflammation and infection of the brain parenchyma secondary to remote or contiguous infections.


Presentation

Patients with brain abscess remain symptomatic for up to 2 weeks in 60% of cases, depending on the severity and the timing of medical intervention. The symptoms are mainly reflective of the size and location of the abscess. Classically, however, fever, headache, and focal neurologic impairments are the main features of brain access occurring in up to 50% of cases. Headache is the most constant feature of brain abscess occurring in 70% of patients. The headache is usually very severe (unresponsive to over-the-counter pain medications) and ipsilateral to the site of the abscess. 

Altered mental status with focal neurologic impairments occurs in 65% of cases while fever occurs in approximately 50% of cases. Altered sensorium may be a result of cerebral edema and may progress to coma. Less common findings include seizures, nausea, vomiting, neck stiffness, and papilledema. Vomiting usually indicates an elevated intracranial pressure. An acute presentation of headache preceding signs of meningeal irritation is strongly suggestive of rupture of the brain abscess.

The symptomatology of brain abscess often reflects the site of the abscess; brain stem abscesses present with facial paresis, dysphagia, and hemiparesis alongside the classic triad of headache, fecver, and neurological deficits. Cerebellar abscesses may present symptoms of movement incordination such as nystagmus, dysmetria, and ataxia. A frontal abscess would typically present with cognitive deficits, poor concentration, aphasia, grand mal seizures, and hemiparesis. Abscesses in the temporal lobe present with ipsiateral aphasia( if it affects the speech center) and visual defects, while occipital lobe abscesses present typically with nuchal rigidity.

Fever
  • Signs and symptoms [ edit ] Fever, headache, and neurological problems, while classic, only occur in 20% of people with brain abscess. [2] The famous triad of fever, headache and focal neurologic findings are highly suggestive of brain abscess.[en.wikipedia.org]
  • Symptoms can include fever, severe headache, nausea and vomiting, and changes in behavior. The goal of treatment is to reduce the pressure in the head and properly drain the infection.[urmc.rochester.edu]
  • Fever and headache subsided soon after antibiotic treatment. However, 2 days after discontinuation of the antibiotics, fever (39 C) recurred, and the patient became drowsy.[stroke.ahajournals.org]
  • Fever, chills, and leukocytosis may develop before the infection is encapsulated, but they may be absent at presentation or subside over time.[merckmanuals.com]
  • Clinically, the patients usually present with vomiting, fever, headache, seizures , focal neurologic signs and eventually, papilloedema and coma, but these manifestations can be subtle in the initial stages [ 3 , 5 ].[esciencecentral.org]
Chills
  • Symptoms of a Salmonella infection include fever, nausea, vomiting, chills. and diarrhea that is sometimes bloody.[foodpoisoningbulletin.com]
  • […] neck stiffness, especially when it occurs with fevers and chills sensitivity to light In babies and young children, most of the symptoms are similar.[healthline.com]
  • They may include: Changes in mental status , such as confusion, slow response or thinking, unable to focus, or sleepiness Decreased ability to feel sensation Fever and chills Headache, seizures , or stiff neck Language problems Loss of muscle function[nlm.nih.gov]
  • Fever, chills, and leukocytosis may develop before the infection is encapsulated, but they may be absent at presentation or subside over time.[merckmanuals.com]
Cyanotic Congenital Heart Disease
  • This paper records the experience of one neurosurgical service with 13 cases of brain abscess in patients with cyanotic congenital heart disease in a 13-year period. Six of the 13 patients in this series had successful surgical treatment.[pediatrics.aappublications.org]
  • Abscess formation can also develop following blood-borne spread from a remote site - eg, in patients with cyanotic congenital heart disease, endocarditis, and dental caries. In at least 20% of cases no source can be identified.[patient.info]
  • Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease (CHD) accounting for 10%.[esciencecentral.org]
  • A brain abscess may form after direct extension of intracranial infections such as subdural empyema, sinusitis, and mastoiditis, hematogenous spread from remote infections including bacterial endocarditis, cyanotic congenital heart disease (right-to-left[symptoma.com]
  • These lesions occur most often with infections of the chest or as a result of cyanotic congenital heart disease.[spinalmedicine.com]
Malaise
  • Symptoms include fever, malaise, irritability, severe headache, convulsions, vomiting, and other signs of intracranial hypertension.[medical-dictionary.thefreedictionary.com]
  • The following morning, Wednesday, I visit my GP, who examines me and finds nothing obvious to explain my growing malaise. Could I have labyrinthitis , a viral inner-ear infection? She agrees it seems the most likely diagnosis.[theguardian.com]
Vomiting
  • WOF signs of increased ICP: decreased LOC, vomiting, abnormal pupil response and depressed respirations.[nurseslabs.com]
  • This elevation similarly stimulates the medullary vomiting center and area postrema , leading to morning vomiting. Other symptoms and findings depend largely on the specific location of the abscess in the brain.[en.wikipedia.org]
  • Any symptoms that suggest a worsening infection, such as fever and vomiting, should be reported to your GP immediately. If your GP isn't available, contact your local out-of-hours service or call NHS 111 .[nhs.uk]
  • Other symptoms in your child can include: projectile vomiting high-pitched crying spasticity in the limbs How is a brain abscess diagnosed? Many of these symptoms closely resemble other diseases or health problems.[healthline.com]
  • Symptoms can include fever, severe headache, nausea and vomiting, and changes in behavior. The goal of treatment is to reduce the pressure in the head and properly drain the infection.[urmc.rochester.edu]
Nausea
  • A doctor visits, says it is probably BPPV and gives me another anti-nausea shot.[theguardian.com]
  • Headache, sleepiness, nausea, weakness on one side of the body, or seizures may result. Imaging of the head is required. Antibiotics are given, sometimes followed by surgery. Brain abscesses are fairly uncommon.[merckmanuals.com]
  • If you also have nausea, vomiting, seizures, personality changes or muscle weakness, seek emergency care. Prognosis Without treatment, a brain abscess can be fatal. Most people with a brain abscess are treated successfully.[womenshealthmag.com]
  • Headache, nausea, vomiting, lethargy, seizures, personality changes, papilledema, and focal neurologic deficits develop over days to weeks; fever may be absent at presentation. Do contrast-enhanced MRI or, if unavailable, contrast-enhanced CT.[merckmanuals.com]
Headache
  • Classically, however, fever, headache, and focal neurologic impairments are the main features of brain access occurring in up to 50% of cases. Headache is the most constant feature of brain abscess occurring in 70% of patients.[symptoma.com]
  • Signs and symptoms [ edit ] Fever, headache, and neurological problems, while classic, only occur in 20% of people with brain abscess. [2] The famous triad of fever, headache and focal neurologic findings are highly suggestive of brain abscess.[en.wikipedia.org]
  • A man died 72 hours after suffering crippling headaches when doctors failed to diagnose a deadly infection.[dailymail.co.uk]
  • […] low in density due to necrosis of brain tissue Biopsy confirmed this to be a glioma (malignant brain tumour) Cerebral abscesses can look identical and so should be considered as a differential diagnosis of a ring-enhancing lesion Clinical information Headache[radiologymasterclass.co.uk]
  • More than 75% of people with a brain abscess have a dull, achy headache. For many people this is the only symptom.[womenshealthmag.com]
Seizure
  • Patients and families need to be advised of neurologic deficits that may remain after treatment (hemiparesis, seizures, visual deficits, and cranial nerve palsies).[nurseslabs.com]
  • If seizures are a problem you may need anticonvulsant medications, which may continue even after the abscess has been successfully treated.[womenshealthmag.com]
  • These include: slurred speech muscle weakness or paralysis seizures occurring in a person with no previous history of seizures If you or someone you know experiences any of these symptoms, phone 999 immediately and ask for an ambulance.[nhs.uk]
Confusion
  • The most frequent presenting symptoms are headache, drowsiness, confusion , seizures , hemiparesis or speech difficulties together with fever with a rapidly progressive course.[en.wikipedia.org]
  • Symptoms of a brain abscess Brain abscess symptoms may include: Headache Vomiting Fever Confusion and general changes in mental state, including inability to focus Vision changes Weakness and difficulty with muscle function Seizures Decreased sensation[upmc.com]
  • Headache , which is often severe and cannot be relieved by taking painkillers Changes in mental state - for example appearing very confused Weakness or paralysis on one side of the body A high temperature (fever) of or above 38c (100.4f) Seizures (fits[webmd.boots.com]
  • Common presenting symptoms include fever, headache, changes in mental state (drowsiness, confusion), focal neurological deficits, grand mal seizures, nausea and vomiting, neck stiffness.[patient.info]
  • Symptoms of a brain abscess The symptoms of a brain abscess may develop quickly or slowly but can include: headache – which is often severe, located in a single section of the head and can't be relieved with painkillers changes in mental state – such as confusion[nhs.uk]
Stroke
  • National Survey of Stroke. Stroke . 1981;12(suppl 1):I-13-I-31. Silver FL, Norris JW, Lewis AJ, Hachinski VC. Early mortality following stroke: a prospective review. Stroke . 1984 ; 15 : 492 -496. Bamford J, Dennis M, Sandercock P, Burn J, Warlow C.[stroke.ahajournals.org]
  • Feet Carpal Tunnel Syndrome Diet and Nutrition Emergency Supplies Fall Prevention Fibromyalgia Fitness and Health Hearing Loss Home Health Care and Safety Industrial and Public Health Safety Occupational Health Safety Sight Impaired Sleeping - COPD Stroke[activeforever.com]
  • Colin Mayes was taken to hospital in Swansea after being struck by the extreme pain as well as numbness, with medics fearing he was suffering a stroke.[dailymail.co.uk]
  • However, autopsy studies have detected a PFO in 20–35% of adults, and a cross-sectional study has implicated PFOs in the pathogenesis of embolic stroke [ 7 – 9 ].[jmedicalcasereports.com]
  • […] genes Risk factors include: Stress or fatigue Weather extremes Oily skin, or skin problems such as acne Heavy alcohol use, or using lotions that contain alcohol Obesity Nervous system disorders, including Parkinson disease , traumatic brain injury, or stroke[aspirus.org]
Neck Stiffness
  • Symptoms Patients may complain of headaches, low-grade fever, neck stiffness, and nausea or vomiting. Some will present with seizures or mental status changes.[neurosurgery.ufl.edu]
  • stiffness, especially when it occurs with fevers and chills sensitivity to light In babies and young children, most of the symptoms are similar.[healthline.com]
  • Other symptoms may include nausea and vomiting, neck stiffness, seizures, personality changes and muscular weakness on one side of the body. Diagnosis Diagnosing a brain abscess is not easy because the early symptoms are so general.[womenshealthmag.com]

Workup

A contrast-enhanced MRI is the diagnostic modality of choice to confirm a suspected case of brain abscess. A contrast-enhance CT is a useful alternative if an MRI is unavailable. Either imaging study classically reveals a mass with ring enhancement. However, this finding only indicates a space-occupying lesion, therefore, is indistinguishable from other space-occupying lesions such as tumors. 

CT-guided aspiration or surgical excision of the abscess may be necessary for culture. A lumbar puncture is contraindiacated in the presence of an intracranial space-occupying lesion.

Cerebrospinal Fluid Abnormality
  • Lumbar puncture is not done because it may precipitate transtentorial herniation and because CSF findings are nonspecific (see Table: Cerebrospinal Fluid Abnormalities in Various Disorders ).[merckmanuals.com]
Suppression
  • Those with weakened immune systems, chronic disease, or who take drugs that suppress the immune system are most at risk of developing brain abscesses.[upmc.com]
  • It can be a complication in patients whose immune systems have been suppressed through therapy or disease.[nurseslabs.com]
  • […] will likely prescribe a shampoo, cream, ointment, or lotion containing either a stronger dose of the above medicines, or contain any of the following medicines: Cicloprox Sodium sulfacetamide A corticosteroid Tacrolimus or pimecrolimus (medicines that suppress[aspirus.org]
  • The following raise your chance of developing a brain abscess: A weakened immune system (such as in people with HIV/AIDS ) Chronic disease, such as cancer Drugs that suppress the immune system (corticosteroids or chemotherapy ) Congenital heart disease[nlm.nih.gov]
Elevated Sedimentation Rate
  • Laboratory investigation revealed severe leucocytosis (WBC count: 16, 6 1O³) with 94, 3% polymorph nuclear cells, 0, 4 % lymphocytes and elevated sedimentation rate of 60 mm / h. HBs ag antiHIV1-2 and ag anti HCV were negative.[ajns.paans.org]
Brain Edema
  • This may be done surgically by opening the cranium, or medically by administering hypertonic solutions of slowly metabolized materials, such as mannitol, intravenously. brain edema an important part of a number of acute diseases, e.g. lead poisoning,[medical-dictionary.thefreedictionary.com]
  • The final stage of brain abscess is a consequence of progressive encephalitis, or brain edema and elevated intracranial pressure with compression and displacement of the brain stem, causing paralysis of the respiratory center.[minclinic.ru]

Treatment

Antibiotics are the mainstay of treatment of brain abscess. This could be combined with surgical drainage or stereotactic aspiration of the abscess. Aspiration or drainage is mostly indicated for isolated abscesses which are greater than 2 cm in diameter and are also surgically accessible. Abscesses less than 2 cm in diameter can be treated only with antibiotics.

Empirical antibiotic therapy consists of IV cefotaxime 2g every 4 hours or IV ceftriaxone 2g 12 hourly plus IV metronidazole (if bacteroides species is suspected) at 5mg/kg loading dise, then 7.5mg/kg IV 6 hourly or vancomycin 1g 12 hourly (if  Staphylococcus aureus or MRSA is suspected). Treatment are thereafter altered in accordance to the results of culture and sensitivity.

Treatment monitoring with serial MRI or CT is necessary. Unresolved abscesses with antibiotic treatment require surgical drainage. Corticosteroids are indicted in cases of elevated intracranial pressure and is given as dexamethasone IV 10mg stat, followed by 4mg 6 hourly for 4 days. Additionally, prophylactic anticonvulsant may be administered.

Prognosis

The prognosis of brain abscess has improved significantly over the years. Prompt diagnosis and early initiation of treatment reduce mortality significantly. However, in less than half of the survivors, there may be irreversible neurologic sequelae such as hemiparesis.

Mortality rate from brain abscess is maintained at less than 13% with altered mental status being the main negative prognostic factor. Other poor prognostic factors include chronic use of steroids, co-existing cyanotic heart disease, immunosuppresive status, norcardia asteroides or naegleria fowleri as the causative organism, and intraventricular abscess rupture.

Etiology

Brain abscess may arise from bacterial, fungal, or parasitic infections. Furthermore, it could occur from infections of polymicrobial origin. However, at least 10% of brain abscesses are idiopathic, most of which are assumed to be of bacterial etiology [3].

A brain abscess may form after direct extension of intracranial infections such as subdural empyema, sinusitis, and mastoiditis, hematogenous spread from remote infections including bacterial endocarditis, cyanotic congenital heart disease (right-to-left shunt) or intravenous drug abuse. Penetrating head wounds from trauma or neurosurgical procedures are also common etiopathogenic factors of brain abscesses.

Common agents implicated in brain abscess include staphylococcus species, Streptococcus pyogenes, Streptococcus milleri, fungal species including aspergillus fumigatus, candida albicans, and parasitic agents such as cryptocoocus neoformans, toxoplasma gondii, trypanosoma species, naegleria fowler, entamoeba histolytica, and echinicoccus granulosus.

Bacterial causes of brain abscess are usually anaerobic, but may be mixed with aerobes. Staphylococcal infection is implicated in endocarditis and penetrating head wounds. Toxoplasma gondii is the most common causative agent of brain abscess in HIV patients.

Epidemiology

Approximately 2,500 cases of brain abscess are diagnosed every year in the United States [3] [4]. The disease is most common in adults under 30. Furthermore, the most pediatric population affected are children within the ages of 4 to 7 years. Brain abscess is more prevalent in areas with high prevalence of HIV [5]. Generally, brain abscesses constitute a small proportion of space-occupying intracranial lesions.

In the United states, over the years, the incidence of brain abscess has increased due to an increase in prevalence of HIV. Fungal brain abscess has also been noted to be of a higher frequency as a result of frequent administration of broad-spectrum antibiotics and immunosuppressants.

Generally, brain abscess is a rare disease in developed countries, being very common in developing nations. This is attributable to the frequency of risk factors of the disease in those countries.

Mortality from brain abscesses have reduced significantly due to the availability of diagnostic imaging studies and antibiotic therapy. Ruptured brain abscess , however, is associated with up to 80% mortality rate. Neurologic complications may occur in 20-79% of survivors of brain abscess and these complications are commonly due to delayed diagnosis and late commencement of antibiotic treatment [6].

Brain abscess occurs more commonly in males than females. Furthermore, it is more common before the forth decade of life. In children, the most common risk factor for subdural empyma is bacterial meningitis, therefore, hemophilus influenza vaccine has contributed to the significant reduction in the prevalence of brain abscess in young children.

Sex distribution
Age distribution

Pathophysiology

Brain abscesses often form in the white matter adjacent to the cerebral cortex, at which location there is high vascularity which may promote fibrosis and encapsculation [3].

Cerebral abscesses are formed in three stages which include [7]:

1. Early cerebritis: this is the initial stage and is characterized by inflammatory changes such as neutrophil infiltration and activation of glial cells at the site of infection. Tissue necrosis is also observed at this stage. Early cerebritis usually lasts for about 3 days before progressing to the next stage.

2. Late cerebritis: this stage lasts for the next 5 - 6 days and is characterized by further inflammatory changes mainly comprising of lymphocytic infiltration.

3. Frank abscess formation: this final stage usually occurs after the 10th day and is characterized by focally encapsulated purulent collection.

The blood-brain-barrier is highly permeable in all stages of abscess formation as evidenced by contrast enhancement on imaging studies. The advantage of this high permeability of the blood-brain-barrier is the high penetrance of antibiotics.

The commonest site of brain abscesses include the fronto-temporal, fronto-parietal, cerebellar and occipital lobes [8]. 

Generally, development of brain abscesses from contiguous infections make up the most common route of the disease, comprising 45-50% of cases. Whereas, hematogenous spread and penetrating head injury makes up 25% and 10% of cases of brain abscess respectively. The remaining 15% of cases are idiopathic [9].

Common contiguous infections which lead to formation of brain abscesses include osteomyelitis of the posterior walls of the paranasal sinuses, chronic otitis media, mastoididis, and dental infections [10]. Of all the common intracranial sources of brain abscess, sinusitis is least common [11]. Multiple abscesses are more frequently caused by hematogenous spread from remote infections and they often occur within the areas of distribution of the middle cerebral artery. The commonest site of multiple abscesses from hematogenous spread is the frontal lobe while the occipital lobe is the least common site [12]. The parietal and cerebellar lobes are also common sites of hematogenous seeding from remote infections.

Prevention

Prevention of brain abscesses involves prevention and proper management of risk factors.

HIV patients on highly active antiretroviral therapy (HAART) reduce their risk of brain abscess. Proper and aggressive treatment of high-risk intracranial infections also significantly reduce the risk and incidence of brain abscesses. However, some studies have reported that progression of brain abscess from sinusitis may occur despite appropriate treatment [13]. Antibiotic prophylaxis prior to invasive dental procedures may also reduce the risk of development of brain abscess [14].

Summary

Brain abscesses are life-threatening infections and are a subset of intracranial abscesses [1].

Brain abscesses are caused by bacteria, fungi, and parasites, often in the setting of an existing risk factor which may include contiguous intracranial infections, remote infections, immunosuppressive states, chonic steroid use, cyanotic congenital heart disease, penetrating head injuries, and neurosurgical procedures. However, 15% of cases of brain abscess are idiopathic [2].

Brain abscesses present with a classic triad of fever, severe headache, and nuchal rigidity. These features, however, occur in about 70% of patients, nonetheless, they make up the most constant features of a brain abscess. Other common features of a brain abscess include altered sensorium, hemiparesis, facial paresis, dysmetria, visual disturbances, and signs of a raised intracranial pressure. The prevailing symptoms are often reflective of the size and site of the abscess.

Antibiotics are the mainstay of treatment of brain abscesses, however, antibiotic therapy may be combined with surgical drainage of the abscess if certain criteria are met. Early diagnosis and prompt treatment are often associated with significant reduction in mortality.

Patient Information

Overview.

A brain abscess is a collection of pus and dead cells in the brain. It may be caused by a bacterial, fungal, or parasitic infection.

Etiology/Pathophysiology.

Brain abscesses usually occur due to infection of the brain tissue by microrganisms such as bacteria, fungi, and parasites. These infections usually occur in the presence of a predisposing factor such as HIV, a weak immune system, infections of tissues in the head such as ear infections, sinus and dental infections, infections in organs far from the brain such as an infection of the lining of the heart, intravenous drug abuse, and surgical procedures or injuries to the head in which microorganisms gain easy entry from the exterior into the brain.

Infections of tissues in the head make up the main source of brain abscesses. However, in a few cases, the source of the abscess may not be determined.

Presentation.

The symptoms which classically occur in patients with brain abscess include fever, headache, and loss of brain control over certain activities such as muscle movement, speech, and facial expression. These symptoms may occur suddenly or gradually. Usually, the headache occurs on the side of the head where the abscess is located and it is often unresponsive to over-the-counter pain killers.

Other common symptoms of brain abscess include disorientation, confusion, coma, convulsions, visual impairments, difficulty speaking or moving one part of the body, and inability to concentrate.

Workup.

Once doctors suspect a brain abscess in a patient from the symptoms or findings on examination of the nervous system, they order a magnetic resonance imaging or contrast tomography (CT) scan to locate the abscess. The abscess may also be tested to determine what organism has caused it.

Other tests that doctors might order include blood culture, complete blood count, and chest X-rays.

Treatment.

A brain abscess must be treated urgently as it is a fatal disease. Antibiotics are the mainstay of treatment and they may be combined with surgical drainage of the abscess. However, surgery is not recommended if the abscess is small in diameter (< 2cm), if there is more than one abscess, or if the abscess would be too difficult to reach.

The antibiotic treatment needs to be given for several weeks to be effective and the abscess needs to be monitored for regression. There are other drugs which help in the management of a patient with brain abscess, these include anticonvulsants, steroids, and diuretics (which reduce swelling of the brain by removing excess fluid from it)

Prognosis.

A brain abscess is very deadly if left untreated. Therefore, a prompt diagnosis with timely commencement of treatment reduces the risk of death from a brain abscess. However, some patients who are successfully treated may have some permenant problems with their brain function.

Prevention.

Prevention is very vital in reducing the risk of this disease. Prevention entails timely and adequate treatment of infections in the head, HIV , and heart infections. HIV patients should also be on appropriate and adequate treatment to prevent this disease. 

References

Article

  1. Muzumdar D, Jhawar S, Goel A. Brain abscess: an overview. Int J Surg. 2011. 9(2):136-44. 
  2. Mathisen GE, Johnson JP. Brain abscess. Clin Infect Dis. 1997 Oct. 25(4):763-79. 
  3. Hall WA, Truwit CL. The surgical management of infections involving the cerebrum. Neurosurgery. 2008;62(Suppl 2):519S-530S.
  4. Hall WA. Brain abscess: still a surgical entity. World Neurosurg. 2011;75:616-617.
  5. Bensalem MK, Berger JR. HIV and the central nervous system. Compr Ther. 2002 Spring. 28(1):23-33.
  6. Tseng JH, Tseng MY. Brain abscess in 142 patients: factors influencing outcome and mortality. Surg Neurol. 2006 Jun. 65(6):557-62; discussion 562.
  7. Britt RH, Enzmann DR, Placone RC Jr, et al. Experimental anaerobic brain abscess. Computerized tomographic and neuropathological correlations. J Neurosurg. 1984;60:1148-1159.
  8. Nielsen H, Gyldensted C, Harmsen A. Cerebral abscess. Aetiology and pathogenesis, symptoms, diagnosis and treatment. A review of 200 cases from 1935-1976. Acta Neurol Scand. 1982 Jun. 65(6):609-22.
  9. Helweg-Larsen J, Astradsson A, Richhall H, Erdal J, Laursen A, Brennum J. Pyogenic brain abscess, a 15 year survey. BMC Infect Dis. 2012. 12:332.
  10. Brook I, Friedman EM. Intracranial complications of sinusitis in children. A sequela of periapical abscess.Ann Otol Rhinol Laryngol. 1982 Jan-Feb. 91(1 Pt 1):41-3.
  11. Glickstein JS, Chandra RK, Thompson JW. Intracranial complications of pediatric sinusitis. Otolaryngol Head Neck Surg. 2006 May. 134(5):733-6.
  12. Carpenter J, Stapleton S, Holliman R. Retrospective analysis of 49 cases of brain abscess and review of the literature. Eur J Clin Microbiol Infect Dis. 2007 Jan. 26:1-11. 
  13. Jones NS, Walker JL, Bassi S, et al. The intracranial complications of rhinosinusitis: can they be prevented? Laryngoscope. 2002;112:59-63.
  14. Corson MA, Postlethwaite KP, Seymour RA. Are dental infections a cause of brain abscess? Oral Dis. 2001;7:61-65.

Symptoms

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