Intramedullary spinal cord abscesses are infrequently encountered in everyday neurosurgical practice.

Hart reported the earliest documented spinal cord abscess in 1830. Since then, fewer than 100 cases have been reported in the medical literature. With modern antibiotics and neurosurgical techniques, even fewer of these infections are expected to be encountered in the future. Since the original publication of this article, several other case reports have been published that discuss intramedullary spinal cord abscesses.[1] These case reports, while detailing several unusual presentations of patients with intramedullary spinal cord abscesses, add little to the core concepts promulgated in the original article. Patients with intramedullary spinal cord abscesses present with neurological findings related to the level of spinal cord involvement; MRI with gadolinium is still the procedure of choice for early diagnosis; and successful outcomes depend upon early diagnosis, aggressive surgical treatment, and appropriate antibiotic treatment following surgery. Even when these guidelines are followed, 70% of patients are left with neurological sequelae. See the image below.

Abscess that compresses the spinal cord and its vasculature.

Problem
Spinal cord abscesses arise in spinal cord parenchyma and can be solitary or multiple, contiguous or isolated, and chronic or acute, depending upon the organism and individual patient. As may be expected, solitary lesions are more common and most likely appear in the thoracic cord. Holocord abscesses have been reported in approximately 5 patients. Some authors divide these abscesses into primary and secondary, depending on the source of infection. Abscesses are considered primary when no other infection source can be found. Secondary abscesses arise from another infection site, either distant from or contiguous to the spinal cord, most commonly from the lung, spine, heart valves, and genitourinary system. Intramedullary spinal cord abscesses most commonly arise from a secondary source such as the cardiopulmonary system or from a contiguous source such as the mediastinum. These classifications rarely affect treatment or patient outcome.

Epidemiology
Frequency

Fewer than 100 cases have been reported. Spinal cord abscesses occur more frequently in males than females with a peak incidence in the first and third decades of life. Too few cases have been reported to define any racial predilection. Patients with a history of intravenous drug abuse are at particularly high risk, as are other immunocompromised patients such as those with HIV, diabetes, or multiple organ failure.

Etiology
The most common organisms cultured from spinal cord abscesses include Staphylococcus and Streptococcus species, followed by gram-negative organisms. Mixed flora abscesses are also encountered. Other unusual organisms have been reported, including Actinomyces, Listeria, Proteus, Pseudomonas, Histoplasma capsulatum, and the tapeworm Sparganum. In 1899, Hoche demonstrated that abscesses may occur in areas of infarction, thus explaining the common incidence of septic spread to the lower half of the thoracic cord. The Batson plexus (the confluence of epidural veins in the spinal canal) may contribute to the origin of an abscess by allowing organisms to lodge and thus develop in the spinal cord and its surrounding parenchyma.

Pathophysiology
Spinal cord abscesses have many of the same characteristics of abscesses in other locations. Blood vessel involvement surrounded by an area of infection characterizes hematogenous spread. Areas of softening and early abscess formation characterize subacute infections (1-2 wk duration), whereas a classic abscess wall of fibrotic gliosis surrounding necrotic purulent material characterizes chronic infections. However, spinal cord abscesses do not destroy fiber tracts. Instead, the abscess displaces fiber tracts and spreads along axonal pathways.[2]

Presentation
As with most neurological diseases, signs and symptoms depend upon the abscess location and duration. In an acute presentation, symptoms of infection (eg, fever, chills, back pain, malaise) are common. Neurological symptoms and signs include weakness, paresthesia, dysesthesia, bladder and bowel incontinence, and acute paraplegia. The neurological signs and symptoms are dependent upon the location in the spinal cord of the abscess; the most common location for an intramedullary abscess is the thoracic spinal cord. Clinical symptoms are similar to those of patients with epidural abscesses, but percussion tenderness is not noted. In more chronic cases, signs and symptoms mimic those of an intramedullary tumor, and neurological symptoms predominate over those of a systemic infection. The neurological progression is gradual. A high degree of awareness is necessary to diagnose chronic spinal cord abscess; in contrast, acute abscesses are generally encountered in extremely ill patients presenting with acute onset of back pain.[3]

Indications
The presumptive diagnosis of intramedullary abscess requires prompt definitive diagnosis. This of course necessitates demonstration of an infection with subsequent identification of

that organism; therefore, laminectomy to diagnose and culture the organism is usually required.

Relevant Anatomy
Since abscesses may occur anywhere along the spinal axis, anatomy varies with location involved. As noted above, the most common location for an intramedullary abscess is the posterior thoracic spinal cord.

Contraindications
No well-defined contraindications exist to treating spinal cord abscesses.

Laboratory Studies

Cerebrospinal fluid (CSF) examination may show elevated protein and leukocyte levels but can be within reference ranges. Cultures with sensitivities from abscess aspirate are needed to identify infective organisms. Cultures should include tests for aerobic and anaerobic bacteria, fungi, and tuberculosis. Slides should also be taken to look for parasites. Even with appropriate culture techniques, 25-40% of abscesses are microbiologically sterile.

Imaging Studies

The procedure of choice for diagnosing a possible intramedullary spinal cord abscess is gadolinium-enhanced MRI.[4, 5, 6, 7] o If a high probability of spinal abnormality is present, an MRI of the area will demonstrate the mass. o MRI is also valuable in demonstrating any associated disease process (eg, epidural or subdural infection, bone involvement, dermal sinus).[8] o MRI does not differentiate among the types of masses, ie, between tumor and abscess, although an abscess generally demonstrates ring-enhancement, while a metastatic lesion generally demonstrates a nodular pattern of enhancement. o Spinal cord abscesses produce homogenous spinal cord enlargement on T1weighted images but produce high signal intensity on T2-weighted images. o The abscess margin enhances brightly with gadolinium. Most other diagnostic modalities are ineffectual in showing an abscess. o Plain radiographs show only bony changes (if present). o Myelography usually shows only widening of the spinal cord.

Medical Therapy
Treatment involves a combination of 3 modalities: surgical drainage of the abscess cavity, identification of the infecting organism, and administration of appropriate antibiotics for a proper length of time. During the entire course of treatment, steroids are used to reduce spinal cord swelling and edema associated with the abscess.

As mentioned in Lab Studies, cultures of the abscess cavity should include tests for aerobic and anaerobic bacteria, fungi, and tuberculosis. Slides looking for parasites are also recommended. Prior to identifying the organism, administer a broad-spectrum antipenicillinase penicillin. Once the organisms are identified and sensitivities established, the appropriate antibiotics can be administered.

Surgical Therapy
Once MRI has localized the abscess, laminectomy is performed to expose the lesion and surrounding cord.[5] Laminectomy is usually performed one level above and below the abscess edges for complete abscess visualization. The dura is opened and the area of spinal cord involvement, as indicated by swelling, hemorrhage, and distended veins, is identified. At this point, aspiration of the lesion is performed for culture of both aerobic and anaerobic organisms as well as for fungus and tuberculosis. Immediately complete Gram stain and India ink preparation. Perform a myelotomy over the length of the abscess, and completely drain the abscess cavity. Irrigate the wound and abscess cavity with antibiotic solution, and perform closure in anatomical layers. A drain is optional.

Preoperative Details
During the preoperative and postoperative phases, dexamethasone is used to reduce cord swelling. The usual dosage is 4-10 mg every 6 hours.

Postoperative Details
Intravenous antibiotic therapy is continued for at least 4 weeks following surgery. During the preoperative and postoperative phases, dexamethasone is used to reduce cord swelling. The usual dosage is 4-10 mg every 6 hours. Steroids are tapered on a delayed basis (eg, after 2 wk of treatment).

Follow-up
Obtain a follow-up MRI to detect recurrence of the abscess. However, enhancement of the cavity will likely continue for several weeks. For excellent patient education resources, visit eMedicineHealth's Infections Center and Brain and Nervous System Center. Also, see eMedicineHealth's patient education articles Brain Infection and Antibiotics.

Complications
Neurologic deficits such as paraplegia may occur, depending upon the rapidity with which the abscess is diagnosed and treated and the spinal cord level. Since the abscess and inflammatory process involve the surrounding vasculature, spine cord infarction may lead to irreversible paraplegia.

Outcome and Prognosis

The outcome is generally good with appropriate use of antibiotics and surgical treatment. However, the abscess location determines the residual neurologic deficits. The patient's degree of sepsis ultimately establishes overall mortality. With the advent of modern antibiotics and lower surgical mortality, most abscesses are treated successfully. With steroids and more timely localization through MRI, neurologic deficits can be reduced. However, patients may be affected by devastating neurologic sequelae and may succumb to this disease. Overall mortality rates vary from 10-20%. Moreover,

approximately 70% of patients demonstrate residual neurological sequelae following appropriate treatment. Importantly, a significant percentage of patients have recurrence of the abscess. Consequently, repeat MRIs are essential in patients' longterm and follow-up care.

Future and Controversies

With modern antibiotics and neurosurgical techniques, even fewer spinal cord abscesses are expected to be encountered in the future.

Paraspinal Abscess

Overview of Paraspinal Abscess

Infections can develop in the area immediately adjacent to the spine. These can come from infectious processes that involve the bones or intervertebral discs. They can, also, come from infections that involve the structures of the abdomen, the chest or the neck. Paraspinal abscess's can lead to damage or destruction of the spine or the discs. Left untreated, involvement of the spinal canal or nervous system may also occur. Chronic infections of the spine, such as tuberculosis, can lead to spinal deformity and paralysis. Occasionally, paraspinous abscess's that develop in the lumbar spine can have pus track along the psoas muscle towards the groin. It can result in lower abdominal pain or a lower abdominal mass.

Causes of Paraspinal Abscess

Systemic infection, or sepsis, and transient inoculation of the blood stream with bacteria, bacteremia, can both lead to paraspinal infections. The infections may originate by bacteria deposited in areas adjacent to the spine. Infections of the organs of the neck, the chest and the abdomen, can all lead to abscess formation in and about the spine. Osteomyelitis, which can also occur from sepsis or bacteremia, can produce paraspinal infections. Disc space infections can originate in a similar fashion, and produce paraspinal infections. Operative procedures on the spine can all produce a paraspinal abscess as a complication. Occasionally, injections of the spine with local anesthetics or steroids can lead to contamination of the area and abscess formation.

Signs and Symptoms of Paraspinal Abscess

Acute paraspinal infections are most commonly bacterial. They produce severe pain in the region of the spine that is affected. Fever and chills usually develop. There is usually limited motion of the spine that is affected, and movement typically produces severe muscle spasms. If the infection invades the spinal canal, an epidural abscess may develop. Compression of the spinal cord or the cauda equina can lead to paralysis or varying degrees of weakness, numbness and bladder dysfunction.

A spinal epidural abscess threatens the spinal cord or cauda equina by compression and also by vascular compromise (see images below). If untreated, an expanding suppurative infection in the spinal epidural space impinges on the spinal cord, producing sensory symptoms and signs, motor dysfunction, and, ultimately, paralysis and death. Intervention early in the course of the disease undoubtedly improves the outcome. Frequently, diagnosis is understandably delayed because the initial presentation may be only nonspecific back pain. One half of cases are estimated to be misdiagnosed or have a delayed diagnosis.[1] At times, radicular symptoms may lead to a chief complaint of chest pain or abdominal pain[2] , mimicking a myocardial infarction or an acute abdomen.[3]

Cervical epidural abscess with spinal cord

compression and spinal cord edema. epidural abscess lumbar area.

Spinal

Pathophysiology
The spinal epidural space is not a uniform space. Posteriorly, the epidural space contains fat, small arteries, and the venous plexus. Infections in this space may spread over several vertebral levels. Anteriorly, the epidural space is a potential space with the dura tightly adherent to the vertebral bodies and ligaments. Abscesses occur more frequently in the larger posterior epidural space. Most spinal epidural abscesses occur in the thoracic area, which is anatomically the longest of the spinal regions. Some series suggest that dorsal spinal epidural abscesses are much more likely to present with weakness and severe neurologic deficit than ventral spinal epidural abscesses.[4] Hematogenous spread with seeding of the epidural space is the suspected source of infection in most children and is thought to occur in many adults as well. Reported sources of infection are numerous and include bacterial endocarditis, infected indwelling catheters, urinary tract infection, peritoneal and retroperitoneal infections, and others. Direct extension of infection from vertebral osteomyelitis occurs in adults and rarely in children. Epidural catheters and injections may lead to direct innoculation of the epidural space. The source of infection is not identified in many patients. The more clinically significant effects of the epidural abscess may be from involvement of the vascular supply to the spinal cord and subsequent infarction rather than direct compression. Staphylococcus aureus is the most commonly reported pathogen[5] , though many other bacteria have been implicated, including Staphylococcus and Pseudomonas species, Escherichia coli, Brucella, and Mycobacterium tuberculosis. Methicillin-resistant Staphylococcus aureus (MRSA) is

increasingly reported particularly in patients with a history of MRSA abscesses, spinal surgery, or implanted devices.

Epidemiology
Frequency
United States

The frequency in large tertiary care centers is estimated to be about 2.8 cases per 10,000 admissions. The incidence is suspected to be increasing in relation to intravenous (IV) drug abuse.[6]
International

Because these abscesses occur rarely, the frequency is unknown. It probably parallels the US experience of rarity, although limited diagnostic capabilities in medically underserved countries might increase its importance as a health risk.

Mortality/Morbidity
If untreated, spinal epidural abscess causes progressive paraplegia and death.

Sex
Older studies found an equal sex ratio; more recent data indicate a male predominance, likely reflecting the pattern of IV drug use.

Age
The average age is older than 50 years, but spinal epidural abscess can occur at any age.

History
Clinical presentation may be quite variable. The clinical triad of fever, back pain, and neurologic deficit is not present in most patients.[5, 7] Early presentations may be subtle, and atypical presentations are not unusual. A 4-phase sequential evolution has been described, with (1) localized spinal pain, (2) radicular pain and paresthesias, (3) muscular weakness, sensory loss, and sphincter dysfunction, and finally (4) paralysis.[1]

The virulence of the infecting organism and the mode of infection contribute to the tempo of this progression. Abscesses from hematogenous spread tend to progress

rapidly, while abscesses from osteomyelitis or discitis may evolve over weeks or months with slow progression of symptoms. Frequently the patient gives a history of back strain or mild injury. An evident source of infection in skin or soft tissue may be found. IV drug users are a high-risk group. Occurrences have been cited even in patients with a remote history of IV drug abuse.[6] Cases are frequently reported in patients with diabetes mellitus, which is a risk factor in 50% of reported patients; alcoholism; and conditions involving chronic immunosuppression. Hematogenous seeding of the epidural space with abscess formation may stem from intravenous lines, urinary catheters, or implantable devices. Direct inoculation of the epidural space may follow spinal surgery, epidural catheter placement, or epidural injections. Symptoms may include the following: o Fever, present in only about one third of patients o Localized back pain in most patients, often the first symptom o Radiculopathy with radiating or lancinating pain, including chest or abdominal pain (At times this may simulate myocardial infarction or other causes of chest or abdominal pain.) o Spinal cord syndromes, typically involving paraparesis with prospective progression to paraplegia (Epidural abscesses at the level of the cauda equina cause symptoms consistent with cauda equina syndrome rather than a spinal cord syndrome.) o Central cord syndrome from epidural abscess has also been reported.[8] o Sphincter dysfunction, including incontinence or increased residual urine volumes o Headache and neck pain may be present, especially with cervical epidural abscesses. (Of course, these symptoms might also suggest meningitis.)

Physical

In some patients, fever is found at presentation. Physical findings vary with the degree of spinal cord compression or dysfunction. In the most advanced cases, a transverse cord syndrome is seen with motor and sensory levels found with neurologic examination. Localized tenderness to percussion or palpation at the site of

the abscess may be noted. Paraspinal muscle spasm may be present. Signs of spinal cord dysfunction may be observed. o Complete transverse spinal cord syndrome with paraplegia and sphincter dysfunction o Incomplete spinal cord syndromes [9] o Unilateral motor or sensory deficits [9] o Gait ataxia Reflexes may vary from absent to hyperreflexia with clonus and extensor plantar (Babinski) responses. Areflexia may indicate spinal shock with transient inhibition of spinal reflexes. Nuchal stiffness or rigidity may be present, notably with cervical epidural abscesses.

Causes

Most cases arise from hematogenous seeding of the epidural space from a distant source of infection. A few cases are the result of direct extension of infection from the spine or paraspinal tissues. Sources of hematogenous infection o Skin and soft tissue o Infected catheter o Bacterial endocarditis o Respiratory tract infection o Urinary tract infection o Dental abscess o Others Sources of contiguous spread o Vertebral osteomyelitis o Retropharyngeal abscess o Dermal sinus tract o Psoas abscess o Penetrating injury o Epidural injections or catheters Cervical Spondylosis: Diagnosis and Management Epidural Hematoma HIV-1 Associated Vacuolar Myelopathy Leptomeningeal Carcinomatosis Metastatic Disease to the Spine and Related Structures Multiple Sclerosis Spinal Cord Hemorrhage Spinal Cord Infarction Tropical Myeloneuropathies Vitamin B-12 Associated Neurological Diseases

Laboratory Studies

CBC count, blood cultures, and preoperative lab studies. Leukocytosis is present in about two thirds of patients.[1] Elevated erythrocyte sedimentation rate (ESR): In one report, the mean ESR was 51 mm/h.[11] ESR may be highly elevated. Leukocytosis and ESR elevation are nonspecific laboratory findings and are not invariably present. Neither the presence of these findings nor the degree of laboratory abnormality is specific for spinal epidural abscess.[1] A treatment guideline incorporating ESR, C-reactive protein, and other risk factors has been proposed based on a small patient series.[12]

Imaging Studies

Immediate imaging of the spine and spinal cord is imperative when the diagnosis is clinically suspected. If available, spinal MRI is the procedure of choice. Recall that symptoms are often defined by spinal cord level, while MRI is ordered by regional or vertebral levels. Because abscesses frequently extend for several levels, be certain to order the anatomically correct region. If MRI is unavailable, CT myelography or conventional myelography can reveal an intraspinal extramedullary mass a "surgical" lesion.

Other Tests
Lumbar puncture (LP) is relatively contraindicated if spinal epidural abscess is suspected. However, LP may be essential to exclude meningitis from the differential diagnosis. Lumbar puncture runs the risk of introducing purulent material into the subarachnoid space. Some advocate slowly advancing the needle with gentle syringe aspiration if spinal epidural abscess is suspected; if purulent material is encountered, it should be aspirated gently to obtain laboratory specimens, and the needle should not be advanced further.

Cerebrospinal fluid (CSF) may show inflammatory cells, often a mixture of polymorphonuclear and mononuclear cells. Cell counts usually are increased, ranging from 10-1000 leukocytes/L. CSF protein usually is elevated above 100 mg/dL but may be higher, particularly if spinal block is present. CSF glucose is usually normal; depression may indicate coexisting meningitis.

Medical Care

Treatment most often consists of both medical[13] and surgical therapy. Empiric antibiotic coverage should include antistaphylococcal antibiotics. With the increasing incidence of methicillin-resistant staphylococcal infections, coverage that includes antibiotics effective against MRSA is recommended. If the infection follows a neurosurgical procedure, an antistaphylococcal penicillin, a third-generation cephalosporin, and an aminoglycoside are prescribed in combination. Culture results guide definitive therapy. If the patient remains neurologically stable and has a mechanically stable spine, some recommend that antibiotic treatment be delayed until material is obtained for a culture.[14] Antibiotic treatment with CT-guided aspiration of the epidural space is increasingly used in patients without neurologic deficits. Resolution of the abscess with antibiotics alone has been reported in patients who are not candidates for surgery because of spine instability or coexisting medical problems. Deterioration of clinical and functional status while undergoing antibiotic therapy alone has been observed and may dictate emergency surgical decompression. Because of the rarity of the disorder, no randomized trial results are available to guide the clinician.

Surgical Care

Emergency surgical decompression of the spinal cord with drainage of the abscess is the usual surgical treatment.[15] Successful treatment with a combination of abscess aspiration and antibiotic treatment has been reported and seems to be used increasingly. Increasing neurologic deficit, persistent severe pain, or persistent fever and leukocytosis are all indications for decompressive surgery. Patients with spinal epidural abscess may be clinically unstable because of concomitant systemic infection, shock, complications of diabetes mellitus, or other complications. As a result, an increased surgical risk often must be weighed in the decision process.

Consultations

Consultation with a spine surgeon should be requested when spinal epidural abscess is detected or strongly suspected. Consultation with an infectious disease specialist may be helpful in the selection of antibiotics and combinations.

Medication Summary

Antibiotic treatment should be initiated as soon as the diagnosis is reasonably considered, and is most often used in conjunction with abscess aspiration or surgical therapy. The usual duration of antibiotic therapy is 3-4 weeks, but may be lengthened in the presence of osteomyelitis. As mentioned above, in select stable patients, antibiotic therapy may be briefly delayed until material is obtained for culture.

Antibiotics
Class Summary
Because S aureus is a common pathogen, antistaphylococcal drugs should be included in the treatment regimen. An antistaphylococcal penicillin, a cephalosporin, or vancomycin may be used. Again, with the increasing incidence of methicillin-resistant staphylococcal infections, coverage that includes antibiotics effective against MRSA is recommended. If the patient has undergone a neurosurgical procedure recently, the penicillin should be combined with a third-generation cephalosporin and an aminoglycoside. Gram-stain and culture results are used to guide therapy. View full drug information

Ceftriaxone (Rocephin)
Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial growth. View full drug information

Nafcillin (Unipen)
Treats infections caused by penicillinase-producing staphylococci. Used to initiate therapy in any patient in whom penicillin G-resistant staphylococcal infection suspected. Should not be used for treatment of penicillin G-susceptible staphylococci. Parenteral therapy used initially in severe infections. Very severe infections may require very high doses. As condition improves, parenteral therapy should be changed to oral therapy. Because of occasional occurrence of thrombophlebitis associated with parenteral route, particularly in the elderly, parenteral route should be used only for short term (24-48 h) and changed to oral route, if clinically possible. View full drug information

Cefazolin (Ancef, Kefzol, Zolicef)

First-generation semisynthetic cephalosporin, which by binding to penicillin-binding proteins arrests bacterial cell wall synthesis and inhibits bacterial growth. Active primarily against skin flora, including S aureus. Total daily dosage is same for both IV and IM routes. View full drug information

Metronidazole (Flagyl)
Used in combination with other antibiotics in epidural abscess following neurosurgical procedures. Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells, and intermediate-metabolized compounds formed bind DNA and inhibit protein synthesis, causing cell death. View full drug information

Gentamicin (Gentacidin, Garamycin)

Used in combination with other antibiotics for epidural abscess following neurosurgical procedures. Aminoglycoside antibiotic used for gram-negative bacterial coverage. Commonly used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution. May be administered IV or IM. View full drug information

Vancomycin (Vancocin)
Often used when MRSA or other resistant organisms are suspected. Potent antibiotic directed against gram-positive organisms and active against enterococci species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or whose conditions have failed to respond to penicillins and cephalosporins, or those who have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients with renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Further Inpatient Care

Frequent neurologic assessment to detect any progression of neurologic deficit, particularly weakness, is required. Postsurgical patients require monitoring of neurologic status as well. If the patient has a deficit from spinal cord damage, nursing attention for skin care, catheter care, and physical therapy may be necessary.

Further Outpatient Care

Rehabilitation for any residual neurologic deficit may be necessary. This would include restrengthening programs and ambulation retraining. Home health care may help provide ongoing antibiotic and physical therapy.

Transfer
Transfer to a facility with spinal cord imaging and appropriate surgical resources may be necessary.

Complications
The many complications of spinal cord injury include bladder dysfunction, decubiti, supine hypertension, recurrent sepsis, and other problems.

Prognosis

No studies have been done to assist in predicting prognosis. Prognosis in general is related to the duration of spinal cord dysfunction and the degree of cord impairment at the time of diagnosis.

Patient Education
For patient education resources, see the Infections Center and Brain and Nervous System Center, as well as Brain Infection and Antibiotics.