on 21-May-2022 (Sat)

Meningitis is an inflammatory disease of the leptomeninges, the tissues surrounding the brain and spinal cord, and is characterized by an abnormal number of white blood cells (WBCs) in the cerebrospinal fluid (CSF) in the majority of patients [1].

The meninges consist of three parts: the pia, arachnoid, and dura maters ( figure 1)

Bacterial meningitis reflects infection of the arachnoid mater and the CSF in both the subarachnoid space and the cerebral ventricles.

The major causes of community-acquired bacterial meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, primarily in patients over 50 years of age or those who have deficiencies in cell-mediated immunity, Listeria monocytogenes (table 1).

The major causes of health care-associated ventriculitis and meningitis are different (usually staphylococci and aerobic gram-negative bacilli) and occur more commonly after neurosurgical procedures (eg, post-craniotomy, ventriculoperitoneal shunts, lumbar shunts, external ventricular drains or following head trauma such as basilar skull fracture with or without clinical evidence of leak of cerebrospinal fluid) [2]

In the largest prospective study of 1412 episodes of bacterial meningitis, for example, approximately half of the patients presented less than 24 hours after onset of illness [3].

Any form of bacterial meningitis that is untreated or treated very late in its course is almost uniformly fatal.

The classic triad of acute bacterial meningitis, which occurs in 41 percent of patients, consists of fever, nuchal rigidity, and a change in mental status, usually of sudden onset [3,4]. Older patients (age >60 years) more commonly present with the triad than younger patients (58 versus 36 percent) [5].

The most common clinical features include a severe headache (84 percent), fever greater than 38°C (74 percent), stiff neck (74 percent), a Glasgow Coma scale <14 (71 percent), and nausea (62 percent) [3,4,6]

In a 2004 prospective study of 696 cases of community-acquired bacterial meningitis, almost all patients (95 percent) presented with at least two of four symptoms (ie, headache, fever, stiff neck, and altered mental status) [ 4]. The absence of all of these findings essentially excludes the presence of bacterial meningitis [7].

Concomitant infections may include sinusitis or otitis (34 percent), pneumonia (9 percent), and endocarditis (1 percent) [3]

In addition to the classic findings, less common manifestations are seizures (23 percent), aphasia or hemi- or monoparesis (22 percent), coma (13 percent), cranial nerve palsy (9 percent), rash (8 percent), and papilledema (4 percent) [3,4,8,9].

In an observational study of 696 patients with community-acquired bacterial meningitis, cerebral infarction occurred in 25 percent of episodes and in 36 percent of patients with pneumococcal meningitis [10]. Delayed cerebral infarctions have been described in 1 to 4 percent of patients with bacterial meningitis with a possible association with adjunctive dexamethasone [11]

Patients with Listeria meningitis have an increased tendency to have seizures and focal neurologic deficits early in the course of infection. In addition, some patients may present with rhombencephalitis affecting the brainstem and cerebellum, manifested as ataxia, cranial nerve palsies, and/or nystagmus.

Certain bacteria, particularly N. meningitidis, can cause characteristic skin manifestations, such as petechiae and palpable purpura. In two large series of patients with community-acquired bacterial meningitis, rash was present in 11 and 26 percent; among those with rash, 75 and 92 percent were associated with meningococcal meningitis [4,8].

However, others have observed a rash in ≤26 percent of cases of meningococcal meningitis and, if present, the rash was more likely to be scanty or more atypical appearing than the rash seen in patients with meningococcal septicemia [15]. A petechial rash is not specific for meningococcal infection, and some patients with meningococcal meningitis have a maculopapular rash [8]

Arthritis occurs in some patients with bacterial meningitis. In a case series of 696 episodes of community-acquired bacterial meningitis, arthritis was diagnosed in 48 (7 percent) of the episodes, with N. meningitidis the etiologic agent in two-thirds of these joint infections [16]. Joint fluid aspiration was performed in 23 patients and was positive by culture in 6 (26 percent). Recognition of the concurrent arthritis is important since prolonged antibiotic therapy is necessary. (See "Septic arthritis in adults".)

Although patients may not complain specifically of a stiff neck, it is important to assess for meningeal irritation. Passive or active flexion of the neck will usually result in an inability to touch the chin to the chest. Difficulty in lateral motion of the neck is a less reliable finding.

Tests to illustrate meningismus (such as Kernig and Brudzinski signs) were originally developed and tested in patients with severe, late-stage untreated bacterial and tuberculous meningitis in the preantibiotic era (table 2)

● The classic Brudzinski sign refers to spontaneous flexion of the hips during attempted passive flexion of the neck.

● The Kernig sign refers to the inability or reluctance to allow full extension of the knee when the hip is flexed 90 degrees. The Kernig test is usually performed in the supine position, but it can be tested in the seated patient.

Nuchal rigidity and the Kernig and Brudzinski signs were described over a century ago. These tests may be less sensitive in modern day community-acquired bacterial meningitis. As an example, in a large, well-designed prospective study of 297 patients with suspected meningitis, the sensitivity was extremely low (5 percent for each sign and 30 percent for nuchal rigidity); the specificity was 95 percent for each sign and 68 percent for nuchal rigidity [17]

Jolt accentuation of headache may be a more sensitive maneuver for the diagnosis of meningitis. A positive test consists of accentuation of headache by horizontal rotation of the head at a frequency of two to three times per second.

The diagnostic value of this maneuver has been evaluated in several studies with mixed results [18-20]. Although one study showed a sensitivity of jolt accentuation for the diagnosis of meningitis of 97 percent, other studies have revealed lower sensitivity and specificity highlighting the limited predictive value of the test in the diagnosis of meningitis.

Serum electrolytes and glucose, blood urea nitrogen, and creatinine concentrations are helpful in determining the cerebrospinal fluid- (CSF) to-blood glucose ratio. It is important to draw the serum glucose within one hour of obtaining the lumbar puncture to have a reliable ratio [21].

In addition, coagulation studies may be indicated, especially if petechiae or purpuric lesions are noted [ 22]

The white blood cell (WBC) count is usually elevated, with a shift toward immature forms; however, severe infection can be associated with leukopenia. The platelet count may also be reduced. Leukopenia and thrombocytopenia have correlated with a poor outcome in patients with bacterial meningitis [23,24].

Coagulation studies may be consistent with disseminated intravascular coagulation

Serum chemistry results are usually commensurate with the severity of the overall process and may reveal an anion gap metabolic acidosis or hyponatremia; in one series, hyponatremia was present in 30 percent of patients but was usually mild and did not require specific treatment [25]

Initial blood tests should include a complete blood count with differential and platelet count and two aerobic blood cultures of appropriate volume (ideally, prior to the initiation of antimicrobial therapy).

Blood cultures are often positive and can be useful in the event that CSF cannot be obtained before the administration of antimicrobials. Approximately 50 to 90 percent of patients with bacterial meningitis have positive blood cultures [3,4,6]; lower yields have been reported in some studies in patients with meningococcal infection [26]

Tests of serum and urine for bacterial antigens, as well as cultures of mucosal surfaces for the causative pathogen, are not generally helpful

Every patient with suspected meningitis should have CSF obtained unless lumbar puncture (LP) is contraindicated

Although there are no absolute contraindications to performing the procedure, caution should be used in patients with (see "Lumbar puncture: Technique, indications, contraindications, and complications in adults", section on 'Contraindications'):

● Possible raised intracranial pressure with risk for cerebral herniation due to obstructive hydrocephalus, cerebral edema, or space-occupying lesion

● Thrombocytopenia or other bleeding diathesis, including ongoing anticoagulant therapy

● Suspected spinal epidural abscess

A head CT should be performed before LP in adults with suspected bacterial meningitis who have one or more of the following risk factors (algorithm 1) [30-32]:

● Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic cell transplantation)

● History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)

● New onset seizure (within one week of presentation)

● Papilledema

● Abnormal level of consciousness

● Focal neurologic deficit

Patients without these indications should not undergo a CT scan as it is of no clinical benefit and delays therapy [33]

It has been suggested that a normal CT scan does not always mean that performance of an LP is safe and that certain clinical signs of impending herniation (ie, deteriorating level of consciousness, particularly a Glasgow Coma scale <11; brainstem signs including pupillary changes, posturing, or irregular respirations; or a very recent seizure) may be predictive of patients in whom an LP should be delayed irrespective of CT findings (table 3) [36]. (See "Lumbar puncture: Technique, indications, contraindications, and complications in adults", section on 'Cerebral herniation'.)

If LP is delayed or deferred — It is essential that antimicrobial therapy not be delayed if there is a contraindication to or inability to perform an LP, or if the LP is delayed by the need for cranial imaging. In any of these situations, blood cultures should be obtained and empiric antibiotics administered as soon as is possible (before the imaging study in patients who require imaging).

In addition, dexamethasone (0.15 mg/kg intravenously every 6 hours) should be given shortly before or at the same time as the antimicrobial agents if the preponderance of clinical and laboratory evidence suggests bacterial meningitis with a plan to stop therapy, if indicated, when the evaluation is complete.

Adjunctive dexamethasone should not be given to patients who have already received antimicrobial therapy because it is unlikely to improve patient outcome even though the European and United Kingdom guidelines recommend administering dexamethasone up to 4 and 12 hours after receipt of antimicrobial therapy, respectively [ 37]. Indications for adjunctive dexamethasone are discussed in greater detail separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Avoidance of delay'.)

Prior administration of antimicrobials tends to have minimal effects on the chemistry and cytology findings [28,38] but can reduce the yield of Gram stain and culture [26-28].

However, a pathogen can still be cultured from the CSF in most patients up to several hours after the administration of antimicrobial agents [ 27,28], with the possible exception of the meningococcus

Opening pressure — The opening pressure with the patient lying in the lateral decubitus position should be measured and documented. The opening pressure is typically elevated in patients with bacterial meningitis. In the series of 301 adults cited above, the mean opening pressure was approximately 350 mm H₂O (normal up to 200 mm H₂O) [3]. However, there is a wide range of values as illustrated in a report of 296 episodes of community-acquired bacterial meningitis: 39 percent had values ≥300 mm H₂O, while 9 percent had values below 140 mm H₂O [8]

Characteristic findings in bacterial meningitis include a CSF glucose concentration <40 mg/dL (<2.22 mmol/L), a CSF to serum glucose ratio of ≤0.4, a protein concentration >200 mg/dL (>2000 mg/L), and a WBC count above 1000/microL, with a percentage of neutrophils usually greater than 80 percent [3,32,39]

he spectrum of CSF values in bacterial meningitis is so wide, however, that the absence of one or more of the typical findings is of little value [ 4,8].

For example, in a prospective study of 1412 adults with bacterial meningitis, a CSF WBC >1000/microL was seen in only 66 percent of patients [ 3].

Why some patients have milder CSF abnormalities cannot usually be identified. Potential causes include early presentation, recent prior antimicrobial therapy, and neutropenia. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'CSF in CNS infection'.)

An observational study found that bacterial meningitis was highly probable (≥99 percent certainty) when any one of the following parameters was present: a CSF glucose concentration below 34 mg/dL (1.9 mmol/L), a protein concentration above 220 mg/dL (2200 mg/L), a WBC count above 2000/microL, or a neutrophil count more than 1180/microL [40]. However, clinicians must recognize that many exceptions exist and that empiric antimicrobial therapy is warranted when bacterial meningitis is suspected clinically even if the CSF abnormalities are not diagnostic

A false-positive elevation of the CSF WBC count can be found after traumatic LP or in patients with intracerebral or subarachnoid hemorrhage in which both red blood cells (RBCs) and WBCs are introduced into the subarachnoid space. If a traumatic LP is suspected and the peripheral WBC count is not abnormally low or high, a good rule of thumb for estimating the adjusted WBC count is to subtract one WBC for every 500 to 1000 RBCs measured in the CSF. This "corrected" CSF WBC has better diagnostic accuracy in differentiating culture-positive bacterial meningitis than patients with intracerebral hemorrhage alone [41]. The formula in the following calculator can also be used to determine the adjusted WBC count in the presence of CSF RBCs (calculator 1) [41,42]

Two meta-analyses that included 25 studies (1692 patients) and 31 studies (1885 patients) concluded that the diagnostic accuracy of CSF lactate was superior to that of CSF WBC count, glucose, and protein concentration in differentiating bacterial from aseptic meningitis [43,44], although sensitivity was lower in patients who received antimicrobial treatment prior to LP [43], and CSF lactate may be elevated in patients with other CNS diseases.

A CSF lactate may help differentiate health care-associated ventriculitis from chemical meningitis in patients with recent neurosurgical procedures, but it is only performed in approximately 50 percent of the patients [ 45]

● Gram-positive diplococci suggest pneumococcal infection (picture 1).

● Gram-negative diplococci suggest meningococcal infection (picture 2).

● Small pleomorphic gram-negative coccobacilli suggest Haemophilus influenzae infection (picture 3).

● Gram-positive rods and coccobacilli suggest listerial infection (picture 4).

The Gram stain is positive in 10 to 15 percent of patients who have bacterial meningitis but negative CSF cultures [8]. As noted above, the yield of both Gram stain and culture may be reduced by prior antibiotic therapy [26-28]

The reported sensitivity of Gram stain for bacterial meningitis has varied from 50 to 90 percent; however, the specificity approaches 100 percent [4,11,46]

A rapid multiplex PCR that tests for the most common viruses, bacteria, and fungi is now widely available and has been shown to be useful, especially in those with a negative-CSF Gram stain or culture, or in those who have received prior antimicrobial therapy.

Problems with false-positive results have been reported with PCR but false negatives are very uncommon [52]

Molecular diagnosis of bacterial meningitis is discussed in greater detail separately. (See "Molecular diagnosis of central nervous system infections", section on 'Meningitis'.)

Isolation of bacteria from blood cultures in a patient with CSF pleocytosis also confirms the diagnosis, even if the CSF culture remains negative

Differentiation of these disorders from bacterial meningitis requires careful examination of cerebrospinal fluid (CSF) parameters (table 4) and neuroimaging (when indicated), as well as consideration of any epidemiologic factors that would raise the possibility of specific bacterial or nonbacterial central nervous system infections

Viral meningitis – Aseptic (usually viral) meningitis is a less severe disease that is often monitored in the outpatient setting without antimicrobial therapy, whereas bacterial meningitis is a life-threatening illness that requires hospital admission. Similar to bacterial meningitis, viral meningitis presents acutely with classic signs and symptoms of meningitis. Unlike bacterial meningitis, the CSF normally has a lymphocytic pleocytosis, normal glucose, moderate elevation of protein, and negative-CSF Gram stain and culture. Definitive diagnosis of viral meningitis is generally made by CSF polymerase chain reaction (PCR), although serologies are typically used for the diagnosis of meningitis due to arboviruses (eg, West Nile virus).

TB meningitis – Patients with tuberculous (TB) meningitis may have classic signs and symptoms of meningitis at presentation, however, it is generally a subacute process. CSF exam typically reveals a lymphocyte predominant pleocytosis with elevated protein and decreased glucose. Certain scoring systems (eg, the Lancet consensus scoring system and the Thwaites system) have been developed to help differentiate bacterial from TB meningitis [54]; these are based primarily on clinical and CSF findings. A definitive diagnosis of TB meningitis is made by identification of mycobacterium from the CSF either by culture or PCR.

Fungal meningitis – Several fungal species may cause meningitis including Candida, Cryptococcus, Histoplasma, Blastomyces, and Coccidioides. Although fungal meningitis may present with classic symptoms of meningitis, it often is a subacute process in patients with epidemiologic risk factors for fungal disease (eg, immunocompromise, HIV).

Generalized seizures without meningitis – Generalized seizures may also induce a mild transient CSF pleocytosis, although this has not been well studied [55-57]. However, CSF pleocytosis should not be ascribed to seizure activity alone unless the fluid is clear and colorless, the opening pressure and CSF glucose are normal, the CSF Gram stain is negative, and the patient has no clinical evidence of bacterial meningitis

When the Gram stain is negative, studies in both adults and children have concluded that, in the setting of an elevated CSF white blood cell (WBC) count, no single CSF biochemical variable can reliably exclude bacterial meningitis [40,46,58]

The number of definite indications for LP has decreased with the advent of better neuroimaging procedures including computed tomography (CT) scans and magnetic resonance imaging (MRI), but urgent LP is still indicated to diagnose two serious conditions [1,2]:

● Suspected CNS infection (with the exception of brain abscess or a parameningeal process).

● Suspected SAH in a patient with a negative CT scan [3]. The use of cerebrospinal fluid (CSF) examination in the evaluation of a patient with suspected SAH is discussed in detail separately. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Lumbar puncture'.)

A nonurgent LP is indicated in the diagnosis of many other conditions. The findings are discussed in the appropriate topic reviews:

● Idiopathic intracranial hypertension (pseudotumor cerebri)

● Carcinomatous meningitis

● Normal pressure hydrocephalus

● CNS syphilis

● CNS lymphoma

● Autoimmune encephalitis

Conditions in which LP is rarely diagnostic but still useful include:

● Multiple sclerosis

● Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy

● Paraneoplastic syndromes

● Neurosarcoidosis

● CNS vasculitis

In many situations, high-risk patients can be identified and risks can be mitigated. These are discussed in detail in relation to the complications with which they are associated. (See 'Complications' below.)

The choice of needle type (cutting versus atraumatic) and bore size can influence the risk of a post-LP headache, but also may increase the technical difficulty of the procedure. This is discussed in detail separately. (See "Post dural puncture headache", section on 'Prevention of PDPH after dural puncture'.)

The correct level of entry of the spinal needle is most easily determined with the patient sitting upright or standing. The highest points of the iliac crests should be identified visually and confirmed by palpation; a direct line joining these is a guide to the fourth lumbar vertebral body. However, this line may intersect the spine at points ranging from L1-L2 to L4-L5 [6], and tends to point to a higher spinal level in females and in patients with obesity [7].

The lumbar spinous processes of L3, L4, and L5, and the interspaces between, can usually be directly identified by palpation. The spinal needle can be safely inserted into the subarachnoid space at the L3-4 or L4-5 interspace, since this is well below the termination of the spinal cord in most patients.

An alternate approach to obtaining cerebrospinal fluid (CSF) with a paramedian needle insertion through the L5-S1 space (Taylor approach) (figure 1) has been successfully used in a patient with advanced ankylosing spondylitis [8]

Correct patient positioning is an important determinant of success in obtaining CSF. The patient is instructed to remain in the fetal position with the neck, back, and limbs held in flexion. The lower lumbar spine should be flexed with the back perfectly perpendicular to the edge of a bed or examining table. The hips and legs should be parallel to each other and perpendicular to the table. Pillows placed under the head and between the knees may improve patient comfort

The overlying skin should be cleaned with alcohol and a disinfectant such as povidone-iodine or chlorhexidine (0.5 percent in alcohol 70 percent); the antiseptic should be allowed to dry before the procedure is begun.

Many product inserts of chlorhexidine-containing solutions warn against use of chlorhexidine prior to LP because of a concern that it can cause arachnoiditis. The evidence that it does so is very limited, and many experts believe that chlorhexidine has an advantage over povidone-iodine because of its onset, efficacy, and potency [ 9-13].

After the skin is cleaned and allowed to dry, a sterile drape with an opening over the lumbar spine is placed on the patient

Face masks should be used by individuals who place a catheter or inject material into the spinal canal as recommended by the Healthcare Infection Control Practices Advisory Committee and the Centers for Disease Control and Prevention (CDC) [14]. While routine use of face masks during diagnostic LP and neuroradiologic imaging procedures involving LP has been recommended by some [15-17], others question the practicality and necessity of the use of face masks since infections are rare and there is no proof that face masks prevent such infections [18,19]

Local anesthesia (eg, lidocaine) is infiltrated into the previously identified lumbar intervertebral space and a 20- or 22-gauge spinal needle containing a stylet is inserted into the lumbar intervertebral space

The spinal needle may be advanced slowly, angling slightly toward the head, as if aiming towards the umbilicus. The flat surface of the bevel of the needle should be positioned to face the patient's flanks to allow the needle to spread rather than cut the dural sac (the fibers of which run parallel to the spinal axis). The approximate distance of the epidural space from the skin is 45 to 55 mm on average but is variable and may be longer in patients with obesity [7,20,21]

Many clinicians choose to advance the needle incrementally, removing the stylet periodically to check for CSF flow, then reinserting the stylet until the subarachnoid space is entered [ 22]. Some report a higher rate of successful LP when the stylet is removed, just after the skin is punctured and before it is passed into the subarachnoid space in order to better observe the flow of CSF upon entry of the subarachnoid space [23,24]; however, this technique may be associated with a risk of epidermoid tumor, possibly infection, or failure to get flow of CSF. (See 'Epidermoid tumor' below.)

Once CSF appears and begins to flow through the needle, a manometer should be placed over the hub of the needle (figure 2). The patient should be instructed to slowly straighten or extend the legs to allow free flow of CSF within the subarachnoid space and the opening pressure should be measured

While the pressure measurement is affected by the position of the legs, the available evidence suggests that the effect is likely to be small. In one review, pressures were elevated by only 1 to 2 cm H ₂O in four of five studies studying this effect; however, in one study, changing position from a straight to a fully flexed position resulted in an increase in pressure of 6.4 mmHg (approximately 8.7 cm H₂O) [25]

A total of 8 to 15 mL of CSF is typically removed during routine LP. However, when special studies are required, such as cytology or cultures for organisms that grow less readily (eg, fungi or mycobacteria), 40 mL of fluid can safely be removed

Aspiration of CSF should not be attempted, as it may increase the risk of bleeding [ 22].

The stylet should be replaced before the spinal needle is removed, as this can reduce the risk of post-LP headache.

No trials have shown that bed rest following LP significantly decreases the risk of post-LP headache compared with immediate mobilization [27,28].

The Queckenstedt maneuver can be used to demonstrate that there is free flow of fluid from the ventricles to the lumbar space. This maneuver is performed by measuring the CSF pressure and then observing the change in pressure after manual compression of both jugular veins. However, this test is rarely useful in modern practice, since newer techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) readily identify most obstructing spinal or basilar lesions

A subsequently published randomized trial involving 100 adult patients undergoing LP in the emergency department found no significant difference in outcomes with ultrasound guidance [34].

LP is a relatively safe procedure, but minor and major complications can occur even when standard infection control measures and good technique are used. These complications include:

● Post-LP headache

● Infection

● Bleeding

● Cerebral herniation

● Minor neurologic symptoms such as radicular pain or numbness

● Late onset of epidermoid tumors of the thecal sac

● Back pain

The risk of complications was studied in a cohort of 376 patients who underwent LP for evaluation of acute cerebrovascular disease [35]. The following frequency of complications was noted: backache (25 percent), headache (22 percent), headache and backache (12 percent), severe radicular pain (15 percent), and paraparesis (1.5 percent). Severe pain or paraparesis occurred in 6.7 percent of patients receiving anticoagulants following the procedure and in none of the 34 patients who did not receive anticoagulants.

Headache, which occurs in 10 to 30 percent of patients, is one of the most common complications following LP. Post-LP headache is caused by leakage of cerebrospinal fluid (CSF) from the dura and traction on pain-sensitive structures. Patients characteristically present with frontal or occipital headache within 24 to 48 hours of the procedure, which is exacerbated in an upright position and improved in the supine position. Associated symptoms may include nausea, vomiting, dizziness, tinnitus, and visual changes.

Meningitis is an uncommon complication of LP. In a review of 179 cases of post-LP meningitis reported in the medical literature between 1952 and 2005, half of all cases occurred after spinal anesthesia; only 9 percent occurred after diagnostic LP. The most commonly isolated causative organisms were Streptococcus salivarius (30 percent), Streptococcus viridans (29 percent), alpha-hemolytic strep (11 percent), Staphylococcus aureus (9 percent), and Pseudomonas aeruginosa (8 percent) [36].

An LP through a spinal epidural abscess can result in the spread of bacteria into the subarachnoid space. Because an LP is not needed for diagnosis, the procedure should not be performed in most patients with suspected epidural abscess in the lumbar region [37].

We and other authors believe that theoretical concerns about inducing meningitis in patients with bacteremia should not be used as the basis to forego LP if meningitis is suspected [19]

There are rare case reports of discitis and vertebral osteomyelitis following LP. Most cases were due to normal skin flora such as Cutibacterium species and coagulase negative staphylococci [45-47]. These complications presumably result from direct inoculation of bacteria into the vertebral bone.

The CSF is normally acellular, although up to five red blood cells (RBCs) are considered normal after LP due to incidental trauma to a capillary or venule. A higher number of RBCs is seen in some patients in whom calculation of the white blood cell (WBC)-to-RBC ratio and the presence or absence of xanthochromia may differentiate LP-induced from true central nervous system (CNS) bleeding.

Serious bleeding that results in spinal cord compromise is rare in the absence of bleeding risk [48]. Patients who have thrombocytopenia or other bleeding disorders or those who received anticoagulant therapy prior to or immediately after undergoing LP have an increased risk of bleeding

In one series, spinal hematoma developed in 7 of 342 patients (2 percent) who received anticoagulant therapy after undergoing LP; five of these patients developed paraparesis [35]. In one literature review, 47 percent of 21 published cases of spinal hematoma following LP occurred in patients with a coagulopathy [49]. Thus, a high index of suspicion of spinal hematoma should be maintained in all patients who develop neurologic symptoms after an LP, including those with no known coagulopathy. In rare cases, intraventricular, intracerebral, and subarachnoid hemorrhage (SAH) have also been reported as complications of LP [50,51]

We are unaware of any study that has systematically examined interventions to reduce the risk of bleeding following LP based upon the degree of thrombocytopenia or clotting study abnormalities. Thus, at present the only guidepost is "clinical judgment."

We generally advise not performing an LP in patients with coagulation defects who are actively bleeding, have severe thrombocytopenia (eg, platelet counts <50,000 to 80,000/microL), or an international normalized ratio (INR) >1.4, without correcting the underlying abnormalities [52,53]

For elective procedures in a patient receiving systemic anticoagulation, observational studies and expert opinion have suggested stopping the agents for a specified time period prior to spinal anesthesia or LP (table 1) [55-57]:

● Unfractionated intravenous heparin drips – Two to four hours.

● Low-molecular-weight heparin – 12 to 24 hours.

● Warfarin – Five to seven days.

● Newer oral anticoagulants (NOACs), apixaban, edoxaban, and rivaroxaban – 72 hours. Dabigatran should be held 48 to 96 hours based on renal function.

● Subcutaneous heparin – <10,000 units per day is not believed to pose a substantial risk for bleeding.

None of these approaches have been carefully assessed for efficacy or risk, and all presume that the underlying indications for anticoagulation therapy allow a temporary suspension of treatment

While the optimal timing of restarting anticoagulation after LP is not known, the incidence of spinal hematoma in one series was much lower when anticoagulation was started at least one hour after the LP [35]. NOACs can be restarted six to eight hours after an atraumatic spinal or epidural anesthesia or clean LP; however, in traumatic procedures with increased risk of bleeding, the guidelines recommend restarting NOACs 48 to 72 hours after complete hemostasis [57]

Antiplatelet therapy with aspirin and nonsteroidal antiinflammatory agents has not been shown to increase the risk of serious bleeding following LP. In a prospective study of 924 patients who underwent orthopedic procedures with spinal or epidural anesthesia, 386 patients were taking antiplatelet therapy prior to surgery; 193 were taking aspirin [58]. Neither aspirin nor any other antiplatelet agents were associated with an increased risk of bleeding. However, none of these patients were taking clopidogrel, ticlopidine, or a GP IIb/IIIa receptor antagonist.

Given the unknown risk of bleeding with thienopyridine derivatives (clopidogrel, ticlopidine, prasugrel, ticagrelor), it may be reasonable to suspend treatment with these agents, when possible, for one to two weeks prior to an elective LP, while pharmacologic data suggest that for GP IIb/IIIa receptor antagonists, a shorter period of treatment cessation (8 hours for tirofiban and eptifibatide and 24 to 48 hours for abciximab) may be indicated [56]

Patients who have persistent back pain or neurologic findings (eg, weakness, decreased sensation, or incontinence) after undergoing LP require urgent evaluation (usually spinal magnetic resonance imaging [MRI]) for possible spinal hematoma [59]

The appropriate treatment for patients with significant or progressing neurologic deficits is prompt surgical intervention, usually a laminectomy, and evacuation of the blood. Timely decompression of the hematoma is essential to avoid permanent loss of neurologic function [60,61]. Patients with mild symptoms or early signs of recovery may be managed conservatively with vigilant monitoring; dexamethasone may be administered to mitigate neurologic injury [49,50].

The most serious complication of LP is cerebral herniation. Suspected increased intracranial pressure (ICP) due to an intracranial mass lesion, cerebral edema, or obstructive hydrocephalus is a relative contraindication to performance of an LP and also requires independent assessment and treatment

In another series of 1533 patients with bacterial meningitis, 47 (3 percent) had a clinical deterioration after LP [64]. Cardiorespiratory collapse, loss of consciousness, and death may follow. (See "Evaluation and management of elevated intracranial pressure in adults".)

A 1969 study of 30 patients with increased ICP who deteriorated after LP attempted to identify the clinical features of patients who were at greatest risk for this complication [65]. The following findings were noted: 73 percent had focal findings on neurologic examination (including dysphagia, hemiparesis, and cranial nerve palsies), 30 percent had documented papilledema prior to the LP, and 30 percent had evidence of increased ICP on plain skull films (erosion of the posterior clinoid processes). Deterioration occurred immediately in one-half of the patients, with the remainder declining within 12 hours

A more recent series compared patients who did and did not deteriorate after LP and found that interrater reliability regarding the presence of a contraindication on computed tomography (CT) was only moderate (kappa = 0.47) and that a similar proportion of patients in both groups had such a contraindication (14 versus 11 percent) [ 64].

Moreover, CT scanning is not necessary in all patients prior to LP and may not be adequate to exclude elevated ICP in others [67,68].

This was best illustrated in a prospective study of 301 adults with suspected meningitis [66]. The following findings were noted:

● Among the 235 (78 percent) who underwent CT scan before LP, 24 percent had an abnormal finding but only 5 percent (11 patients) had a mass effect

● The risk of an abnormal CT scan was associated with specific clinical features (presence of impaired cellular immunity, history of previous CNS disease, or a seizure within the previous week), as well as certain findings on neurologic examination (reduced level of consciousness, and focal motor or cranial abnormalities)

● Among 96 patients with none of these abnormalities, only three had an abnormal CT scan; one of the three misclassified patients had a mild mass effect, but all three underwent LP without herniation

● Compared with patients who did not undergo CT scan before LP, those who underwent CT scan before LP had an average of a two-hour delay in diagnosis and a one-hour delay in therapy

Based upon these observations, we do not perform a CT scan before an LP in patients with suspected bacterial meningitis unless one or more risk factors is present:

● Altered mentation

● Focal neurologic signs

● Papilledema

● Seizure within the previous week

● Impaired cellular immunity

However, the CT scan should also be scrutinized for more subtle signs including diffuse brain swelling as manifest by loss of differentiation between gray and white matter and effacement of sulci, as well as ventricular enlargement and effacement of the basal cisterns [70]

Management of elevated intracranial pressure — Independent of the decision to perform LP, patients with possible elevated ICP based upon the above clinical features may require urgent life-saving interventions to lower ICP that may include head elevation, hyperventilation to a partial pressure of carbon dioxide (PCO₂) of 26 to 30 mmHg, and intravenous mannitol (1 to 1.5 g/kg). When indicated, these should not await CT scan. These same measures should be instituted if a patient develops signs of herniation after LP. The evaluation and management of patients with elevated ICP is discussed in detail separately. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Urgent situations'.)

Epidermoid tumor — The formation of an epidermoid spinal cord tumor is a rare complication of LP that may become evident years after the procedure is performed [71-73]. Most reported cases are children ages 5 to 12 years who had an LP in infancy; however, this has also been described in adults [74-76]. It may be caused by epidermoid tissue that is transplanted into the spinal canal during LP without a stylet, or with one that is poorly fitting. This complication probably can be avoided by using spinal needles with tight-fitting stylets during LP [77,78]

Abducens palsy — Both unilateral and bilateral abducens palsy are reported complications of LP [79-81]. This is believed to result from intracranial hypotension and is generally accompanied by other clinical features of post-LP headache. Most patients recover completely within days to weeks. Other cranial nerve palsies are rarely reported [82]

Radicular symptoms and low back pain — It is not uncommon (13 percent in one series) for patients to experience transient electrical-type pain in one leg during the procedure [83]. However, more sustained radicular symptoms or radicular injury appear to be rare [84].

Up to one-third of patients complain of localized back pain after LP; this may persist for several days, but rarely beyond [83]

Post dural puncture headache (PDPH), also known as post lumbar puncture (LP) headache, is a common complication of diagnostic LP. It also can occur following spinal anesthesia or, more commonly, inadvertent dural puncture during attempted epidural catheter placement. The headache is usually positional (worse when upright, better when lying flat) and is often accompanied by neck stiffness, photophobia, nausea, or subjective hearing symptoms

The precise etiology of headache after dural puncture is unclear, but is thought to relate to leakage of cerebrospinal fluid (CSF) through the dural hole created by the needle.

However, not all patients with PDPH have low CSF pressure, and not all patients with significant CSF leak develop a headache.

hree pathophysiologic mechanisms have been proposed:

● CSF hypotension results in compensatory meningeal venodilation and blood volume expansion, with headache caused by acute venous distention. This mechanism is consistent with magnetic resonance imaging (MRI) in several reported cases of PDPH [1,2].

● Intracranial hypotension related to CSF leak may cause sagging of intracranial structures and stretch of sensory intracranial nerves, causing pain and cranial nerve palsies. In one study of seven patients with intracranial hypotension, MRI findings of downward displacement of the brain were associated with headache, and resolved along with the headache symptoms [3]. Traction of the upper cervical nerves may cause PDPH associated neck, back and shoulder pain [4].

● Altered craniospinal elasticity after lumbar puncture (LP) results in increased caudal compliance relative to intracranial compliance and acute intracranial venodilation in the upright position [5].

The incidence of PDPH varies widely, depending on patient (eg, age, gender, pregnancy, body mass index [BMI]) and procedural (eg, needle size and type, bevel orientation for cutting needles) risk factors.

PDPH after lumbar puncture (LP) occurs in approximately 11 percent of cases when a standard, traumatic needle is used [9].

Patient risk factors — In various studies, common patient risk factors for PDPH have included female gender, pregnancy, age 18 to 50 years compared with older or younger ages, and a prior history of headache

Age – In most studies, extremes of age are associated with lower incidence of PDPH, with young adults (18 to 50 years of age) having the highest risk [23,24,31,37-39]. As an example, in one prospective study of patients who had spinal anesthesia with 25 or 27 gauge Quincke (ie, traumatic) needles, PDPH occurred in 11 percent of patients aged 31 to 50 years, compared with 4 percent of others [24].

Prior headaches – History of prior headaches (both PDPH and chronic headaches) may be a risk factor for PDPH [4,23,31-33]; although, this has not been observed in all studies [34-36]

Pregnancy – Pregnancy confers an additional risk for PDPH, possibly due to increased cerebral vasodilation in response to cerebrospinal fluid (CSF) hypotension, related to high levels of circulating estrogen [24,26].

Female gender – Several studies have found that women have a two to three times increased risk for PDPH compared with men [23-25]

Low opening pressure – Low opening pressure during lumbar puncture (LP) may also predict an increased risk of PDPH [42]. However, a 2019 case-control retrospective study and systematic literature review found no association between either opening pressure or closing pressure and PDPH risk [43]

Volume of CSF removed – PDPH may have distinct temporal and prognostic profiles depending on the volume of CSF removed, particularly for high volume CSF removal. A systematic literature review found that high volume CSF removal (ie, 20 to 30 mL) may be associated with increased risk of immediate PDPH, but decreased risk of PDPH at 24 hours, compared with lower volume CSF removal [43].

High volume CSF removal with lowered closing pressure may help reduce further CSF leakage to heal the dural hole

Low body mass index (BMI) – The literature on the effect of BMI on the risk of PDPH is inconclusive

Procedural risk factors — The choice of spinal needle and procedural factors can affect the risk of PDPH. We suggest the use of pencil point (atraumatic) needles for spinal anesthesia and diagnostic LP.

Needle tip – For both diagnostic LP and spinal anesthesia, we recommend the use of spinal needles with a pencil point tip, rather than needles with a sharp cutting tip. The use of pencil point spinal needles reduces the risk of PDPH compared with cutting needles of the same size [8,52-54]

The incidence of PDPH was significantly lower in the atraumatic group compared with the conventional group (4.2 versus 11 percent, relative risk [RR] 0.40, 95% CI 0.34-0.47, absolute risk reduction 6.8 percent, number needed to treat to avoid one headache 15)

In addition, use of atraumatic needles was associated with a significant reduction in the need for EBP (RR 0.5, 95% CI 0.33-0.75). There was no significant difference between groups for the success rate of LP on first attempt, LP failure rate, incidence of traumatic tap, or backache.

Needle size – Larger conventional needle size (ie, lower needle gauge) is correlated with an increased incidence of PDPH, as demonstrated in a 2016 meta-analysis that included 12 studies with over 3100 patients who had neuraxial anesthesia with cutting needles [55]. As examples from the meta-analysis, the incidence of PDPH with a 22 or 23 gauge Quincke needle ranged from 8 to 25 percent, whereas the incidence of PDPH with a 27 gauge Quincke needle ranged from 0 to 14 percent

Smaller spinal needles may be technically more difficult to use, as they tend to bend during insertion. Thus they are typically used with an introducer needle, which is inserted through the skin and along the desired needle path. Flow rate is slower than with larger bore needles; confirmatory CSF appears more slowly in the needle hub, and collection of CSF is slower. In our practice, spinal anesthesia is performed using a small gauge noncutting needle (ie, 25 gauge Whitacre).

The optimal size of spinal needle may be different for spinal anesthesia versus diagnostic LP in which opening pressure and/or CSF sampling is required. In one laboratory study that compared flow rates and the rate of accurate pressure transduction for various cutting and pencil point spinal needles, the 20 gauge Sprotte needles provided rapid pressure transduction (>90 percent of true pressure within one minute) and an optimal flow rate, defined as 2 mL per minute. [56].

Needle orientation – PDPH is more than twice as likely if a cutting spinal or epidural needle is inserted with the bevel perpendicular, rather than parallel, to the long axis of the spine [31,57-59]. As an example, in one study, 218 patients who underwent nonobstetric surgery with spinal anesthesia using a 27 gauge Quincke needle were randomly assigned to have the needle inserted parallel or transverse to the long axis of the spine [59]. PDPH occurred in 4 percent of patients in the parallel group, and 23 percent of patients in the transverse group

Reinsertion of stylet – Whether reinserting the stylet before removing the spinal needle reduces the risk of PDPH is unclear. Available data suggest that reinsertion does not reduce PDPH when a cutting needle is used, and the data regarding the use of pencil point needles is equivocal. Authors to this topic do not routinely reinsert the stylet before removing a spinal needle

Placement of spinal needle in the sitting as opposed to lateral position [66] and a higher number of needle passes may be associated with increased risk for PDPH in spinal anesthetics, but the evidence is conflicting [31,67].

Paramedian approach to the spinal space and decreased operator experience [68,69] may confer additional increased risk for PDPH, but results are limited and conflicting between the orthopedic and obstetric populations [70,71].

In epidural placements, studies have failed to show a difference in PDPH risk with the use of air versus saline for the loss of resistance technique to identify the epidural space across all patient populations [72,73]. The onset of headache may be sooner in obstetric patients when air is used for loss of resistance, likely related to pneumocephalus rather than low pressure headache [20]

Bed rest – Despite common recommendations for bed rest following dural puncture, this remedy has not been shown to significantly decrease the risk of PDPH [4,74-77].

While of no use for prevention of PDPH, bed rest does decrease the intensity of the headache. (See 'Treatment' below.)

There is a theoretical role for abdominal compression with a tight abdominal binder for prevention and/or treatment of PDPH. The rationale for such treatment is that increased intra-abdominal pressure may be transmitted to the epidural space, may help to seal the dural puncture and decrease cerebrospinal fluid (CSF) leak, and may improve an existing headache

Prophylactic drug therapy – Based on the limited evidence available, we do not recommend administration of prophylactic medications after UDP or LP to prevent PDPH.

In addition, ondansetron may reduce the risk of PDPH. In one randomized trial, 210 women were randomly assigned to receive ondansetron 0.15 mg/kg IV or saline during spinal anesthesia with a 25 gauge Quincke needle for cesarean delivery [84]. PDPH occurred in 5 percent of patients who received ondansetron, compared with 21 percent of patients who did not. Ondansetron may trigger migraine headache in susceptible patients [85]. Further research is needed to elucidate the role of these drugs in PDPH prevention.

In obstetric and general surgical populations, oral caffeine has not been shown to prevent PDPH after dural puncture [86,87].

Epidural blood patch (EBP) is an effective treatment for PDPH, and may also be performed prophylactically before a headache occurs for patients in whom an epidural catheter is placed after an inadvertent dural puncture.

We do not routinely perform prophylactic EBP, since the efficacy is unclear [88-93].

Patients with PDPH typically present with frontal or occipital headache that is worse with sitting or standing, and relieved by lying flat. The headache tends to be worse if it occurs in the first 24 hours, and associated symptoms are more common with severe headaches. In some patients, the symptoms of PDPH are similar to their previously experienced migraine headaches, except that there is an added postural component

Associated symptoms occur in up to 70 percent of patients [24], and may include nausea, neck stiffness, low back pain, vertigo, vision changes (diplopia, blurred vision, or photophobia), dizziness, or auditory disturbances (tinnitus, hearing loss) [42]. In one study of 133 patients who developed PDPH after diagnostic lumbar puncture (LP), neck stiffness was reported in 55.6 percent, shoulder stiffness in 46.6 percent, nausea and vomiting in 33 percent, tinnitus in 22 percent, and photophobia in 23 percent. [4].