Guillain–Barré syndrome

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Guillain%E2%80%93Barr%C3%A9_syndrome

  

Guillain–Barré syndrome
Other names	Guillain–Barré–Strohl syndrome, Landry's paralysis, postinfectious polyneuritis[1]
A handheld spirometry device, which can be used to anticipate breathing complications of Guillain–Barré syndrome
Pronunciation	UK: /ˈɡiːjæ̃ ˈbæreɪ/ US: /ɡiˈjæn bəˈreɪ/ French: [ɡilɛ̃ baʁe]
Specialty	Neurology
Symptoms	Muscle weakness beginning in the feet and hands
Complications	Breathing difficulties, heart and blood pressure problems
Usual onset	Rapid (hours to weeks)
Causes	Unknown
Diagnostic method	Based on symptoms, nerve conduction studies, lumbar puncture
Treatment	Supportive care, intravenous immunoglobulin, plasmapheresis
Prognosis	Weeks to years for recovery
Frequency	2 per 100,000 people per year
Deaths	7.5% of those affected

Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. The initial symptoms are typically changes in sensation or pain along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body, with both sides being involved. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15 percent of people developing weakness of the breathing muscles and, therefore, requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.

Although the cause is unknown, the underlying mechanism involves an autoimmune disorder in which the body's immune system mistakenly attacks the peripheral nerves and damages their myelin insulation. Sometimes this immune dysfunction is triggered by an infection or, less commonly by surgery and rarely by vaccination. The diagnosis is usually made based on the signs and symptoms, through the exclusion of alternative causes, and supported by tests such as nerve conduction studies and examination of the cerebrospinal fluid. There are a number of subtypes based on the areas of weakness, results of nerve conduction studies and the presence of certain antibodies. It is classified as an acute polyneuropathy.

In those with severe weakness, prompt treatment with intravenous immunoglobulins or plasmapheresis, together with supportive care, will lead to good recovery in the majority of people. Recovery may take weeks to years, with about a third having some permanent weakness. Globally, death occurs in about 7.5% of those affected. Guillain–Barré syndrome is rare, at one or two cases per 100,000 people every year. Both sexes and all parts of the world have similar rates of disease. The syndrome is named after the French neurologists Georges Guillain and Jean Alexandre Barré, who, together with French physician André Strohl, described the condition in 1916.

Signs and symptoms

The first symptoms of Guillain–Barré syndrome are numbness, tingling, and pain, alone or in combination. This is followed by weakness of the legs and arms that affects both sides equally and worsens over time. The weakness can take half a day to over two weeks to reach maximum severity, and then becomes steady. In one in five people, the weakness continues to progress for as long as four weeks. The muscles of the neck may also be affected, and about half experience involvement of the cranial nerves which supply the head and face; this may lead to weakness of the muscles of the face, swallowing difficulties and sometimes weakness of the eye muscles. In 8%, the weakness affects only the legs (paraplegia or paraparesis). Involvement of the muscles that control the bladder and anus is unusual. In total, about a third of people with Guillain–Barré syndrome continue to be able to walk. Once the weakness has stopped progressing, it persists at a stable level ("plateau phase") before improvement occurs. The plateau phase can take between two days and six months, but the most common duration is a week. Pain-related symptoms affect more than half, and include back pain, painful tingling, muscle pain and pain in the head and neck relating to irritation of the lining of the brain.

Many people with Guillain–Barré syndrome have experienced the signs and symptoms of an infection in the 3–6 weeks prior to the onset of the neurological symptoms. This may consist of upper respiratory tract infection (rhinitis, sore throat) or diarrhea.

In children, particularly those younger than six years old, the diagnosis can be difficult and the condition is often initially mistaken (sometimes for up to two weeks) for other causes of pains and difficulty walking, such as viral infections, or bone and joint problems.

On neurological examination, characteristic features are the reduced strength of muscles and reduced or absent tendon reflexes (hypo- or areflexia, respectively). However, a small proportion have normal reflexes in affected limbs before developing areflexia, and some may have exaggerated reflexes. In the Miller Fisher variant of Guillain–Barré syndrome (see below), a triad of weakness of the eye muscles, abnormalities in coordination, as well as absent reflexes can be found. The level of consciousness is normally unaffected in Guillain–Barré syndrome, but the Bickerstaff brainstem encephalitis subtype may feature drowsiness, sleepiness, or coma.

Respiratory failure

A quarter of all people with Guillain–Barré syndrome develop weakness of the breathing muscles leading to respiratory failure, the inability to breathe adequately to maintain healthy levels of oxygen and/or carbon dioxide in the blood. This life-threatening scenario is complicated by other medical problems such as pneumonia, severe infections, blood clots in the lungs and bleeding in the digestive tract in 60% of those who require artificial ventilation.

Autonomic dysfunction

The autonomic or involuntary nervous system, which is involved in the control of body functions such as heart rate and blood pressure, is affected in two thirds of people with Guillain–Barré syndrome, but the impact is variable. Twenty percent may experience severe blood-pressure fluctuations and irregularities in the heart beat, sometimes to the point that the heart beat stops and requiring pacemaker-based treatment. Other associated problems are abnormalities in perspiration and changes in the reactivity of the pupils. Autonomic nervous system involvement can affect even those who do not have severe muscle weakness.

Causes

A scanning electron microscope-derived image of Campylobacter jejuni, which triggers about 30% of cases of Guillain–Barré syndrome

Two thirds of people with Guillain–Barré syndrome have experienced an infection before the onset of the condition. Most commonly these are episodes of gastroenteritis or a respiratory tract infection. In many cases, the exact nature of the infection can be confirmed. Approximately 30% of cases are provoked by Campylobacter jejuni bacteria, which cause diarrhea. A further 10% are attributable to cytomegalovirus (CMV, HHV-5). Despite this, only very few people with Campylobacter or CMV infections develop Guillain–Barré syndrome (0.25–0.65 per 1000 and 0.6–2.2 per 1000 episodes, respectively). The strain of Campylobacter involved may determine the risk of GBS; different forms of the bacteria have different lipopolysaccharides on their surface, and some may induce illness (see below) while others will not.

Links between other infections and GBS are less certain. Two other herpesviruses (Epstein–Barr virus/HHV-4 and varicella zoster virus/HHV-3) and the bacterium Mycoplasma pneumoniae have been associated with GBS. The tropical viral infection dengue fever and Zika virus have also been associated with episodes of GBS. Previous hepatitis E virus infection has been found to be more common in people with Guillain–Barré syndrome.

Some cases may be triggered by the influenza virus and potentially influenza vaccine. An increased incidence of Guillain–Barré syndrome followed influenza immunization that followed the 1976 swine flu outbreak (H1N1 A/NJ/76); 8.8 cases per million recipients developed the complication. Since then, close monitoring of cases attributable to vaccination has demonstrated that influenza itself can induce GBS. Small increases in incidence have been observed in subsequent vaccination campaigns, but not to the same extent. The 2009 flu pandemic vaccine (against pandemic swine flu virus H1N1/PDM09) did not cause a significant increase in cases. It is considered that the benefits of vaccination in preventing influenza outweigh the small risks of GBS after vaccination. In fact, natural influenza infection is a stronger risk factor for the development of GBS than is influenza vaccination and getting the vaccination actually reduces the risk of GBS overall by lowering the risk of catching influenza. Even those who have previously experienced Guillain–Barré syndrome are considered safe to receive the vaccine in the future. Nevertheless, in the United States GBS after seasonal influenza vaccination is listed on the federal government's vaccine injury table and compensation may be available through the National Vaccine Injury Compensation Program. Other vaccines, such as those against poliomyelitis, tetanus or measles, have not been associated with a risk of GBS.

Mechanism

Structure of a typical neuron

Neuron
Dendrite Soma Axon Nucleus Node of Ranvier Axon terminal Schwann cell Myelin sheath

Guillain–Barré syndrome – nerve damage

The nerve dysfunction in Guillain–Barré syndrome is caused by an immune attack on the nerve cells of the peripheral nervous system and their support structures. The nerve cells have their body (the soma) in the spinal cord and a long projection (the axon) that carries electrical nerve impulses to the neuromuscular junction where the impulse is transferred to the muscle. Axons are wrapped in a sheath of Schwann cells that contain myelin. Between Schwann cells are gaps (nodes of Ranvier) where the axon is exposed. Different types of Guillain–Barré syndrome feature different types of immune attack. The demyelinating variant (AIDP, see below) features damage to the myelin sheath by white blood cells (T lymphocytes and macrophages); this process is preceded by activation of a group of blood proteins known as complement. In contrast, the axonal variant is mediated by IgG antibodies and complement against the cell membrane covering the axon without direct lymphocyte involvement.

Various antibodies directed at nerve cells have been reported in Guillain–Barré syndrome. In the axonal subtype, these antibodies have been shown to bind to gangliosides, a group of substances found in peripheral nerves. A ganglioside is a molecule consisting of ceramide bound to a small group of hexose-type sugars and containing various numbers of N-acetylneuraminic acid groups. The key four gangliosides against which antibodies have been described are GM1, GD1a, GT1a, and GQ1b, with different anti-ganglioside antibodies being associated with particular features; for instance, GQ1b antibodies have been linked with Miller Fisher variant GBS and related forms including Bickerstaff encephalitis. The production of these antibodies after an infection is probably the result of molecular mimicry, where the immune system is reacting to microbial substances, but the resultant antibodies also react with substances occurring naturally in the body. After a Campylobacter infection, the body produces antibodies of the IgA class; only a small proportion of people also produce IgG antibodies against bacterial substance cell wall substances (e.g. lipooligosaccharides) that crossreact with human nerve cell gangliosides. It is not currently known how this process escapes central tolerance to gangliosides, which is meant to suppress the production of antibodies against the body's own substances. Not all antiganglioside antibodies cause disease, and it has recently been suggested that some antibodies bind to more than one type of epitope simultaneously (heterodimeric binding) and that this determines the response. Furthermore, the development of pathogenic antibodies may depend on the presence of other strains of bacteria in the bowel.

Diagnosis

The diagnosis of Guillain–Barré syndrome depends on findings such as rapid development of muscle paralysis, absent reflexes, absence of fever, and a likely cause. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and nerve conduction studies are supportive investigations commonly performed in the diagnosis of GBS. Testing for antiganglioside antibodies is often performed, but their contribution to diagnosis is usually limited. Blood tests are generally performed to exclude the possibility of another cause for weakness, such as a low level of potassium in the blood. An abnormally low level of sodium in the blood is often encountered in Guillain–Barré syndrome. This has been attributed to the inappropriate secretion of antidiuretic hormone, leading to relative retention of water.

In many cases, magnetic resonance imaging of the spinal cord is performed to distinguish between Guillain–Barré syndrome and other conditions causing limb weakness, such as spinal cord compression. If an MRI scan shows enhancement of the nerve roots, this may be indicative of GBS. In children, this feature is present in 95% of scans, but it is not specific to Guillain–Barré syndrome, so other confirmation is also needed.

Spinal fluid

Cerebrospinal fluid envelops the brain and the spine, and lumbar puncture or spinal tap is the removal of a small amount of fluid using a needle inserted between the lumbar vertebrae. Characteristic findings in Guillain–Barré syndrome are an elevated protein level, usually greater than 0.55 g/L, and fewer than 10 white blood cells per cubic millimeter of fluid ("albuminocytological dissociation"). This pattern distinguishes Guillain–Barré syndrome from other conditions (such as lymphoma and poliomyelitis) in which both the protein and the cell count are elevated. Elevated CSF protein levels are found in approximately 50% of patients in the first 3 days after onset of weakness, which increases to 80% after the first week.

Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered.

Neurophysiology

Directly assessing nerve conduction of electrical impulses can exclude other causes of acute muscle weakness, as well as distinguish the different types of Guillain–Barré syndrome. Needle electromyography (EMG) and nerve conduction studies may be performed. In the first two weeks, these investigations may not show any abnormality. Neurophysiology studies are not required for the diagnosis.

Formal criteria exist for each of the main subtypes of Guillain–Barré syndrome (AIDP and AMAN/AMSAN, see below), but these may misclassify some cases (particularly where there is reversible conduction failure) and therefore changes to these criteria have been proposed. Sometimes, repeated testing may be helpful.

Clinical subtypes

A number of subtypes of Guillain–Barré syndrome are recognized. Despite this, many people have overlapping symptoms that can make the classification difficult in individual cases. All types have partial forms. For instance, some people experience only isolated eye-movement or coordination problems; these are thought to be a subtype of Miller Fisher syndrome and have similar antiganglioside antibody patterns.

Type	Symptoms	Population affected	Nerve conduction studies	Antiganglioside antibodies
Acute inflammatory demyelinating polyneuropathy (AIDP)	Sensory symptoms and muscle weakness, often with cranial nerve weakness and autonomic involvement	Most common in Europe and North America	Demyelinating polyneuropathy	No clear association
Acute motor axonal neuropathy (AMAN)	Isolated muscle weakness without sensory symptoms in less than 10%; cranial nerve involvement uncommon	Rare in Europe and North America, substantial proportion (30-65%) in Asia and Central and South America; sometimes called "Chinese paralytic syndrome"	Axonal polyneuropathy, normal sensory action potential	GM1a/b, GD1a & GalNac-GD1a
Acute motor and sensory axonal neuropathy (AMSAN)	Severe muscle weakness similar to AMAN but with sensory loss	-	Axonal polyneuropathy, reduced or absent sensory action potential	GM1, GD1a
Pharyngeal-cervical-brachial variant	Weakness particularly of the throat muscles, and face, neck, and shoulder muscles	-	Generally normal, sometimes axonal neuropathy in arms	Mostly GT1a, occasionally GQ1b, rarely GD1a
Miller Fisher syndrome	Ataxia, eye muscle weakness, areflexia but usually no limb weakness	This variant occurs more commonly in men than in women (2:1 ratio). Cases typically occur in the spring and the average age of occurrence is 43 years old.	Generally normal, sometimes discrete changes in sensory conduction or H-reflex detected	GQ1b, GT1a

Other diagnostic entities are often included in the spectrum of Guillain–Barré syndrome. Bickerstaff's brainstem encephalitis, for instance, is part of the group of conditions now regarded as forms of Miller Fisher syndrome (anti-GQ1b antibody syndrome), as well as a related condition labelled "acute ataxic hypersomnolence" where coordination problems and drowsiness are present but no muscle weakness can be detected. BBE is characterized by the rapid onset of ophthalmoplegia, ataxia, and disturbance of consciousness, and may be associated with absent or decreased tendon reflexes and as well as Babinski's sign. The course of the disease is usually monophasic, but recurrent episodes have been reported. MRI abnormalities in the brainstem have been reported in 11%.

Whether isolated acute sensory loss can be regarded as a form of Guillain–Barré syndrome is a matter of dispute; this is a rare occurrence compared to GBS with muscle weakness but no sensory symptoms.

Treatment

Immunotherapy

Plasmapheresis and intravenous immunoglobulins (IVIG) are the two main immunotherapy treatments for GBS. Plasmapheresis attempts to reduce the body's attack on the nervous system by filtering antibodies out of the bloodstream. Similarly, administration of IVIG neutralizes harmful antibodies and inflammation. These two treatments are equally effective, but a combination of the two is not significantly better than either alone. Plasmapheresis speeds recovery when used within four weeks of the onset of symptoms. IVIG works as well as plasmapheresis when started within two weeks of the onset of symptoms, and has fewer complications. IVIG is usually used first because of its ease of administration and safety. Its use is not without risk; occasionally it causes liver inflammation, or in rare cases, kidney failure. Glucocorticoids alone have not been found to be effective in speeding recovery and could potentially delay recovery.

Respiratory failure

Respiratory failure may require intubation of the trachea and breathing support through mechanical ventilation, generally on an intensive care unit. The need for ventilatory support can be anticipated by measurement of two spirometry-based breathing tests: the forced vital capacity (FVC) and the negative inspiratory force (NIF). An FVC of less than 15 ml per kilogram body weight or an NIF of less than 60 cmH₂O are considered markers of severe respiratory failure.

Pain

While pain is common in people with Guillain–Barré syndrome, studies comparing different types of pain medication are insufficient to make a recommendation as to which should be used.

Rehabilitation

Following the acute phase, around 40% of people require intensive rehabilitation with the help of a multidisciplinary team to focus on improving activities of daily living (ADLs). Studies into the subject have been limited, but it is likely that intensive rehabilitation improves long-term symptoms. Teams may include physical therapists, occupational therapists, speech language pathologists, social workers, psychologists, other allied health professionals and nurses. The team usually works under the supervision of a neurologist or rehabilitation physician directing treatment goals.

Physiotherapy interventions include strength, endurance and gait training with graduated increases in mobility, maintenance of posture and alignment as well as joint function. Occupational therapy aims to improve everyday function with domestic and community tasks as well as driving and work. Home modifications, gait aids, orthotics and splints may be provided. Speech-language pathology input may be required in those with speech and swallowing problems, as well as to support communication in those who require ongoing breathing support (often through a tracheostomy). Nutritional support may be provided by the team and by dietitians. Psychologists may provide counseling and support. Psychological interventions may also be required for anxiety, fear and depression.

Prognosis

Guillain–Barré syndrome can lead to death as a result of a number of complications: severe infections, blood clots, and cardiac arrest likely due to autonomic neuropathy. Despite optimum care, this occurs in about 5% of cases.

There is a variation in the rate and extent of recovery. The prognosis of Guillain–Barré syndrome is determined mainly by age (those over 40 may have a poorer outcome), and by the severity of symptoms after two weeks. Furthermore, those who experienced diarrhea before the onset of disease have a worse prognosis. On the nerve conduction study, the presence of conduction block predicts poorer outcome at 6 months. In those who have received intravenous immunoglobulins, a smaller increase in IgG in the blood two weeks after administration is associated with poorer mobility outcomes at six months than those whose IgG level increased substantially. If the disease continues to progress beyond four weeks, or there are multiple fluctuations in the severity (more than two in eight weeks), the diagnosis may be chronic inflammatory demyelinating polyneuropathy, which is treated differently.

In research studies, the outcome from an episode of Guillain–Barré syndrome is recorded on a scale from 0 to 6, where 0 denotes completely healthy; 1 very minor symptoms but able to run; 2 able to walk but not to run; 3 requiring a stick or other support; 4 confined to bed or chair; 5 requiring long-term respiratory support; 6 death.

The health-related quality of life (HRQL) after an attack of Guillain–Barré syndrome can be significantly impaired. About a fifth are unable to walk unaided after six months, and many experience chronic pain, fatigue and difficulty with work, education, hobbies and social activities. HRQL improves significantly in the first year.

Epidemiology

In Western countries, the number of new episodes per year has been estimated to be between 0.89 and 1.89 cases per 100,000 people. Children and young adults are less likely to be affected than the elderly: the risk increases by 20% for every decade of life. Men are more likely to develop Guillain–Barré syndrome than women; the relative risk for men is 1.78 compared to women.

The distribution of subtypes varies between countries. In Europe and the United States, 60–80% of people with Guillain–Barré syndrome have the demyelinating subtype (AIDP), and AMAN affects only a small number (6–7%). In Asia and Central and South America, that proportion is significantly higher (30–65%). This may be related to the exposure to different kinds of infection, but also the genetic characteristics of that population. Miller Fisher variant is thought to be more common in Southeast Asia.

History

Georges Guillain, together with Barré and Strohl, described two cases of self-limiting acute paralysis with peculiar changes in the cerebrospinal fluid. He succeeded his teacher Pierre Marie as professor of neurology at the Salpêtrière hospital in Paris in 1925.

 

French physician Jean-Baptiste Octave Landry first described the disorder in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl diagnosed two soldiers with the illness and described the key diagnostic abnormality—albuminocytological dissociation—of increased spinal fluid protein concentration but a normal cell count.

Canadian neurologist C. Miller Fisher described the variant that bears his name in 1956. British neurologist Edwin Bickerstaff, based in Birmingham, described the brainstem encephalitis type in 1951 with Philip Cloake, and made further contributions with another paper in 1957. Guillain had reported on some of these features prior to their full description in 1938. Further subtypes have been described since then, such as the form featuring pure ataxia and the type causing pharyngeal-cervical-brachial weakness. The axonal subtype was first described in the 1990s.

Diagnostic criteria were developed in the late 1970s after the series of cases associated with swine flu vaccination. These were refined in 1990. The case definition was revised by the Brighton Collaboration for vaccine safety in 2009, but is mainly intended for research. Plasma exchange was first used in 1978 and its benefit confirmed in larger studies in 1985. Intravenous immunoglobulins were introduced in 1988, and its non-inferiority compared to plasma exchange was demonstrated in studies in the early 1990s.

Research directions

The understanding of the disease mechanism of Guillain–Barré syndrome has evolved in recent years. Development of new treatments has been limited since immunotherapy was introduced in the 1980s and 1990s. Current research is aimed at demonstrating whether some people who have received IVIg might benefit from a second course if the antibody levels measured in blood after treatment have shown only a small increase. Studies of the immunosuppressive drugs mycophenolate mofetil, brain-derived neurotrophic factor and interferon beta (IFN-β) have not demonstrated benefit to support their widespread use.

An animal model (experimental autoimmune neuritis in rats) is often used for studies, and some agents have shown promise: glatiramer acetate, quinpramine, fasudil (an inhibitor of the Rho-kinase enzyme), and the heart drug flecainide. An antibody targeted against the anti-GD3 antiganglioside antibody has shown benefit in laboratory research. Given the role of the complement system in GBS, it has been suggested that complement inhibitors (such as the drug eculizumab) may be effective.

Lumbar puncture

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Lumbar_puncture 

 

Lumbar puncture
Lumbar puncture in a sitting position. The reddish-brown swirls on the patient's back are tincture of iodine (an antiseptic).
Other names	Spinal tap
ICD-9-CM	03.31
MeSH	D013129
eMedicine	80773

Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to help diagnose diseases of the central nervous system, including the brain and spine. Examples of these conditions include meningitis and subarachnoid hemorrhage. It may also be used therapeutically in some conditions. Increased intracranial pressure (pressure in the skull) is a contraindication, due to risk of brain matter being compressed and pushed toward the spine. Sometimes, lumbar puncture cannot be performed safely (for example due to a severe bleeding tendency). It is regarded as a safe procedure, but post-dural-puncture headache is a common side effect.

The procedure is typically performed under local anesthesia using a sterile technique. A hypodermic needle is used to access the subarachnoid space and fluid collected. Fluid may be sent for biochemical, microbiological, and cytological analysis. Using ultrasound to landmark may increase success.

Lumbar puncture was first introduced in 1891 by the German physician Heinrich Quincke.

Medical uses

The reason for a lumbar puncture may be to make a diagnosis or to treat a disease.

Diagnosis

The chief diagnostic indications of lumbar puncture are for collection of cerebrospinal fluid (CSF). Analysis of CSF may exclude infectious, inflammatory, and neoplastic diseases affecting the central nervous system. The most common purpose is in suspected meningitis, since there is no other reliable tool with which meningitis, a life-threatening but highly treatable condition, can be excluded. A lumbar puncture can also be used to detect whether someone has 'Stage 1' or 'Stage 2' Trypanosoma brucei. Young infants commonly require lumbar puncture as a part of the routine workup for fever without a source. This is due to higher rates of meningitis than in older persons. Infants also do not reliably show classic symptoms of meningeal irritation (meningismus) like neck stiffness and headache the way adults do. In any age group, subarachnoid hemorrhage, hydrocephalus, benign intracranial hypertension, and many other diagnoses may be supported or excluded with this test. It may also be used to detect the presence of malignant cells in the CSF, as in carcinomatous meningitis or medulloblastoma. CSF containing less than 10 red blood cells (RBCs)/mm³ constitutes a "negative" tap in the context of a workup for subarachnoid hemorrhage, for example. Taps that are "positive" have an RBC count of 100/mm³ or more.

Treatment

Lumbar punctures may also be done to inject medications into the cerebrospinal fluid ("intrathecally"), particularly for spinal anesthesia or chemotherapy. 

Serial lumbar punctures may be useful in temporary treatment of idiopathic intracranial hypertension (IIH). This disease is characterized by increased pressure of CSF which may cause headache and permanent loss of vision. While mainstays of treatment are medication, in some cases lumbar puncture performed multiple times may improve symptoms. It is not recommended as a staple of treatment due to discomfort and risk of the procedure, and the short duration of its efficacy.

Additionally, some people with normal pressure hydrocephalus (characterized by urinary incontinence, a changed ability to walk properly, and dementia) receive some relief of symptoms after removal of CSF.

Contraindications

Lumbar puncture should not be performed in the following situations:

• Idiopathic (unidentified cause) increased intracranial pressure (ICP)
  • Rationale: lumbar puncture in the presence of raised ICP may cause uncal herniation
  • Exception: therapeutic use of lumbar puncture to reduce ICP, but only if obstruction (for example in the third ventricle of the brain) has been ruled out
  • Precaution
    • CT brain, especially in the following situations
      • Age >65
      • Reduced GCS
      • Recent history of seizure
      • Focal neurological signs
      • Abnormal respiratory pattern
      • Hypertension with bradycardia and deteriorating consciousness
    • Ophthalmoscopy for papilledema
• Bleeding diathesis (relative)
  • Coagulopathy
  • Decreased platelet count (<50 10="" sup="" x="">9

/L)

Infections

• Skin infection at puncture site

Vertebral deformities (scoliosis or kyphosis), in hands of an inexperienced physician.^[11][12]

Adverse effects

Headache

Post spinal headache with nausea is the most common complication; it often responds to pain medications and infusion of fluids. It was long taught that this complication can be prevented by strict maintenance of a supine posture for two hours after the successful puncture; this has not been borne out in modern studies involving large numbers of people. Doing the procedure with the person on their side might decrease the risk.^[13] Intravenous caffeine injection is often quite effective in aborting these spinal headaches. A headache that is persistent despite a long period of bedrest and occurs only when sitting up may be indicative of a CSF leak from the lumbar puncture site. It can be treated by more bedrest, or by an epidural blood patch, where the person's own blood is injected back into the site of leakage to cause a clot to form and seal off the leak.

The risk of headache and need for analgesia and blood patch is much reduced if "atraumatic" needles are used. This does not affect the success rate of the procedure in other ways.

Other

Contact between the side of the lumbar puncture needle and a spinal nerve root can result in anomalous sensations (paresthesia) in a leg during the procedure; this is harmless and people can be warned about it in advance to minimize their anxiety if it should occur.

Serious complications of a properly performed lumbar puncture are extremely rare. They include spinal or epidural bleeding, adhesive arachnoiditis and trauma to the spinal cord or spinal nerve roots resulting in weakness or loss of sensation, or even paraplegia. The latter is exceedingly rare, since the level at which the spinal cord ends (normally the inferior border of L1, although it is slightly lower in infants) is several vertebral spaces above the proper location for a lumbar puncture (L3/L4). There are case reports of lumbar puncture resulting in perforation of abnormal dural arterio-venous malformations, resulting in catastrophic epidural hemorrhage; this is exceedingly rare.

The procedure is not recommended when epidural infection is present or suspected, when topical infections or dermatological conditions pose a risk of infection at the puncture site or in patients with severe psychosis or neurosis with back pain. Some authorities believe that withdrawal of fluid when initial pressures are abnormal could result in spinal cord compression or cerebral herniation; others believe that such events are merely coincidental in time, occurring independently as a result of the same pathology that the lumbar puncture was performed to diagnose. In any case, computed tomography of the brain is often performed prior to lumbar puncture if an intracranial mass is suspected.

Technique

Mechanism

The brain and spinal cord are enveloped by a layer of cerebrospinal fluid, 125-150 ml in total (in adults) which acts as a shock absorber and provides a medium for the transfer of nutrients and waste products. The majority is produced by the choroid plexus in the brain and circulates from there to other areas, before being reabsorbed into the circulation (predominantly by the arachnoid granulations).

The cerebrospinal fluid can be accessed most safely in the lumbar cistern. Below the first or second lumbar vertebrae (L1 or L2) the spinal cord terminates (conus medullaris). Nerves continue down the spine below this, but in a loose bundle of nerve fibers called the cauda equina. There is lower risk with inserting a needle into the spine at the level of the cauda equina because these loose fibers move out of the way of the needle without being damaged. The lumbar cistern extends into the sacrum.

Procedure

Illustration depicting lumbar puncture (spinal tap)

 

Spinal needles used in lumbar puncture.

 

Illustration depicting common positions for lumbar puncture procedure.

The person is usually placed on their side (left more commonly than right). The patient bends the neck so the chin is close to the chest, hunches the back, and brings knees toward the chest. This approximates a fetal position as much as possible. Patients may also sit on a stool and bend their head and shoulders forward. The area around the lower back is prepared using aseptic technique. Once the appropriate location is palpated, local anaesthetic is infiltrated under the skin and then injected along the intended path of the spinal needle. A spinal needle is inserted between the lumbar vertebrae L3/L4, L4/L5 or L5/S1 and pushed in until there is a "give" as it enters the lumbar cistern wherein the ligamentum flavum is housed. The needle is again pushed until there is a second 'give' that indicates the needle is now past the dura mater. The arachnoid membrane and the dura mater exist in flush contact with one another in the living person's spine due to fluid pressure from CSF in the subarachnoid space pushing the arachnoid membrane out towards the dura. Therefore, once the needle has pierced the dura mater it has also traversed the thinner arachnoid membrane. The needle is then in the subarachnoid space. The stylet from the spinal needle is then withdrawn and drops of cerebrospinal fluid are collected. The opening pressure of the cerebrospinal fluid may be taken during this collection by using a simple column manometer. The procedure is ended by withdrawing the needle while placing pressure on the puncture site. The spinal level is so selected to avoid spinal injuries. In the past, the patient would lie on their back for at least six hours and be monitored for signs of neurological problems. There is no scientific evidence that this provides any benefit. The technique described is almost identical to that used in spinal anesthesia, except that spinal anesthesia is more often done with the patient in a seated position.

The upright seated position is advantageous in that there is less distortion of spinal anatomy which allows for easier withdrawal of fluid. Some practitioners prefer it for lumbar puncture in obese patients, where lying on their side would cause a scoliosis and unreliable anatomical landmarks. However, opening pressures are notoriously unreliable when measured in the seated position. Therefore, patients will ideally lie on their side if practitioners need to measure opening pressure. 

Reinsertion of the stylet may decrease the rate of post lumbar puncture headaches.

Although not available in all clinical settings, use of ultrasound is helpful for visualizing the interspinous space and assessing the depth of the spine from the skin. Use of ultrasound reduces the number of needle insertions and redirections, and results in higher rates of successful lumbar puncture. If the procedure is difficult, such as in people with spinal deformities such as scoliosis, it can also be performed under fluoroscopy (under continuous X-ray imaging).

Children

In children, a sitting flexed position was as successful as lying on the side with respect to obtaining non-traumatic CSF, CSF for culture, and cell count. There was a higher success rate in obtaining CSF in the first attempt in infants younger than 12 months in the sitting flexed position.

The spine of an infant at the time of birth differs from the adult spine. The conus medullaris (bottom of the spinal cord) terminates at the level of L1 in adults, but may range in term neonates (newly born babies) from L1-L3 levels. It is important to insert the spinal needle below the conus medullaris at the L3/L4 or L4/L5 interspinous levels. With growth of the spine, the conus typically reaches the adult level (L1) by 2 years of age.

The ligamentum flavum and dura mater are not as thick in infants and children as they are in adults. Therefore, it is difficult to assess when the needle passes through them into the subarachnoid space because the characteristic "pop" or "give" may be subtle or nonexistent in the pediatric lumbar puncture. To decrease the chances of inserting the spinal needle too far, some clinicians use the "Cincinnati" method. This method involves removing the stylet of the spinal needle once the needle has advanced through the dermis. After removal of the stylet, the needle is inserted until CSF starts to come out of the needle. Once all of the CSF is collected, the stylet is then reinserted before removal of the needle.

Interpretation

Analysis of the cerebrospinal fluid generally includes a cell count and determination of the glucose and protein concentrations. The other analytical studies of cerebrospinal fluid are conducted according to the diagnostic suspicion.

Pressure determination

Lumbar puncture in a child suspected of having meningitis.

Increased CSF pressure can indicate congestive heart failure, cerebral edema, subarachnoid hemorrhage, hypo-osmolality resulting from hemodialysis, meningeal inflammation, purulent meningitis or tuberculous meningitis, hydrocephalus, or pseudotumor cerebri. In the setting of raised pressure (or normal pressure hydrocephalus, where the pressure is normal but there is excessive CSF), lumbar puncture may be therapeutic.

Decreased CSF pressure can indicate complete subarachnoid blockage, leakage of spinal fluid, severe dehydration, hyperosmolality, or circulatory collapse. Significant changes in pressure during the procedure can indicate tumors or spinal blockage resulting in a large pool of CSF, or hydrocephalus associated with large volumes of CSF.

Cell count

The presence of white blood cells in cerebrospinal fluid is called pleocytosis. A small number of monocytes can be normal; the presence of granulocytes is always an abnormal finding. A large number of granulocytes often heralds bacterial meningitis. White cells can also indicate reaction to repeated lumbar punctures, reactions to prior injections of medicines or dyes, central nervous system hemorrhage, leukemia, recent epileptic seizure, or a metastatic tumor. When peripheral blood contaminates the withdrawn CSF, a common procedural complication, white blood cells will be present along with erythrocytes, and their ratio will be the same as that in the peripheral blood. 

The finding of erythrophagocytosis, where phagocytosed erythrocytes are observed, signifies haemorrhage into the CSF that preceded the lumbar puncture. Therefore, when erythrocytes are detected in the CSF sample, erythrophagocytosis suggests causes other than a traumatic tap, such as intracranial haemorrhage and haemorrhagic herpetic encephalitis. In which case, further investigations are warranted, including imaging and viral culture.

Microbiology

CSF can be sent to the microbiology lab for various types of smears and cultures to diagnose infections.

• Gram staining may demonstrate gram positive bacteria in bacterial meningitis.
• Microbiological culture is the gold standard for detecting bacterial meningitis. Bacteria, fungi, and viruses can all be cultured by using different techniques.
• Polymerase chain reaction (PCR) has been a great advance in the diagnosis of some types of meningitis, such as meningitis from herpesvirus and enterovirus. It has high sensitivity and specificity for many infections of the CNS, is fast, and can be done with small volumes of CSF. Even though testing is expensive, cost analyses of PCR testing in neonatal patients demonstrated savings via reduced cost of hospitalization.
• Numerous antibody-mediated tests for CSF are available in some countries: these include rapid tests for antigens of common bacterial pathogens, treponemal titers for the diagnosis of neurosyphilis and Lyme disease, Coccidioides antibody, and others.
• The India ink test is still used for detection of meningitis caused by Cryptococcus neoformans, but the cryptococcal antigen (CrAg) test has a higher sensitivity.

Chemistry

Several substances found in cerebrospinal fluid are available for diagnostic measurement.

• Glucose is present in the CSF; the level is usually about 60% that in the peripheral circulation. A fingerstick or venipuncture at the time of lumbar puncture may therefore be performed to assess peripheral glucose levels and determine a predicted CSF glucose value. Decreased glucose levels can indicate fungal, tuberculous or pyogenic infections; lymphomas; leukemia spreading to the meninges; meningoencephalitic mumps; or hypoglycemia. A glucose level of less than one third of blood glucose levels in association with low CSF lactate levels is typical in hereditary CSF glucose transporter deficiency also known as De Vivo disease.
• Increased glucose levels in the fluid can indicate diabetes, although the 60% rule still applies.
• Increased levels of glutamine are often involved with hepatic encephalopathies, Reye's syndrome, hepatic coma, cirrhosis, hypercapnia and depression.
• Increased levels of lactate can occur the presence of cancer of the CNS, multiple sclerosis, heritable mitochondrial disease, low blood pressure, low serum phosphorus, respiratory alkalosis, idiopathic seizures, traumatic brain injury, cerebral ischemia, brain abscess, hydrocephalus, hypocapnia or bacterial meningitis.
• The enzyme lactate dehydrogenase can be measured to help distinguish meningitides of bacterial origin, which are often associated with high levels of the enzyme, from those of viral origin in which the enzyme is low or absent.
• Changes in total protein content of cerebrospinal fluid can result from pathologically increased permeability of the blood-cerebrospinal fluid barrier, obstructions of CSF circulation, meningitis, neurosyphilis, brain abscesses, subarachnoid hemorrhage, polio, collagen disease or Guillain–Barré syndrome, leakage of CSF, increases in intracranial pressure, or hyperthyroidism. Very high levels of protein may indicate tuberculous meningitis or spinal block.
• IgG synthetic rate is calculated from measured IgG and total protein levels; it is elevated in immune disorders such as multiple sclerosis, transverse myelitis, and neuromyelitis optica of Devic. Oligoclonal bands may be detected in CSF but not in serum, suggesting intrathecal antibody production.

Infection	Appearance	WBCs / mm3	Protein (g/l)	Glucose
Normal	Clear	<5 font="">	0.15 to 0.45	> 2/3 of blood glucose
Bacterial	Yellowish, turbid	> 1,000 (mostly PMNs)	> 1	Low
Viral	Clear	< 200 (mostly lymphocytes)	Mild increase	Normal or mildly low
Tuberculosis	Yellowish and viscous	Modest increase	Markedly Increased	Decreased
Fungal	Yellowish and viscous	< 50 (mostly lymphocytes)	Initially normal than increased	Normal or mildly low

History

Lumbar puncture, early 20th century.

The first technique for accessing the dural space was described by the London physician Walter Essex Wynter. In 1889 he developed a crude cut down with cannulation in four patients with tuberculous meningitis. The main purpose was the treatment of raised intracranial pressure rather than for diagnosis. The technique for needle lumbar puncture was then introduced by the German physician Heinrich Quincke, who credits Wynter with the earlier discovery; he first reported his experiences at an internal medicine conference in Wiesbaden, Germany, in 1891. He subsequently published a book on the subject.

The lumbar puncture procedure was taken to the United States by Arthur H. Wentworth an assistant professor at the Harvard Medical School, based at Children's Hospital. In 1893 he published a long paper on diagnosing cerebrospinal meningitis by examining spinal fluid. However, he was criticized by antivivisectionists for having obtained spinal fluid from children. He was acquitted, but, nevertheless, he was uninvited from the then forming Johns Hopkins School of Medicine, where he would have been the first professor of pediatrics.

Historically lumbar punctures were also employed in the process of performing a pneumoencephalography, a nowadays obsolete X-ray imaging study of the brain that was performed extensively from the 1920s until the advent of modern non-invasive neuroimaging techniques such as MRI and CT in the 1970s. During this quite painful procedure, CSF was replaced with air or some other gas via the lumbar puncture in order to enhance the appearance of certain areas of the brain on plain radiographs.