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This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2007) |
| Lumbar puncture |
| Intervention |
A patient undergoes a lumbar puncture at the hands of a neurologist. The reddish-brown swirls on the patient's back are tincture of iodine (an antiseptic).
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| ICD-9-CM |
03.31 |
| MeSH |
D013129 |
A lumbar puncture (or LP, and colloquially known as a spinal tap) is a diagnostic and at times therapeutic procedure that is performed to collect a sample of cerebrospinal fluid (CSF) for biochemical, microbiological, and cytological analysis, or very rarely as a treatment ("therapeutic lumbar puncture") to relieve increased intracranial pressure.
Contents
- 1 Indications
- 1.1 Diagnostic
- 1.2 Therapeutic
- 2 Contraindications
- 3 Procedure
- 4 Risks
- 5 Diagnostics
- 6 History
- 7 References
- 8 External links
Indications[edit source | edit]
The indications of lumbar puncture may be diagnostic[1][2] or therapeutic.[1]
Diagnostic[edit source | edit]
The chief diagnostic indications of lumbar puncture is for collection of cerebrospinal fluid and its evaluation to exclude infectious,[1][3] inflammatory[1] and neoplastic diseases[1] affecting the central nervous system. The most common purpose is in case of suspected meningitis,[4] since there is no other reliable tool with which meningitis, a life-threatening but highly treatable condition, can be excluded. Young infants commonly require lumbar puncture as a part of the routine workup for fever without a source, as they have a much higher risk of meningitis than older persons and do not reliably show signs of meningeal irritation (meningismus).[4] 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.
Therapeutic[edit source | edit]
Lumbar punctures may also be done to inject medications into the cerebrospinal fluid ("intrathecally"), particularly for spinal anesthesia[5] or chemotherapy. Lumbar punctures can also be used as a treatment for elevated intracranial pressure, such as occurs with cryptococcal meningitis, by removing fluid and decreasing the pressure.
Contraindications[edit source | edit]
Lumbar puncture should not be performed in the following situations
- Idiopathic (unidentified cause) increased intracranial pressure (ICP)
- Rationale: lumbar puncture in the presence of increased ICP may cause uncal herniation
- Exception: therapeutic use of lumbar puncture to reduce ICP
- Precaution
- CT brain is advocated by some, especially in the following situations
- Age >65
- Reduced GCS or conscious state
- Recent history of seizure
- Focal neurological signs
- Ophthalmoscopy for papilledema
- Bleeding diathesis
- Coagulopathy
- Decreased platelet count (<50 x 109/L)
- Infections[6]
- Skin infection at puncture site
- Sepsis
- Abnormal respiratory pattern
- Hypertension with bradycardia and deteriorating consciousness
- Vertebral deformities (scoliosis or kyphosis), in hands of an inexperienced physician.[7][8]
Procedure[edit source | edit]
Illustration depicting lumbar puncture (spinal tap)
Spinal needles used in lumbar puncture.
In performing a lumbar puncture, first the patient is usually placed in a left (or right) lateral position with their neck bent in full flexion and knees bent in full flexion up to their chest, approximating a fetal position as much as possible. It is also possible to have the patient 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[5] or L5/S1[5] and pushed in until there is a "give" that indicates the needle is past the ligamentum flavum. The needle is again pushed until there is a second 'give' that indicates the needle is now past the dura mater. Since 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), once the needle has pierced the dura mater it has also traversed the thinner arachnoid membrane and is now 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.[5] In the past, the patient would often be asked to lie on their back for at least six hours and be monitored for signs of neurological problems, though 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. It is preferred by some practitioners when a lumbar puncture is performed on an obese patient where having them lie on their side would cause a scoliosis and unreliable anatomical landmarks. On the other hand, opening pressures are notoriously unreliable when measured on a seated patient and therefore the left or right lateral (lying down) position is preferred if an opening pressure needs to be measured. Patient anxiety during the procedure can lead to increased CSF pressure, especially if the person holds their breath, tenses their muscles or flexes their knees too tightly against their chest. Diagnostic analysis of changes in fluid pressure during lumbar puncture procedures requires attention both to the patient's condition during the procedure and to their medical history.[citation needed] Reinsertion of the stylet may decrease the rate of post lumbar puncture headaches.[8]
Risks[edit source | edit]
Post spinal headache with nausea is the most common complication; it often responds to analgesics and infusion of fluids. It was long taught that this complication can often 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 patients. Merritt's Neurology (10th edition), in the section on lumbar puncture, notes that intravenous caffeine injection is often quite effective in aborting these so-called "spinal headaches." 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 patients can be warned about it in advance to minimize their anxiety if it should occur. 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 patient's own blood is injected back into the site of leakage to cause a clot to form and seal off the leak.
Serious complications of a properly performed lumbar puncture are extremely rare.[1] They include spinal or epidural bleeding, adhesive arachnoiditis and trauma to the spinal cord[5] 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. Failure rates can go up to 28% and therefore there is need for skill and experience.[5]
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.
Removal of cerebrospinal fluid resulting in reduced fluid pressure has been shown to correlate with greater reduction of cerebral blood flow among patients with Alzheimer's disease. Its clinical significance is uncertain.
Diagnostics[edit source | edit]
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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.[1]
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.
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. Lumbar puncture for the purpose of reducing pressure is performed in some patients with idiopathic intracranial hypertension (also called pseudotumor cerebri.)
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,[9] where phagocytosed erythrocytes is 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.
Several substances found in cerebrospinal fluid are available for diagnostic measurement.
- Measurement of chloride levels may aid in detecting the presence of tuberculous meningitis.[10][11][12][13]
- Glucose is usually present in the CSF; the level is usually about 60% that in the peripheral circulation.[14] 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[11] can indicate fungal, tuberculous[12] 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.[15]
- Increased glucose levels in the fluid can indicate diabetes, although the 60% rule still applies.[16][17]
- Increased levels of glutamine[18] are often involved with hepatic encephalopathies,[19][20] Reye's syndrome,[21][22] hepatic coma, cirrhosis,[20] hypercapnia and depression.[23]
- 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.[16]
- 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.[24]
- Changes in total protein content of cerebrospinal fluid can result from pathologically increased permeability of the blood-cerebrospinal fluid barrier,[25] 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.
- 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,[26][27] but the cryptococcal antigen (CrAg) test has a higher sensitivity.[28]
- CSF can be sent to the microbiology lab for various types of smears and cultures to diagnose infections.
- Polymerase chain reaction (PCR) has been a great advance in the diagnosis of some types of meningitis. 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, it saves cost of hospitalization.
History[edit source | edit]
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.[29] 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.[30] He subsequently published a book on the subject.[31][32]
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.[33] His career took a nosedive, however, when antivivisectionists criticized him for having obtained spinal fluid from children. He was acquitted, but he was uninvited from the then forming Johns Hopkins School of Medicine, where he would have been the first professor of pediatrics.[citation needed]
References[edit source | edit]
- ^ a b c d e f g Sempere, AP; Berenguer-Ruiz, L; Lezcano-Rodas, M; Mira-Berenguer, F; Waez, M (2007 Oct 1-15). "[Lumbar puncture: its indications, contraindications, complications and technique]". Revista de neurologia 45 (7): 433–6. PMID 17918111.
- ^ Gröschel, K; Schnaudigel, S; Pilgram, SM; Wasser, K; Kastrup, A (2008 Jan). "[The diagnostic lumbar puncture]". Deutsche Medizinische Wochenschrift 133 (1–2): 39–41. doi:10.1055/s-2008-1017470. PMID 18095209.
- ^ Matata, C; Michael, B; Garner, V; Solomon, T (2012 Oct 24-30). "Lumbar puncture: diagnosing acute central nervous system infections". Nursing standard (Royal College of Nursing (Great Britain) : 1987) 27 (8): 49–56; quiz 58. PMID 23189602.
- ^ a b Visintin, C; Mugglestone, MA; Fields, EJ; Jacklin, P; Murphy, MS; Pollard, AJ; Guideline Development, Group; National Institute for Health and Clinical, Excellence (2010 Jun 28). "Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance". BMJ (Clinical research ed.) 340: c3209. doi:10.1136/bmj.c3209. PMID 20584794.
- ^ a b c d e f López, T; Sánchez, FJ; Garzón, JC; Muriel, C (2012 Jan). "Spinal anesthesia in pediatric patients". Minerva anestesiologica 78 (1): 78–87. doi:10.1111/j.1460-9592.2011.03769.x. PMID 22211775Epub 2011 Dec 28
- ^ Mary Louise Turgeon (2005). Clinical hematology: theory and procedures. Lippincott Williams & Wilkins. pp. 401–. ISBN 978-0-7817-5007-3. Retrieved 28 October 2010.
- ^ Roos KL (March 2003). "Lumbar puncture". Semin Neurol 23 (1): 105–14. doi:10.1055/s-2003-40758. PMID 12870112.
- ^ a b Straus SE, Thorpe KE, Holroyd-Leduc J (October 2006). "How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis?". JAMA 296 (16): 2012–22. doi:10.1001/jama.296.16.2012. PMID 17062865.
- ^ Harald Kluge (2007). Atlas of CSF cytology. Thieme. pp. 45–46. ISBN 978-3-13-143161-5. Retrieved 28 October 2010.
- ^ Gierson, HW; Owens, GJ (1961 Feb). "Chloride content of the cerebrospinal fluid.". California medicine 94 (2): 77–8. PMC 1575452. PMID 13705167.
- ^ a b Hendry, E (1939 Jun). "The blood and spinal fluid sugar and chloride content in meningitis". Archives of disease in childhood 14 (78): 159–72. doi:10.1136/adc.14.78.159. PMC 1975626. PMID 21032142.
- ^ a b Gierson, HW; Marx, JI (1955 Apr). "Tuberculous meningitis: the diagnostic and prognostic significance of spinal fluid sugar and chloride". Annals of internal medicine 42 (4): 902–8. doi:10.7326/0003-4819-42-4-902. PMID 14362261.
- ^ Ramkissoon, A; Coovadia, HM (1988 May 7). "Chloride levels in meningitis". South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 73 (9): 522–3. PMID 3375941.
- ^ Nigrovic, Lise E.; Kimia, Amir A.; Shah, Samir S.; Neuman, Mark I. (9 February 2012). "Relationship between Cerebrospinal Fluid Glucose and Serum Glucose". New England Journal of Medicine 366 (6): 576–578. doi:10.1056/NEJMc1111080. PMID 22316468.
- ^ De Vivo, Darryl C.; Trifiletti, Rosario R.; Jacobson, Ronald I.; Ronen, Gabriel M.; Behmand, Ramin A.; Harik, Sami I. (5 September 1991). "Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay". New England Journal of Medicine 325 (10): 703–709. doi:10.1056/NEJM199109053251006. PMID 1714544.
- ^ a b Leen, Wilhelmina G.; Willemsen, Michèl A.; Wevers, Ron A.; Verbeek, Marcel M.; Mendelson, John E. (5 August 2012). "Cerebrospinal Fluid Glucose and Lactate: Age-Specific Reference Values and Implications for Clinical Practice". In Mendelson, John E. PLoS ONE 7 (8): e42745. doi:10.1371/journal.pone.0042745. PMC 3412827. PMID 22880096.
- ^ Servo, C; Pitkänen, E (1975 Dec). "Variation in polyol levels in cerebrospinal fluid and serum in diabetic patients". Diabetologia 11 (6): 575–80. doi:10.1007/BF01222109. PMID 1205026.
- ^ "Cerebrospinal Fluid Glutamine". clinicallabtesting.com. Retrieved 11 August 2013.
- ^ Hourani, Benjamin T.; Hamlin, EM; Reynolds, TB (1 June 1971). "Cerebrospinal Fluid Glutamine as a Measure of Hepatic Encephalopathy". Archives of Internal Medicine 127 (6): 1033–6. doi:10.1001/archinte.1971.00310180049005. PMID 5578559.
- ^ a b Cascino, A; Cangiano, C; Fiaccadori, F; Ghinelli, F; Merli, M; Pelosi, G; Riggio, O; Rossi Fanelli, F; Sacchini, D; Stortoni, M; Capocaccia, L (1982 Sep). "Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy". Digestive diseases and sciences 27 (9): 828–32. doi:10.1007/BF01391377. PMID 7105954.
- ^ Glasgow, Allen M.; Dhiensiri, Kamnual (June 1974). "Improved Assay for Spinal Fluid Glutamine, and Values for Children with Reye's Syndrome". Clinical Chemistry 20 (6): 642–644. PMID 4830166.
- ^ Watanabe, A; Takei, N; Higashi, T; Shiota, T; Nakatsukasa, H; Fujiwara, M; Sakata, T; Nagashima, H (1984 Oct). "Glutamic acid and glutamine levels in serum and cerebrospinal fluid in hepatic encephalopathy". Biochemical medicine 32 (2): 225–31. doi:10.1016/0006-2944(84)90076-0. PMID 6150706.
- ^ Levine, J; Panchalingam, K; Rapoport, A; Gershon, S; McClure, RJ; Pettegrew, JW (2000 Apr 1). "Increased cerebrospinal fluid glutamine levels in depressed patients". Biological psychiatry 47 (7): 586–93. doi:10.1016/S0006-3223(99)00284-X. PMID 10745050.
- ^ Jay H. Stein (1998). Internal Medicine. Elsevier Health Sciences. pp. 1408–. ISBN 978-0-8151-8698-4. Retrieved 12 August 2013.
- ^ Reiber, Hansotto (2003). "Proteins in cerebrospinal fluid and blood: Barriers, CSF flow rate and source-related dynamics". Restorative Neurology and Neuroscience 21 (3–4): 79–96. PMID 14530572.
- ^ Zerpa, R; Huicho, L; Guillén, A (1996 Sep). "Modified India ink preparation for Cryptococcus neoformans in cerebrospinal fluid specimens.". Journal of clinical microbiology 34 (9): 2290–1. PMID 8862601.
- ^ Shashikala; Kanungo, R; Srinivasan, S; Mathew, R; Kannan, M (2004 Jul-Sep). "Unusual morphological forms of Cryptococcus neoformans in cerebrospinal fluid.". Indian journal of medical microbiology 22 (3): 188–90. PMID 17642731.
- ^ Antinori, Spinello; Radice, Anna; Galimberti, Laura; Magni, Carlo; Fasan, Marco; Parravicini, Carlo (2005 Nov). "The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis.". Journal of clinical microbiology 43 (11): 5828–9. doi:10.1128/JCM.43.11.5828-5829.2005. PMC 1287839. PMID 16272534.
- ^ Wynter W. E. (1891). "Four Cases of Tubercular Meningitis in Which Paracentesis of the Theca Vertebralis Was Performed for the Relief of Fluid Pressure". Lancet 1 (3531): 981–2. doi:10.1016/S0140-6736(02)16784-5.
- ^ Quincke HI (1891). Verhandlungen des Congresses für Innere Medizin, Zehnter Congress, Wiesbaden 10. pp. 321–331.
- ^ Quincke HI (1902). Die Technik der Lumbalpunktion. Berlin & Vienna.
- ^ Heinrich Irenaeus Quincke at Who Named It?
- ^ Susan E. Lederer (1997). Subjected to Science: Human Experimentation in America Before the Second World War. JHU Press. p. 216. ISBN 9780801857096. . Page 62 has a reference to an 1896 publication in Boston Med. Surg. J
External links[edit source | edit]
- eMedicine: Lumbar puncture
- Medstudents: Procedures: Lumbar puncture
- Video of lumbar puncture
- Ellenby, MS; Tegtmeyer, K; Lai, S; Braner, DA (2006 Sep 28). "Videos in clinical medicine. Lumbar puncture". The New England journal of medicine 355 (13): e12. doi:10.1056/NEJMvcm054952. PMID 17005943.
- CSF Interpretation: Clinical Practice Guidelines, The Royal Children's Hospital, Melbourne.
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Surgery, Nervous system: neurosurgical and other procedures (ICD-9-CM V3 01–05+89.1, ICD-10-PCS 00–01)
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| Skull |
Craniotomy · Craniectomy (Decompressive craniectomy) · Cranioplasty
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| CNS |
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Brain
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thalamus and globus pallidus: Thalamotomy · Thalamic stimulator · Pallidotomy
ventricular system: Ventriculostomy · Suboccipital puncture · Intracranial pressure monitoring
cerebrum: Psychosurgery (Lobotomy, Bilateral cingulotomy) · Hemispherectomy · Anterior temporal lobectomy
pituitary: Hypophysectomy
hippocampus: Amygdalohippocampectomy
Brain biopsy
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Cerebral meninges
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Meningeal biopsy
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Spinal cord and spinal canal
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Spinal cord and roots (Cordotomy, Rhizotomy)
Vertebrae and intervertebral discs: see Template:Bone, cartilage, and joint procedures
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Medical imaging
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CT head · Cerebral angiography · Pneumoencephalography · Echoencephalography/Transcranial doppler · MRI of brain and brain stem · Brain PET · SPECT of brain · Myelography
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Diagnostic
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Electroencephalography · Lumbar puncture · Polysomnography
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CPRs
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Glasgow Coma Scale · Mini-mental state examination · NIH stroke scale · CHADS score
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| PNS |
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Cranial and peripheral nerves
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Nerve block · Vagotomy
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Sympathetic nerves or ganglia
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Ganglionectomy · Sympathectomy (Endoscopic thoracic sympathectomy)
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Nerves (general)
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Axotomy · Neurectomy · Nerve biopsy
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Diagnostic
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Nerve conduction study · Electromyography
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Medical imaging
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Magnetic resonance neurography
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anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp
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noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr
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proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
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anat (h/r/t/c/b/l/s/a)/phys (r)/devp/prot/nttr/nttm/ntrp
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noco/auto/cong/tumr, sysi/epon, injr
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