Neurol Sci DOI 10.1007/s10072-015-2104-6
HISTORY OF NEUROLOGY
Cerebrospinal fluid and lumbar puncture: the story of a necessary procedure in the history of medicine Sandro Zambito Marsala • Manuela Gioulis Michele Pistacchi
•
Received: 15 October 2014 / Accepted: 2 February 2015 Springer-Verlag Italia 2015
Abstract The aim of our work was to investigate the different historical stages that led gradually to the discovery of the anatomical structures that form and contain cerebrospinal fluid (CSF), until the Quincke idea, to collect the liquid directly at the lumbar level delivering to humanity a diagnostic tool present and absolutely irreplaceable in everyday clinical practice. This is done through consultation of all the historical medical literature, together with the critical examination of the original articles when available in the most rigorous chronological and speculative order, which enabled knowledge advancement. Keywords
Lumbar puncture Cerebrospinal fluid
A brief history of anatomy and physiology of the cerebrospinal fluid The existence of fluid within the brain was certainly observed by the earliest anatomists. The Egyptian physician Imhotep probably was the first to discover intracranial cerebrospinal fluid in vivo in 3000 BC. Indeed, the description was found in The Papyrus of Smith of 1600 BC [1, 2].
S. Zambito Marsala and M. Pistacchi have equally contributed to the manuscript. S. Zambito Marsala (&) M. Gioulis San Martino Hospital, Neurology, Viale Europa 22, CAP 32100 Belluno, Italy e-mail: [email protected] M. Pistacchi Neurology Service, Santorso Hospital, via Garziere 73, 36014 Santorso, VI, Italy
Meninges and ventricles were discovered 5000 years ago and people believed the essence of human activity and thought closely related within these structures. Hippocrates and his School (430–350 BC) cited the existence of a liquid around the falx cerebri [3]. Moreover, they described hydrocephalus condition both in man and domestic animals, being aware that the excess of fluid determined swelling and cranial deformity. However, they were not able to provide clear evidences where inside the head, this storage might be located. Hippocratics believed the head’s express function was to attract fluid from elsewhere inside the body. Aristotle [4], unlike Plato and Hippocrates, recognized the heart as crucial for the fluid movement while the brain was considered a modulator of the liquid temperature. Afterwards, two physicians of the city of Alexandria, namely Erasistratus and Herophilus (300 BC), provided descriptions of the meninges and ventricles: lateral, third, and fourth [5, 6]. Unfortunately, these authors could not benefit the experience of Rufus of Ephesus, (98–117 BC) who although strongly influenced Arabic medicine, was poor considered in the Western world, until the middle of the sixteenth century. If Erasistratus had been able to read the writings of Rufus of Ephesus, the medieval mentality on the subject would have been greatly changed. Later through Marinus of Tyre, the pneumatic theory reached Claudius Galen of Pergamum (129-99) who elaborated Erasistratus concepts in a detailed topographical anatomy of the ventricular system [7]. These evidences needed a long elaboration, since dissection reached a rigorous methodology. Herein, we should specify that dissection was rarely performed until the rise of the school of Bologna, in the early sixteenth century. Unfortunately, for a period of over a thousand years, Galen’s anatomical descriptions were rarely widespread, and his work in their original form was
123
Neurol Sci
not available in the Western world, until the twelfth century, because of the absolute prohibition imposed by religious establishment in anatomy study. Meanwhile, Galenical knowledge was popular in the Arab world. Long time later, Nicolo Massa in his 1536 publication Liber Introductorius Anatomiae described the presence of cerebrospinal fluid (CSF) within cerebral ventricles based on postmortem autopsies [8]. Then, ventricular system anatomy advanced with Andreas Vesalius (1514–1564) and later Julius Aranzi (1530–1589) studies [9, 10] in 1587 with an accurate description of the lateral ventricles system and choroid plexus anatomy. Moreover, Vesalius described the passage between the third to the fourth ventricle named ‘‘aqueduct’’ (later called from Fransois de le Boe of ‘‘Silvio’’ (1614–1672). Subsequently, Willis recognized CSF as a product of distillation of the pineal gland and choroidal plexuses, and Vieussens, who also observed the fluid, believed that the valve was attached for separating the contents of the cerebral and subtentorial ventricles. However, several doubts existed whether the fluid existed in the living or was merely a postmortem precipitation. Some authors like Haller, believed that the cerebral ventricles contained a vapor capable of condensation, which gravitated as water into the spinal spaces. The anatomo-physiological structures and boundaries became more clearly defined in 1692, when Valsalva observed a watery fluid around the spinal cord of a dog, after neck dissection [11]. This evidence was a resultant of their autopsy technique, consisting in a plane section through head and neck. Further strong evidences concerned the effective presence and function of CSF are attributed to Emanuel Swedenborg (1688–1772). He performed numerous dissections between 1736 and 1740. Swedenborg summarized his observations on brain, spinal cord, and blood circulation in a manuscript between 1741 and 1744. Unfortunately, he had no medical credentials, so he was unable to find a publisher. The manuscript was then discovered in Stockholm, more than one century later and finally published and translated in 1887 [12]. Swedenborg referred to the CSF as ‘‘spirituous lymph’’ and ‘‘highly gifted juice’’ that is dispensed from the roof of the fourth ventricle to the medulla oblongata, and the spinal cord [12]. His manuscript also contained comments on the subarachnoid space and the arachnoid membrane. Swedenborg recognized the cerebral cortex as the seat of thought and the source of the sensory and motor functions of the extremities. Then, Albrecht von Haller (1708–1777) based his descriptions on anatomic observations and physiologic experiments, in 1747, in a landmark work in physiology [13], described that the ‘‘water’’ in the brain is secreted into the
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ventricles and absorbed in the veins; in case of excess secretion, it descends to the base of the skull and into the ‘‘spinal marrow,’’ resulting in hydrocephalus. The final complete description of CSF was provided by Domenico Felice Cotugno (1736–1822) in 1743. Cotugno demonstrated (1774) in the ventricles of the living animal the presence of fluid rather than of a vapor. In 1764 he explained in the ‘‘De ischiade nervosa commentarius,’’ the reason why anatomists had ignored the collection of fluid around the brain and spinal cord, arguing the erroneous method in which corpses were dissected, as above mentioned [14]. The modern period begin with Francois Magendie (1783–1855) author of three notable communications published in the Journal de physiologie experimentale et pathologique. Magendie realized the physiological significance of the CSF in brain and ventricles, but he considered the liquor surrounded the brain and inside the ventricles at autopsy, as a consequence of disease [15, 16]. The pioneer work of Magendie anyway established the physiological basis of knowledge of the future development of neurosurgery [17]. The evidence that CSF was produced inside the choroid plexus was provided in 1854 by J Faivre [18]. Hence, the subsequent discoveries substantiated the anatomic pathway and the physiology of the cerebrospinal fluid (Hubert von Luschka) [19] including the demonstration of the CSF fluid production and absorption (Ernest Key and Gustav Retzius) [20]. Nowadays we know that CSF, whose volume is 140–150 ml, is secreted from the choroid plexus into the cerebral ventricles. It circulates within the cerebral ventricles, flowing through intra ventricles foramen, then passes into the third ventricle, and arrives into the fourth ventricle, where, through Magendie and Luschka foramen, it reaches the cisterna magna and the subarachnoid space. From the fourth ventricle, it continues flowing to central canal spinal cord. Most of cerebrospinal fluid is then reabsorbed through the arachnoid villi in the venous sinus of dura mater, while a little part is then reabsorbed directly in the subarachnoid space, through veins and lymphatic vessels. The existence of the barrier was first discovered by Paul Ehrlich in the late nineteenth century [21, 22], when injecting some pigments into an organism, noticed that they colored any organ except the brain. Ehrlich attributed this evidence to the simple inability of the brain to absorb pigments. However, in a subsequent experiment following in 1913, Edwin Goldmann (one of Ehrlich’s students) injected the pigment directly into the spinal fluid. Differently, in this case the brain dyed, against the rest of the body. This clearly demonstrated the existence of a real barrier. He concluded the blood vessels created themselves the
Neurol Sci
barrier, since no definite membrane could be observed. The concept of cerebral blood barrier (then called ‘‘blood–brain barrier’’) was proposed by Lina Stern in 1921 [23]. Its existence could not be proved until the introduction of the scanning electron microscope in the field of medical sciences in the sixties.
When lumbar puncture became a diagnostic procedure Horace Gray [24] was probably the first to perform a drilling within the cerebral ventricles, although the first attempts date back to 1893 with Wyss. The first experiments to perform a cerebral ventricular puncture date 1856 with Middeldorpf through trephining. These moments herald the idea of collecting the CSF in more accessible and less invasive anatomical areas. Heinrich Ireneo Quincke (1842–1922) was researching a safe and simple way to remove the excess fluid in children with hydrocephalus. Since 1872 he studied the physiology of the cerebrospinal fluid in dogs, placing a cannula into the subarachnoid space in the upper part of the lumbar region. He injected the red sulfide of mercury into the subarachnoid space to demonstrate the ‘‘Flu¨ssigkeit’’ or flow. Finally in 1891, however, he realized to obtain the cerebrospinal fluid directly at lumbar level [25]. Likewise in Kiel he was concerned about severe headaches associated with hydrocephalus and, after reading the cases published by Sir. Essex Wynter, he described the first lumbar puncture in ‘‘Uber hydrocephalus’’ at the Tenth Congress of Internal Medicine at Wiesbaden in April 1891 [26]. Certainly in Kiel he performed the first lumbar puncture for therapeutic purposes in December 1890, in a child of 21 months in a coma and on suspicion of tuberculous meningitis. He reached to the subarachnoid space in the lumbar zone with a needle and a cannula and inserted between the third and fourth lumbar vertebral arch to drain the cerebrospinal fluid. The child obtained an improvement of symptomatology. Herein, the original description: ‘‘Case 2 was a boy aged 1 year nine-month coma with suspected tuberculous meningitis, three lumbar punctures were performed at intervals of 3 days in December 1890.: pierced in the lumbar subarachnoid space through a cannula 2 cm. Depth between the third and fourth lumbar vertebral arches and drip I downed a few cubic centimeters of aqueous fluid… you could see clearly increases with maturity and decline of inspiration.’’… The child improved and the nature of meningitis or meningismus remained uncertain. In April 1891, Quincke improved the headache of a 25-year-old man with hydrocephalus by lumbar puncture. Previously in 1888, Quincke removed cerebrospinal fluid
from the ventricles in the brain of a 12-year-old boy, through the holes directly on the skull. On 21 September 1891, he described the lumbar puncture performed on five children and five adults [25]. Moreover, Quincke is credited to be the first to examine in detail the constituents of CSF. He counted the cells, measured total protein by the Kjeldahl method and identified the presence of bacteria in the fluid in pathological circumstances. Essex Wynter with previous studies at the Epsom College, Surrey, in 1891 conceived the first therapeutic procedure that would allow access to the cerebrospinal fluid at the lumbar level. Described at the journal The Lancet were four cases of aspiration of cerebrospinal fluid in during of meningitis [27]. The main purpose was the treatment of intracranial pressure rather than for diagnosis [27]. The first case described concerned a boy aged within 3 years, treated in February 1889 with a diagnosis of meningitis as a result of an ear infection. The second case, treated in February 1890, was a girl of 1 year. The third case was a child of 2 years. Finally, the fourth case was a girl of 13 months. The last three cases described were all suffering from tuberculous meningitis. During the same year but with a different procedure slightly more invasive, Wynter succeeded to get CSF at lumbar level. He conceived a L2 small incision, come down to the dura mater, then inserted a Southey tube with a rubber drainage and subsequently withdrew the infected fluid by reducing the pressure (Southey tubes were still in use in 1960, and were used to relieve dropsy in the legs that had been left in charge during the night to drain liters of fluid oedema in a large bucket). The procedure determined short-term relief; unfortunately, all four patients subsequently died. Wynter did not report these cases until the publication of the May 2, 1891 in Lancet; hence, Quincke is credited as the first performer of the lumbar puncture. Notwithstanding Quincke himself acknowledged the work of Wynter in an internal medicine conference in Wiesbaden in 1891 [26] and later published a book on the subject [25]. The lumbar puncture procedure was transferred in the United States by Arthur H. Wentworth MD, an assistant professor at Harvard Medical School, based in Children’s Hospital. Afterwards in August 1895, Dr. Arthur H. Wentworth achieved the first lumbar puncture at the Children’s Hospital of Boston [28]. ‘‘We punctured the spinal canal, using for the purpose the needle from an antitoxin syringe, and withdrew six cubic centimetres of a clear fluid which looked like distilled water. No tubercle bacilli were found…. Immediately after tapping the canal the child became restless,
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throwing herself about the bed, clutching at her hair and giving vent to short cries. The pulse rose to over 250 in the minute, the respiration was superficial, and the skin was cool and slightly livid. Subcutaneous injections of brandy and ether were given, heaters applied, and the foot of the bed raised. This condition persisted about the same for threequarters of an hour, and then the child became quieter. During the attack I felt considerable uneasiness because I was unprepared for such a result and did not know but that it would terminate fatally. I now believe that the symptoms were due to headache, caused by the removal of fluid, and that her life was not endangered’’ [29]. Later, a considerable technical amelioration resulted from Hans Heinrich Georg Queckenstedt (1876–1918) studies, while serving in the Army in 1916 he developed the homonymous test to detect spinal cord compression. He initiated to study CSF dynamics and components and he noticed the fluctuations of CSF pressure with breathing. This observation combined with Valsalva maneuver and jugular compression led to the development of the test published in 1916, during his service in World War I. He himself described as: ‘‘ The narrowed [spinal] channel impedes movement of fluid with an Increase in pressure above the compression site… The increment in pressure above the obstruction can be Demonstrated by compression of the neck…, Which Produces an Increase in venous blood in the cranial cavity, with concomitant reduction in space for the cerebrospinal fluid… The fluid pressure increased at time immediately Transmitted Throughout the system can normally be… Demonstrate with a manometer attached to a lumbar puncture needle. In lesions of the cord Manometric the change is greatly retarded‘‘ [30]. Lumbar puncture was performed with the patient in the lateral decubitus position. Queckenstedt measured opening pressure. Then, his assistant compressed both jugular veins, leading to a sharp increase in the pressure of the spinal fluid transmitted to the lumbar region within 10–12 s, followed by a drop in blood pressure when the pressure was released jugular. In the case of stenosis of the spinal canal, there was a reduced or absent response in gauge pressure, recorded as a positive sign. This maneuver is still called: Queckenstedt maneuver [30].
Elements of CSF diagnosis Quincke also realized the meaning of laboratoristic CSF examination. Through the Kjeldahl method, he got the amount of content protein together with the investigation of bacteria growth. But the first complete description of the chemical composition of the CSF was provided in 1911 by William Mestrezat (1883–1928) about 20 years later the first description of Quincke [31]. The first report of the diagnostic value of CSF biochemical analysis was
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proposed in 1893 by Ludwig Lichtheim (1845–1928). He noted that glucose levels were low in both bacterial and tuberculosis meningitis [32]. This observation allowed subsequent determination of the glucose concentration in CSF in clinical routine. Later on, the diagnosis of bacterial meningitis became possible with the progress of microbiology development. These advances included the description of a technique for bacteria staining in 1875 BC by Carl Weigert (1845–1904). Thereafter, a novel method for bacteria cultivation was determined, in 1877, later advanced in 1881 to obtain pure cultures, both techniques being developed by Robert Koch (1843–1910). These findings facilitated Hans Christian Gram (1853) who produced the remarkable ‘‘Gram stain’’, published in 1884, to allow the first bacteria differentiation. One year later, Franz Ziehl (1857–1926) and Friedrich Neelsen (1854–1894) conceived the Ziehl–Neelsen method for mycobacterium identification [33]. In 1906, August von Wasserman (1866–1925) applied his serological test, the ‘‘Wasserman reaction’’ in CSF for the diagnosis of syphilis [34]. Ultimately, diagnostic CSF cytology took place with the recognition of tumor cells in 1904 by Henry Dufour [35] leading to routine examination of cerebrospinal fluid for cancer cells or primitive extensive disease in the central nervous system. Qualitative abnormalities in CSF immunoglobulins in the form of oligoclonal bands were reported in patients with multiple sclerosis in 1959 by Ewald Frick, who used immunoelectrophoresis, and in 1967 by Hans Link, using agar gel electrophoresis [36, 37]. The demonstration of oligoclonal bands in CSF by isoelectric focusing was first reported in 1972 by P. Delmotte [38]. Quantitative measurements of CSF immunoglobulins were refined since the early 1970s to distinguish true intrathecal synthesis of immunoglobulins. These methods allowed the development of the ‘‘immunoglobulin index’’ in 1972 by B. Delpech and E. Lichtblau [39]. Oligoclonal bands and immunoglobulin index study in the CSF are still fundamental diagnostic tools in the clinical practice, particularly in the diagnostic panel of demyelinating diseases. In recent years, the clinical laboratory research has proposed more and more new molecular markers for an early and wider comprehensive approach to inflammatory, autoimmune, degenerative and neoplastic diseases.
Conclusions We must show deep gratitude to the different historical moments that over the centuries conveyed the medical thought to understand the importance of cerebrospinal fluid, the anatomical structures that constitute and
Neurol Sci
containing it, up to the superior analysis, that acknowledged the development of the lumbar puncture, as a simple tool, both diagnostic and therapeutic, essential and irreplaceable in everyday clinical practice. An indissoluble wire ties the first Egyptian scholars to Quincke’s work, up to the current microbiology and molecular biology discoveries applied in CSF diagnostic. To Quincke is the merit of having enabled the idea of Wynter, simpler, less invasive, and widely applicable in clinical diagnostics. To Quincke is also the merit of having understood the importance of the chemical analysis of the cerebrospinal fluid. Few moments in the history of medicine have proved so incredibly present, and never surpassed, in the perpetual, difficult course of medical diagnosis. Conflict of interest interest
The authors declare they have no conflict of
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References 27. 1. Marshall LH, Magoun HW (1998) Discoveries in the human brain: neuroscience prehistory, brain structure and function, 1st edn. Humana Press, Totowa 2. Finger S (2000) Minds behind the brain: a history of the pioneers and their discoveries, 1st edn. Oxford University Press, NewYork 3. Pearce JMS (2003) Fragments of neurological history, 1st edn. Imperial College Press, London 4. Aristotle (1882) On the parts of animals. Trans. W. Ogle. Kegan Paul, Trench and Co., London 5. Rufus og Epheus (1879) Oeuvres Trans. C. Daremberg and C. E. Ruelle, Paris 6. Herbowski L (2013) The maze of the cerebrospinal fluid discovery. Ann Res Int 2013:596027 7. Rocca J (1997) Galen and the ventricular system. J History Neurosci 6(3):227–239 8. N.Massa (1536) Liber Introductorius Anatomiae, Francesco Bindoni et Masseo Pasini, 1st edn, Venetio, Italy 9. Gurunluoglu Raffi et al (2011) Giulio Cesare Aranzio (Arantius) (1530–89) in the pageant of anatomy and surgery. J Med Biograpy 19(2):63–69 10. Observationes anatomicae. Basel, 1579, Venice, 1587 11. Zema MJ, Restivo B, Sos T, Sniderman KW, Kline S (1980) Left ventricular dysfunction—bedside Valsalva manoeuvre. Br Heart J 44:560–569 12. Swedenborg E (1887)The brain, considered anatomically, physiologically and philosophically. (translated and edited by R.L. Tafel), London 13. Haller A von (1747) Primae lineae physiologiae in usum praelectionum academicarum. In: A Vandenhoeck (ed), Gottingae 14. Viets H (1935) Domenico Cotugno: his description of the cerebrospinal fluid. Bull Inst Hist Med 3:701–738 15. Magendie F (1825) Treatise on a liquid that is found within the cranium and the spinal canal of man and mammals. J Physiol Exp Pathol 5:27–37 16. Magendie F (1827) Further notes on the cerebrospinal fluid. J Physiol Exp Pathol 7(5–27):66–82 17. Tubbs RS, Loukas M, Shoja MM, Shokouhi G, Oakes WJ (2008) Franc¸ois Magendie (1783–1855) and his contributions to the
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foundations of neuroscience and neurosurgery. J Neurosurg 108(5):1038–1042 Faivre J (1854) Recherches sur la structure du conarium et des plexus choroides chez l’homme et les animaux. Gaz Med Paris 9:555 Von Luschka H (1982) Die Adergeflechte des menschlichen Gehirns. Leipzig, G Reimer, 1855. cited by Torack RM. Historical aspects of normal and abnormal brain fluids: I. Cerebrospinal fluid. Arch Neurol 39:197–201 Key A, Retzius G (1876) Studien in der Anatomie des Nervensystems und des Bindgewebes. Samson and Wallin, Stockholm Martha Marquardt (1949) ‘‘Paul Ehrlich’’ Londra, William Heinemann Medical books LTD, London, Chapter 3, pp 22–26 Martha Marquardt (1949) ‘‘Paul Ehrlich’’ Londra, William Heinemann Medical books LTD, London, Chapter 4, pp 29–30 Lina Stern: Science and fate by A.A. Vein. Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands Gray Horance (1921) History of lumbar puncture (rachicentesis) the operation and the idea. Arch NeurPsych 6(1):61–69 Quincke HJ (1891) Die Lumbalpunction des Hydrocephalus. Berl Klin Wochenschr 28:929–965 Quincke H (1891) Verhandlungen des Congresses fu¨r Innere Medizin, Zehnter Congress. Wiesbaden 10:321–331 Wynter WE (1891) Four cases of tubercular meningitis in which paracentesis was performed for the relief of fluid pressure. Lancet 1:981–982 Arthur Wethworth and first lumbar puncture at the Boston children’s Hospital in 1985 T.E.C., Jr. Pediatrics, Spet 1978; 62:401 Susan E (1997)Lederer 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 Queckenstedt HHG. Zur Diagnose der Ru¨ckenmarkskompression. Deutsche Zeitschrift fu¨r Nervenheilkunde, 1916;55: 325–333, Cited in:Talbott JH. A biographical history of medicine: excerpts and essays on the men and their work, New York: Grunne and Stratton, 1970:983 Mestrezat W (1911) Le liquide cephalo-rachidien normal et pathologique, valeur clinique de l’examen chimique. These No.17 Lichtheim L (1893) Re: the proposal of Quincke to withdraw cerebrospinal fluid by lumbar puncture in cases of brain disease. Dtsch Med Wochenschr 19:1234 Bulloch W (1938) The history of bacteriology, 1st edn. Oxford University Press, London Von Wassermann A, Plaut F (1906) Ueber das Vorhandensein Syphilitischer Antistoffe in der Cerebrospinal fluissigkeit von Paralytikern. Dtsch Med Wochenschr 32:1769–1772 Marks V, Marrack D (1960) Tumour cells in the cerebrospinal fluid. J Neurol Neurosurg Psychiatry 23:194–201 Frick E (1959) Immunophoretische Untersuchungen am Liquor cerebrospinalis. Klin Wochenschr 37:645–651 Link H (1967) Immunoglobulin G and low molecular weight proteins in human cerebrospinal fluid: chemical and immunological characterisation with special reference to multiple sclerosis. Acta Neurol Scand 43(Suppl 28):1–136 Delmotte P (1972) Resultats comparatifs de l’electrophorese en agar et de l’examen par electrofocalisation des gammaglobulines du liquide cephalorachidien. Acta Neurol Belg 72:226–234 Delpech B, Lichtblau E (1972) Etude quantitative des immunoglobulines G et de l’albumine du liquide cephalorachidien. Clin Chim Acta 37:15–23
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HISTORY OF NEUROLOGY
Cerebrospinal fluid and lumbar puncture: the story of a necessary procedure in the history of medicine Sandro Zambito Marsala • Manuela Gioulis Michele Pistacchi
•
Received: 15 October 2014 / Accepted: 2 February 2015 Springer-Verlag Italia 2015
Abstract The aim of our work was to investigate the different historical stages that led gradually to the discovery of the anatomical structures that form and contain cerebrospinal fluid (CSF), until the Quincke idea, to collect the liquid directly at the lumbar level delivering to humanity a diagnostic tool present and absolutely irreplaceable in everyday clinical practice. This is done through consultation of all the historical medical literature, together with the critical examination of the original articles when available in the most rigorous chronological and speculative order, which enabled knowledge advancement. Keywords
Lumbar puncture Cerebrospinal fluid
A brief history of anatomy and physiology of the cerebrospinal fluid The existence of fluid within the brain was certainly observed by the earliest anatomists. The Egyptian physician Imhotep probably was the first to discover intracranial cerebrospinal fluid in vivo in 3000 BC. Indeed, the description was found in The Papyrus of Smith of 1600 BC [1, 2].
S. Zambito Marsala and M. Pistacchi have equally contributed to the manuscript. S. Zambito Marsala (&) M. Gioulis San Martino Hospital, Neurology, Viale Europa 22, CAP 32100 Belluno, Italy e-mail: [email protected] M. Pistacchi Neurology Service, Santorso Hospital, via Garziere 73, 36014 Santorso, VI, Italy
Meninges and ventricles were discovered 5000 years ago and people believed the essence of human activity and thought closely related within these structures. Hippocrates and his School (430–350 BC) cited the existence of a liquid around the falx cerebri [3]. Moreover, they described hydrocephalus condition both in man and domestic animals, being aware that the excess of fluid determined swelling and cranial deformity. However, they were not able to provide clear evidences where inside the head, this storage might be located. Hippocratics believed the head’s express function was to attract fluid from elsewhere inside the body. Aristotle [4], unlike Plato and Hippocrates, recognized the heart as crucial for the fluid movement while the brain was considered a modulator of the liquid temperature. Afterwards, two physicians of the city of Alexandria, namely Erasistratus and Herophilus (300 BC), provided descriptions of the meninges and ventricles: lateral, third, and fourth [5, 6]. Unfortunately, these authors could not benefit the experience of Rufus of Ephesus, (98–117 BC) who although strongly influenced Arabic medicine, was poor considered in the Western world, until the middle of the sixteenth century. If Erasistratus had been able to read the writings of Rufus of Ephesus, the medieval mentality on the subject would have been greatly changed. Later through Marinus of Tyre, the pneumatic theory reached Claudius Galen of Pergamum (129-99) who elaborated Erasistratus concepts in a detailed topographical anatomy of the ventricular system [7]. These evidences needed a long elaboration, since dissection reached a rigorous methodology. Herein, we should specify that dissection was rarely performed until the rise of the school of Bologna, in the early sixteenth century. Unfortunately, for a period of over a thousand years, Galen’s anatomical descriptions were rarely widespread, and his work in their original form was
123
Neurol Sci
not available in the Western world, until the twelfth century, because of the absolute prohibition imposed by religious establishment in anatomy study. Meanwhile, Galenical knowledge was popular in the Arab world. Long time later, Nicolo Massa in his 1536 publication Liber Introductorius Anatomiae described the presence of cerebrospinal fluid (CSF) within cerebral ventricles based on postmortem autopsies [8]. Then, ventricular system anatomy advanced with Andreas Vesalius (1514–1564) and later Julius Aranzi (1530–1589) studies [9, 10] in 1587 with an accurate description of the lateral ventricles system and choroid plexus anatomy. Moreover, Vesalius described the passage between the third to the fourth ventricle named ‘‘aqueduct’’ (later called from Fransois de le Boe of ‘‘Silvio’’ (1614–1672). Subsequently, Willis recognized CSF as a product of distillation of the pineal gland and choroidal plexuses, and Vieussens, who also observed the fluid, believed that the valve was attached for separating the contents of the cerebral and subtentorial ventricles. However, several doubts existed whether the fluid existed in the living or was merely a postmortem precipitation. Some authors like Haller, believed that the cerebral ventricles contained a vapor capable of condensation, which gravitated as water into the spinal spaces. The anatomo-physiological structures and boundaries became more clearly defined in 1692, when Valsalva observed a watery fluid around the spinal cord of a dog, after neck dissection [11]. This evidence was a resultant of their autopsy technique, consisting in a plane section through head and neck. Further strong evidences concerned the effective presence and function of CSF are attributed to Emanuel Swedenborg (1688–1772). He performed numerous dissections between 1736 and 1740. Swedenborg summarized his observations on brain, spinal cord, and blood circulation in a manuscript between 1741 and 1744. Unfortunately, he had no medical credentials, so he was unable to find a publisher. The manuscript was then discovered in Stockholm, more than one century later and finally published and translated in 1887 [12]. Swedenborg referred to the CSF as ‘‘spirituous lymph’’ and ‘‘highly gifted juice’’ that is dispensed from the roof of the fourth ventricle to the medulla oblongata, and the spinal cord [12]. His manuscript also contained comments on the subarachnoid space and the arachnoid membrane. Swedenborg recognized the cerebral cortex as the seat of thought and the source of the sensory and motor functions of the extremities. Then, Albrecht von Haller (1708–1777) based his descriptions on anatomic observations and physiologic experiments, in 1747, in a landmark work in physiology [13], described that the ‘‘water’’ in the brain is secreted into the
123
ventricles and absorbed in the veins; in case of excess secretion, it descends to the base of the skull and into the ‘‘spinal marrow,’’ resulting in hydrocephalus. The final complete description of CSF was provided by Domenico Felice Cotugno (1736–1822) in 1743. Cotugno demonstrated (1774) in the ventricles of the living animal the presence of fluid rather than of a vapor. In 1764 he explained in the ‘‘De ischiade nervosa commentarius,’’ the reason why anatomists had ignored the collection of fluid around the brain and spinal cord, arguing the erroneous method in which corpses were dissected, as above mentioned [14]. The modern period begin with Francois Magendie (1783–1855) author of three notable communications published in the Journal de physiologie experimentale et pathologique. Magendie realized the physiological significance of the CSF in brain and ventricles, but he considered the liquor surrounded the brain and inside the ventricles at autopsy, as a consequence of disease [15, 16]. The pioneer work of Magendie anyway established the physiological basis of knowledge of the future development of neurosurgery [17]. The evidence that CSF was produced inside the choroid plexus was provided in 1854 by J Faivre [18]. Hence, the subsequent discoveries substantiated the anatomic pathway and the physiology of the cerebrospinal fluid (Hubert von Luschka) [19] including the demonstration of the CSF fluid production and absorption (Ernest Key and Gustav Retzius) [20]. Nowadays we know that CSF, whose volume is 140–150 ml, is secreted from the choroid plexus into the cerebral ventricles. It circulates within the cerebral ventricles, flowing through intra ventricles foramen, then passes into the third ventricle, and arrives into the fourth ventricle, where, through Magendie and Luschka foramen, it reaches the cisterna magna and the subarachnoid space. From the fourth ventricle, it continues flowing to central canal spinal cord. Most of cerebrospinal fluid is then reabsorbed through the arachnoid villi in the venous sinus of dura mater, while a little part is then reabsorbed directly in the subarachnoid space, through veins and lymphatic vessels. The existence of the barrier was first discovered by Paul Ehrlich in the late nineteenth century [21, 22], when injecting some pigments into an organism, noticed that they colored any organ except the brain. Ehrlich attributed this evidence to the simple inability of the brain to absorb pigments. However, in a subsequent experiment following in 1913, Edwin Goldmann (one of Ehrlich’s students) injected the pigment directly into the spinal fluid. Differently, in this case the brain dyed, against the rest of the body. This clearly demonstrated the existence of a real barrier. He concluded the blood vessels created themselves the
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barrier, since no definite membrane could be observed. The concept of cerebral blood barrier (then called ‘‘blood–brain barrier’’) was proposed by Lina Stern in 1921 [23]. Its existence could not be proved until the introduction of the scanning electron microscope in the field of medical sciences in the sixties.
When lumbar puncture became a diagnostic procedure Horace Gray [24] was probably the first to perform a drilling within the cerebral ventricles, although the first attempts date back to 1893 with Wyss. The first experiments to perform a cerebral ventricular puncture date 1856 with Middeldorpf through trephining. These moments herald the idea of collecting the CSF in more accessible and less invasive anatomical areas. Heinrich Ireneo Quincke (1842–1922) was researching a safe and simple way to remove the excess fluid in children with hydrocephalus. Since 1872 he studied the physiology of the cerebrospinal fluid in dogs, placing a cannula into the subarachnoid space in the upper part of the lumbar region. He injected the red sulfide of mercury into the subarachnoid space to demonstrate the ‘‘Flu¨ssigkeit’’ or flow. Finally in 1891, however, he realized to obtain the cerebrospinal fluid directly at lumbar level [25]. Likewise in Kiel he was concerned about severe headaches associated with hydrocephalus and, after reading the cases published by Sir. Essex Wynter, he described the first lumbar puncture in ‘‘Uber hydrocephalus’’ at the Tenth Congress of Internal Medicine at Wiesbaden in April 1891 [26]. Certainly in Kiel he performed the first lumbar puncture for therapeutic purposes in December 1890, in a child of 21 months in a coma and on suspicion of tuberculous meningitis. He reached to the subarachnoid space in the lumbar zone with a needle and a cannula and inserted between the third and fourth lumbar vertebral arch to drain the cerebrospinal fluid. The child obtained an improvement of symptomatology. Herein, the original description: ‘‘Case 2 was a boy aged 1 year nine-month coma with suspected tuberculous meningitis, three lumbar punctures were performed at intervals of 3 days in December 1890.: pierced in the lumbar subarachnoid space through a cannula 2 cm. Depth between the third and fourth lumbar vertebral arches and drip I downed a few cubic centimeters of aqueous fluid… you could see clearly increases with maturity and decline of inspiration.’’… The child improved and the nature of meningitis or meningismus remained uncertain. In April 1891, Quincke improved the headache of a 25-year-old man with hydrocephalus by lumbar puncture. Previously in 1888, Quincke removed cerebrospinal fluid
from the ventricles in the brain of a 12-year-old boy, through the holes directly on the skull. On 21 September 1891, he described the lumbar puncture performed on five children and five adults [25]. Moreover, Quincke is credited to be the first to examine in detail the constituents of CSF. He counted the cells, measured total protein by the Kjeldahl method and identified the presence of bacteria in the fluid in pathological circumstances. Essex Wynter with previous studies at the Epsom College, Surrey, in 1891 conceived the first therapeutic procedure that would allow access to the cerebrospinal fluid at the lumbar level. Described at the journal The Lancet were four cases of aspiration of cerebrospinal fluid in during of meningitis [27]. The main purpose was the treatment of intracranial pressure rather than for diagnosis [27]. The first case described concerned a boy aged within 3 years, treated in February 1889 with a diagnosis of meningitis as a result of an ear infection. The second case, treated in February 1890, was a girl of 1 year. The third case was a child of 2 years. Finally, the fourth case was a girl of 13 months. The last three cases described were all suffering from tuberculous meningitis. During the same year but with a different procedure slightly more invasive, Wynter succeeded to get CSF at lumbar level. He conceived a L2 small incision, come down to the dura mater, then inserted a Southey tube with a rubber drainage and subsequently withdrew the infected fluid by reducing the pressure (Southey tubes were still in use in 1960, and were used to relieve dropsy in the legs that had been left in charge during the night to drain liters of fluid oedema in a large bucket). The procedure determined short-term relief; unfortunately, all four patients subsequently died. Wynter did not report these cases until the publication of the May 2, 1891 in Lancet; hence, Quincke is credited as the first performer of the lumbar puncture. Notwithstanding Quincke himself acknowledged the work of Wynter in an internal medicine conference in Wiesbaden in 1891 [26] and later published a book on the subject [25]. The lumbar puncture procedure was transferred in the United States by Arthur H. Wentworth MD, an assistant professor at Harvard Medical School, based in Children’s Hospital. Afterwards in August 1895, Dr. Arthur H. Wentworth achieved the first lumbar puncture at the Children’s Hospital of Boston [28]. ‘‘We punctured the spinal canal, using for the purpose the needle from an antitoxin syringe, and withdrew six cubic centimetres of a clear fluid which looked like distilled water. No tubercle bacilli were found…. Immediately after tapping the canal the child became restless,
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throwing herself about the bed, clutching at her hair and giving vent to short cries. The pulse rose to over 250 in the minute, the respiration was superficial, and the skin was cool and slightly livid. Subcutaneous injections of brandy and ether were given, heaters applied, and the foot of the bed raised. This condition persisted about the same for threequarters of an hour, and then the child became quieter. During the attack I felt considerable uneasiness because I was unprepared for such a result and did not know but that it would terminate fatally. I now believe that the symptoms were due to headache, caused by the removal of fluid, and that her life was not endangered’’ [29]. Later, a considerable technical amelioration resulted from Hans Heinrich Georg Queckenstedt (1876–1918) studies, while serving in the Army in 1916 he developed the homonymous test to detect spinal cord compression. He initiated to study CSF dynamics and components and he noticed the fluctuations of CSF pressure with breathing. This observation combined with Valsalva maneuver and jugular compression led to the development of the test published in 1916, during his service in World War I. He himself described as: ‘‘ The narrowed [spinal] channel impedes movement of fluid with an Increase in pressure above the compression site… The increment in pressure above the obstruction can be Demonstrated by compression of the neck…, Which Produces an Increase in venous blood in the cranial cavity, with concomitant reduction in space for the cerebrospinal fluid… The fluid pressure increased at time immediately Transmitted Throughout the system can normally be… Demonstrate with a manometer attached to a lumbar puncture needle. In lesions of the cord Manometric the change is greatly retarded‘‘ [30]. Lumbar puncture was performed with the patient in the lateral decubitus position. Queckenstedt measured opening pressure. Then, his assistant compressed both jugular veins, leading to a sharp increase in the pressure of the spinal fluid transmitted to the lumbar region within 10–12 s, followed by a drop in blood pressure when the pressure was released jugular. In the case of stenosis of the spinal canal, there was a reduced or absent response in gauge pressure, recorded as a positive sign. This maneuver is still called: Queckenstedt maneuver [30].
Elements of CSF diagnosis Quincke also realized the meaning of laboratoristic CSF examination. Through the Kjeldahl method, he got the amount of content protein together with the investigation of bacteria growth. But the first complete description of the chemical composition of the CSF was provided in 1911 by William Mestrezat (1883–1928) about 20 years later the first description of Quincke [31]. The first report of the diagnostic value of CSF biochemical analysis was
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proposed in 1893 by Ludwig Lichtheim (1845–1928). He noted that glucose levels were low in both bacterial and tuberculosis meningitis [32]. This observation allowed subsequent determination of the glucose concentration in CSF in clinical routine. Later on, the diagnosis of bacterial meningitis became possible with the progress of microbiology development. These advances included the description of a technique for bacteria staining in 1875 BC by Carl Weigert (1845–1904). Thereafter, a novel method for bacteria cultivation was determined, in 1877, later advanced in 1881 to obtain pure cultures, both techniques being developed by Robert Koch (1843–1910). These findings facilitated Hans Christian Gram (1853) who produced the remarkable ‘‘Gram stain’’, published in 1884, to allow the first bacteria differentiation. One year later, Franz Ziehl (1857–1926) and Friedrich Neelsen (1854–1894) conceived the Ziehl–Neelsen method for mycobacterium identification [33]. In 1906, August von Wasserman (1866–1925) applied his serological test, the ‘‘Wasserman reaction’’ in CSF for the diagnosis of syphilis [34]. Ultimately, diagnostic CSF cytology took place with the recognition of tumor cells in 1904 by Henry Dufour [35] leading to routine examination of cerebrospinal fluid for cancer cells or primitive extensive disease in the central nervous system. Qualitative abnormalities in CSF immunoglobulins in the form of oligoclonal bands were reported in patients with multiple sclerosis in 1959 by Ewald Frick, who used immunoelectrophoresis, and in 1967 by Hans Link, using agar gel electrophoresis [36, 37]. The demonstration of oligoclonal bands in CSF by isoelectric focusing was first reported in 1972 by P. Delmotte [38]. Quantitative measurements of CSF immunoglobulins were refined since the early 1970s to distinguish true intrathecal synthesis of immunoglobulins. These methods allowed the development of the ‘‘immunoglobulin index’’ in 1972 by B. Delpech and E. Lichtblau [39]. Oligoclonal bands and immunoglobulin index study in the CSF are still fundamental diagnostic tools in the clinical practice, particularly in the diagnostic panel of demyelinating diseases. In recent years, the clinical laboratory research has proposed more and more new molecular markers for an early and wider comprehensive approach to inflammatory, autoimmune, degenerative and neoplastic diseases.
Conclusions We must show deep gratitude to the different historical moments that over the centuries conveyed the medical thought to understand the importance of cerebrospinal fluid, the anatomical structures that constitute and
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containing it, up to the superior analysis, that acknowledged the development of the lumbar puncture, as a simple tool, both diagnostic and therapeutic, essential and irreplaceable in everyday clinical practice. An indissoluble wire ties the first Egyptian scholars to Quincke’s work, up to the current microbiology and molecular biology discoveries applied in CSF diagnostic. To Quincke is the merit of having enabled the idea of Wynter, simpler, less invasive, and widely applicable in clinical diagnostics. To Quincke is also the merit of having understood the importance of the chemical analysis of the cerebrospinal fluid. Few moments in the history of medicine have proved so incredibly present, and never surpassed, in the perpetual, difficult course of medical diagnosis. Conflict of interest interest
The authors declare they have no conflict of
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