Medical Hypotheses 75 (2010) 238–240

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Arachnoid granules: Dandy was Dandy, Cushing and Weed were not
Charles P. Maurizi *
103 Bartlett Way, Centerville, GA 31028, USA

a r t i c l e i n f o s u m m a r y

Article history: Errors can be instructive. It seems that Harvey Cushing and Louis Weed provided the medical world with
Received 16 February 2010 a faulty theory of cerebrospinal fluid absorption. Louis Weed, working in Harvey Cushing’s laboratory, ini-
Accepted 23 February 2010 tially studied the movement of substances in the cerebrospinal fluid by using low-pressure studies.
Results of the low-pressure studies were considered unsatisfactory and high pressure experiments were
undertaken and these had results similar to earlier work done by others in human cadavers. High pres-
sure results demonstrating movement of fluid through the arachnoid granules were deemed correct.
Because of Cushing’s position of authority, the theory became accepted as fact and in time proved to
be entrenched dogma.
Walter Dandy demonstrated in experiments on hydrocephalus and the surgical removal of the arach-
noid granule system that the fluid was produced by the choroid plexuses and not absorbed by the arach-
noid granules. His work was dismissed by Weed as unreliable.
Examination of the pattern of deposition of corpora amylacea on the surface of the brain provides evi-
dence that cerebrospinal fluid does not pass through arachnoid granules but passes through the choroid
fissure and is recycled through choroid plexus portals. The choroid plexus portal theory can explain the
findings in the low-pressure experiments of Weed. Bias and pride seem to be the source of the faulty the-
ory. Entrenched dogma is resistant to challenge.
Ó 2010 Elsevier Ltd. All rights reserved.

Introduction in neurosurgery as Cushing’s assistant. Cushing, Dandy and Weed

Errors can be instructive. An error has been promulgated in
medical textbooks for almost 100 years. The error was based on a
faulty theory that became accepted as fact and over decades of
time became entrenched dogma that proved to be resistant to
the challenge of new theories.
The theory presently held in textbooks, which is the absorption
of cerebrospinal fluid (CSF) by the arachnoid granule system, is
based on high pressure, non-physiological experiments in animals
undertaken by Louis Weed working in Harvey Cushing’s labora-
tory. Walter Dandy challenged the theory by surgically removing
the arachnoid system. His work was ignored.
A theory based on choroid plexus portals, with the recycling of
CSF through the choroid fissure, can explain the findings noted in
experimental hydrocephalus and why surgical removal of the
arachnoid granule system does not cause hydrocephalus. The text-
book theory does not provide an explanation.
This article will attempt to explain the mechanism by which a
faulty theory became dogma. Excerpts from publications of Harvey
Cushing, Louis Weed and Walter Dandy will be cited.
Cushing and Dandy were trained by William Halsted in surgical
technique at the Johns Hopkins Hospital. Dandy received training
* Tel.: +1 478 971 1614.
E-mail address: maurizicp@aol.com
were bright, hard working, inventive men and each made signifi-
cant contributions to medical knowledge and education. Biograph-
ical material on all three men can be found on internet searches.
Correspondence between Walter Dandy and his parents written
in the years 1910–1914 give insight into what went wrong [1].
The author will present comments on the scientific arguments of-
fered by these individuals; however, readers should come to their
own conclusions.
The circulation of cerebrospinal fluid
When neuroactive substances in the CSF seemed to have global
effect on the brain and behavior, the flow and direction of CSF flow,
became a subject of interest [2]. For many decades, anatomic
pathologists have noted the microscopic formation of corpora
amylacea on the surface of the human brain. Corpora increase in
number with normal aging and are found in even greater numbers
in neurodegenerative diseases, such as Alzheimer’s disease. They
are small spherical bodies composed of brain tissue cellular debris.
Using the hypothesis that corpora are derived from substances
present in CSF and that the bulk flow of CSF would determine
the pattern of corpora distribution, histological sections of brain
were examined. Brain tissue underlying the arachnoid granules,
the site of the textbook theory of CSF absorption, had only
sparse corpora, while tissue in the choroid fissure had many. This

0306-9877/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2010.02.030
 C.P. Maurizi / Medical Hypotheses 75 (2010) 238–240
observation led to the conclusion that the arachnoid granules were
not in a zone of bulk CSF flow and that CSF cycled back into the
ventricular system using the choroid fissure for passage [3]. The
arachnoid granule theory of CSF flow has additional observed fail-
ings [4].
Genesis of the error
Weed, 1914
‘‘After transection of the spinal cord a cannula was tied in the
subarachnoid space and injections were made at pressures
slightly above the normal cerebrospinal tension (i.e. 130–
180 mm H2O). These were continued for periods of 4–6 h; con-
stant pressure systems were used so that the fluid absorbed did
not affect the pressure. The animals were maintained under com-
plete anesthesia throughout the period of observation. Suspen-
sions of lampblack, finely ground and filtered, in saline solution
were first employed; these were replaced in subsequent experi-
ments by diluted india ink (in which the granules of carbon are
even more finely divided). At the end of the period of injection
the spinal cord and brain were removed in one piece, keeping in-
tact the meninges, and the tissue block then hardened in 10%
formol.
By this method of long continued injection under low pressures
both suspensions yielded approximately identical results. Subse-
quently, on macroscopic examination, the black granules could
be followed in the spinal subarachnoid space upward to the cister-
nae about the cerebellum and to all of the basilar pockets of fluid.
But over the cerebral convexities no granules could be seen with
the naked eye. The amount of this granular material was not great
as one passed from the region of injection; on microscopic exami-
nation the reason for this became apparent. The granules were
caught and apparently held firmly in the meshes of the arachnoid
network” [5].
Comment: The low-pressure experiment demonstrated the site
of bulk adsorption of CSF by the choroid plexus portals. Weed’s
theory of ink entrapment does not make sense. Why would the
ink pass the spinal cord arachnoid and suddenly become
trapped in the arachnoid of the basal cisterns? Apparently
Cushing was not satisfied with the low-pressure results and
high pressure experiments were undertaken.
‘‘When, however, the subarachnoid injections were made under
very high pressure (150 mm Hg) the subdural collections of gran-
ules became very markedly accentuated. The subdural space was
distended with the carbon suspensions, while the subarachnoid
was practically collapsed. The study of the arachnoid villi in these
cases proved to be instructive. The chain of carbon granules pene-
trated between the arachnoid villus and the dense strands of dura,
apparently breaking the delicate structures which approximated
villus to dura, and, finally, came to lie just beneath endothelium
in the wall of the sinus. In this situation the carbon granules occu-
pied the area that the arachnoid usually held, and they undoubt-
edly entered the sinus as they could be found in the lumen. (The
finding of the granules of carbon in the lumen of the sinus should
be expected in this case as the high pressures used were sufficient
to kill the animal through paralysis of the respiratory center.) Un-
der these circumstances, with no blood flowing through the sinus,
any granules which passed into it should remain practically in situ”
[5].
Comment: The presently held textbook theory of arachnoid
granule absorption of bulk CSF flow is based on experiments
on human cadavers and with experiments under lethal pres-
sures in animals.
239
Cushing, 1914
‘‘The first reports in this present series of papers deal with ques-
tions of fluid outflow rather than with fluid formation. The method
of injection and precipitation which Weed has employed is so far
superior to other methods which have been utilized in studying
drainage from serous cavities that it was certain to give results in
his skillful hands, particularly in the less carefully studied and
more complex mesothelial cavities of the central nervous system.
He has demonstrated with apparent conclusiveness that the arach-
noid prolongations, tufts or villi, which project into the dura are
the essential elements in the fluid outflow” [6].
Comment: In view of the fact that Weed was working in Cush-
ing’s laboratory as Cushing’s subordinate, such a statement
seems to be an example of scientific self-coronation.
Weed, 1938
‘‘Dandy’s [8] later experiment consisted of the production of a
unilateral internal hydrocephalus by obstruction of one foramen
of Monro; when this plugging of the foramen was accompanied
by extirpation of the choroid plexus, no dilatation followed. These
observations by Dandy cannot be looked upon as demonstrating
the production of the fluid by the plexus. The lack of histological
control in his experimental animals where the choroid plexus were
supposedly extirpated and the possibility of an intracortical escape
through the operative wound vitiated many of the conclusions” [7].
Comment: Weed’s arguments are weak. Dandy’s idea is simple
and seems to be good evidence for CSF production by the cho-
roid plexus. The choroid plexus is a grossly identifiable struc-
ture and none was seen on postmortem examination of the
experimental animals. What histological confirmation is
needed? Intracortical escape of CSF seems to be a figment of
Weed’s imagination. He fails to mention the bilateral experi-
ment in Dandy’s article, which will be quoted later in this paper.
Weed, 1938
‘‘But the general idea of passage of cerebrospinal fluid through
those special structures, the arachnoid villi, was questioned by
Dandy (1929) [8]. His experiments consisted in freeing the brain
from its connexion with the sagittal, circular and transverse si-
nuses, leaving the pia-arachnoid seemingly intact. As no discom-
fort in the experimental dogs was subsequently observed, Dandy
was led to conclude that the arachnoid villi played no role in
absorption. Such a conclusion seems unwarranted as it takes no ac-
count of the fact that the animals possessed intact spinal villi; it
takes no account of the possibility of regeneration or re-establish-
ment of channels from the arachnoid membrane into the dural si-
nuses: it takes no account of the fact that an increased pressure of
the cerebrospinal fluid may lead to the same rate of absorption
with smaller absorptive surfaces. No histological findings were
published by Dandy so that it is impossible to ascertain the phys-
iological or reparative processes within the crania of the experi-
mental animals” [7].
Comment: Attributing the ability of spinal villi to easily absorb
CSF when the cranial villi are removed is incompatible with
Weed’s earlier conclusion that ‘‘Absorption from the cranial
subarachnoid space is much more rapid and much greater in
amount than from the spinal portion” [5]. In order to prevent
hydrocephalus, regenerated arachnoid villi would need to be
functional within hours. If such a mechanism was possible,
communicating hydrocephalus would not exist. Attributing
240 C.P. Maurizi / Medical Hypotheses 75 (2010) 238–240
increased CSF pressure as the process of increased absorption
from a smaller absorptive surface is a faulty argument because
there was no evidence of increased CSF pressure. Hydrocepha-
lus is a gross observation. What histological confirmation is
needed? Dandy’s experiment demonstrates that bulk flow of
CSF does not pass through the arachnoid granules, villi or tufts.
Dandy, 1919
‘‘In a few dogs the choroid plexus was extirpated from both lat-
eral ventricles and at the same operation or shortly thereafter the
aqueduct of Sylvius was occluded. In these animals hydrocephalus
developed and involved both lateral ventricles and the third ventri-
cle. There was, however, a pronounced retardation in the develop-
ment of the hydrocephalus when compared with that which
follows the introduction of a similar occlusion, but without a bilat-
eral choroid plexectomy. Hydrocephalus develops because the
amount of cerebrospinal fluid which is produced by the choroid
plexus of the third ventricle and which cannot escape through
the closed aqueduct of Sylvius, is still greater than the amount of
the absorption which is possible from the three ventricles” [9].
Comment: The experiment demonstrates the choroid plexus
origin of CSF and that bulk adsorption of CSF does not occur
in the third or lateral ventricles. It also eliminates Weed’s
notion of intracortical escape of CSF as a valid objection to Dan-
dy’s conclusions.
Dandy, 1919
‘‘In a recent paper this type of hydrocephalus was shown to be
due to adhesions which obliterated the cisternae. The adhesions
were not present over the entire brain, but mainly at the base
and around the incisura tentorii; that is, where the major effects
of meningitis are usually distributed” [9].
Comment: Dandy recognized the importance of basilar adhe-
sions in the development of communicating hydrocephalus
but did not understand the function of choroid plexus portals.
Dandy, 1919
‘‘Undisputed increase of cerebrospinal fluid from vascular
occlusion can be assured only when a pure vascular obstruction ex-
ists, as in thrombosis. The authentic cases in which thrombosis of
the vein of Galeni or straight sinus are few, but apparently
definite. . .”
‘‘Experimentally, we have been able to establish this point with
accuracy. In a series of 10 dogs we have ligated the great vein of
Galen and the straight sinus in varying places. In a single instance
hydrocephalus resulted, and in this case the obstruction was
placed at the point of origin of the large vein of Galen” [9].
Comment: Dandy was in error. Increased venous pressure
causes the syndrome of pseudotumor cerebri in which hydro-
cephalus does not develop. The dog that developed hydroceph-
alus probably obstructed the choroid plexus portals due to
subarachnoid hemorrhage or inflammation. Increased venous
pressure does not increase CSF production. CSF is created by
the metabolic work of the choroid plexus epithelium. When
choroid plexus portals are obstructed, excess CSF accumulates
with development of communicating hydrocephalus. Three fig-
ures from a previous publication provide a possible explanation
for the development of normopressure, communicating hydro-
cephalus and the ventricular entry of substances [10].
Correspondence, 1910–1914
A long history of conflict between Harvey Cushing and Walter
Dandy is noted in the archives of the Congress of Neurological Sur-
geons. Letters exchanged between Dandy and his parents give in-
sight that something more than personality was the problem.
Dandy’s work was admired by Halsted but belittled by Cushing
[1]. Why? Weed tried to negate Dandy’s results on the production
of CSF by the choroid plexus and lack of absorption by the arach-
noid villus system with weak arguments. Why?
Pride (Wikipedia): In almost every list Pride (Latin, superbia), or
hubris, is considered the original and most serious of the seven
deadly sins, and indeed the ultimate source from which the oth-
ers arise. It is identified as a desire to be more important or
attractive than others, failing to acknowledge the good work
of others. Hubris (Encarta Dictionary) the excessive pride or
ambition that usually leads to the downfall of a hero in classical
tragedy.
Sadly, Cushing and Weed were unable to acknowledge the
merit in Dandy’s experiments and correct their error; an error
that has handicapped understanding the function of CSF and
its influence on the brain.
Conclusion
Experimental bias and pride can throttle critical thinking.
Conflicts of interest statement
None declared.
References
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[5] Weed LH. Studies of cerebro-spinal fluid. No. III. The pathways of escape from
the subarachnoid spaces with particular reference to arachnoid villi. J Med Res
1914;31:51–91.
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