HISTORICAL LIBRARY

Salomón Hakim and the Discovery

of Normal-Pressure Hydrocephalus
Matthew B. Wallenstein, MD
Department of Neurological Surgery,
The Neurological Institute,
Columbia University,
New York, New York
Guy M. McKhann II, MD
Department of Neurological Surgery,
The Neurological Institute,
Columbia University,
New York, New York
Reprint requests:
Guy M. McKhann II, MD,
Department of Neurological Surgery,
The Neurological Institute,
Columbia University,
710 W 168th St,
New York, NY 10032.
E-mail: gm317@columbia.edu
INTRODUCTION: Normal-pressure hydrocephalus (NPH) is a chronic neurological disorder
characterized by enlarged ventricles and a triad of clinical symptoms affecting gait, cog-
nition, and urinary continence. Salomón Hakim first identified the syndrome in 1957 at
the Hospital San Juan de Dios in Bogotá, Colombia. Even after decades of international
focus and thousands of publications on his disorder, Hakim’s story remains largely untold.
METHODS: In this historical review, we explore the discovery of NPH through a series of
personal interviews with Professor Hakim and his family, discussions with former col-
leagues, and review of the relevant medical literature.
RESULTS: Professor Hakim first published his thesis in 1964 and 6 case reports of NPH in
The New England Journal of Medicine and the Journal of the Neurological Sciences in 1965.
Hakim rose to the forefront of academic medicine as he described a newfound ability to
reverse symptoms of “neurodegeneration” that had long been considered irreversible.
CONCLUSIONS: As we learn more about NPH, the fascinating story of Professor Hakim,
the father of NPH, is of both historical relevance and current interest.
KEY WORDS: Discovery, Hakim, Historical review, Normal pressure hydrocephalus

Neurosurgery 67:155-159, 2010 DOI: 10.1227/01.NEU.0000370058.12120.0E www.neurosurgery- online.com

Received, July 27, 2009.
Accepted, January 15, 2010.

N
Copyright © 2010 by the ormal-pressure hydrocephalus (NPH) is
Congress of Neurological Surgeons
a chronic neurological disorder character-
ized by enlarged ventricles and a triad of
clinical symptoms affecting gait, cognition, and
urinary continence. Salomón Hakim first iden-
tified the syndrome in 1957 at the Hospital San
Juan de Dios in Bogotá, Colombia. Hakim pub-
lished a thesis in 1964 and 6 case reports of NPH
in The New England Journal of Medicine and the
Journal of the Neurological Sciences in 1965.1-3
Hakim rose to the forefront of academic medicine
as he described a newfound ability to reverse
symptoms of neurodegeneration that had long
been considered irreversible.
In many ways, Hakim was a typical scientific
pioneer. He was precocious as a child and driven
and determined as a young man. He has > 75
publications and patents, as well as dozens of
awards, including one from the President of
Colombia and another from the King of Spain.
However, despite decades of international focus
and thousands of publications on his disorder,
Dr Hakim’s story remains largely untold. We pro-
ABBREVIATIONS: MGH, Massachusetts General
Hospital; NPH, normal-pressure hydrocephalus
vide an in-depth review of Dr Hakim’s discovery
of NPH based on information from a variety of
sources. These include a 1968 profile of Hakim
in Life en Español, a review of the relevant med-
ical literature, and a series of interviews with Drs
Salomón Hakim, Carlos Hakim, J.P. Mohr, and
Harold Conn.
EARLY LIFE AND CAREER
Hakim, whose surname means doctor or wise
man in Arabic, was born in Barranquilla, Colombia,
in 1922 to a family of Lebanese immigrants. In
his youth, he exercised an extraordinary curios-
ity for physics and electricity. As a child, Hakim
would lock himself in his bedroom for hours,
making electric circuits out of wires and light
bulbs. Hakim’s interests expanded to electromag-
netism and engineering in middle school. At 12
years of age, he started building radios.
Hakim enrolled in medical school in 1944 and
chose to pursue a career in neurosurgery. His love
of physics and electricity continued to influence
his studies as he examined electrical output dur-
ing digestion, the effect of current on uterine con-
traction, and the use of electrolysis to stimulate

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WALLENSTEIN AND MCKHANN
calcium formation. Hakim had already demonstrated natural tal-
ent and ambition, but his research opportunities were limited in
Colombia. After finishing his residency in Bogotá, Hakim trav-
eled to the United States in 1950 to accept a fellowship at The
Lahey Clinic in Boston, Massachusetts. In 1954, he returned to
Boston as a research fellow in neuropathology at the Massachusetts
General Hospital (MGH).
THE ROAD TO DISCOVERY
As part of his research fellowship, Hakim conducted autopsies
of patients with Alzheimer disease and other neurodegenerative
diseases. Most of these cases demonstrated hydrocephalus ex vacuo,
a ventricular enlargement secondary to cerebral atrophy. Every so
often, however, Hakim found cases of enlarged ventricles with-
out loss of brain parenchyma. No one at the MGH could explain
this unusual pathology, now known to be a distinguishing feature
of NPH. Hakim thought there must be an explanation. Soon he
would find it.
In 1957, Hakim returned to the Hospital San Juan de Dios in
Colombia. This is where he encountered his first living case of
NPH, or symptomatic occult hydrocephalus as it was originally
called. The patient was a 16-year-old boy with severe head trauma
from a motorcar accident. Surgeons performed a posterior frontal
burr hole to relieve pressure from a right subdural hematoma. The
operation was successful, but the patient remained in a semico-
matose state and was diagnosed with irreversible brain damage.
At this point, the boy’s family contacted Hakim for advice. A
pneumoencephalogram indicated ventricular enlargement (Figure
1), but intracranial pressure remained normal at 150 mm. Hakim
decided to remove 15 mL of cerebrospinal fluid (CSF) for labo-
ratory testing. To his surprise, the patient improved the follow-
ing day and spoke for the first time in months. He relapsed a few
days later but improved again after a second lumbar drainage.
Hakim implanted a ventriculoatrial shunt. The patient responded
immediately and felt well enough to return to school 3 months
FIGURE 1. A pneumoencephalogram of Hakim’s first normal-pressure hydro-
cephalus patient who presented with enlarged ventricles despite normal cere-
brospinal fluid pressure. These images appeared in Hakim’s thesis in 1964
and in the Journal of the Neurological Sciences in 1965.2,3
156 | VOLUME 67 | NUMBER 1 | JULY 2010
later. The case report appeared in Hakim’s thesis in 1964 and in
Journal of the Neurological Sciences in 1965.2,3
Many physicians would have stopped there. In fact, Foltz and
Ward4 had previously reported a case of communicating hydro-
cephalus with normal CSF pressure in 1956. However, they offered
no explanation of their findings, described their case as a rare med-
ical anomaly, and did not pursue the issue further. Hakim, in con-
trast, continued to ask himself questions. How can ventriculomegaly
arise from normal intracranial pressure? Why would a patient with
normal CSF pressure respond to spinal fluid drainage and shunt
placement? Hakim’s knowledge of physical principles led him to
the answer. “Pressure is force per unit area and force is pressure
times area in total,” Hakim reasoned at the time. “Therefore if
this young man has an enlarged ventricle, the pressure that we
had accepted as normal is causing him damage. What happened
is that in his case the pressure was no longer normal because he had
a larger area than normal…. Caramba! This is new, I hadn’t been
aware of this before”5 (Figure 2).
The idea that ventricles could enlarge in the presence of nor-
mal CSF pressure was a novel idea at the time. Hakim based his
reasoning on the Pascal law that force equals pressure multiplied
by area. The Pascal law explains the hydraulic press phenome-
non in which force exerted on a small column of liquid is mag-
nified to a larger column because the pressure in a closed system
remains constant. This idea also applies to the illustration in
Figure 3. The pressure is constant as the balloon inflates, despite
the change in volume and the increase in elastic force of the rub-
ber. Similarly, normal intracranial pressure in a patient with
enlarged ventricles exerts a greater-than-normal force on the brain
because the same pressure is multiplied over a larger ventricular
surface. Hakim called this the hydraulic press effect. “Thus the
pressure in both the small and large ventricle is equal, but the
force in the larger ventricle has increased in proportion to its
increased surface.”3
FIGURE 2. Dr Salomón Hakim describes the physical properties of normal-
pressure hydrocephalus in a photograph that appeared in Life en Español in
1968.5
www.neurosurgery-online.com
 DISCOVERY OF NORMAL-PRESSURE HYDROCEPHALUS

In their seminal article, the

authors presented 3 cases of NPH
with a full reversal of symptoms
after shunt placement. They
described in detail the classic
triad of gait imbalance, cogni-
tive decline, and urinary incon-
tinence, as well as ventriculo-
megaly and its relation to the
hydraulic press effect. “The
importance of recognizing this
condition lies in the opportu-
nity it affords of rescuing from
oblivion at least a few of the vast
number of middle-aged or elderly
patients now labeled as having
senile dementia or ‘cerebral arte-
riosclerosis.’”1
2
FIGURE 3. A demonstration of the hydraulic press effect presented by Hakim in his 1964 thesis. Notice that the pressure The article captured the atten-
remains constant as the balloon inflates, despite increasing elastic force of the rubber. Enlarged ventricles may have nor- tion of everyone in the field. J.P.
mal cerebrospinal fluid pressure, but the force exerted on the ventricular walls is greater than normal because of a larger Mohr, now a prominent stroke
surface area. Hakim called this the hydraulic press effect.
neurologist at Columbia Uni-
versity College of Physicians and
AFTER THE DISCOVERY Surgeons, was a research fellow at the MGH when Hakim and
coauthors gave the first presentations of NPH in grand rounds and
After publishing a thesis on NPH in 1964,2 Hakim called Dr clinical conferences. Mohr remarked, “A whole storm of energy
Raymond Adams at Harvard (C.A. Hakim, telephone interviews, got underway to see if the putative mechanism was right or wrong”
July 2007-November 2009) to describe this new neurological con- (J.P. Mohr, personal interview, July 16, 2007).
dition. “There is nothing new in this field,” Adams replied. After the publication in 1965, researchers embarked on an effort
“Everything has already been published. Perhaps you don’t have to further characterize NPH and to predict shunt responsiveness.
good libraries in Colombia.” Ironically, Adams would eventually In addition to spinal drainage and pneumoencephalogram, new
become the lead author of the groundbreaking New England Journal diagnostic tools were developed every 5 to 10 years, including
of Medicine article1 and would receive much of the credit for Hakim’s radionuclide cisternogram, lumboventricular perfusion, lumbar
discovery of NPH. The initial skepticism never bothered Hakim: infusion, somatosensory evoked potentials, and external lumbar
“Of course, in the beginning it was a rather difficult thing to under- drainage. Magnetic resonance imaging and computed tomography
stand, how the ventricles could enlarge with normal pressure” (S. have since replaced the pneumoencephalogram, and many of the
Hakim and C.A. Hakim, telephone interview, August 9, 2007).
A few months later, an American citizen working at the US
Embassy in Colombia came to Hakim with symptoms of NPH.
Hakim recommended spinal drainage and shunting, but the
patient’s husband wanted to fly back to the United States before
doing anything else. Hakim explained, “No one in the US is aware
of this condition, and if you go by yourself no one will know what
to do”(C.A. Hakim, telephone interviews, July 2007—November
2009). As a compromise, Hakim decided to accompany the patient
to Boston, where they met with staff from the MGH Department
of Neurology and the initially skeptical Dr Adams (Figure 4). The
patient demonstrated dramatic improvement after spinal drainage
and shunting. This patient led to the seminal publication1 in The
New England Journal of Medicine that fueled great excitement in
the field. Adams was the neurology service chief and took much FIGURE 4. Dr Salomón Hakim (right) with coauthor Raymond Adams
(left). Although Adams was initially skeptical of Hakim’s discovery, he would
of the credit as lead author. The other coauthors included Hakim, eventually become the lead author of the groundbreaking The New England
Dr C. Miller Fisher, who detailed the clinical picture of NPH,6 and Journal of Medicine article.1
neurosurgeons Dr Robert Ojemann and Dr William Sweet.

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WALLENSTEIN AND MCKHANN
other techniques are now considered unsafe or outdated. Researchers
also developed alternatives to shunting such as removing the
choroid plexi or reducing CSF production with acetazolamide.
These alternatives were shown to lack efficacy. Today, shunt implan-
tation is still considered the standard treatment for NPH, although
endoscopic third ventriculostomy is under active investigation as
a potential viable alternative.
The state of treatable dementia at the time of Hakim’s dis-
covery was limited largely to endocrine disorders and vitamin
deficiencies. The concept of NPH appealed to so many not only
because of its novelty but also because it offered an ability to
reverse what had long been considered irreversible. The final
paragraph in The New England Journal of Medicine article reads,
“Recognition and treatment of these cases is of great importance
since it will result in what amounts to a ‘cure’ of a clinical con-
dition that closely resembles presenile or senile dementia.”1 “‘A
cure for senile dementia,’” Mohr (personal interview, July 16,
2007) read aloud. “Who would not respond to that? Everybody
did. Everybody.”
Not everyone responded so positively, however. H. Houston
Merritt, world-renowned neurologist and dean emeritus of
Columbia University College of Physicians and Surgeons, pub-
licly questioned the existence of NPH throughout his career.
Mohr (personal interview, July 16, 2007) explained, “Merritt
was initially opposed to the idea and had seen one of the three
patients with the condition [from the 1965 article], and he was
left with the impression that he doubted [NPH] as the diagno-
sis.” In fact, during a grand rounds conference in 1965, Merritt
implied that Adams and Hakim ought to lose their professor-
ships for publishing premature observations. However, he later
added, “I am just making the point that the matter is not fully
understood and should be” (J.P. Mohr, personal interview, July
16, 2007). In a twist of fate, Merritt later developed symptoms
of NPH and died of complications from a shunt operation in
Boston in 1979.
NPH was still regarded with ambiguity by many, even after it
began to be embraced by the broader scientific community. The
lack of a definitive diagnostic test and questions surrounding
enlarged ventricles with normal pressure contributed to the con-
fusion. In the beginning, there was no computed tomography or
magnetic resonance imaging, and even with these modalities, the
diagnosis of NPH remained largely clinical. A number of factors
continued to fuel skepticism regarding NPH, particularly in the
neurology community. These included the lack of a definitive
noninvasive preoperative study; the imprecision and variability
of various more invasive studies, ranging from cisternogram to
lumbar CSF drainage to CSF infusion study; and the high degree
of clinical overlap with other conditions that affect older patients.
In addition, high rates of shunt complications in the elderly plagued
the NPH field until the advent of the programmable valve in
1988. Improved diagnostic accuracy, advanced magnetic reso-
nance imaging techniques, and implementation of programmable
valves eventually resulted in improved outcomes in patients with
NPH and allayed many of the surgical concerns.
158 | VOLUME 67 | NUMBER 1 | JULY 2010
Hakim was intimately involved in the NPH field throughout
his career. He regularly gave presentations and speeches, debated
prominent members of the neurological community, and even
made a 25-minute 16-mm film about NPH. After his discovery,
Hakim continued to conduct research on NPH and shunt dynam-
ics, further characterizing the physics of CSF pressure and the
pathophysiology NPH.
Today, NPH affects up to 9% to 14% of patients living in
extended-care and assisted-living facilities.7 Despite 42 years of
research and its relatively high prevalence, NPH continues to
remain an elusive disorder with no clear origin or gold-standard
diagnostic criteria. Misdiagnosis is still commonplace as a result.
Dr Harold Conn, a hepatologist at Yale University, recently pub-
lished a case report of his personal experience with NPH.8 It
took a full 10 years from the onset of symptoms before physicians
identified NPH as the diagnosis. Conn made a significant recov-
ery after shunt placement, after which he chose to dedicate his
life to raising awareness of NPH and the potential reversibility
of its symptoms. Conn has since become close friends with
Hakim and his family (H.O. Conn, telephone interview, July
20, 2007).
THE HAKIM VALVE
In addition to his work with NPH, Hakim developed surgical
valves in his home machine shop in Bogotá (Figure 5). In the late
1940s and 1950s, shunt operations were performed with slit valves
that regulated CSF flow but did not monitor pressure. The first
of these was the Spitz valve introduced in 1949. In 1966, Hakim
developed a unidirectional, pressure-regulating valve that was
more efficient and safer than previous valves. The Hakim valve
consisted of a stainless steel cone and a synthetic sapphire ball
with spring-loaded pressure control.
FIGURE 5. Hakim in his home machine shop with his eldest son, Carlos,
who would go on to develop the programmable valve.5 Hakim entertained
his children with preserved brains and model sponges from his experiments. Today,
3 of his 4 children are involved in neuroscience and neurosurgery.
www.neurosurgery-online.com

Carlos Hakim, Hakim’s eldest son, has continued his father’s
legacy as a neuroscientist and engineer. After receiving a joint PhD
from Massachusetts Institute of Technology and Harvard University,
Carlos developed a programmable valve that is now produced and
distributed by Johnson & Johnson. It has 18 pressure settings in
10-mm increments, and it allows transcutaneous adjustment to
avoid multiple operations for overdrainage or underdrainage.
Another theoretical advantage of the programmable valve is that
it prevents ventricular collapse by increasing CSF pressure as the
ventricles decrease in size.
LIFE AND LEGACY
Hakim’s discovery brought him international esteem. He has
delivered > 85 guest lectures in 33 different countries through-
out his career. He has 30 patents and 45 publications—-7 in The
New England Journal of Medicine—-and > 30 honors and awards
from world leaders and prestigious medical societies.
Hakim has a strong personality and a brilliant mind. As a young
man, Hakim’s ambition was unmatched. He regularly worked 14-
to 18-hour days, sometimes spending entire nights experimenting
in the machine shop laboratory in his home. He exclaimed, “The
concept that one should sleep a certain number of hours a day
and get up at such and such a time…ridiculous!”5 To this day,
Hakim has not taken a single nap.
Hakim’s children have carried on their father’s life work in
neuroscience. Two of his sons are neurosurgeons, and another,
Carlos, is currently studying the pathophysiology of NPH and
its underlying causes. Hakim is now 87 years old, and he con-
tinues to contribute to the field. He occasionally speaks at neu-
rological conferences, and he published a review of NPH with
two of his sons in 2001.9 “What is really nice is the relationship
that I have with my father and that we have been able to work
together so many years,” Carlos explains. “[My father] contin-
ues to be active, not as energetic obviously, but we continue to share
a lot of ideas” (C.A. Hakim, telephone interviews, July 2007—
November 2009).
The identification of NPH in 1957 brought Hakim to the fore-
front of academic medicine. His case reports in The New England
Journal of Medicine and Journal of the Neurological Sciences broad-
cast his discovery to the world and inspired thousands of publica-
tions on NPH.1,3 Hakim’s persistence in the face of doubt and
his confidence in the face of uncertainty enabled him to affect the
lives of patients and academics alike.
REFERENCES
1. Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. Symptomatic occult
hydrocephalus with “normal” cerebrospinal fluid pressure: a treatable syndrome. N
Engl J Med. 1965;273:117–126.
NEUROSURGERY
DISCOVERY OF NORMAL-PRESSURE HYDROCEPHALUS
2. Hakim S. Some Observations on CSF Pressure: Hydrocephalic Syndrome in Adults
With “Normal” CSF Pressure [thesis in Spanish]. Bogotá, Colombia: Javeriana
University School of Medicine; 1964. Thesis No. 957.
3. Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus
with normal cerebrospinal fluid pressure: observations on cerebrospinal fluid hydro-
dynamics. J Neurol Sci. 1965;2(4):307–327.
4. Foltz EL, Ward AA Jr. Communicating hydrocephalus from subarachnoid bleed-
ing. J Neurosurg. 1956;13(6):546–566.
5. Segura J, McCoy SAD. A man of heart gives his all to the study of the brain [in
Spanish]. Life en Español. 1968;46–57.
6. Fisher CM. The clinical picture in occult hydrocephalus. Clin Neurosurg. 1977;
24:270–284.
7. Marmarou A, Young HF, Aygok GA. Estimated incidence of normal-pressure
hydrocephalus and shunt outcome in patients residing in assisted-living and
extended-care facilities. Neurosurg Focus. 2007;22(4):1–7.
8. Conn HO. Normal pressure hydrocephalus: a case report by a physician who is
the patient. Clin Med. 2007;7(3):296–299.
9. Hakim CA, Hakim R, Hakim S. Normal-pressure hydrocephalus. Neurosurg Clin
N Am. 2001;12(4):761–763.
Acknowledgments
We acknowledge Harold Conn, Carlos Hakim, Salomón Hakim, Jon Krakauer,
J.P. Mohr, and Pietro Mazzoni.
Comment 200495
COMMENTS
I n this elegant report the authors remind us of the debt neurosurgery
owes Dr Hakim for his discovery of normal pressure hydrocephalus
(NPH).In fact, there are a few discoveries in neurosurgery that have made
a similar societal impact. Discovery of NPH has improved the quality of
life in a vast number of individuals world over. Prior to Dr Hakim’s ingen-
ious work these patients would have been consigned to a less than digni-
fied life of dependency and despair. Kudos to Dr Hakim!
Ivan Ciric
Evanston, Illinois
T his is a enlightening historical vignette describing the career of a
remarkable man. I had the pleasure of meeting Dr Hakim, accompa-
nied by 2 of his sons, several years ago and can attest to the mental for-
titude of this gentleman. The tale of Dr Adams’ initial dismissal of Dr
Hakim’s observations is telling. It bespeaks of the importance of keep-
ing an open mind when bright, young scientists and clinicians approach
us with ideas that challenge our own. It is of course difficult to judge, in
retrospect, what credit Raymond Adams deserves in regard to the “discov-
ery” of NPH. It is my understanding that the author order of the classic
1965 paper in the New England Journal of Medicine: Adams RD, Fisher
CM, Hakim S, Ojemann RG, Sweet WH, was chosen alphabetically.
Louis Pasteur once said, “chance favors the prepared mind.” Dr Hakim’s
upbringing and education were clearly integral to his eventual success in
medicine. Perhaps medical schools should be looking for more students,
like young Salomon Hakim, with engineering and physics backgrounds.
Marvin Bergsneider
Los Angeles, California
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