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256

Section 3

Organic syndromes of schizophrenia: other neurological disorders

Julian Trollor

Facts box

cannot be easily separated out from the impact of
r

NPH alone.

Normal pressure hydrocephalus (NPH)

presents as a progressive syndrome of gait
History of the association

disturbance, impaired cognition, and loss of
bladder control.

The father of medicine, Hippocrates (460–370 BC),
r

first coined the term “hydrocephalus” but believed
Noncognitive psychiatric and behavioral
it to be a manifestation of fluid collection external
manifestations of NPH appear common but
to the brain. This thinking dominated the approach
have not been systematically studied.

r

of our physician ancestors for the next 1,000 years,
A number of reports suggest that NPH can
until the description of infantile hydrocephalus by
induce schizophrenia-like symptoms, and
the founder of surgery, Abul Qasim Al-Zahravi, also
these appear more likely in cases of
known as Albucasis (AD 936–1013). More recently,
secondary NPH.

r

hydrocephalus has been divided broadly into three key
Case reports indicate that when presenting as
categories, relating to disorders of cerebrospinal fluid
a manifestation of NPH, psychotic symptoms
production, circulation, and absorption. Although the
may improve with appropriate surgical
precise mechanism underpinning the development of
management of NPH.

NPH is obscure in many cases, NPH is generally
r
There is potential for delayed recognition of
included in the latter group. It is further classified as
NPH in situations where psychiatric and
either primary (idiopathic), or secondary (most com-behavioral symptoms dominate the
monly following intracranial hemorrhage, infection,
presentation.

or trauma). Hakim and Adams’
[1]
original descrip-r
The pathogenesis of psychotic symptoms in
tion of the clinical presentation and surgical treatment
NPH has not been examined but symptoms
of NPH began a focus on the classical triad of symp-are assumed to arise in part from the impact
toms that continues to the present day. However, this
of NPH on fronto-subcortical and basal
narrow focus has meant that other aspects of the dis-forebrain networks.

order, including broader psychiatric and behavioral
aspects, have largely been ignored.

The capacity of normal pressure hydrocephalus
(NPH) to induce a reversible dementia syndrome is
enlargement

well known. There is a less well-defined relationship
Schizophrenia has a long-established association
between NPH and schizophrenia-like psychosis.

with ventricular enlargement. To the contemporary
Although evidence supporting a link between the two
reader, the distinction between schizophrenia and
disorders is limited, available data supports an associ-NPH is clear. However, historically this bound-ation. The specificity of the relationship between the
ary has not always been so well defined. Early air
two disorders is, however, confounded by the impact
encephalographic studies of patients had shown an
of etiological factors intrinsic to NPH itself. These
association between schizophrenia and enlargement
factors may in themselves contribute vulnerability to
of the ventricular system
[2]
. Later, the clinical triad
257

psychotic disorder, and their effects on brain function
of gait disturbance, incontinence, and dementia
Organic Syndromes of Schizophrenia – Section 3

associated with NPH was described
[1],
as was
chiatric causation); brain imaging findings (includ-the favorable response to insertion of a ventricular
ing computerized tomography or MRI of the brain
shunt
[3].
An association between schizophrenia
demonstrating ventricular enlargement without evi-and ventricular enlargement was later confirmed by
dence of CSF obstruction), and clinical findings (gait
computerized tomography studies
[4, 5].
However,
or balance disturbance plus either disturbed cogni-the significance of the ventricular enlargement to
tion or incontinence). With the removal of the specific
the pathophysiology of schizophrenia remained
exclusion clause for antecedent events, these criteria
uncertain. Nyback and colleagues
[6]
postulated an
could also provide a guide for diagnosis in secondary
association between acute schizophrenic psychoses
NPH. Behavioral and personality changes are noted in
and disturbance in cerebrospinal fluid (CSF) circu-this diagnostic system but are de-emphasized by their
lation. The observation of abnormal CSF flows in
inclusion under cognitive manifestations.

10 of 30 patients with schizophrenia studied using
isotope cysternography
[7]
threatened to confuse the
Schizophrenia-like psychosis and

distinction between hydrocephalus per se and ventricular enlargement associated with schizophrenia.

hydrocephalus

This was further compounded by the early reports of a
A small literature exists in which hydrocephalus
favorable response to shunting observed in some indi-appears associated with symptoms of schizophrenia. A
viduals with both psychotic symptoms and NPH
[8]
or
distinction appears in the literature between individu-aqueduct stenosis
[9]
. However, with time and further
als with stenosis of the Sylvian aqueduct and those with
clarification of the concepts, the distinction between
NPH. Non-tumoral stenosis of the aqueduct usually
subtle, nonprogressive ventricular enlargement seen
presents in infancy or childhood, where it may be asso-in association schizophrenia and that observed in
ciated with specific genetic syndromes
[14],
perina-NPH became more apparent.

tal insult, or developmental anomaly. Less commonly,
aqueduct stenosis may present in early adulthood
[9].

Clinical presentation of normal

Psychotic symptoms have been reported in individuals with aqueduct stenosis
[9, 15, 16, 17].
For some
pressure hydrocephalus

adult patients, the presentation with psychotic symp-Normal pressure hydrocephalus is considered the
toms may be the trigger for the discovery of previously
“quintessential” reversible dementia and is character-occult aqueduct stenosis
[9].
The distinction of the lat-ized by the clinical triad of gait disturbance, inconti-ter cases from NPH is clear where, in retrospect, a
nence, and dementia
[1].
A number of behavioral and
neurodevelopmental insult or delayed developmental
psychiatric symptoms have been observed accompa-trajectory suggests decompensation of longstanding
nying, or preceeding NPH diagnosis. These include
compensated occult hydrocephalus. However, in other
aggression
[10],
affective disorders including depres-situations, the distinction of cases of late aqueduct
sion
[11]
and mania
[12],
and schizophreniform psy-stenosis from NPH may be less clear. It has been pro-chosis
[8].
However, systematic study of the range of
posed that aqueduct stenosis could occur as a late con-behavioral and psychiatric manifestations of NPH has
sequence of a communicating hydrocephalus such as
not yet been undertaken.

NPH
[18].
Smith
[19]
summarized the possible mechA number of barriers to effective assessment and
anisms that could relate to mechanical compression of
treatment of NPH exist. These include a lack of consen-the midbrain as the ventricular system expands
[20]
or

sus on assessment methods, lack of systematic data on
proliferative gliosis of the aqueduct
[21].

prevalence and treatment outcomes, variability in clin-There are a small number of reported cases of psy-ical presentation, and disparity of clinician approach
chotic symptoms arising in the context of idiopathic [8,
in diagnosis and treatment. Evidence-based guidelines
11,
22, 23,
24] and secondary
[8, 10, 22, 25, 26]
NPH in
for classification of probable and possible idiopathic
the literature. The temporal association between psy-NPH have been proposed
[13]
and encompass specific
chotic symptoms and clinical signs of NPH is remark-aspects of history (including insidious onset with pro-ably variable in these case reports. A clear temporal
gression of symptoms with time in individuals over 40

relationship between onset of psychosis and classical
years of age, minimum symptoms duration 3 months,
signs and symptoms of NPH is more likely to reflect
258

no clear antecedent, and no alternative medical or psy-a specific association between the two disorders. Of
Chapter 19 – Normal pressure hydrocephalus

particular interest are cases in which psychotic symp-implications of delayed diagnosis of NPH, it is impor-toms are a close antecedent to definitive manifestations
tant to examine the possible contributors to this phe-of NPH
[10, 22, 23, 26].
The complete elimination of
nomenon. Motor and cognitive manifestations of NPH

psychotic symptoms with shunting in these cases also
may be misattributed as side effects of neuroleptic
argues for a specific etiological contribution of NPH

treatment. Cognitive deterioration may be attributed
to psychosis. However, in a number of cases the speci-solely to other physical treatments (such as electrocon-ficity of the association is clouded by other vulnera-vulsive therapy). Other physical manifestations such
bility factors for psychosis, including recent traumatic
as bladder instability or neurological signs may not
brain injury
[10, 26].
With few exceptions
[23],
there
be so readily assessed in the context of treatment
is very limited data to suggest idiopathic NPH as a
within a psychiatric facility. However, the accessibil-clear and immediate precipitant of psychotic symp-ity of neuroimaging facilities, and their almost rou-toms. This suggests that in the absence of other vul-tine use in first-episode psychosis mean that the major-nerability factors, idiopathic NPH is rarely associated
ity of patients with close temporal association between
with psychotic symptoms.

NPH and psychotic symptoms can be readily identi-In contrast to the above, cases have been reported
fied. Because the likelihood of NPH rises with advanc-in which psychotic symptoms precede obvious clin-ing age, it is particularly important that clinicians be
ical signs and symptoms of NPH by many months
aware of the manifestations of NPH in those present-

[11],
or even years
[8].
The long lag between onset
ing with an index episode of psychiatric disorder later
of psychosis and definitive signs of NPH in some of
in life. In those with chronic mental disorders, NPH

these cases would suggest it was unlikely that the psy-may be suggested by a change in clinical presentation
chotic symptoms experienced were a direct manifesta-associated with abnormality of gait, cognitive distur-tion of hydrocephalus. However, both authors report
bance, or incontinence.

resolution of psychotic symptoms with appropriate
surgical management of NPH, suggesting at least a
Pathogenesis of psychotic symptoms in

permissive role of emerging NPH in production
of psychotic symptoms. Schizophrenia-like psychosis
normal pressure hydrocephalus

may arise decades after identification of NPH
[27].

NPH is a syndrome dominated by subcortical and
Such cases are atypical and, in this setting, the two dis-basal forebrain impairments that appear to arise as
orders are less likely to be specifically associated.

a direct consequence of the compressive effects of
Amelioration of psychotic symptoms following
ventricular expansion. Neuropsychological testing of
ventricular shunting for NPH has been reported in a
individuals with NPH most commonly reveals slowed
number of contexts, including where both a short and
information processing, reduced psychomotor speed,
a long delay is noted between onset of psychosis and
and a “frontal” pattern of memory dysfunction char-obvious manifestations of NPH. Although case reports
acterized by reduced retrieval efficiency
[28, 29, 30].