is a syndrome characterized by a gradual onset of symptoms, including
memory loss and decline in such cognitive abilities as thinking and
decision making. Dementia is extremely prevalent in the elderly
population, with a severe dementia affecting approximately 5% of people
above 65 years of age.
Diagnostic features include,
memory impairment and at least one of the
aphasia, apraxia, agnosia,
disturbances in executive functioning.
In addition, the cognitive impairments must
be severe enough to cause impairment in social and occupational
Importantly, the decline must represent a decline from a previously higher
level of functioning.
Finally, the diagnosis of dementia should not be made if the cognitive
deficits occur exclusively during the course of a delirium.
There are many types and causes; the three
major causes of dementia of neurosurgical interest are normal pressure
subdural hematoma, and intracranial mass lesion. Together, they account
for only 3.5% of dementia, most of them due to NPH.
NPH is discussed in this section.
Normal pressure hydrocephalus:
NPH is a state of
chronic hydrocephalus in which the CSF pressure is in physiologic range,
but a slight pressure gradient persists between the ventricles and the
brain. There is ventriculomegaly without a rise in intracranial pressure (ICT)
as a result of insidious obstruction of the CSF circulation due to
subarchnoid block. It is also called low pressure hydrocephalus, occult
hydrocephalus, and hydrocephalic dementia.
pressure hydrocephalus can be a reversible or treatable disorder. It is
thought to account for about 5% of all dementias. The incidence is about 1
out of 100,000 people.
Hakim and Adams first described normal pressure hydrocephalus in 1965.
The NPH syndrome has continued to present many questions with regard to
the most reliable diagnostic and prognostic factors. In addition the high
rate of complications associated with shunting makes treatment highly
45% of the cases are idiopathic and most of the patients are elderly. The
high prevalence of atherosclerotic disease of the cerebral arterioles and
veins vessels has been blamed. Changes in CBF and the CSF chemistry may
play a part. The CSF obstruction may provide the driving force by
establishing a transmantle gradient. The other possible factors are
increased pulse pressure in the ventricles.
The rest are due to defective archnoid villi. The archnoid villi, and
subsequently subarchnoid pathways, may get obliterated in SAH, infections,
trauma, and intracranial surgery resulting in NPH.
The exact pathogenic cascade leading to hydrocephalus with normal CSF
pressure and the typical symptomatology is not yet completely understood.
It has been hypothesized that NPH is initiated by an increase in the
ventricular CSF pressure with resulting changes in the tangential and
radial stresses within the brain parenchyma. At first the ventricular
dilatation is small and combined with compensation of the raised CSF
pressure by the compressibility of the low pressure venous system. As the
pressure remains high over hours and days, there is a net shift of water
content from the brain although the water content in the periventricular
white matter increases due to movement of CSF across the mechanically
damaged ependyma under a hydrostatic gradient. The yielding or plastic
deformation of the tissue leads to relaxation of tangential stresses in
the brain parenchyma and consequently to an increase of subdural
stresses. Loss of protein and lipids in the brain parenchyma occurs due
to chronic stress. In this stage CSF pressure returns to normal values,
for instance by decreased CSF absorption resistance by reopening of
previously blocked pathways or new routes being opened up, or decreased
CSF production. The ventricular dilatation persists due to decreased
resistance of the brain parenchyma. Very small transmantle pressures (2-4
mmHg) are able to maintain the ventricular dilatation under these
The pathophysiology of symptoms in NPH is related to dysfunction of
periventricular structures. This can be explained by the increased initial
tangential stress in this region, the hydrostatic edema which may occur
due to destruction of the ependyma and later on the loss of protein and
lipids. Besides, a pre or coexisting vulnerability of the white matter
caused by ischemia, hypoxia, head trauma and the effects of ageing may be
required for the development of the NPH syndrome.
NPH can occur
at any age, but
is mainly a disease of the elderly. The occurrence of NPH in children is
claimed by some. Symptoms in children are different from symptoms in the
elderly and include abnormal limb posturing, irritability, and vomiting.
The estimated prevalence among mentally disturbed elderly people ranges
from 0 to 5.6%.
The important clinical signs are mental changes, urinary incontinence, and
The cardinal aspect of
the mental change is the slowing of mental processes without any
aberration. Mental deterioration in NPH is due a disorder of frontal lobe
systems which have extensive connections with the basal ganglia
(especially the caudate nucleus), the thalamus (especially the dorsomedial
nucleus), the hippocampus, the amygdale, the cingulated gyrus, the septal
nuclei, and the hypo-thalamus. All these structures are interconnected by
long pathways through the deep white matter of the brain, most
particularly the periventricular regions and the centrum semiovale. The
typical features are a loss of creativity difficulties with task
performance in daily life, poor scores on tests for formulation and
maintenance of strategies, self monitoring for errors in performance, and
ability to ignore irrelevant distracting stimuli. Problems initiating and
sustaining actions may occur. Apathy and inattention in early stages may
precede short term memory deficits. Akinetic mutism manifests in the late
spells, and disturbances of balance may precede a slow, short, shuffling,
wide based, and unsteady gait. The pathophysiology of gait disturbances is
considered to be multifactorial, involving several periventricular
structures such as the corticospinal tract, the caudate nucleus and its
caudatocortical connections with other extrapyramidal nuclei and the
frontal cortex. The gait disturbance is a subcortical motor control
disorder rather than a phenomenon of spasticity or apraxia.
They may be bed ridden
in the late stages.
It is an important
component of the clinical picture. Urge incontinence is frequently the
first sign. The pathophysiology may be related to dysfunction of the
superior frontal gyrus and the anterior cingulated gyrus. In later stages
loss of sphincter control may occur due to severe frontal lobe
Late stages there may
be faecal incontinence.
There is no papilledema,
but occasionally nystagmus may be seen with increased tendon reflexes. The
primitive reflexes of sucking and grasping appear in the late stages.
Neuropsychological tests of frontal lobe function help to evaluate the
degeneration may coexist with NPH and thus present difficulties in
decision making. Some knowledge on other causes of dementia helps.
Dementias can be sub-classified as cortical
or subcortical dementia.
Cortical dementias often involve aphasias,
apraxia, and/or agnosia, and include, Alzheimer's disease and Jacob-Creuztfeld
Subcortical dementia is characterized by
intact language and visuo-spatial function, and include Parkinson's,
disease, Huntington’s disease, HIV infection,
In NPH there are no
illusions, hallucinations or irrational speech (frontal lobe inertia).
Brief notes on some of the causes of dementia
are given below:
Alzheimer's disease is considered
the most common cause (50%).
precedes gait disturbances and urinary incontinence. There are features
of cognitive dementia in neuropsychological tests. There is significant
cortical atrophy on CT and MRI. Hippocampal atrophy on coronal CT is
related to Alzheimer’s disease and correlates to poor shunt response
concerning cognitive improvement in suspected NPH. SPECT reveals
diminished uptake in temporoparietal areas.
Vascular dementia: Formerly known as multi-infarct dementia
(MID). Results from brain damage caused by multiple strokes (infarcts)
within the brain. Symptoms can include disorientation, confusion and
behavioral changes. Vascular dementia is neither reversible nor curable,
but treatment of underlying conditions (e.g., high blood pressure) may
There may be
superficial cortical and/or deep lacunar infarcts on CT-scan or MRI. Normal
radiology does not rule out vascular dementia.
disease: A disease affecting control of muscle activity,
resulting in tremors, stiffness and speech impediment. In late stages,
dementia can occur, including Alzheimer's disease. Parkinson drugs can
improve steadiness and control, but have no effect on mental
Pick's disease: A rare brain disease that closely resembles
Alzheimer's, with personality changes and disorientation that may
precede memory loss.
There is atrophy of
frontal poles and temporal poles on CT-scan or MRI, and diminished
uptake in frontal lobes in SPECT. It is difficult to differentiate from
Alzheimer’s disease. As with
Alzheimer's disease, diagnosis is difficult, and can only be confirmed
Creutzfeldt-Jakob disease (CJD): A rare, fatal brain
disease caused by infection. Symptoms are failing memory, changes in
behavior and lack of muscular coordination.
These are features of
cortical dysfunction. EEG shows periodic synchronous discharge.
body dementia (DLB): Also referred to as DLB (Dementia
with Lewy Bodies). A disease recognized only in recent years, in
which the symptoms are a combination of Alzheimer's disease and
Parkinson's disease. Usually, dementia symptoms are initially present
followed by the abnormal movements associated with Parkinson's. There is
no treatment currently available.
Huntington's disease: A hereditary disorder characterized
by irregular movements of the limbs and facial muscles, a decline in
thinking ability, and personality changes. In contrast to Alzheimer's,
Huntington's can be positively diagnosed, and its movement disorders and
psychiatric symptoms controlled with drugs. The progressive nature of
the disease cannot be stopped.
Binswanger's disease: An extremely rare dementia marked by
loss of memory, mood changes, abnormal blood pressure, and disease of
the heart valves or large blood vessels in the neck. Other symptoms may
include tremors, difficulty walking, incontinence and depression.
Binswanger's is slowly progressive, often marked by periods of partial
recovery, and is not at present curable.
There is diffuse
periventricular hypodensities and lacunar infarcts on CT and MRI.
There is pseudobulbar
palsy and rigidity with vertical gaze paresis and impairment of
convergence. In a later stage horizontal gaze paresis and downward gaze
pareis. On CT-scan and MRI, there are hypodensities in different
anatomical regions such as the substantia nigra and superior colliculli.
In addition, there is atrophy of mesencephalon and pons, later followed
by distension of the aqueduct and fourth ventricle and atrophy of
temporal lobes.There is diminished uptake in frontal lobes with normal
cortical uptake in SPECT.
Depression: A psychiatric condition marked by sadness,
inactivity, difficulty with thinking and concentration, feelings of
hopelessness, and in some cases, suicidal tendencies. Many severely
depressed persons also display symptoms of memory loss.
Dementia related to depression,
alcoholism, drug interaction, thyroid and other problems may be
reversible if detected early.
scan is the primary mode of investigation and shows dilated ventricles
with normal sylvian fissures and sulci. Periventricular low density
suggests transependymal flow.
may provide additional information of the cerebral parenchyma. CSF
flow changes may be studied in MRI. Even if there is some degree of
cerebral atrophy, shunting may help.
Further tests are
normally required if CT and MRI are inconclusive.
Lumbar CSF drainage
of about 50ml may help in evaluation; clinical improvement after CSF
drainage implying good response to shunting. This test is not always
reliable, but most commonly employed.
CSF absorption test,
first described by Katzman and Hussey in 1970, helps differentiate between
presenile dementia and NPH. Saline infused into the lumbar subarchnoid
space at a rate of approximately twice the normal rate of CSF formation
produces a slow rise in CSF pressure in patients with normal absorption
capacity. But when the CSF absorption is delayed as in NPH, the CSF
pressure rises suddenly which predicts good response to a shunt procedure.
helps to study the CSF circulation. The most commonly used isotope is
iodine 131-labelled human serum albumin (RiHSA). The isotope is
introduced into the lumbar intrathecal space. Normally, activity will
appear within the cisterna magna after half an hour; after about two hours
activity will appear in the basal cisterns and after about 6 hours over
the cerebral hemispheres. By 24 hours the activity is concentrated in the
parasagittal region. Normally visualization of the ventricular system will
not occur. By 48 hours only slight diffuse activity is generally evident,
and symmetry of distribution on anteroposterior views is the rule. This
test is of no use in non-communicating hydrocephalus. Isotope
cisternography in NPH is characterized by cisternoventricular reflux, lack
of isotope in the anterior basal cisterns, and delayed clearance from the
ventricles. Water soluble contrast, instead of an isotope, helps in a more
scan (single photon emission computerized tomography) may reveal global
diminished uptake, suggesting a global hypometabolism, in NPH, and help to
differentiate from other causes of dementia.
Xenon enhanced CT
scan provides a method for cerebral blood flow (CBF) measurement. The
xenon concentration within brain is determined from the CT scans collected
during a 6 minute xenon inhalation. The CT scans enhance with time, and
xenon concentration can be calculated by subtracting the values of the
enhanced scans from the baseline CT. In NPH the regional cerebral blood
flow is decreased in the hippocampal regions and in the frontal and
parietal white matter.
may predict the outcome of shunt surgery. Those who show transient
increases in ICP (Lundberg B waves) on 24 hours monitoring do well after
a shunt surgery, while those with a flat tracing do not.
CSF drainage through a
ventriculoperitoneal or ventriculoatrial shunt gives good results.
Acetazolamide 250-500/d decreases CSF production and seemed helpful in one
small uncontrolled study. Occasional reports claim no benefit with shunt.
Some surgeons prefer to
use a low pressure shunt. Others recommend a medium pressure shunt.
The mental symptoms
improve rapidly and the improvement continues for weeks. Gait takes a
In some cases,
improvement after shunting may be delayed for several weeks to months. In
some cases, for unknown reasons, improvement is only temporary.
On the basis of
numerous studies, in patients with a known etiology and the complete
clinical triad, improvement after shunting will occur in 60-75% of cases.
In idiopathic NPH, this percentage drops to 10-40%.
in ventriculomegaly is not always seen or proportionate to the clinical
improvement. However, there is increased CBF in both grey and white matter
following the surgery.
It is interesting to
note that good outcome following a shunt has been reported in degenerative
brain diseases without all the classical features of NPH. The presence of
atherosclerotic changes does not influence the results; however, careful
selection of patients is warranted before shunt surgery.
The following factors
suggest a favorable outcome:
1) Shorter duration
2) Presence of urinary
incontinence and early onset of gait abnormalities.
ventricular enlargement with minimal or absent cortical atrophy.
Enlargement of the third ventricle is also predictive of good response to
4) MRI-scan: A
distinction can be made between shunt responsive NPH (true NPH) and shunt
refractive NPH (false NPH) on the basis of T1 and T2 of the water proton
of the perventricular white matter. In the true NPH group both T1 and T2
of the periventricular white matter are significantly prolonged. In the
false NPH group there is only a significant prolongation of T1.
Pronounced aqueductal flow void extending into the 3rd and 4th
ventricle is an indicator of increased (hyperdynamic) aqueductal CSF flow
and shunt responsive NPH syndrome.
5) A good response to
Lumbar CSF drainage.
6) Altered CSF dynamics
in 24hours CSF pressure monitoring.
7) CSF levels of delta
sleep inducing peptide (DSIP), peptide YY (PYY) and somatostatin (SOM) are
decreased in NPH. Levels of DSIP, SOM and VIP (vasoactive intestinal
peptide) increase significantly in parallel to the clinical improvement
after the shunt operation in NPH patients.