Dementia & Normal pressure hydrocephalus:

 
Dr. A. Vincent Thamburaj,   
Neurosurgeon, Apollo Hospitals,  Chennai , India.

Dementia 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 following:

           aphasia, apraxia, agnosia, disturbances in executive functioning.

In addition, the cognitive impairments must be severe enough to cause impairment in social and occupational functioning. 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 hydrocephalus (NPH), 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. Normal 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 controversial.   

Etiology: 

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.  

Pathophysiology: 

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 conditions. 

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. 

Clinical features: 

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 disturbed gait.  

Mental changes:

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 stages. 

 

Gait disturbances:

Retropulsy, falling 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.

 

Urinary incontinence:

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 dysfunction.

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 dementia. 

 

Differential diagnosis: 

 

Occasionally cerebral 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 disease.

Subcortical dementia is characterized by intact language and visuo-spatial function, and include Parkinson's,  Binswanger’s disease, Huntington’s disease, HIV infection, and depression.

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:  Alzheimer's disease is considered the most common cause (50%). Dementia often 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 halt progression. There may be superficial cortical and/or deep lacunar infarcts on CT-scan or MRI. Normal radiology does not rule out vascular dementia.

Parkinson's 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 deterioration.

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 by autopsy.

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.

Lewy 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. 

Progressive supranuclear palsy: 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. 

Investigations: 

CT scan is the primary mode of investigation and shows dilated ventricles with normal sylvian fissures and sulci. Periventricular low density suggests transependymal flow.

MRI 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. 

NPH- CT

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.  

Isotope/contrast Cisternography 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 precise evaluation.  

SPECT 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.  

Continuous ICP monitoring 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.

Treatment: 

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 longer time.

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%.  

 

Postoperative reduction 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 of symptoms.  

2) Presence of urinary incontinence and early onset of gait abnormalities.  

3) CT-scan: ventricular enlargement with minimal or absent cortical atrophy.  Enlargement of the third ventricle is also predictive of good response to shunt.  

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.

 
 

 

 

 

 

 

 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

 

 

 

 

 

 


 

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