Timothy C. Hain, MD.• Page last modified: March 18, 2020
In the poorly named syndrome of normal pressure hydrocephalus (NPH), there is the triad ("Hakim's triad") of an apraxic gait, urinary incontinence and memory loss. The syndrome was first recognized in 1965 (Adams, Fisher et al. 1965; Hakim and Adams 1965), perhaps due to the general availablity of the new technology of the brain CT scan. NPH has been written about extensively and there are 1000's of articles in the medical literature. There is a similar situation with idiopathic intracranial hypertension.
|Jaraj et al, 2016||70+||26/1235 (2%) same population as below|
|Jaraj et al, 2014||
|Hiraoka, K., et al. (2008).||65+ Japan (170 persons)||2.9%|
|Tanaka, N., et al. (2009).||65+ Japan (567 persons)||1.4%|
|Marmarou, A., et al. (2007).||Nursing home residents in 4 facilities||9-14% (probable sample bias)|
|Brean, A. and P. K. Eide (2008).||220,000 persons in Norway||21.9/100,000 (.022%) -- presumably a much lower age.|
NPH's prevalence estimates vary widely -- see the table above. In our opinion, the lower estimates of about 1-2% in the population 70 and older are more likely to be correct. It is not common in the general population -- NPH appears to increase dramatically with age.
The reason for the name of "NPH", is that while the cerebral ventricles are enlarged (see diagnosis section below), when pressure is measured through a lumbar puncture (spinal tap), pressure is within normal limits. It is nevertheless thought that at some times, CSF pressure must be too high. The name NPH is a poor one because it it implies that pressure is always normal. NPH differs from "hydrocephalus", where CSF pressure is higher than normal. NPH is attributed to scarring of the arachnoid granulations that absorb CSF. In theory, it may also be caused by overproduction of CSF.
In Benign Intracranial Hypertension (another poorly named syndrome), there is also increased CSF pressure -- in this case easily measurable on lumbar puncture, but there is no obvious cause (such as a tumor or infection). Because BIH is associated with visual loss, it is not truly benign (Friedman et al, 2013). Other terms used for the same situation are pseudotumor cerebri syndrome (PTCS), aind idiopathic intracranial hypertension (IIH). Probably the best of these is the IIH, but the pseudotumor acronym (PTCS) is the more commonly used.
BIH/PTCS/IIH usually occurs in young obese women. Classic signs are headaches or blurred vision, possibly accompanied by pulsatile tinnitus, hearing loss and dizziness. Papilloedema (swelling of the optic disk) is the most common examination finding. Blindness can eventually result from BIH.
Narrowing of the venous sinuses.
Bilateral narrowing of the transverse venous sinuses is sometimes seen in BIH/PCTS/IIH. This narrowing makes it harder for blood to drain from the brain, and increases pressure. Unilateral narrowing may not be that important -- according to Durst(Durst et al., 2016), the prevalence of unilateral transverse stenosis or hypoplasia is 33% in otherwise normal persons. Bilateral stenosis is more specific (Baykan, Ekizoglu, & Altiokka Uzun, 2015).
There are numerous other causes of PTCS -- idiopathic, blockage of other venous sinuses such as the sagittal sinus, various medications and exposures. For example, hyper vitaminosis A, as well as tetracycline and fluoroquinolone type antibiotic. A number of miscellaneous medical conditions that include some highly prevalent ones (e.g. sleep apnea, anemia). Recently, fluoroquinolone antibiotics have been added to the list of risk factors (Sodhi et al, 2017). BIH in obese women is attributed to increased intrabdominal pressure, which hinders cerebral venous return (Sugerman et al, 1997)
Papilledema is not always appreciated, or sometimes appreciated when it doesn't exist. (Favoni et al, 2018).
Friedman et al (2013) proposed the following criteria for two forms of PTCS:
PTCS (pseudotumor cerebri syndrome) criteria
PTCS (pseudotumor cerebri syndrome) without papilloedema, also known as "idiopathic intracranial hypertension without papilledema" or IIHWOP
Criteria 2-5 above and 6th nerve palsy
Criteria 2-5 above and at least 1 of the following -- it would seem pretty hard not to have one of these below:
- empty sella (found in 5% of normal population)
- flattening of posterior aspect of globe
- distention of perioptic subarachnoid space
- transverse venous sinus stenosis (also very common -- 30% of the population)
A 49 year old woman was found to have enlarged ventricles on MRI testing. The MRI test was provoked by spells of shaking and unsteadiness. While at work, she would fall sideways into a wall without loss of consciousness. She was referred for evaluation to the authors clinical practice and a diagnosis of NPH was made from the symptoms and MRI. Diamox (a medication to lower CSF pressure) was tried but it was not effective.
She was admitted to the hospital and posturography was done. This documented very poor balance. Thirty cc of spinal fluid were next removed under Xray control and her posturography was repeated. The repeat study showed greatly improved balance. She felt normal for about 3 days thereafter but then imbalance returned.
She was then sent for an elective ventriculoperitoneal (VP) shunt with a Codman programmable valve. This was performed without complication, and balance has been normal thereafter.
This T2 MRI image shows how the Evans index is computed. This particular one has an index of 57.13/140.82, or 0.405
The "consensus" opinion regarding diagnosis of NPH is that it requires the following:
(Tsakanikas and Relkin 2007)
It is interesting that in the above criteria there is a requirement for a "clearly defined etiology". In other words, lack of knowledge about a neurological event would be enough to prevent a neurologist from making a diagnosis of NPH. This seems odd. It also is odd that there is a requirement for "dementia", but in another bullet point, there should be "mild or absent cognitive impairment. Overall, this list of points seems to us to be just interesting but hardly reliable.
In persons with the diagnostic picture of NPH, MRI or CT testing is generally done and is normal or shows slight enlargement of the ventricles. There is no papilloedema on examination (excluding frank hydrocephalus)
The incontinence in NPH is attributed to a combination of several factors (Sakakibara, et al. 2008)
The most practical test for diagnosis, in the authors opinion, is the "tap" test. This entails removal of CSF through a therapeutic lumbar puncture (Wikkelso, Andersson et al. 1982). This can be combined with checking for chronic infections, as well measurement of gait and postural stability as well as cognitive function (Williams et al, 2008; Ravdin et al, 2008). An improvement in postural stability the following day, after removal of CSF, is diagnostic of NPH. In our clinical practice, we use computerized posturography as our main outcome measure -- obviously this emphasizes the effect on gait. Some authors use a more rapid gait as an indicator of response (Bottcher et al, 2016). These authors have also reported that an improvement in the oVEMP test is also an indicator of response. We find this difficult to follow.
A more difficult test than the "tap" test is continuous lumbar drainage (Panagiotopoulos, Konstantinou et al. 2005). Again gait and cognitive function are assessed post lumbar drainage. This test is likely more accurate, but require an inpatient admission to a specialized unit, and also has more risks. We are frankly dubious that this very expensive process is warranted.
In persons with the picture of BIH, lumbar puncture shows increased CSF pressure with normal cells and protein. MRI or CT scan generally shows normal sized ventricles. Pulsatile tinnitus should be reduced or eliminated by pressure over the jugular vein.
|Prior to shunt (NPH)||After Shunt (4 years)|
Treatment of NPH relies on shunting. About 60% of patients have immediate improvement, about 30% prolonged improvement. In our practice at CDH, we estimate that about 50% of patients who improve after a diagnostic tap, improve after a shunt. Many of our patients with enlarged ventricles opt not to have a shunt (or the spinal fluid removal test) as well.
The American Academy of Neurology (2015) provided guidelines regarding shunting and prediction of response. They wrote: "Shunting is possibly effective in iNPH (96% chance subjective improvement, 83% chance improvement on timed walk test at 6 months) (3 Class III). Serious adverse event risk was 11% (1 Class III). Predictors of success included elevated Ro (1 Class I, multiple Class II), impaired cerebral blood flow reactivity to acetazolamide (by SPECT) (1 Class I), and positive response to either external lumbar drainage (1 Class III) or repeated lumbar punctures. Age may not be a prognostic factor (1 Class II). Data are insufficient to judge efficacy of radionuclide cisternography or aqueductal flow measurement by MRI." R0 is a measure of outflow resistance during CSF-IT (i.e. infusion of artificial CSF). This criterian is thus somewhat invasive. Note also that this guideline was based on a total of 3 publications during 2004 and 2011.
There was some pushback on the recommendation to shunt NPH. Saper (2016), the editor of the Annals of Neurology journal, stated in an editorial that due to a report of 11% adverse events (in a study of 54 patients) of Kahlon et al (2007), he felt that "neurologists should seriously consider calling a moratorium on shunting procedures for iNPH until evidence of efficacy is obtained ..." Dr. Saper states that the Kahlon study was "one of the few that reported adverse events". Dr. Saper does not discuss the other studies that had less adverse events. One wonders if this particular neurosurgery team simply had more problems. He wrote this article in response to a "practice guideline" supporting shunting. (Halpirin et al, 2015). Of course, editorials are not generally rigorous and undergo no peer review (unlike the practice guideline that Dr. Saper disagrees with). So overall, it seems that the issue is unsettled, and that there should be good reasons to proceed.
There are many possible serious complications to consider including:
- Shunt malfunction (20%)
- Subdural hematoma (2-17%)
- Seizure (3-11%)
- Shunt infection (3-6%)
- Intracerebral hematoma (3%)
Lumbar shunts are generally thought to fail after about 6 months, and as many as 100% require one or more shunt revisions. In most centers that do lumbar shunts, the revision:new shunt ratio is about 3:1.
Conventional VP shunts may be effective, and they have the advantage of less likelihood of needing revision as they do not have the tendency to close off by themselves. In our opinion, a VP shunt that is adjustable from the outside is presently the best solution for NPH as it avoids the need for shunt revision and also can be adjusted to optimize function without more surgery. An example of this approach is discussed in the case above.
Treatment of BIH is similar to treatment of NPH. It may also include shunting, but also may be managed with serial lumbar punctures, optic nerve sheath decompression, and acetazolamide to lower CSF pressure. Bariatric surgery may be appropriate in those with BIH with obesity.
Recently, in persons with BIH and abnormal MRVs, stenting has been reported as a fairly effective treatment for pseudotumor associated with bilateral transverse sinus stenosis. (Dinkin & Patsalides, 2017a, 2017b; Gross, Albuquerque, Moon, & McDougall, 2016; Lenck et al., 2017). A metanalysis in 2013 was fairly positive (Teleb et al., 2013). Venous stenting has been reported to improve pulsatile tinitus. (Boddu et al, 2016)