NORMAL PRESSURE HYDROCEPHALUS

Hakim and Adams first described

the syndrome of Idiopathic NormalPressure Hydrocephalus (IN PH) in1965. 1,2In tWo articles they reported six

patients with a triad of "mild impairmentof the memory, slowness and paucity ofthought and action, unsteadiness of gaitand unwitting urinary incontinence." Inthree out of the six patients rhe etiologywas unknown, whilehead trauma (2)and

a cystof the third ventricle accounted forthe other three patients.

Their observation was based on a

syndrome, known at the time, of second-ary hydrocephalus. In this disorder, hy-drocephalus developed as a result ofblood or inflammatory cells in the cere-brospinal fluid (CSF), blocking reab-sorption. WIth expanding hydrocephalusdue to increasedpressure, patients wouldusually develop impaired consciousness,headache, and subsequent gait abnormal-ity and bladder incontinence. Therefore,what was new was the normal CSF pres-sure and the idiopathic nature of the dis-ease.

In 1982, CM Fisher underscored

the importance of the gait disturbancein the description of NPH. 3 He de-scribed 30 patients over 60 years of age,evaluated personally,who presented pri-marilywith gait disturbance, hydroceph-alus on CT scan and responsiveness toCSF drainage, either by shunting or byspinal punctUre.None of the patients haddementia preceding the gait abnormal-ity, although both problems could bepresent. He reported that the onset ofgait abnormality before cognitivedeclinepredicted a better prognosis after shunt-mg.

In 1986, Graff-Radford and

Godersky correlated clinical symptomsand shunt responsiveness. 4 In their se-ries of 21 patients shunted for INPH,16 patients improved. Of these, 11 hada gait abnormality that preceded the de-mentia, while 5 had a simultaneous pre-sentation. Of the 5 patients who did notimprove, 3 had a dementing illnesspriorto a gait abnormality, 2 had a concomi-tant presentation and in only one did the

372

ANEL YSSA D'ABREAU, MD

gait disturbance precede the dementia.Basedon those ~ndings, the authors con-cluded that gait abnormality precedingthe dementia was a good prognostic fac-tor in the selection of patients for shunt-mg.

INPH is often considered one of the

rare reversiblecausesof dementia, which

iswhy it isso commonly discussed.How-ever, its importance as a potential causeof reversible dementia is debatable. In a

recent meta-analysis of 39 articles ad-dressing reversibility in dementia, 7042patients with cognitive impairment(5620 with dementia) were assessed. 5

Potential reversibility was found in 9%of the patients, of whom only 0.6% ofthe patients actually reversed. In 2.2%of these patients a surgically amenablecondition was found, including NPH(idiopathic or secondary), subdural he-matomas and cerebral tumors. Accord-

ing to this analysis, the estimatedincidence of shunt-responsive NPH is2.2 per million per year.

Similar figures can be derived frommemory clinic reports. 6In a stUdyof71consecutive patients sent for evaluationof possible INPH, 36 patients did notmeet criteria based on history, physicaland neurological examination andneuroimaging. The most common diag-nosis in the excluded population wascerebrovascular disease. Thirty-five pa-tients were admitted to the neurosurgeryward for hydrodynamic studies,of whom13 were considered shunt candidates.

Only 8 patients respond to shunting.Considering shunt responsiveness as theonly criterion to confirm the diagnosisof INPH, the calculated incidence of

INPH in this population was 1.5 permillion per year.

The pathophysiology of INPH isunclear, and many theories have beenproposed. It is important to differentiateprimary from secondary cases of NPH.The latter usually develops after menin-gitis, subarachnoid hemorrhage or headtrauma. Secondary cases have a muchbetter prognosis and stUdies evaluatingNPH should differentiate betWeenthose

tWo populations. 7

Although isolated intracranial pres-sure (ICP) measurements in INPH are

within the normal range, continuous ICPmonitoring demonstrates an increase inthe occurrence of B-waves in these pa-tients. 8While B-wavesare a physiologi-cal phenomena of unclear etiology, theirpresence in 50% or more of the record-ing time in NPH patients predicts a goodshunting response according to somestudies.

The associationbetWeenINPH and

hypertension, subcortical andperiventricular white matter abnormali-ties (WMD) suggests a possible cere-brovascular role in the development ofINPH. 9 The presence of WMD doesnot preclude shunting, however it car-ries a poorer prognosis. 10

Abnormalities in the cerebral blood

flow (CBF) in the periventricular areasand subcortical white areas,mostly in thefrontal lobes have been demonstrated in

different studies utilizing multiple tech-niques.II Someexpertsbelievethealter-ations in CBF, also known as "miseryperfusion", are responsible for the symp-toms. Some reports have suggestedreversibility or a decrease in those abnor-malities after successfulshunting or CSFdrainage. Unfortunately, the differenttechniques used in the different stUdies,may explain the variability of the results.

Pathological changes at the arach-noid level were described as a potentialculprit in the abnormalities in CSF flow,secondary to deficits in absorption. Bi-opsy stUdiesdo not corroborate this view.Pathological abnormalities in the arach-noid, when observed, do not correlate

with results of CSF hydrodynamic stud-ies or shunt responsiveness. 12In addi-tion, deficits in absorption at thearachnoid levelwould not create a pres-sure gradient betWeen convexities andventricles, and would therefore not lead

to hydrocephalus. 7Any doctor with geriatricexperience

knows that the typical "clinical triad" isa relative common finding in the elderly.Many other diseaseprocesses,either alone

MEDICINE AND HEALTH / RHODE ISLAND

(

or in combinarion, may produce a simi-lar clinical picture. Some characreristics,as described below, are considered help-ful in the differential diagnosis, althoughthere is no pathognomonic clinical or. . .ImagIng sIgn.

The gait abnormality in INPH isof "frontal dysequilibrium" or frontal gaitdisorder type.The most common symp-toms describedbypatients are imbalance,tiredness oflegs, legweaknessand, as thedisease progresses, shorter steps, shuf-fling, scuffing and slow turning. 1,2,3Atriad of hypokinetic gait, associatedwitha wide base, decreased step height anddisturbance of dynamic equilibrium isconsidered "characteristic" ofINPH. 13

The differentiation between INPH

and Parkinson's diseasecan be challeng-

ing. According to one study, in IN PHthe most helpful gait parameters are thewide-based gait, with outward feet rota-tion, decreased range of motion of thelowerextremities,with little or no reduc-

tion of arm swing. In contrast, PD usu-ally has associated extrapyramidalfeatures and the patients respond to vi-sual and acoustic cues. 13

Cortical features such as apraxia,

agnosia and aphasia are absent in INPH.Problems with attention, concentration,

forgetfulness, apathy and mental slow-ing are the rule.Neuropsychologicaltests,although helpful in characterizing thedeficit, are not good predictors of shunt-ing outcome, and in most studies theimprovement in extended neuropsycho-logical batteries is minimal. 14

Iddon et al demonstrated the

unpredictability of the cognitiveresponseto shunt. 15In this study they evaluated11 patients with INPH, 5 in the de-mented range (mini-mental state exami-nation-MMSE<24), and 6 with

MMSE>24. After shunting, the de-mented patients demonstrated signifi-cant improvement in their MMSE andthe Kendrick Object Learning Test(KOLT) which assessesrecall of every-

day objects after a brief presentation pe-riod of a black-and-white illustration ofthem scores.On the other hand, the non-

demented patients demonstrated de-creasedverbal fluency, impaired spatial

recognition and attentional set shiftingtask. Even though the subjects demon-strated improvement of gait after shunt-

ing, the impairment on tests sensitive tofrontal dysfunction remained.

Urinaty urgency is common in theearlier stages;incontinence is a later sign.7 Urodynamic studies demonstrate hy-perreflexia and instability of the bladderdetrusor muscle, but there isno evidence

of defectivebladder control. This suggestsdamage in the periventricular pathwaysto the sacralbladder center and decreasedinhibition of bladder contractions.

IDIOPATHIC

NORMAL PRESSURE

HYDROCEPHALUS

IS AN

OVERESTIMA TED,

UNCOMMON

DISORDER, WITH A

COMMON CLINICAL

TRIAD IN THE

ELDERLY

POPULATION.

The diagnosis of IN PH relies onclinical criteria, neuro-imaging evidenceof hydrocephalus and ideallyevidence ofabnormalities in CSF hydrodynamics.Vanneste et al evaluated the predictivevalue of clinical criteria and CT in the

diagnosis of INPH. 16By using strictlyclinical (predominant gait disturbance,absent to mild cognitive deficit) and CTcriteria (rounded frontal horns, moder-ate ventriculomegaly, absence of whitematter diseaseand cortical atrophy), the

positive predictive value (PPV) was65%, and the negative predictive value(NPV) was 76%. Ineffective shuntingwas observed in 11% of the patients,while missed improvement occurred in13%. More liberal criteria would haveresulted in a PPV of 58%, ineffective

shunting in 37% and missed improve-ment in 5% of the patients. The authorsconcluded that clinicalcriteria associated

with appropriate neuroimaging is thestandard by which new diagnostic test-ing should be used to improve diagnos-tic accuracy and shunt responsiveness.

CSF drainage by lumbar puncture,often considered a "gold standard" in thediagnosis ofINPH, has a vety high inci-dence of false negatives; and a prospec-tivestudy failedto provide any significantadditional information compared to con-servative clinical and neuroimaging cri-teria were utilized to select patients for

shunting. 17Continuous CSF drainageposes a similar problem. In addition, itrequires hospital admission, technicalexpertise, and is not always benign. 18Cysternography does not improve thediagnostic accuracy of clinical and CTcriteria combined, although many doc-tors still use it. 19Continuous intracra-

nial pressure monitoring is a usefulprocedure and resultshave been uniform.Strong evidence supports that the fre-quent occurrence of B-waves (>50% ofthe recording time) in patients withINPH predicts a good response to shunt-ing. 7 Unfortunately continuous ICPmonitoring is not a routine procedure inmost neurosurgical centers.

There are many other diagnosticmodalities, such as the infusion test, theconductance test, cerebrovascular and

metabolic imaging studies. None hasconsistently demonstrated a significantimprovement in predicting shunt-re-sponsiveness. 7

The differential diagnosis of NPHincludes Alzheimer's disease and related

dementias, various causes of Parkin-

sonism, most notably Parkinson'sdisease,dementia with Lewy bodies (DLB) and"multi-infarct encephalopathy". Beforeconsidering the diagnosis ofINPH, oneshould exclude other possible explana-tions rather than the other way around.As mentioned before, INPH, is a rela-

tivelyrare disease,with an incidence com-parable to Creutzfeld-Jacob disease,whileAlzheimer's disease, Parkinson's disease,DLB and multi-infarct state are common

pathologies.The predictors of a positive shunt

response are gait predominant disorderthat precedes any cognitive changes, ashort histoty or absence of cognitive im-pairment, a known cause for the devel-opment of the hydrocephalus, absenceof white matter lesion in neuroimagingstudies. When available, the presence ofB-waves for at least 50% of the record-

ing time, improvement of symptoms af-

373VOL. 87 No. 12 DECEMBER 2004

ter CSF drainage and CSF outflow resistanceover 18mmH G/ml per minute are also valuable prognostic factors. In con-trast, severedementia, dementia as the first symptom and se-vere atrophy or white matter diseaseon the MRI arepredictorsof a negative response to shunting 7.

One may argue that it is appropriate to shunt a demented,gait-impaired patient, to improve the gait, even though n.osignificant improvement will be expected in cognitive fimc-tion. In that case, the family should have realistic expecta-tions, and be informed of the risks of the shunt. The mean

chance of significant improvement after shunting is 30 to 40%in INPH and 50-70% in secondary cases.Complications rangebetween 20-40% of the cases, and include strokes, subdural

hematomas, shunt malfunctioning, seizures and problems re-lated to the anesthesia. Serious complications (death, severeresidual deficit) usually arise in patients with severe co-mor-bidities, and are observed in less than 8% of the patients withINPH. 7,20 Dementia is the least likely symptom to improveespecially if severe.

In conclusion, INPH is an overestimated, uncommon

disorder, with a common clinical triad in the elderly popula-tion. Potential improvement (but probably not reversibiliry)of the gait more than the cognitive dysfunction can be ex-pected only in highly selected patients.

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7. Vanneste JAL.] NeuroI2000;247:5-14.8. Symon L, Dorsch NW Lancet 1972;2:1291-2.9. Krauss JK, Regel JP, Werner V, et al. Stroke 1996:27:24-9.10. Krauss JK, RegelJP, Vach W, et al. Neurosurg 1997;40:491-6.11. Owler BK, Pickard JD. Acta Neurol Scand 2001 ;104:325-42.12. Bech RA, Juhler M, Waldemar G, et al. Neurosurg

1997;40:497-502.

13. Stoltze H, Kuhtz-Buschbeck JP, Drticke H, et al. ] NeurolNeurosurg Psychiatry 2001;70:289-97.

14. Savolainen S, Hurskainen H, Paljarvi L, et al. Acta Neurochir2002; 144:515-23.

15. Iddon JL, Pickard JD, Cross JL, et al.] Neurol Neurosurg Psy-chiatry 1999;67:723-32.

16. VannesteJ, Augustijn P,Tan WF, Dirven c.] NeurolNeurosurgPsychiatry 1993;56:251-6.

17. Maim J, Kristensen B, Karlsson T, et al. Arch Neurol1995;52:783-9.

18. Walchenbach R, Geiger E, Thomeer RTWM, Vanneste JAL.] Neurl Neurosurg Psychiatry 2002;72:503-6.

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Anelyssa D'Abreau, MD, aformer fellow in geriatric neu-rologyat Brown Medical School/Memorial Hospital of Rl, is ageriatric neurologist at the State University of Campinas(UN/CAMP), Brazil.

CORRESPONDENCE:

Anelyssa D'Abreu, MDe-mail: anelyssa@hotmail.com

MEDICINE AND HEALTH / RHODE ISLAND