1. A 73-year-old man with an unremarkable pastmedical history presented after a 3-year history of progressive forgetfulness and poor balance as well as recent onset of urinary incontinence. Examination showed impaired memory and difficulties with calculations and visuospatial skills. Language was normal. MMSE was 23/30. The rest of the neurologic examination was notable for diminished postural reflexes and abnormal gait with signs of gait apraxia.

2. Laboratory tests did not reveal any treatable cause ofdementia. CT brain demonstrated enlarged ventricles and hypodensity of the white matter. Lumbar puncture was performed with normal opening pressure, and 30 cc of CSF was collected. CSF analysis was normal. The patients gait transiently improved with better stride and improved postural reflexes. 3. What will you do next? What other tests are available to diagnose NPH? What are the treatment options available? What are the available shunt surgeries and types? Can you predict the success of a shunt surgery? If so,how? 4. Historical aspect Hakim-Adamssyndrome / Hydrocephalic dementia / Internal hydrocephalus Salomn Hakim Dow (1922-2011) Colombian neurosurgeon 5. In 1965, Hakim and Adams described a syndrome of progressive cognitive decline gait impairment and urinary incontinence in the context of ventricular dilatation and normal Pcsf measurement during LP a condition subsequently referred to as NPHHakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci. Jul-Aug 1965;2(4):307-27. 6. Pathophysiology An increased subarachnoid space volume does notaccompany increased ventricular volume. Distortion of the central portion of the corona radiata by the distended ventricles. The periventricular white matter anatomically includes the sacral motor fibers that innervate the legs and the bladder, thus explaining the abnormal gait and incontinence. Compression of the brainstem structures (ie, pedunculopontine nucleus) could also be responsible for gait dysfunction, particularly the freezing of gait that has been well described. Dementia results from distortion of the periventricular limbic system. 7. Pathophysiology CSF absorption at the arachnoid villi CSF pressure Force = Pressure X Area force against the brain than the same pressure in normal-sized ventricles Ventricular enlargement With further enlargement of the ventricles, CSF pressure returns to normal 8. Idiopathic 50%Secondary Subarachnoid hemorrhage Head trauma Infectious or carcinomatous meningitis CSF protein levels (including elevation due to intraspinal tumors) 9. Epidemiology The incidence of INPH has been reported to bebetween 1.8 cases per 100,000 individuals and 2.2 cases per 1,000,000 individuals. Age > 60 years Slight male preponderanceKrauss JK et al. (2004) Normal pressure hydrocephalus: survey on contemporary diagnostic algorithms and therapeutic decision-making in clinical practice. Acta Neurochir (Wien) 146: 379388 10. Guidelines for the Diagnosis and Management of Idiopathic Normal Pressure HydrocephalusVOLUME 57 | NUMBER 3 | SEPTEMBER 2005 SUPPLEMENT 11. History Brain imaging Clinical Physiological 12. 1. History 1.2. 3. 4.5. 6.Insidious onset (versus acute) Origin after age 40 yr A minimum duration of at least 3 to 6 mo No evidence of an antecedent event such as head trauma, intracerebral hemorrhage, meningitis, or other known causes of secondary hydrocephalus Progression over time No other neurological, psychiatric, or general medical conditions that are sufficient to explain the presenting symptoms 13. 2. Brain imaging Ventricular enlargement not entirely attributable to cerebral atrophy or congenital enlargement (Evans index 0.3 or comparable measure) 2. No macroscopic obstruction to CSF flow 3. At least one of the following supportive features 1.a) b) c)d)Enlargement of the temporal horns of the lateral ventricles not entirely attributable to hippocampus atrophy Callosal angle of 40 degrees or more Evidence of altered brain water content, including periventricular signal changes on CT and MRI not attributable to microvascular ischemic changes or demyelination An aqueductal or fourth ventricular flow void on MRI 14. Brain imaging findings supportive of an INPH diagnosis 1. A brain imaging study performed before onset of symptoms showing smaller ventricular size or without evidence of hydrocephalus 2. Radionuclide cisternogram showing delayed clearance of radiotracer over the cerebral convexities after 4872 h 3. Cine MRI study or other technique showing increased ventricular flow rate 4. A SPECT-acetazolamide challenge showing decreased periventricular perfusion that is not altered by acetazolamide 15. 3. Clinical Clinical Gait disturbance Cognition impairment Urinary symptoms With respect to gait/balance, at least two of the following should be present and not be entirely attributable to other conditions a) b) c) d) e) f) g) h) i)Decreased step height Decreased step length Decreased cadence (speed of walking) Increased trunk sway during walking Widened standing base Toes turned outward on walking Retropulsion (spontaneous or provoked) En bloc turning (turning requiring three or more steps for 180 degrees) Impaired walking balance, as evidenced by two or more corrections out of eight steps on tandem gait testing 16. With respect to cognition, evidence of at least two ofthe following on examination that is not fully attributable to other conditions a) b) c) d)e) f)g)Psychomotor slowing (increased response latency) Decreased fine motor speed Decreased fine motor accuracy Difficulty dividing or maintaining attention Impaired recall, especially for recent events Executive dysfunction, such as impairment in multistep procedures, working memory, formulation of abstractions/similarities, insight Behavioral or personality changes 17. In the domain of urinary continence, either one ofthe following should be present 1. 2. 3.4.Episodic or persistent urinary incontinence not attributable to primary urological disorders Persistent urinary incontinence Urinary and fecal incontinence Or any two of the following should be present a)b)c)Urinary urgency as defined by frequent perception of a pressing need to void Urinary frequency as defined by more than six voiding episodes in an average 12-hour period despite normal fluid intake Nocturia as defined by the need to urinate more than two times in an average night 18. 4. Physiological CSF opening pressure in the range of 518 mm Hg (or70245 mm H2O) as determined by a lumbar puncture or a comparable procedure. Appropriately measured pressures that are significantly higher or lower than this range are not consistent with a probable NPH diagnosis. 19. Comparison of cognitive deficits in Alzheimers disease and NPH 20. Comparison of NPH, Alzheimers and Parkinsons disease 21. Possible INPH 22. Unlikely INPH No evidence of ventriculomegaly 2. Signs of increased intracranial pressure such as papilledema 3. No component of the clinical triad of INPH is present 4. Symptoms explained by other causes (e.g., spinal stenosis) 1. 23. Ventricular size Normal vs. NPH 24. Conditions that may present similarly to INPH or present comorbidly 25. What is the role of measuring CSF OP? In normal volunteers, the CSF-OP averages 122 34 mm H2O (8.8 0.9 mm Hg) LP - left lateral recumbent position. In patients with INPH, the CSF-OP averages 150 45 mm H2O (11 3.3 mm Hg) Slightly higher than normal Transient high pressures (B waves) are detectable during prolonged intraventricular monitoring in adults with INPH . CSF-OP is a poor measure of the complex temporal profile of intraventricular pressure variations that occur in hydrocephalus patients. CSF-OP measurement may be most useful in identifying hydrocephalic conditions other than INPH, particularly when the OP is elevated above 18 mm Hg (245 mm H2O). - 26. Shunt-responsive and shuntnonresponsive INPH Favorable response to shunting will vary from 46 to 63% . The best indicator for shunt responsiveness was patients with the complete triad and achieved a61.2% rate of improvement CSF lumbar tap, external lumbar drainage, or CSF resistance studies. 27. Leonardo da Vinci (14521519): anatomic study of the ventricular system with the infundibulum of the third ventricle in exaggerated proportion, in accordance with Galen 28. Predictive Value of Radionuclide Cisternography Pre-CT era Injecting an isotope (131I labeled serum albumin or 111Inpentetate) via a lumbar puncture, followed by intermittent two-dimensional gamma imaging over the course of 24 to 48 hours. Two abnormal isotope distribution and time course patterns were noted in hydrocephalic patients: 1) ventricular reflux and 2) delayed ascent and prolonged activity of the isotope over thecerebral convexities. Evidence-based support for its use in INPH does notsupport its continued use on a routine basis. 29. Summary Based on the one Class III study, cisternography doesnot improve the diagnostic accuracy of identifying INPH and therefore is not included as an option. 30. Predictive Value of ICP Monitoring The average opening pressures in the cited INPHstudies range from 8.8 1.3 mm Hg to 14.62 1.5 mm Hg. Many secondary NPH patients present with low or normal ICPs, although the finding of a baseline elevated ICP raises the suspicion of secondary NPH. A consensus of European and United States experts, combined with the results of limited published works, placed the expected range of INPH opening pressure between 60 and 240 mm H2O, or 4.4 to 17.6 mm Hg. 31. It has been proposed that the increased frequency in B waves is indicative of lowered compliance and/or may play an important role in the pathophysiology of the ventriculomegaly andneuronal dysfunction. On the basis of expert opinion, an upper limit of 240 mm H2O (17.6 mm Hg) has been selected as acceptable for analysis as an INPH patient. 32. Summary The measurement of ICP should be considered duringthe diagnostic/prognostic phase of INPH. An elevated ICP should prompt a reassessment to rule out a secondary cause of NPH. Class III evidence does not currently support continuous ICP monitoring to determine the frequency of B or A waves. 33. Predictive Value of CSF Removal via High-volume Tap Test In the classic description of NPH by Adams et al., three hydrocephalic patients were presented, two posttraumatic and one diagnosed as having INPH. In each patient, a spinal tap was performed, and avolume of CSF on the order of 15 ml was removed, with improvement noted in all three patients. The tap test, has evolved in that now most clinicians who use it tend to remove much larger volumes of CSF (4050 ml). 34. Most experts agree that an objective improvement ingait, either by a quantitative method or by blinded videotape review, is preferable. The usefulness of before-and-after neuropsychiatric testing has not been validated for this test or even surgical treatment of INPH, and the degree of improvement in any variable also lacks validation. Moreover, INPH patients have normal daily fluctuations in symptoms, and that motivation can transiently improve performance. 35. Summary On the basis of a single Class II study1, the test had only62% sensitivity and 33% specificity. A multicenter Class II study2 did report a 100% positive predictive rate. Given these limited data, the CSF tap test may have good PPV for INPH; however, specificity is low, suggesting that many patients who might benefit from shunting will be missed. The tap test therefore is listed as a Guideline for the prognostic evaluation of INPH, with the caveat that INPH candidates not be excluded on the basis of a negative tap test. 1. Malm M, Kristensen B, Karlsson T, Fagerlund M, Elfuerson J, Ekstedt J: The predictive value of cerebrospinal fluid dynamic tests in patients with the idiopathic adult hydrocephalus syndrome. Arch Neurol 52:783789, 1995. 2. Walchenbach R, Geiger E, Thomeer RT, Vanneste J: The value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry 72:503506, 2002. 36. Predictive Value of the ELD Test ELD was initially described by Haan and Thomeer andconsisted of draining 10 ml of CSF per hour for a period of 72 hours (total, 720 ml). Now, 300 ml 5 days Prolonged external catheter drainage imposes increased risks of complications Overdrainage complications can occur as a result of inadvertent catheter disconnections or changes in patient position, which may result in very large and rapid CSF loss. Patients with severe short-term memory dysfunction are at highest risk because of lowered patient compliance with remaining still in bed. 37. sensitivity compared with the CSF tap test More patients who do not improve with a large-volumeCSF tap test will show improvement with prolonged drainage and benefit from shunting. The PPV is high, ranging from 80 to 100% The most effective test for identifying INPH. However, hospital admission is required. 38. Predictive Value of CSF Ro Ro = Impedance of flow offered by the CSF absorptionpathways. Katzman test - a pump introduces mock CSF fluid / saline at a known rate via a needle placed in the lumbar SA space. The Ro is the difference in the final steady-state pressure reached and the initial pressure divided by the infused flow rate. The bolus method involves injecting usually 4 ml, into the lumbar subarachnoid space at a rate of 1 ml/s. The advantage of the bolus method is that it also provides a measure of the brain compliance, as defined by the pressure-volume index Katzman R, Hussey F: A simple constant-infusion manometric test for measurement of CSF absorption: Part IRationale and method. Neurology 20:534544, 1970. 39. The sole Class II prospective study found marginalsensitivity, specificity, and PPV values. The reported accuracy of resistance measures may be higher than that of the CSF tap test. Therefore, determination of CSF Ro may be helpful in increasing prognostic accuracy for identifying INPH when tap test results are negative.Malm M, Kristensen B, Karlsson T, Fagerlund M, Elfuerson J, Ekstedt J: The predictive value of cerebrospinal fluid dynamic tests in patients with the idiopathic adult hydrocephalus syndrome. Arch Neurol 52:783789, 1995. 40. Predictive Value of Aqueductal CSF Flow Velocity It has been proposed that NPH patients have a higherCSF flow velocity through the cerebral aqueduct. This was first noted by an exaggerated aqueductal flow void on axial MRI scans For example, Luetmer et al. suggested that velocities greater than 18 ml/min were predictive for good outcome after shunting. The pathophysiological basis of increased CSF flow void velocity in INPH has not been established. Luetmer PH, Huston J, Friedman JA, Dixon GR, Petersen RC, Jack CR, McClelland RL, Ebersold MJ: Measurement of cerebrospinal fluid flow at the cerebral aqueduct by use of phase contrast magnetic resonance imaging: Technique validation and utility in diagnosing idiopathic normal pressure hydrocephalus. Neurosurgery 50:534544, 2002. 41. PCCMR imaging CSF dynamic study in a 74-year-old patient with NPH. A, Midline sagittal T1-weighted MR imaging is used to graphically describe the phase-contrast cine series. The section is placed at the level of the inferior colliculus, perpendicular to a line drawn through the distal aqueduct. B, Axial section in which region of interest is drawn as close as possible to the aqueduct border. C, Respective absolute values of CSF during 16 cardiac phases are reported on the graph. The flow plot demonstrates sinusoidal pattern of flow where negative values represent aqueductal systolic CSF volume (microliter) outflow and positive values represent diastolic CSF volume inflow. Scollato A et al. AJNR Am J Neuroradiol 2008;29:192-1972008 by American Society of Neuroradiology 42. Summary On the basis of current evidence, neither MRI CSFflow void sign nor quantitative CSF flow velocity seems to have significant diagnostic value. However, CSF stroke volume may potentially have greater prognostic value than aqueductal flow void. The prognostic role of MRI for shunt-responsive INPH requires further study. 43. Identifying Shunt-responsive Patients Clinical Evaluation Supplemental Testing Tap Test Resistance Testing External Lumbar Drainage 44. Without further supplemental testing, the degree ofcertainty for improvement after shunt placement for probable and possible INPH ranges from as high as 61% to less than 50% One or more of the following three tests is recommended: CSF tap test, Ro determination, and/or ELD; based on desired prognostic value, personal experience, and equipment/personnel availability 45. CSF OP - In identifying other hydrocephalic conditions Radionuclide Cisternography - Does not improve diagnostic accuracy ICP monitoring In diagnostic / prognostic phase No evidence to support ICP monitoring for A / B waves CSF tap test - Good PPV, but many patients who might benefit from shunting will be missed ELD test - Increased sensitivity and PPV CSF Ro- increasing prognostic accuracy for identifying INPH when tap test results are negative Aqueductal CSF Flow Velocity - neither MRI CSF flow void sign nor quantitative CSF flow velocity seems to have significant diagnostic value. 46. Surgical management of INPH Selected patients can make a remarkable and prolongedimprovement after the placement of a shunt Risk-benefit ratio The 72-hour external lumbar drainage test may give some indication Systemic anticoagulation: Standard neurosurgical precautions should be taken, including stopping antiplatelet medications for the required period before surgery and not restarting them immediately. There are no studies or expert consensus addressing whether or not restarting full anticoagulation with warfarin is a contraindication to a CSF shunt for INPH. 47. Is there a penalty for delaying treatment? The natural history of untreated INPH has not beenstudied well. There is no published documentation on INPH patients returning to normal without treatment. Conversely, there are no published reports demonstrating that INPH is invariably a progressive disorder. 48. Response to Surgical Intervention Many, if not most, INPH patients have comorbid brainconditions. Periventricular white matter ischemia is commonly seen in INPH patients. Patients with severe cerebrovascular disease do not respond as well to shunting but may still derive some benefit from the procedure. The neurological decline sometimes seen despite shunt placement in INPH may be related to the progression of comorbid conditions Even temporary improvements ranging from 1 to 3 years may make a substantial difference in quality of life. 49. Complications Associated with Shunting Anesthesia-related risks (such as myocardial infarction) Acute intracerebral hemorrhage is the primary procedure-related risk Infection Seizures Shunt obstruction Subdural fluid collection and hematoma Overdrainage headaches Shunt underdrainage (failure to improve despite a patent shunt). 50. Subdural effusion vs. hematoma The incidence of subdural hematomas after a shunt forINPH is from 2 to 17% To what extent subdural effusions are a risk factor of a subdural hematoma? Small subdural effusions may be clinically silent Conversely, the incidence of subdural effusions seems tobe related to the degree of shunt drainage, because the incidence was greater in low- versus medium-pressure valves 51. Schematic of the first clinically successful regulatory valve for control of hydrocephalus, introduced by Nulsen and Spitz in 1949.Nulsen F, Spitz EB. Treatment of hydrocephalus by direct shunt from ventricle to jugular vein. Surg Forum 1951;2:399-409 52. Does the type of valve affect the incidence of subdural collection? Unclear. The use of flow-limiting valves or ASDs to reduce theincidence of subdural hematomas has yet to be proved. Adjustable valves allow more conservative treatment of subdural effusions by adjustment of valve pressure. If preoperative intracranial pressure is measured routinely, valve type or pressure is selected on the basis of reasonable physiological grounds and follow-up neuroimaging studies are obtained in a timely manner, then the incidence rate of subdural hematomas presumably will be minimized. 53. Which shunt to perform? VP shunt vs. VA shunt - no prospective or retrospectivestudy in INPH VA shunts - preferred for INPH by some experts. Shunt nephrosis, caused by a long-standing undiagnosedlow-grade shunt infection has not been reported in INPH patients. Lumboperitoneal shunt can be considered, if VP shunt iscontraindicated Mechanical malfunctions Fewer options of valve types Ventriculopleural shunts were historically more popular Pleural effusions Used only when no other option is available or if maximum CSF drainage is desired. Ventriculo-superior sagittal sinus shunts, but long-termresults are still pending 54. When to avoid VP shunt? History of peritonitis History of peritoneal adhesions from multipleprevious abdominal operations Severe constipation Truncal obesity Pre-existing seizure disorder 55. Any role for ETV? May be beneficial in NPH patients who demonstratehigh ventricular CSF outflow resistance in combination with low lumbar CSF outflow resistance 56. Valve Type and/or Setting Selection Simple Differential-pressure Valves Valve opens if the pressure difference exceeds a set value. A spring-loaded ball check valve / leaves of a slit valve Low-pressure (2040 mm H2O), medium-pressure (5090 mm H2O), and high-pressure (100140 mm H2O) The valve pressure settings were relatively small compared with the negative ICP developed by a hydrostatic column of CSF draining to the peritoneum in the upright position (siphoning). In vivo, mean CSF flow rates may be significantly as the valve mechanism is closed mojority of the time Expert opinion strongly recommends against the use of dorsal-slit valves for INPH due to overdrainage. 57. Antisiphon Devices (ASDs) Mechanisms developed to counteract gravity-dependent drainage The ASD is situated in series distal to a differentialpressure valve. Effective in preventing postural intracranial hypotension. For INPH, siphoning has not been proved to be harmful. In patients in whom the baseline ICP is truly normal (including the lack of frequent B waves), placing a shunt with an ASD that is aimed at producing a normal intracranial pressure may be ineffective 58. Flow-limiting valves NMT Orbis-Sigma and Phoenix valves Multistage differential-pressure valves that, in at least oneoperating mode, limit the CSF flow rate by narrowing the aperture through the differential pressure valve mechanism. Valves are designed to operate in the flow-rate-limiting mode under normal conditions and then switch to a high flow rate under conditions of high intracranial pressure. The Codman FloGuard valve is a recently introduced valve that adds in series a dual-stage flow-limiting device to an adjustable differential pressure valve. It is designed to prevent gravity-dependent overdrainage by selectively reducing high CSF flow rates when the patient is the upright position. 59. Dual-stage Differential-pressure Valve Designs The Miethke dual-switch valve uses a dual-stage differential pressure valve design to prevent overdrainage complications. High-density tantalum spheres move within the valve in response to gravity so that the supine and upright positions have low-pressure or very-high-pressure (400 mm H2O) differential-pressure valve settings, respectively. The effectiveness of the Miethke dual-switch valve for INPH has not been established. A lower incidence of subdural hematoma formation with the Miethke dual-switch valve as compared with the OrbisSigma and simple differential-pressure valves. 60. Adjustable (Programmable) Valves Adjustable valves have been designed that allow for the opening pressure of the differential-pressure valve mechanism to be changed noninvasively. The Sophy and Codman-Medos valves PS Medical Strata valve (incorporating an ASD) Codman FloGuard valve (a flow-restricting device) An advantage has not been established in a prospective manner. 61. Sophy valve 62. All programmable valves work on the same principle: Magnetically movable rotor changes pre-load of spring supporting ball in cone 63. Dutch NPH study valve comparison Valve pressures selected were low (3040 mm H2O) vs. medium (5090 mm H2O). Valve pressure selection does not make a difference in NPH No evidence suggesting the usefulness of a programmable valve - may not be valid or reasonable, given the reported experience with adjustable valves for INPH, in which the much higher valve pressures than those used in the Dutch NPH study were optimal for the management The valve pressures used in the Dutch NPH study were too low given the high incidence of subduraleffusions. It is premature to conclude that valve pressure setting is inconsequential with regard to outcome with INPH. 64. The choice of valve type and setting should be basedon empirical reasoning and a basic understanding of shunt hydrodynamics. The most conservative choice is a valve incorporating an ASD, with the understanding that underdrainage (despite a low opening pressure) may occur in a small percentage of patients because of the ASD. Programmable valve may be beneficial in the management of INPH because of the ability to manage both underdrainage and overdrainage problems nonoperatively. 65. Flow chart for management of subdural fluid collections 66. Flow chart for management of nonresponders 67. Flow chart for surgical management of the INPH patient 68. Points to remember The most effective supplemental test for identifyingsurgery responsive INPH is ELD in excess of 300 ml The commonest and often the first symptom in patients with NPH is gait impairment The most likely component of the symptom triad to improve after CSF diversion is gait abnormality 69. Update Diagnostic marker for iNPH CSF protein lipocalin-type prostaglandin D synthase (L-PGDS)1. Brooks M. CSF Protein a Diagnostic Marker for Idiopathic NPH? Medscape Medical News. July 05, 2013. Available at http://www.medscape.com/viewarticle/807381. Accessed July 16, 2013. 2. Nishida N, Nagata N, Toda H, Ishikawa M, Urade Y, Iwasaki K. L-PGDS could be a surrogate marker of frontal lobe dysfunction in idiopathic NPH [abstract 1014]. Available at http://www.mdsabstracts.com/abstract.asp?MeetingID=798&id=107057. Accessed July 16, 2013.