Current Practice in Neurosciences

Normal Pressure Hydrocephalus‑Diagnostic Dilemmas and Selection of Patients for Surgery

MAY 2021

VOLUME 3, ISSUE 3

Jinendra Kumar Ramalingam, Ponraj K Sundaram Department of Neurosurgery, Goa Medical College, Goa, India Ramalingam and Sundaram: Normal pressure hydrocephalus

1 Normal‑pressure hydrocephalus (NPH) was first described in 1965 by Hakim & Adams 2 as a syndrome characterized by a triad of gait difficulty, cognitive dysfunction and 3 urinary incontinence in the presence of ventriculomegaly and normal cerebrospinal [1,2] 4 fluid (CSF) pressure. NPH is now increasingly recognized as a cause of dementia in aging societies. The diagnosis of NPH, however, is challenging as the clinical presentation 5 overlaps with that of other dementias and neurological conditions occurring in this age 6 group. Confirmation of diagnosis requires multiple investigative modalities including 7 radiological imaging, nuclear medicine scanning, CSF flow dynamics and biomarker 8 studies, many of which are not readily available in most centres. In spite of the ambiguity 9 in the etiopathogenesis of this condition, a simple CSF shunt procedure provides 10 a favorable outcome in appropriately selected patients. The management protocol, 11 therefore, needs to be optimized and a judicious approach is mandatory to avoid missing 12 the diagnosis as well as to prevent shunt insertion in the wrong patient. 13 14 Terminology and Definitions 15 NPH presents with the typical triad of gait disturbance, cognitive impairment and urinary 16 incontinence. NPH is classified as: 17 • Idiopathic NPH (iNPH): where no etiology can be determined 18 • Secondary NPH (sNPH): where the clinical syndrome occurs after a prior neurological 19 illness such as subarachnoid hemorrhage (SAH), meningitis, traumatic brain 20 injury (TBI), ischemic stroke and intracerebral hematoma (ICH).[3] 21 22 Demography 23 24 The prevalence of iNPH has been estimated to be 10 per 100,000 to 22 per 100,000. It is roughly estimated that 1.3% of the adult population above 65 years and 5.9% of those 25 aged ≥80 years may exhibit some clinical features of NPH %.[4,5] While sNPH can occur 26 at any age, iNPH generally occurs in adults during the 6th and 7th decades of life.[6] 27 28 Pathophysiology of iNPH 29 30 Unlike sNPH, the cause and pathophysiology of iNPH are unknown. Several interactive 31 mechanisms have been postulated to explain the pathology, clinical features and 32 investigative findings seen in iNPH. An understanding of these mechanisms will help 33 to interpret the diagnostic investigations. The pathological changes seen in iNPH can be 34 summarized as follows: 35 1. Decreased CSF absorption: Reduced venous outflow due to venous sinus stenosis resulting in increased sinus pressure has been reported with a consequent increase in 36 CSF outflow resistance (Rout). An increase of only 3‑4 mm Hg pressure in the superior 37 sagittal sinus can impair CSF absorption through the arachnoid granulations.[7‑10] 38 Further, a decreased cerebral compliance in the elderly causes the subarachnoid 39 spaces to be more rigid creating more resistance to CSF flow.[11] 40 2. Glymphatic impairment: This newly identified system facilitates the bulk flow of 41 CSF and interstitial solutes from the subarachnoid spaces into the brain along the 42 para‑arterial and interstitial spaces and eventually into the para‑venous space and then 43 into the cervical lymphatics thus helping clear excess fluid and waste metabolites from 44 CNS. This process involves aquaporin‑4(AQP‑4) channels on the astrocytic endfeet surrounding the perivascular spaces. Adequate arterial pulsations, sleep and intact 45 AQP‑4 channels are important for the proper functioning of this system.[12] This system 46 has been found to be abnormal in iNPH resulting in reduced clearance of neurotoxic 47 substances, such as beta‑amyloid (Aβ) and hyperphosphorylated tau (HP tau).[13,14] 48 3. Hyperdynamic CSF flow: Normal arterial pulsations cause a pulsatile oscillation 49 of CSF flow in phase with the cardiac cycle leading to caudal flow during systole 50 and upward flow during diastole. The arterial pulsations are normally dampened 51 in the young by the compliant brain and CSF spaces. In the elderly, there is a direct 52 transmission of the vascular pulsations to the ventricles with hyperdynamic CSF flow 53 in the aqueduct because of decreased pulsatility of atherosclerotic arteries and rigid brain and subarachnoid spaces.[15,16] Further, the pulsatile flow is frequently reversed 54 with retrograde flow back into ventricles during diastole.[17,18] and the sustained 55 pulsatile pressure gradient leads to ventricular dilatation and transependymal 56 seepage seen as periventricular white matter (PVWM) hyperintensities on MRI.[19‑,22]

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1 Compression and stretching of white matter fibres secondary to ventriculomegaly 2 may lead to iNPH symptoms.[23] Also, a decrease in gray matter density in the insula, 3 caudate nucleus and thalamus have been noted in iNPH, possibly due to increased [24] 4 transmantle pressure caused by ventriculomegaly. 4. Cerebral Hypoperfusion: Abnormal CSF dynamics leads to ventriculomegaly, which 5 causes cerebral blood flow( CBF) reduction in PVWM, gray matter and basal ganglia 6 as shown by multiple imaging modalities.[25-27] Hypoperfusion further leads to a series 7 of pathophysiological changes including alterations in brain metabolism, gliosis, 8 neuroinflammation, and blood‑brain barrier impairments.[28] 9 10 All of the above factors lead to both white matter and gray matter injury which results 11 in the clinical features seen in iNPH. 12 13 Clinical Features in iNPH

14 [29‑33] 15 a. Gait disturbance Gait abnormality is seen in the presence of normal muscle tone, power, sensory findings and deep tendon reflexes. The gait can be video‑recorded 16 for comparison subsequently. The following characteristic patterns may be seen: 17 • Small, slow, shuffling steps with short variable stride length and decreased height 18 clearance. Differs from Parkinsonian gait by being broad‑based with externally 19 rotated legs; having normal arm swing and unaffected by external cues. Appears 20 to walk “duck‑footed”. Practice does not improve gait in contrast to Parkinson’s 21 patients who can improve stride length and cadence with external cues such as 22 counting. 23 • Apraxia: gait appears to freeze during initiation, turning and walking in a narrow 24 area • Magnetic: Difficulty in lifting foot off the ground 25 • Difficulty in getting up from a chair with instability 26 • Falls due to loss of balance while turning or legs giving way 27 Gait can also be assessed quantitatively with the “Timed Up & Go (TUG)” test and 28 short distance straight walking test for a 10‑meter distance. For the TUG test, the 29 subject is asked to rise from a standard armchair, walk to a spot 3 meters away 30 and return to the chair to sit down.[34] 31 b. Cognitive impairment[30,35] 32 Usually occurs after gait and urinary dysfunction have set in. Compared with 33 Alzheimer’s disease (AD), frontal lobe symptoms are disproportionately severe, and the impairment of memory and orientation is comparatively milder. Cognitive 34 impairment in NPH manifests as a subcortical dementia with psychomotor slowing, 35 decreased attention, impaired memory (memory recognition is better preserved 36 than recall), decreased verbal fluency, dysexecutive syndrome in the form of slow 37 processing speed and impaired problem solving. Objective methods of evaluation 38 include: Mini Mental Status Examination (MMSE)[36], Wechsler Adult Intelligence 39 Scale‑III (WAIS‑III) digital symbol coding and symbol search tasks[37], Frontal 40 Assessment Battery (FAB).[38] [39] 41 c. Urinary incontinence 42 Dribbling of urine occurs in 90.9% and incontinence in 74.5% of patients with iNPH. Detrusor hyperactivity with decreased bladder capacity is postulated to cause 43 increased frequency and urgency. 44 In general, in patients with iNPH[40‑43], gait disturbance occurs in 94‑100%, cognitive 45 impairment in 78‑98%, urinary symptoms in 60‑92% and a complete triad is observed in 46 60% of patients. Other clinical features[44] include an elicitable snout reflex in 84%, eyebrow 47 reflex in 77%, paratonia in 61%, palmomental reflex in 61% and bradykinesia in 55%.[45] 48 49 Investigations 50 51 The investigations for a patient with features in the described triad are directed towards 52 answering the following questions: 53 1) Is hydrocephalus present? 2) Is the hydrocephalus characteristic of NPH? 54 3) Do the investigations account for the clinical presentation and rule out other 55 neurodegenerative disorders? 56 4) Will CSF shunt surgery help?

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1 Radiological Investigations 2 3 1. Evan’s index(EI)>0.3[Figure 1A]: Ventriculomegaly with EI >0.3 seen in initial 4 screening CT/MRI is suspicious of iNPH. 5 2. Disproportionately enlarged subarachnoid space hydrocephalus (DESH) [Figure 2]. DESH is considered a typical MRI finding to diagnose iNPH and is seen in 6 64% of iNPH patients (77% positive predictive value with definitive iNPH).[46] 7 DESH findings are indicative of dysfunctional CSF absorption in the cranial 8 subarachnoid spaces and its presence helps in differentiating iNPH from 9 Alzheimer’s disease[24,47]. iNPH is identified best in coronal MRI images with the 10 following findings: 11 a. Ventriculomegaly 12 b. “High convexity tightness”‑ obliteration of subarachnoid spaces over high parietal 13 convexities and midline 14 c. Widening of subarachnoid spaces at and below Sylvian fissure d. Oval shaped isolated widening of some sulci 15 When at least one of the clinical findings in the triad is associated with DESH, the 16 CSF tap test is generally positive and improvement can be expected after shunt 17 insertion.[40,48] DESH findings normalize after shunt intervention.[49,50] 18 Absence of DESH findings in 36% of shunt responders indicates that DESH 19 findings should not be the sole criterion for the diagnosis of iNPH.[46] 20 3. Ventricular enlargement in the vertical plane (z‑EI‑ Evan’s index along z-axis) 21 [Figure 1B]: Lateral ventricle enlargement in iNPH occurs preferentially in the vertical 22 plane along the z‑axis and this is measured on the coronal MRI slice perpendicular 23 24 25 26 27 28 29 30 31 32 33 34 A B 35 Figure 1: (A) Evan’s Index (EI) = a/b, where: a = maximum width of both frontal horns; b = maximum intracranial 36 width at same section. EI > 0.3 is significant. (B) Z‑EI (Evan’s Index in z‑axis) = a/b, where: a = Height of frontal horn 37 in z‑axis; b = midline diameter of skull in section passing through anterior commissure perpendicular to AC‑PC line. 38 Z‑EI > 0.42 is significant 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 Figure 2: DESH: Showing high convexity tightness with communicating hydrocephalus. Compressed subarachnoid 56 spaces are seen at high convexity and midline (blue arrows) with enlarged sylvian fissure (red arrow)

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1 to the anterior commissure (AC)‑posterior commissure (PC) line at the level of AC; 2 a value >0.42 has been found to be superior to EI > 0.3.[51] 3 4. Narrowed Callosal angle (CA) [Figure 3]: In most patients with iNPH, the CA is 4 narrow and is an indirect measure of DESH. It is the angle between the superior walls of the lateral ventricles in a coronal MRI slice passing through PC perpendicular to 5 AC‑PC line. CA <90° helps differentiate from Alzheimer’s disease (97% sensitivity, 6 88% specificity & positive predictive value of 93%).[52] 7 5. Decreased Brain‑Ventricle ratios (BVR) at AC and PC [Figure 4]: It is measured as the 8 ratio of the height of brain tissue above lateral ventricle and height of lateral ventricle 9 in the same coronal slice perpendicular to AC‑PC line. BVR <1.0 at the coronal plane 10 through AC and <1.5 at that through PC is suggestive of iNPH.[53] 11 6. Dilatation of the temporal horn of the lateral ventricle[52] helps to predict a successful 12 shunt response. [54] 13 7. Narrowing of the posterior part of the cingulate sulcus [Figure 5] In healthy individuals, the posterior part of the sulcus is equal or wider than the anterior part 14 of the sulcus. 15 8. Periventricular white matter changes (leukoaraiosis) on MRI Suggests associated 16 ischemic complications with changes inversely correlating with a positive CSF tap 17 test.[55] 18 9. Increased fractional anisotropy (FA)‑ Microstructural changes in the PVWM can 19 be assessed noninvasively using diffusion tensor imaging; an increase in FA in the 20 corticospinal tract is seen in iNPH.[56] 21 10. Increased Aqueductal stroke volume (ASV): ASV, the mean volume of CSF passing 22 through the aqueduct during both systole and diastole, is calculated on phase‑contrast cine MRI (PCCMR). PCCMR has shown a significant increase in stroke volume through 23 the aqueduct in iNPH (sensitivity of 78‑85% and specificity of 100% for diagnosing 24 iNPH)[57] and ASV>/= 42ul serves as a selection criterion for patients with a good 25 probability of improvement after shunting.[58] ASV and reversed flow rate can predict 26 response to shunting insertion and tend to normalize after surgery.[59] 27 11. Convexity apparent hyperperfusion (CAPPAH) sign seen in cerebral blood 28 flow (CBF) studies with SPECT (single –photon emission computed tomography) 29 30 31 32 33 34 35 36 37 Figure 3: Callosal angle (CA) is measured between the superior walls of the lateral ventricles at a slice perpendicular 38 to AC‑PC line and passing through PC. CA < 90° in most iNPH cases 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 Figure 4: Brain‑ Ventricle Ratio (BVR). BVR = a/b, where: a = z‑axis length of brain above ventricle; b = height of the 56 ventricle

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1 reflects DESH findings. CBF is observed to be decreased in the perisylvian areas 2 and increased in the high parietal convexity areas and this typical finding in iNPH [60,61] 3 is called CAPPAH. 4 12. Regional decrease of CBF on Arterial Spin‑Labeling (ASL) perfusion MRI: This technique does not need a contrast or special isotopes for measuring CBF[62,63] and 5 provides information about regional CBF similar to that seen on SPECT. 6 7 CSF Studies 8 9 a. CSF Tap test: It is useful both for diagnosis of iNPH and for identifying shunt 10 responders and carries a sensitivity of 58% (26‑87%) and specificity of 75% (33‑100%).[64] 11 The CSF test involves removal of 30‑50 ml of lumbar CSF with an assessment of triad 12 of functions at 2‑4 hours, 24 hours and multiple times through the first week after [42,65,66] 13 tap Evaluation is recommended using iNPHGS [Table 1], MMSE, TUG test, [66‑68] 14 short‑distance straight walking test and video recording of gait disturbance. Improvement in the triad of symptoms after the tap test suggests iNPH and a high 15 likelihood of improvement after shunt insertion. Improvement may be noted in the 16 form of increased stride length, shorter time taken to cover a predetermined distance, 17 better turning, decreased freezing and improved scores on cognition tests. Definite 18 guidelines to confirm improvement have not been described and is often customized 19 and individualized to the patient’s preoperative score. However, a negative tap test 20 does not exclude iNPH and false negatives may show improvement after shunt 21 insertion. False‑negative response also may occur if the CSF tap test is done long [70,71] 22 after the onset of symptoms. Gait disturbance is reported to improve earlier than [42,66] 23 cognitive impairment or urinary incontinence after shunting. The predictability of response to shunt surgery based on findings in the CSF tap test 24 was done in a multicentre study(SINPHONI) involving 100 patients. The patients 25 were evaluated before and after CSF tap using three parameters: 1) iNPHGS 2) 26 MMSE score 3) timing during TUG test. In addition, the opening CSF pressure was 27 considered. Gait was evaluated after 24-48 hours while improvement in micturition 28 and MMSE scores were evaluated after one week. An improvement of one grade in 29 any of the parameters of iNPHGS, increase in MMSE score by three or more points 30 or >10% improvement in the TUG test was considered a positive response for the tap 31 test. The study found that the change in the total score in iNPHGS had a sensitivity of 32 71.3% and specificity of 65% for predicting shunt response; the sensitivity reportedly 33 34 35 36 37 38 39 40 41 42 43 44 a b 45 Figure 5: Cingulate Sulcus: Anterior part (blue arrow) compared with posterior part (red arrow). In (a) with NPH, the posterior cingulate sulcus is obliterated 46 47 48 Table 1: iNPH Grading Scale (iNPHGS) 49 Grade Gait disturbance Dementia Urinary incontinence 50 0 Normal Within normal range Absent 51 1 Unstable but independent No apparent dementia but Absent but with pollakiuria or gait apathetic urinary urgency 52 2 Walking with a cane Socially dependent but Sometimes at night 53 independent at home 54 3 Walking with two canes or a Partially dependent at home Sometimes during day 55 walking frame 56 4 Walking not possible Totally dependent Frequent

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1 increased to 82.5% when iNPHGS was considered in tandem with CSF opening 2 pressure of >15 cm of water.[69] 3 When the tap test is negative in a patient with a strong suspicion of iNPH, one of the 4 following three options may be chosen: repeating the tap test, continuous lumbar drainage over 72 hours to enhance tap test sensitivity or empirically performing 5 shunt surgery. If DESH is seen and the CSF tap test is negative in the presence of 6 characteristic symptoms, shunting is likely to alleviate the symptoms in the absence 7 of other comorbidities.[42,66] 8 b. Continuous intracranial pressure (ICP) monitoring: This is an invasive test rarely used 9 for diagnosing iNPH. It may be useful when marked ventriculomegaly is seen and a 10 differential diagnosis of arrested or symptomatic hydrocephalus is considered[72]. The 11 baseline ICP, pressure waves and CSF pulse pressure are assessed. Invasiveness of 12 the test is a major limitation, and there is conflicting evidence on its correlation with [73,74] 13 shunt response. 14 c. CSF infusion test: CSF circulation dynamics can be assessed by injection (bolus/constant infusion) of saline into lumbar thecal space to measure CSF 15 outflow resistance (R ). Higher outflow resistance is reported to be a predictor 16 out of shunt effectiveness. There are some limitations with this test: it is invasive, Rout 17 measured in the spinal CSF compartment may not correctly reflect the intracranial 18 Rout or that of the entire cerebrospinal space and shunt insertion has been found [73,75,76] 19 to be effective even in some even in some patients with low Rout In the Dutch 20 study by Boon et al., the response rate to shunting was 92% in the group with

21 Rout ≥18 mm Hg/ml/min but 66% in the group with lower Rout(<18 mmHg/ml/ [50] 22 min) also showed improvement. 23 d. CSF biomarkers: CSF phosphorylated tau (p‑tau) and total tau (t‑tau) are biomarkers whose values are lower in iNPH than in Alzheimer’s disease (AD) and help to 24 differentiate iNPH from AD.[77,78] 25 26 Diagnosis of iNPH 27 28 There is no single diagnostic test to include or exclude patients for shunting and 29 the decision for the shunt is a calibrated one, considering the clinical picture and 30 available investigation findings. “Possible iNPH” may be considered even if EI 31 is <0.3 when other indices like CA <90 degrees, z‑EI >0.42, BVR at AC level <1 32 and/or BVR at PC level <1.5 are found on MR imaging. When the clinical picture 33 is typical and the investigations clearly suggest the presence of iNPH, the decision 34 for shunt surgery is straightforward. But in the case of equivocal findings, the diagnosis has to proceed in a stepwise manner from possible iNPH to probable iNPH 35 and then to definite iNPH through proper clinical evaluation and interpretation 36 of investigations[79]. 37 38 In a Swedish study, DESH, narrow callosal angle and dilated temporal horns on 39 MRI were found to predict a positive shunt response but their absence did not 40 imply lack of response to shunt; patients with callosal angle >90 degrees (4/7; 41 57%), no DESH (23/36; 64%) and temporal horn< 5mm (7/15; 47%) also showed [80] 42 improvement with shunt. 43 i. Possible iNPH is considered based on the following criteria: 1. Presence of more than one symptom in the clinical triad; 44 2. Other neurological or non‑neurological conditions should not account for the 45 clinical picture; and 46 3. There should not have been a preceding condition that could have caused the 47 ventricular dilation (like SAH, TBI, meningitis). 48 ii. Probable iNPH is considered in a subject with possible iNPH with:

49 1. CSF pressure of 20 cm H2O or less and normal CSF content on lumbar puncture; 50 and 51 2. One of the following two features: 52 a. DESH on MRI along with gait disturbance as described in the section on 53 clinical features or b. Improvement of symptoms after CSF tap test and/or drainage test. 54 Lack of improvement after the first CSF tap test may warrant a second 55 tap test or CSF drainage to look for improvement when iNPH is strongly 56 suspected.

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1 iii. Definite iNPH/Shunt responder 2 When a patient with suspected iNPH shows objective clinical improvement after 3 shunt surgery, he is said to have definite iNPH. 4 iv. Asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM) 5 Patients with AVIM on follow‑up can develop iNPH over time; these asymptomatic patients should hence be monitored carefully.[80] 6 v. Symptomatic patients suspected to have iNPH but with EI <0.3 or no finding of DESH 7 on MRI 8 No guidelines are currently available for the management of such patients who are 9 labelled to have “non‑DESH iNPH”. 10 11 Differential Diagnosis of Dementia 12 13 Dementia as a presenting symptom is seen in both cortical and subcortical dementias. 14 AD and frontotemporal dementia are grouped under cortical dementias while vascular 15 dementia, Parkinson’s disease, Parkinson plus disorders like multisystem atrophy (MSA), 16 corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and dementia 17 with Lewy bodies (DLB) are included along with iNPH under subcortical dementias. 18 While the clinical profile is of importance in differentiating between the different causes 19 of dementia, the presence of ventriculomegaly with DESH (EI >0.3) or typical non‑DESH 20 findings when EI < 0.3 on imaging point toward a possible diagnosis of iNPH. Clinical 21 profile and imaging findings go hand in hand when considering a diagnosis of iNPH. 22 23 Management 24 25 A CSF shunt procedure is the treatment of choice once the diagnosis of iNPH is 26 confirmed. Different CSF diversion procedures used are ventriculoperitoneal shunt (VPS), 27 ventriculoatrial shunt (VAS), lumboperitoneal shunt (LPS) and endoscopic third 28 ventriculostomy (ETV). 29 The most common and effective procedure employed worldwide for iNPH is VPS. In VPS, 30 there is no significant difference with respect to complication and revision rates when 31 either the frontal or parietal burr hole is used for insertion of the ventricular catheter.[82] 32 In the SINPHONI multicentre trial, at one year after surgery, both VPS and LPS were 33 equally effective with similar 1‑year improvement rates on iNPHGS (77% vs 75%) and did 34 not have significantly different severe adverse events (VPS‑15%; LPS‑22%) or non‑serious 35 adverse events (VPS‑20%; LPS‑27.6%). LPS does not have the complications associated 36 with the passage of ventricular catheter but suffers from the disadvantages of difficulties 37 in catheter insertion into the spinal thecal sac affected severely by spinal degenerative 38 disease and higher chances of mechanical failure requiring tube replacement.[83]However, 39 LPS suffers from a higher occurrence of CSF overdrainage complications.[66] 40 41 VAS was as effective as VPS and required fewer shunt revisions than VPS but was associated with a higher incidence of subdural hematomas (VAS‑12.7%; VPS‑5.5%; 42 P = 0.006). VAS is an option in the presence of intraperitoneal adhesions, as with those 43 who have undergone multiple abdominal surgeries.[83] 44 45 ETV has been attempted with improvement seen in 50%[85] but is associated with 46 significantly higher mortality (ETV-3.2%; VPS-0.5%) and higher surgical complications 47 (ETV-17.9%; VPS-11.8%) and is now seldom recommended for iNPH.[86] 48 49 In a meta‑analysis comparing shunting with fixed‑pressure valves and 50 programmable‑pressure valves, the rate of symptomatic improvement was 51 unchanged (76% vs. 74%). However, subdural collections (12% vs. 9%) and shunt 52 revisions rates (32% vs. 12%) were found to be significantly higher with fixed pressure valve shunts.[87] Although programmable pressure‑valve shunt is costlier, the expenses 53 incurred in addressing the complications arising from the use of fixed‑pressure valve 54 have been offset by using programmable pressure valves.[88] Available evidence thus 55 suggests that a shunt with a programmable pressure valve is the current standard of 56 care recommended for iNPH patients.

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1 Secondary NPH 2 3 Secondary NPH can occur in any age group while iNPH mostly affects elderly patients. 4 The onset of symptoms in sNPH is less insidious when compared to iNPH. Atypical 5 symptoms like seizures, altered consciousness and neurologic deficits may be seen [90] 6 in sNPH. Further, sNPH patients do not show the typical radiological features 7 associated with iNPH but may show residual findings of the causative disease along with hydrocephalus; these patients are more likely to exhibit non DESH features of 8 contraction of all subarachnoid spaces and ventricles that are enlarged symmetrically in 9 all directions in contrast to the z‑axial expansion of the lateral ventricles seen in iNPH.[89] 10 11 As sNPH may result from several different causes, it is difficult to design practical 12 guidelines for optimizing treatment and diagnosis.[91] As in iNPH, the diagnosis is made 13 based on clinical history, neurological examination and brain imaging and the treatment 14 is a CSF diversion procedure. The need for shunt insertion is determined by tests used 15 for iNPH such as CSF tap test, CSF drainage and CSF dynamic studies. CSF dynamic 16 studies can help in deciding on shunt placement in suspected sNPH patients with atypical 17 symptoms[92] and can help in predicting outcomes in such patients[93,94] Lower rates of 18 improvement after shunting are seen in patients with iNPH when compared to those [91] 19 with sNPH probably due to the brain atrophy that is seen in addition to hydrocephalic [95,96] 20 features in patients with iNPH. 21 Management of iNPH^ at our center 22 23 • Presence of one or more typical features of the triad of symptoms. 24 • Examination showing features of subcortical type of dementia without focal neurologcal deficitis 25 • No definite history of causative factors such as TBI, SAH, Meningitis Possible • Preliminary CT/MRI shows communicating hydrocephalus & no 26 iNPH additional pathology 27 28 • Multiplanar MRI showing atleast one of following: DESH/ narrow callosal angle/ dilated temporal horn / narrowed posterior cingulate 29 sulcus and no additional pathology • CSF : normal pressure and normal analysis 30 Probable • CSF tap test positive ( if negative and index of suspicion high, test 31 iNPH repeated after 2 weeks) 32 33 • V-P shunt using programmable pressure valve • Frontal burr hole^^ insertion of ventricular end; pressure setting 34 kept high initially and brought down every 2 weeks till desirable Decision for response is seen without overdrainage complications 35 shunt 36 37 38 ^sNPH diagnosis is considered in the appropriate clinical situation (TBI, SAH or meningitis) when 39 there is clinical worsening or lack of further improvement after initial recovery. Serial imaging 40 is generally available for these patients and usually shows progressive ventricular dilatation. 41 CSF analysis is always done and the CSF tap test is done for confirmation in doubtful situations. 42 43 ^^Perceived advantages: Fewer errors in positioning shunt tip; the valve chamber can be positioned 44 easily in a subgaleal pocket unlike in retro‑auricular area with tight fascia; ease of access for 45 pressure setting subsequently. 46 47 Conclusions 48 49 NPH, idiopathic or secondary, is an extremely disabling condition seen of uncertain 50 etiopathogenesis which can be reversed to a significant level by prompt diagnosis and 51 appropriate treatment. An accurate diagnosis can be made when the three basic steps of proper history taking and clinical examination, imaging and CSF tap test are performed 52 serially with careful interpretation of the results obtained at each step. Advanced 53 radiological imaging provides valuable additional information which can aid in the 54 diagnostic process in borderline patients with suspicious diagnosis. Timely intervention 55 with a shunt with a programmable pressure valve leads to a favourable outcome in most 56 patients.

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13 Core Editorial Committee

Dr. Girish Menon, KMC, Manipal - Chairperson

Dr. P. Sarat Chandra, AIIMS, New Delhi- Editor, Neurology India

Dr. D.Muzumdar, KEM Hosptial, Mumbai - Member

Dr. Ashish Suri, AIIMS, New Delhi - Member

Dr. Dwarakanath Srinivas, NIMHANS, Bengaluru - Member

Dr. Pravin Salunke, PGIMER, Chandigarh - Member

Ex-officio members

President- Dr. Lokendra Singh

President Elect - Dr. V.P. Singh

Secretary - Dr. N.Muthukumar

Treasurer - Dr. Daljit Singh