This document provides information on normal pressure hydrocephalus (NPH), including its causes, symptoms, diagnosis, treatment with shunt surgery, and patient outcomes. It discusses how NPH presents with a triad of gait disturbance, urinary incontinence, and dementia. Diagnostic tests include brain imaging and CSF flow studies. Patients with mild symptoms and gait issues are most likely to benefit from shunt surgery, while those with significant dementia tend to show little improvement. However, long-term outcomes of shunt surgery are variable, with benefits often declining over time.

1. Normal Pressure Hydrocephalus Jerry Ryan MD University of Wisconsin - Madison

2. Objectives 1. Evaluate patients suspected of having NPH and distinguish NPH from other causes of gait disturbance, incontinence and dementia 2. Identify patients who need referral for consideration of treatment of NPH. 3. Understand treatment of NPH and follow patients who have received neurosurgical interventions for NPH in the office. 4. Educate patients with NPH and their families about the disorder.

3. How big is the problem? Prevalence Normal Pressure Hydrocephalus (NPH) Estimates vary from 0- 5% as a cause for dementia Some of variation due to inconsistent definition of NPH Study of 166 patients shunted for presumed NPH calculated incidence of shunt responsive NPH to be one patient per 2.2 million persons per year J Vanneste, P Augustijn, C Dirven, WF Tan and ZD Goedhart Neurology 1992;42:54–9

4. So why do I need to know about NPH? Potentially reversible cause of significant morbidity Recent direct to consumer advertising

5. What should Family Physicians know about NPH? Diagnostic features Diagnostic studies Limitations of prognostic studies Patients likely to benefit from treatment Complications of treatment Patient follow up

6. Etiology 50% cases idiopathic Leading theory is impairment of CSF outflow Intraventricular pressure studies reveal waves of increased pressure- B-waves Adult hydrocephalus syndrome Adult symptomatic hydrocephalus

7. Etiology 50% cases NPH secondary to other illnesses Subarachnoid hemorrhage Meningitis Cranial trauma Secondary NPH has higher response rate to shunting than idiopathic NPH

8. Pathophysiology Ventricle enlargement leads to periventricular ischemia regardless of etiology Compression and stretching of arterioles and venules Arterial hypertension and cerebral arteriosclerosis increased in NPH

9. CSF pathway CSF produced by choroid plexus at rate approximately 20 ml/hr Flows from lateral ventricles through foramina of Monro into third ventricle Enters fourth ventricle through aqueduct of Sylvius Enters subarachnoid space Resorbed by arachnoid villi at top of brain

10. CSF pathway

11. Diagnostic Triad Gait Disturbance Urinary Incontinence Dementia

12. Diagnostic Triad Gait disturbance No classic gait disturbance Gait may be wide based, shuffling More severely affected patients have “magnetic gait”- feet stuck to ground and difficult to initiate walking Difficulties with walking motions resolve with minimal support of patient or lying patient down May resemble Parkinson’s gait Not associated with limb weakness Hyperreflexia

13. Diagnostic Triad Urinary Incontinence True incontinence found only in severely affected patients Urinary urgency in most patients with NPH Due to stretching of periventricular nerve fibers and loss of detrusor inhibition Bladder sphincter muscle unaffected

14. Diagnostic Triad Dementia Presence of dementia in NPH extremely variable Some shunt responsive patients have little or no dementia Dementia usually least responsive of symptoms to intervention Mental status changes may resemble depression

15. Differential Diagnoses- Alzheimer’s (AD) Both AD and NPH cause memory impairment AD- “cortical” abnormalities Aphasia, Apraxia, Agnosia Impaired recognition and encoding deficits NPH- “subcortical” abnormalities Memory impairment but intact recognition Slow information processing Difficulty with complex tasks

16. Cognitive Impairments AD versus NPH Auditory memory Attention/concentration Executive function Behavior/personality changes Motor and psychomotor skills Visuospatial skills Language Reading Borderline Impaired Psychomotor slowing Fine motor speed Fine motor accuracy Memory Learning Orientation Attention/concentration Executive function Writing Impaired NPH AD

17. Differential Diagnoses- Alzheimer’s (AD) AD and NPH can usually be distinguished with formal neuropsychological testing Primary care office testing may not be adequate to distinguish Mental impairment early in course of AD but usually late in course of NPH and often minimal impairment AD often associated with hippocampal atrophy on imaging studies

18. Differential Diagnoses- Parkinson’s Disease Both NPH and Parkinson’s Disease (PD) can have similar gait disturbances Hypokinesia Freezing Imbalance Extrapyramidal symptoms Trial of levadopa can help distinguish between PD and NPH

19. Differential Diagnoses- Other Depression Subcortical arteriosclerotic encephalopathy Multi-infarct encephalopathy Chronic alcoholism B 12 , Folate deficiency Electrolyte abnormalities Cervical or lumbar stenosis Peripheral neuropathy

20. Diagnostic studies Ventricle enlargement on CT or MRI Severity graded by ratio of maximal frontal horn width divided by transverse inner diameter of skull 0.32 minimal for NPH but 0.40 more typical Lack of hippocampus or cortical atrophy Periventricular and cortical white matter lesions may be found in patients with NPH Large number white matter lesions may be marker for poor response to shunting

21. Normal Ventricles

22. Enlarged Ventricles

23. Enlarged Ventricles

24. Enlarged Ventricles

25. Enlarged Ventricles

26. So now that I know it’s NPH what next? Response to shunting varies significantly between patients Study 166 shunted NPH patients Overall response 36%, only 21% significant improvement Only 15% of patients with idiopathic NPH showed marked improvement J Vanneste, P Augustijn, C Dirven, WF Tan and ZD Goedhart Neurology 1992;42:54–9

27. Any Problems With Shunting? Complications of shunting Low immediate post-surgical risks Severe to moderate shunt related morbidity of 28% Infection Shunt malfunction Intracranial bleed Death or severe morbidity 7% J Vanneste, P Augustijn, C Dirven, WF Tan and ZD Goedhart Neurology 1992;42:54-9

28. Overdrainage

29. Are Benefits of Shunting Long Lasting? Most studies show fairly significant decline in benefits over time Initial improvement 60-75% of patients Sustained improvement only 24-42% Results confounded due to high mortality from co-morbid conditions 57% patients dead within 5 years in study by Raftopoulos et.al.

30. How can I tell who will benefit? Good response to shunting Clinical presentation Gait disturbance preceded mental impairment Short duration of mild mental impairment Known cause of NPH- e.g. infection, bleed

31. How can I tell who will benefit? Good response to shunting Special studies Lack of white matter lesions on MRI Marked resolution of symptoms with CSF drainage One time removal 30-50 cc CSF Multi-day drainage of 100-150 cc CSF B-waves greater than 50% of time with continuous intracranial pressure (ICP) monitoring Resistance to CSF outflow greater than 18 mmHg

32. How can I tell who will benefit? Poor response to shunting Severe dementia Dementia presenting symptom MRI abnormalities Cerebral atrophy Multiple white matter lesions

33. How can I tell who will benefit? Indeterminate significance Patient age Duration of symptoms Lack of response to removal CSF

34. How accurate are predictors of response to shunting? Normal pressure hydrocephalus: an update, Stein, SC, Neurosurgery Quarterly (2001) 11 (1):26–35

35. How accurate are predictors of response to shunting? Normal pressure hydrocephalus: an update, Stein, SC, Neurosurgery Quarterly (2001) 11 (1):26–35

36. NPH Guidelines Worldwide group of experts assembled to develop guidelines for diagnosis and treatment of NPH Meetings supported by shunt manufacturer Limited number of RCT’s noted by group Report published in Neurosurgery: Vol. 57 (3), Sept 2005 Supplement

37. Diagnosis- Probable Idiopathic NPH History Insidious onset Age over 40 Symptom duration 3-6 months No antecedent event known to cause secondary NPH Progressive over time No other medical, psychiatric or neurological condition that could cause symptoms

38. Diagnosis- Probable Idiopathic NPH Brain imaging Ventricular enlargement not attributable to cerebral atrophy or congenital disorder No macroscopic obstruction present At least one of the following Enlargement of lateral horns not attributable to hippocampus atrophy Callosal angle greater or equal to 40 degrees Evidence of altered brain water content on imaging not attributable ischemia or demylination An aqueductal or fourth ventricular flow void on MRI

39. Callosal angle Angle of roof of lateral ventricles in A-P projection

40. MRI flow void Loss of MRI signal due to flow of CSF Normal aqueduct Abnormal aqueduct

41. MRI flow void Normal fourth ventricle Abnormal fourth ventricle

42. Diagnosis- Probable Idiopathic NPH Clinical Gait/Balance- at least two of following present Decreased step height Decreased step length Decreased cadence/speed Decreased trunk sway Widened stance Toes turned outward while walking En bloc turning- turns take three or more steps Impaired balance- two or more corrective steps for eight steps on tandem gait testing

43. Diagnosis- Probable Idiopathic NPH Cognition- two of following present Psychomotor slowing Decreased fine motor speed Decreased fine motor accuracy Difficulty dividing or maintaining attention Impaired recall especially for recent events Impairment of executive functions- multi-step procedures, working memory, formulation of abstractions, insight Behavioral or personality changes

44. Diagnosis- Probable Idiopathic NPH Urinary Symptoms- one of following Episodic urinary incontinence not attributable to other causes Persistent urinary incontinence Fecal and urinary incontinence OR One of following Urinary urgency Urinary frequency- 6 or more voids in 12 hour period Nocturia- more than two voids in night

45. Diagnosis- Probable Idiopathic NPH Physiological Opening pressure 5-18 mmHg

46. Possible INPH History- Symptoms are Subacute or indeterminate onset Onset any time after childhood <3 months or indeterminate duration May follow trauma, hemorrhage or meningitis Symptoms not entirely explained by co-existing neurological conditions Non-progressive or not clearly progressive

47. Possible INPH Brain imaging- Ventricular enlargement associated with following Cerebral atrophy of sufficient severity to explain ventricular enlargement Structural lesion that may increase ventricular size

48. Possible INPH Clinical Incontinence and/or cognitive impairment in absence of gait or balance dysfunction Gait disturbance or dementia alone Physiological Opening pressure unavailable or outside of range for probable NPH

49. Unlikely INPH No ventriculomegaly Signs of increased intracranial pressure such as papilledema No component of clinical triad Symptoms explained by other causes (eg, spinal stenosis)

50. UCLA workup for NPH and selecting shunt candidates Ventricular enlargement by CT or MRI (Evans Index >0.3) Complete history and neurological exam, neuropsychiatric testing and gait analysis Patients with significant dementia component referred for more extensive evaluation to rule out Alzheimer’s Disease of other forms of dementia

51. UCLA workup for NPH and selecting shunt candidates Patients felt at risk for NPH undergo intracranial pressure monitoring Inserted with local anesthesia Fine wire placed just under calvarium Elevated pressure- shunt B-waves- further evaluation

52. UCLA workup for NPH and selecting shunt candidates Cerebrospinal Fluid Outflow Resistance Lumbar puncture performed Artificial spinal fluid infused Rise in ICP recorded by previously inserted ICP monitor Resistance to absorbtion of infused fluid calculated High resistance- shunt Normal resistance- further testing

53. UCLA workup for NPH and selecting shunt candidates Trial CSF drainage 3 day trial Small volumes removed- 30-50 cc Improved symptoms- shunt No improvement- no further studies, shunt no longer considered

54. UCLA workup for NPH and selecting shunt candidates Studies not performed Cisternogram High volume CSF drainage PET scan SPECT scan Tests felt not warranted due to expense or increased patient risk MRI flow void not routinely done as felt to be non-specific Further testing felt to add minimal additional prognostic information

55. Yet another workup Treating Normal Pressure Hydrocephalus, Luciano, M, AAFP CME Bulletin, 2004, Vol. 3 (4)

56. Yet another workup Treating Normal Pressure Hydrocephalus, Luciano, M, AAFP CME Bulletin, 2004, Vol. 3 (4)

57. What kind of shunt is used? Externally programmable valve allows transcutaneous adjustment CSF outflow resistance

58. What kind of shunt is used?

59. Shunt placement

60. Shunt Valve Adjustments

61. Now that my patient has had a shunt what happens next? Monitoring of mental function Patients should have neuropsychiatric testing prior to shunt Periodic testing post shunt to document improvement

62. Now that my patient has had a shunt what happens next? Monitor for complications of shunt Infection Shunt malfunction Excessive CSF drainage Subdural hematoma

63. Summary Best patients for shunt have gait disturbance with mild mental impairment Improvement with CSF drainage predict good response to shunt but lack of improvement of limited prognostic value Patients with significant dementia and limited gait disturbance unlikely to benefit from shunt.

64. Cochrane Database Conclusion: There is no evidence to indicate whether placement of a shunt is effective in the management of NPH. Conclusion based upon lack of randomized controlled trials

65. Suggested references Diagnosis and management of normal pressure hydrocephalus, Vanneste, JA, JNeurol (2000) 247:5–14 Neurosurgery: Vol. 57(3) Supplement, September 2005 Normal pressure hydrocephalus: an update, Stein, SC, Neurosurgery Quarterly (2001) 11 (1):26–35 University of California- Los Angeles- http://www.neurosurgery.ucla.edu/Diagnoses/Adult/AdultDis_1.html University of Virginia- http://www.healthsystem.virginia.edu/internet/neurogram/neurogram3_3_nph.cfm