Williams Diagnosis of NPH-Greenville wide UWhsc.ghs.org/wp-content/uploads/2015/09/Williams-Diagnosis-of-NPH-Greenville_wide_UW.pdf–I have been awarded a grant from NASA for LP on

Michael A. Williams, MD January 16, 2016

Greenville Health System 1

Diagnosis of iNPH and the Role of Neurologists in the Longitudinal Treatment of iNPHMichael A. Williams, MDProfessor of Neurology and Neurological SurgeryDirector, Adult and Transitional HydrocephalusUniversity of Washington School of Medicine

Disclosure

> Within the last 12 months:– I receive grant support from NeuroDx Development for work related to SBIR

R43NS067770-01A1– I receive grant support from the National Space Biomedical Research Institute (NSBRI)

for projects SMST02802 and CA02801– I have been awarded a grant from NASA for LP on the ISS– I am an unpaid volunteer Board Member of the Hydrocephalus Association– I received an honorarium and travel expenses from Codman Neuro (Canada) in 2014

to speak in Toronto– I am on the Technical Advisory Board of Aqueduct Critical Care and have unexercised

stock options valued <$500

M.A. Williams / Greenville Health System / January 16, 2016 2

50th Anniversary of iNPH


50th Anniversary of iNPH

Video courtesy of Carlos Hakim

Hakim’s Case #1 Military Hospital, Bogotá, 1962


10th Anniversary of the 1st NIH Workshop


Learning Objectives

> By the end of the presentation, learners will be able to:– Identify the signs, symptoms and neuroimaging features

of iNPH– Describe the use of key diagnostic tests, such as lumbar

puncture or continuous CSF drainage, to identify patients likely to respond to shunt surgery

– Describe the key neurologic principle in the longitudinal care of patients with iNPH




> AND, an article in the April 2016 ofContinuum that Ihave written with Jan Malm from theUniversity of Umeåin Sweden


Organized Approach

> Assessment– Clinical evaluation– Treatment of other disorders before undertaking specific testing for iNPH– Testing that is specific for prognosticating treatment response in iNPH

> Treatment– Shunt surgery– Longitudinal follow-up


Clinical Evaluation

9

iNPH Definition

> iNPH is a treatable form of dementia, gait apraxia and urinary incontinence that may be the underlying cause in 5% of demented patients


Comparative Prevalence

> Prevalence of probable iNPH: 0.2% of persons age 70–79 and 5.9% of those age >80 (Neurology 2014; 82:1449-1454)

> 700,000 persons in the US may have iNPH(2010 Census) (CDC 2012 data 43M over age 65 in 2012)– Brain tumor in the U.S.: __________

> American Brain Tumor Association web site– MS: ________

> National MS Society web site– Myasthenia gravis: _____

> Myasthenia Gravis Foundation web site


Comparative Prevalence

> Prevalence of probable iNPH: 0.2% of persons age 70–79 and 5.9% of those age >80 (Neurology 2014; 82:1449-1454)

> 700,000 persons in the US may have iNPH(2010 Census) (CDC 2012 data 43M over age 65 in 2012)– Brain tumor in the U.S.: 700-750,000

> American Brain Tumor Association web site– MS: ~400,000

> National MS Society web site– Myasthenia gravis: 60,000

> Myasthenia Gravis Foundation web site




iNPH Definition

> iNPH is a treatable form of dementia, gait apraxia and urinary incontinence that may be the underlying cause in 5% of demented patients

> Problem: These are the 3 most common symptoms among the elderly!

> Differential Diagnosis! Differential Diagnosis!! Differential Diagnosis!!!


iNPH Diagnosis

> iNPH clinically overlaps with many conditions of the elderly– Vascular dementia– Degenerative dementias or disease– Cervical stenosis/myelopathy– Lumbar stenosis– Peripheral neuropathy

> These conditions can co-exist with iNPH and they can all mimic iNPH symptoms

> iNPH is a comorbidity among comorbidities


Have you ever seen this patient?

> Elderly patient with possible iNPH, and– Coronary artery disease– Knee or hip prosthesis (or both)– Lumbar or cervical stenosis– Diabetes– Peripheral neuropathy– Periventricular white matter hyperintensities– Evans Index 0.32– Possible atrophy (?AD or FTD or Lewy body)– Prostate cancer (♂) or pelvic floor laxity (♀)– Hearing impairment– Mild cataracts– Taking a diuretic and 10 other medications

M.A. Williams / Greenville Health System / January 16, 2016 15 M.A. Williams / Greenville Health System / January 16, 2016 16

Disorders that may

have all 3 symptoms

Disorders that may

have all 3 symptoms

Disorders that may have 2 symptoms

Disorders that may have 2 symptoms

Disorders that may

have only 1 symptom

Disorders that may

have only 1 symptom

Disorders that aggravate symptoms

Disorders that aggravate symptoms

iNPH: Gait

> Higher-level gait disorder– Difficulty integrating sensory information about the position of the body in

its environment, including the effect of gravity, resulting in disturbed postural and locomotor reflexes in the absence of primary sensorimotor deficits

> Difficulty with transitional movements – Sitting to standing or standing to sitting

> Gait initiation failure, shuffling and poor foot clearance, tripping, falling, or festination; unstable multistep turns; and retropulsion or anteropulsion of stance

> Hard to distinguish from degenerative disorders with motor involvement, such as Parkinsonism or dementia with Lewy bodies


iNPH: Gait

> Spasticity, hyperreflexia and UMN findings are not typical of iNPH> Sense of imbalance, but not vertigo> Asymmetry is not typical of iNPH> Impaired mobility

– Mobility is the functional capacity to move oneself around inside and outside the home to perform activities of daily living, to work, and to socialize

> Not all gait impairment limits mobility




iNPH: Incontinence

> Urinary urgency and frequency– When I gotta go, I gotta go!

> Appears to be a hyperreflexic bladder– Inability to inhibit bladder emptying

> Interaction with impaired gait and urinary urgency> Men and women have different differential diagnoses> Incontinence without awareness is not typical


iNPH: Dementia

> Frontal-Subcortical type– Apathy, amotivation– Psychomotor slowing– Disrupted complex information processing– Impaired ability to manipulate acquired knowledge

> Not typical are: – Impaired language and naming, rapid forgetting not

helped by cues, failure to recognize family, or delirium


Effects of Gait and Dementia

> In our experience, impaired gait and falling is more likely to get patients to the doctor than dementia is

> Impaired memory limits the effectiveness of physical therapy before shunt surgery– Because patients may be unable to remember their learning

from previous sessions


Neuroimaging

> The terms hydrocephalus and ventriculomegaly are notsynonymous

> Although all patients with iNPH should have enlarged ventricles, not all elderly patients with enlarged ventricles have iNPH


Neuroimaging

> International and Japanese Guidelines recommend Evans index ≥ 0.3

> No obstruction to CSF flow> Periventricular white matter hyperintensities are a common

finding in the elderly> Pulsation artifact (flow void) in the Sylvian aqueduct> Bowing, effacement of the corpus callosum> “Ventricular enlargement out of proportion to cortical atrophy”

is unsubstantiated


Thinning of Corpus Callosum




DESH-Disproportionately Enlarged Subarachnoid Space Hydrocephalus

> DESH– Dilation due to impaired CSF

resorption at arachnoid villi– “Major subtype of iNPH”

> High, Tight Convexity– Best seen on coronal views and

thought to distinguish iNPHfrom AD (i.e., cortical atrophy)

M.A. Williams / Greenville Health System / January 16, 2016 25Kitagaki H, et al. AJNR 1998; 19:1277–1284


Evans Ratio 0.32Evans Ratio 0.32

Cisternography


Cisternography

> Should show delayed CSF transit through the ventricles and subarachnoid space due to increased resistance to CSF outflow

> At best, cisternography has a positive predictive value of 50% or less

> Cisternography is of little use if the purpose of testing is to predict response to a shunt

> It is not included as a diagnostic option in the International or the Japanese Guidelines


Treatment of Other Disorders

29

Rationale

> The time required to treat other disorders does not diminish the likelihood of shunt responsiveness

> If the patient’s symptoms resolve, then testing for iNPH may no longer be necessary

> Initiating treatment of an underlying disorder while testing for iNPH makes it difficult to determine if any response is a result of: – Removal of CSF, or– Treatment of the underlying disorder




Examples

> Only cognitive impairment or only incontinence – work up for other disorders first

> Gait and urinary symptoms only – think spinal cord (e.g., cervical stenosis)> Delirium

– If you’re called to evaluate a patient who was admitted because they worsened at home and they have a UTI or other systemic illness….

– WAIT. DO NOT LP THEM. – See them in clinic after discharge. The risk of misattribution is high.

> Initiating treatment (e.g. carbidopa/levodopa) or withdrawing treatment (e.g., benzodiazepines) – wait until everything is stable


Testing Specific for iNPH

3 Main Tests

> “Large volume LP”– AKA Tap Test

> CSF drainage via temporary spinal catheter– AKA external lumbar drainage (ELD)

> Infusion testing


iNPH Guidelines Diagnostic AlgorithmNeurosurgery 2005:57:S2-17-S2-28


Japanese iNPH Guidelines


Japanese Algorithm




Large-Volume LP (Tap Test)

> The patient’s gait must be examined before the LP (Tinetti, TUG, timed 10-meter walk, other scales)

> 18- or 20-Ga needle, 30–50 mL CSF> Do not have the patient lie flat afterward> You want a CSF leak, and nausea is rare> I send the patient and family out for lunch> It is rare for immediate improvement to occur> Re-examine the gait (Tinetti, TUG, etc.) 2–3 hrs after LP


Spinal Catheter Insertion

> Spinal catheter insertion– 16-gauge catheter via a 14-gauge Touhy needle

> Requires hospitalization (4-6 days)> ICP monitoring (optional for 2 days)> Continuous controlled CSF drainage (3 days)> First described in 1988 by Haan and Thomeer


Spinal Catheter Insertion


CSF RemovalSpinal Catheter Insertion

> Continuous controlled CSF drainage (3 days)– Goal of 10 cc/hr

> Double the amount going through a shunt> Half of normal CSF production> Drip chamber adjusted every 4 hours (at my institution)

> Monitor clinical responses, such as gait, balance, urinary urgency / incontinence, cognition

> 90% positive predictive value > Marmarou et al. J Neurosurg 2005;102:987-997

> Low rate of false negative (5-10%)M.A. Williams / Greenville Health System / January 16, 2016 40

Gait Progression and Recovery

> 5/2/02: 78-year-old man with gait and balance difficulty, thinking and memory difficulty, and urinary urgency. Exam most notable for gait impairment

> MRI small vessel disease or iNPH– 1999: Cane– 3/02: LP shows no response– 3/02: Walker– 9/02: Steps stutter in tight places– 3/03: Rolling walker


Tinetti ME. Performance-Oriented Assessment of Mobility Problems in Elderly Patients. Journal American Geriatric Society 1986; 34:119-126.


28 point score (Balance-16; Gait-12)

19-24 points at risk for falling

<19 points at high risk for falling

28 point score (Balance-16; Gait-12)

19-24 points at risk for falling

<19 points at high risk for falling



Tinetti Before and After Shunt Surgery


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GaitBalanceTotal1924

Spinal Catheter Protocol

Shunt Surgery

Tinetti Before and After Shunt Surgery


Spinal Catheter Protocol

Shunt Surgery

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GaitBalanceTotal1924

Pcsf (ICP) Monitoring

> Same Pcsf waveform abnormalities as for brain tumor or acute injury– A-waves and B-waves

> B-wave correlation with shunt response varies from 50% to 90%> Can be done with IVC or spinal catheter> CSF leakage around the catheter can cause falsely low ICP


B-waves


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-5

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23:15 23:20 23:25 23:30 23:35 23:40 23:46

Time

ICP

(mm

Hg)

Risk of Spinal Catheters

> Review of 5-year experience found infection in 15/419 (3.6%)> Gram negative organisms predominate> Rate can be lowered to 2% or less with meticulous attention

to sterile technique with topical chlorhexidine and single-dose pre-procedural antibiotics (Greenberg B, Williams MA. Neurosurgery 2008; 62:431-436)

> At my previous institution, we had no infections in over 4 years until we had one in February 2015


CSF Outflow Resistance

> Resistance (Rout) or conductance (1/Rout)> Infusion of artificial CSF via a spinal needle while recording

Pcsf simultaneously> Class I evidence that these tests predict shunt outcome

(Dutch NPH Study)(See also the work of Malm and Eklund at Umeå, Sweden)

– Rout above 18 mm Hg/ml/min– Conductance above 0.12 ml/min/mmHg

> More popular in Europe than in the US> But still no consensus on diagnostic thresholds




CSF Outflow Resistance


BaselineLevel 1

Level 2Level 3

Level 4Level 5

Level 6

Relaxation

Post-Tap Test-5

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(mm

Hg)

Celda CSF Infusion Protocol

Physiologically Based Tests

> Characteristics of physiologically based tests:– Invasiveness– Labor intensity– Generally high predictive value

> Labor intensity makes them unpopular– Rarely used outside academic medical centers

> What we really need is an accurate test that’s easy > It does not exist


Longitudinal Treatment of iNPHThe Role of Neurologists

Improved Outcomes

> Properly selected patients have a favorable benefit : risk ratio> Contemporary studies show that up to 90% of patients

selected on the basis of response to CSF drainage improve after shunt surgery

> Attention to these patients longitudinally results in sustained improvement for >7 years

> Some of my patients have been with me for over 20 years


Prevailing Model of Care for iNPH

> NPH is often managed as a “1-visit” diagnosis and treatment disease, like an appendix or broken bone– See the neurologist for diagnosis– See the neurosurgeon for shunt surgery– Say good-bye

> Neurologists have not been taught the skills and knowledge to manage iNPH patients longitudinally after shunt surgery


A Better Model of Care for iNPH

> iNPH is a chronic, manageable disease, like epilepsy or parkinsonism– See the neurologist for diagnosis– See the neurosurgeon for shunt surgery– See the neurologist for longitudinal follow-up– Refer back to the neurosurgeon if surgical issues arise

> So…what do we do as neurologists?




Think Like a Neurologist

> See patients at regular intervals> Take an appropriate history for all 3 symptoms> Examine the patient

– Evaluate the shunt– Cognitive screen (MMSE or MoCA)– Gait assessment

> Program the shunt as indicated (CPT 62252)


Shunt Malfunction

> About 1/3 shunts will eventually malfunction– Causing hydrocephalus symptoms to return– But it can be diagnosed and treated– In adults, obstruction is nearly always in the distal catheter

> It is not possible to predict which patients will have shunt obstruction, or when

> Shunt obstruction in iNPH is not an emergency


Avoid Tunnel Vision


Hydrocephalusor ShuntMalfunction

Avoid Tunnel Vision


Hydrocephalusor ShuntMalfunction

Worsening ofexistingconditions

New diagnosesor conditions

Parallel Reasoning

> Simultaneously consider whether the symptoms are from– Shunt malfunction

> Overdrainage vs obstruction

– Other diagnoses> Differential Diagnosis!

Differential Diagnosis!! Differential Diagnosis!!!

> Differential diagnosis is the “value added” of neurologistsin the longitudinal care of patients with iNPH


Lagging Symptom Recovery

> After shunt surgery, if 1 symptom lags behind the others in recovery

> Consider an underlying 2nd diagnosis– Incontinence– Gait– Cognition




Transient Worsening of Symptoms

> Transient worsening of latent neurologic symptoms with systemic illness is seen in iNPH, just as it is with other neurologic disorders

> Acute or subacute worsening should trigger a search for an intercurrent illness (e.g., UTI)

> Worsening after a known illness or hospitalization should be tempered by patience– Counsel the patient to wait for recovery


Insidious Worsening of Symptoms

> If, after initial improvement after shunt surgery, symptoms worsen over weeks or months, consider:– Shunt malfunction– Worsening of a concurrent disorder, such as microvascular disease– Worsening of the iNPH beyond the point of symptom reversibility


Knowing When to Seek Consultation

> Patients with severe ventriculomegaly> Patients who first received a shunt or

endoscopic third ventriculostomy in childhood or as young adults

> Patients who have congenital or childhood-acquired hydrocephalus but were not treated

> Patients who require chronic anticoagulation

> Patients with severe neurologic impairment> Patients with atypical presentations

(eg, no gait impairment)> Patients who need shunt adjustments

> Patients with shunt complications, including wound dehiscence or suspected shunt infection, subdural hematoma in need of surgical evacuation, or intraperitoneal complications

High-Complexity Patients to Consider Referring to a Tertiary Center for Hydrocephalus


Final Thoughts

> Neurologists have an important role in the care of patients with hydrocephalus– Diagnosis– Referral– Follow up

> I hope we’ve encouraged you to look for hydrocephalus and given you the knowledge to better diagnose and treat patients with it


Thank you for your kind attention!

Documents

Williams Diagnosis of NPH-Greenville wide UWhsc.ghs.org/wp-content/uploads/2015/09/Williams-Diagnosis-of-NPH-Greenville_wide_UW.pdf–I have been awarded a grant from NASA for LP on