CPT-3 in Normal Pressure Hydrocephalus

Normal pressure hydrocephalus (NPH) is a syndrome involving the clinical triad of gait
disturbance, urinary incontinence, and cognitive dysfunction, in the context of ventricular
enlargement out of proportion to parenchymal atrophy with normal intracranial pressure.

In the 1980's, a protocol for quantitative measurement of symptom response to large volume
CSF tap (40-50ml) was developed, as a method for evaluating suitability for undergoing
ventricular shunting surgery. A 2016 systematic review of the literature noted heterogeneous
findings within the eight prospective cohort studies that were included in analysis, but
concluded that there appeared to be support for the CSF-TT as a rule-in screen for response
to shunt placement.

Unfortunately, no extant literature has analyzed the independent predictive power of a
clinically significant reaction time improvement in response to CSF-TT (widely defined across
the literature as 5% improvement) to subsequent response to ventricular shunting. This
frustrates an a priori power analysis. However, a rough estimate was calculated based on data
presented within one of the aforementioned reviewed studies that identified an improvement in
reaction time in response to CSF-TT, as well as an improvement in reaction time to subsequent
shunting.

The authors reported that 17 of 68 (25%) of the patients were labeled as positive-responders
to CSF-TT, defined as meeting at least 2 of the following criteria: 1) 5% improvement in
reaction time, 2) 5% improvement in gait (time or steps), 3) 25% improvement on visuospatial
recall task, 4) 25% improvement on visuospatial recognition task. Of those 17 positive
responders, 16 (94%) met the same positive-response criteria, post-shunting. If we use a 50%
response rate as a proportion null hypothesis, this gives us a z-statistic = 3.63, or f2 =
3.71. G*Power analysis, for a 4-predictor regression (i.e., the aforementioned indicators
used), estimates a necessary sample size of 16. The primary limitation of this approach is
that it is unclear which of the 2+ positive response criteria were met. However, review of
the pre- versus post-shunting data suggests reaction time was significantly improved
(p<0.001; Cohen's d = 0.399), suggesting it is reasonable to infer the domain was favorably
impacted by the temporary effects of a CSF-TT.

Patients will undergo pre-tap testing on the morning of their CSF-TT. The administration of
the Conners Continual Performance Test - version 3 (CPT-3), an automated 14-minute
computerized measure of reaction-time and sustained attention, will be added to the current
neurocognitive screen being used (i.e., the Montreal Cognitive Assessment, MoCA). The current
CSF-TT protocol's quantitative methods for measuring urinary incontinence and gait will
continue to be collected. These patients will receive post-tap CPT-3 and MoCA testing
one-to-three hours post-tap, and again at 2-3 days post-CSF-TT, during the follow-up
appointment with Neurosurgery. For those that undergo ventricular shunt placement, the CPT-3
will be administered at their post-operative follow-up appointment (~3 months
post-operation).

Inclusion Criteria:

- patients being referred for CSF tap test as part of routine clinical assessment of
idiopathic Normal Pressure Hydrocephalus by their medical provider

- adults older than 18 years old

Exclusion Criteria:

- premorbid neurodegenerative disease (e.g. Alzheimer's Disease, Frontotemproal
Dementia, Parkinson's Disease)

- serious acquired brain injury such as moderate to severe traumatic brain injury, large
ischemic strokes

- seizure disorders

- serious neuropsychiatric disease (e.g. schizophrenia, bipolar disorder, major
depressive disorder, active alcohol or drug abuse)

- untreated vitamin deficiencies (B12, Wernicke-Korsakoff Syndrome)