deficits of language and speech in idiopathic normal
TRANSCRIPT
Deficits of Language and Speech in Idiopathic Normal Pressure Hydrocephalus
CitationChung, Esther H. 2018. Deficits of Language and Speech in Idiopathic Normal Pressure Hydrocephalus. Doctoral dissertation, Harvard Medical School.
Permanent linkhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41973460
Terms of UseThis article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Share Your StoryThe Harvard community has made this article openly available.Please share how this access benefits you. Submit a story .
Accessibility
1
Title Page
Scholarly Report submitted in partial fulfillment of the MD Degree at Harvard Medical School
Date: 28 February 2018
Student Name: Esther H. Chung
Scholarly Report Title: Deficits of Language and Speech in Idiopathic Normal Pressure
Hydrocephalus
Mentor Name(s) and Affiliations: Mary-Ellen Meadows, PhD, Dept. of Neurology, Brigham
and Women’s Hospital
Collaborators, with Affiliations: Mark D. Johnson, MD, PhD, Dept. of Neurosurgery, UMass
Memorial Hospital
2
Abstract
Title: Deficits of Language and Speech in Idiopathic Normal Pressure Hydrocephalus
Esther H. Chung, BA, Thu-Trang Hickman, MPH, Mary-Ellen Meadows, PhD and Mark D.
Johnson, MD, PhD
Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is a disorder of unknown etiology
characterized by gait instability, incontinence and dementia. Symptoms can be ameliorated by
shunt placement for cerebrospinal fluid drainage. Although language and speech impairments
have not traditionally been associated with iNPH, anecdotal reports commonly indicate
otherwise. This study’s objective was to determine the prevalence and nature of language and
speech difficulties in iNPH, and whether these deficits improve after shunt placement.
Methods: We analyzed the medical records of 529 patients who underwent shunt placement for
iNPH at our institution between July 2001 and March 2015 for deficits in language or speech at
initial presentation. A subset of 71 patients underwent formal pre-operative neurocognitive
assessments, and thirteen of these patients also underwent post-operative testing at least 6
months after shunt insertion. Improvement was assessed using the Reliable Change Index.
Results: In the retrospective study of 529 patients, language deficits were identified in 23.1%,
speech deficits in 12.9% and writing deficits in 4% of patients. Analysis of 71 prospectively
collected pre-operative neurocognitive evaluations revealed semantic verbal fluency and fine
motor impairments in more than two-thirds of patients. Of the 13 patients who underwent both
pre- and post-operative testing, 84.6% experienced significant improvements in language and
executive function.
Conclusions: We demonstrate that 70.4% and 67.6% of patients with shunt-responsive iNPH
originally present with language and fine motor difficulties respectively. Improvement in these
symptoms after shunting indicates that deficits in language are an integral component of iNPH
pathology and should be considered during the diagnosis and management of this disorder.
3
Table of Contents
Glossary of Abbreviations 4
Section 1: Introduction 5
Section 2: Student role 6
Section 3: Methods 6
Section 4: Results 9
Section 5: Discussion 12
Section 6: Acknowledgements 15
References 16
Figures 19
4
Glossary of Abbreviations
iNPH idiopathic normal pressure hydrocephalus
CSF cerebrospinal fluid
TT tap test
AD Alzheimer’s disease
WTAR Wechsler Test of Adult Reading
MMSE mini-mental state examination
WAIS-III Wechsler Adult Intelligence Scale-III
HVLT-R Hopkins Verbal Learning Test-Revised
PHQ-9 Patient Health Questionnaire-9
IQ Intelligence Quotient
5
Section 1: Introduction
Idiopathic Normal Pressure Hydrocephalus (iNPH) is a neurological disorder of unknown
etiology that is characterized by gait instability, incontinence and dementia.(1,2) Imaging
findings include enlarged cerebral ventricles, deep white matter or periventricular white matter
abnormalities and alterations in the size of the subarachnoid spaces.(3) It has been estimated
that about 1.4% of patients over the age of 65 and up to 14% of patients in nursing homes have
iNPH, most of whom are undiagnosed.(4–6) Given that the triad of symptoms in iNPH can be
ameliorated by shunt placement for cerebrospinal fluid (CSF) drainage, this disorder has been
classified as one of the reversible dementias with improvements seen in up to 80% of patients
after CSF drainage.(7–10)
Although most patients undergo lumbar CSF drainage trials to predict outcomes after
shunt placement, the prediction of shunt success has been inconsistent.(11) Evidence-based
literature reviews have established that several diagnostic tests used to identify the syndrome,
including a positive CSF tap test (TT), are insufficient for the accurate diagnosis of iNPH.(12,13)
The low sensitivity and negative predictive value of tests used to identify “shunt-responders”
calls for continued investigation of predictors of disease and shunt response. The Adult
Hydrocephalus Database offers one of the largest cohorts of iNPH patients published to date,
from which we can better assess the clinical picture of this enigmatic syndrome.
The causes of iNPH are not known, but clinical studies of iNPH patients and analyses of
CSF biomarker profiles are beginning to guide etiological hypotheses and clinical management.
To identify patients with iNPH and to better assess candidacy for shunt placement, in-depth
neurocognitive testing serves as an important adjunct to the assessment of gait impairment. The
literature has primarily associated acquired language disorders with the “cortical dementia” seen
in neurodegenerative diseases such as Alzheimer’s Disease (AD) and frontotemporal
dementia.(14–16) Cortical deficits can encompass language, visuospatial abilities and executive
function, depending on the presentation. On the other hand, the dementia of iNPH has been
traditionally characterized as “subcortical,” consistent with changes in general cognitive
processes (i.e. decreased processing speed, attention deficits, severe motor abnormalities),
which can then impact memory and overall cognitive function.(16)
A recent study in a relatively small sample of 32 iNPH and 32 AD patients noted that
deficits in executive function and visuospatial abilities were more profound in iNPH than in AD,
while deficits in language were only noted in the latter.(15) This lends overall support to the
notion that iNPH may actually present with a more mixed cortical and subcortical cognitive
6
profile; yet the study still leaves language out of the profile. On the other hand, numerous
anecdotal reports from healthcare providers, patients and their families suggest that the
presence of difficulties with language and speech should not exclude iNPH from the differential
diagnoses. To date, the prevalence and character of language difficulties in iNPH are not well
understood. Very little is known about the progressive impairment in word-finding and other
aspects of expressive and receptive language in patients with dementia and/or
ventriculomegaly.(14) If these specific deficits can be rapidly reversed after shunt placement,
this would not only suggest that iNPH involves more widespread cortical and subcortical
dysfunction, but it would also be useful in more accurately identifying candidates for a trial of
CSF drainage.
Section 2: Student Role
I completed the entire project, with help and advice on the statistical analysis and
interpretation of the results from Dr. Johnson, Dr. Meadows and Ms. Hickman.
Section 3: Methods
Retrospective Study Design and Data Collection
This study was conducted under the auspices of a human subjects research protocol
approved by the Partners IRB Committee. We retrospectively reviewed the medical records of
patients diagnosed with disorders of CSF flow at Brigham and Women’s Hospital between July
2001 and May 2015 to identify patients who underwent evaluation for iNPH. Patients were
selected for evaluation of possible iNPH if they had communicating hydrocephalus on cranial
images, gait disturbance, urinary urgency/incontinence, cognitive impairment, and no clearly
identifiable cause of their symptoms. At the time of the first clinic visit, clinical and demographic
data were collected using a patient questionnaire. We combined this prospectively collected
data with additional notes documented by all care providers in the electronic medical record.
After an evaluation that included a thorough medical history, neurological examination, CT/MR
imaging, and lumbar CSF drainage trials, 529 patients (267 men and 262 women) were
identified to have probable iNPH and subsequently underwent ventriculoperitoneal shunt
placement. The median and mean duration of symptoms prior to evaluation for iNPH were 24
7
months and 29.6 ± 20.9 months (mean ± SD), respectively. About two-thirds of patients
presented with the classic triad of gait difficulty, urinary incontinence, and cognitive impairment.
Patients were then coded into three stratified categories: language, motor-related
speech or motor-related writing deficits. Language difficulties were further divided into
subcategories of receptive language, expressive language, and other (i.e. difficulties reading,
non-motor writing, and/or other combinations). Receptive language deficits were defined as
difficulty understanding simple or complex statements or commands during the patient’s
neurological examination. Expressive language deficits were defined as difficulty translating
thoughts into sensible words and sentences expressed in grammatically correct syntax.
Expressive language was further subdivided into difficulties with word-finding or overall verbal
fluency. To be explicit in defining our stratifications, speech difficulties were strictly defined as
motor-related speech disorders arising from deficits in the motoric mechanics of oral
communication. As opposed to expressive language, which refers to the ability to communicate
information, speech deficits were defined by dysfunction in neuromuscular activity. This latter
category was further subdivided into dysarthria (slurred speech), stuttering, overall slowness of
speech, and combined and/or uncharacterized presentations. The categorizations of this
retrospective study are represented in Figure 1.
Prospective Study Design and Data Collection
Formal pre-operative neurocognitive evaluations of patients awaiting shunt placement
(n=71) were conducted by a clinical neuropsychologist. The pre-surgical battery for iNPH
included the following cognitive tests: Wechsler Test of Adult Reading (WTAR) for premorbid
estimate of IQ,(17) the mini-mental state examination (MMSE) as a basic cognitive screen of
attention (WORLD reversal, Serial 7 Subtraction tests),(18) Digit Span subtest from the
Wechsler Adult Intelligence Scale-III (WAIS-III), Phonemic (FAS) and semantic (Animals) for
verbal fluency,(19) Trails Making Test A for processing speed and Test B for executive
function,(20) Grooved Pegboard Test for fine motor skills,(21) Hopkins Verbal Learning Test-
Revised (HVLT-R) for verbal learning and verbal memory,(22) clock drawing for visuospatial
function, and Patient Health Questionnaire-9 (PHQ-9) for emotional function. Specifically
regarding the verbal fluency assessments, the FAS test evaluates phonemic fluency, whereas
the Animals test evaluates semantic fluency. Each category of verbal fluency has distinct neural
correlates with a relative importance of the left inferior temporal cortex in semantic versus
phonemic, and of the pre-supplementary motor area and head of caudate bilaterally in
phonemic versus semantic.(23) Additionally, the Grooved Pegboard test for upper extremity
8
dexterity was used to assess fine motor skills that may reflect deficits in writing ability and
speech.(24,25)
Each evaluation takes approximately 2 hours to complete. Post-operative neurocognitive
evaluations (n=13) using the same battery with alternate forms for memory and phonemic and
semantic fluency were completed during patient follow-up at least 6-18 months after shunt
placement.
The Z scores for each subtest score for every patient were calculated and assessed
using normative data from published reports or test manuals, taking into account age, gender
and education. Impairment was defined as a Z score > -1.5 standard deviations (SD) below the
mean.(26,27) Subsequently, improvement after shunt placement was assessed using the
Reliable Change Index for each neurocognitive variable.(28) This measures whether the change
(increased or decreased) in the individual’s score is statistically significant (P<0.05).
Additionally, we identified a significant change in scores by defining “improvement” as an
absolute change greater than 1 SD.(29)
Ventriculoperitoneal Shunt Surgery
Patients for whom a trial of CSF drainage supported a diagnosis of probable iNPH
underwent surgical implantation of a ventriculoperitoneal shunt as treatment for their symptoms.
The shunts generally contained programmable valves (Codman, Inc.) programmed initially to a
setting of 120 mm of water. Valve settings were adjusted post-operatively as needed to
maximize symptom improvement and minimize signs or symptoms of overdrainage such as
positional headaches or subdural hematomas.
Statistical Analysis
The SAS statistical software program (SAS Inc, NC, version 9.3) and Microsoft Excel
2011(Microsoft Office, version 14.0.0) was used for all database analyses. The Reliable Change
Index for each neurocognitive test score was calculated using pre-programmed score change
calculators on Microsoft Excel spreadsheets. Statistical significance was set at the P<0.05 level.
All statistical analyses were performed by T.H., E.C., and M.M.
Outcomes Assessment
Patients were evaluated by a group of board certified neurosurgeons and/or neurologists
before and after CSF drainage trials and shunt placement. Patients who showed signs of
improvement in gait, incontinence or cognition after a trial of CSF drainage were offered
9
ventriculoperitoneal shunt placement. Patients were evaluated post-operatively at 2 weeks and
at 6 weeks, and were then followed with periodic monthly or annual clinic visits as needed for a
period of up to 11 years. Changes in gait were based upon assessments of Timed Up and Go
test times, gait speed, step height, cadence, balance, the need for gait assistive devices and the
number of falls.(30) Changes in urinary/fecal incontinence or urgency were assessed in
collaboration with nursing staff, caregivers and patients. Changes in cognitive function were
assessed using neurological examinations, formal neurocognitive evaluations, statements by
caregivers and patient self-reports. These criteria were collectively used to categorize the
overall degree of improvement as improved or not improved.
For the retrospective cohort of 529 patients, the mean duration of follow up after shunt
placement was 32.3 ± 30.8 months, with a range of 1 to 132 months. The median duration of
follow up was 22 months. Based on the aforementioned criteria, the overall rate of positive
shunt-response was found to be 79%. Approximately 78% of patients who presented with the
classic iNPH triad improved after shunt placement.
Section 4: Results
Retrospective study on language, speech, and writing deficits in iNPH
Prevalence and characterization of deficits in iNPH
Of the 529 patients who underwent shunt placement for iNPH at the Brigham and
Women’s Hospital between July 2001 and March 2015, 23.1% presented with language
difficulties, 12.9% presented with motor-related speech difficulties, and 4% presented with
motor-related writing deficits (Figure 2A).
Of those patients who presented with deficits in language (Figure 2B), 75.4% specifically
demonstrated deficits in expressive language, while 10.7% exhibited difficulties in receptive
language. An additional 10.7% presented with difficulties in both expressive and receptive
language, while 3.3% displayed difficulties with reading and writing complete, grammatically
correct sentences. Among the subset of patients who presented with expressive language
deficits, word-finding difficulties were notably prevalent at 43.9%. Word-finding difficulty was
commonly self-reported by patients and their families during history taking, as well as noted by
healthcare providers during their respective examinations. Deficits in overall verbal fluency were
also prevalent, affecting 29.0% of the subgroup of patients with expressive language difficulties.
10
Here, verbal fluency was defined as difficulty in accessing proper grammar structure, sound
forms and/or vocabulary in order to communicate with ease.
Among patients who presented with deficits in motor-related speech (Figure 2C), the
most common difficulties included dysarthria (25.0%), overall slowness of speech (27.9%), and
stuttering/shakiness (10.3%).
Prospective study of neurocognitive dysfunctions in iNPH
Quantitative characterization of neurocognitive dysfunctions in iNPH
Prior to shunt placement for iNPH, 71 patients underwent formal pre-operative
neurocognitive evaluations. The pre-surgical battery for iNPH included a variety of cognitive
tests as detailed above in the Methods section.
We defined impairment as a Z score > -1.5 SD below the mean, standardized for patient
age, sex, and level of education. Data analysis revealed that at least half of the iNPH patient
population demonstrated impairments across the selected neurocognitive evaluations (Figure
3). Baseline testing of premorbid intelligence (IQ) of this patient pool was tested using the
WTAR, which assess abilities usually unaffected by cognitive decline associated with
neurological damage. Nearly three-quarters of patients tested above average on this measure
(Z score > 0). In contrast, patient scores were skewed toward below average in the MMSE and
Trails A test, which account for overall cognitive deficits and attention/processing speed,
respectively. Additionally, the distributions of Z scores on the FAS and Animals verbal fluency
tests, and on the Grooved Pegboard fine motor skill test, were spread predominantly below the
quantitative level of impairment. Approximately two-thirds of patients scored below average on
the MMSE and Trails A tests, which primarily test subcortical functions, while more than 75%
ranged below average on the Animals, Trails B and Grooved Pegboard tests, which primarily
assess cortical functions. Prospectively collected formal pre-operative neurocognitive
evaluations indicate that cortical dementia (i.e. declines in language ability, fine motor skills and
executive function) is indeed characteristic of the neurocognitive profile of patients with iNPH.
Prevalence of neurocognitive dysfunctions in iNPH
Analysis of the 71 prospectively performed pre-operative neurocognitive evaluations
revealed the presence of a variety of language deficits (Figure 4). Assessment of cortical
functions indicated that semantic verbal fluency was impaired in 67.6% of iNPH patients, and
phonemic verbal fluency was impaired in 53.5% of these patients. When upper extremity
11
dexterity associated with writing and left cortex-controlled motor speech functions were
examined, fine motor coordination on the Grooved Pegboard test was found to be impaired in
67.6% of patients. Executive function, as determined by set switching in the Trails B test, was
impaired in 69.0% of patients. Looking next at “subcortical” functions, 42.2% of patients
demonstrated impaired cognitive processing speed, as measured by the Trails A test, and
35.2% of patients had impaired attention in the context of overall cognitive status as assessed in
the MMSE. Overall, cortical dysfunction, specifically in semantic verbal fluency, executive
function and fine motor skills, was more prevalent among the iNPH population than subcortical
dysfunction.
Focused analysis of pre- and post-operative cognitive evaluations
Analysis of 13 iNPH patients who received neurocognitive evaluations before and after
shunt placement revealed that 12 out of 13 experienced overall improvements in gait, urinary
incontinence and/or cognition. To identify post-operative changes in cognitive function,
significant improvement or decline (P<0.05) after shunt placement was assessed using the
Reliable Change Index for each neurocognitive subtest.
On the FAS and Animals test, 31.0% demonstrated significant improvement in semantic
or phonemic verbal fluency, while 7.7% declined. On the Trails A test, 23.1% demonstrated
significant improvement in processing speed, while 15.0% declined. Notably, in the Trails B set
switching test, 38.5% improved in executive function, while 23.1% declined. On the Grooved
Pegboard test of the dominant hand, 30.8% demonstrated significant improvement in fine motor
dexterity, while 7.7% declined. In HVLT-R Total Recall, 23.1% of patients showed significant
improvement in verbal learning, while 7.7% declined. In HVLT-R Delayed Recall, 38.5% of
patients demonstrated significant improvement in verbal retrieval and verbal memory, while
7.7% declined.
Considering significant improvements in language and executive function together,
84.6% of these patients (11 out of 13) improved in overall cortical function, with significant
improvements seen in language and executive function. Of these patients whose cortical
dementia improved (n=11), nearly two-thirds (63.6%) improved specifically in language-related
functions, including verbal fluency, verbal learning, and/or verbal memory. Looking at language-
related functions in isolation, 53.8% (7 out of 13) of patients improved. There was also
improvement seen in subcortical functioning, as assessed by increased processing speed in
23.1% (3 out of 13) of patients. Fine motor coordination skills were improved as well in 30.8% of
patients (4 out of 13). Two patients, one of whom did not show overall improvement in
12
symptoms post-operatively, were reported to be co-morbid for Alzheimer’s disease. However,
both patients’ gait and subsequent quality of life were documented to have improved over time.
Section 5: Discussion
In this study, we present data both from a retrospective medical record review of 529
iNPH patients as well as prospectively performed pre-operative neurocognitive evaluations of 71
iNPH patients that reveal the prevalence and nature of speech and language difficulties in iNPH.
Whereas the retrospective analysis suggested a prevalence of 23.1% (122 out of 529), the more
rigorous prospective analysis using formal neurocognitive battery measures revealed a
prevalence of language-related deficits of 70.4% (50 out of 71) among patients with shunt-
responsive iNPH. Our study is the first to demonstrate language difficulties in a majority of
shunt-responsive iNPH patients. Analysis of the 71 neurocognitive evaluations completed prior
to shunt placement revealed impairments specifically in verbal fluency, supporting our findings
from a retrospective analysis of a larger iNPH cohort (n=529) that language and speech deficits
occur commonly in this disorder. We also prospectively identified fine motor deficits in
approximately 71.0% of patients with iNPH, indicating that such deficits are not limited to lower
extremity function.
Contrary to the current dogma, we find that the presence of language or speech
difficulties is not a negative predictor of iNPH. A comparison of data from our retrospective and
prospective studies suggests that the estimate of 23.1% of iNPH patients who reported
“language difficulty” in the retrospective study is an underestimate of the true prevalence of
deficits in language in iNPH. Difficulties with speech and writing may also be more prevalent
than were noted in hospital records. Formal assessment of impairments in speech and
language are needed to more consistently identify deficits in these areas in patients with
possible iNPH. While the symptoms of gait disturbance and urinary incontinence are easier to
identify and are more commonly reported by patients and caregivers, the third symptom of
“subcortical dementia” is neither well-defined nor comprehensive. Along with accurate gait
analyses, patients with potential iNPH would benefit from careful neurological assessments of
cognition and language both before and after shunt placement surgery.
Current research recommends supplemental tests, including prolonged CSF drainage, to
increase diagnostic accuracy in iNPH.(13) However, tailored neuropsychological assessments
may also help to differentiate iNPH from other diseases that can mimic this disorder. For
example, our study demonstrates that patients with iNPH do not display the baseline decline in
13
premorbid IQ or intellectual function seen in patients with progressing AD.(31) In support of the
notion that iNPH is primarily characterized by a decline in subcortical functions of the brain, past
studies have focused on significant differences between iNPH patients and age-, sex- and
MMSE-matched probable AD patients in terms of their performance on various tests of attention
and psychomotor speed.(15,16,31) In contrast, our study has revealed that patients with iNPH
demonstrate significant cortical impairment, including deficits in language, fine motor skills, and
executive function. These findings indicate that patients with iNPH may present with more of a
“mixed dementia” characterized by declining subcortical and cortical function.
Until now, there has been no general agreement concerning which cognitive functions
are more likely to be restored after shunt placement.(10) In this study, pre- and post-operative
neurocognitive evaluations revealed that 84.6% of iNPH patients (11 out of 13) experienced
improvement in one or more areas of cortical function after shunt surgery, with two-thirds
demonstrating significant improvement in language functions. Overall, more than half of patients
scored significantly higher on tests of language-related functions after shunt placement.
Improvement was also seen in subcortical functions and fine motor skills. These post-shunt
improvements not only affirm the profile of a mixed cortical and subcortical dementia in this
disease, but they also reveal the existence of pathophysiological mechanisms underlying
language processing and production that can be reversed by CSF drainage in iNPH patients.
Pathologic changes in iNPH are widespread and include cortical thinning of white matter in most
areas of the brain, including inferior and posterior regions.(15,32,33) Previous studies on
cognitive dysfunction in iNPH have delved focally into frontal lobe functions of attention,
executive function and memory,(34–36) but our findings indicate that a more comprehensive
characterization of iNPH dementia is warranted.
There are several strengths and limitations of the current study. The large number of
iNPH patients included in this study (n = 529) allowed us to unambiguously document the
presence of speech and language dysfunctions in iNPH, as well as other deficits (e.g. writing
deficits) that occur less commonly in this disorder. As always, studies involving the retrospective
review of medical records raises concerns of potential selection bias or recall bias that could
lead to inaccurate estimates of incidence or prevalence. Indeed, our analysis of prospectively
collected data from formal neurocognitive evaluations in a subset of 71 patients who were later
proven to have shunt-responsive iNPH revealed a much higher prevalence language deficits
among iNPH patients than was observed in the retrospective analysis. This analysis thus serves
as a valuable addition to the larger retrospective analysis.
14
We obtained pre-operative and post-operative neurocognitive evaluations in a small
group (n = 13) of iNPH patients. Our analysis demonstrated clear improvements in language
and speech functions in a majority of affected iNPH patients. These data provide a rational
basis for a similar study involving a larger group of iNPH patients to replicate these findings.
Given the high prevalence of deficits in language and speech in patients with iNPH, our
findings endorse the integration of a standardized iNPH neurocognitive assessment battery into
the clinical diagnosis and management of iNPH. Limiting factors include both the lengthy
duration and inherently strenuous nature of multiple neurocognitive tests for iNPH patients,
given their advanced age and the impairments associated with this disorder. However, future
streamlining of the neurocognitive battery and strategic scheduling of post-operative
appointments with both neurosurgery and neurology will facilitate the accrual of additional post-
shunt placement data and allow us to more clearly define the cognitive deficits in iNPH.
15
Section 6: Acknowledgments
This work was supported by a generous gift from Susan and Frederick B. Sontag.
16
References
1. Graff-Radford NR. Normal Pressure Hydrocephalus. Vol. 25, Neurologic Clinics. 2007. p.
809–32.
2. Miller BH. Symptomatic occult hydrocephalus with “normal cerebrospinal fluid pressure”.
Va Med Mon (1918). 1970;97(11):693–5.
3. Virhammar J, Laurell K, Cesarini KG, Larsson E-M. Preoperative Prognostic Value of MRI
Findings in 108 Patients with Idiopathic Normal Pressure Hydrocephalus. AJNR Am J
Neuroradiol. 2014;58:1–8.
4. Tanaka N, Yamaguchi S, Ishikawa H, Ishii H, Meguro K. Prevalence of possible idiopathic
normal-pressure hydrocephalus in Japan: The Osaki-Tajiri project. Neuroepidemiology.
2009;32(3):171–5.
5. Iseki C, Takahashi Y, Wada M, Kawanami T, Adachi M, Kato T. Incidence of idiopathic
normal pressure hydrocephalus (iNPH): A 10-year follow-up study of a rural community in
Japan. J Neurol Sci. 2014;339(1-2):108–12.
6. Marmarou A, Young HF, Aygok G a. Estimated incidence of normal pressure
hydrocephalus and shunt outcome in patients residing in assisted-living and extended-
care facilities. Neurosurg Focus. 2007;22(4):E1.
7. Kazui H, Miyajima M, Mori E, Ishikawa M, Hirai O, Kuwana N, et al. Lumboperitoneal
shunt surgery for idiopathic normal pressure hydrocephalus (SINPHONI-2): An open-
label randomised trial. Lancet Neurol. 2015;14(6):585–94.
8. Golz L, Ruppert F-H, Meier U, Lemcke J. Outcome of modern shunt therapy in patients
with idiopathic normal pressure hydrocephalus 6 years postoperatively. J Neurosurg.
2014;121(4):771–5.
9. Koivisto AM, Alafuzoff I, Savolainen S, Sutela A, Rummukainen J, Kurki M, et al. Poor
cognitive outcome in shunt-responsive idiopathic normal pressure hydrocephalus.
Neurosurgery. 2013;72(1):1–8.
10. Picascia M, Zangaglia R, Bernini S, Minafra B, Sinforiani E, Pacchetti C. A review of
cognitive impairment and differential diagnosis in idiopathic normal pressure
hydrocephalus. Funct Neurol. CIC Edizioni Internationali; 2015 Jan;30(4):217–28.
11. McGirt MJ, Woodworth G, Coon AL, Thomas G, Williams MA, Rigamonti D, et al.
Diagnosis, Treatment, and Analysis of Long-term Outcomes in Idiopathic Normal-
Pressure Hydrocephalus. Neurosurgery. 2005;57(4):699–705.
12. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic
17
normal-pressure hydrocephalus. Vol. 57, Neurosurgery. 2005. p. S4–16; discussion ii – v.
13. Marmarou A, Bergsneider M, Klinge P, Relkin N, Black PML. INPH guidelines, part III:
The value of supplemental prognostic tests for the preoperative assessment of idiopathic
normal-pressure hydrocephalus. Vol. 57, Neurosurgery. 2005.
14. Malm J, Graff-Radford NR, Ishikawa M, Kristensen B, Leinonen V, Mori E, et al. Influence
of comorbidities in idiopathic normal pressure hydrocephalus - research and clinical care.
A report of the ISHCSF task force on comorbidities in INPH. Fluids Barriers CNS.
2013;10(1):22.
15. Saito M, Nishio Y, Kanno S, Uchiyama M, Hayashi A, Takagi M, et al. Cognitive profile of
idiopathic normal pressure hydrocephalus. Dement Geriatr Cogn Dis Extra.
2011;1(1):202–11.
16. Whitehouse PJ, Lerner A, Hedera P, Heilman KM, Valenstein E. Dementia. Clinical
neuropsychology (3rd ed.). 1993. 603-645 p.
17. Green RE a, Melo B, Christensen B, Ngo L-A, Monette G, Bradbury C. Measuring
premorbid IQ in traumatic brain injury: an examination of the validity of the Wechsler Test
of Adult Reading (WTAR). J Clin Exp Neuropsychol. 2008;30(2):163–72.
18. Wallace M, Kurlowicz L. The Mini Mental State Examination (MMSE). try this Best Pract
Nurs Care to Older Adults from Hartford Inst Geriatr Nurs. 1999;(3).
19. Tombaugh TN, Kozak J, Rees L. Normative data stratified by age and education for two
measures of verbal fluency: FAS and animal naming. Arch Clin Neuropsychol.
1999;14(2):167–77.
20. Tombaugh TN. Trail Making Test A and B: Normative data stratified by age and
education. Arch Clin Neuropsychol. 2004;19(2):203–14.
21. Ruff RM, Parker SB. Gender- and age-specific changes in motor speed and eye-hand
coordination in adults: normative values for the Finger Tapping and Grooved Pegboard
Tests. Percept Mot Skills. 1993;76(3 Pt 2):1219–30.
22. Benedict RHB, Schretlen D, Groninger L, Brandt J. Hopkins Verbal Learning Test –
Revised: Normative Data and Analysis of Inter-Form and Test-Retest Reliability. Clin
Neuropsychol. 1998;12(1):43–55.
23. Grogan A, Green DW, Ali N, Crinion JT, Price CJ. Structural correlates of semantic and
phonemic fluency ability in first and second languages. Cereb Cortex. 2009;19(11):2690–
8.
24. Kornse DD, Manni JL, Rubenstein H, Graziani LJ. Developmental apraxia of speech and
manual dexterity. J Commun Disord. 1981;14(4):321–30.
18
25. Puente AE, McCaffrey RJ. Handbook of neuropsychological assessment: A
biopsychosocial perspective. Neuropsychologia. 1994.
26. Jak AJ, Bondi MW, Delano-Wood L, Wierenga C, Corey-Bloom J, Salmon DP, et al.
Quantification of five neuropsychological approaches to defining mild cognitive
impairment. Am J Geriatr Psychiatry. 2009;17(5):368–75.
27. Tuokko HA, McDowell I. An overview of mild cognitive impairment. Mild cognitive
impairment: International perspectives. 2006. p. 3–28.
28. Jacobson NS, Truax P. Clinical significance: A statistical approach to defining meaningful
change in psychotherapy research. J Consult Clin Psychol. 1991;59(1):12–9.
29. Thomas G, McGirt MJ, Woodworth GF, Heidler J, Rigamonti D, Hillis AE, et al. Baseline
neuropsychological profile and cognitive response to cerebrospinal fluid shunting for
idiopathic normal pressure hydrocephalus. Dement Geriatr Cogn Disord. 2005;20(2-
3):163–8.
30. Beauchet O, Fantino B, Allali G, Muir SW, Montero-Odasso M, Annweiler C. Timed up
and go test and risk of falls in older adults : a systematic review. J Nutr Heal Aging.
2011;15(10):6–11.
31. McFarlane J, Welch J, Rodgers J. Severity of Alzheimer’s disease and effect on
premorbid measures of intelligence. Br J Clin Psychol. 2006;45(Pt 4):453–63.
32. Kang K, Ko PW, Jin M, Suk K, Lee HW. Idiopathic normal-pressure hydrocephalus,
cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test. J Clin Neurosci.
2014;21(8):1398–403.
33. Sasaki H, Ishii K, Kono AK, Miyamoto N, Fukuda T, Shimada K, et al. Cerebral perfusion
pattern of idiopathic normal pressure hydrocephalus studied by SPECT and statistical
brain mapping. Ann Nucl Med. 2007;21(1):39–45.
34. Iddon JL, Pickard JD, Cross JJ, Griffiths PD, Czosnyka M, Sahakian BJ. Specific patterns
of cognitive impairment in patients with idiopathic normal pressure hydrocephalus and
Alzheimer’s disease: a pilot study. J Neurol Neurosurg Psychiatry. 1999;723–32.
35. Ogino A, Kazui H, Miyoshi N, Hashimoto M, Ohkawa S, Tokunaga H, et al. Cognitive
impairment in patients with idiopathic normal pressure hydrocephalus. Dement Geriatr
Cogn Disord. 2006;21(2):113–9.
36. Walchenbach R, Geiger E, Thomeer RTWM, Vanneste J a L. The value of temporary
external lumbar CSF drainage in predicting the outcome of shunting on normal pressure
hydrocephalus. J Neurol Neurosurg Psychiatry. 2002;72(4):503–6.
19
Figures
Figure 1. Retrospective study design. Flow diagram depicting the stratification of deficits in language, speech and writing among iNPH patients.
20
Figure 2. Retrospective analysis of the prevalence and characterization of language and speech deficits in iNPH (n=529). A) Prevalence of language difficulties, motor-related speech difficulties and motor-related writing difficulties prior to shunt placement. B) Stratification of the 122 patients with language deficits into those demonstrating deficits in expressive versus receptive language, those who display both, and those with more complex manifestations of language function. Expressive language difficulties include symptoms of word-finding difficulty and verbal fluency in conversation. Receptive language difficulties include inability to comprehend simple and multistep statements or commands during hospital visits. C) Categorization of the 68 patients with motor-related speech deficits into those with dysarthria, overall slowness, stuttering and combinations/other.
21
Figure 3. Boxplots depicting the distribution of pre-operative neurocognitive battery Z scores of shunt-responsive iNPH patients (n=71). Raw data were obtained from prospective formal neurocognitive evaluations of 71 possible iNPH patients prior to lumbar CSF drainage trials and shunt placement for iNPH. Impairment on the various neuropsychiatric assessment tools was defined as a Z score greater than 1.5 SD below the mean (standardized for age, sex, and education level). Descriptions of the tests included in the iNPH battery can be found in the Methods section. A majority of patients demonstrated above average premorbid IQ, but nearly three-quarters of patients attained scores below average or at the level of impairment across a number of neurocognitive tests.
22
Figure 4. Analysis of prospectively collected data on the prevalence of language and speech dysfunction in 71 iNPH patients. Impairments in cortical functions (including language, fine motor, executive function) and subcortical functions (including processing speed and attention) were assessed using formal neurocognitive evaluations completed prior to shunt placement. Deficits in semantic verbal fluency and executive function, as well as fine motor skills, are prevalent among the iNPH population.
iNPH
pat
ient
s(n
=71)
0% 10% 20% 30% 40% 50% 60% 70% 80%
0.35
0.42
0.69
0.68
0.54
0.68
Impaired verbal fluency - semanticImpaired verbal fluency - phonemicImpaired fine motor coordinationImpaired executive function - set switchingImpaired cognitive processing speedImpaired attention / concentration
23
Figure 5. Focused analysis of pre- and post-operative cognitive evaluations reveal improved outcomes in various cognitive functions. Thirteen iNPH patients received neurocognitive evaluations before and after shunt placement. Significant improvement or decline (P<0.05) post-surgery was assessed using the Reliable Change Index for each neurocognitive subtest.