To the Editor: Idiopathic normal pressure hydrocephalus (iNPH) patients present disturbances in gait, cognition, and/or control of urination with neuroimaging characterized by enlargement of the cerebral ventricles. Typically, gait disturbance in iNPH patients is the initial and most prominent symptom, but motor impairments can also extend to upper extremity.

The cerebrospinal fluid (CSF) tap test (TT), in which the symptoms of iNPH patients are assessed before and after drainage of 30–50 mL CSF by lumbar puncture, is a commonly used auxiliary test for predicting shunt responsiveness. Standard methods for determining the CSF TT response are based on the clinical impression of changes in gait after lumber puncture. iNPH patients who are unable to ambulate (e.g., the patient is wheelchair bound) may not be able to comply with the gait evaluation but still benefit from shunt placement. The grooved pegboard test (GPT) and symbol-digit modalities test (SDMT) are psychometric measures of upper extremity motor and psychomotor speed. Herein, we sought to identify whether these tests could be used to objectively assess responsiveness to the CSF TT.

We retrospectively reviewed patients with possible iNPH who were admitted to the Neurological or Neurosurgery Department of Peking Union Medical College Hospital for the CSF TT from March, 2013 to January, 2020. All patients were diagnosed according to the guidelines for the clinical diagnosis of iNPH published in 2005[1] and the Chinese consensus for iNPH.[2] The patients were recruited in the study according to the following criteria: (1) Patients completed the multi-time point assessment of walking and neuropsychological tests; and (2) Patients had undergone GPT and SDMT at least three times, including a baseline test. The exclusion criteria were as follows: (1) Patients who were unable to finish GPT and SDMT for any reason; and (2) Patients who could not tolerate 30 mL CSF drainage during the CSF TT. The Ethics Committee of the Peking Union Medical College Hospital approved this study (No. ZS-2505). All patients or their relatives signed written consent forms to participate. Age, sex, medical histories, and initial and full-blown symptoms were recorded. Patients also completed the mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), and activities of daily living (ADL) questionnaire. Patients underwent a brief neuropsychological battery assessment including the SDMT, Trail Making Test A, and the Stroop Color Word Task-C. The iNPH Grading Scale (iNPHGS) was used to rate the severity of each fundamental symptom of iNPH patients. All subjects underwent a CSF TT and head magnetic resonance imaging (MRI).

Before and after the CSF TT, cognitive function and walking ability were evaluated by means of the 5 m up and go test (TUG), the 10 m walking test, the GPT (Model 32025, Lafayette Instrument, Lafayette, Indiana, USA), and a brief executive function battery. A video of the patients’ walking test performance was recorded. GPT and SDMT results were transformed to Z-scores according to the norm. The complex visual motor speed index was calculated as the mean of the GPT Z-score and SDMT Z-score according to the literature.[3] Additional evaluations were conducted at 8 h, 24 h, and 72 h after CSF TT. The criteria for CSF TT responders were chosen according to our previous report.[4]

The continuous variables were described as mean ± standard deviation or median (Q1, Q3), as appropriate. The differences in the GPT, SDMT, and complex visual motor speed performance among the different time points were analyzed using a nonparametric paired sign rank sum test. The improvement ratio between the CSF TT responder and CSF TT non-responder groups were compared by the Mann–Whitney U test. The correlation between upper extremity motor function and diffusion tensor imaging (DTI) parameters was analyzed using Spearman’s correlation test. All statistical analyses were performed with SPSS 13.0 software (SPSS Inc., Chicago, IL, USA).

The patients were recruited for this study included 29 CSF TT responders and 36 CSF TT non-responders. Among the 65 patients, 18 cases underwent DTI test, which was a selected test for patients. The regions of interest (ROIs) of DTI were the bilateral anterior and posterior periventricular white matter. The detailed method is provided in Supplementary Material, https://links.lww.com/CM9/B841.

There were no statistically significant differences in age, sex, disease duration, iNPHGS scores, MMSE scores, MoCA scores, or 10 m walking time (all P >0.05), but there was a statistically significant difference in ADL questionnaire scores (t = 2.53, P = 0.02) [Supplementary Table 1, https://links.lww.com/CM9/B841] between the CSF TT responder and CSF TT non-responder groups. The GPT scores, SDMT performance, and complex visual motor index were statistically significantly improved at 24 h and 72 h after the CSF TT compared with those before the CSF TT (all P <0.01) [Supplementary Table 2, https://links.lww.com/CM9/B841]. We also correlated the improvement ratio of upper extremity test performance after CSF TT with the improvement ratio of the TUG scores, 10 m walking time, and steps on the same evaluation time. The results showed that the improvement ratio of the complex visual motor speed index at 72 h after the CSF TT was statistically significantly correlated with the improvement ratio of the TUG time (r = 0.32, P = 0.02) and borderline correlated with the 10 m walking step improvement ratio (r = 0.27, P = 0.05). Furthermore, we also found that there was a statistically significant difference in the maximum improvement ratio of the complex visual motor speed index (combined GPT with symbol-digit modalities) between the CSF TT responder and CSF TT non-responder groups (0.20 [0.15, 0.43] vs. 0.12 [0.02, 0.31], U = 256.5, P = 0.04). The maximum improvement ratios of the GPT scores were not significantly different between the two groups (0.24 [0.14, 0.32] vs. 0.19 [0.11, 0.36], U = 432.0, P = 0.24). The maximum improvement ratios of the SDMT scores were also not significantly different between the two groups (0.31 [0.16, 0.41] vs. 0.14 [0, 0.46], U = 292.5, P = 0.10) [Figure 1].

Figure 1:

Difference in the maximum improvement ratio of the upper limb-related tests between the CSF TT responder and CSF TT non-responder groups. *P <0.05. CSF: Cerebrospinal fluid; TT: Tap test.

Head MRI examinations included clinical routine neuroimaging and DTI that were obtained by using a 1.5 T MRI unit (Signa Excite, General Electric, Milwaukee, WI, USA). During analyzing the DTI of iNPH patients, we found that the GPT performance borderline correlated with the left periventricular anterior horn fractional anisotropy (FA) and mean diffusivity (MD) values (r = –0.42, P = 0.08; r = –0.48, P = 0.05). The GPT results statistically significantly correlated with the right periventricular anterior horn FA values (r = –0.57, P = 0.01). The SDMT results were statistically significantly correlated with bilateral periventricular anterior FA and MD values (all P <0.05) [Supplementary Table 3, https://links.lww.com/CM9/B841]. Similar patterns were found in the correlation analysis of periventricular white matter lesion DTI parameters with the 10 m walking time and the TUG time results (all P <0.05) [Supplementary Table 3, https://links.lww.com/CM9/B841].

The present findings demonstrate that upper extremity motor functions can improve following a TT, providing an additional clinical response measure. The GPT, SDMT, and complex visual motor index could measure the changes after the CSF TT. The maximum improvement ratio of the complex visual motor index was statistically significantly higher in CSF TT responders than in CSF TT non-responders [0.20 (0.15, 0.43) vs. 0.12 (0.02, 0.31), U = 256.5, P = 0.04]. Our data supported that upper extremity motor function was impacted in iNPH patients, although lower extremity motor function is the primary concern in iNPH patients. There have been several studies on upper extremity motor function testing, for instance, line tracing tasks, GPT and finger tapping test, after CSF drainage tests, and shunting operations in iNPH patients.[3,5,6] We also found that the complex visual motor speed index was more useful in demonstrating significant differences between the CSF TT responder and CSF TT non-responder groups. The complex visual motor speed index might be a promising candidate measure to identify CSF TT responders. The correlation between upper extremity motor function and gait in iNPH patients was supported by the association of GPT scores, SDMT scores, and the complex visual motor index performance improvement ratio with the walking test improvement ratio at the corresponding time point. Furthermore, this study found that the GPT and SDMT results correlated with the DTI parameters of anterior periventricular horn white matter lesions. As has been reported, the reduction in the irregular type of periventricular hyperintensity located around the frontal horns after surgery was associated with clinical improvements in iNPH patients.[7] We speculated that the improvement of the upper extremity motor function in iNPH patients after CSF TT drainage was related to the periventricular hyperintensity located around the frontal horns and might be reversible through shunting. All the relationships supported that upper extremity motor function could be a reliable and useful assessment tool for iNPH patients.

The strength of our study is the multiple time point assessments of upper extremity motor function. The study confirmed the enhancement of motor function following CSF TT, and was beneficial in determining the most suitable assessment time point and most effective measurements. Our study had several limitations. First, the sample size of patients undergoing surgery was small, and the predictive effect of upper extremity motor test performance on shunting outcome was not investigated. Second, only 18 patients underwent DTI analysis. Third, this was a pilot and retrospective study, and GPT and SDMT performance was analyzed among patients with iNPH who were able to walk and complete multiple time point evaluations after CSF TT. The application of the GPT in patients who are unable to ambulate needs to be explored in the future.

Funding

This study was supported by grants from the National Key Research and Development Program of China (No. 2020YFA0804500), the CAMS Innovation fund for Medical Sciences (No. 2016-12 M-1-004), and the National Natural Science Foundation of China (No. 81550021).

Conflicts of interest

None.

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