Timing of surgical treatment for idiopathic normal pressure hydrocephalus: association between treatment delay and reduced short-term benefit.

OBJECTIVE A growing body of evidence suggests that longer durations of preoperative symptoms may correlate with worse postoperative outcomes following cerebrospinal fluid (CSF) diversion for treatment of idiopathic normal pressure hydrocephalus (iNPH). The aim of this study is to determine whether the duration of preoperative symptoms alters postoperative outcomes in patients treated for iNPH. METHODS The authors conducted a retrospective review of 393 cases of iNPH involving patients treated with ventriculoperitoneal (VP) shunting. The duration of symptoms prior to the operative intervention was recorded. The following outcome variables were assessed at baseline, 6 months postoperatively, and at last follow-up: gait performance, urinary continence, and cognition. RESULTS The patients' median age at shunt placement was 74 years. Increased symptom duration was significantly associated with worse gait outcomes (relative risk (RR) 1.055 per year of symptoms, p = 0.037), and an overall absence of improvement in any of the classic triad symptomology (RR 1.053 per year of symptoms, p = 0.033) at 6 months postoperatively. Additionally, there were trends toward significance for symptom duration increasing the risk of having no 6-month postoperative improvement in urinary incontinence (RR 1.049 per year of symptoms, p = 0.069) or cognitive symptoms (RR 1.051 per year of symptoms, p = 0.069). However, no statistically significant differences were noted in these outcomes at last follow-up (median 31 months). Age stratification by decade revealed that prolonging symptom duration was significantly associated with lower Mini-Mental Status Examination scores in patients aged 60-70 years, and lack of cognitive improvement in patients aged 70-80 years. CONCLUSIONS Patients with iNPH with longer duration of preoperative symptoms may not receive the same short-term benefits of surgical intervention as patients with shorter duration of preoperative symptoms. However, with longer follow-up, the patients generally reached the same end point. Therefore, when managing patients with iNPH, it may take longer to see the benefits of CSF shunting when patients present with a longer duration of preoperative symptoms.

The mutational landscape of spinal chordomas and their sensitive detection using circulating tumor DNA.

BACKGROUND: Chordomas are the most common primary spinal column malignancy in the United States. The aim of this study was to determine whether chordomas may be detected by evaluating mutations in circulating tumor DNA (ctDNA). METHODS: Thirty-two patients with a biopsy-confirmed diagnosis of chordoma had blood drawn pre-operatively and/or at follow-up appointments. Mutations in the primary tumor were identified by whole exome sequencing and liquid biopsy by ddPCR and/or RACE-Seq was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. RESULTS: At the time of initial blood draw, 87.1% of patients were ctDNA positive (P <.001). Follow-up blood draws in twenty of the patients suggest that ctDNA levels may reflect the clinical status of the disease. Patients with positive ctDNA levels were more likely to have greater mutant allele frequencies in their primary tumors (P = .004) and undergo radiotherapy (P = .02), and the presence of ctDNA may correlate with response to systemic chemotherapy and/or disease recurrence. CONCLUSIONS: Detection of ctDNA mutations may allow for the detection and monitoring of disease progression for chordomas.

Health Care Expenditures of Medicare Beneficiaries with Normal Pressure Hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is an underdiagnosed and undertreated condition affecting the elderly population and with costs associated with its surgical management reported to be less than those associated with conservative management. OBJECTIVE: To determine if the rate of diagnosis of NPH has improved over the last decade, the rate of treatment has increased, and if surgical treatment costs and socioeconomic factors related to receipt of treatment have changed over time compared with conservative therapy. METHODS: A retrospective study based on data from a nationally representative random sample of 2,378,637 Medicare beneficiaries (2006-2010) was performed. Shunt surgery, shunt revision, replacement, and removal were analyzed as independent variables. RESULTS: A total of 2321 patients with NPH were included, with 580 (24.99%) receiving a first shunt procedure. The adjusted effect of the procedure is that total 5-year expenditures are $11,676 more per patient (P < 0.001) than expenditures associated with nonsurgical management. Shunt revision ($22,715, P < 0.01) and/or replacement ($46,607, P < 0.001) add significantly to 5-year expenditures. Socioeconomic factors including African American race (P = 0.006); age 75-79 years (P = 0.024), 80-84 years (P < 0.001), and ≥85 years (P < 0.001); and Medicaid (P < 0.001) have significant negative associations with shunt surgery. CONCLUSIONS: There was a 1.66-fold increase in the rate of diagnosis of NPH, from 0.12% in 1999 to 0.2% in 2008. The total costs per surgical patient rose by approximately 145% to 160% comparing 2001 and 2010. This increase was mainly due to hospital (by 167% to 168%) and home health costs (by 118% to 148%). Providing appropriate care across the socioeconomic spectrum warrants further study and requires identifying the factors that limit access to care.

Aqueductal Cerebrospinal Fluid Stroke Volume Flow in a Rodent Model of Chronic Communicating Hydrocephalus: Establishing a Homogeneous Study Population for Cerebrospinal Fluid Dynamics Exploration.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts. OBJECTIVE: To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus. METHODS: Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days. RESULTS: Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P = 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P = 0.015), 60 (P = 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days. CONCLUSIONS: An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days.

Ventricular Volume Dynamics During the Development of Adult Chronic Communicating Hydrocephalus in a Rodent Model.

INTRODUCTION: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood. OBJECTIVE: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms. METHODS: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings. RESULTS: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013). CONCLUSIONS: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended.

Alzheimer's disease pathology and shunt surgery outcome in normal pressure hydrocephalus.

We aimed to determine whether presence of AD neuropathology predicted cognitive, gait and balance measures in patients with idiopathic normal pressure hydrocephalus (iNPH) after shunt surgery. This is a prospective study of gait and balance measured by Timed Up and Go (TUG) and Tinetti tests, and cognitive function measured by Mini Mental Status Exam (MMSE), before and after shunt surgery in participants 65 years and older with iNPH at the Johns Hopkins University. Random effects models were used and adjusted for confounders. 88 participants were included in the analysis with a median (IQR) time of 104 (57-213) days between surgery and follow-up. 23 (25%) participants had neuritic plaques present (NP+) and were significantly older [76.4 (6.0) years], but were otherwise similar in all demographics and outcome measures, when compared to the group without neuritic plaques (NP-). NP- and NP+ participants equally improved on measures of TUG (ß = -3.27, 95% CI -6.24, -0.30, p = 0.03; ß = -2.37, 95% CI -3.90, -0.86, p = 0.02, respectively), Tinetti-total (ß = 1.95, 95% CI 1.11, 2.78, p<0.001; ß = 1.72, 95% CI 0.90, 2.53, p<0.001, respectively), -balance (ß = 0.81, 95% CI 0.23, 1.38, p = 0.006; ß = 0.87, 95% CI 0.40, 1.34, p<0.001, respectively) and -gait (ß = 1.03, 95% CI 0.61, 1.45, p<0.001; ß = 0.84, 95% CI 0.16, 1.53, p = 0.02, respectively), while neither NP- nor NP+ showed significant improvement on MMSE (ß = 0.10, 95% CI -0.27, 0.46, p = 0.61, ß = 0.41, 95% CI -0.27, 1.09, p = 0.24, respectively). In summary, 26% of participants with iNPH had coexisting AD pathology, which does not significantly influence the clinical response to shunt surgery.

Ventriculoatrial versus ventriculoperitoneal shunt complications in idiopathic normal pressure hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a devastating condition that affects the elderly population. Although ventriculoatrial (VA) shunts can be used to manage iNPH, concerns for associated cardiopulmonary and renal complications have decreased their use. However, the rate of these complications is not well understood within this population of patients. PATIENTS AND METHODS: A retrospective review of the electronic medical records of patients diagnosed with iNPH by the senior author between 1993 and 2015 was performed. Demographic information and baseline symptoms were assessed. Complications including infection, shunt obstruction, overdrainage, cardiopulmonary events, renal dysfunction, and shunt revision were recorded. Complication rates were compared between VA and VP shunted patients. Statistical analysis using Chi-square test, Fisher's exact test, logistic regression, Wald t-test, Poisson regression, ANOVA, and ANCOVA was performed. RESULTS: 496 Patients, including 150 receiving VA shunts and 346 receiving VP shunts, were included in the study. The median age was 74 and 73 for VA and VP shunted patients, respectively, with slight male predominance in both (58.0% and 58.4% for VA and VP groups, respectively). A total of 36.0% of VA shunted patients and 42.5% of VP shunted patients experienced at least one post-operative complication. Overdrainage was the most commonly experienced complication in both VA (27.4%) and VP patients (19.9%). Infection occurred in only 2.0% of patients, and renal complications occurred in 1.3%. No patients had cardiopulmonary complications. VA shunted patients were significantly less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients (p=0.008 and <0.001, respectively). Only dizziness and gait disturbance at baseline were correlated with a shorter time to revision in VA shunted patients (p=0.002 for both). CONCLUSION: Although cardiopulmonary and renal complications are serious concerns associated with VA shunt placement, they were uncommon in patients with iNPH. VA shunted patients were less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients. Therefore, VA shunts should be considered as an alternative primary treatment option in the iNPH population.

Predictors of Ventriculoperitoneal Shunt Revision in Patients with Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: Few studies have focused on predictive factors of ventriculoperitoneal (VP) shunt revision in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to determine whether comorbidities and baseline symptoms are associated with the need for shunt revision. METHODS: A retrospective review of patients with iNPH treated with VP shunts by the senior author from 1993 to 2013 was conducted. Demographics and baseline symptoms were compared between patients with and without shunt revision. The need for revision, total number of revisions, and time to first revision were examined. Statistical analysis was performed using simple logistic, linear, and Poisson regression, and a multivariate analysis was performed. RESULTS: A total of 347 patients with iNPH who received VP shunts were included. One hundred patients (28.8%) required shunt revision, with an average of 1.38 ± 0.76 revisions per patient. Mean time to revision was 19.2 ± 31.7 months. Gait and cognitive symptoms were associated with fewer revisions (incidence rate ratio, 0.45 and 0.67; P = 0.03 and 0.004, respectively). Headaches and urinary incontinence showed a greater time to revision (32.0 and 12.0 months; P = 0.014 and <0.0005, respectively). Gait instability demonstrated decreased time to revision (P < 0.0005). CONCLUSIONS: Preoperative symptoms, such as headaches, gait instability, cognitive decline, and urinary incontinence, were significantly correlated with number of revisions and time to first revision. These factors should be considered during the initial counseling of prognosis for patients with iNPH receiving VP shunts.

NPH Log: Validation of a New Assessment Tool Leading to Earlier Diagnosis of Normal Pressure Hydrocephalus.

INTRODUCTION: Early treatment of normal pressure hydrocephalus (NPH) yields better postoperative outcomes. Our current tests often fail to detect significant changes at early stages. We developed a new scoring system (LP log score) to determine if this tool is more sensitive in detecting clinical differences than current tests. MATERIAL AND METHODS: Sixty-two consecutive new patients with suspected idiopathic NPH were studied. Secondary, previously treated and obstructive cases were not included. We collected age, pre- and post-lumbar puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log scores. The LP log score is recorded at baseline and for seven consecutive days after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the diagnostic accuracy of the tests for surgical indication. RESULTS: The post-LP log showed improvement in 90% of people with good baseline gait tests and in 93% of people who did not show any pre-LP and post-LP change in gait tests. Sensitivity, specificity, and accuracy to detect intention to treat when positive post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and 34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%, respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%, respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and post-LP Tinetti improvement were not associated with a surgical indication (p > 0.05). LP log improvement was associated with surgical indication odds ratio (OR): 24.5 95% CI (2.4-248.12) (p = 0.007). CONCLUSIONS: LP log showed better sensitivity, diagnostic accuracy, and association with surgical indication than the current diagnostic approach. An LP log may be useful detecting NPH patients at earlier stages and, therefore, yield better surgical outcomes.