Successful weaning versus permanent cerebrospinal fluid diversion after aneurysmal subarachnoid hemorrhage: post hoc analysis of a Swiss multicenter study.

OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

Longitudinal neuropsychological assessment after aneurysmal subarachnoid hemorrhage and its relationship with delayed cerebral ischemia: a prospective Swiss multicenter study.

OBJECTIVE: While prior retrospective studies have suggested that delayed cerebral ischemia (DCI) is a predictor of neuropsychological deficits after aneurysmal subarachnoid hemorrhage (aSAH), all studies to date have shown a high risk of bias. This study was designed to determine the impact of DCI on the longitudinal neuropsychological outcome after aSAH, and importantly, it includes a baseline examination after aSAH but before DCI onset to reduce the risk of bias. METHODS: In a prospective, multicenter study (8 Swiss centers), 112 consecutive alert patients underwent serial neuropsychological assessments (Montreal Cognitive Assessment [MoCA]) before and after the DCI period (first assessment, < 72 hours after aSAH; second, 14 days after aSAH; third, 3 months after aSAH). The authors compared standardized MoCA scores and determined the likelihood for a clinically meaningful decline of ≥ 2 points from baseline in patients with DCI versus those without. RESULTS: The authors screened 519 patients, enrolled 128, and obtained complete data in 112 (87.5%; mean [± SD] age 53.9 ± 13.9 years; 66.1% female; 73% World Federation of Neurosurgical Societies [WFNS] grade I, 17% WFNS grade II, 10% WFNS grades III-V), of whom 30 (26.8%) developed DCI. MoCA z-scores were worse in the DCI group at baseline (-2.6 vs -1.4, p = 0.013) and 14 days (-3.4 vs -0.9, p < 0.001), and 3 months (-0.8 vs 0.0, p = 0.037) after aSAH. Patients with DCI were more likely to experience a decline of ≥ 2 points in MoCA score at 14 days after aSAH (adjusted OR [aOR] 3.02, 95% CI 1.07-8.54; p = 0.037), but the likelihood was similar to that in patients without DCI at 3 months after aSAH (aOR 1.58, 95% CI 0.28-8.89; p = 0.606). CONCLUSIONS: Aneurysmal SAH patients experiencing DCI have worse neuropsychological function before and until 3 months after the DCI period. DCI itself is responsible for a temporary and clinically meaningful decline in neuropsychological function, but its effect on the MoCA score could not be measured at the time of the 3-month follow-up in patients with low-grade aSAH with little or no impairment of consciousness. Whether these findings can be extrapolated to patients with high-grade aSAH remains unclear. Clinical trial registration no.: NCT03032471 (ClinicalTrials.gov).

Asomatognosia: Structured Interview and Assessment of Visuomotor Imagery.

Asomatognosia designates the experience that one's body has faded from awareness. It is typically a somaesthetic experience but may target the visual modality ("asomatoscopy"). Frequently associated symptoms are the loss of ownership or agency over a limb. Here, we elaborate on the rigorous nosographic classification of asomatognosia and introduce a structured interview to capture both its core symptoms and associated signs of bodily estrangement. We additionally report the case of a pure left-sided hemiasomatognosia occurring after surgical removal of a meningioma in the right atrium. Despite the wide lesions of the right angular gyrus and of the temporo-parietal junction, the patient did not present visuospatial deficits or bodily awareness disorders other than hemiasomatognosia. The patient and 10 matched controls' motor imagery was formally assessed with a limb laterality task in which they had to decide whether hands and feet presented under different angles of rotation depicted a left or a right limb. Bayesian statistics showed that patient's reaction times were significantly impaired exclusively for the left foot and especially for mental rotations requiring somatomotor rather than visual limb representations. This was in accordance with a more enduring left-sided hemiasomatognosia for the lower limbs confined to the somesthetic modality. Our findings shed new light on motor imagery in asomatognosia and encourage the future use of the structured interview introduced here. In addition, the limb laterality task may capture phenomenological elements of a case by chronometric means. This allows a more standardized reporting of phenomenological detail and improves communication across different clinical facilities.

Screening tools for early neuropsychological impairment after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Although most aneurysmal subarachnoid hemorrhage (aSAH) patients suffer from neuropsychological disabilities, outcome estimation is commonly based only on functional disability scales such as the modified Rankin Scale (mRS). Moreover, early neuropsychological screening tools are not used routinely. OBJECTIVE: To study whether two simple neuropsychological screening tools identify neuropsychological deficits (NPDs), among aSAH patients categorized with favorable outcome (mRS 0-2) at discharge. METHODS: We reviewed 170 consecutive aSAH patients that were registered in a prospective institutional database. We included all patients graded by the mRS at discharge, and who had additionally been evaluated by a neuropsychologist and/or occupational therapist using the Montreal Cognitive Assessment (MoCA) and/or Rapid Evaluation of Cognitive Function (ERFC). The proportion of patients with scores indicative of NPDs in each test were reported, and spearman correlation tests calculated the coefficients between the both neuropsychological test results and the mRS. RESULTS: Of the 42 patients (24.7%) that were evaluated by at least one neuropsychological test, 34 (81.0%) were rated mRS 0-2 at discharge. Among these 34 patients, NPDs were identified in 14 (53.9%) according to the MoCA and 8 (66.7%) according to the ERFC. The mRS score was not correlated with the performance in the MoCA or ERFC. CONCLUSION: The two screening tools implemented here frequently identified NPDs among aSAH patients that were categorized with favorable outcome according to the mRS. Our results suggest that MoCA or ERFC could be used to screen early NPDs in favorable outcome patients, who in turn might benefit from early neuropsychological rehabilitation.

Influence of the Intensive Care Unit Environment on the Reliability of the Montreal Cognitive Assessment.

Background: Neuropsychological screening becomes increasingly important for the evaluation of subarachnoid hemorrhage (SAH) and stroke patients. It is often performed during the surveillance period on the intensive (ICU), while it remains unknown, whether the distraction in this environment influences the results. We aimed to study the reliability of the Montreal Cognitive Assessment (MoCA) in the ICU environment. Methods: Consecutive stable patients with recent brain injury (tumor, trauma, stroke, etc.) were evaluated twice within 36 h using official parallel versions of the MoCA (ΔMoCA). The sequence of assessment was randomized into (a) busy ICU first or (b) quiet office first with subsequent crossover. For repeated MoCA, we determined sequence, period, location effects, and the intraclass correlation coefficient (ICC). Results: N = 50 patients were studied [n = 30 (60%) male], with a mean age of 57 years. The assessment's sequence ["ICU first" mean ΔMoCA -1.14 (SD 2.34) vs. "Office first" -0.73 (SD 1.52)] did not influence the MoCA (p = 0.47). On the 2nd period, participants scored 0.96 points worse (SD 2.01; p = 0.001), indicating no MoCA learning effect but a possible difference in parallel versions. There was no location effect (p = 0.31) with ΔMoCA between locations (Office minus ICU) of -0.32 (SD 2.21). The ICC for repeated MoCA was 0.87 (95% CI 0.79-0.92). Conclusions: The reliability of the MoCA was excellent, independent from the testing environment being ICU or office. This finding is helpful for patient care and studies investigating the effect of a therapeutic intervention on the neuropsychological outcome after SAH, stroke or traumatic brain injury.

Measuring the Impact of Delayed Cerebral Ischemia on Neuropsychological Outcome After Aneurysmal Subarachnoid Hemorrhage-Protocol of a Swiss Nationwide Observational Study (MoCA-DCI Study).

BACKGROUND: The exact relationship between delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and neuropsychological impairment remains unknown, as previous studies lacked a baseline examination after aneurysm occlusion but before the DCI-period. Neuropsychological evaluation of acutely ill patients is often applied in a busy intensive care unit (ICU), where distraction represents a bias to the obtained results. OBJECTIVE: To evaluate the relationship between DCI and neuropsychological outcome after aSAH by comparing the Montreal Cognitive Assessment (MoCA) results in aSAH patients with and without DCI at 3 mo with a baseline examination before the DCI-period (part 1). To determine the reliability of the MoCA, when applied in an ICU setting (part 2). METHODS: Prospective, multicenter, and observational study performed at all Swiss neurovascular centers. For part 1, n = 240 consecutive aSAH patients and for part 2, n = 50 patients with acute brain injury are recruited. EXPECTED OUTCOMES: Part 1: Effect size of the relationship between DCI and neuropsychological outcome (MoCA). Part 2: Reliability measures for the MoCA. DISCUSSION: The institutional review boards approved this study on July 4, 2017 under case number BASEC 2017-00103. After completion, the results will be offered to an international scientific journal for peer-reviewed publication. This study determines the exact impact of DCI on the neuropsychological outcome after aSAH, unbiased by confounding factors such as early brain injury or patient-specific characteristics. The study provides unique insights in the neuropsychological state of patients in the early period after aSAH.

Time to be "smart"-Opportunities Arising From Smartphone-Based Behavioral Analysis in Daily Patient Care.

While pathologies of the central nervous system (CNS) are often associated with neuropsychological deficits, adequate quantification and monitoring of such deficits remains challenging. Due to their complex nature, comprehensive neuropsychological evaluations are needed, which are time-consuming, resource-intensive and do not adequately account for daily or hourly fluctuations of a patient's condition. Innovative approaches are required to improve the diagnostics and continuous monitoring of brain function, ideally in the form of a simple, objective, time-saving and inexpensive tool that overcomes the aforementioned weaknesses of conventional assessments. As smartphones are widely used and integrated in virtually every aspect of our lives, their potential regarding the acquisition of data representing an individual's behavior and health is enormous. Alterations in a patient's physical or mental health state may be recognized as behavioral deviation from the physiological range of the normal population, but also in comparison to the patient's individual baseline assessment. As smartphone-based assessment allows for continuous monitoring and therefore accounts for possible fluctuations or transiently occurring abnormalities in a patient's neurologic state, it may serve as a surveillance tool in the acute setting for early recognition of complications, or in the long-term outpatient setting to quantify rehabilitation or disease progress. This may be particularly interesting for regions of the world where healthcare resources for comprehensive clinical/neuropsychological examinations are insufficient or distances to healthcare providers are long. Here, we highlight the potential of smartphone-based behavioral monitoring in healthcare. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03516162.

Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years.

OBJECTIVE: To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS). METHODS: Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue. RESULTS: We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients' perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders. CONCLUSIONS: Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS.

The relevance of cortical lesions in patients with multiple sclerosis.

BACKGROUND: Recent studies suggest that cortical lesions in multiple sclerosis (MS) substantially contribute to clinical disease severity. The present study aimed at investigating clinical, neuroanatomical, and cognitive correlates of these cortical lesions with a novel approach, i.e. by comparing two samples of relapsing-remitting multiple sclerosis (RRMS) patients, one group with and the other without cortical lesions. METHODS: High-resolution structural MRI was acquired from 42 RRMS patients and 43 controls (HC). The patient group was dichotomized based on the presence versus absence of DIR-hyperintense cortex-involving lesions, resulting in a cortical lesion group (CL, n = 32) and a non-cortical lesion group (nCL, n =10). Cognitive functioning was assessed in all participants with a comprehensive neuropsychological battery, covering mnestic, executive, and attentional functions. RESULTS: Highest densities of cortical lesions in the CL group were observed in the bilateral parahippocampal gyrus. Relative to HC, patients with cortical lesions - but not those without - showed significant global cortical thinning and mnestic deficits. The two patient groups did not differ from each other regarding demographic and basic disease characteristics such as EDSS scores. CONCLUSION: The appearance of cortical lesions in MS patients is associated with cortical thinning as well as mnestic deficits, which might be key characteristics of a 'cortically dominant' MS subtype.

Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates.

Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology.

Cognitive Impairment in Multiple Sclerosis: Clinical Manifestation, Neuroimaging Correlates, and Treatment.

Cognitive impairment is found in up to 70% of patients with multiple sclerosis (MS). Once thought of as a variant of subcortical dementia with a characteristic set of deficits, we now know that MS-related cognitive impairment can have many faces. This conceptual change in neuropsychology is embedded in a paradigm shift in the neuroscientific understanding of MS over the past 25 years: Partly based on modern neuroimaging techniques, the classical view of MS as an inflammatory demyelinating disease affecting the white matter of the central nervous system has been extended. In particular, many studies have shown that the MS pathology also includes neurodegeneration, and that gray matter structures such as the cerebral cortex can also show focal lesions, atrophy, or both. The authors present an updated summary of the clinical manifestation and neuroimaging correlates of cognitive impairment in MS, and discuss the relatively few treatment options available to date.

Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner.

Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters - including cortical thinning and T2 lesion load - to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal - but not figural - fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.