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.

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.

Successful Identification and Assessment of the Superior Cluneal Nerves with High-Resolution Sonography.

BACKGROUND: Low back pain is a disabling and common condition, whose etiology often remains unknown. A suggested, however rarely considered, cause is neuropathy of the medial branch of the superior cluneal nerves (mSCN)-either at the level of the originating roots or at the point where it crosses the iliac crest, where it is ensheathed by an osseo-ligamentous tunnel. Diagnosis and treatment have, to date, been restricted to clinical assessment and blind infiltration with local anesthetics. OBJECTIVE: To determine whether visualization and assessment of the mSCN with high-resolution ultrasound (HRUS) is feasible. STUDY DESIGN: Interventional cadaver study and case series. METHODS: Visualization of the mSCN was assessed in 7 anatomic specimens, and findings were confirmed by HRUS-guided ink marking of the nerve and consecutive dissection. Further, a patient chart and image review was performed of patients assessed at our department with the diagnosis of mSCN neuropathy. RESULTS: The mSCN could be visualized in 12 of 14 cases in anatomical specimens, as confirmed by dissection. Nine patients were diagnosed with mSCN syndrome of idiopathic or traumatic origin. Diagnosis was confirmed in all of them, with complete resolution of symptoms after HRUS-guided selective nerve block. LIMITATIONS: These findings are first results that need to be evaluated in a systematic, prospective and controlled manner. CONCLUSION: We hereby confirm that it is possible to visualize the mSCN in the majority of anatomical specimens. The patients described may indicate a higher incidence of mSCN syndrome than has been recognized. mSCN syndrome should be considered in patients with low back pain of unknown origin, and HRUS may be able to facilitate nerve detection and US-guided nerve block.

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND: In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS: To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS: We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS: This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.

Maxillary dental arch biometry: assessment with fetal MR imaging.

OBJECTIVE: To define normal growth of the fetal maxillary dental arch using magnetic resonance imaging. METHOD: Four hundred twenty-four consecutive fetuses (18 to 37 weeks) with a morphologically normal anatomy or only minor malformations, not affecting bone growth and face anatomy were included. On axial T2-weighted images the dental arch length and width were measured. The measurements were correlated with gestational age and the biparietal diameter (BPD) of the fetal head using correlation and regression analysis. RESULTS: A linear growth relationship was observed between the dental arch length and gestational age (r = 0.86; p = < 0.0001; y = -1.85 + 0.75 × gestational age) and the dental arch width and gestational age (r = 0.92; p = < 0.0001; y = -2.19 + 1.05 × gestational age). A significant correlation was found between the dental arch length and the BPD (r = 0.903; p = < 0.0001) and the dental arch width and the BPD (r = 0.927; p = < 0.0001). The interobserver variability showed good agreement for the dental arch length (intraclass coefficient 0.981; r = 0.963) and width (intraclass coefficient 0.987; r = 0.974), respectively. CONCLUSION: We present a nomogram for the in utero assessment of the fetal dental arch. These data may help in the early detection of abnormal dental arch development.

Assessment of lung development in isolated congenital diaphragmatic hernia using signal intensity ratios on fetal MR imaging.

OBJECTIVES: To investigate developmental changes in the apparently unaffected contralateral lung by using signal intensity ratios (SIR) and lung volumes (LV), and to search for correlation with clinical outcome. METHODS: Twenty-five fetuses (22-37 weeks' gestation) were examined. Lung/liver signal intensity ratios (LLSIR) were assessed on T1-weighted and T2-weighted sequences for both lungs, then together with LV compared with age-matched controls of 91 fetuses by using the U test. Differences in LLSIRs and lung volumes were correlated with neonatal outcomes. RESULTS: LLSIRs in fetuses with congenital diaphragmatic hernia (CDH) were significantly higher in both lungs on T1-weighted images and significantly lower on T2-weighted images, compared with normals (p < 0.05), increasing on T2-weighted imaging and decreasing on T1-weighted imaging during gestation. Total LV were significantly smaller in the CDH group than in controls (p < 0.05). No significant differences in LLSIR of the two lungs were found. Outcomes correlated significantly with total LV, but not with LLSIR. CONCLUSION: Changes in LLSIR seem to reflect developmental impairment in CDH; however, they provide no additional information in predicting outcome. LV remains the best indicator on fetal MR imaging of neonatal survival in isolated, left-sided CDH.

Preterm birth and disruptive cerebellar development: assessment of perinatal risk factors.

OBJECTIVE: Abnormal cerebellar development was recently recognized to be related to prematurity. Aim of the present study was to evaluate preterm birth and possible peri- and postnatal risk factors associated with this type of brain injury. PATIENTS AND METHODS: We report on a series of 35 very low birth weight infants (birth weight 986+/-257g S.D.) born between 24 and 32 weeks of gestation (27.0+/-1.8 weeks of gestation S.D.) sustaining disruption of cerebellar development after preterm birth. Perinatal medical records of study patients were compared to 41 preterm control infants (birth weight 900+/-358g S.D., gestational age 26.3+/-2.1 weeks S.D.) with normal cerebellar development on MRI scan. RESULTS: A severely compromised postnatal condition with consecutive intubation and catecholamine support was found to be significant risk factor. Additional supratentorial hemorrhagic brain injury followed by posthemorrhagic hydrocephalus, neurosurgical interventions and hemosiderin deposits on the cerebellar surface were significantly related to disruptive cerebellar development. No other differences in perinatal factors were found between the groups. CONCLUSION: Premature birth between 24 and 32 gestational weeks associated with poor postnatal conditions and complicated supratentorial hemorrhagic brain lesions represents a high-risk situation for disruption of cerebellar development.

International validation of novel pyrogen tests based on human monocytoid cells.

It is a requirement that parenteral medicines be tested for pyrogens (fever causing agents) using one of two animal-based tests: the rabbit pyrogen test and the bacterial endotoxin test. Understanding the human fever reaction has led to novel non-animal alternative tests based on in vitro activation of human monocytoid cells in response to pyrogens. Using 13 prototypic drugs, clean or contaminated with pyrogens, we have validated blindly six novel pyrogen tests in ten laboratories. Compared with the rabbit test, the new tests have a lower limit of detection and are more accurate as well as cost and time efficient. In contrast to the bacterial endotoxin test, all tests are able to detect Gram-positive pyrogens. The validation process showed that at least four of the tests meet quality criteria for pyrogen detection. These validated in vitro pyrogen tests overcome several shortcomings of animal-based pyrogen tests. Our data suggest that animal testing could be completely replaced by these evidence-based pyrogen tests and highlight their potential to further improve drug safety.