Neuropsychological Functioning in Patients with Cushing's Disease and Cushing's Syndrome.

PURPOSE: To present a systematic review of the presence and severity of neuropsychological impairment in the six main neuropsychological domains (attention, executive function, language, visuospatial processing, intelligence, and memory) in patients with Cushing's disease (CD) and/or Cushing's Syndrome (CS) at various stages of the illness. The work aims to identify neuropsychological leverage points for focused diagnosis and rehabilitation in CS/CD patients. METHODS: A pubmed literature search was performed and augmented by searching the reference lists of review articles identified by this search strategy. After excluding irrelevant hits, we systematically extracted data from 27 studies for each main neuropsychological domain, differentiating between active disease, short- and long-term remission. RESULTS: The literature gives evidence for neuropsychological impairment in all domains in Cushing patients with active disease. The most consistent impairments concerned memory and visuo-spatial processing, whereas the data are discordant for all other domains. Significant improvement of neuropsychological function - although not returning to normal in all domains - is shown in short-term and long-term remission of the disease. However, the published literature is thin, suffering from repetitive subsample analyses publishing, methodological concerns as lack of control for confounders such as depression. CONCLUSIONS: Memory is the most extensively investigated domain in CS/CD patients and impairment is most prominent in active disease. Patients should be counseled that neuropsychological function will improve with normalization of hypercortisolism and over time. More studies with more stringent methodological criteria, larger patient samples and controlling for confounders are required to enhance our understanding of neuropsychological function in patients with CS/CD.

Coping and Health-Related Quality of Life after Closed Head Injury.

OBJECTIVES: In the present study the relationship between illness coping and health-related quality of life (HRQOL) in patients after closed head injury (CHI) was analyzed. Furthermore, the study was performed to assess the relative significance of clinical, neuroradiological, psychosocial variables and coping activities after CHI. We hypothesized that the effect of a depressive coping style is significantly stronger than that of all other variables considered. PATIENTS AND METHODS: This cross-sectional study took place at the outpatient clinic of the Department of Neurosurgery of the University of Technology (RWTH) Aachen, Germany. Of a total of 98 patients 1-2 years after CHI living in the catchment area of the university hospital fulfilling the inclusion criteria 63 individuals (mean age 40.6 years; 46 males) with a mean of 17.6 months after CHI took part in the study. HRQOL was assessed by means of the Aachen Life Quality Questionnaire (ALQI) and illness coping by the Freiburger Fragebogen zur Krankheitsverarbeitung (FKV). RESULTS: The patients complained most frequently of impairments in their HRQOL in the areas of free-time activities and social contact. The most intensely used coping activities were distraction and self-management, active problem-oriented coping and religion and looking for sense. Regression analyses revealed exclusively the depressive coping style as the most important predictor of subjectively impaired HRQOL explaining up to 44% of the variance. There was only a modest relationship between patient age and active problem-oriented coping (r = .43; p < .01). The degree of education was negatively associated (r= -.35; p < .01) with depressive coping. A moderate severity of the injury led to significantly more intense activities in the area of minimizing and wishful thinking as compared to a mild CHI (p < .05). CONCLUSIONS: In patients after CHI rehabilitation measures should focus to the HRQOL areas of free-time activities and social contact. Specific psychological interventions are called for in order to tackle the obviously dysfunctional depressive coping style.

Analysis of Brain Natriuretic Peptide Serum Levels in Patients with Symptomatic Chronic Subdural Hematoma: A Potential Reliable Biomarker.

The purpose of this study was to analyze brain natriuretic peptide (BNP) serum levels of patients with chronic subdural hematoma (cSDH) and their clinical implication. Patients with cSDH who underwent surgery in our department between November 2016 and October 2019 were eligible for enrollment in the study. Patients with recurrent bleedings, traumatic brain injury, cSDH associated with other intracranial pathologies, and those with a history of congestive heart failure, renal or endocrine disease were excluded. We measured BNP serum levels pre- and post-operatively and at discharge. The BNP values were analyzed with respect to patient medical history and neurological condition. The Glasgow Coma Scale score and the modified Rankin Scale score classified the clinical and neurological condition at the time of admission and discharge, respectively. The data of 100 surgically treated patients with cSDH (mean age 73.2, range 42 - 94 years, male/female 3.5:1) were analyzed. Pre-operative BNP serum levels (BNP-1) were elevated in 67% of the patients (n = 67; median = 101.6 pg/mL; p < 0.001). These serum levels increased after surgery (p < 0.001) and decreased thereafter (p < 0.001), reaching a level at discharge (day 7) that was not statistically different from BNP-1 (p > 0.05). In addition, elevated BNP-1 showed a significant statistical association with the presence of atrial fibrillation (p < 0.01) and antiplatelet and/or anticoagulant therapy (p < 0.01). This study provides new evidence regarding BNP serum levels and their secretion pattern in patients with cSDH. Whether BNP-1 can predict the long-term functional outcome of patients with cSDH is being investigated in this ongoing prospective study.

Higher sensitivity for traumatic cerebral microbleeds at 7 T ultra-high field MRI: is it clinically significant for the acute state of the patients and later quality of life?

BACKGROUND: The present study evaluates the possible prognostic benefits of 7 T susceptibility weighted imaging (SWI) of traumatic cerebral microbleeds (TMBs) over 3 T SWI to predict the acute clinical state and subjective impairments, including health-related quality of life (HRQOL), after closed head injury (CHI). METHODS: The study group comprised 10 participants with known TMBs All subjects underwent 3 T magnetic resonance imaging (MRI) and 7 T MRI, respectively. Location and count of TMBs were independently evaluated by two neuroradiologists. The initial Glasgow Coma Scale (GCS), the duration of coma and further clinical data were taken from the patients records. HRQOL was assessed by means of a questionnaire. Memory complaints and neurological symptoms were inquired at the time of the MRI examinations. RESULTS: SWI revealed a total of 485 TMBs at 3 T, 584 TMBs at 7 T with similar spatial resolution, and 684 TMBs at 7 T with a factor of 10 higher spatial resolution. The TMBs depicted by 7 T high-resolution SWI were correlated with the duration of coma (Spearman's rho of 0.77). The corresponding association with TMBs in 3 T MRI SWI showed a Spearman's rho of 0.71. The initial GCS score and TMBs correlated with a Spearman's rho of -0.35 at 3 T SWI MRI and a rho of -0.33 at 7 T high-resolution SWI, respectively. The physical aspect of HRQOL correlated substantially with the count of TMBs (rho = 0.44 for 3 T SWI and rho = 0.35 for both 7 T SWI sequences, respectively). CONCLUSIONS: The number of TMBs showed a substantial association with indicators of the acute clinical state and chronic neurobehavioral parameters after CHI, but there was no additional advantage of 7 T MRI. These preliminary findings warrant a larger prospective study for the future.

Development, reliability, validity and sensitivity of the Sino-Nasal Outcome Test for Neurosurgery (SNOT-NC).

BACKGROUND: The transnasal endoscopic approach to lesions of the skull base has come into routine practice in recent years. Standardized questionnaires to assess the postoperative sequelae are missing. The authors present a custom-made questionnaire for the sino-nasal outcome test for neurosurgery (SNOT-NC) in accordance with the SNOT-22. METHODS: The SNOT-NC was developed with respect to the German version of the Sino-Nasal Outcome Test (SNOT-22) which is used for patients suffering from rhinosinusitis. It consists of 23 items covering "Nasal Discomfort", Sleep Problems/Reduced Productivity", "Ear and Head Discomfort", "Visual Impairment" and "olfactory impairment". The SNOT-NC was specifically adapted to patients undergoing transnasal operations of skull base lesions. The Short Form 36 health survey (SF-36), a nasal ad hoc questionnaire and the "Sniffin' Sticks" test were used for analyzing convergent and divergent validity. The psychometric and clinimetric analyses were performed using the data of 102 consecutive patients treated by transnasal operations for skull base lesions. RESULTS: Factorial validity was secured by a confirmatory factor analysis. The internal consistency (Cronbach's Alpha) for the subscales ranged from .62 to .85, while it was .84 for the whole instrument. The Guttman's lower reliability limits range estimates corresponded closely to the Cronbach's Alpha coefficients obtained. Examination of convergent and divergent validity revealed substantial associations between the SNOT-NC and a wide range of related nasal symptoms (p < .05). Different aspects of sensitivity were analyzed statistically with Cohen's t statistic for change (pairwise t tests) exhibiting at least p < .05) underlining the sensitivity of the SNOT-NC. CONCLUSIONS: The SNOT-NC appears to be a valid, reliable and sensitive measure for assessing the clinical outcome of patients undergoing transnasal endoscopic skull base surgery. The SNOT-NC proved to be a valuable tool to assess the nasal discomfort outcome of patients at follow-up examinations. Further analyses encompassing analyses for retest reliability are called for the future.

Relative health-related quality of life after treatment of unruptured intracranial aneurysms: long-term outcomes and influencing factors.

Health-related quality of life (HRQOL) is an important clinical outcome parameter. Its analysis is particularly meaningful to patients with minor functional impairment. The main goal of this study was to assess long-term data of HRQOL and their variables for patients undergoing treatment for unruptured intracranial aneurysms (UIAs). Therefore, a cross-sectional study of HRQOL (SF-36 questionnaire) was conducted in patients treated for UIA using a telephone survey assessing numerous medical and sociodemographic variables. A total of 96 patients with a follow up longer than 36 months post-treatment were included. HRQOL results were compared with the German reference population. Uni- and multivariate analyses were performed to detect variables with an impact on outcome. After a mean follow up of 57.75 ± 13.56 months, patients with treated UIAs showed a significant decrease in the mental health domains 'role emotional' and 'social functioning' and the 'mental health component score' (MHCS) compared with the age- and sex-matched reference population. Overall, 47% of the patients showed a clinically and psychosocially relevant decrease compared with the mean MHCS of the reference population. Multivariate analysis suggests that mainly the treatment modality (coiling versus clipping) and additional remaining untreated UIAs negatively impacted mental HRQOL. In conclusion, the partly significant losses in HRQOL identify the necessity for less-wearing treatment strategies and a better prediction of risk of UIA rupture. Our results indicate that certain factors in the guidance and management of patients undergoing endovascular treatment may negatively affect their mental HRQOL. The relevance of additional UIAs remaining untreated on HRQOL is a new finding that should be considered in the counseling of patients with multiple UIAs.

Degenerative Cervical Myelopathy in Higher-Aged Patients: How Do They Benefit from Surgery?

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common reason for spinal cord disease in elderly patients. This study analyzes the preoperative status and postoperative outcome of higher-aged patients in comparison to young and elderly patients in order to determine the benefit to those patients from DCM surgery. METHODS: A retrospective analysis of the clinical data, radiological findings, and operative reports of 411 patients treated surgically between 2007 and 2016 suffering from DCM was performed. The preoperative and postoperative neurological functions were evaluated using the modified Japanese Orthopedic Association Score (mJOA Score), the postoperative mJOA Score improvement, the neurological recovery rate (NRR) of the mJOA Score, and the minimum clinically important difference (MCID). The Charlson Comorbidity Index (CCI) was used to evaluate the impact of comorbidities on the preoperative and postoperative mJOA Score. The comparisons were performed between the following age groups: G1: ≤50 years, G2: 51-70 years, and G3: >70 years. RESULTS: The preoperative and postoperative mJOA Score was significantly lower in G3 than in G2 and G1 (p < 0.0001). However, the mean mJOA Score's improvement did not differ significantly (p = 0.81) between those groups six months after surgery (G1: 1.99 ± 1.04, G2: 2.01 ± 1.04, G: 2.00 ± 0.91). Furthermore, the MCID showed a significant improvement in every age-group. The CCI was evaluated for each age-group, showing a statistically significant group effect (p < 0.0001). Analysis of variance revealed a significant group effect on the delay (weeks) between symptom onset and surgery (p = 0.003). The duration of the stay at the hospital did differ significantly between the age groups (p < 0.0001). CONCLUSION: Preoperative and postoperative mJOA Scores, but not the extent of postoperative improvement, are affected by the patients' age. Therefore, patients should be considered for DCM surgery regardless of their age.

Acute administration of cyclosporine A does not impair attention or memory performance in healthy men.

There is clinical and experimental evidence that treatment with immunosuppressive and antiproliferative drugs such as the calcineurin inhibitor cyclosporine A (CsA) is associated with mental health problems and neuropsychological disturbances in patients. However, it remains unclear whether and to what extent cognitive functions such as memory and attention processes are affected by the pharmacological treatment. This is partly because of the fact that it is difficult to refer the observed neuropsychological disturbances in patients to the drug itself, to drug-induced immune suppression, or to interaction with other medication or comorbidities. Thus, in a double-blind study with healthy male participants (n=30), we investigated whether short-term intake of therapeutic doses of CsA (4×2.5 mg/kg) affects attention, working memory performance, and anxiety levels, measured with the Tests of Attentional Performance and the State-Trait Anxiety Inventory. The data indicate that short-term CsA-administration and subsequent suppression in interleukin-2 production are accompanied neither by a decrease in attention or memory performance nor by increased anxiety levels in healthy male volunteers, suggesting that the short-term intake of CsA does not impair cognitive functioning. Further studies in healthy humans are needed to determine neurocognitive functions and mood states after short-term or subchronic treatment with different immunosuppressive and antiproliferative drugs.

Short- and long-term neurobehavioral effects of lumbar puncture and shunting in patients with malabsorptive hydrocephalus after subarachnoid haemorrhage: An explorative case study.

BACKGROUND: The neuropsychological effects of lumbar puncture and shunting in terms of cognitive functioning and quality of life were analyzed prospectively in four patients with malabsorptive hydrocephalus who became symptomatic in the chronic state after aneurysmal subarachnoid haemorrhage (SAH). METHODS: A comprehensive battery of neuropsychological tests was applied to four patients before and shortly after lumbar puncture and six months later. In three of them a shunt has been inserted, one patient was treated by repeated lumbar punctures. In addition, the patients completed a quality of life and a depression questionnaire before lumbar puncture and after shunting. The data were analyzed using single-case methodology. RESULTS: Hydrocephalus was associated with pronounced cognitive deficits in terms of functions of attention, short- and long-term memory, concentration and motor fine-coordination but not with a general mental deterioration. Quality of life and affect were also substantially impaired. Neuropsychological tests of fronto-cortical cognitive capacity, motor fine coordination and reaction time proved to be sensitive for the short-term effects of lumbar puncture. Memory functions and the capacity of divided attention needed more time for regeneration and improved substantially after shunt implantation. CONCLUSIONS: We found a complex pattern of cognitive improvement after lumbar puncture and shunting. Furthermore, our results also show a typical cluster of cognitive deficits associated with malabsorptive hydrocephalus including motor dysfunction. These preliminary findings should be confirmed in larger patient samples.

A retrospective and consecutive analysis of the epidemiology and management of spinal cavernomas over the last 20 years in a single center.

Spinal cavernous malformations (SCM) are rare lesions often presenting with acute onset of symptoms and progressive neurological deterioration due to hemorrhage into the spinal cord. With the aid of modern techniques, their surgical removal became much safer. The present study was undertaken to analyze the outcome of our series of surgically and conservatively treated patients with SCM. Over a period of 20 years, 20 surgically treated and 5 conservatively managed patients with spinal cavernous malformations were identified and enrolled into this analysis. Demographic data, clinical symptoms, localization and extension of the cavernoma, as well as pre- and postoperative neurological status were obtained. The clinical status was assessed using the Frankel score. Patients were followed up clinically and by MRI. Before surgery, 90% (18/20) of our surgical patients were classified as Frankel D (93.8%), whereas two patients (10%) were graded C. None of the patients had a worse Frankel score at the time of discharge. Eighty percent of them (16 cases) remained unchanged, and 20% (4 patients) improved during the first follow-up (mean 6.3 months, range 2-17 months). All improved patients had a superficially located SCM and were operated early (≤3 months). No worsening was observed during extended follow-up (range 9-134 months, mean 44.7 months). Five nonsurgically treated patients showed no significant clinical deterioration over a period of 6.7 years (mean, range 2.9-8 years). SCM localization and number of involved segments had no influence on outcome. Our data show that SCM can be resected with favorable neurological outcome by using intraoperative neuromonitoring. Within the follow-up period, patients treated conservatively remained in a stable neurological condition.

Subarachnoid hemorrhage as a psychological trauma.

OBJECT: Despite the progress made in the management of subarachnoid hemorrhage (SAH), many patients complain of persistent psychosocial and cognitive problems. The present study was performed to explore the significance of psychological traumatization by the bleeding with respect to psychosocial results after SAH. METHODS: A series of 45 patients were examined in a cross-sectional study an average of 49.4 months after SAH by means of a quality-of-life questionnaire, the Beck Depression Inventory, the German version of the Impact of Event Scale (IES), and a clinical interview (Structured Clinical Interview for DSM Disorders) to make the diagnosis of chronic posttraumatic stress disorder (PTSD). Twenty-nine patients underwent surgery for treatment of a ruptured aneurysm; the remaining 16 patients had SAH of unknown origin. RESULTS: Twelve patients (27%) exhibited PTSD, and almost two-thirds of the 45 patients in the study reported substantial fear of recurrent hemorrhage. Not only the presence of PTSD but the severity of psychological traumatization as assessed by the IES explained up to 40% of the variance of the self- and proxy-rated impairments. Multivariate analyses revealed psychological traumatization (IES) and neurological state on admission (Hunt and Hess grade) as substantial predictors of the self- and proxy-rated quality of life, explaining 31% and 42% of the variance, respectively. CONCLUSIONS: Even several years after SAH, the severity of psychological traumatization by the bleeding substantially determines the degree of psychosocial impairment. In the future, this issue should be addressed in the care of these patients. Furthermore, the development of psychological interventions is called for to prevent the emergence of PTSD after SAH.

Intramedullary spinal cord astrocytomas: the influence of localization and tumor extension on resectability and functional outcome.

BACKGROUND: Intramedullary spinal cord tumors (IMSCT) are rare lesions, ependymomas and astrocytomas being the most common ones. Different studies have been published showing results of different treatment strategies as extensive/ limited surgery, biopsy and adjuvant radiation therapy with regard to functional outcome and survival. The present study was undertaken to analyse our series of surgically treated intramedullary astrocytomas in order to identify factors with impact on functional outcome and resectability. METHODS: Over a period of 20 years, among 215 patients with IMSCT 22 patients with astrocytomas were identified and enrolled into this analysis. Demographic data, clinical symptoms, localization and extension of the tumor, resection rate as well as pre- and postoperative neurological status were obtained. Patients were followed-up clinically and by MRI. RESULTS: Complete resection rate was higher in cervically located tumors (9 of 10) compared to non-cervical tumors (7 of 12). Tumor extension (1-3 segments vs. > 3 segments involved) did not influence on the resection rate. Cervical tumors showed a trend for better postoperative functional outcome than non-cervical lesions (3 of 10 cervical but 6 of 12 non-cervical tumors deteriorated postoperatively). In tumors extending more than 3 segments postoperative worsening was significantly increased. CONCLUSIONS: The present study shows a better resectability and functional outcome for cervically located intramedullary astrocytomas. Tumors extending more than three segments deteriorated significantly. These findings may help for decision-making process and treatment of these tumors.

The venous angioarchitecture of sporadic cerebral cavernous malformations: a susceptibility weighted imaging study at 7 T MRI.

BACKGROUND AND PURPOSE: To test the hypothesis that sporadic cerebral cavernous malformations (CCMs) are systematically associated with venous malformations (VMs) using susceptibility weighted imaging (SWI) at 7 Tesla (T) field MRI. METHODS: A prospective unselected series of 20 patients with symptomatic or asymptomatic sporadic CCM diagnosed using 1.5 T MRI was additionally scanned using high resolution (250 µm(2) in-plane) SWI at 7 T MRI. Imaging data were analysed to examine the presence and formation of CCM associated venous vessel structures. Interobserver agreement was assessed using kappa statistics. RESULTS: In the 20 patients harbouring 23 CCMs, a solitary or multiple venous drainage was found in all lesions. A 'typical' VM was found in seven lesions. In the other cases, associated abnormal venous structures were also depicted although they appeared structurally different. Excellent interobserver agreement was achieved (95% confidence interval 0.92 to 0.99). CONCLUSIONS: Our data support previous assumptions that sporadic CCMs are systematically associated with local venous abnormalities involving larger outflow vessels. However, the typical appearance of a VM was not confirmed in all cases. The role of the venous environment in the pathomechanism of CCMs remains unclear.