Neurocognitive Impairment After Propofol With Relevance for Neurosurgical Patients and Awake Craniotomies-A Prospective Observational Study.

Background: Short-acting anesthetics are used for rapid recovery, especially for neurological testing during awake craniotomy. Extent and duration of neurocognitive impairment are ambiguous. Methods: Prospective evaluation of patients undergoing craniotomy for tumor resection during general anesthesia with propofol (N of craniotomies = 35). Lexical word fluency, digit span and trail making were tested preoperatively and up to 24 h after extubation. Results were stratified for age, tumor localization and hemisphere of surgery. Results in digit span test were compared to 21 patients during awake craniotomies. Results: Word fluency was reduced to 30, 33, 47, and 87% of preoperative values 10, 30, 60 min and 24 h after extubation, respectively. Digit span was decreased to 41, 47, 55, and 86%. Performances were still significantly impaired 24 h after extubation, especially in elderly. Results of digit span test were not worse in patients with left hemisphere surgery. Significance of difference to baseline remained, when patients with left or frontal lesions, i.e., brain areas essential for these tests, were excluded from analysis. Time for trail making was increased by 87% at 1 h after extubation, and recovered within 24 h. In 21 patients undergoing awake craniotomies without pharmacological sedation, digit span was unaffected during intraoperative testing. Conclusion: Selected aspects of higher cognitive functions are compromised for up to 24 h after propofol anesthesia for craniotomy. Propofol and the direct effects of surgical resection on brain networks may be two major factors contributing (possibly jointly) to the observed deficits. Neurocognitive testing was unimpaired in patients undergoing awake craniotomies without sedation.

Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study.

BACKGROUND: Combined radiochemotherapy followed by maintenance chemotherapy with cisplatin, lomustine and vincristine within the NOA-07 study resulted in considerable short-term toxicity in adult medulloblastoma patients. Here we investigated the long-term impact of this treatment, focusing on neurocognitive functioning and health-related quality of life (HRQoL). METHODS: Neurocognitive functioning and HRQoL scores over time were determined, and differences between the post-treatment and follow-up assessments were calculated up to 18 months for neurocognition and 60 months for HRQoL. RESULTS: 28/30 patients were analyzed. The three preselected HRQoL scales (role, social and cognitive functioning) showed improved scores, to a clinically relevant extent (≥ 10 points), compared to post-treatment levels up to 30 months, but decreased afterwards. Z-scores for verbal working memory were worse during follow-up compared to post-treatment scores and remained impaired during 18 months follow-up (i.e. z-score below - 1 standard deviation). Attention was impaired post-treatment, and remained impaired to a clinically relevant extent during follow-up. Coordination/processing speed and lexical verbal fluency improved compared to post-treatment scores, and remained within the normal range thereafter. Other tests of verbal fluency were stable over time, with z-scores within the normal range. CONCLUSIONS: This long-term follow-up study showed that the NOA-07 treatment regimen was not associated with a deterioration in HRQoL in the post-treatment period. Verbal working memory deteriorated, while other neurocognitive domains did not seem to be impacted negatively by the treatment.

Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07).

Background: Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy. Methods: The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy. Results: Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock. Conclusions: Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

Influence of Formal Education on Cognitive Reserve in Patients with Multiple Sclerosis.

The concept of cognitive reserve (CR) and its influence on cognitive impairment has attracted increasing interest. One hundred twenty-eight patients with multiple sclerosis (MS) from Southern Germany were evaluated during the years 2000 to 2012. Twenty-seven neuropsychological (NP) tests were applied regarding basic cognitive functions, attention, executive functions, visual perception and construction, memory and learning, problem solving, and language. By this retrospective approach, a comprehensive NP profile of the investigated individuals was established. An effect of timespan of formal education on CR was observed. Enrichment by reading, physical activities, and challenging vocational practices had more profound effects in patients who had undergone a shorter educational period compared to a longer educational period. In summary, our study demonstrates that the advantage of longer formal education periods, compared to shorter formal education periods, can be counterbalanced by high frequencies of reading, physical activities, and challenging vocational practices in patients with MS.

The impact of sedation on brain mapping: a prospective, interdisciplinary, clinical trial.

BACKGROUND: During awake craniotomies, patients may either be awake for the entire duration of the surgical intervention (awake-awake-awake craniotomy, AAA) or initially sedated (asleep-awake-asleep craniotomy, SAS). OBJECTIVE: To examine whether prior sedation in SAS may restrict brain mapping, we conducted neuropsychological tests in patients by means of a standardized anesthetic regimen comparable to an SAS. METHODS: We prospectively examined patients undergoing surgery either under total intravenous anesthesia (TIVA) or under regional anesthesia with slight sedation (RAS). The tests included the DO40 picture-naming test, the digit span, the Regensburg Word Fluency Test, and the finger-tapping test. Each test was conducted 3 times for every patient in the TIVA and RAS groups, once before surgery and twice within about 35 minutes after the end of sedation. Patients undergoing AAA were examined preoperatively and intraoperatively. RESULTS: In the AAA group, no significant difference was found between preoperative and intraoperative test results. In the TIVA and RAS groups, postoperative tests showed worse results than preoperative tests. In most tests, patients improved from the first to the second postoperative test. CONCLUSION: Cognitive and motor performance were significantly influenced by prior sedation in the TIVA and RAS groups, but not in the AAA group. Therefore, prior sedation may be assumed to cause a change in the baselines, which may compromise brain mapping and thus endanger a patient's neurological outcome in the case of an SAS.

Awake craniotomies without any sedation: the awake-awake-awake technique.

BACKGROUND: Temporary anaesthesia or analgosedation used for awake craniotomies carry substantial risks like hemodynamic instabilities, airway obstruction, hypoventilation, nausea and vomiting, agitation, and interference with test performances. We tested the actual need for sedatives and opioids in 50 patients undergoing awake craniotomy for brain tumour resection in eloquent or motoric brain areas when cranial nerve blocks, permanent presence of a contact person, and therapeutic communication are provided. METHODS: Therapeutic communication was based on the assumption that patients in such an extreme medical situation enter a natural trance-like state with elevated suggestibility. The anaesthesiologist acted as a continuous guide, using a strong rapport, nonverbal communication, hypnotic suggestions, such as dissociation to a "safe place", and the reframing of disturbing noises, while simultaneously avoiding negative suggestions. Analgesics or sedatives were at hand according to the principle "as much as necessary, but not more than needed". RESULTS: No sedation was necessary for any of the patients besides for the treatment of seizures. Only two-thirds of the patients requested remifentanil, with a mean dosage of 96 µg before the end of tumour resection and a total of 156 µg. Hemodynamic reactions indicative of stress were mainly seen during nerve blockades and neurological testing. Postoperative vigilance tests showed equal or higher scores than preoperative tests. CONCLUSIONS: The main challenges for patients undergoing awake craniotomies include anxiety and fears, terrifying noises and surroundings, immobility, loss of control, and the feeling of helplessness and being left alone. In such situations, psychological support might be more helpful than the pharmacological approach. With adequate therapeutic communication, patients do not require any sedation and no or only low-dose opioid treatment during awake craniotomies, leaving patients fully awake and competent during the entire surgical procedure without stress. This approach can be termed "awake-awake-awake-technique".

"Imagine your neighbor mows the lawn": a pilot study of psychological sequelae due to awake craniotomy: clinical article.

OBJECT: Although it has been reported that awake neurosurgical procedures are well tolerated, the long-term occurrence of general psychological sequelae has not yet been investigated. This study assessed the frequency and effects of psychological symptoms after an awake craniotomy on health-related quality of life (HRQOL). METHODS: Sixteen patients undergoing an awake surgery were surveyed with a self-developed questionnaire, the Posttraumatic Stress Disorder Inventory For Awake Surgery Patients, which adopts the core components of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) posttraumatic stress disorder (PTSD) criteria. The mean time between surgery and data collection was 97.3 ± 93.2 weeks. Health-related quality of life was assessed with the 36-Item Short Form Health Survey. RESULTS: Forty-four percent of the patients stated that they had experienced either repetitive distressing recollections or dreams related to the awake surgery, 18.8% stated persistent avoidance of stimuli associated with the awake surgery, and symptoms of increased arousal occurred in 62.5%. Two patients presented with postoperative psychological sequelae resembling PTSD symptoms. Younger age at surgery and female sex were risk factors for symptoms of increased arousal. The experience of intense anxiety during awake surgery appears to favor the development of postsurgical PTSD symptoms, while recurrent distressing recollections particularly affect HRQOL negatively. CONCLUSIONS: In many cases awake craniotomy is necessary to preserve language and motor function. However, in some cases awake craniotomy can lead to postoperative psychological sequelae resembling PTSD symptoms. Therefore, possible long-term effects of an awake surgery should be considered and discussed with the patient when planning this type of surgery.

Aggressiveness in different presentations of cluster headache: results from a controlled multicentric study.

BACKGROUND: The hypothalamus has been discussed as a pivotal structure for both cluster headache (CH) and aggressiveness, but little is known about the extent of self-reported aggressiveness in patients with CH. PATIENTS AND METHODS: Twenty-six patients with chronic, 25 with active episodic and 22 with episodic CH outside the active period were examined interictally with a validated questionnaire quantifying factors of aggression and compared with 24 migraine patients and 31 headache-free volunteers. RESULTS: The ANOVA was significant for the subscale 'self-aggression/depression' (F(4, 123) = 5.771, p < 0.001) with significant differences between chronic and episodic CH and healthy volunteers. No significant changes were found for other subscales and the sum scale (F(4, 123) < 1.421, p > 0.230). Especially in the clinically most affected group of patients (chronic CH and active episodic CH), high levels of "self-aggression/depression" correlate with higher prevalence of depressive symptoms and higher impairment measured on an emotional and functional level. DISCUSSION: Self-aggressive and depressive cognitions with highest scores in chronic CH seem to be reactive as they correlate with depressive symptoms and impairment. They should be considered as an important therapeutic target since they impair the patient's life significantly.

A lightning strike to the head causing a visual cortex defect with simple and complex visual hallucinations.

The case of a 23-year-old mountaineer who was hit by a lightning strike to the occiput causing a large central visual field defect and bilateral tympanic membrane ruptures is described. Owing to extreme agitation, the patient was sent into a drug-induced coma for 3 days. After extubation, she experienced simple and complex visual hallucinations for several days, but otherwise largely recovered. Neuropsychological tests revealed deficits in fast visual detection tasks and non-verbal learning and indicated a right temporal lobe dysfunction, consistent with a right temporal focus on electroencephalography. At 4 months after the accident, she developed a psychological reaction consisting of nightmares, with reappearance of the complex visual hallucinations and a depressive syndrome. Using the European Cooperation for Lightning Detection network, a meteorological system for lightning surveillance, the exact geographical location and nature of the lightning strike were retrospectively retraced.

A lightning strike to the head causing a visual cortex defect with simple and complex visual hallucinations.

The case of a 23-year-old mountaineer who was hit by a lightning strike to the occiput causing a large central visual field defect and bilateral tympanic membrane ruptures is described. Owing to extreme agitation, the patient was set to a drug-induced coma for 3 days. After extubation, she experienced simple and complex visual hallucinations for several days, but otherwise recovered largely. Neuropsychological tests revealed deficits in fast visual detection tasks and non-verbal learning, and indicated a right temporal lobe dysfunction, consistent with a right temporal focus on electroencephalography. Four months after the accident, she developed a psychological reaction consisting of nightmares with reappearance of the complex visual hallucinations and a depressive syndrome. Using the European Cooperation for Lightning Detection network, a meteorological system for lightning surveillance, the exact geographical location and nature of the lightning flash were retrospectively retraced.

Long-term outcome after hemicraniectomy for space occupying right hemispheric MCA infarction.

OBJECTIVE: To examine the long-term prognosis in patients with 'malignant' supratentorial ischemia of the right hemisphere treated with hemicraniectomy, especially in respect to depression, with a focus on age as a possible predictor of outcome. METHODS: We performed a prospective, long-term, follow-up examination in 23 survivors of 32 patients (mortality 28.1%) treated with hemicraniectomy for malignant middle cerebral artery (MCA) infarction of the right hemisphere, who were identified in our data bank since 1993. Long-term was defined as at least 20 months after craniectomy. Outcome data consisted of the items functionality, depression and quality of life. Tests applied included the Barthel Index (BI), the modified Rankin Scale (mRS), Beck Depression Inventory (BDI) and stroke-specific quality of life (QoL) scale. RESULTS: Of the 23 patients 15 (65.2%) had a BI>or=60, 11 (47.8%) a mRS<4 and 9 (39.1%) a SS-QOL>or=60%, each representing a favourable outcome. In retrospect, 14 (60.9%) patients approved the surgery. Depression, i.e. a BDI>9, was diagnosed in 13 (56.5%) patients and 5 (38.5%) of them were treated with antidepressants. In a multiple linear regression analysis age at craniectomy was a predictor of a low BI (beta=-0.863; p=0.031), but not of the other outcome parameters. CONCLUSIONS: Depression is a common and rarely treated long-term complication after 'malignant' right hemispheric ischemia. While high age is a strong predictor of poor functional outcome, it has no impact on depression and retrospective approval of craniectomy.