Five-level cervical corpectomy for neurofibromatosis-associated spinal deformity: case report

Purpose

To describe a successful five-level cervical corpectomy and circumferential reconstruction in a patient with a plexiform neurofibroma causing a severe kyphotic deformity.

Methods

Case report.

Results

43-year-old man with history of Neurofibromatosis presented with signs and symptoms of myelopathy with spastic lower extremities and gait difficulties. Imaging studies demonstrated a severe kyphotic deformity of the cervical spine with associated cord compression secondary to an anteriorly positioned plexiform neurofibroma. Two-stage surgical procedure was designed to treat this lesion. Stage I consisted of tracheostomy placement, transmandibular, circumglossal approach to the anterior cervical spine, C2–C6 corpectomies, and C1–C7 reconstruction with a custom titanium cage/plate. Stage II consisted of suboccipital craniectomy, C1–C2 laminectomies, and occipital-cervical thoracic instrumented fusion (O-T8). There were no operative complications, but the patient did develop a small pulmonary embolism post-operatively treated with anticoagulation. Patient required two-weeks of inpatient rehabilitation following surgery. Gastrostomy tube and tracheostomy were successfully discontinued with preserved swallowing and respiratory function. Patient-reported outcome measurements revealed significant and sustained improvement post-operatively.

Conclusions

Five-level cervical corpectomy including C2 can be safely and successfully performed via a transmandibular, circumglossal approach. Circumferential reconstruction utilizing a custom anterior titanium cage and plate system manufactured from a pre-operative CT scan was utilized in this case. Long segment occipital-cervical-thoracic reconstruction is recommended in such a case. Using such a technique, improvement in myelopathy, correction of deformity, and improved quality of life can be achieved.

     

Cyclooxygenase inhibitors in urinary bladder cancer: in vitro and in vivo effects

More than 14,000 people die from invasive transitional cell carcinoma (TCC) of the urinary bladder yearly in the United States. Cyclooxygenase (COX)-inhibiting drugs are emerging as potential antitumor agents in TCC. The optimal in vitro or in vivo systems to investigate COX inhibitor antitumor effects have not been defined. The purpose of this study was to determine COX-1 and COX-2 expression and antitumor effects of COX inhibitors in human TCC cell lines (HT1376, RT4, and UMUC3 cells) and xenografts derived from those cell lines. COX-2 expression (Western blot, immunocytochemistry) was high in HT1376, modest in RT4, and absent in UMUC3 cells in vitro. Similarly, COX-2 expression was noted in RT4 but not UMUC3 xenografts. COX-2 expression in HT1376 xenografts was slightly lower than that observed in vitro. None of four COX inhibitors evaluated (celecoxib, piroxicam, valeryl salicylate, and NS398) reduced TCC growth in standard in vitro proliferation assays at concentrations that could be safely achieved in vivo (< or =5 micromol/L). Higher celecoxib concentrations (> or =50 micromol/L) inhibited proliferation and induced apoptosis in all three cell lines. Celecoxib or piroxicam treatment in athymic mice significantly delayed progression of HT1376 xenografts, which express COX-2, but not UMUC3 xenografts that lack COX-2 expression. In conclusion, standard in vitro assays were not useful in predicting COX inhibitor antitumor effects observed in vivo. Athymic mice bearing TCC xenografts provide a useful in vivo system for COX inhibitor studies. Results of this study provide justification for further evaluation of COX inhibitors as antitumor agents against TCC.     

Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures

INTRODUCTION: This study investigated whether two levels of mean arterial pressure (MAP) during cardiopulmonary bypass did influence per-operative fluid shifts. METHODS: Sixteen pigs underwent 60 minutes of normothermic cardiopulmonary bypass (CPB) followed by 90 minutes of hypothermic CPB. Eight animals had a MAP of 60-80mmHg by norepinephrine (HP group). Another 8 animals had a MAP of 40-45 mmHg by phentolamine (LP group). Blood chemistry, plasma/interstitial colloid osmotic pressures, plasma volume, fluid balance, fluid extravasation rate and tissue water content were measured or calculated. RESULTS: The plasma volume was significantly lower in the HP group compared with the LP group after 60 minutes of CPB. Net fluid balance was 0.18 (0.05) ml x kg(-1) x min(-1) in the HP group and 0.21 ml x kg(-1) x min(-1) in the LP group (P > 0.05) while fluid extravasation rate was 1.18 (0.5) and 1.13 (0.4) ml x kg(-1) x min(-1) in the HP group and the LP group during CPB (P > 0.05). CONCLUSION: Net fluid balance and fluid extravasation rate were similar in the animals with elevated and with lowered MAP during CPB.     

Identification of Subgroups of Schizophrenia Patients With Changes in Either Immune or Growth Factor and Hormonal Pathways

Schizophrenia is a heterogeneous disorder normally diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. However, these criteria do not necessarily reflect differences in underlying molecular abnormalities of the disorder. Here, we have used multiplexed immunoassay analyses to measure immune molecules, growth factors, and hormones important to schizophrenia in acutely ill antipsychotic-naive patients (n = 180) and matched controls (n = 398). We found that using the resulting molecular profiles, we were capable of separating schizophrenia patients into 2 significantly distinct subgroups with predominant molecular abnormalities in either immune molecules or growth factors and hormones. These molecular profiles were tested using an independent cohort, and this showed the same separation into 2 subgroups. This suggests that distinct abnormalities occur in specific molecular pathways in schizophrenia patients. This may be of relevance for intervention studies that specifically target particular molecular mechanisms and could be a first step to further define the complex schizophrenia syndrome based on molecular profiles.Key words: schizophrenia, subtypes, diagnosis, molecular profiling, immune factors, growth factors     

Mood Instability and Psychosis: Analyses of British National Survey Data

Background: We used British national survey data to test specific hypotheses that mood instability (1) is associated with psychosis and individual psychotic phenomena, (2) predicts the later emergence of auditory hallucinations and paranoid ideation, and (3) mediates the link between child sexual abuse and psychosis. Methods: We analyzed data from the 2000 and 2007 UK national surveys of psychiatric morbidity (N = 8580 and 7403, respectively). The 2000 survey included an 18-month follow-up of a subsample (N = 2406). Mood instability was assessed from the Structured Clinical Interview for DSM-IV Axis II (SCID-II) questionnaire. Our dependent variables comprised auditory hallucinations, paranoid ideation, the presence of psychosis overall, and a 15-item paranoia scale. Results: Mood instability was strongly associated in cross-sectional analyses with psychosis (2000: OR: 7.5; 95% CI: I 4.1–13.8; 2007: OR: 21.4; CI: 9.7–41.2), paranoid ideation (2000: OR: 4.7; CI: 4.1–5.4; 2007: OR: 5.7; CI: 4.9–6.7), auditory hallucinations (2000: OR: 3.4; CI: 2.6–4.4; 2007: OR 3.5; CI: 2.7–4.7), and paranoia total score (2000: Coefficient: 3.6; CI: 3.3–3.9), remaining so after adjustment for current mood state. Baseline mood instability significantly predicted 18-month inceptions of paranoid ideation (OR: 2.3; CI: 1.6–3.3) and of auditory hallucinations (OR: 2.6; CI: 1.5–4.4). Finally, it mediated a third of the total association of child sexual abuse with psychosis and persecutory ideation and a quarter of that with auditory hallucinations. Conclusions: Mood instability is a prominent feature of psychotic experience and may have a role in its genesis. Targeting mood instability could lead to innovative treatments for psychosis.Key words: epidemiology, psychopathology, paranoia, auditory hallucination, child sexual abuse     

Self-disturbances in Schizophrenia: History,Phenomenology, and Relevant Findings From Research on Metacognition

With a tradition of examining self-disturbances (Ichstörungen) in schizophrenia, phenomenological psychiatry studies the person’s subjective experience without imposing theoretical agenda on what is reported. Although this tradition offers promising interface with current neurobiological models of schizophrenia, both the concept of Ichstörung and its history are not well understood. In this article, we discuss the meaning of Ichstörung, the role it played in the development of the concept of schizophrenia, and recent research on metacognition that allows for the quantitative study of the link between self-disturbance and outcome in schizophrenia. Phenomenological psychiatrists such as Blankenburg, Binswanger, and Conrad interpreted the Ichstörung as disturbed relationship to self and others, thus challenging recent efforts to interpret self-disturbance as diminished pure passive self-affection, which putatively “explains” schizophrenia and its various symptoms. Narrative is a reflective, embodied process, which requires a dynamic shifting of perspectives which, when compromised, may reflect disrupted binding of the components of self-experience. The Metacognition Assessment Scale—abbreviated as MAS-A—suggests that persons with schizophrenia tend to produce narratives with reductions in the binding processes required to produce an integrated, embodied self within narrated life stories, and in interactive relationships with others.Key words: Ichstörung (self-disturbance), embodied cognition, metacognition, narrative, phenomenological psychiatry, psychosis, quality of life, recovery     

Misperceptions of Facial Emotions Among Youth Aged 9–14 Years Who Present Multiple Antecedents of Schizophrenia

Similar to adults with schizophrenia, youth at high risk for developing schizophrenia present difficulties in recognizing emotions in faces. These difficulties might index vulnerability for schizophrenia and play a role in the development of the illness. Facial emotion recognition (FER) impairments have been implicated in declining social functioning during the prodromal phase of illness and are thus a potential target for early intervention efforts. This study examined 9- to 14-year-old children: 34 children who presented a triad of well-replicated antecedents of schizophrenia (ASz), including motor and/or speech delays, clinically relevant internalizing and/or externalizing problems, and psychotic-like experiences (PLEs), and 34 typically developing (TD) children who presented none of these antecedents. An established FER task (ER40) was used to assess correct recognition of happy, sad, angry, fearful, and neutral expressions, and facial emotion misperception responses were made for each emotion type. Relative to TD children, ASz children presented an overall impairment in FER. Further, ASz children misattributed neutral expressions to face displaying other emotions and also more often mislabeled a neutral expression as sad compared with healthy peers. The inability to accurately discriminate subtle differences in facial emotion and the misinterpretation of neutral expressions as sad may contribute to the initiation and/or persistence of PLEs. Interventions that are effective in teaching adults to recognize emotions in faces could potentially benefit children presenting with antecedents of schizophrenia.Key words: emotion recognition, high risk, child and adolescent psychopathology, social functioning, psychotic-like experiencesPeople with schizophrenia display a marked impairment in recognizing emotions in the faces of others, particularly anger, sadness, and fear, and less difficulty recognizing happy expressions.^1,2 Facial emotion recognition (FER) difficulties are associated with poor social functioning³ and have implications for the development, course, and outcome of the disorder.⁴ Yet, interventions to improve FER performance (eg, Training of Affect Recognition)⁵ can reduce these deficits and elicit generalized improvement in other social cognitive domains.⁶FER impairments are apparent not only among individuals with chronic schizophrenia (for review see Kohler et al 2010)² but also among individuals experiencing a first episode of psychosis^7,8 and among unaffected adolescent (though only for neutral facial expressions)⁹ and adult first-degree relatives of individuals with schizophrenia.¹⁰ Thus, abnormalities in FER are present at illness onset and may also index vulnerabil ity for schizophrenia. Prospective studies following individuals at elevated risk for developing schizophrenia are needed to determine the extent to which impairments of FER precede illness and represent potential targets for early intervention. Among symptomatic, help-seeking individuals meeting ultra-high risk (UHR) criteria for psychosis,^7,8,11–13 evidence for FER impairments is mixed. Two studies reported FER impairments relative to healthy participants,^7,11 while another study indicated specific difficulties in correctly identifying neutral expressions.¹³ A study of a large British birth cohort comprising 5267 children reported no association between FER at 8 years and subclinical psychotic symptoms at 12 years.¹⁴ By contrast, a recent cross-sectional study of 748 children aged 10–13 years indicated that those reporting psychotic-like experiences (PLEs) on questionnaires were poorer at recognizing facial emotional expressions, primarily sadness.¹⁵ Unfortunately, as with many previous FER studies, no information was provided about the nature of the facial emotion misperceptions committed when processing facial expressions. Though PLEs in childhood are significantly associated with later psychotic illness,^16,17 they are also associated with an increased risk of anxiety disorders¹⁶ and other psychiatric disorders including affective disorders, drug use disorders, and personality disorders,¹⁸ albeit to a lesser extent. Thus, PLEs constitute a relatively nonspecific marker of risk for subsequent psychiatric disorders. Further, cross-sectional data from the general population indicate significant comorbidity of PLEs with emotional and behavioral problems,^19,20 implying that the observed relationship between PLEs and FER reported by Roddy et al¹⁵ might reflect the presence of unreported internalizing and/or externalizing psychopathology.To better characterize the nature of FER associated with schizophrenia, several studies have examined facial emotion misperceptions. Relative to healthy adults, individuals with schizophrenia more often mislabel negative emotions to faces displaying no or neutral expressions.^21,22 Adolescent relatives of individuals with schizophrenia, compared with adolescents from healthy families, also more often incorrectly label neutral expressions as displaying negative emotions, predominantly mislabeling them as sad.⁹ Among individuals with schizophrenia, and individuals at high risk for psychosis,²³ functional imaging has revealed hyperactivation of the amygdala during the processing of neutral expressions, which could reflect emotional salience being assigned to neutral stimuli.²⁴ It has been suggested that the tendency to misinterpret neutral facial expressions as displaying emotion may contribute to the development of positive symptoms in schizophrenia.²³ Previous research indicates that facial emotion misperceptions might constitute the cognitive mechanism contributing to the social impairment that characterizes UHR samples¹³ and is a critical component to understanding FER difficulties in samples at risk for schizophrenia.Until recently, there has been no practical method for identifying children who are at elevated risk for schizophrenia. Despite the high heritability of schizophrenia, only approximately one-third of individuals with schizophrenia have a first- or second-degree relative with the illness. Consequently, a positive family history identifies only a subset of children who will develop the illness.²⁵ Prospective investigations of birth cohorts have demonstrated consistently that, by middle childhood, individuals who later developed schizophrenia presented delays in motor and language development; disturbances in social, emotional, and behavioral functioning; and PLEs.¹⁷ Based on this evidence, we developed questionnaires, to be completed by children aged 9–12 years and their primary caregiver, to identify children who present a triad of these replicated antecedents of schizophrenia (ASz).^26,27 We defined ASz to include (1) early speech and/or motor developmental delays/abnormalities; (2) social, emotional, and/or behavioral problems in the clinical range; and (3) PLEs. It is thought that the identification of children who present multiple antecedents of schizophrenia that have been replicated in prospective longitudinal studies will offer greater sensitivity and specificity for later development of schizophrenia than any one antecedent.We are currently following the development of ASz children to determine the specificity and sensitivity of the triad of antecedents for later schizophrenia development. We anticipate that some ASz children will develop schizophrenia and spectrum disorders, some will develop other disorders, and others will remain healthy. In the interim, our investigations have shown that ASz children, compared with typically developing (TD) children who present no antecedents and no family history of schizophrenia or a spectrum disorder, are characterized by features observed among adults with schizophrenia including (1) deficits in performance on standardized intelligence and neuropsychological tests of executive function and memory,²⁸ (2) dyskinetic movement abnormalities,²⁹ (3) reduction in the amplitude of the error-related negativity event-related potential component generated in the anterior cingulate that indexes internal monitoring of behavior,³⁰ and (4) structural brain abnormalities in the superior/middle temporal gyri.³¹ Further, among children aged 9–12 years, two-thirds (69%) of those presenting with the triad of antecedents report distress and/or functional impairment associated with their PLEs.²⁷This study sought to determine whether ASz children present FER difficulties similar to those reported among individuals with schizophrenia and at-risk youth, after accounting for intelligence quotient (IQ) differences between ASz and TD groups,²⁸ which may contribute to FER performance. The study examined overall performance on FER tasks, as well as the specific nature of facial emotion misperceptions. We hypothesized that ASz children would be less accurate than TD children in identifying emotions in facial expressions and that they would more often mislabel neutral faces with other emotion expressions. In particular, we anticipated that ASz children would misidentify neutral expressions as sad, as was reported in a study of youth with family histories of schizophrenia using the same FER task.⁹     

Combining Self-Affirmation and Implementation Intentions: Evidence of Detrimental Effects on Behavioral Outcomes

Background

There is limited evidence that self-affirmation manipulations can promote health behavior change.

Purpose

The purpose of this study was to explore whether the efficacy of a self-affirmation manipulation at promoting exercise could be enhanced by an implementation intention intervention.

Methods

Participants (Study 1?N?=?120, Study 2?N?=?116) were allocated to one of four conditions resulting from the two (self-affirmation manipulation: no affirmation, affirmation) by two (implementation intention manipulation: no implementation intention, implementation intention) experimental design. Exercise behavior was assessed 1 week post-intervention.

Results

Contrary to prediction, those participants receiving both manipulations were significantly less likely to increase the amount they exercised compared to those receiving only the self-affirmation manipulation.

Conclusion

Incorporating an implementation intention manipulation alongside a self-affirmation manipulation had a detrimental effect on exercise behavior; participants receiving both manipulations exercised significantly less in the week following the intervention.