Do we have the right PROMs for measuring outcomes in lumbar spinal surgery?

PURPOSE: Patient-reported outcome measures (PROMs) have become an important part of routine auditing of outcomes in spinal surgery in the UK. PROMs can be used to help assess the quality of care provided by surgical units by determining the comparative health status of patients, before and after surgery. This study was designed to review the PROMs used to assess outcomes in spinal surgery and to determine if they are fit for the purpose. METHODS: A systematic literature search was undertaken to identify studies that reported PROMs data following lumbar spinal surgery. The PROMs that were used in each study were recorded and a separate search was undertaken to determine the evidence regarding the validity of each measure. RESULTS: The initial search identified 1142 abstracts, which were reduced through de-duplication, filtering and review to 58 articles, which were retrieved and reviewed in full. The search identified that the majority of studies used either the Oswestry Disability Index (ODI), SF-36, Roland-Morris Disability Questionnaire (RMDQ) and EQ-5D along with visual analogue scales or numeric rating scales for back and leg pain. CONCLUSIONS: The consistent use of PROMs supports the comparison of outcomes from different studies, although there was minimal evidence regarding the specificity and sensitivity of these measures for use with lumbar spinal patients. Our review highlights the need to determine a consensus regarding the use and reporting of outcome measures within the lumbar spine literature.

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

The in vitro antibiofilm activity of selected culinary herbs and medicinal plants against Listeria monocytogenes.

AIMS: The antibiofilm activity of extracts obtained from selected herbs, spices, beverages and commercially important medicinal plants was investigated on Listeria monocytogenes. METHODS AND RESULTS: The growth and development of the biofilm was assessed using the crystal violet (CV) assay. The respiratory activity was assessed using the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The majority of extracts tested prevented cell adhesion to the polyvinyl chloride (PVC) surface. Seven of the 15 extracts reduced biofilm adhesion of both the clinical and the type strains by at least 50%. In contrast, inhibition of a preformed biofilm was more difficult to achieve, with only three extracts (Rosmarinus officinalis, Mentha piperita and Melaleuca alternifolia) inhibiting the growth of both strains by at least 50%. CONCLUSIONS: Although most extracts were able to reduce initial cell attachment, inhibition of growth in a preformed biofilm was more difficult to achieve. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to reduce biofilm biomass as shown by several plant extracts warrants further investigation to explore the use of natural products in antibiofilm adhesion.

Taste pathways in rat brainstem.

By means of a combination of electrophysiological and anatomical procedures, the projections of the anterior portion of the solitary nucleus were traced to the parabrachial nuclei in the pons, structures hitherto not considered to be included in the taste pathway. Responses to taste stimuli were recorded from this pontine area. Lesions in the pontine taste area resulted in degeneration of fibers reaching the lingual area in the thalamus.

Kernel Fisher discriminant for shape-based classification in epilepsy.

In this paper, we present the application of kernel Fisher discriminant in the statistical analysis of shape deformations that indicate the hemispheric location of an epileptic focus. The scans of two classes of patients with epilepsy, those with a right and those with a left anterior medial temporal lobe focus (RATL and LATL), as validated by clinical consensus and subsequent surgery, were compared to a set of age and sex matched healthy volunteers using both volume and shape based features. Shape-based features are derived from the displacement field characterizing the non-rigid deformation between the left and right hippocampi of a control or a patient as the case may be. Using the shape-based features, the results show a significant improvement in distinguishing between the controls and the rest (RATL and LATL) vis-a-vis volume-based features. Using a novel feature, namely, the normalized histogram of the 3D displacement field, we also achieved significant improvement over the volume-based feature in classifying the patients as belonging to either of the two classes LATL or RATL, respectively. It should be noted that automated identification of hemispherical foci of epilepsy has not been previously reported.

Exploiting human anatomical variability as a link between genome and cognome.

Although talents and disabilities appear to run in families, direct links between genes and cognitive ability are difficult to establish. Investigators are currently searching for intermediate phenotypes with plausible links to both genome and cognome (the cognitive phenotype). Cortical anatomy could provide one such intermediate phenotype. Variation in cortical size, asymmetry and sulcal pattern is influenced by genetic variation in neurotrophic factors and can predict variation in verbal and mathematical talent. Anecdotal evidence suggests that individuals with a rare morphological variant of Sylvian fissure sometimes have superior visualization ability combined with verbal deficits. Documentation of such 'cognitive cortical syndromes' might prove as genetically informative as the identification of dysmorphic syndromes associated with mental retardation. A necessary prerequisite for the establishment of such syndromes is a reliable technique for the identification of cortical patterns. Recent technical advances in software for automatically labeling and measuring cortical sulci now provide the possibility of establishing standard measures for their shape, size and location. Such measures are a prerequisite for genetic studies of cortical patterns that could illuminate the neurodevelopmental pathways by which genes affect cognitive ability.

Lymphocyte blastogenesis induced by potassium chloride extracts of allogeneic breast carcinoma and lymphoid cells.

Lymphocytes from cancer patients and normal individuals demonstrated blastogenesis with allogeneic potassium chloride (3 M KCl) extracts of breast carcinoma cells. Normal individuals reacted with a greater frequency and stronger blastogenic responses to tumor extracts than did breast carcinoma patients; allogeneic extracts may have elicited recognition of normal alloantigens rather than tumor-associated antigens. Normal individuals also responded to 3 M KCl extracts of allogeneic pooled normal leukocytes, normal breast tissue, and other cancers, but did not react to extracts of autologous leukocytes.

Cell-mediated immune responses of breast cancer patients to autologous tumor-associated antigens.

Lymphocyte proliferation assays with autologous tumor material in mixed leukocyte-tumor interactions (MLTI) were employed to monitor tumor-associated cell-mediated immune responses of peripheral blood lymphocytes from patients with carcinoma of the breast. In addition, leukocyte migration inhibition (LMI) assays were employed to compare reactivity to autologous breast-tumor extracts versus allogeneic breast-tumor extracts. Positive lymphoproliferative responses to tumor-associated antigens (TAA) were observed in the MLTI assay with the use of either intact autologous tumor cells or crude extracts (in mug and ng quantities) in 12 of 34 (35%) breast cancer patients studied. Positive reactivity to tumor, but not to normal tissue of reactive patients, was observed in repeated assays. Finally, patients demonstrating positive MLTI responses to autologous tumor extracts likewise responded in LMI assays to these same autologus extracts as well as to allogeneic breast-tumor extracts, but not to non-breast-tumor extracts. Thus breast tumors appeared to possess common TAA among both male and female patients.

Successful silver impregnation of degenerating axons after long survivals in the human brain.

Degenerating axons in the human brain were successfully impregnated with reduced silver methods. The appearance of degenerating fibers did not differ markedly with survival times of three weeks and two, six, and twelve years following cerebral infarction or contusion of the brain. Impregnated fibers were found only along the appropriate corticofugal pathways. Electron microscopic examination of Vibratome-cut, silver-stained sections demonstrated silver deposition almost exclusively within axon fragments. Previous studies using anterograde degeneration methods in the human brain have limited their choice of cases to those with short periods of survival. Relaxing the restriction of short survival times extends the range of cases which can be used to study neural connections which may be unique to, or different in, the human brain.

Cumulative effect of anatomical risk factors for schizophrenia: an MRI study.

BACKGROUND: Although schizophrenic and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between groups are low. This study investigated the cumulative effect of deviant brain structure on diagnosis. METHODS: Hemisphere and third ventricle volume and the normalized (Talairach) location of three association cortex sulcal landmarks were measured on high-resolution MRI scans in 37 male patients with schizophrenia and 33 male control subjects matched on age, handedness, and parental socioeconomic status. RESULTS: While there were few group differences on individual anatomical measures, the 10 variables reliably discriminated between the two groups when used in concert in a discriminant function analysis (F[10.59] = 3.6, p < .0009) with 77% of the subjects correctly classified. Five of the measures (left posterior cingulate, left inferior frontal sulcus, right sylvian fissure, and left and right halves of the third ventricle) correlated significantly with the discriminant function (p < .005). CONCLUSIONS: This is the first study to demonstrate that schizophrenics can be distinguished from matched controls on the basis of brain anatomy alone. The risk of schizophrenia may depend on the total amount of neural deviance, rather than on anomalies in a single structure or circuit.

Developmental changes in olfactory bulb projections revealed by degeneration argyrophilia.

The maturation of the main and accessory olfactory bulb projections to the ventral forebrain of the golden hamster has been traced by using the Fink-Heimer silver technique to stain degenerating axons and terminal arborizations after bulbectomy at different ages between birth and 33 days. In the youngest pups, long-lasting degeneration argyrophilia (LLDA) is found in two regions of prepiriform cortex: at the level of the rostral tubercle and rostral amygdala. By five days of age the caudal region exhibiting a long-lasting degeneration reaction extends from the middle of the olfactory tubercle to the middle of the amygdala. The olfactory tubercle, medial and cortical amygdala and entorhinal cortex subsequently develop substantial LLDA at ages varying between 9 and 13 days. In a previous study (Leonard, '74b) the onset of LLDA in optic tract terminals in the superior colliculus was found to coincide with the age of eye opening and the onset of a stage of rapid snyapse formation. Since different olfactory responses appear at different times during the golden hamster pup's first two weeks of postnatal life, it seems possible that the onset of LLDA in different regions of the olfactory projection at different ages may be related to the onset of different specific olfactory functions.

Central control of song in the canary, Serinus canarius.

We have traced central nervous pathways controlling bird song in the canary using a combination of behavioral and anatomical techniques. Unilateral electrolytic brain lesions were made in adult male canaries whose song had been previously recorded and analysed on a sound spectrograph. After several days of postoperative recording, the birds were sacrificed and their brains processed histologically for degeneration staining with the Fink-Heimer technique. Although large lesions in the neostriatum and rostral hyperstriatum had no effect on song, severe song deficits followed damage to a discrete large-celled area in the caudal hyperstriatum ventrale (HVc). Degenerating fibers were traced from this region to two other discrete nuclei in the forebrain: one in the parolfactory lobe (area X, a teardrop-shaped small-celled nucleus); and a round large-celled nucleus in the archistriatum (RA). Unilateral lesion of X had no effect on song; lesions of RA, however, caused severe song deficits. Degenerating fibers from RA joined the occipitomesencephalic tract and had widespread ipsilateral projections to the thalamus, nucleus intercollicularis of the midbrain, reticular formation, and medulla. It is of particular interest that direct connections were found onto the cells of the motor nucleus innervating the syrinx, the organ of song production. Unilateral lesions of n. intercollicularis (previously implicated in the control of vocal behavior) had little effect on song. One bilateral lesion of HVc resulted in permanent (9 months) and complete elimination of the audible components of song, although the bird assumed the posture and movements typical of song. Preliminary data suggest that lesions of the left hemisphere result in greater deficits than lesions of the right one. This finding is consistent with earlier reports that the left syrinx controls the majority of song components. Results reported here suggest a localization of vocal control in the canary brain with an overlying left hemispheric dominance.

Morphologic cerebral asymmetries and handedness. The pars triangularis and planum temporale.

OBJECTIVE: To explore the relationship between morphologic cerebral asymmetries of the pars triangularis (PTr) and the planum temporale (PT) measured on three-dimensional, gradient-echo, magnetic resonance imaging scans of healthy right- and left-handed subjects. DESIGN: (Blinded) comparison of healthy right- and left-handed subjects who underwent magnetic resonance imaging. SETTING: The Seimens 1-T Magnetom (Seimens, Iselin, NH) at the University of Florida Health Science Center, Gainesville. SUBJECTS: Healthy right-handed (n = 8) and left-handed (n = 8) subjects matched for age, sex, and educational level. MAIN OUTCOME MEASURES: (1) Average length of the PTr (anterior ascending and anterior descending rami), (2) average length of the PT, (3) asymmetry quotients ([left-right]/[(left+right) (0.5)]) of the PTr and PT, and (4) combined asymmetry quotients of the PTr and PT. RESULTS: There was a significant leftward asymmetry of the PTr and PT in the right-handed subjects, but there was no significant asymmetry in the left-handed subjects. When the combined asymmetry quotient of the PTr and PT was calculated, the right-handed subjects had a leftward asymmetry (87.5% [n = 7]) or left was equal to right (12.5% [n = 1]), and the left-handed subjects had a leftward asymmetry (62.5% [n = 5]), left was equal to right (12.5% [n = 1]), or a rightward asymmetry (25% [n = 2]). In the left-handed subjects, writing posture seemed to predict these combined asymmetry quotients, ie, left-handed subjects using an inverted writing posture had a leftward asymmetry and left-handed subjects using a non-inverted writing posture had a rightward asymmetry of the perisylvian speech-language regions. CONCLUSIONS: On three-dimensional, gradient-echo, magnetic resonance imaging scans, we found a significant leftward asymmetry of the PTr and PT. When the groups were divided into right- and left-handed subjects, the former had a significant leftward asymmetry of the PTr and PT, while the latter did not. Measurements of the PTr and PT appear to be important indexes of the known functional asymmetries of the perisylvian speech-language regions.

Anomalous cerebral structure in dyslexia revealed with magnetic resonance imaging.

OBJECTIVE: To develop quantitative methods for identifying cerebral anomalies on magnetic resonance images of subjects with language disorders and other learning disabilities. DESIGN: Partially blinded comparison of subjects with dyslexia, unaffected relatives, and a control group balanced for age and socioeconomic status. Criterion standard: clinical diagnosis of dyslexia by physician or learning disabilities specialist on the basis of clinical assessment and family history. SETTINGS: Hospital pediatric neurology clinic and private reading clinic. VOLUNTEERS: individuals with dyslexia (seven male and two female, aged 15 to 65 years) from professional families; unaffected first- and second-degree relatives (four male and six female, aged 6 to 63 years) available in the geographical area; and controls (five male and seven female, aged 14 to 52 years). INTERVENTIONS: Gradient echo three-dimensional scan in Seimens 1-Tesla Magnetom; 128 1.25-mm consecutive sagittal images. MAIN OUTCOME MEASURES: (1) Average length of the temporal (T) and parietal (P) banks of the planum temporale; (2) interhemispheric coefficients of asymmetry for T and P banks: Left-Right interhemispheric coefficients of asymmetry = (L-R)/[(L+R)/2]; (3) intrahemispheric coefficients of asymmetry = (T-P)/[(T+P)/2]; and (4) qualitative assessment of gyral variants in the parietotemporal operculum. RESULTS: All groups had left-sided asymmetry for the temporal bank and right-sided asymmetry for the parietal bank. The group with dyslexia had exaggerated asymmetries, owing to a significant shift of right planar tissue from the temporal to parietal bank. They also had a higher incidence of cerebral anomalies bilaterally (subjects with dyslexia, six of nine; relatives, two of 10; and controls, zero of 12). CONCLUSIONS: Quantitative assessment of high-resolution magnetic resonance images can reveal functionally relevant variations and anomalies in cerebral structure. Further refinement of these measurement techniques should improve the diagnosis, classification, and treatment of language disorders and other learning disabilities.

Digitizing the moving face during dynamic displays of emotion.

Humans typically decode facial signals during dynamic interactions in which the face moves. In this study, we digitized real time video signals in order to examine movement asymmetries across the face during emotional and nonemotional expressions. Forty dextral males were tested. For each expression, a 400 ms video segment was analyzed for changes in signal value (pixel intensity) over consecutive frames. The upper and lower face regions were examined separately due to differences in the cortical enervation of facial muscles in the upper (bilateral) vs lower face (contralateral). Results revealed distinctly different movement asymmetries over the lower and upper hemiface. In the upper face, more movement occurred over the right side for most facial expressions, regardless of emotionality. The latter finding questions the assumption that muscles of the upper face are symmetrical and/or bilaterally enervated in a symmetrical manner. In the lower face, negative expressions linked to fight-flight emotions (i.e. fear, anger) were associated with greater left sided movement, whereas happiness tended to be associated with more right sided movement. No consistent pattern of movement asymmetry occurred for nonemotional expressions. Although the valence-related movement asymmetries in the lower face are consistent with neuropsychological models of emotional expressivity, it remains unclear whether they reflect activation or inhibitory hemispheric mechanisms. Taken together, these data suggest that multiple factors may contribute to expressive movement asymmetries of the face.

Planum temporale asymmetry and language dominance.

Language is lateralized to the left hemisphere in most individuals, and leftward asymmetry of the planum temporale has been reported in postmortem and imaging studies. In this study we measured the planum temporale on magnetic resonance imaging (MR) scans of patients (11 right-handers, 1 non-right-hander) who had selective hemispheric anesthesia or Wada testing performed for language lateralization. All subjects who had language lateralized to the left hemisphere (11 right-handers) had a leftward asymmetry of the planum temporale. One subject who had language lateralized to the right hemisphere (non-right-hander) had a strong rightward asymmetry of the planum temporale. These data suggest that planum temporale asymmetries determined by MR are associated with language dominance and may predict language laterality.

The terminal nerve projects centrally in the hamster.

The projections of the peripheral and intracerebral portions of the hamster terminal nerve were examined with lesion and immunocytochemical techniques. After transection, proximal processes of the terminal nerve accumulate luteinizing hormone-releasing hormone-immunoreactive material, while the distal processes disintegrate and are no longer stained. It thus becomes possible to determine the direction of conduction of terminal nerve axons. The results of transection at the level of the cribriform plate, along the olfactory bulb, and in the ventral forebrain were all consistent in indicating a centripetal direction of conduction. Immunoreactive material collected distal to the lesion at each of these levels. All peripheral lesions eliminated processes coursing into and through the terminal ganglion at the base of the ventral forebrain. These lesions left intact, however, the terminal ganglion projections to the accessory olfactory bulb and ventral forebrain. These results indicate a centripetal projection from terminal neurons in the nasal cavity, along the olfactory bulbs and within the terminal ganglion to successively more caudal levels. This suggests that neural messages are conveyed from nasal cavity to the brain through this route. Because immunoreactive fibers were found within the sensory epithelium of the vomeronasal organ a sensory and/or sensory modulatory action is suggested.

Acetylcholinesterase and luteinizing hormone-releasing hormone distinguish separate populations of terminal nerve neurons.

The terminal nerve is composed of a morphologically heterogeneous population of unipolar, bipolar and multipolar neurons located in the nasal and intracranial cavities of vertebrates. The question has arisen as to whether these neurons are neurochemically heterogeneous and therefore possibly functionally different as well. Among the substances localized in the terminal nerve are acetylcholinesterase and luteinizing hormone-releasing hormone-like immunoreactive material. We have developed a double-label procedure, combining immunocytochemistry and enzyme histochemistry to determine whether these two substances are localized within different populations of terminal nerve neurons. Compatibility of the two procedures was accomplished by modifications of the fixative and primary antibody solutions. In the immunocytochemical step, the avidin-biotin-peroxidase complex coupled to a new chromogen, Chromo-red, produced a bright red reaction product in neurons containing luteinizing hormone-releasing hormone-like material. This reaction product was easily differentiated from the black silver-intensified acetylcholinesterase label. In both neonatal and adult preparations, a large population of terminal neurons contained the acetylcholinesterase label only, whereas a smaller population contained both acetylcholinesterase and luteinizing hormone-releasing hormone-like material. The acetylcholinesterase-containing population of neurons was concentrated peripherally and included multipolar neurons. In contrast neurons with the two substances co-localized were unipolar or bipolar and were concentrated centrally. The simultaneous visualization of acetylcholinesterase and luteinizing hormone-releasing hormone-like material in the same tissue section enable the differentiation of two separate neurochemically defined populations of terminal neurons. The distribution of these two neuronal types was the same in neonatal and adult animals. These data provide support for a functional diversity of terminal neurons.

Magnetic resonance imaging of cerebral anomalies in subjects with resistance to thyroid hormone.

OBJECTIVE: Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. METHOD: Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of six contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl's transverse gyri (primary auditory cortex) were noted. RESULTS: There was a significantly increased frequency of anomalous Sylvian fissures in the left hemisphere in males with RTH (AM: 70%; AF: 30%; UM: 28% UF: 28%). Also, there was an increased frequency of anomalous Sylvian fissures on the left combined with multiple Heschl's gyri in either hemisphere in males with RTH (AM: 50%; AF: 9%; UM: 6%; UF: 0%). However, RTH subjects with anomalies did not have an increased frequency of ADHD as compared with RTH subjects with no anomalies. CONCLUSIONS: Abnormal thyroid hormone action in the male fetus early during brain development may be associated with grossly observable cerebral anomalies of the left hemisphere. The effects of mutations in the thyroid receptor beta gene provide a model system for studying the complex interaction of genetic and nongenetic factors on brain and behavioral development.

Angelman and Prader-Willi syndrome: a magnetic resonance imaging study of differences in cerebral structure.

Recent improvements in magnetic resonance imaging techniques now allow the developing brain to be visualized in sufficient detail to perform "in vivo neuropathology." In this study we compared the cortical morphology in six children with Angelman and four with Prader-Willi syndrome. These two syndromes are of special interest because, although they are both caused by deletions in the same region of chromosome 15, Angelman children are far more severely affected, and do not speak. We measured the length of the banks of the Sylvian fissure in a gapless series of thin sagittal images. Angelman children had a significantly larger proportion (75%) of anomalous fissures than the Prader-Willi children (12%). Anomalous cortical growth could result from mistimed expression and recognition of macromolecules involved in axonal guidance, target recognition, and pruning. We hypothesize that misrouting of long projection axons may be related to the Sylvian fissure anomalies and the language disorder in Angelman syndrome.