Concussion (Post Concussion Syndrome)
Summary: Despite concussions being treated as acute or self-limited, many continue to have effects. An ongoing problem is the acceptance by both patients and caregivers that the new level of functioning is "normal."
NeuroRehabilitation. 2011 Jan 1;29(4):317-29.
Etiology of the post-concussion syndrome: Physiogenesis and psychogenesis revisited.
Silverberg ND, Iverson GL.
G.F. Strong Rehab Centre, Vancouver, Canada Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, Canada.
In his seminal article, Physiogenesis and Psychogenesis in the 'Post-Concussional Syndrome,' Lishman (1988) proposed that neurobiological factors account for the development of the post-concussion syndrome and psychological factors become primarily responsible for maintaining it in the chronic phase. Over the 20 years that followed, researchers have advanced our understanding of the etiology of the post-concussion syndrome. Our review of this evidence suggests that neurobiological and psychological factors play a causal role in post-concussion symptoms from the outset, and thus, Lishman's causal model should be updated. If we can clinically identify individuals on a trajectory of poor recovery in the acute post-injury stage, then we can direct secondary prevention towards modifiable risk factors.
Semin Clin Neuropsychiatry. 1997 Jul;2(3):177-187.
Minor Traumatic Brain Injury: A Review of Physiogenesis and Psychogenesis.
Memory Disorders Research Center, Boston, MA, USA
Mild Traumatic Brain Injury (TBI) has a well defined neuropathology. The natural history of recovery is well understood. The appropriate somatic and psychological treatments are known. Nevertheless, a subset of patients do not recover and may even worsen with time-the persistent post concussive syndrome (PPCS). They are frequently involved in litigation. The risk factors for PPCS are known, and management strategies are available. There is a great risk of inappropriately attributing PPCS to direct neurological injury that cannot be supported by any objective measure. The symptoms and the cognitive deficits in these patients, even when defined by ostensibly objective testing, have no specificity. Accurately distinguishing among the many possible diagnoses in these patients is critical to avoid iatrogenic disability and incorrect treatment.
Pediatrics. 2006 Apr;117(4):e663-74. Epub 2006 Mar 13.
Health care utilization and needs after pediatric traumatic brain injury.
Slomine BS, McCarthy ML, Ding R, MacKenzie EJ, Jaffe KM, Aitken ME, Durbin DR, Christensen JR, Dorsch AM, Paidas CN; CHAT Study Group.
Department of Neuropsychology, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. firstname.lastname@example.org
Children with moderate to severe traumatic brain injury (TBI) show early neurobehavioral deficits that can persist several years after injury. Despite the negative impact that TBI can have on a child's physical, cognitive, and psychosocial well-being, only 1 study to date has documented the receipt of health care services after acute care and the needs of children after TBI. The purpose of this study was to document the health care use and needs of children after a TBI and to identify factors that are associated with unmet or unrecognized health care needs during the first year after injury.
The health care use and needs of children who sustained a TBI were obtained via telephone interview with a primary caregiver at 2 and 12 months after injury. Of the 330 who enrolled in the study, 302 (92%) completed the 3-month and 288 (87%) completed the 12-month follow-up interviews. The health care needs of each child were categorized as no need, met need, unmet need, or unrecognized need on the basis of the child's use of post-acute services, the caregiver's report of unmet need, and the caregiver's report of the child's functioning as measured by the Pediatric Quality of Life Inventory (PedsQL). Regardless of the use of services or level of function, children of caregivers who reported an unmet need for a health care service were defined as having unmet need. Children who were categorized as having no needs were defined as those who did not receive services; whose caregiver did not report unmet need for a service; and the whose physical, socioemotional, and cognitive functioning was reported to be normal by the caregiver. Children with met needs were those who used services in a particular domain and whose caregivers did not report need for additional services. Finally, children with unrecognized needs were those whose caregiver reported cognitive, physical, or socioemotional dysfunction; who were not receiving services to address the dysfunction; and whose caregiver did not report unmet need for services. Polytomous logistic regression was used to model unmet and unrecognized need at 3 and 12 months after injury as a function of child, family, and injury characteristics.
At 3 months after injury, 62% of the study sample reported receiving at least 1 outpatient health care service. Most frequently, children visited a doctor (56%) or a physical therapist (27%); however, 37% of caregivers reported that their child did not see a physician at all during the first year after injury. At 3 and 12 months after injury, 26% and 31% of children, respectively, had unmet/unrecognized health care needs. The most frequent type of unmet or unrecognized need was for cognitive services. The top 3 reasons for unmet need at 3 and 12 months were (1) not recommended by doctor (34% and 31%); (2) not recommended/provided by school (16% and 17%); and (3) cost too much (16% and 16%). Factors that were associated with unmet or unrecognized need changed over time. At 3 months after injury, the caregivers of children with a preexisting psychosocial condition were 3 times more likely to report unmet need compared with children who did not have one. Also, female caregivers were significantly more likely to report unmet need compared with male caregivers. Finally, the caregivers of children with Medicaid were almost 2 times more likely to report unmet need compared with children who were covered by commercial insurance. The only factor that was associated with unrecognized need at 3 months after injury was abnormal family functioning. At 12 months after injury, although TBI severity was not significant, children who sustained a major associated injury were 2 times more likely to report unmet need compared with children who did not. Consistent with the 3-month results, the caregivers of children with Medicaid were significantly more likely to report unmet needs at 1 year after injury. In addition to poor family functioning's being associated with unrecognized need, nonwhite children were significantly more likely to have unrecognized needs at 1 year compared with white children.
A substantial proportion of children with TBI had unmet or unrecognized health care needs during the first year after injury. It is recommended that pediatricians be involved in the post-acute care follow-up of children with TBI to ensure that the injured child's needs are being addressed in a timely and appropriate manner. One of the recommendations that trauma center providers should make on hospital discharge is that the parent/primary caregiver schedule a visit with the child's pediatrician regardless of the post-acute services that the child may be receiving. Because unmet and unrecognized need was highest for cognitive services, it is important to screen for cognitive dysfunction in the primary care setting. Finally, because the health care needs of children with TBI change over time, it is important for pediatricians to monitor their recovery to ensure that children with TBI receive the services that they need to restore their health after injury.
Neurocrit Care. 2010 Jun;12(3):324-36.
Metabolic crisis after traumatic brain injury is associated with a novel microdialysis proteome.
Lakshmanan R, Loo JA, Drake T, Leblanc J, Ytterberg AJ, McArthur DL, Etchepare M, Vespa PM.
UCLA Department of Chemistry and Biochemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
To examine if the metabolic distress after traumatic brain injury (TBI) is associated with a unique proteome.
Patients with severe TBI prospectively underwent cerebral microdialysis for the initial 96 h after injury. Hourly sampling of metabolism was performed and patients were categorized as having normal or abnormal metabolism as evidenced by the lactate/pyruvate ratio (LPR) threshold of 40. The microdialysate was frozen for proteomic batch processing retrospectively. We employed two different routes of proteomic techniques utilizing mass spectrometry (MS) and categorized as diagnostic and biomarker identification approaches. The diagnostic approach was aimed at finding a signature of MS peaks which can differentiate these two groups. We did this by enriching for intact peptides followed by MALDI-MS analysis. For the biomarker identification approach, we applied classical bottom-up (trypsin digestion followed by LC-MS/MS) proteomic methodologies.
Five patients were studied, 3 of whom had abnormal metabolism and 2 who had normal metabolism. By comparison, the abnormal group had higher LPR (1609 +/- 3691 vs. 15.5 +/- 6.8, P < 0.001), higher glutamate (157 +/- 84 vs. 1.8 +/- 1.4 microM, P < 0.001), and lower glucose (0.27 +/- 0.35 vs. 1.8 +/- 1.1 mmol/l, P < 0.001). The abnormal group demonstrated 13 unique proteins as compared with the normal group in the microdialysate. These proteins consisted of cytoarchitectural proteins, as well as blood breakdown proteins, and a few mitochondrial proteins. A unique as yet to be characterized peptide was found at m/z (mass/charge) 4733.5, which may represent a novel biomarker of metabolic distress.
Metabolic distress after TBI is associated with a differential proteome that indicates cellular destruction during the acute phase of illness. This suggests that metabolic distress has immediate cellular consequences after TBI.
Mol Cell Biochem. 2010 Feb;335(1-2):127-36. Epub 2009 Sep 17.
Regulated expression of pancreatic triglyceride lipase after rat traumatic brain injury.
Jia J, Yan M, Lu Z, Sun M, He J, Xia C.
Cytoneurobiology Unit & Laboratory of Aging and Nervous Diseases, Medical College of Soochow University, Suzhou Industrial Park, Suzhou, Jiangsu 215123, People's Republic of China.
Pancreatic triglyceride lipase (PTL), an enzyme of digestive system, plays very important roles in the digestion and absorption of lipids. However, its distribution and function in the central nervous system (CNS) remains unclear. In the present study, we mainly investigated the expression and cellular localization of PTL during traumatic brain injury (TBI). Western blot and RT-PCR analysis revealed that PTL was present in normal rat brain cortex. It gradually increased, reached a peak at the 3rd day after TBI, and then decreased. Double immunofluorescence staining showed that PTL was co-expressed with neuron, but had a few colocalizations in astrocytes. When TBI occurred in the rat cortex, the expression of PTL gradually increased, reached the peak at the 3rd day after TBI, and then decreased. Importantly, more PTL was colocalized with astrocytes, which is positive for proliferating cell nuclear antigen (PCNA). In addition, Western blot detection showed that the 3rd day post injury was not only the proliferation peak indicated by the elevated expression of PCNA, glial fibrillary acidic protein (GFAP) and cyclin D1, but also the apoptotic peak implied by the alteration of caspase-3 and bcl-2. These data suggested that PTL may be involved in the pathophysiology of TBI and PTL may be complicated after injury, more PTL was colocalized with astrocytes. Importantly, injury-induced expression of PTL was colabelled by proliferating cell nuclear antigen (proliferating cells marker), and the western blot for GFAP, PCNA and cyclin D1, showed that 3 days post injury was the proliferation peak, in coincidence to it, the protein level change of caspase-3 and bcl-2 revealed that the stage was peak of apoptotic too. These data suggested that PTL may be involved in the pathophysiology of TBI and that PTL may be implicated in the proliferation of astrocytes and the recovery of neurological outcomes. But the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of PTL after brain injury.
In addition to CEL and PLA2, the pancreas also secretes pancreatic triglyceride lipase (PTL) in response to a lipid meal (14). This protein is a member of the lipase gene family and has been shown in association with colipase to be the primary enzyme in the digestive tract capable of hydrolyzing triglycerides in emulsified lipid particles
Gastroenterology. 1998 Jan;114(1):123-9.
Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release.
Hildebrand P, Petrig C, Burckhardt B, Ketterer S, Lengsfeld H, Fleury A, Hadváry P, Beglinger C.
Division of gastroenterology, University Hospital, Basel, Switzerland.
BACKGROUND & AIMS:
The hypothesis that cholecystokinin release requires adequate dietary fat digestion in the small intestine was investigated in 10 healthy volunteers, and the consequences of reduced fat hydrolysis on pancreaticobiliary secretions were assessed.
Fat hydrolysis was inhibited by intraduodenal perfusion of tetrahydrolipstatin, an irreversible lipase inhibitor. An oil emulsion containing 0, 30, 60, or 120 mg tetrahydrolipstatin was perfused. After a 40-minute basal period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses.
In the control without tetrahydrolipstatin, lipase output increased threefold with meal ingestion and remained doubled for 4 hours. At the ligament of Treitz, free fatty acid concentration averaged 60% of total fatty acids. Increasing doses of tetrahydrolipstatin induced a dose-dependent inhibition of duodenal lipase activity (P < 0.01); 120 mg tetrahydrolipstatin eliminated the postprandial lipase peak activity, free fatty acid levels decreased to < 5% of total fatty acids, and plasma cholecystokinin levels were suppressed by 77% (P < 0.01). Amylase and trypsin outputs were reduced by 77% and 59%, respectively, and bilirubin secretion was virtually abolished (P < 0.01).
These findings show that tetrahydrolipstatin prevents triglyceride hydrolysis and that plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion require adequate triglyceride digestion. These data also support the concept of negative feedback regulation of cholecystokinin secretion.
Am J Physiol Gastrointest Liver Physiol. 2003 May;284(5):G798-807. Epub 2003 Jan 10.
Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.
Feinle C, O'Donovan D, Doran S, Andrews JM, Wishart J, Chapman I, Horowitz M.
University of Adelaide Department of Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. email@example.com
The presence of nutrients in the small intestine slows gastric emptying and suppresses appetite and food intake; these effects are partly mediated by the release of gut hormones, including CCK. We investigated the hypothesis that the modulation of antropyloroduodenal motility, suppression of appetite, and stimulation of CCK and glucagon-like peptide-1 secretion by intraduodenal fat are dependent on triglyceride hydrolysis by lipase. Sixteen healthy, young, lean men were studied twice in double-blind, randomized, crossover fashion. Ratings for appetite-related sensations, antropyloroduodenal motility, and plasma CCK and glucagon-like peptide-1 concentrations were measured during a 120-min duodenal infusion of a triglyceride emulsion (2.8 kcal/min) on one day with, on the other day without, 120 mg tetrahydrolipstatin, a potent lipase inhibitor. Immediately after the duodenal fat infusion, food intake at a buffet lunch was quantified. Lipase inhibition with tetrahydrolipstatin was associated with reductions in tonic and phasic pyloric pressures, increased numbers of isolated antral and duodenal pressure waves, and stimulation of antropyloroduodenal pressure-wave sequences (all P < 0.05). Scores for prospective consumption and food intake at lunch were greater, and nausea scores were slightly less, and the rises in plasma CCK and glucagon-like peptide-1 were abolished (all P < 0.05). In conclusion, lipase inhibition attenuates the effects of duodenal fat on antropyloroduodenal motility, appetite, and CCK and glucagon-like peptide-1 secretion.
Physiol Behav. 2009 Aug 4;98(1-2):198-204. Epub 2009 May 22.
Dose-response effects of PEGylated cholecystokinin on the behavioral satiety sequence.
Verbaeys I, León-Tamariz F, De Buyser K, Buyse J, Decuypere E, Pottel H, Cokelaere M.
Interdisciplinary Research Center, Katholieke Universiteit Leuven, Campus Kortrijk, Etienne Sabbelaan 53, B-8500, Kortrijk, Belgium. firstname.lastname@example.org
Cholecystokinin (CCK) is known to have a short biological half-life. In order to prolong the half-life and create a new investigative tool, we previously PEGylated the peptide, yielding PEG-CCK(9), and demonstrated that it had a dose-dependent prolonged anorectic effect. The aim of this study was to investigate whether PEG-CCK(9) reduces food intake by inducing satiation or by abnormal physiological effects, such as pain, malaise, or nausea. An observational study was performed to examine the effects of different doses of PEG-CCK(9) (1, 2, 4, 8, or 16 microg kg(-1)) on feeding and other behaviors. The behavioral sequence associated with satiety (BSS), i.e. the orderly progression from eating, through grooming and activity, to resting, was analyzed. From the lowest dose tested (1 microg kg(-1)), PEG-CCK(9) caused a dose-dependent reduction in food intake due to a dose-related reduction in both the duration and frequency of eating and a dose-dependent increase in duration of rest. A dose-dependent acceleration in the temporal profile of the BSS was observed, while the normal structure of feeding behaviors was well preserved, except at the dose of 16 microg kg(-1) of PEG-CCK(9), at which a decrease in eating rate and grooming behavior was observed, together with the occurrence of a significant number of abdominal cramps. These findings suggest that the hypophagic response to PEG-CCK(9) is mainly induced by natural mechanisms of satiety, although abnormal physiological effects, such as abdominal cramps, might reinforce the food inhibitory effect, especially at high doses of PEG-CCK(9) (>8 microg kg(-1)).