✓ The effect of steroid administration on metabolic rate and nitrogen excretion was examined in 20 head-injured patients alternately assigned to receive either methylprednisolone for 14 days or no steroid treatment. Although metabolic rate, caloric intake, and nitrogen intake were not different between the two groups, the patients who received steroids had a 30% higher excretion of nitrogen during the first 6 days after injury than did the patients not receiving steroids. All patients had an increase in nitrogen excretion through the 2nd week, peaking on Day 11. By Day 21 after injury, the patients had an average cumulative nitrogen loss of 162 gm and had lost an average of 5 kg body weight regardless of whether they had received steroids. Serum albumin levels decreased in the steroid-treated patients but returned to nearly normal by Day 21 in the untreated group. Immunosuppression, evidenced by a lower initial total lymphocyte count and a higher incidence of infections, was present in the steroid group; hyperglycemia requiring insulin treatment was more common in those patients.
Claudia S. Robertson, Guy L. Clifton and J. Clay Goodman
Claudia S. Robertson, Richard Foltz, Robert G. Grossman and J. Clay Goodman
✓ The authors have studied the protection against ischemic damage to rabbit spinal cord by pretreatment with agents that block neuronal activity and directly or indirectly reduce tissue metabolism. Hypothermia, thiopental, magnesium, lidocaine, and naloxone were used to pretreat the spinal cord prior to ischemia. Hypothermia and thiopental provided comparable protection: they each increased the duration of ischemia required to produce neurological deficits in 50% of the animals from 26 to 41 minutes. They also increased from 10 to 30 minutes the time that the postsynaptic waves of the spinal somatosensory evoked potential (SSEP) could be absent and the animal still have neurological recovery. Hypothermia and thiopental, when used together, increased the duration of ischemia required to produce neurological deficits to 57 minutes in 50% of the animals. Naloxone increased the duration of ischemia required to produce neurological deficits to 36 minutes in 50% of the animals, and increased to 20 minutes the time that the postsynaptic waves of the SSEP could be absent and the animal still have neurological recovery. Magnesium pretreatment improved neurological outcome, possibly by improving collateral circulation as the SSEP did not fail completely during aortic occlusion in all animals. Lidocaine was not beneficial, perhaps because of the prolonged hypotension that resulted.
Claudia S. Robertson, Robert G. Grossman, J. Clay Goodman and Raj K. Narayan
✓ Cerebral ischemia is a common mechanism of secondary brain injury following severe head injury. The cerebral metabolic rate of oxygen (CMRO2) and of lactate (CMRL), as well as cerebral blood flow (CBF) were measured daily for 5 days after head injury in 44 comatose head-injured patients to determine if metabolic changes could identify the patients who would develop cerebral infarction. Of 41 patients whose CBF remained at levels regarded as adequate to prevent infarction (CBF ≥ 0.2 ml/gm/min), the six who showed a cerebral infarction on computerized tomography (CT) scans exhibited characteristic cerebral metabolic patterns: a CMRO2 of less than 0.6 µmol/gm/min on one or more of the days monitored, and markedly elevated cerebral lactate production (CMRL < −0.06 µmol/gm/min) on Days 1 and/or 2 after injury. Patients who had no areas of infarction on serial CT scans typically had a CMRO2 of 0.6 µmol/gm/min or higher and a low cerebral lactate production. Measurement of CMRO2 and CMRL can be obtained at the bedside and can indicate the presence of an evolving ischemic infarct after head injury.
Steffen Albrecht, J. Clay Goodman, Sri Rajagopolan, Moise Levy, David A. Cech and Linda D. Cooley
✓ Gorlin's syndrome, also known as multiple basal cell carcinoma syndrome, is a familial tumor condition with autosomal-dominant inheritance. Patients develop multiple basal cell carcinomas beginning in childhood. They also have a typical dysmorphic facies, skeletal malformations, and a particular type of epithelial cyst of the jaws. Recent evidence localizes a Gorlin's syndrome locus on chromosome 9 at band q31. Both tumors and malformations of the central nervous system occur with Gorlin's syndrome. Medulloblastoma is the primary brain tumor most frequently associated with this syndrome; over 40 such cases have been reported. However, only seven cases of meningioma associated with Gorlin's syndrome have been described.
The authors report the case of a woman with Gorlin's syndrome whose mother and maternal grandfather also had the condition. The patient was found to have a medulloblastoma at 4 years of age and presented with a large bifrontal meningioma at 19 years of age. The meningioma was histologically malignant and had a complex karyotype with multiple translocations including a t(5;9) with the breakpoint on chromosome 9 located at 9q32. The constitutional karyotype of the mother was normal. No mutations of exons 5 to 9 of the p53 gene were detected using single-stranded conformational polymorphism analysis.
Roukoz Chamoun, Dima Suki, Shankar P. Gopinath, J. Clay Goodman and Claudia Robertson
Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors' objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value.
A prospective study of patients with severe TBI was conducted with an inclusion criterion of a Glasgow Coma Scale score ≤ 8 within 48 hours of injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO2, jugular venous O2 saturation, and cerebral microdialysis. Patients received standard care including mass evacuation when indicated and treatment of elevated intracranial pressure values. Demographic data, CT findings, and outcome at 6 months of follow-up were recorded.
One hundred sixty-five patients were included in the study. Initially high glutamate values were predictive of a poor outcome. The mortality rate was 30.3% among patients with glutamate levels > 20 μmol/L, compared with 18% among those with levels ≤ 20 μmol/L.
Two general patterns were recognized: Pattern 1, glutamate levels tended to normalize over the monitoring period (120 hours); and Pattern 2, glutamate levels tended to increase with time or remain abnormally elevated. Patients showing Pattern 1 had a lower mortality rate (17.1 vs 39.6%) and a better 6-month functional outcome among survivors (41.2 vs 20.7%).
Glutamate levels measured by microdialysis appear to have an important role in TBI. Data in this study suggest that glutamate levels are correlated with the mortality rate and 6-month functional outcome.
Claudia S. Robertson, J. Clay Goodman, Raj K. Narayan, Charles F. Contant and Robert G. Grossman
✓ The role of intravenous infusion of glucose in limiting ketogenesis and the effect of glucose on cerebral metabolism following severe head injury were studied in 21 comatose patients. The patients were randomly assigned to alimentation with or without glucose. Systemic protein wasting, arterial concentrations of energy substrates, and cerebral metabolism of these energy substrates were monitored for 5 days postinjury. Both groups were in negative nitrogen balance, and had wasting of systemic proteins despite substantial protein intake. Blood and cerebrospinal fluid (CSF) glucose concentrations were highest on Day 1, but remained higher than normal fasting levels on all days of study, even in the patients who received no exogenous glucose. Although there were no differences in blood or CSF glucose concentrations in the two groups of patients, the glucose group had higher plasma insulin levels, with a mean ± standard deviation of 14.8 ± 7.3 µU/ml compared to 10.3 ± 4.2 µU/ml in the saline group. The blood concentrations of β-hydroxybutyrate, acetoacetate, pyruvate, glycerol, and the free fatty acids were higher in the saline group than in the glucose group. Cerebral oxygen consumption was similar in the two groups, while the cerebral metabolism of glucose and of the ketone bodies was dependent on whether glucose was administered. In the glucose group, glucose was the only energy substrate utilized by the brain. In the saline group, the ketone bodies β-hydroxybutyrate and acetoacetate replaced glucose to the extent of 16% of the brain's total energy production. Cerebral lactate production and CSF lactate concentration were lower in the saline group. These studies suggest that administration of glucose during the early recovery period of severe head injury is a major cause of suppressed ketogenesis, and may increase production of lactic acid by the traumatized brain by limiting the availability of nonglycolytic energy substrates.
Sungho Lee, Hyunsoo Hwang, Jose-Miguel Yamal, J. Clay Goodman, Imoigele P. Aisiku, Shankar Gopinath and Claudia S. Robertson
Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.
The authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.
Two hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).
Admission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.
Bharat Guthikonda, Emilie Rouah, Bhuvanaswari Krishnan, Suzanne Z. Powell, J. Clay Goodman, Shankar P. Gopinath and Richard K. Simpson
Whipple disease is a multisystem infectious disease caused by Tropheryma whippleii. It commonly affects the CNS and produces neurological symptoms in 10–20% of cases. Central nervous system Whipple disease occurring in patients with AIDS is extremely rare. The authors present a case of a newly diagnosed AIDS patient in whom intracranial Whipple disease was diagnosed by stereotactic brain biopsy.