Cognitive functioning in long-term survivors of high-grade glioma

1994 ◽  
Vol 80 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Yvonne M. Archibald ◽  
Diane Lunn ◽  
Lesley A. Ruttan ◽  
David R. Macdonald ◽  
Rolando F. Del Maestro ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
High Grade Glioma ◽  
High Grade ◽  
Content Type ◽  
Group 2 ◽  
Long Term Survivors ◽  
Disease Free ◽  
Fine Print ◽  
Group 1

✓ In a pilot study, two groups of patients with malignant glioma underwent sequential neuropsychological evaluations after successful tumor treatment. Group 1 included nine patients treated from 1981 to 1985; all patients received irradiation and eight underwent chemotherapy. The baseline neuropsychological assessment was performed 1 to 63 months after tumor diagnosis, with follow-up evaluations at irregular intervals over the next 3 to 7 years. Six patients in Group 1 exhibited impairment on most measures at baseline; subsequently, two patients developed profound cognitive impairment. Initially, three patients functioned in the average range on most tasks; thereafter, two deteriorated on one measure each. Group 2 was ascertained prospectively and included 16 patients treated from 1985 to 1987, all of whom received irradiation and chemotherapy. The first evaluation was performed 18 months after diagnosis, then every 6 months for 2 years, and then yearly. Compared to a control group, those in Group 2 had significant cognitive impairment at baseline. Cognitive performance did not change over the next 12 months in 10 patients who remained free of tumor, but within 2 years of baseline testing, deterioration on specific tasks was evident in two of seven disease-free survivors. When last tested, five of six disease-free survivors had deteriorated on one or more measures. Unlike Group 1, severe global cognitive impairment was not seen, perhaps because Group 2 was followed for a shorter time. Verbal and nonverbal composite scores derived from intelligence quotient (IQ) tests showed less impairment at baseline than did other measures and were more likely to remain stable subsequently. Verbal memory and sustained attention were the most impaired at baseline, and verbal learning and flexibility in thinking showed the greatest tendency to decline over time. Cognitive functioning in survivors of high-grade glioma is best measured and monitored by tests that probe a broader spectrum of abilities than IQ. Neuropsychological measures used in this analysis lacked sensitivity at the lower end of the impaired range. Future studies should use tests better able to discern cognitive differences at low performance levels. Based on this experience, the authors conclude that most long-term survivors of high-grade glioma will have significant cognitive difficulties, usually evident by the first assessment; some patients will develop profound impairment years later, and few are capable of fully independent living.

Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery

2002 ◽  
Vol 97 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Arun P. Amar ◽  
William T. Couldwell ◽  
Joseph C. T. Chen ◽  
Martin H. Weiss
Keyword(s):  
Prolactin Level ◽  
Serum Prolactin ◽  
Surgical Removal ◽  
Consecutive Series ◽  
Cure Rate ◽  
Content Type ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

Object. Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of “recurrent” tumors. Methods. Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (≤ 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome. Conclusions. Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

Evaluation of brain-stem dysfunction following severe fluid-percussion head injury to the cat

1991 ◽  
Vol 74 (2) ◽  
pp. 270-277 ◽  
Author(s):  
Katsuji Shima ◽  
Anthony Marmarou
Keyword(s):  
Brain Stem ◽  
Content Type ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Brain Stem Injury ◽  
Group 2 ◽  
High Level ◽  
Subarachnoid Hemorrhages ◽  
Fine Print ◽  
Group 1

✓ The degree of brain-stem dysfunction associated with high-level fluid-percussion injury (3.0 to 3.8 atm) was investigated in anesthetized cats. Measurements were made of the animals' intracranial pressure (ICP), pressure-volume index (PVI), far-field brain-stem auditory evoked responses (BAER's), and cerebral blood flow (CBF). The animals were classified into two groups based on the severity of neuropathological damage to the brain stem after trauma: Group 1 had mild intraparenchymal and subarachnoid hemorrhages and Group 2 had severe intraparenchymal and subarachnoid hemorrhages. The ICP values in Group 1 were insignificantly lower than those in Group 2, while the PVI values in Group 2 were clearly lower (p < 0.05). Immediately after the injury, peaks II, III, and IV of the BAER's demonstrated a transitory and marked suppression. One Group 1 and two Group 2 animals showed the disappearance of peak V. In Group 1, the latencies of peak II, III, and IV gradually increased until 60 to 150 minutes postinjury, then returned to 95% of baseline value at 8 hours; however, the animals in Group 2 showed poor recovery of latencies. Two hours after brain injury, the CBF decreased to 40% of the preinjury measurement in both groups (p < 0.001). In contrast to Group 2, the CBF in Group 1 returned to 86.8% of the preinjury measurement by 8 hours following the injury. Changes in PVI, BAER, and CBF correlated well with the degree of brain-stem injury following severe head injury'- These data indicate that high-level fluid-percussion injury (> 3.0 atm) is predominantly a model of brain-stem injury.

A novel rat model for the study of intraosseous metastatic spine cancer

2005 ◽  
Vol 2 (3) ◽  
pp. 303-307 ◽  
Author(s):  
Ajay Mantha ◽  
Federico G. Legnani ◽  
Carlos A. Bagley ◽  
Gary L. Gallia ◽  
Ira Garonzik ◽  
...  
Keyword(s):  
Rat Model ◽  
Breast Adenocarcinoma ◽  
Rank Test ◽  
Functional Score ◽  
Histopathological Analysis ◽  
Sham Operation ◽  
Content Type ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

Object. Although metastatic spinal disease constitutes a significant percentage of all spinal column tumors, an accessible and reproducible animal model has not been reported. In this study the authors describe the technique for creating an intraosseous spinal tumor model in rats and present a functional and histological analysis. Methods. Eighteen female Fischer 344 rats were randomized into two groups. Group 1 animals underwent a transabdominal exposure and implantation of CRL-1666 breast adenocarcinoma into the L-6 vertebral body (VB). Animals in Group 2 underwent a sham operation. Hindlimb function was tested daily by using the Basso-Beattie-Bresnahan scale. Sixteen days after tumor implantation, animals were killed and their spines were removed for histological assessment. Statistical analysis was performed using the Wilcoxon signed-rank test. By Day 15 functional analysis showed a significant decrease in motor function in Group 1 animals (median functional score 2 of 21) compared with Group 2 rats (median functional score 21 of 21) (p = 0.0217). The onset of paraparesis in Group 1 occurred within 14 to 16 days of surgery. Histopathological analysis showed tumor proliferation through the VB and into the spinal canal, with marked osteolytic activity and spinal cord compression. Conclusions. Analysis of these findings demonstrates the consistency of tumor growth in this model and validates the utility of functional testing for onset of paresis. This new rat model allows for the preclinical evaluation of novel therapeutic treatments for patients harboring metastatic spine disease.

Prognostic significance of magnetic resonance imaging in the acute phase of cervical spine injury

1992 ◽  
Vol 76 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Dale M. Schaefer ◽  
Adam E. Flanders ◽  
Jewell L. Osterholm ◽  
Bruce E. Northrup
Keyword(s):  
Cervical Spine ◽  
Mr Imaging ◽  
Prognostic Significance ◽  
Spinal Segment ◽  
Content Type ◽  
Group 3 ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

✓ Fifty-seven patients with acute cervical spine injuries and associated major neurological deficit were examined within 2 weeks of injury by magnetic resonance (MR) imaging. All patients had abnormal scans, indicating intramedullary lesions. This study was undertaken to determine if the early MR imaging pattern had a prognostic relationship to the eventual neurological outcome. Three different MR imaging patterns were observed in these patients: 21 patients had patterns characteristic of intramedullary hematoma (Group 1); 17 had intramedullary edema over more than one spinal segment, but no hemorrhage (Group 2); and 19 had restricted zones of intramedullary edema involving one spinal segment or less (Group 3). The neurological state was determined using standard motor index scores at admission and at follow-up examination. Characteristically, the patients in Group 1 had admission motor scores significantly lower than the other two groups. At follow-up examination, the median percent motor recovery was 9% for Group 1, 41% for Group 2, and 72% for Group 3. These studies suggest that the MR imaging pattern observed in the acutely injured human spinal cord has a prognostic significance in the final outcome of the motor system. It is only when an accurate prognosis can be given at the outset that useful treatment data might be collected for homogeneous injury groups, and accurately based long-term planning made for the best patient care.

scholarly journals Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ana S. Guerreiro Stucklin ◽  
Scott Ryall ◽  
Kohei Fukuoka ◽  
Michal Zapotocky ◽  
Alvaro Lassaletta ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Strategies ◽  
Low Grade ◽  
High Grade ◽  
Term Survival ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.

Efficacy of protracted dose-dense temozolomide (TMZ) in patients with progressive high-grade glioma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
M. U. Abacioglu ◽  
H. B. Caglar ◽  
P. F. Yumuk ◽  
Z. Akgun ◽  
B. M. Atasoy ◽  
...  
Keyword(s):  
Study Drug ◽  
High Grade Glioma ◽  
Median Number ◽  
High Grade ◽  
Female Ratio ◽  
Best Response ◽  
Group 2 ◽  
Grade 3 ◽  
Dose Dense ◽  
Group 1

e13018 Background: The study was aimed to evaluate the efficacy of TMZ on a protracted dose-dense schedule after standard 5-day TMZ regimen in patients with progressive high-grade glioma. Methods: In this phase II prospective study, patients who had progression on standard 5-day TMZ for recurrence (group 1) or recurrence after concurrent radiotherapy+TMZ and ≥ 2 cycles of adjuvant TMZ (group 2) for high-grade glioma received TMZ 100 mg/m2× 21 q28 days until progression according to MacDonald's criteria. Patients were included in the study after ethical committee approval and written informed consent. The primary end-point was 6 months PFS. Secondary end-points were OS and toxicity. Results: Between October 2006 and October 2008, 25 patients were included in the study. Nine of the patients were group 1 and 16 of them were group 2. Male/female ratio was 18/7. The median age was 50 (range, 18–70) and median KPS score was 80 (range, 50–100). The histopathology was glioblastoma in 18 and grade 3 glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma) in 7. The median cycles of 5-day TMZ received before study entry was 6 (range, 2–18) in group 1 and 6 (2–7) in group 2. With a median follow up of 6 months (1–14 months) the median number of 21-day TMZ cycles received was 2 (range, 1–8). Radiological evaluation could not be performed in 5 patients because of early clinical progression. The best response during treatment was partial response in 2 (8%), stable disease in 9 (36%), and progression in 9 (36%) out of 20 patients assessed. The median time to progression was 2 months (1–8 months) and 6 months PFS rate was 11%. The median OS time was 8 months and 1 year OS rate was 38%. Out of 80 cycles received there was no anemia; 5 (6%) grade 1, 8 (10%) grade 2, 2 (3%) grade 3 leucopenia; 1 (1%) grade 1, 2 (3%) grade 2, 1 (1%) grade 3, 1 (1%) grade 4 thrombocytopenia; 9 (11%) grade 1, 7 (9%) grade 2, 32 (40%) grade 3, and 11 (14%) grade 4 lymphopenia. Study was terminated in 2 patients (one with grade 4 thrombocytopenia and the other with grade 4 hepatic toxicity). There was no dose reduction in the study drug due to toxicity. Conclusions: Protracted dose-dense TMZ after 5-day schedule for recurrent or progressive disease has modest efficacy with tolerable toxicity. No significant financial relationships to disclose.

Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy

2003 ◽  
Vol 98 (5) ◽  
pp. 1040-1044 ◽  
Author(s):  
Bettina Pfausler ◽  
Heinrich Spiss ◽  
Ronny Beer ◽  
Andreas Kampfl ◽  
Klaus Engelhardt ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Trough Level ◽  
Once Daily ◽  
Content Type ◽  
Treatment Groups ◽  
Efficacious Treatment ◽  
Group 2 ◽  
Vancomycin Level ◽  
Fine Print ◽  
Group 1

Object. Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study. Methods. Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five (median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 ± 0.4 µg/ml in Group 1 and 565.58 ± 168.71 µg/ml 1 hour after vancomycin application in Group 2 (mean ± standard deviation). Vancomycin levels above the recommended trough level of 5 µg/ml in CSF were never reached in Group 1, whereas in Group 2 they were below the trough level (3.74 ± 0.66 µg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained. Conclusions. Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

Neuroendoscopic approach to tectal tumors: a consecutive series

1999 ◽  
Vol 91 (6) ◽  
pp. 964-970 ◽  
Author(s):  
Kazunari Oka ◽  
Yoshiaki Kin ◽  
Yoshinori Go ◽  
Yushi Ueno ◽  
Katsuyuki Hirakawa ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Signal Intensity ◽  
Obstructive Hydrocephalus ◽  
Consecutive Series ◽  
Content Type ◽  
Group 3 ◽  
Group 2 ◽  
Operative Notes ◽  
Fine Print ◽  
Group 1

Object. The authors report a consecutive series of 10 patients who presented with signs and symptoms caused by tectal tumors. Clinical findings, radiographic features, neuroendoscopic management strategies, and histological findings are reported and discussed.Methods. Since January 1990, 11 neuroendoscopic procedures were performed in 10 patients who harbored tectal tumors. The patients were followed for an average of 5 years (range 2 months-11 years), and a retrospective study was conducted in which case notes, radiological findings, operative notes, and histopathological findings were assessed. Magnetic resonance (MR) imaging was performed, and the images were used to classify patients into three groups: those with hypertrophy of the tectum in whom isointensity appeared on T1-weighted images (Group 1); those with a tectal tumor occupying the cerebral aqueduct in whom decreased signal intensity appeared on T1-weighted images, as well as no enhancement after gadolinium administration (Group 2); and those with a tectal tumor in whom mixed signal intensity and conspicuous evidence of contrast enhancement appeared on T1-weighted images (Group 3). The results of histological examination were consistent with MR imaging features: in Group 1, glial tissue or gliosis; in Group 2, benign astrocytoma; and in Group 3, malignant astrocytoma. Cerebrospinal fluid diversion was the only surgical treatment that provided relief from obstructive hydrocephalus. One patient in Group 3 underwent radiotherapy and subsequent partial tumor removal under neuroendoscopic guidance. Thereafter, the tumor remained in decline. All patients had normal intellectual status after undergoing surgery in which a neuroendoscope was used.Conclusions. Neuroendoscopic procedures can provide histological diagnosis, define the tumor—midbrain interrelationship, and be highly effective in treating obstructive hydrocephalus and in removing tectal tumors. This procedure may receive clinical application as a new management strategy for tectal glioma.

Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury

2001 ◽  
Vol 94 (5) ◽  
pp. 697-705 ◽  
Author(s):  
Kees H. Polderman ◽  
Saskia M. Peerdeman ◽  
Armand R. J. Girbes
Keyword(s):  
Head Injury ◽  
Severe Head Injury ◽  
Control Group ◽  
Induced Hypothermia ◽  
Content Type ◽  
Cooling Period ◽  
Urine Production ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

Object. Induced hypothermia in patients with severe head injury may prevent additional brain injury and improve outcome. However, this treatment is associated with severe side effects, including life-threatening cardiac tachyarrhythmias. The authors hypothesized that these arrhythmias might be caused by electrolyte disorders and therefore studied the effects of induced hypothermia on urine production and electrolyte levels in patients with severe head injury. Methods. Urine production, urine electrolyte excretion, and plasma levels of Mg, phosphate, K, Ca, and Na were measured in 41 patients with severe head injury. Twenty-one patients (Group 1, study group) were treated using induced hypothermia and pentobarbital administration, and 20 patients (Group 2, controls) were treated with pentobarbital administration alone. In Group 1, Mg levels decreased from 0.98 ± 0.15 to 0.58 ± 0.13 mmol/L (mean ± standard deviation; p < 0.01), phosphate levels from 1.09 ± 0.19 to 0.51 ± 0.18 mmol/L (p < 0.01), Ca levels from 2.13 ± 0.25 to 1.94 ± 0.14 mmol/L (p < 0.01), and K levels from 4.2 ± 0.59 to 3.6 ± 0.7 mmol/L (p < 0.01) during the first 6 hours of cooling. Electrolyte levels in the control Group 2 remained unchanged. Electrolyte depletion in Group 1 occurred despite the fact that moderate and, in some cases, substantial doses of electrolyte supplementation were given to many patients, and supplementation doses were often increased during the cooling period. Average urine production increased during the cooling period, from 219 ± 70 to 485 ± 209 ml/hour. When the targeted core temperature of 32°C was reached, urine production returned to levels that approximated precooling levels (241 ± 102 ml/hour). Electrolyte levels rose in response to high-dose supplementation. In the control group, urine production and electrolyte excretion remained unchanged throughout the study period. Conclusions. Induced hypothermia is associated with severe electrolyte depletion, which is at least partly due to increased urinary excretion through hypothermia-induced polyuria. This may be the mechanism through which induced hypothermia can lead to arrhythmias. When using this promising new treatment in patients with severe head injury, stroke, or postanoxic coma following cardiopulmonary resuscitation, prophylactic electrolyte supplementation should be considered and electrolyte levels should be monitored frequently.

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