Soft Tissue Dissection in the Transcondylar Approach: A Modified Layered Technique to Maximize Lateral Access.

Objective While the transcondylar approach is technically challenging, it provides generous ventral and caudal exposure to the craniovertebral junction. This approach requires navigation around multiple eloquent neurovascular structures including the lower cranial nerves, vertebral artery and its branches, and the brainstem. Superficial exposure, including incision location and muscle dissection, can dramatically affect the surgical angle and maneuverability at depth. Methods We demonstrate the transcondylar approach in a step-by-step fashion in a formalin-embalmed, latex-injected cadaver head. Dissection within each layer of the suboccipital muscles was performed. A small cohort with an illustrative case is also included herein. Results The sternocleidomastoid (SCM) muscle was retracted anteriorly; the splenium capitis, semispinalis capitis, and longissimus capitis muscles were disconnected from the superior nuchal line and reflected inferomedially. The suboccipital muscle group was fully exposed. The superior and inferior oblique muscles were disconnected from the transverse process of C1. The superior oblique and the rectus capitis posterior major muscles were then dissected off the inferior nuchal line, and the suboccipital muscle group was retracted inferomedially en bloc . The greater auricular nerve was retracted laterally with the SCM, and the greater occipital nerve was retracted inferomedially with the suboccipital muscle group. Conclusion This technique avoids the obstructive muscle bulk that results from a myocutaneous approach while maximizing deep exposure. Understanding the detailed muscular anatomical relationship with the insertion location and suboccipital nerves is key to complete and safe extracranial dissection. Diligent dissection helps minimize postoperative pain and muscle spasm while optimizing the closure technique.

Spontaneous resolution of traumatic cervical epidural hematoma: illustrative case.

BACKGROUND: Cervical epidural hematomas are rare and can arise for many reasons. Patients typically present with pain and/or symptoms of spinal cord compression. Prompt surgical decompression is typically pursued when deficits are present in an effort to improve long-term neurological outcomes. However, the authors report the case of a patient with a traumatic dorsal cervical epidural hematoma with spontaneous resolution within 16 hours. OBSERVATIONS: A 49-year-old male with a history of C5-6 anterior cervical fusion 3 years prior presented with neck pain after blunt force trauma. The exam revealed only tenderness in the cervical spine. Initial computed tomography revealed fractures of C1 and C4. Urgent magnetic resonance imaging (MRI) demonstrated a dorsal cervical epidural hematoma causing compression of the spinal cord from the occiput to C5. An operation was scheduled for the following morning; however, after he reported new symptoms, repeat MRI was performed, which confirmed no evidence of a cervical epidural hematoma. LESSONS: This case demonstrates that a traumatic cervical epidural hematoma can resolve spontaneously within a short time frame. Close monitoring of these patients is vital, and it is important to reimage patients if new signs and/or symptoms arise to potentially change the timing and/or nature of the proposed surgery. https://thejns.org/doi/10.3171/CASE24167.

Bilateral cerebellopontine angle lipomas in an infant with encephalocele: illustrative case.

BACKGROUND: Bilateral cerebellopontine angle (CPA) lipomas are extremely rare. Herein the authors present a case of bilateral CPA lipomas in an infant along with a literature review of bilateral CPA lipomas. OBSERVATIONS: A newborn girl was incidentally found to have bilateral CPA lipomas during the workup for an occipital encephalocele. The encephalocele was repaired primarily on day 2 after birth. The patient demonstrated no symptoms associated with the bilateral CPA lipomas. Eight cases of bilateral CPA lipomas were identified in the literature review and are summarized. Conservative management is the consensus strategy, given minimum growth of the tumor and the high risk of surgical intervention. LESSONS: This is the first reported case of bilateral CPA lipomas in an infant as well as the first with a coexisting intracranial malformation. Intracranial lipomas share an extremely low growth rate and typically do not cause severe symptoms. The management of asymptomatic or mildly symptomatic bilateral CPA lipomas is usually conservative.

Open Surgical Approaches for Meningiomas.

Meningiomas are the most common intracranial extra-axial primary tumor. Although most are low grade and slow growing, resection can be technically challenging, particularly when located at the skull base. Appropriate craniotomy and approach selection are of paramount importance to minimize brain retraction, optimize exposure, and achieve complete resection. This article summarizes various craniotomies and their approaches to meningiomas, and illustrates some nuances in performing these techniques with cadaveric dissection and operative videos.

Specific gene expression signatures of low grade meningiomas.

Introduction: Meningiomas are the most common primary central nervous system (CNS) tumors in adults, representing approximately one-third of all primary adult CNS tumors. Although several recent publications have proposed alternative grading systems of meningiomas that incorporate genomic and/or epigenomic data to better predict meningioma recurrence and progression-free survival, our understanding of driving forces of meningioma development is still limited. Objective: To define gene expression signatures of the most common subtypes of meningiomas to better understand cellular processes and signaling pathways specific for each tumor genotype. Methods: We used RNA sequencing (RNA-seq) to determine whole transcriptome profiles of twenty meningiomas with genomic alterations including NF2 inactivation, loss of chr1p, and missense mutations in TRAF7, AKT1 and KLF4. Results: The analysis revealed that meningiomas with NF2 gene inactivation expressed higher levels of BCL2 and GLI1 compared with tumors harboring TRAF7 missense mutations. Moreover, NF2 meningiomas were subdivided into two distinct groups based on additional loss of chr1p. NF2 tumors with intact chr1p were characterized by the high expression of tumor suppressor PTCH2 compared to NF2 tumors with chr1p loss. Taken together with the high expression of BCL2 and GLI1, these results suggest that activation of Sonic Hedgehog pathway may contribute to NF2 meningioma development. In contrast, NF2 tumors with chr1p loss expressed high levels of transcription factor FOXD3 and its antisense RNA FOXD3-AS1. Examination of TRAF7 tumors demonstrated that TRAF7 regulates a number of biomechanically responsive genes (KRT6a, KRT16, IL1RL1, and AQP3 among others). Interestingly, AKT1 and KLF4 meningiomas expressed genes specific for PI3K/AKT signaling pathway, suggesting overlapping gene signatures between the two subtypes. In addition, KLF4 meningiomas had high expression of carcinoembryonic antigen family members CEACAM6 and CEACAM5. Conclusions: Each group of meningiomas displayed a unique gene expression signature suggesting signaling pathways potentially implicated in tumorigenesis. These findings will improve our understanding of meningioma tumorigenesis and prognosis.

Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review.

Surgery is an important treatment modality for the majority of solid organ cancers. Unfortunately, cancer recurrence following surgery of curative intent is common, and typically results in refractory disease and patient death. Surgery and other perioperative interventions induce a biological state conducive to the survival and growth of residual cancer cells released from the primary tumour intraoperatively, which may influence the risk of a subsequent metastatic disease. Evidence is accumulating that anaesthetic and analgesic interventions could affect many of these pathophysiological processes, influencing risk of cancer recurrence in either a beneficial or detrimental way. Much of this evidence is from experimental in vitro and in vivo models, with clinical evidence largely limited to retrospective observational studies or post hoc analysis of RCTs originally designed to evaluate non-cancer outcomes. This narrative review summarises the current state of evidence regarding the potential effect of perioperative anaesthetic and analgesic interventions on cancer biology and clinical outcomes. Proving a causal link will require data from prospective RCTs with oncological outcomes as primary endpoints, a number of which will report in the coming years. Until then, there is insufficient evidence to recommend any particular anaesthetic or analgesic technique for patients undergoing tumour resection surgery on the basis that it might alter the risk of recurrence or metastasis.

Neuroactive amino acids in focally epileptic human brain: a review.

Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degradation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.

Congenital malformations due to antiepileptic drugs.

To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital malformations in offspring without drug exposure was 3.1%, versus an incidence with drug exposure of 9.0%. The highest incidence in offspring exposed to a single AED occurred with primidone (PRM; 14.3%), which was followed by valproate (VPA; 11.1%), phenytoin (PHT; 9.1%), carbamazepine (CBZ; 5.7%), and phenobarbital (PB; 5.1%). The VPA dose and level positively correlated with the incidence of malformations. This study first determined a cut-off value of VPA dose and level at 1000 mg/day and 70 microg/ml, respectively, to avoid the occurrence of malformations. The incidence of malformations increases as the number of drugs increases, and as the total daily dose increases. Specific combinations of AEDs such as VPA + CBZ and PHT + PRM + PB produced a higher incidence of congenital malformations. The incidence of malformations was not associated with any background factors studied except for the presence of malformations in siblings. These results indicate that the increased incidence of congenital malformations was caused primarily by AEDs, suggesting that malformations can be prevented by improvements in drug regimen, and by avoiding polypharmacy and high levels of VPA (more than 70 microg/ml) in the treatment of epileptic women of childbearimg age.

Self-reported ballet classes undertaken at age 10-12 years and hip bone mineral density in later life.

The major effect of weightbearing exercise on adult bone mass may be exerted during childhood. We examined the relationship between reported hours of ballet classes per week undertaken as a child and adult bone mineral density (BMD) at the hip, spine, and forearm. We performed a retrospective cohort study in 99 female retired dancers (mean age 51 years, SD 14 years) and 99 normal controls, derived from a twin study, matched hierarchically for age, height, weight and menopausal status. Starting age of ballet was recalled and weekly hours of ballet as a child was self-reported on two occasions. BMD was measured using dualenergy X-ray absorptiometry and reported as a Z-score. Self-reported hours of ballet class undertaken per week at each age between 10 and 12 years was positively associated with a difference in BMD between dancers and controls at both the femoral neck site (beta = 0.73, p = 0.001) and the total hip site (beta = 0.55, p < 0.01). These associations were unaffected by adjustment for covariates including measures of adult activity (current physical activity, years of fulltime ballet), measures of menstrual disturbance (age of menarche, history of irregular menses), dietary history (calcium intake as a child, adolescent or adult) or lifestyle factors (lifetime smoking, lifetime alcohol). Although starting age of ballet was negatively associated with weight-adjusted within-pair hip BMD difference, it was no longer associated after adjustment for weekly hours of ballet. There was no relationship between hours of ballet undertaken as a child and differences in BMD at the lumbar spine or upper limb, at any age. Our data suggest that classical ballet classes undertaken between the ages of 10 and 12 years are independently and positively associated with a difference in hip BMD between dancers and controls. The findings are consistent with the hypothesis that this age range identifies a stage of development when the proximal femur is particularly responsive to weightbearing exercise.

Phospholipid biosynthetic enzymes in human brain.

Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis. However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect. Thus, the objective of our study was to characterize the enzymes involved, in particular, whether differences existed in the relative affinity of substrates for the enzymes of phosphatidylethanolamine (PE) compared to those of phosphatidylcholine (PC) synthesis. The concentration of choline in rapidly frozen human brain biopsies ranged from 32-186 nmol/g tissue, a concentration similar to that determined previously for ethanolamine. Since human brain ethanolamine kinase possessed a much lower affinity for ethanolamine (Km = 460 microM) than choline kinase did for choline (Km = 17 microM), the activity of ethanolamine kinase in vivo may be more dependent on substrate availability than that of choline kinase. In addition, whereas ethanolamine kinase was inhibited by choline, and to a lesser extent by phosphocholine, choline kinase activity was unaffected by the presence of ethanolamine, or phosphoethanolamine, and only weakly inhibited by phosphocholine. Phosphoethanolamine cytidylyltransferase (PECT) and phosphocholine cytidylyltransferase (PCCT) also displayed dissimilar characteristics, with PECT and PCCT being located predominantly in the cytosolic and particulate fractions, respectively. Both PECT and PCCT exhibited a low affinity for CTP (Km approximately 1.2 mM), suggesting that the activities of these enzymes, and by implication, the rate of phospholipid synthesis, are highly dependent upon the cellular concentration of CTP. In conclusion our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more dependent upon substrate (ethanolamine) availability than that of PC synthesis.

Multiple forms of the enzyme glycerophosphodiesterase are present in human brain.

Brain levels of glycerophosphodiesters, including glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), are altered in many human central nervous system disorders. Although much information is available on the enzymes responsible for the formation of these phospholipid metabolites, little information is known regarding their catabolism, by glycerophosphodiesterases, in human brain. In both autopsied and biopsied temporal cortex, a phosphocholine-producing glycerophosphodiesterase activity was observed. In the presence of 1 mM EDTA, the enzyme possessed a pH optimum of 9.0, while the addition of 5 mM zinc acetate shifted the pH optimum to 10.5. When assayed at pH 9.0 in the absence of zinc acetate, the Km and Vmax were 104 +/- 2 microM and 77 +/- 18 nmol/h/mg protein, respectively, while assaying at pH 10.5 in the presence of 5mM zinc acetate yielded a Km of 964 +/- 56 microM, and a Vmax of 534 +/- 114 nmol/h/mg protein. Furthermore, whereas submillimolar concentrations of zinc acetate stimulated the activity of the enzyme in a dose-dependent manner when assayed at pH 10.5 (EC50 =20.3 +/- 3.0 microM), this did not result in a reciprocal inhibition of glycerophosphocholine phosphodiesterase (GPC PD) activity when assayed at a more acidic pH. This may suggest that human brain contains two phosphocholine-producing GPC PD activities, differentiable by their sensitivity to zinc ions. An activity capable of hydrolyzing GPE to form phosphoethanolamine could not be detected in either biopsied or autopsied brain. However, a choline/ethanolamine-producing glycerophosphodiesterase activity could be readily detected in biopsied, but not autopsied brain. this novel enzyme possessed a neutral pH optimum and was dependent upon divalent cations for activity. In conclusion, human brain contains at least two different glycerophosphodiesterases, a phosphocholine, and a choline/ethanolamine-producing activity, only one of which can be detected in autopsied tissue. The results of previous studies measuring brain glycerophosphodiesterase activity in degenerative brain conditions may need to be reevaluated in the light of these observations.

Determinants of bone mass in 10- to 26-year-old females: a twin study.

This cross-sectional twin study aimed to quantify the roles of constitutional and lifestyle factors on bone mass in adolescent and young adult women. Areal bone density (BMD) at the lumbar spine, femoral neck, Ward's triangle, and total hip, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry (DXA) in 215 female volunteer twin pairs (122 monozygotic [MZ], 93 dizygotic [DZ]) aged 10 to 26 years. Height, weight, menarchial history, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Mean BMD increased with age to around 16 years, when it reached a plateau. Within-pair differences in BMD at the lumbar spine (expressed as a percentage of the pair mean BMD) were univariately associated with pair differences in menarchial status (14 +/- 3%), height (0.7 +/- 0.1% per cm), weight (0.4 +/- 0.1% per kg), lean mass (1.0 +/- 0.1% per kg), and fat mass (0.5 +/- 0.1% per kg). Only menarchial status, height, and lean mass, however, were independent predictors. At the proximal femoral sites, within-pair BMD differences were associated with within-pair lean mass differences (1.0 to 1.1 +/- 0.2%/kg), and no other factor was significant. The same conclusions applied to within-pair differences in BMD/height. Total body BMC was independently associated with menarchial status, height, lean mass, and fat mass; the effects of the latter two variables were stronger in pairs both premenarchial. After adjusting for constitutional factors, no lifestyle factor was independently predictive. By reducing collinearity, the cotwin method clearly identified that lean mass, not fat mass, was the major independent determinant of bone mass at the hip, both pre- and postmenarche.

Activity of S-adenosylmethionine decarboxylase, a key regulatory enzyme in polyamine biosynthesis, is increased in epileptogenic human cortex.

OBJECTIVE: We measured the activity of S-adenosylmethionine decarboxylase, a key regulatory enzyme of polyamine biosynthesis, in the temporal cortex of patients with epilepsy. DESIGN: Cortical surgical specimens were obtained following anterior temporal lobe resection for intractable epilepsy. Enzyme activity was compared in nonepileptogenic (n = 16) and epileptogenic (spontaneously discharging; n = 19) regions. RESULTS: Mean enzyme activity was increased by 44% in samples from epileptogenic cortex compared with samples from nonepileptic regions. The S-adenosylmethionine decarboxylase activity in regions of focal epileptogenic discharges was also increased in five patients compared with paired samples from the nonepileptogenic portion of the same gyrus (+55%). CONCLUSIONS: Elevated activity of S-adenosylmethionine decarboxylase in regions of active epileptogenic cortical discharges suggests that a disturbance of the polyamine system may be involved in the maintenance of hypersynchronous discharges, perhaps through a modulatory action at the excitatory N-methyl-D-aspartate-preferring glutamate receptor.

Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease.

We followed 16 patients with a variety of mitochondrial diseases over one to four periods of treatment (2 months each) with coenzyme Q10 plus vitamins K3 and C, riboflavin, thiamine, and niacin, using independent measures of oxidative metabolism to assess efficacy. There were large (> threefold) increases in serum coenzyme Q10 concentrations with treatment, but no measure of oxidative metabolism showed significant improvement with treatment for the group, nor did any individual patient show significant, reproducible, objective clinical improvement. The results suggest that coenzyme Q10 plus vitamin therapy does not significantly improve mitochondrial oxidative metabolism in patients with mitochondrial disease in general. Any clinical benefit that may follow from short-term administration appears slight.

Excitatory amino acids modulate phosphoinositide signal transduction in human epileptic neocortex.

Stimulation of phosphoinositide (PI) hydrolysis by norepinephrine (NE), carbachol (Carb), and excitatory amino acids (EAAs) was measured in slices prepared from neocortex excised during epilepsy surgery. NE and Carb markedly enhanced PI turnover (EC50: NE, 12 microM; Carb, 661 microM) as reflected by [3H]inositol monophosphate (IP1) accumulation in tissue slices prelabeled with [3H]myoinositol. These effects were dose-dependent, saturable, and five to six times higher than basal IP1 accumulation. A weaker stimulation (twofold) was observed with quisqualate (QUIS; EC50, 1.1 microM) and glutamate (GLU; EC50, greater than 1 mM), while minimal or no stimulation was seen with kainate (KA) and N-methyl-D-aspartate (NMDA). Agonist-stimulated PI turnover was significantly reduced in samples from actively spiking epileptic neocortex versus nonspiking areas as defined by electrocorticography (NE, -23%, p less than 0.05; Carb, -44%, p less than 0.01). Preincubation of slices with various EEAs inhibited Carb-induced IP1 formation. The maximal extent of inhibition (1 mM) was both amino acid-dependent (IC50: NMDA, 5 microM; KA, 3.3 microM; QUIS, 47 microM; GLU, greater than 1 mM). These data suggest that epileptic activity modulates PI metabolism and alters receptor-effector coupling. As important mediators of epileptogenesis, EAAs may interfere++ with the efficiency of this second messenger system.

Developmental anterobasal temporal encephalocele and temporal lobe epilepsy.

The authors describe the association between an antero-basal temporal lobe encephalocele and medically intractable temporal lobe epilepsy in three patients treated successfully by surgery. Two men and one woman, aged 26 to 37 years (mean 31 years), had onset of complex automatism and generalized seizures in their second and fourth decades (mean age 22.7 years). They had been epileptic for 6 to 14 years (mean 8.3 years) before surgery. Preoperative electroencephalograms localized ictal epileptic activity to the left mesial temporal lobe in all cases, and neuropsychological testing revealed dominant temporal lobe dysfunction. Magnetic resonance (MR) imaging demonstrated an anteromedial basal temporal encephalocele extending into the pterygopalatine fossa through a bone defect at the base of the greater sphenoid wing in the region of the foramen rotundum and pterygoid process, a discrete center of embryonal chondrification. At surgery, the encephaloceles were found in front of the uncus, and an area of gliosis extended from the encephalocele to the amygdalohippocampal region. All patients have been seizure-free following anterior temporal resection and amygdalohippocampectomy including the encephalocele. These three cases delineate a condition of disordered embryogenesis wherein a developmental anterobasal temporal encephalocele acts as the substrate for temporal lobe epilepsy. This lesion may be diagnosed preoperatively with MR imaging and should be considered in the differential diagnosis of late-onset temporal lobe epilepsy.

Protein kinase C activity and intracellular distribution in surgically excised human epileptic neocortex.

Protein kinase C (PKC) activity assayed by phosphorylation of exogenous histone, was measured in neocortex obtained from 32 patients following surgery for focal epilepsy and from 6 non-epileptic patients. PKC activity was not significantly different in either the particulate or cytosolic fraction from epileptic foci (n = 17) versus samples from non-spiking regions (n = 22) or neocortex from non-epileptic patients (n = 6). From 67% to 70% of total PKC activity was present in the cytosolic fraction. Phosphorylation of endogenous cytosolic substrate proteins was also not significantly different in epileptic foci.

Alterations in cholecystokinin peptide and mRNA in actively epileptic human temporal cortical foci.

The cholecystokinin (CCK) content of temporal cortex, obtained at neurosurgery from 22 patients with temporal lobe epilepsy, was measured by a specific radioimmunoassay. Tissue immunoreactivity was identified as authentic sulfated CCK-8 by reverse phase high performance liquid chromatography. Several samples were also analyzed by RNA blot hybridization for preproCCK mRNA. The CCK content of cortical tissue from which active epileptic spiking was recorded at the time of surgery (11 patients) was significantly decreased (20% lower) in comparison to tissue samples from a second group of 11 patients in whom the lateral temporal cortex was electrographically free of epileptiform spikes. These data suggest that the decrease may be due to continuous release of CCK as a result of abnormal neuronal firing within the focus. This hypothesis may also be consistent with our observation of a slight increase (67%) in preproCCK mRNA in the actively spiking group compared to the non-spiking cortical samples.

Metabolism of prostaglandin D2 by human cerebral cortex into 9 alpha, 11 beta-prostaglandin F2 by an active NADPH-dependent 11-ketoreductase.

In homogenates of rat cerebral neocortex prostaglandin D2 (PGD2) was found to be quantitatively the main PG biosynthesized by a cytosolic PGD synthetase from endogenously released arachidonic acid. Amounts of 628 ng/g wet weight were found after 30-min incubation periods compared with basal levels of 2.3 ng/g wet weight. In human cerebral cortex, whether obtained at biopsy or postmortem, only small amounts of PGD2 (4.5-11.7 ng/g wet weight/30 min) were formed. Furthermore, PGD2, added to homogenates of human biopsy temporal cortex, was converted efficiently into 9 alpha,11 beta-PGF2 by a NADPH-dependent 11-ketoreductase as has been reported in other human tissues (liver and lung). PGF2 alpha was determined directly as the n-butylboronate derivative. It became clear that 9 alpha,11 beta-PGF2 was formed in considerably greater amounts than PGF2 alpha and that other metabolites are also formed. These results can account for the low amounts of PGD2 found in incubations of human brain tissue. The rat brain does not contain 11-ketoreductase activity. The present results indicate that the 9 alpha,11 beta-PGF2 must be considered along with other eicosanoids in pathophysiological situations in brain.