Brain and optic chiasmal herniation following cabergoline treatment for a giant prolactinoma: wait or intervene?

OBJECTIVE: Dopamine agonists (DA) are the treatment of choice in patients with macroprolactinomas. Brain and optic chiasm herniation are unusual complications following treatment with DA. REPORT: We present a case of a giant prolactinoma complicated by visual deterioration following cabergoline treatment. A 42-year-old man was admitted with seizures, right visual loss and visual defect in the upper left temporal quadrant. Magnetic resonance imaging (MRI) identified a giant adenoma, which proved to be a prolactinoma, compressing the optic chiasm and extending into the suprasellar region. Treatment with cabergoline was initiated resulting in improvement in visual fields, tumor shrinkage and prolactin level decrease. Five months later and despite tumor reduction, a deterioration of his visual fields was observed. The second MRI revealed brain and optic chiasmal herniation into the pituitary sella. Cabergoline dose was reduced and surgical resection of the adenoma along with untethering of the optic nerve was performed leading to improvement of the visual defects. CONCLUSIONS: This report describes a rare case of brain and optic chiasmal herniation attributed to DA therapy for a macroprolactinoma. It is important for clinicians to examine visual fields and promptly identify any visual deterioration in patients with macroprolactinomas receiving DA treatment.

Intraparenchymal haemorrhage and uncal herniation resulting from dobutamine stress echocardiography.

Intracranial haemorrhage (ICH) resulting from dobutamine stress echocardiography (DSE) is a rare complication in an otherwise relatively safe procedure. There has been one previously reported case of ICH associated with DSE in a patient who was fully anticoagulated. The authors report a second case of ICH associated with DSE leading to a poor outcome. Unlike the previous report, this patient was not fully anticoagulated and bleeding resulted from uncontrolled hypertension. Clinicians should be attentive to the risk of ICH associated with DSE in the setting of uncontrolled hypertension.

Encephalocele following a periconceptional exposure to efavirenz: a case report.

The use of Efaverinz in reproductive age women needs caution as its use in the first trimster of pregnancy is reportedly associated with an increased risk of neural tube defect (NTD) in the newborn. This concern is based on evidence from animal studies and two human case reports. We report here yet another case of encephalocele born from a mother who was taking efaverenze during conception and the first 8 weeks of gestation, the critical time in the pathogenesis of NTDs.

The manifestation of cocaine-induced midline destructive lesion in bone tissue and its identification in human skeletal remains.

Cocaine-induced midline destructive lesion (CIMDL) is a condition that may arise in response to chronic insufflation ("snorting") of cocaine. It is clinically diagnosed when the nasal septum, lateral nasal walls, and/or hard palate show signs of destruction in association with cocaine use. Although its true incidence is unknown, CIMDL is not an uncommon clinical finding amongst intranasal cocaine abusers and is likely to be encountered by forensic anthropologists and medical examiners working worldwide. Given the preponderance of drug abusers amongst the subjects of forensic casework, the ability to diagnose CIMDL in dry bone may provide crucial insight into an investigation and even help confirm an individual identification. This paper aims to make practicing forensic anthropologists aware of CIMDL. Through the analysis of existing clinical literature, patient CT scans, and histology sections, it works toward the establishment of formal diagnostic criteria for identifying CIMDL in human skeletal remains. Lytic destruction regularly involves the vomer and frequently extends to the perpendicular plate of the ethmoid, the palatal process of the maxillae or the palatine bones, and the inferior nasal conchae. The middle nasal conchae, medial walls of the maxillary sinuses, ethmoid sinuses, and cribriform plate are often damaged. Destruction may also implicate the superior nasal conchae, the orbit, and the sphenoid. Bones affected by CIMDL may contain necrotic lesions or may be absent entirely. Lesions show minimal, if any, signs of repair. The author proposes that this lack of new bone formation may be mediated by potentially elevated leptin levels in cocaine abusers and CIMDL patients and may be the key to differentiating CIMDL from other lytic processes of the midface.

Maternal occupational exposure to organic solvents during early pregnancy and risks of neural tube defects and orofacial clefts.

OBJECTIVES: Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs). METHODS: Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking. RESULTS: The prevalence of exposure to any solvent among mothers of NTD cases (n = 511), OFC cases (n = 1163) and controls (n = 2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR = 1.96, CI 1.34 to 2.87), especially spina bifida (OR = 2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data. CONCLUSIONS: The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.

Brain and optic chiasmal herniations into sella after cabergoline therapy of giant prolactinoma.

Optic chiasmal herniation following dopamine agonist therapy is a rare complication in patients with giant prolactinomas. But there are a few case reports of brain and chiasmal herniation following medical therapy in such cases. We report a young man who developed secondary visual loss and seizures after 6 months of medical treatment with cabergoline for giant prolactinoma. Magnetic resonance imaging of hypothalamic pituitary region revealed optic chiasmal and frontal lobe herniation into sella. There was marginal improvement in his vision after cabergoline dose reduction. The present case report highlights frontal lobe herniation in conjunction with optic chiasmal herniation as a very rare complication of medical therapy of giant prolactinoma. Different treatment options of this condition are being discussed.

Encephalocele--a single institution African experience.

OBJECTIVE: This study seeks to find out the presentation, management and complications of encephaloceles in an African setting. DESIGN: a retrospective study reviewing the age and sex of the patients, type and contents of encephaloceles, associated anomalies, preoperative evaluation and investigations, surgical approaches, intra- and post-operative complications as well as follow-up outcomes. SETTING: Bethany Crippled Children's centre and Bethanykids at Kijabe Hospital (BKKH), between January 1998 and August 2006. PATIENTS: Of the 53 patients seen, 23 were males and 30 females. The median age at presentation was four months. RESULTS: The follow-up period extended to eight years. Twenty nine patients had occipital encephaloceles, and 39 were operated using the direct external approach. Cererobrospinal fluid leak was the most common post-operative complication. Recurrence occurred in four patients and death in six. CONCLUSIONS: Most of the encephalocele patients manage d at BKKH had good outcomes and proceeded to live normal or near-normal lives. Our study confirms that even in resource-constrained areas, children with encephaloceles can be successfully managed with acceptable outcomes.

[Implication of dexamethasone adjunctive therapy after the onset of cerebral vasculitis in Streptococcus pneumoniae meningitis]. / Implication du traitement adjuvant par dexaméthasone dans la survenue d'une artérite septique cérébrale au cours d'une méningite à Streptococcus pneumoniae.

Few adverse effects have been reported with adjunctive dexamethasone treatment in pneumococcal meningitis. Nevertheless, we report a case of cerebral vasculitis. A 49-year-old man was admitted for fever and altered mental status. Lumbar puncture revealed a high inflammatory response and Streptococcus pneumoniae was identified by culture. Antibacterial therapy and adjunctive dexamethasone treatment were initiated as recommended. The immediate outcome was favorable but due to the onset of focal cerebral abnormalities, a CT scan was performed on the ninth day showing cerebral vasculitis. The patient died on the thirteenth day despite antibacterial therapy and resuscitation. In our case, a secondary neurological worsening appeared when adjunctive dexamethasone treatment was stopped suggesting a rebound effect. Observation of similar cases may lead to modifying adjunctive dexamethasone treatment protocol in bacterial meningitis.

Acute brain herniation from lead toxicity.

A 4-year-old black boy was admitted to the hospital with vomiting, low-grade fever, and dehydration that were thought to be caused by viral gastroenteritis. He proceeded over the next 12 hours to rapidly deteriorate with brain herniation leading to brain death. The ultimate cause of death was found to be acute lead intoxication from a swallowed foreign body.

Examination of meningocele induced by the antitumor agent DE-310 in rat fetuses.

The antitumor drug, DE-310, is the slow release form of the camptothecin derivative DX-8951. We investigated a toxicological profile of meningoceles in SD rat fetuses, whose mothers received intravenous DE-310 at several doses, and the time course changes of histology. DE-310 induced a meningocele in the posterior fontanelle of live fetuses by the four-time administration of 0.3 mg/(kgday) or more during the organogenetic period, or by a single administration of 1.0 mg/kg, particularly, between days 7 and 13 of gestation with an incidence of 100%. The meningocele was caused by the principal ingredient DX-8951. The earliest histological change was focal congestion between the skin and cerebrum, followed by the formation of a space covered by thinned epidermis with necrosed basal cells, hemorrhage in the surrounding connective tissues, cerebrum and ventricles, cavitation of the cerebrum, and incomplete formation of the skull bones and subarachnoid space. DE-310 was characterized as preferentially inducing meningocele (meningoencephalocele in severe cases) in rat fetuses.

Severe complications after intrathecal methotrexate (MTX) for treatment of primary central nervous system lymphoma (PCNSL).

Primary central nervous system lymphoma (PCNSL) is a rare and highly malignant tumor with increasing incidence. Survival has improved with the use of nonsurgical treatment modalities, of which methotrexate (MTX)-based intrathecal chemotherapy has been an important option. Here, we describe devastating complications in three patients with diffuse large B-cell lymphomas. After intrathecal MTX therapy two patients died secondary to fulminant brain edema. A third patient developed severe dementia, gait disturbance and urinary incontinence due to leukencephalopathy. Since bulky disease was present in all three patients, CSF flow may have been impaired. This might have exposed adjacent tissue to prolonged toxic drug concentrations. Regarding the severe complications seen in these patients, it is useful to consider high-dose intravenous MTX treatment only in periventricular PCNSL.

Successful treatment of refractory cerebral oedema in ecstasy/cocaine-induced fulminant hepatic failure using a new high-efficacy liver detoxification device (FPSA-Prometheus).

Ecstasy-induced fulminant hepatic failure is associated with high mortality. If complicated by cerebral oedema, orthotopic liver transplantation is the only established treatment. We report a case of combined ecstasy/cocaine-induced fulminant hepatic failure presenting with severe rhabdomyolysis, myocardial infarction and multiorgan failure. Transplantation was declined by the transplant surgeons because of a history of intravenous drug abuse. As excessive hyperammonaemia (318 mumol/l) and refractory transtentorial herniation developed, treatment with a new liver detoxification device combining high-flux haemodialysis and adsorption (FPSA-Prometheus) was initiated. Within a few hours of treatment, ammonia levels normalised. Cerebral oedema was greatly reduced by day 4 and hepatic function gradually recovered. Following neurologic rehabilitation for ischaemic sequelae of herniation, the patient was discharged from hospital with only minimal deficits. In conclusion, efficient extracorporeal detoxification may be an option for reversal of hyperammonaemia and refractory cerebral oedema in ecstasy/cocaine-induced acute liver failure.

Pilot dose-escalation study of caffeine plus ethanol (caffeinol) in acute ischemic stroke.

BACKGROUND AND PURPOSE: In animal models, the combination of caffeine and ethanol (caffeinol) provides robust neuroprotection at blood levels that should be easily and safely achieved in humans. This study was designed to determine the safety and tolerability of ascending doses of this combination in stroke patients. METHODS: This Food and Drug Administration-approved open-label, single-arm, dose-escalation study had 3 original dose groups: group 1, caffeine 6 mg/kg plus ethanol 0.2 g/kg; groups 2 and 3, incremental increases of caffeine and ethanol by 2 mg/kg and 0.2 g/kg, respectively. Intravenous thrombolysis was encouraged if patients qualified. Drug was started within 6 hours of stroke onset, and blood levels of caffeine and ethanol were drawn at baseline and end of infusion. The target blood caffeine and ethanol ranges were 8 to 10 microg/mL and 30 to 50 mg/dL, respectively. Clinical outcome measurements included the National Institutes of Health Stroke Scale at the end of infusion, at 24 hours, and at discharge. Potential complications from caffeine and ethanol were recorded. Cases were reviewed by an independent stroke neurologist for safety. RESULTS: A total of 23 patients were recruited. Target blood caffeine and ethanol levels were reached in 0 of the 4 patients in the first group. The second dose group (caffeine 8 mg/kg plus ethanol 0.4 g/kg) included 8 patients. The median end-of-infusion caffeine and ethanol levels were within the desired target ranges. Two days after infusion, 1 patient in this group with preexisting cardiac disease and end-of-infusion caffeine and ethanol levels of 10.7 microg/mL and 69 mg/dL developed reversible congestive heart failure and required transfer to an intensive care unit. The original third dose group was canceled given achievement of target blood caffeine and ethanol levels in group 2. However, 3 new dose groups were created in an attempt to minimize the dose of ethanol. Although blood levels were proportional to dose, none of these new dose groups provided optimal blood levels. Congestive heart failure occurred in 1 other patient with previously asymptomatic cardiomyopathy. No other side effects were noted. Concomitant thrombolytic therapy was given in 8 patients, 1 of whom died of intracerebral hemorrhage. CONCLUSIONS: Caffeinol alone or combined with intravenous tissue plasminogen activator can be administered safely. Caffeine 8 mg/kg plus ethanol 0.4 g/kg produces target caffeine and ethanol levels of 8 to 10 microg/mL and 30 to 50 mg/dL, respectively. A randomized, placebo-controlled trial is needed to determine the neuroprotective effect of this combination.

[Upper and lower neural tube defects: prevalence and association with illnesses and drugs]. / Defectos del tubo neural altos y bajos, prevalencia, y asociación con enfermedades y medicamentos.

OBJECTIVE: To determine the prevalence of upper and lower neural tube defects and identify its association with the exposure to illnesses and drugs during pregnancy. MATERIAL AND METHODS: This is a case-control study of 107 newborns with upper neural tube defects, 59 with lower neural tube defects, and 166 newborns without malformations, in 56,926 consecutive births between 1989 and 1997. The exposure was documented by a direct interview to the mother of those subject of study. The association was measured by the odds ratios, with confidence interval of 95%. RESULTS: The prevalence of upper neural tube defects was of 1.9 for 1,000 newborn (alive or dead) and of lower neural tube defects of 1.0 for 1,000. The exposure to illnesses of less than a month of duration was associated with upper neural tube defects (OR = 3.11; IC = 1.34-7.39) the most important was flu; also the exposure to drugs (OR = 5.85; IC = 2.97-11.62), the most prominent was acetaminophen. These factors of risk were not associated with lower neural tube defects. The mother's occupation, illness of more than a month of duration and X-ray exposure were not associated with of upper and lower neural tube defects. CONCLUSIONS: More studies are needed in the association among illnesses of less than a month of duration and drugs with upper neural tube defects. The different exposure frequencies between upper and lower neural tube defects suggest heterogeneity.

Nonaccidental endosulfan intoxication: a case report with toxicokinetic calculations and tissue concentrations.

CASE REPORT: A case of nonaccidental endosulfan intoxication in a previously healthy 43-year-old male patient is reported. On admission, the patient had few symptoms, but refractory seizures began 1 hour after ingestion. The patient died on the fourth day after admission showing clinical signs of cerebral herniation confirmed at autopsy. Blood, urine, and tissue samples were analyzed for alpha-endosulfan, beta-endosulfan, and endosulfan sulfate by capillary gas chromatography with electron capture detection. Concentration versus time data for endosulfan were fitted using the program MW/Pharm, assuming complete bioavailability although it is recognized that the bioavailability of endosulfan after ingestion may have been low and the calculated clearance was primarily due to redistribution. Hemoperfusion was shown to be ineffective.

Altered zinc metabolism contributes to the developmental toxicity of 2-ethylhexanoic acid, 2-ethylhexanol and valproic acid.

It has been hypothesized that the developmental toxicity of certain compounds is, in part, due to maternal toxicity resulting in alterations in zinc (Zn) metabolism that affects the developing conceptus. In the present work the effects of developmentally toxic doses of 2-ethylhexanoic acid (EHXA), 2-ethylhexanol (EHXO), and valproic acid (VPA) on Zn metabolism were investigated in the pregnant rat. In experiment 1, dams were intubated with EHXA (3.13, 6.25, 9.38 or 12.5 mmol/kg), EHXO (6.25, 9.38 or 12.5 mmol/kg), VPA (1.56, 3.13, 6.25 or 9.38 mmol/kg), or corn oil (control; 1.0 ml/kg) at 14:00 h on gestation day (GD) 11.5, intubated with 32 microCi 65Zn at 22:00 h, and then killed at 08:00 h on GD 12.5. At the higher dose levels of EHXA and EHXO, and at all dosages of VPA, the percentage of 65Zn retained in maternal liver was higher, while that in the embryos was lower, than in controls. Chemical-associated changes in 65Zn distribution were associated with increased maternal liver metallothionein (MT) concentrations. In experiment 2, dams were fed diets containing 1, 25 or 97 microg Zn/g from GD 0-16 and intubated with 3.5 mmol EHXA or 1.0 ml corn oil/kg/d from GD 8-15. Dams were killed on GD 16 or 19. High incidences of encephalocele and tail defects were noted in the GD 16 fetuses of EHXA-treated dams fed either the low or adequate Zn diet, the highest incidences being in the low Zn group. On GD 19 the incidence of tail defects tended to be higher in the EHXA groups than in oil-treated controls, the highest incidence occurring in the low Zn EHXA group. Encephalocele was only observed in the low Zn EHXA-treated group. Fetal weight and crown-rump lengths were decreased by EHXA treatment and low dietary Zn. The incidence of rib anomalies was higher in the EHXA-exposed groups than in their respective oil controls. In experiment 3, GD 10.5 embryos collected from control dams were cultured for 48 h in serum from control or EHXA-treated male rats fed 4.5 or 25.0 microg Zn/g diets. Embryos cultured in either EHXA or low Zn sera exhibited delayed development; the addition of Zn to these sera eliminated their developmental toxicity. These results support the hypothesis that certain chemicals which induce maternal toxicity act, in part, to influence embryonic Zn metabolism and trigger abnormal development. Importantly, the teratogenic effects of these chemicals can be modulated by dietary Zn intake.