Fulminant radiation-induced necrosis after stereotactic radiation therapy to the posterior fossa. Case report and review of the literature.

The problem of radiation-induced necrosis of normal brain surrounding the target area has been a major catalyst for the development of stereotactically focused radiation therapy. According to current opinion, the effects of stereotactic irradiation are confined to the region targeted. The authors present a case in which the administration of a conventional dose of stereotactically focused irradiation for treatment of a pilocytic astrocytoma produced fulminant necrosis that necessitated a combination of intensive surgical and medical management, after which the patient improved over the course of 1 year. Concomitant with his improvement, the initially remarkable findings on magnetic resonance imaging gradually resolved. In this presentation the authors emphasize the need to evaluate alternatives carefully before a decision is made to administer therapeutic irradiation. Furthermore, they explore the roles that target, host, and dosage factors play in hypersensitivity to radiation injury, the detection of these factors before treatment, and the administration of radioprotective agents. With the growing use of stereotactically focused irradiation as a primary treatment modality for a variety of neurosurgical conditions, it is important to be cognizant of its uncommon but potentially lethal side effects. A cooperative multicenter database in which the outcomes and morbidity following stereotactic irradiation are recorded is essential to the detection of relatively uncommon but severe complications such as those observed in this case.

Fatal hyperthermia in hot baths in individuals with multiple sclerosis.

The authors report the case of a 47-year-old black man with a history of multiple sclerosis who was found dead in a bathtub, head above water, with a body temperature of 105.7 F. Results of a complete autopsy and toxicologic screen were negative. Individuals with multiple sclerosis, if immersed in hot water, develop motor weakness, which may be so severe as to prevent them from getting out of the water, whether they be in a bathtub or whirlpool bath. In this case, the individual was trapped in a bathtub in which there was a continuous flow of hot water. This overwhelmed an already impaired thermoregulatory mechanism, causing hyperthermia and death.

An unusual case of the complete Currarino triad: case report, discussion of the literature and the embryogenic implications.

OBJECTIVE AND IMPORTANCE: We present and illustrate an unusual case of the complete familial Currarino triad (an association between a bony sacral defect, a presacral mass, and an anorectal malformation) in which the teratoma arose from the conus medullaris and contained mature neurons, glia, and branching ependymal canals that were in communication with a terminal syrinx. The embryogenic implications are discussed. CLINICAL PRESENTATION: The patient was a term neonate when discovered to have imperforate anus. Further workup revealed lumbosacral dysraphism with a presacral mass, a rectovaginal fistula, and a single pelvic kidney. The family pedigree revealed a familial transmission pattern; the patient had a second cousin with anal atresia and a first cousin with similar sacral anomalies. The motor level was L4 with trace L5, and there was absent sensation in the sacral dermatomes. INTERVENTION: A diverting colostomy was performed on Day 14, and the infant returned at 3 months of age to undergo near-total resection through the previous abdominal approach. Only a subtotal resection was possible because the mass arose from the low-lying conus and was firmly adherent to the sacral nerve roots and iliac vessel. Follow-up magnetic resonance imaging performed 18 months after surgery revealed that the residual tumor had not progressed. CONCLUSION: Complete Currarino triad is rare and is familial in half of the cases. The special features of the tumor in our case were the presence of mature neurons with ependymal canals and its origin from the conus. The possible embryogenesis may provide evidence that the caudal notochord is important for organized secondary neurulation.

Myofibrillar myopathy: no evidence of apoptosis by TUNEL.

The pathogenesis of myofibrillar myopathy (MFM) is not known. Muscle biopsy specimens demonstrate increased expression of cell cycle regulatory proteins as well as the ectopic expression of lamin B and nuclear matrix protein in the cytoplasm, suggesting the possibility of apoptosis. The authors investigated for apoptosis using the TUNEL method in six muscle biopsy specimens from patients with MFM. There was no evidence of apoptotic myonuclei in any of the MFM muscle biopsies. Further studies regarding the pathogenesis of MFM and the possible role of mitotic catastrophe are needed.

The wide spectrum of myofibrillar myopathy suggests a multifactorial etiology and pathogenesis.

BACKGROUND: Myofibrillar myopathy (MFM) is characterized by nonhyaline lesions (foci of myofibrillar destruction) and hyaline lesions (cytoplasmic inclusions composed of compacted myofibrillar residues) on light and electron microscopy. Immunocytochemistry demonstrates the abnormal expression of desmin and numerous other proteins. The clinical, laboratory, and histologic features of MFM are heterogeneous, making a diagnosis difficult. RESULTS: We diagnosed eight patients with MFM over the preceding 3 years. MFM was inherited in an autosomal dominant pattern in one patient, developed sporadically in five patients, and was induced by an experimental chemotherapy, Elinafide (Knoll, Parsippany, NJ), in two patients. Age at onset ranged from 14 to 64 years. The pattern of weakness was variable but involved proximal and distal muscles. Five patients had evidence of a cardiomyopathy. Electromyography demonstrated muscle membrane instability and small, polyphasic motor unit potentials. Serum creatine kinase levels were normal to moderately elevated (<10x normal). Light and electron microscopy demonstrated the characteristic pattern of nonhyaline and hyaline lesions and the associated abnormalities on immunocytochemistry. CONCLUSIONS: Patients demonstrate a wide spectrum of clinical, laboratory, and histologic abnormalities. Chemotherapy-induced MFM has abnormalities on immunocytochemistry similar to the those of hereditary and sporadic cases. The pathogenesis of MFM is likely heterogeneous. However, MFM is distinctive in that it can preferentially affect distal muscles and has a frequent association with cardiomyopathy. The cardiomyopathy may be amenable to treatment with pacemaker insertion or cardiac transplantation.

Evaluation of neuromuscular symptoms in veterans of the Persian Gulf War.

OBJECTIVE: To comprehensively evaluate complaints of muscle fatigue, weakness, and myalgias in Persian Gulf veterans (PGV). BACKGROUND: Approximately 700,000 American troops were deployed to the Persian Gulf during Desert Shield and Desert Storm. Upon return from the Gulf, some PGV developed unexplained illnesses, and special referral centers were established for the evaluation of these patients. Among the most common symptoms of these PGV are fatigue, weakness, and myalgias. An Institute of Medicine committee recommended further exploration into the possible etiologies of these complaints. METHODS: Twenty PGV with severe muscle fatigue, weakness, or myalgias that interfered with their daily activities were referred for an extensive prospective neuromuscular evaluation. Routine laboratory studies included serum creatine kinase (CK), erythrocyte sedimentation rate, thyroid function tests, and exercise forearm tests. All patients received nerve conduction studies (NCS), repetitive nerve stimulation, quantitative and single-fiber electromyography (EMG), and muscle biopsies. RESULTS: Manual muscle strength examinations were normal in all patients. Six patients had mildly elevated CKs (range 223 to 768 IU/l); otherwise, laboratory tests were unremarkable. NCS were normal except in 2 patients with carpal tunnel syndrome. Quantitative EMGs were normal. One patient had mildly increased jitter on single-fiber EMG. Muscle biopsies demonstrated minor nonspecific abnormalities in 5 patients (i.e., increased central nuclei, rare necrotic fibers, tubular aggregates). CONCLUSIONS: Despite severe subjective symptoms, most of our patients had no objective evidence of neuromuscular disease. Mildly increased CKs or nonspecific histologic abnormalities on muscle biopsy were evident in 8 patients but were not believed to be clinically significant in most. We found no evidence of a specific neuromuscular disorder in any patient. Exposures to toxins during the Persian Gulf War were not likely responsible for our patients' symptoms.

Anti-intercellular adhesion molecule-1 (ICAM-1) antibody treatment prevents central and peripheral nervous system disease in autoimmune-prone mice.

Abnormal neurological functioning similar to that seen in systemic lupus erythematosus (SLE) patients is detectable in an SLE-prone murine strain (MRL/lpr) by 8-10 weeks and is severe by 18 weeks of age. The purpose of this study was to evaluate the effectiveness of murine antiintercellular adhesion molecule-1 (ICAM-1) in suppressing neurological disease in MRL/lpr mice. Beginning at 6 weeks of age, five MRL/lpr mice received 5 weekly intraperitoneal injections of anti-ICAM-1-containing culture supernatant in phosphate-buffered saline (PBS) whereas four animals were treated with non-anti-ICAM-1 containing supernatant in PBS. A decline in neurological functioning began in control mice by 10 weeks, but anti-ICAM-1 treated mice remained normal throughout the study. All control mice had vasculitic skin lesions by 14 weeks of age whereas none of the anti-ICAM-1 treated mice ever developed skin lesions. Nerve conduction studies performed on all mice prior to sacrifice showed sciatic compound motor action potentials of anti-ICAM-1 treated mice that were of higher amplitude and shorter latency than those of controls. Inflammation in the sciatic nerve was more common in control mice. Brain histology revealed a similar degree of choroid plexus inflammation in both groups. Our study demonstrated that anti-ICAM-1 was effective in suppressing neurological abnormalities in MRL/lpr mice and may potentially be useful therapy in human SLE.

Effect of hyperbaric oxygenation on peripheral nerve regeneration in adult male rabbits.

Oxygen environments were used to study the regenerative effects of hyperbaric oxygen on crushed sciatic nerves in 30 adult male rabbits. Six different oxygen environments were used, and treatments were initiated 4 days post injury. Transmission electron microscopy and light microscopy were used to evaluate the regenerative morphology of crushed nerves. The morphology of crushed nerves after 7 wk of treatment with compressed oxygen at 202, 242, and 303 kPa resembled normal uncrushed nerves, with nerve fibers uniformly distributed throughout the section. The treatment groups receiving 202 kPa compressed air, 100% normobaric oxygen, or ambient air did not display morphologies similar to normal uncrushed nerve. The nerves in these animals were edematous and contained disarrayed nerve fibers. Myelination in the animals receiving 100% O2 at high pressures resembled undamaged nerves. Collagen and blood vessels were more evident in the lower pressure/oxygen tension treatments than in the animals receiving 100% O2 at higher pressures. The neurofilamentous material inside the crushed control axons was dense, whereas in the axons of animals treated with compressed O2 it was loosely packed. These differences in morphology suggest that treatments consisting of 100% O2 under pressure can accelerate a peripheral nerve's recovery from a crush injury.

Tomaculous neuropathy: a clinical and electrophysiological study in patients with and without 1.5-Mb deletions in chromosome 17p11.2.

Tomaculous neuropathy is the descriptive term for the "sausagelike" swellings of myelin characteristic of hereditary neuropathy with liability to pressure palsies (HNPP). A 1.5-Mb deletion in chromosome 17p11.2 is present in the majority but not all cases of HNPP. We reviewed the clinical and electrophysiological features of 18 patients with tomaculous neuropathy and compared these features between patients with and without the typical large deletion. Patients presented with a variety of pressure-induced nerve palsies and brachial plexopathies. Two patients presented with generalized symmetric sensorimotor polyneuropathies. Four patients were older than their respective probands but were as yet asymptomatic. Nerve conduction studies demonstrated prolonged distal latencies out of proportion to slowing of conduction velocities, suggesting a distally accentuated myelinopathy. DNA analysis revealed the 1.5-Mb deletion in all the familial cases and in 3 of the sporadic patients. The clinical and electrophysiological features were similar between patients with and without the 1.5-Mb deletion in chromosome 17p11.2.

Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles.

Transgenic mice carrying heterologous genes directed by a 670-bp segment of the regulatory sequence from the human transferrin (TF) gene demonstrated high expression in brain. Mice carrying the chimeric 0.67kbTF-CAT gene expressed TF-CAT in neurons and glial cells of the nucleus basalis, the cerebrum, corpus callosum, cerebellum, and hippocampus. In brains from two independent TF-CAT transgenic founder lines, copy number of TF-CAT mRNA exceeded the number of mRNA transcripts encoding either mouse endogenous transferrin or mouse endogenous amyloid precursor protein. In two transgenic founder lines, the chloramphenicol acetyltransferase (CAT) protein synthesized from the TF-CAT mRNA was estimated to be 0.10-0.15% of the total soluble proteins of the brain. High expression observed in brain indicates that the 0.67kbTF promoter is a promising director of brain expression of heterologous genes. Therefore, the promoter has been used to express the three common human apolipoprotein E (apoE) alleles in transgenic mouse brains. The apoE alleles have been implicated in the expression of Alzheimer disease, and the human apoE isoforms are reported to interact with different affinities to the brain beta-amyloid and tau protein in vitro. Results of this study demonstrate high expression and production of human apoE proteins in transgenic mouse brains. The model may be used to characterize the interaction of human apoE isoforms with other brain proteins and provide information helpful in designing therapeutic strategies for Alzheimer disease.

Evaluation of histopathologic changes in an animal model of mechanical corpus callosum impingement as seen in hydrocephalus.

RATIONALE AND OBJECTIVES: We evaluated histologic changes associated with chronic impingement of the corpus callosum. Similar callosal impingement has been postulated to be responsible for some of the symptoms in people who have hydrocephalus. METHODS: Eight rats with callosal impingement produced by surgical implantation of a blunt blade in the interhemispheric fissure and four control animals with no callosal impingement were evaluated by magnetic resonance (MR) imaging and by direct histologic evaluation after autopsy. The histologic evaluations occurred 1 month after surgery in half the animals and 6 months after surgery in the other half. RESULTS: MR imaging results showed that the implanted blade was in a good position in all animals. Histologically, the corpus callosum appeared normal 1 month after implantation of the impingement blade. Six months after surgery, the experimental group demonstrated decreased callosal thickness and a loss of axonal fibers in the corpus callosum both near and remote to the blade. CONCLUSION: Chronic impingement of the corpus callosum was associated with callosal thinning and by loss of callosal axons. Further research will be required to investigate the possible relation of these histologic findings to the clinical findings in normal-pressure hydrocephalus.

Neonatal nemaline myopathy with abundant intranuclear rods.

A term hypotonic female infant was born to a primigravida mother. The infant required mechanical ventilation from birth until death at 5 weeks of age. An elevated serum creatine kinase of 1300 IU l-1 lead to a quadriceps muscle biopsy at 3 days of age. The biopsy showed numerous intranuclear inclusions on light microscopy. Electron microscopy revealed the inclusions to be rod (nemaline) bodies and were located in 80% of the muscle nuclei. Cytoplasmic rod bodies were also present in 50% of the muscle fibers, often arising from Z discs. The intranuclear rods were more than ten times larger than the cytoplasmic rods. There have been eight reported cases of abundant intranuclear rods in nemaline myopathy: three adult onset; one childhood onset; and four neonatal (including this case). Six of the cases (all of the neonatal and two adult onset) died due to respiratory failure and pneumonia. While intranuclear rods are unusual in nemaline myopathy, they occur in both adult and neonatal cases, and their presence is often associated with a fatal outcome.

Perinatal effects of Gardnerella vaginalis deciduitis in the rabbit.

OBJECTIVE: We determined the effects of intrauterine infection with Gardnerella vaginalis on maternal and fetal outcome in the rabbit. STUDY DESIGN: Both uterine horns of rabbits on day 20 or 21 of gestation (70% of gestation) were inoculated hysteroscopically with either 0.2 ml of 10(5) to 10(7) CFU/ml of G. vaginalis or saline solution. Animals were killed on day 4 or earlier if premature delivery occurred. The following outcome parameters were evaluated: febrile morbidity, preterm labor and delivery, maternal cultures, fetal birth weight, and fetal neuropathologic findings. RESULTS: G. vaginalis intrauterine inoculation uniformly resulted in amnionitis and deciduitis. Animals inoculated with G. vaginalis had no greater incidence of fever and preterm delivery than did saline-treated control animals. However, intrauterine infection with G. vaginalis resulted in a significant decrease in the live birth rate when compared with that of controls (80% vs 95%, p < 0.03). G. vaginalis deciduitis was associated with as 23% reduction in the birth weight of the surviving fetuses. Furthermore, animals in the G. vaginalis study group had a 60% incidence of severe brain injury compared with 0% in the saline solution group. CONCLUSION: G. vaginalis amnionitis and deciduitis produced minimal maternal morbidity but were associated with decreased birth weight and brain injury in surviving fetuses; thus it appears that G. vaginalis selectively functions as a fetal, but not maternal, pathogen in the rabbit.

Rostral transfontanel herniation.

Upward transtentorial herniation as a result of mass effect in the posterior fossa has been described in adults by several authors. We report the case of a premature infant, small for gestational age, who experienced rostral herniation of a portion of frontal lobe through the anterior fontanel as the result of a hemorrhagic cerebellar infarction followed by a large parieto-occipital intracerebral hemorrhage.

Sellar and juxtasellar neoplasms.

Magnetic resonance imaging is the modality of choice for evaluating lesions in and around the sella turcica. The article highlights various neoplasms of the pituitary gland and the juxtasellar region. The differentiating imaging characteristics and clinical presentations of these neoplasms are discussed. Even with the best imaging techniques available, however, biopsy or excision of the lesion is still necessary to establish the histologic diagnosis.

Congenital ceroid-lipofuscinosis.

A term infant, observed at birth to be microcephalic, developed status epilepticus and died 36 hours later. At autopsy a markedly atrophic brain was found which, by microscopic examination, demonstrated changes consistent with neuronal ceroid-lipofuscinosis. Cerebral lipidosis with microcephaly presenting at birth is extremely rare. Congenital neuronal ceroid-lipofuscinosis is an atypical form of ceroid-lipofuscinosis and should be considered in the differential diagnosis of the microcephalic neonate with seizures.

MRI of radiation induced spinal cord glioma.

Radiation induced neoplasms of the spinal cord are rare lesions. This report details the MR evaluation of a patient with radiation induced astrocytoma of the cervical cord. The diagnosis of second primary neoplasm should be considered in patients with prior radiation therapy when MRI demonstrates an intramedullary lesion.

Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme.

Recessive mutations, revealed by loss of the wild-type allele, have been associated with the development of a variety of cancers in children and adults. Polymorphic chromosome 10 markers were used to screen paired tumor and lymphocyte DNA samples in 13 patients with glioblastoma multiforme. Ten patients showed loss of constitutional heterozygosity in the tumor samples. This finding suggests that a recessive gene involved in the development of glioblastoma multiforme is present on chromosome 10.