Typical Central Nervous System Research Articles

Embryonic Intermediate Filaments, Nestin and Vimentin, Expression in the Spinal Cords of Rats with Experimental Autoimmune Encephalomyelitis

Intermediate filaments, including nestin and vimentin, are found in specific cell types in central nervous system (CNS) tissues, particularly immature glial cells and multipotent progenitor cells. In the present study, the expression patterns of nestin and vimentin in the spinal cords of rats with experimental autoimmune encephalomyelitis (EAE) and the response of cells containing filaments against acute autoimmune injury were examined by immunohistochemistry. Nestin immunostaining was only weakly detected in vascular endothelial cells but not in any cell types in the spinal cord in normal and adjuvant-immunized rats. At the peak stage of EAE, nestin-immunoreativity was recognized in some astrocytes in the gray matter and white matter. Vimentin was immunopositive in some astrocytes and macrophages in EAE lesions, while vimentin was normally detected in ependymal cells of central canals in the rat spinal cords.We postulate that normal animals may contain multipotent progenitor cells in the spinal cord parenchyma as well as in the subpial lesion and ependyma. Multipotent progenitor cells may activate to transform into necessary cells, including neurons, astrocytes or oligodendrocytes, depending on CNS needs. Appropriate control of progenitor cells in the injured CNS is an alternative choice for CNS remodeling.

Vagus nerve stimulation for partial seizures.

Vagus nerve stimulation (VNS) has recently been introduced as an adjunct for treating patients with seizures. The aim of this systematic review was to overview the current evidence for the effects of vagus nerve stimulation, when used as an adjunctive treatment for patients with drug-resistant partial epilepsy. To determine the effects of VNS high-level stimulation compared to low-level (presumed subtherapeutic dose) stimulation. We searched the Cochrane Epilepsy Group trials register, MEDLINE (January 1966 to October 2000) and The Cochrane Controlled Trials Register (Cochrane Library Issue 4, 2000). Randomized, double-blind controlled trials of VNS comparing high and low stimulation paradigms. Studies in adults or children with drug-resistant partial seizures. Two reviewers independently selected trials for inclusion and extracted data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. Results of the overall efficacy analysis show that VNS stimulation using the high stimulation paradigm was significantly better than low stimulation. The overall OR (95% Confidence Interval (CI)) for 50% responders across all studies is 1.93 (1.1,3.3). This effect did not vary substantially and remained statistically significant for both the best and worst case scenarios. Results for the outcome "withdrawal of allocated treatment" suggest that VNS is well tolerated as no significant difference was found between the high and low stimulation groups, and withdrawals were rare. Statistically significant adverse effects associated with implantation (low versus baseline) were hoarseness, cough, pain and paresthesia. Statistically significant adverse effects associated with stimulation (high versus low) were hoarseness and dyspnea, suggesting the implantation is associated with hoarseness, but the stimulation produces additional hoarseness. VNS for partial seizures appears to be an effective and well tolerated treatment. Adverse effects of hoarseness, cough, pain, paresthesias and dyspnea are associated with the treatment but appear to be reasonably well tolerated as dropouts were rare. Typical central nervous system adverse effects of antiepileptic drugs such as ataxia, dizziness, fatigue, nausea and somnolence were not statistically significantly associated with VNS treatment.

Changes in P2Y and P2X purinoceptors in reactive glia following axonal degeneration in the rat optic nerve

Purinoceptors have been shown to be important in mediating Ca 2+ signalling in glial cells and it has been proposed that they may have a role in their response to injury. To investigate this, the glial response to adenosine 5′triphosphate (ATP) was measured in situ, in optic nerves from juvenile rats that were enucleated at postnatal day (P) 1; age-matched normal nerves were used as controls. The optic nerve is a typical central nervous system (CNS) white matter tract containing axons and glial cells, but not neurones or synapses. Following neonatal enucleation, axons degenerate and oligodendrocytes do not develop, so that the optic nerve is populated predominantly by reactive astrocytes, with a minor population of activated microglia. Application of 1 mM ATP evoked a large and rapid increase in glial [Ca 2+] i in fura-2 ratiometric whole nerve recordings from normal and gliotic axon-free nerves. Significantly, the response to ATP had a prolonged duration in gliotic axon-free nerves and there was as shift in the agonist rank order of potency from ATP = ADP > UTP ⪢ α,β-metATP to ATP > ADP = UTP = α,β-metATP. The results indicate an in situ role for ATP signalling in reactive astrocytes, via metabotropic P2Y 1 and P2Y 2/4 purinoceptors and ionotropic P2X purinoreceptors. The change in the purinoceptor profile following axon degeneration suggests a special role for P2X purinoceptors in mediating the glial reaction to CNS injury.

Fetal Alcohol Syndrome

1. Helen M. Thackray, MD* 2. Cynthia Tifft, MD, PhD† 1. 2. *Clinical Fellow, Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD. 3. 4. †Chair, Department of Medical Genetics, Children’s National Medical Center, Washington, DC. Objectives After completing this article, readers should be able to: 1. Describe the signs of fetal alcohol syndrome in the context of in utero exposure to alcohol. 2. Describe the relationship of facial characteristics and neuorobehavioral findings in fetal alcohol syndrome with age. 3. Compare and contrast the neurobehavioral aspects of children who have fetal alcohol syndrome with children who have other diagnoses and similar intelligence quotients. 4. Delineate the causes of fetal alcohol syndrome. Alcohol is the most common human teratogen, but its significant physical and neurobehavioral effects are completely preventable. Fetal alcohol syndrome (FAS) was described initially in case reports by Lemoine in 1968 and Jones and Smith in 1973. It is a pattern of physical, behavioral, and cognitive abnormalities seen in individuals exposed to alcohol in utero. The association between these findings and maternal use of alcohol during pregnancy has been well documented, with studies in both animals and humans suggesting teratogenicity from as little as one binge drinking episode in early pregnancy. The diagnostic criteria are not a result of fetal physical dependence or addiction or the presence of alcohol in the neonate at delivery; rather, they are teratogenic effects caused by in utero exposure to alcohol in the mother’s blood. In 1996, following a congressional mandate that the Institute of Medicine and National Academy of Sciences study FAS and related birth defects, these institutions published a review of the current understanding of FAS and revised the diagnostic criteria. Despite increased awareness of this preventable birth defect, new cases continue to occur in significant numbers and are routinely under-recognized by medical personnel. It is imperative that maternal alcohol use and its sequelae be considered and addressed in daily pediatric practice. The purpose of this article is to review the diagnosis, epidemiology, management, prognosis, and prevention of FAS. FAS represents a …

Experience from a multidisciplinary "dizzy" clinic.

To describe the experience of a combined otolaryngology and neurology multidisciplinary clinic in the evaluation, investigation, and management of patients with dizziness. Prospective clinical study. Patients were seen in a tertiary referral, multidisciplinary clinic at The Toronto Hospital, University of Toronto, Ontario, Canada. A thorough history, formal otoneurologic examination, and appropriate laboratory investigations were performed. After their assessment, the patient's diagnoses were classified as peripheral, central, psychogenic, or undiagnosed and were then subdivided into specific clinical diagnoses. The first 812 consecutive patients seen in the multidisciplinary clinic from January 1, 1993 to December 31, 1998 are reported. Five hundred twenty-five (64.7%) patients were found to have a peripheral vestibular cause for their dizziness, 66 (8.1%) had a central cause, 108 (13.3%) had a diagnosis unknown, and 73 (9.0%) were thought to be psychogenic. In 40 (4.9%) patients, a peripheral and central cause were found. More than one type of peripheral disorder was noted in 17.9% of patients with a peripheral vestibular cause for their dizziness, and 12.3% of patients with a central cause for their dizziness had more than one specific type of central nervous system disorder. Most patients that were seen in a multidisciplinary clinic had a peripheral vestibular disorder. Central causes of dizziness were relatively uncommon. Serious diseases such as tumor, multiple sclerosis, and encephalitis were rare and unlikely to present with dizziness only. It is important to realize that a patient may have more than one type of disorder accounting for the symptoms, which may represent a spectrum of disease affecting the inner ear.

Pharmacological Evaluation of Ricinine, a Central Nervous System Stimulant Isolated from Ricinus communis

The extract of the pericarp of castor bean ( Ricinus communis) showed some typical central nervous system stimulant effects when administered to mice. The animals became exophthalmic, presented tremors and clonic seizures and died a few minutes after receiving larger doses of the extract. At lower doses the extract improved memory consolidation and showed some neuroleptic-like properties, such as a decrease in exploratory behavior and catalepsy. The memory-improving effect and the seizure-eliciting properties of the extract were also observed with the administration of ricinine, a neutral alkaloid isolated from the extract. However, the neuroleptic-like properties of the extract were not observed with ricinine. As the therapeutic index of ricinine is of the order of 200, the compound may be considered as a promising cognition-enhancing drug that may be used for the treatment of human amnesias.

Disproportionate Recruitment of CD8 + T Cells into the Central Nervous System by Professional Antigen-Presenting Cells

Inappropriate immune responses, thought to exacerbate or even to initiate several types of central nervous system (CNS) neuropathology, could arise from failures by either the CNS or the immune system. The extent that the inappropriate appearance of antigen-presenting cell (APC) function contributes to CNS inflammation and pathology is still under debate. Therefore, we characterized the response initiated when professional APCs (dendritic cells) presenting non-CNS antigens were injected into the CNS. These dendritic cells expressed numerous T-cell chemokines, but only in the presence of antigen did leukocytes accumulate in the ventricles, meninges, sub-arachnoid spaces, and injection site. Within the CNS parenchyma, the injected dendritic cells migrated preferentially into the white matter tracts, yet only a small percentage of the recruited leukocytes entered the CNS parenchyma, and then only in the white matter tracts. Although T-cell recruitment was antigen specific and thus mediated by CD4+ T cells in the models used here, CD8+ T cells accumulated in numbers equal to or greater than that of CD4+ T cells. Few of the recruited T cells expressed activation markers (CD25 and VLA-4), and those that did were primarily in the meninges, injection site, ventricles, and perivascular spaces but not in the parenchyma. These results indicate that 1) the CNS modulates the cellular composition and activation states of responding T-cell populations and that 2) myelin-restricted inflammation need not be initiated by a myelin-specific antigen.

Optical Mesurements of Presynaptic Function: What Keeps Vesicle Traffic Going

Abstract The nervous system has evolved to make use of a variety of mechanisms that allow information to flow and be processed among a large collection of individual cells. The communication between individual brain cells occurs largely at chemical synapses. In these compartments, chemical messengers are packaged into small vesicles that fuse with the cell membrane upon stimulation, releasing neurotransmitter.. The average total number of synaptic vesicles in a typical central nervous system synapse is only a few hundred and as a result an efficient local recycling mechanism operates in order to replenish this pool during periods of even modest neuronal activity. Without this membrane recycling, synapses quickly become depleted of vesicles, and soon fail to communicate information between cells. We make use of optical techniques to follow the trafficking of synaptic vesicles at synapses formed between hippocampal neurons grown in culture. Recycling synaptic vesicles can be readily labeled using the fluorescent amphipathic membrane dye FM 1-43.

The safety of astemizole in pregnancy

Since the introduction of nonsedating selective H1 antagonists, they have been largely used by women of reproductive age for the treatment of seasonal allergic rhinitis, conjunctivitis, chronic urticaria, and other allergic conditions. However, because of tack of human studies on the reproductive safety of these compounds, their manufacturers either cannot support their use in pregnancy, through the product monographs, 1 or label them as relatively safe even when no data exist to support such statements. The issue of documenting pregnancy outcome after exposure to new drugs is even more complex if one considers that over 50% of all pregnancies are unplanned, and therefore it may be sufficient to advise women not to use a compound in pregnancy. Astemizole is a potent long-acting selective H1 blocker antihistamine, which does produce the typical central nervous system depression and drowsiness. In animal studies, doses that were 200to 800-fold the recommended human dose per kilogram did induce teratogenic effects? We report on the first prospective, controlled, observational study of women who took astemizole during the first trimester of pregnancy and their offspring.

Consultation with the Specialist

Many general pediatricians feel that the assessment of an infant or child who has a developmental delay and possible neurologic impairment is one of their most difficult challenges. Frequently the parents or relatives, during the course of a well-child visit, first voice concerns about the failure to attain or master one or more expected developmental milestones. Other times the pediatrician is the first to note a problem with development in one or more areas. One of the most important tasks for the pediatrician is to be able to identify the subset of patients who may have a progressive rather than a static neurologic process and to refer them promptly for further evaluation of a possible neurodegenerative disorder. In the past, the diagnosis of a childhood neurodegenerative disease was associated with a sense of hopelessness; frequently, the need for a definitive diagnosis was questioned. Breakthroughs in our understanding of the genetic and biochemical basis of many of these disorders, together with advances in enzyme replacement and gene therapy, have made antenatal diagnosis, treatments, and even cures a reality. The numerous types of central nervous system (CNS) degenerative diseases encountered in children go beyond the scope of a few pages and are covered well in the standard texts (see the excellent chapter by Johnson and Rapin in Rudolph's Pediatrics, 19th ed, 1991).

Consultation withthe Specialist

Many general pediatricians feel that the assessment of an infant or child who has a developmental delay and possible neurologic impairment is one of their most difficult challenges. Frequently the parents or relatives, during the course of a well-child visit, first voice concerns about the failure to attain or master one or more expected developmental milestones. Other times the pediatrician is the first to note a problem with development in one or more areas. One of the most important tasks for the pediatrician is to be able to identify the subset of patients who may have a progressive rather than a static neurologic process and to refer them promptly for further evaluation of a possible neurodegenerative disorder. In the past, the diagnosis of a childhood neurodegenerative disease was associated with a sense of hopelessness; frequently, the need for a definitive diagnosis was questioned. Breakthroughs in our understanding of the genetic and biochemical basis of many of these disorders, together with advances in enzyme replacement and gene therapy, have made antenatal diagnosis, treatments, and even cures a reality. The numerous types of central nervous system (CNS) degenerative diseases encountered in children go beyond the scope of a few pages and are covered well in the standard texts (see the excellent chapter by Johnson and Rapin in Rudolph9s Pediatrics, 19th ed, 1991).

Pathological findings in gaucher disease type 2 patients following enzyme therapy

The pathological outcomes following intravenous acid β-glucosidase (alglucerase) infusions were compared in two siblings with Gaucher disease type 2, the acute neuronopathic variant. In case 1 enzyme infusions (four doses at 7 months) had no effect when severe progressive visceral and neuronopathic disease were present. Death from progressive disease occurred at 9 months. Case 2 was prenatally diagnosed. Enzyme infusions were initiated presymptomatically at 4 days of age and continued until death at 15.2 months. Development progressed satisfactorily, albeit at a slower than normal rate until age 10 months when progressive brain stem involvement became evident. Death occurred after slowly progressive brain stem dysfunction, but gross motor and cognitive skills were nearly normal. Postmortem light and electron microscope (EM) studies in both cases showed typical central nervous system (CNS) findings and massive infiltration of the lungs and lymph nodes by Gaucher cells. The liver, spleen, and bone marrow, except that in the temporal bone, in case 2 were normal. These studies show that enzyme therapy may slow but does not prevent the development of lethal CNS disease in Gaucher disease type 2, even when initiated presymptomatically. These findings also indicate the nonuniformity of tissue responses to enzyme therapy implying the existence of therapeutically inaccessible compartments that, in less severe variants, may create unexpected long-term disease complications.

Tetrodotoxin-resistant sodium channels.

1. Tetrodotoxin (TTX) has been widely used as a chemical tool for blocking Na+ channels. However, reports are accumulating that some Na+ channels are resistant to TTX in various tissues and in different animal species. Studying the sensitivity of Na+ channels to TTX may provide us with an insight into the evolution of Na+ channels. 2. Na+ channels present in TTX-carrying animals such as pufferfish and some types of shellfish, frogs, salamanders, octopuses, etc., are resistant to TTX. 3. Denervation converts TTX-sensitive Na+ channels to TTX-resistant ones in skeletal muscle cells, i.e., reverting-back phenomenon. Also, undifferentiated skeletal muscle cells contain TTX-resistant Na+ channels. Cardiac muscle cells and some types of smooth muscle cells are considerably insensitive to TTX. 4. TTX-resistant Na+ channels have been found in cell bodies of many peripheral nervous system (PNS) neurons in both immature and mature animals. However, TTX-resistant Na+ channels have been reported in only a few types of central nervous system (CNS). Axons of PNS and CNS neurons are sensitive to TTX. However, some glial cells have TTX-resistant Na+ channels. 5. Properties of TTX-sensitive and TTX-resistant Na+ channels are different. Like Ca2+ channels, TTX-resistant Na+ channels can be blocked by inorganic (Co2+, Mn2+, Ni2+, Cd2+, Zn2+, La3+) and organic (D-600) Ca2+ channel blockers. Usually, TTX-resistant Na+ channels show smaller single-channel conductance, slower kinetics, and a more positive current-voltage relation than TTX-sensitive ones. 6. Molecular aspects of the TTX-resistant Na+ channel have been described. The structure of the channel has been revealed, and changing its amino acid(s) alters the sensitivity of the Na+ channel to TTX. 7. TTX-sensitive Na+ channels seem to be used preferentially in differentiated cells and in higher animals instead of TTX-resistant Na+ channels for rapid and effective processing of information. 8. Possible evolution courses for Na+ and Ca2+ channels are discussed with regard to ontogenesis and phylogenesis.

Central nervous system angiocentric, angiodestructive t-cell lymphoma (lymphomatoid granulomatosis)

Most neurosurgeons and neurologists still consider lymphomatoid granulomatosis (LG) as a type of central nervous system (CNS) vasculitis. However, new insights, primarily from the hematologic literature, have cast doubt on the benign character of this disorder. In this article we (1) report a case of an 18-year-old woman with diffuse CNS disease and no mass lesion who developed multiple small cortical infarcts and dementia secondary to multifocal angiocentric, angiodestructive lymphoma; we (2) review other cases of LG with predominant CNS involvement; we (3) summarize the current understanding of LG, which is now considered to be a premalignant or overt angiocentric, angiodestructive T-cell lymphoma rather than a nonneoplastic vasculitis: the importance to neurologic surgeons and neurologists is that while pulmonary involvement in LG is generally the most prominent finding, patients may present with early or dramatic CNS disease; and we (4) note that although dementia is uncommon in young adults, this report adds yet another rare condition to the long differential list of dementia in this age group.

Vimentin mRNA expression increases after corticospinal axotomy in the adult hamster

We examined changes in vimentin gene expression during Wallerian degeneration after corticospinal axotomy in the adult hamster. Vimentin, which is the product of a type III intermediate filament (IF) gene, is expressed in various cells of mesenchymal origin, including microvascular endothelial cells, microglia and developing astrocytes. While increases in vimentin protein have been observed after various types of central nervous system (CNS) injury, it is not known whether this increase is due to increased vimentin mRNA expression. There is also conflicting evidence as to which cells are expressing increased levels of vimentin. In the present study we used in situ hybridization and double-label immunofluorescence techniques to address these issues. A 35S-labeled vimentin cDNA probe was used for in situ hybridizations of brain stem sections obtained 2, 7 and 14 days after unilateral transection of the corticospinal tract in the caudal medulla of adult hamsters. Autoradiography showed that an increase in vimentin mRNA associated with the degenerating corticospinal tract occurred by 2 days after axotomy and that the levels remained elevated for at least 14 days. Immunoblotting and immunocytochemical studies indicated that vimentin protein levels were increased in the degenerating corticospinal tract. Double-label immunofluorescence revealed many vimentin-positive cells and processes that were also labeled with GFAP antibody. In addition, cells and processes that were vimentin-negative but GFAP-positive were also found in the degenerating tract. We suggest that the reactive cells which possessed both vimentin and GFAP were reactive astrocytes of astroblastic origin while those that expressed only GFAP were derived from mature astrocytes. Other vimentin-positive cells/processes did not label with anti-GFAP and thus were either microglial, endothelial or inflammatory cells. These results demonstrate that an increase in vimentin mRNA occurs during Wallerian degeneration after corticospinal axotomy and that this increase is likely to be due to contributions from more than one cell type.

Anoxic injury of mammalian central white matter: Decreased susceptibility in myelin‐deficient optic nerve

The rat optic nerve, a typical central nervous system white matter tract, rapidly loses excitability when it is exposed to anoxia and is irreversibly damaged by prolonged anoxia. Neonatal optic nerve is extremely resistant to anoxia-induced dysfunction and injury; the adult pattern of response to anoxia appears between 10 and 20 days postnatal, that is, during the period of oligodendroglial proliferation and myelination. To test the hypothesis that myelination, or associated events, confer anoxic susceptibility on developing white matter, we analyzed the effects of anoxia on the myelin-deficient (md) strain of rat. Acutely isolated optic nerves from 19- to 21-day-old md rats and control optic nerves from unaffected male littermates were maintained in vitro at 37 degrees C, and exposed to a standard 60-minute period of anoxia. The supramaximal compound action potential was recorded and amplitude of the compound action potential, expressed as % of amplitude before anoxic exposure, was determined. The compound action potential was nearly abolished within 3 to 6 minutes after onset of anoxia in control optic nerves, while optic nerves from md rats displayed a slower decrease in compound action potential amplitude during anoxia, with a distinct action potential present even after 60 minutes of anoxia. Optic nerves from md rats showed significantly greater recovery of compound action potential (71 +/- 25%) than did control optic nerves (33 +/- 21%; p less than 0.02) after 60 minutes of anoxia. These findings support the hypothesis that myelination, or changes associated with it, may be important in the development of anoxic susceptibility in central white matter.

Role of extracellular calcium in anoxic injury of mammalian central white matter.

White matter (WM) of the mammalian brain is susceptible to anoxic injury, but little is known about the pathophysiology of this process. We studied the mechanisms of anoxic injury in WM using the isolated rat optic nerve, a typical central nervous system WM tract. Optic nerve function, measured as the area under the compound action potential, rapidly failed when exposed to anoxia and recovered to 28.5% of control after a standard 60-min period of anoxia. Irreversible anoxic injury was critically dependent on the molar concentration of extracellular calcium [( Ca2+]o); maintaining the tissue in Ca2(+)-free solution throughout the anoxic period resulted in 100% compound action potential recovery. Increasing perfusion [Ca2+] during anoxia from zero to 4 mM resulted in progressively less recovery. As the introduction of the Ca2(+)-free solution was progressively delayed with respect to the onset of anoxia, a graded decrease in recovery of function was observed, suggesting that in WM the deleterious effects of Ca2+ accumulate slowly during anoxia. At the time of reoxygenation, an additional stepwise increase in injury was observed that was also Ca2(+)-dependent. Mammalian WM, which is relatively resistant to anoxic injury compared with gray matter, is damaged by anoxia in a manner that appears to depend on the gradual accumulation of Ca2+ in a cytoplasmic compartment.

Type-specific expression of protein kinase C isozymes in CNS tumor cells

We examined specific expression of protein kinase C (PK-C) isozymes in cultured human glial and neuronal cell lines, using type-specific monoclonal antibodies MC-1a, -2a, and -3a (Hidaka H. et al., J. Biol. Chem., 263 (1988) 4523–;4526). Immunoblotting experiments revealed that a 80 kDa band of three kinds of glioblastoma cells (A-172, SK-MG-1, SK-MG-4) was stained with MC-3a, whereas that of neuroblastoma cells (SK-N-MC) reacted with MC-2a. Immunoenzymetric assay showed that glioblastoma cells (A-172, SK-MG-1, SK-MG-4) contained 127.6 ± 14.4, 248.8 ± 38.5 and 148.5 ± 35.8 ng/mg protein of type III, respectively, while neuroblastoma cells (SK-N-MC) contained 389.5 ± 20.7 ng/mg protein of type II. These results suggest that PK-C isozymes may be specifically expressed, depending on types of central nervous system (CNS) tumor cells.

Cognitive Function in Long Survivors of Childhood Acute Lymphoblastic Leukemia

Thirty long survivors of childhood acute lymphoblastic leukemia were compared with their healthy siblings on cognitive and neuropsychological measures. The subjects were comparable in treatment variables except for type of central nervous system prophylaxis received. Thirteen were given radiotherapy with intrathecal medication, and seventeen received only intrathecal treatment. Patients receiving only intrathecal medication did not differ from controls. Patients receiving radiotherapy scored lower on several measures including Wechsler Full Scale and Performance IQ. Irradiated girls scored lower than boys on most measures. Children whose clinical management has included radiation therapy appear to be at risk for later mild cognitive deficits. No consistent pattern of neuropsychological deficits has emerged and observed deficit patterns may reflect individual vulnerabilities.

An outbreak of meningo-encephalitis in fallow deer caused by Listeria monocytogenes.

An outbreak of listeric meningo-encephalitis occurred in a population of 1800 fallow deer (Dama dama) in a park during the winter and early spring of 1985 to 1986. Listeriosis was diagnosed in 41 of 42 fallow deer that showed the typical central nervous system signs of circling disease or were found dead. The diagnosis was verified by bacteriological examination of the brains of 35 animals. In five of the seven remaining cases listeriosis was diagnosed by histological examination, and in one animal by clinical signs alone. Listeria monocytogenes was isolated in three of 23 soil samples taken from the park. In addition, L monocytogenes was isolated from the intestinal contents of apparently normal fallow deer. Fifty isolates from animals and soil were serotyped and all of them belonged to serovar 4b except one from brain (serovar 1/2b) and three from intestinal contents (serovar 1/2a). In phage typing of 54 isolates, the 35 isolates from the brain and spleen of diseased animals belonged to the same lysovar, as did most isolates from other sources, but strains from intestinal contents belonged to three other phage types. No external source of L monocytogenes was demonstrated in the outbreak and stress due to the poor beech-mast crop, an increased stocking rate and a sudden change in the weather are suspected as predisposing factors.