Pediatric neurosurgery

Many aspects of pediatric neuro-oncology including epidemiology, diagnosis and treatment are covered by this review. Important advances in the treatment of hydrocephalus and craniosynostosis are also reviewed. A number of congenital conditions involving the cranium and spinal cord are analyzed with respect to optimal treatment and new experimental data are highlighted. Advances in the treatment of pediatric intracranial and extracranial vascular anomalies are reviewed and advances in the understanding of head trauma are emphasized. Finally, a couple of the technical advances in pediatric neurosurgery are highlighted.     

Creutzfeldt-Jakob disease

The historical aspects of spongiform encephalopathies, Creutzfeldt-Jakob disease (CJD) and kuru of man, as well as scrapie and transmissible mink encephalopathy, are outlined. Transmissions of these diseases to animal hosts are presented, with emphasis on CJD transmissions to guinea pigs, hamsters, and mice. The relationship of CJD to scrapie with reference to the pathological findings is discussed. In CJD the incubation period is cut in half in guinea pigs and hamsters in the second passage. The spongiform changes occurring in the neuropil are reviewed. These changes are related to the type of inoculum, e.g., there is more vacuolization after inoculation with brain, and less after inoculation with spleen. Spongiform changes are also dependent upon the route of inoculation; these are more severe in intracerebral inoculation compared to intraperitoneal inoculation. Viremia is present. Maternal transmission and lateral transmission are absent. No virus-like particles are detected, and no other organisms are visible by electron microscopy. Isolations of the causative agent and strains of the agent in spongiform encephalopathies remain elusive. The hypotheses concerning the nature of the agent are critically reviewed. Novel data on the production of tumors derived from CJD brains are presented. Tissue culture cells arising from such brains become permanent lines and are similar to neoplastic lines. When such CJD lines are injected subcutaneously into nude mice, malignant neoplasms are formed. No evidence of an infectious etiology in Alzheimer's disease exists. Reported similarities between this disease and CJD are reviewed. Animal models of CJD are useful for the investigation of dementias.     

Hospital and community based psychiatry: a comparative study between a Danish and an Italian psychiatric service

A Danish (Aarhus) institution-based and an Italian (South-Verona) community-based psychiatric service are compared. The incidence rates are 20/10,000 inhabitants in both areas with more psychotics and fewer neurotics in Aarhus. The admission rate as well as the one year rate of persons in in-patient care are about three times higher in Aarhus. Referrals to day and out-patient care, including home visits, are used 1.5-3.5 times as often in South-Verona, whereas the rates of persons in each of the three types of care are of similar size in the two centres. Geronto-psychiatric disorders are to a greater extent treated within the field of psychiatry in Aarhus. Compulsory admission rates are higher in Aarhus (3.7/10,000 inhabitants) than in South-Verona (1.3/10,000). Admission rates to private hospitals are 9.4/10,000 inhabitants in South-Verona against 3.0/10,000 in Aarhus.     

Glutamate-positive neurons in the somatic sensory cortex of rats and monkeys

The morphology and laminar distribution of neurons labeled with an antiserum prepared against glutamic acid (Glu) conjugated to keyhole limpet hemocyanin have been studied in the somatic sensory cortex of rats and monkeys. In both species, the vast majority of immunostained neurons are pyramidal; some nonpyramidal neurons are also present. Positive neurons are observed in all cortical layers, although variations are found in the percentage of Glu-positive neurons in the different layers. In rats they are most numerous in layer V (36%), followed by layer II (33%), layer III (32%), and layer VI (29%). In layer IV, 13% of all neurons are positive. Immunoreactive neurons are very sparse in layer I. In monkeys, Glu-positive neurons represent 51% of all neurons in layer V, 49% in layer III, 40% in layers II and VI, and 19% in layer IV. No differences are evident in the laminar distribution of Glu-positive neurons among cytoarchitectonic areas 3a, 3b, 1, and 2. As in rats, Glu-positive neurons are very sparse in layer I. Since Glu and GABA metabolisms are closely related, double-labeling experiments were performed in which thin, adjacent paraffin sections were stained alternately with the anti-Glu serum and with an anti-GABA serum. The 2 populations are almost completely segregated, even though a small fraction of neurons (less than 5%) are labeled by the antisera against both antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrastructural study and cholinesterase activity of paired capillaries in the newt brain

We have investigated the ultrastructural and histochemical (AChE and BuChE) features of intracerebral vessels in newt. The blood vessels of the newt brain are paired and end in a closed loop. The two limbs, each of them has delineate the lumen by one endothelial cell, are enclosed within a single basement membrane and are separated from each other by a thin intercapillary wall. The brain capillaries are un-fenestrated and the overlapping endothelial cells were connected by clefts. Ependymal astrocytes extensively ensheath the surface of brain capillaries, but the sheats are incomplete. Pericytes and mast cells are frequently sandwiched in the endothelial basal lamina. Microglial cells are also present adjacent to cerebral vessels. The newt cerebral capillaries are characterized by high levels of AChE. This enzyme is localized in the basal membrane and in extracellular spaces between the overlapping endothelial cells. The vascular walls are instead deprived of BuChE activity. The non-nervous role of cholinesterases is discussed.     

Potential drugs and methods for preventing or delaying the progression of Huntington's disease

Huntington's disease (HD) is an autosomal dominant inherited and progressive neurodegenerative disorder with motor dysfunction and cognitive deficits. Although there are no treatments to delay the appearance and the progression of HD, there are potential drugs currently in preclinical and clinical trials that are focused on HD therapy. The signaling pathways involved in HD are not yet clearly elucidated; however, expression of mutant huntingtin protein is considered a key factor in the induction and/or progression of HD. The demonstration that the onset and progression of HD in models of transgenic mice, in particular, are delayed or improved by the application of neurotrophic factors has emphasized their importance in neuroprotection in HD. In addition, other compounds targeting the HD gene or mutant huntingtin protein are currently in preclinical and clinical testing and may show promising neuroprotective effects. There are current patented drugs that are currently being considered as potential therapeutics for HD. These patented drugs may provide promising therapy for HD.     

Agitation and other noncognitive abnormalities in Alzheimer's disease.

Agitation and other noncognitive abnormalities in patients with Alzheimer's disease are present in at least 50% of patients and are a serious problem for caregivers. Agitation can be divided into aggressive agitation, physically nonaggressive agitation, and verbal agitation. Persecutory delusions of suspiciousness and stealing are the most common psychotic symptoms. Auditory and visual hallucinations are also associated with delusions. Similar to delusions are misidentifications, which are false beliefs probably secondary to agnosia. They occur in one third of patients with dementia of the Alzheimer type in the form of the belief that strangers are living in the home and misidentification of the patient's home and reflection in the mirror. Passive personality changes are present early in the disease, whereas agitation and psychotic symptoms occur with disease progression and predict a more rapid rate of cognitive decline. Agitation and wandering are related to more severe cognitive impairment and psychosocial variables, and neurochemical variables that may be related to behavior disturbance require further study. There are few systematic studies of behavioral or environmental interventions for behavioral symptoms in patients with Alzheimer's disease. Current treatment emphasizes education of families, the formation of Alzheimer units in the nursing home, and adjunctive psychotropic agents to treat well-defined target symptoms.     

Satellite cells as players and targets in normal and diseased muscle

Satellite cells (SC), also termed adult myoblasts, are mononuclear cells of myogenic lineage. They are attached to the muscle fiber plasma membrane and surrounded by a common basement membrane. The characteristic localization differentiates them from embryonic and fetal myoblasts. SC are able to leave the G0 phase in which they usually reside in normal adult muscle, enter the mitotic cycle, and differentiate to express muscle-specific proteins. The activation of SC into the mitotic compartment and their progression to the differentiative compartment are processes which are tightly regulated by myogenic regulatory factors of the MyoD family and the cyclin-dependent kinases and their inhibitors. Those factors are in turn regulated by growth factors and innervation. SC are key features in muscle fiber growth, regeneration, and hypertrophy. Furthermore, they are targets in denervation atrophy, which results in SC loss in the long run. There is evidence from experimental work that SC age, and that they are a heterogeneous cell population in terms of mitotic cycle duration and have the ability to differentiate. Little is known of SC in human diseased muscle beyond their number. SC heterogeneity must be taken into account if future therapy strategies for muscular dystrophies are designed.     

Three-dimensional distribution of astrocytes in zebrafish spinal cord.

We prepared a monoclonal antibody (A-22) that recognizes a 60-kDa protein in the zebrafish brain. The antigen is distributed throughout the brain but is not found outside it. The antibody recognizes star-shaped cells with long processes in the spinal cord. All A-22-positive cells are also GFAP-immunopositive, but there are GFAP-positive cells that are A-22-negative. The cells are connected to small veins and to the surface of the spinal cord. Immunopositive cells are generally homogeneous in size and shape and are found not only in the spinal cord but also in several areas of the brain. These results indicate that the stained cell is an astrocyte. Most of these cells (88%) are distributed in the gray matter of the spinal cord; the remainder (12%) are found in the white matter. Most of the cells in the gray matter are found in the ventral and dorsal horns, but some are also present in the central area along the ventricle. Glial cell bodies form an array along the longitudinal axis and are connected to each other by thick projections. The cellular array is not visible in coronal sections. In contrast, thin processes from the cells extend to the surfaces of veins, to neurons, and to the periphery of the spinal cord. We estimate that there are about 13,500 A-22-positive astrocytes in the spinal cord; however, this represents only 26% of the total number of astrocytes in the spinal cord (approximately 52,000).     

Dorsal root projections to dorsal horn neurons in the cat spinal cord

The projection of dorsal root fibers to the dorsal horn of the spinal cord of the cat has been studied by electron microscopy. Two distinct types of synaptic degeneration are seen with the electron microscope: small knobs which exhibit a marked increase in electron density, and large knobs which fill with neurofilaments. Variations in the distribution of degenerating knobs to the six laminae of the dorsal horn are observed: dense degenerating knobs are found throughout the horn, but are quite rare in laminae I and II. Lamina III exhibits the most dense knobs, and a great many are also present in laminae IV and VI with a somewhat lesser number seen in lamina V. Knobs undergoing neurofilamentous degeneration are found only in laminae V and VI, and are much Jess frequently seen than are dense knobs. The types of synaptic contacts made by degenerating dorsal root fibers also vary from one region of the dorsal horn to another. Dense degenerating knobs synapse primarily with small dendrites in laminae I, II and III, but not at all with large dendrites or nerve cell bodies. In lamina III, dense knobs are seen in axoaxonal synapses, and are always the pre-synaptic component of the synapse. In laminae IV, V and VI dark knobs are commonly seen to synapse upon cell bodies of large and medium sized neurons and their proximal dendrites, but not upon small cell bodies Dense knobs upon small dendrites are common. In degenerating axoaxonal synapses, the dense knob is always the post-synaptic component. Degenerating neurofibrillar knobs are only seen to synapse with cell bodies or larger dendrites in V and VI and not at all other synaptic knobs. The results are correlated with findings by light microscopy. Comparisons are made with some of the known physiological properties of dorsal horn neurons.     

Cerebellar astrocytomas. Part II. Pathologic features indicative of malignancy

The pathologic features which denote poor clinical outcome in a series of 112 cerebellar astrocytomas seen at The Radcliffe Infirmary, Oxford between 1938 and 1984 have been described. These have been reviewed in relation to the findings of numerous other reports in the literature. The conclusions reached are as follows: Pleomorphism: A substantial proportion of cerebellar astrocytomas display significant nuclear and cytoplasmic size variation. This is particularly common after the age of ten. Markedly pleomorphic tumors are, moreover, associated with a very short survival time. Mitotic Figures: Mitotic figures are seen in 8.5% of cerebellar astrocytomas but are found in large numbers, in only 1.1% of cases. They are more common in adults and in totally solid tumors. The presence of any mitotic figures in cerebellar astrocytomas is associated with a marked reduction in survival to death and also a noticeable increase in the rate of recurrence. Cellularity: Marked focal hypercellularity is seen in 13.2% of cerebellar astrocytomas and is especially common in childhood tumors. When marked, it is associated with a significant reduction in survival time to death. Desmoplasia: Desmoplastic reactions adjacent to tumor are seen in one-half of all cerebellar astrocytomas but are only marked in 16% of cases. When marked, however, they are associated with a reduction in overall survival time. Perivascular Pseudorosettes: These are seen in 80.9% of all cerebellar astrocytomas. When found in large numbers, they are more commonly seen in children than in tumors with a mixed cystic and solid form. Their appearance is associated with a favorable outcome when found in association with microcystic change and endothelial hyperplasia but when found in isolation they are associated with poor survival. Necrosis: Small necrotic foci are found in 16.8% of cases. Markedly necrotic tumors are very rare and are more commonly seen in patients with short histories and associated with very poor outcome. Definite malignant features: 1. Pleomorphism, if marked; 2. Mitotic figures, in any number; 3. Cellularity, if marked; 4. Desmoplasia (probably) if marked; 5. Perivascular pseudorosettes, in isolation without microcystic change and endothelial hyperplasia; 6. Necrosis, if marked. Primary malignant cerebellar astrocytomas: These tumors are rare and represent cerebellar astrocytomas with one or more areas containing the aforementioned malignant features. Primary glioblastomas of the cerebellum: These tumors are also rare and resemble both clinically and pathologically glioblastomas found in other parts of the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)     

The concept of 'atypical psychoses': Special reference to its development in Japan

Abstract Reviewing the development of concepts of 'atypical' psychoses in European countries and in the United States shows that there are various terminologies which are given to a group of psychoses unclassifiable within Kraepelinian dichotomy. Bouffee delirante (French school), cycloid psychoses (Leonhard, Perris), reactive psychoses (Scandinavian school) and acute schizoaffective psychoses (Kasanin) are the most common terms. These are consistent in terms of acute onset, polymorphic symptomatology and good prognosis, and are considered to be distinct from major psychoses, especially from typical schizophrenia. The concept atypical psychoses in Japan was developed under the influence of Mitsuda's clinico-genetic studies. According to Mitsuda, atypical psychoses are not mere phenotypical variants of typical schizophrenia and manic-depressive psychosis (MDP) but belong to a genetically different category and are probably heterogeneous. The characteristic features in the Japanese concept of atypical psychoses emphasizes the alteration of consciousness in symptomatology and pays attention to the nosological relationship with epilepsy, as well as with schizophrenia and MDP. Thus, in Japan it is generally considered that atypical psychoses are independent of 'typical' major psychoses and are located nosologically in the border area between typical schizophrenia, MDP and epilepsy.     

The relationship between the auditory cortex and the claustrum in the cat

The relationship between the primary auditory cortex and the claustrum has been re-examined in the cat with axoplasmic flow and axonal degeneration methods. Labelled cells are found in a restricted part of the claustrum after injections of HRP or HRP-WGA in the primary auditory cortex, but they are relatively few in number and are palely stained. The number of labelled cells and their depth of staining are greatest at 72 h (the longest survival time used here), and this survival period an occasional labelled cell is also present in the claustrum of the contralateral hemisphere. No labelled cells are seen after 24 h. After small lesions in the primary auditory cortex, fibre and terminal degeneration are present in the part of the claustrum where labelled cells are seen with axoplasmic flow techniques. It is concluded that there are reciprocal connections between the primary auditory cortex and the claustrum, but the rate of axoplasmic flow is unusually slow.     

Correlation between ultrastructure and histochemistry of lafora bodies

Summary Lafora bodies are composed of fibrillar and granular components in various concentrations. They are located in neuronal cell processes and perikarya and are frequently clearly intermingled with cytoplasmic elements. These components are electron-lucent, show a variable affinity for osmium, and are weakly stained by classical uranyl acetate stain following lead citrate. They exhibit a strong affinity for lead hydroxide and are periodic-acid reactive. They are not stained by the PTA technic for basic protein and/or acidic mucopolysaccharides. These results are in agreement with chemical studies according to which L. B are mostly composed of polyglucosans and suggest that both the granular and fibrillar ultrastructural components contain vic-glycol groups. The ultrastructure of L. B. is very similar to that of corpora amylacea, to deposits in basophilic degeneration of myocardium and in glycogenosis type IV.This work was supported by the Belgian National Fund for Medical Research (Grant No. 576) and by the national multiple sclerosis society.     

Burnout and psychiatrists: what do we know and where to from here?

Medicine in most parts of the world is becoming a stressful profession. Psychiatrists represent a high-risk group among doctors for experiencing burnout, alcohol and drug use, posing suicide risk and other forms of work-related stress. There are reports that entrants in the profession of psychiatrists are decreasing globally. Conceptual issues related to burnout are explored and factors contributing to burnout in psychiatrists are reviewed. Methodologically sound studies are needed to help us understand positive aspects of psychiatry as a profession and the environment psychiatrists work in. Effective treatment programmes for burnout are also needed not only to reduce suffering but also to retain psychiatrists in the profession.     

Differences between delusional disorder and schizophrenia: A mini narrative review

Psychotic syndromes are divided into affective and non-affective forms. Even among the non-affective forms, substantial differences exist. The aim of this relatively brief review is to synthesize what is known about the differences between two non-affective psychoses, schizophrenia and delusional disorder (DD), with respect to clinical, epidemiological, sociodemographic, and treatment response characteristics. A PubMed literature search revealed the following: in schizophrenia, hallucinations, negative symptoms and cognitive symptoms are prominent. They are rare in DD. Compared to schizophrenia patients, individuals with DD maintain relatively good function, and their delusions are believable; many are beliefs that are widely held in the general population. Treatments are generally similar in these two forms of psychosis, with the exception that antidepressants are used more frequently in DD and, for acute treatment, effective antipsychotic doses are lower in DD than in schizophrenia. It is with the hope that the contrasts between these two conditions will aid in the provision of safe and effective treatment for both that this review has been conducted.     

Cerebral developmental venous anomalies: Current concepts

Cerebral developmental venous anomalies are the most frequently encountered cerebral vascular malformation, and as such, are frequently reported as fortuitous findings in computed tomography (CT) and magnetic resonance imaging (MRI) studies. Developmental venous anomalies (DVAs) are generally considered extreme anatomical variations of the cerebral vasculature, and follow a benign clinical course in the vast majority of cases. Here we review current concepts on DVAs with the aim of helping clinicians understand this complex entity. Morphological characteristics that are necessary to conceptualize DVAs are discussed in depth. Images modalities used in diagnosing DVAs are reviewed, including new MRI or CT techniques. Clinical presentation, association with other vascular malformations and cerebral parenchymal abnormalities, and possible physiopathological processes leading to associated imaging or clinical findings are discussed. Atypical forms of DVAs are also reviewed and their clinical significance discussed. Finally, recommendations as to how to manage asymptomatic or symptomatic patients with a DVA are advanced. Ann Neurol 2009;66:271–283     

Pain, nociception and spinal opioid receptors

1. Opioid peptides derived from proenkephalin and prodynorphin are differentially distributed in the spinal cord. Proenkephalin peptides are preferentially located in the sacral portion of the cord while prodynorphin peptides are concentrated in the cervical spinal cord.

2. μ opioid receptor are highly concentrated in superficial layers of the dorsal horn in all the spinal cord.

3. δ opioid receptor are more diffusely distributed in the gray matter of the spinal cord. These sites are principally located in cervical and thoracic portions of the spinal cord.

4. κ opioid receptors are highly concentrated in the superficial layers of the lumbo-sacral spinal cord. Its density decreased in the upper levels of the spinal cord.

5. It appears that μ opioid receptors are indifferentially activated by thermal, pressure and visceral nociceptive inputs. δ receptors are more likely to be involved in thermal nociception while κ opioid binding sites are associated to visceral pain nociceptive inputs.     

Retrohippocampal, hippocampal and related structures of the forebrain in the reeler mutant mouse

Retrohippocampal, hippocampal and some related forebrain regions of the reeler mutant mouse were examined in cresyl violet and myelin stained preparations. All cortical structures are abnormal. The entorhinal cortex, parasubiculum, presubiculum, subiculum, and anterior hippocampal cortex share an anomaly of common quality. All lack an external plexiform layer and their neurons are not arranged in the usual laminae. The positions of neurons are not random, however. Cells of smaller average size and of polymorphic shape are grouped in an outer relatively narrow zone external to a broad zone of larger cells. The histological features of these two cell zones in the mutant are similar to the deep polymorphic cell stratum and the superjacent pyramidal field respectively in the normal animal, but their relative depths in the cortex are reversed. The histological pattern of the mutant hippocampus is less disturbed. Its external plexiform layer is well developed and, although the positions of some neurons are abnormal, there is an explicit laminar pattern and the cytological features of the individual hippocampal cytoarchitectonic fields are readily recognized. It appears from these observations that in a variety of cortical structures, even those which are most disturbed, the positions of neurons are systematically regulated, yet are controlled according to some rule that differs in normal and mutant. The basic developmental event which dictates eventual neuron position probably occurs early and its effects may depend on critical timing or precise location of interacting cells as influenced by the reeler locus.     

A note on transference and alliance: I. Transference--variations on a theme.

Conceptual and pragmatic difficulties are encountered in relating and differentiating transference from alliance. Transference and alliance, along with the real relationship, are component elements of the analytic relationship, and are mutually involved in intermingling and interaction at all points of the analytic process. Variants of transference are discussed with an eye to distinguishing their differentiation from and relationship to alliance components and functions. Forms of transference differentiated are classical transferences (libidinal and aggressive), transference neuroses, transference psychoses, narcissistic transferences, selfobject transferences, transitional relatedness, transferences as psychic reality, and relational or intersubjective transferences. Transference mechanisms--specifically displacement, projection, and projective identification--and their role in transference development are discussed. Differences in the concept of transference conceived classically as opposed to relationally or intersubjectively are explored. Therapeutic advantages and limits of these differentiations are considered.