Schwann cell-onion bulb tumor of the trigeminal nerve: hyperplasia, dysplasia or neoplasia?

Onion bulbs are concentric lamellar structures formed by Schwann or perineurial cells, which may be seen in several generalized or localized diseases of the peripheral nerve. There is debate regarding the pathogenesis of localized tumefactions displaying these microscopic structures. We report the fifth case, to our knowledge, of a Schwann cell-onion bulb tumor, which arose in the trigeminal nerve of a child with an unclassifiable, probably distinct, neurocutaneous syndrome; we also provide evidence for a neoplastic or hamartomatous origin. Molecular studies failed to establish an abnormality in the NF1, NF2, PMP22, or Connexin 32 genes. Similar and previously reported cases are discussed, as well as other onion bulb-forming entities. Received: 9 March 1999 / Revised, accepted: 11 May 1999     

Mechanisms of Pavlovian fear conditioning: has the engram been located?

Uncertainty persists as to whether the amygdala is a crucial site of plasticity for classically conditioned fear or merely a sensory relay to structures generating fear responses. A recent Nature study suggests that associative synaptic changes take place in neurons of the amygdala during fear conditioning, and that these changes require dopamine-mediated modulation. Nevertheless, these findings do not prove that the amygdala is a sufficient site of plasticity for fear memory.     

Enlargement of the spinal cord: Inflammation or neoplasm?

Intramedullary spinal tumours are uncommon lesions that can cause significant difficulties in the differential diagnosis between inflammatory diseases such as multiple sclerosis and acute disseminated encephalomyelitis, and vascular malformations or neoplasms. We report five cases in which the history and the clinical symptoms suggested an inflammatory process of the spinal cord but the MRI characteristics were those of neoplastic lesions. Both non-neoplastic and neoplastic intramedullary lesion may have very similar symptoms, and even CSF abnormalities, but in every one of our cases, a more detailed history and longer observation of the clinical course would have led to the correct diagnosis; in such problem cases, empirical treatment and a follow-up MRI after a month's observation would be a more prudent approach providing that the patient is not rapidly deteriorating.     

Ruptured intracranial aneurysms: has the incidence of early rebleeding been over-estimated?

Of 110 consecutive patients with ruptured intracranial aneurysms, 49 underwent delayed neurological deterioration, involving 57 episodes in all. During the first three weeks after the presenting haemorrhage less than a third of these episodes were due to confirmed rebleeding. Rebleeding episodes were found to have a "flat" distribution in time during this period, but episodes of non-haemorrhagic deterioration "peaked" between days 4-12. This peak coincides with the peak for rebleeding which was described in earlier studies on aneurysms, and it is suggested that confusion between non-haemorrhagic deterioration and rebleeding may have led to a significant over-estimate of the incidence of early rebleeding with important implications for the optimum timing of surgical intervention.     

Assessment of COVID-19 trauma responses. Who has been more traumatized during the pandemic?

Background and ObjectiveTo evaluate the effect of cognitive and sociodemographic characteristics of healthcare and non-healthcare workers on their traumatic responses to the COVID-19 pandemic.MethodsData were collected using an online survey between August-September 2020. The survey included the following scales: Beck Anxiety Inventory (BAI), Anxiety Sensitivity Index (ASI), and Impact of Event Scale-Revised (IES-R). Traumatic responses were categorized into three types: avoidance (IES-R_A), intrusion (IES-R_I), and hyperarousal (IES-R_H).ResultsThe study included a total of 672 participants, comprised of 399 (59.4%) men, and 273 (40.6%) women with a mean age of 39.25 ± 933 years. The results indicated that women had higher IES-R_I (r = .5.78, p < 0.001), IES-R_A (r = 4.47, p < 0.001), and IES-R_H (r = .5.20, p < 0.001) scores compared to men. Patients with a history of psychiatric diseases had significantly higher IES-R_I (r = ?3.82, p < 0.001), IES-R_A (r = ?2.00, p < 0.05), and IES-R_H (r = ?4.06, p < 0.001) scores compared to patients with no history of psychiatric diseases. Non-healthcare workers had significantly higher IES-R_A (r = ?2.69, p < 0.01) scores compared to healthcare workers.ConclusionFemale gender and a positive history of psychiatric diseases were found to lead to an increase in the frequency of all three traumatic responses to COVID-19. Contrary to expectation, being a healthcare worker was not found as a factor facilitating trauma response formation in our study.     

Somatosensory evoked potentials to median nerve stimulation in meningomyelocele: what is occurring in the hindbrain and its connections during growth?

Twenty patients with meningomyelocele (MMC) and shunted hydrocephalus, ranging in age from 3 to 23 years old, underwent serial recording of short-latency somatosensory evoked potentials (SEPs) to median nerve stimulation, on the basis of which to assess the evolution of dysfunction in the brainstem and its connections (cervical spinal cord, cervical nerve roots, lower cranial nerves). Eighteen patients had Chiari type II malformations, none of which was symptomatic. In all 20 patients, serial SEP recordings were obtained repeatedly after periods ranging from 2 to 7 years. The results were as follows: (1) the ratio of interpeak latencies (IPLs) to body height (BH) tended to lengthen gradually after starting in the normal range with growth. (2) In contrast, the ratio IPLs/BH decreased continously to the normal range with growth, after initial prolongation. These findings and our earlier studies of brainstem auditory evoked potentials suggest that compression and traction result in strangulation of the cervical spinal cord and kinked medulla as well as stretching of the cervical nerve roots and lower cranial nerves. However, primary intrinsic functional disorders of the brainstem appeared to improve gradually during growth. The natural history of Chiari type II malformations involves these opposing dynamic phenomena in the hindbrain and its connections.Presented at the XXII Annual Meeting fo the International Society for Pediatric Neurosurgery, Birmingham, 1994     

The origin of vasovagal syncope: to protect the heart or to escape predation?

Major lines of evidence suggest that classical (emotional and orthostatic) vasovagal syncope (VVS) is not a disease, but rather a manifestation of a non-pathological trait. It is, therefore, reasonable to investigate the possible factors that may explain its origin and evolution. We reviewed the data available in the literature on the vasovagal reaction in humans and animals in order to identify possible similarities that might provide insight into the evolution of VVS. We found two processes which appear relevant to the investigation of VVS evolution: fear and threat bradycardia in animals, and the vasovagal reflex during hemorrhagic shock in humans and animals. We suggest that VVS in humans involves physiological mechanisms similar to those found in other vertebrates, and that this may indicate a common evolutionary root. The available data seem to suggest that VVS evolved as an advantageous response to inescapable predators or to stressful and possibly dangerous heart conditions. The inhibition of the sympathetic system, together with activation of the vagal system, characterizes VVS. The consequent slowing of the heart rate induced by VVS may constitute a beneficial break of the cardiac pump, thereby reducing myocardial oxygen consumption. We suggest that classical VVS did not evolve recently in the modern human lineage; rather, it should be regarded as a selected response, which probably evolved in the ancient past as a "defense mechanism" of the organism within some ancestral group(s) of vertebrates.     

Axonal degeneration of the ulnar nerve secondary to carpal tunnel syndrome: fact or fiction?

The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome (n = 35) and group II with mild to moderate carpal tunnel syndrome (n = 47) according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.     

Ancestry of the mammalian preplate and its derivatives: evolutionary relicts or embryonic adaptations?

Mammalian cortical development is preceded by the elaboration of a transient preplate, which is split into a superficial marginal zone and a deep subplate after the arrival of the cortical plate. There has been some controversy in the evolutionary interpretation of this transient structure, as some propose it to represent the ancestral cortex or pallium of non-mammals, while others consider it to be a phylogenetic novelty. The preplate and its derivatives contain components derived by both tangential and radial migration. Tangentially migrating elements include pioneer neurons and interneurons, both of subpallial origin, and Cajal-Retzius cells, mostly of pallial origin. Pioneer neurons were probably present in the ancestors of mammals, but may have changed their original superficial position to one below the developing cortex, thus attracting thalamic afferents in the subcortical white matter, and making them penetrate the cortex radially. In mammals, Cajal-Retzius cells appear to have increased both in number and on their level of reelin expression, perhaps in the context of controlling the final stages of migration in a radially expanding neoocortex. Radial-migrating cells are partly represented by the pyramidal-like cells of the subplate. These neurons resemble the excitatory elements of the adult reptilian cortex, but is not clear whether they are their true homologues. One possibility is that these cells appeared by virtue of a heterochronic process in which the earliest radial elements of the cortical plate began to be produced at progressively earlier developmental stages. Thus, we conclude that the mammalian preplate and its derivatives contain both ancestral and derived elements, all of which have been modified in the course of mammalian evolution to support an increasingly complex cortical plate development.     

Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?

Inhibition of endogenous acetylcholine degradation through cholinesterase inhibitors represents a milestone in symptomatic treatment of cognitive symptoms in mild to moderate stages of Alzheimer's disease. Cholinesterase inhibitors are also under investigation for treating cognitive dysfunction of cerebrovascular origin, but to date they do not have specific indication for vascular dementia or vascular cognitive impairment. This paper reviews the main clinical studies assessing the activity of cholinergic precursors in the treatment of adult-onset dementia disorders of vascular origin. The first cholinergic precursor used phosphatidylcholine (lecithin) did not show any clear clinical benefit on symptoms of dementia disorders. The same is not true for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) and choline alphoscerate for which a modest improvement of cognitive dysfunction in dementia of neurodegenerative and vascular origin is documented. Positive results obtained with selected cholinergic precursors cannot be generalized due to the small numbers of patients studied in appropriate clinical trials. However, they probably would justify reconsideration of the most promising molecules in larger carefully controlled studies.     

On the Neuropathology of Schizophrenia and its Dementia: Neurodevelopmental,Neurodegenerative, or Both?

The neuropathology of schizophrenia has begun to emerge following renewed investigation in the past 20 years. However, there remain inconsistencies in the data and their interpretation. In particular, although the brains of schizophrenics have been reported to show an excess of neurodegenerative changes, especially astrocytic gliosis and Alzheimer's disease, it is unclear whether these features are an intrinsic part of the neuropathology of schizophrenia. Nor is it apparent how they relate to the symptoms of dementia which afflict a proportion of schizophrenics. This review focuses upon these questions. Two main conclusions are drawn. Firstly, the neuropathological features of schizophrenia together support a neurodevelopmental pathogenesis wherein the aforementioned degenerative changes are either epiphenomenal, artefactual, or are limited to a subgroup of cases which are otherwise indistinguishable clinically or pathologically. Secondly, the dementia of schizophrenia is not attributable to Alzheimer's disease nor to any other recognized neuropathological substrate.     

Imaging appearance of the symptomatic perforating artery in patients with lacunar infarction: Occlusion or other vascular pathology?

Lacunar infarction is associated with distinct clinical features. It is thought to result from occlusion of a deep perforating artery in the basal ganglia, centrum semiovale, or brain stem. However, occluded perforating arteries have only rarely been observed at postmortem in patients with lacunar stroke and have not been noted previously on imaging despite the increasing sophistication of the techniques. We observed nine patients with lacunar stroke imaged with computed tomography and magnetic resonance imaging in whom we observed a linear structure with density or signal features consistent with an occluded (or at least abnormal) perforating artery associated with the relevant lacunar infarct. The appearance might also have been caused by a leak of blood and fluid into the perivascular space around the artery, as in several patients the width of the tubular vessel-like structure (>1 mm in diameter) was greater than the expected width of a perforating artery (<0.8 mm in diameter). This interpretation is supported by the fact that the area of infarction was usually around the abnormal vessel, not at the end of it. We describe the patients' clinical and imaging features, and discuss alternative explanations for the imaging appearance and the implications for gaining insights into the cause of lacunar infarction.     

Cervical spinal cord atrophy in the atraumatically born neonate: one form of prenatal or perinatal ischaemic insult?

After atraumatic birth, three neonates presented with muscle hypotonia and weakness. Flaccid paresis of the upper extremities, spasticity of the lower extremities, dissociate sensory loss and autonomic dysfunction developed later. This ruled out the initial, tentative diagnoses of cerebral palsy, spinal muscular atrophy or hereditary neuropathy. Diagnostic imaging revealed marked thinning of the cervical spinal cord in all patients. The possible aetiology of these lesions is considered. In all cases, an antenatal or perinatal infarction is thought to be the most probable cause. Different clinical pictures following intrauterine spinal cord ischemia are discussed. Spinal cord lesion must be considered even after atraumatic birth.     

Motor reflex responses elicited by cutaneous stimulation in the regenerating nerve of man: Axon reflex or ephaptic response?

In 57 of 60 nerves (29 median and 31 ulnar) sutured at the wrist, forearm and arm, we recorded motor responses in thenar or hypothenar muscles by electrical stimulation of the corresponding fingers. Recordings were made at different times during the process of regeneration, ranging from 3 months up to 11 years. The responses showed a constant shape and latency to every stimulation (simple or repetitive). The latency was shorter the more distal the level of injury and the greater the elapsed time from the reinnervation. The point of "reflexion" of the responses is at or very near the line of nerve suture. The electrophysiological behavior of the responses fits well with either the criterion of axon reflex or ephaptic response. We discuss both possibilities and conclude that it is not possible, with the electrophysiological technique that we used, to distinguish between an axon reflex and an ephaptic response.     

Prediction of MS disability by multimodal evoked potentials: Investigation during relapse or in the relapse-free interval?

ObjectiveLittle is known about optimal timing of multimodal evoked potential (EP)-investigations regarding prediction of MS disability. The aim of this study was to investigate whether timing of EP-investigations during a relapse or in the relapse-free interval influences prediction of MS disability.MethodsTwo groups of MS patients with similar age and gender distributions received visual, motor and somatosensory EPs either during a relapse (Group 1) or in the relapse-free interval (Group 2). Expanded Disability Status Score (EDSS) was obtained at baseline (T0) and year 3 (T2). Linear regression analysis was performed to examine the association between EDSS_T2 and a baseline EP compound measure (s-EP-Q_T0) for each group.ResultsMedian EDSS_T0 was 3.0 for Group 1 and 1.5 for Group 2. Mean disease durations were 2.0 and 2.8 years, respectively. Median EDSS_T2 was 2.0 for both groups. The s-EP-Q_T0 significantly predicted EDSS_T2 (R² = 0.47) for patients in Group 2, but not for patients in Group 1 (R² = 0.07).ConclusionIn early MS the functional remnants of relapses are a better predictor for development of medium-term disability than is the extent of impulse propagation impairment measured during relapse.SignificanceThis suggests a role of multimodal EPs in prediction of MS disability if performed in the relapse-free interval.     

Tumor necrosis factor(alpha) and insulin-like growth factor-I in the brain: is the whole greater than the sum of its parts?

The cytokine tumor necrosis factor(alpha) (TNFalpha) and the hormone insulin-like growth factor-I (IGF-I) have both been shown to regulate inflammatory events in the central nervous system (CNS). This review summarizes the seemingly independent roles of TNFalpha and IGF-I in promoting and inhibiting neurodegenerative diseases. We then offer evidence that the combined effects of IGF-I and TNFalpha on neuronal survival can be vastly different when both receptors are stimulated simultaneously, as is likely to occur in vivo. We propose the framework of a molecular model of hormone-cytokine receptor cross talk in which disparate cell surface receptors share intracellular substrates that regulate neuronal survival.     

Transfer of horseradish peroxidase from oligodendrocyte to axon in the myelinating neonatal rat optic nerve: Artefact or transcellular exchange?

In this paper we make the surprising observation that intracellular injection of horseradish peroxidase (HRP) into a single myelinating oligodendrocyte also resulted in localised HRP labelling at the nodes of Ranvier of some axons of the unit. It appeared that HRP had been transferred to the nodal axoplasm from the paranodal loops of the HRP-filled oligodendrocyte. Three HRP-filled oligodendrocytes from isolated optic nerves of 14-day-old rats were analysed by serial section electron microscopy, and HRP was observed in the axonal cytoplasm at three of the nodes of Ranvier delineated by one of the cells. At labelled nodes, HRP was of a uniform intensity throughout the nodal axoplasm. Axonal labelling gradually diminished along the paranodal regions and was not evident in the contiguous internodal axoplasm beyond 20 μm from the node. The myelin sheaths, paranodal loops, and axons appeared normal at labelled nodes, and the paranodal loops and astrocyte perinodal processes adjacent to those of the HRP-filled oligodendrocyte unit did not contain HRP. There was no evidence of extracellular HRP or tissue damage in the surrounding neuropil, and axons neighbouring those enwrapped by the HRP-filled oligodendrocyte did not contain HRP. The possibility that axonal labelling was an artefact of either iontophoretic injection or tissue preparation is discussed. This provocative finding is not definite proof of exchange, but the balance of evidence supports the possibility that there was transcellular exchange of HRP at paranodes between the labelled oligodendrocyte and some of the axons in the unit. The rarity of HRP transfer to axons suggests that it may be a transient or labile event. It is not clear whether oligodendrocyte to axon macromolecular exchange has real physiological and/or pathological significance. © Wiley-Liss, Inc.