Search

Study design:An immunohistological assessment of substance P (SP), its NK1 receptor and claudin-5 in human spinal cord injury (SCI) tissue.Objective:To determine whether SP and NK1 receptor immunoreactivity are altered following human traumatic SCI.Setting:Australia.Summary of background data:SP has been implicated in the development of neurogenic inflammation and subsequent edema development following both traumatic brain injury and ischemic stroke. In these conditions, inhibition of its NK1 receptor has been shown to be neuroprotective as reflected in a reduction of edema and improved functional outcome. However, the role of SP following human SCI has not yet been assessed.Methods:Archived human SCI tissue was grouped according to survival times: control (no injury; n=5); immediate (death within an hour of the incident; n=6); 2-5 h (n=3); 3 days (n=5); 1 week (n=3); and 3-4 weeks (n=6). Sections were assessed for SP, its NK1 receptor and claudin-5 using immunohistochemical techniques.Results:Following SCI, dorsal horn SP immunoreactivity demonstrated a profound decrease compared with control tissue, indicating the loss of SP with SCI. A marked increase in perivascular NK1 staining was demonstrated after SCI compared with control levels. No obvious change in claudin-5 immunoreactivity was present immediately following injury, however, by 1 week post-SCI, decreased levels were noted.Conclusion:This study demonstrates that severe acute traumatic human SCI results in decreased SP and an immediate increase in NK1 receptor immunoreactivity, suggesting that there is a neurogenic inflammatory component following human SCI. [ABSTRACT FROM AUTHOR]

Abstract: Non-accidental head injury (NAHI), also termed the “shaken baby syndrome”, is a major cause of death and severe neurological dysfunction in children under three years of age, but it is debated whether shaking alone is sufficient to produce brain injury and mortality or whether an additional head impact is required. In an attempt to resolve this question, we used a lamb model of NAHI since these animals have a relatively large gyrencephalic brain and weak neck muscles resembling those of a human infant. Three anaesthetised lambs of lower body weight than others in the experimental group died unexpectedly after being shaken, proving that shaking alone can be lethal. In these lambs, axonal injury, neuronal reaction and albumin extravasation were widely distributed in the hemispheric white matter, brainstem and at the craniocervical junction, and of much greater magnitude than in higher body weight lambs which did not die. Moreover, in the eyes of these shaken lambs, there was damage to retinal inner nuclear layer neurons, mild, patchy ganglion cell axonal injury, widespread Muller glial reaction, and uveal albumin extravasation. This study proved that shaking of a subset of lambs can result in death, without an additional head impact being required. [Copyright &y& Elsevier]

Summary: Neuroaxonal dystrophy (NAD) is a morphological abnormality in man and animals that is characterized by the occurrence of numerous axonal swellings (spheroids) in the nervous system. NAD has been described in Suffolk lambs in the USA, Merino lambs in Australia and several breeds of sheep in New Zealand. This paper describes the clinicopathological changes of only the second occurrence of NAD reported in Merino lambs. There were some features (myelin loss, gliosis and visual impairment) in these Australian cases that have not been reported previously in ovine NAD. Application of immunohistochemical markers of axonal transport suggested that disruption of this transport mechanism contributed to spheroid development. [ABSTRACT FROM AUTHOR]

We report an encephalomyelopathy in three 18-month-old Merino sheep with features of adult-onset Alexander’s disease (AD), a human primary astrocytic disorder. The signature histologic finding was the presence of numerous hypereosinophilic, intra-astrocytic inclusions (Rosenthal fibers), mainly in perivascular, subpial, and subependymal sites, especially in the caudal brain stem and spinal cord. Although AD usually results from mutations in the glial fibrillary acidic protein (GFAP) gene, no such mutation was detected in these sheep. However, the annual clinical presentation of this disorder in a few sheep in the affected flock is suggestive of a familial pattern of occurrence. [ABSTRACT FROM PUBLISHER]

Abstract: Cerebral contusions are one of the principal lesions of traumatic brain injury and the attendant oedema formation contributes substantially to the clinicopathological manifestations. While it is now recognised that the membrane channel protein aquaporin-4 (AQP-4) plays a major role in the development and resolution of cerebral oedema, assessments of its expression in and around contusions have produced conflicting results. We used an ovine impact-acceleration model of closed head injury to examine contusion-related AQP-4 expression and found that there was a heterogeneous AQP-4 response within contusions, with some astrocytes being nonviable and immunonegative, while others showed increased AQP-4 expression. Pericontusional astrocytes in the penumbra region generally showed more robust AQP-4 immunopositivity than intracontusional glia. Thus, manipulation of AQP-4 expression could have therapeutic applications in controlling cerebral oedema associated with contusions. [Copyright &y& Elsevier]

Abstract: Pituitary gland metastases, albeit rare, remain an important differential in sellar and suprasellar tumours. Clinical and radiological features of pituitary metastases may be indistinguishable from benign suprasellar lesions such as a pituitary adenoma. Histopathology with immunohistochemical assay remains the key to the diagnosis of pituitary metastasis. We describe four patients with sellar lesions presenting with anterior visual pathway compression initially diagnosed as pituitary adenomas who on immunohistochemistry were found to have metastases to the pituitary. Classification of the cell histology determined the primary site of origin in some patients. This series demonstrates the importance of combining histopathology and immunohistochemistry in the diagnosis of suprasellar lesions. [Copyright &y& Elsevier]

Abstract: Non-accidental head injury (“shaken baby syndrome”) is a major cause of death and disability in infants and young children, but it is uncertain whether shaking alone is sufficient to cause brain damage or an additional head impact is required. Accordingly, we used manual shaking in an ovine model in an attempt to answer this question since lambs have a relatively large gyrencephalic brain and weak neck muscles resembling a human infant. Neuronal perikaryal and axonal reactions were quantified 6 hours after shaking using amyloid precursor protein (APP) immunohistochemistry. Neuronal perikaryal APP was widely distributed in the brain and spinal cord, the first time such a diffuse neuronal stress response after shaking has been demonstrated, but axonal immunoreactivity was minimal and largely confined to the rostral cervical spinal cord at the site of maximal loading. No ischaemic-hypoxic damage was found in haematoxylin and eosin-stained sections. [Copyright &y& Elsevier]

The spectrumof central nervous system (CNS) vascular pathology in systemic lupus erythematosus (SLE) includes small vessel vasculopathy, thromboembolism, perivascular lymphocytic infiltration and, rarely, overt transmural vasculitis. We present the case of a patient, who experienced three CNS relapses over total disease duration of 26 years, with otherwise indolent disease. The first two relapses were suspicious of vasculitis and the last was proven at autopsy. The short duration between final relapse onset and death in this SLE CNS vasculitis case was, to our knowledge, unique. Histopathological investigation demonstrated multiple confluent areas of haemorrhage in the medulla due to an acute small vessel leucocytoclastic vasculitis. [ABSTRACT FROM AUTHOR]

Abstract: Pathological studies of a sural nerve biopsy in a man with Tangier disease presenting as a remitting-relapsing multifocal neuropathy showed abnormalities in the paranodal regions, including lipid deposition (65%) and redundant myelin foldings, with various degrees of myelin splitting and vesiculation (43%) forming small tomacula and abnormal myelin terminal loops (4%). The internodal regions were normal in the majority of myelinated fibres. Abnormal lipid storage was also present in the Schwann cells of the majority of unmyelinated fibres (67%). The evidence suggests that the noncompacted myelin region of the paranode is a preferential site for lipid storage in the myelinated Schwann cell, and that the space-occupying effects of the cholesterol esters leads to paranodal malfunction and tomacula formation as the pathological basis for the multifocal relapsing-remitting clinical course. [Copyright &y& Elsevier]

Summary: Motor Neurone Disease (MND) is one of the commonest neurodegenerative disorders of adulthood. MND characteristically presents with a combination of both upper and lower motor neurone features. Primary Lateral Sclerosis (PLS) is thought to be a variant of MND presenting with purely upper motor neurone signs. Debate continues over whether PLS constitutes a distinct pathological entity or whether it is part of the spectrum of motor neurone diseases that present as an upper motor neurone-predominant form of MND. We present a case of MND with purely upper motor neurone features and a prominent pain component. A pre-mortem diagnosis of PLS was made, however autopsy findings demonstrated both upper and lower motor neurone involvement. We believe these findings support the view that PLS is not a discrete pathological entity, but that it is a part of the range of motor neurone diseases that present with predominant but not exclusive upper motor neurone involvement. This case also highlights the feature that pain may be associated with MND even though it is not appreciated to have a sensory pathology. [Copyright &y& Elsevier]

Diffuse axonal injury (DAI) as defined by detailed microscopic examination was found in 34 of 80 consecutive cases of head trauma surviving for a sufficient length of time to be clinically assessed by the Royal Adelaide Hospital Neurosurgery Unit. The findings indicate that there is a spectrum of axonal injury and that one third of cases of DAI recovered sufficiently to talk between the initial head injury producing coma and subsequent death. The macroscopic "marker" lesions in the corpus callosum and dorsolateral quadrants of the brainstem were present in only 15/34 of the cases and represented the most severe end of the spectrum of DAI. [ABSTRACT FROM AUTHOR]

A 52-year-old man with large cell non-Hodgkin's lymphoma developed a unique pattern of central nervous system involvement by lymphoma while in apparent systemic remission. Despite intermittent neurological episodes suggestive of CNS involvement by lymphoma no evidence of CNS lymphoma was found on repeated cerebrospinal fluid and brain CT scan examinations. At necropsy widespread occlusion of cerebral blood vessels by malignant lymphoid cells was observed with extensive tissue necrosis and haemorrhages. Leukaemic involvement of peripheral blood was not detected on repeated blood film examinations during life. [ABSTRACT FROM AUTHOR]

Genetically proven identical twin sisters with Alzheimer's disease are reported. Both sisters at the age of fifty years developed a dementing illness. Their mother and maternal grandmother developed at the same age a similar illness. It is suggested that in some cases of familial Alzheimer's disease the condition is inherited by a single mutant gene. [ABSTRACT FROM AUTHOR]