Neuropathological evidence for neurosarcoidosis is more widespread than imaging suggests.

We present a single case of a 47 year old male with a relapsing progressive neurological disease characterised by an infiltrative inflammation of the brain and leptomeninges. Investigations revealed the presence of systemic sarcoidosis which was confirmed histologically following a mediastinal lymph node biopsy. The imaging appearances of the brain and spinal canal lesions were compatible with neurological involvement by the same disease. Despite treatment, the patient deteriorated and died. We present the neuropathological findings, correlate these with the imaging features, and find that neuropathological evidence for disease was in this case strikingly more widespread than predicted by imaging ante-mortem.

Cerebral infarction in Behçet's syndrome caused by obliterative focal arteritis.

We present a case in which cerebral infarction was seen and Behcet's syndrome was diagnosed. Following investigation and monitoring, we identified that the cause was a progressive obliterative focal arteritis of the middle cerebral artery. Such an entity has not previously been reported, although similar cases are described which explain the pathophysiology of the disorder.

Survival analysis of germination data in response to temperature for Ornithopus species and other temperate pasture legumes.

Cool temperatures can limit productivity of temperate grazing systems as poor pasture growth rates in winter create feed shortages for livestock. Ornithopus spp. (serradella) are broadly adapted annual pasture legumes that produce high-quality forage in soil types considered marginal for other temperate legume species. However, serradella establishment is perceived to be difficult in cool-season environments. We used survival analysis to compare germination rate and seedling emergence for two serradella species (yellow serradella and French serradella) against three reference species (Medicago sativa, M. polymorpha and Trifolium subterraneum ) in four temperature treatments (10/5, 15/10, 20/15 and 25/20°C; max/min). We also compared shoot relative growth rate and photosynthetic rate at 15/10°C (cool) and 23/18°C (warm). Cool temperatures (10/5, 15/10°C) did not slow germination rates for serradella relative to the reference species, but warm temperatures (20/15, 25/20°C) delayed emergence and reduced post-emergent shoot growth rates. Once established, Ornithopus spp. had similar mean photosynthetic rates and stomatal conductance at cool temperatures to the reference species. We conclude that, contrary to common perception, cool temperatures did not adversely influence germination, emergence, or early growth of Ornithopus spp. relative to the reference species.

Carotid arteritis causing amaurosis fugax and ischaemic cerebrovascular events in neurosarcoidosis.

OBJECTIVE: To present and review the vascular consequences of arteritis in neurosarcoidosis. PATIENT AND METHODS: neurosarcoidosis is typically an inflammatory disorder of the meninges surrounding the brain and spinal cord. Although inflammation of small and medium sized vessels is seen pathologically and vasculitis is occasionally described, a large intracerebral arteritis has not previously been reported. A few case reports exist, however, which describe the vascular consequences of large vessel compromise in the disorder. We review the literature and present a new case with novel MRI features which imply carotid arteritis. RESULTS: The case presented with a disorder of the carotid artery on one side leading to a series of TIAs. Inflammation of the wall of the carotid artery was seen adjacent to a granulomatous leptomeningitis. The disorder responded to immunosuppressive therapy without recurrence. CONCLUSIONS: The imaging features suggest a granulomatous infiltration of the carotid artery wall leading to arteritis followed by disorganisation of the internal elastic lamina and fibrosis. The data provide further insight into the pathogenesis of neurological impairments in neurosarcoidosis. The MRI features of carotid arteritis in neurosarcoidosis have not previously been demonstrated.

Soil erosion predictions from a landscape evolution model - An assessment of a post-mining landform using spatial climate change analogues.

Landscape Evolution Modelling (LEM) technologies provide a means by which it is possible to simulate the long-term geomorphic stability of a conceptual rehabilitated landform. However, simulations rarely consider the potential effects of anthropogenic climate change and consequently risk not accounting for the range of rainfall variability that might be expected in both the near and far future. One issue is that high resolution (both spatial and temporal) rainfall projections incorporating the potential effects of greenhouse forcing are required as input. However, projections of rainfall change are still highly uncertain for many regions, particularly at sub annual/seasonal scales. This is the case for northern Australia, where a decrease or an increase in rainfall post 2030 is considered equally likely based on climate model simulations. The aim of this study is therefore to investigate a spatial analogue approach to develop point scale hourly rainfall scenarios to be used as input to the CAESAR - Lisflood LEM to test the sensitivity of the geomorphic stability of a conceptual rehabilitated landform to potential changes in climate. Importantly, the scenarios incorporate the range of projected potential increase/decrease in rainfall for northern Australia and capture the expected envelope of erosion rates and erosion patterns (i.e. where erosion and deposition occurs) over a 100year modelled period. We show that all rainfall scenarios produce sediment output and gullying greater than that of the surrounding natural system, however a 'wetter' future climate produces the highest output. Importantly, incorporating analogue rainfall scenarios into LEM has the capacity to both improve landform design and enhance the modelling software. Further, the method can be easily transferred to other sites (both nationally and internationally) where rainfall variability is significant and climate change impacts are uncertain.

Neurological complications of Behçet's syndrome.

In this review of the neurological complications of Behçet's syndrome, the clinical features and epidemiology of the systemic disease are summarised before a discussion of the neurological syndromes which may develop is made. Neurological involvement occurs in 9% of cases, and is equally prevalent in each geographical area. Vascular complications occur in 14%, in whom thrombosis of the venous sinuses or cerebral veins occurs, and intracranial hypertension, venous infarction and parenchymal haemorrhage may develop. There is a correlation with the prevalence of peripheral venous thrombosis. Concurrent inflammatory disease of the brain is most uncommon. Inflammation may affect any part of the central nervous system, but most commonly involves a subacute meningoencephalitis of the brainstem and diencephalon. Inflammatory lesions elsewhere in the brain and in the spinal cord may occur, and tumefactive lesions may arise from the diencephalon. Cognitive dysfunction and affective symptoms, including psychosis, may occur, and there are high levels of anxiety and fatigue which are related to the severity of the systemic disease, all of which are more severe in those with neurological involvement. Imaging shows enhancing lesions which often disappear after treatment, but atrophy is common. The CSF is active when there is a meningoencephalitis, and oligoclonal bands do not occur. Treatment is with steroids and immunosuppression. Those with treatment resistant disease respond to biological agents, including TNF alpha, IL-1 and IL-6 antagonists.

Neurology of the cryopyrin-associated periodic fever syndrome.

BACKGROUND AND PURPOSE: The cryopyrin-associated periodic fever syndrome (CAPS) is an autosomal dominant autoinflammatory disorder caused by mutations in the NLRP3 gene and is typified by recurrent episodes of systemic inflammation resulting in fever, urticarial rash and arthralgia. In addition to these systemic aspects, CAPS has multiple neurological manifestations. The largest case series to date is presented focusing on the neurological features of this disorder. METHODS: The case histories of a cohort of 38 UK patients with genetically proven CAPS who were treated with interleukin 1ß (IL-1ß) inhibition as part of a national treatment programme and underwent detailed neurological assessment were reviewed. RESULTS: Across the entire disease course neurological manifestations were present in 95% of patients; 84% had some form of headache; 66% sensorineural hearing loss; 60% myalgia; 34% papilloedema and 26% optic atrophy. Patients with the T348M mutation tended to have a more severe neurological phenotype with an earlier age of onset. Four patients had cerebrospinal fluid examination, three of whom had evidence of aseptic meningitis. There was a marked response to IL-1ß inhibition, which has revolutionized management of these patients (29/32 patients with headache responding). CONCLUSION: Neurological symptoms are extremely common in CAPS and these results highlight the importance of increasing awareness amongst neurologists, particularly as highly effective therapies are available.

Rituximab is effective in severe treatment-resistant neurological Behçet's syndrome.

The objective of this study is to describe a case of severe and treatment-resistant neurological Behçet's syndrome responsive to a novel therapy. This case report describes the patient who failed to respond to conventional therapy but the brain stem lesion resolved with the anti-CD20 biological agent rituximab. Neurological complications are uncommon in Behçet's syndrome; 80% involve a meningoencephalitis which can be severe and relapsing. This is the first report of effectiveness of rituximab in this uncommon disease.

Bilateral Inflammatory Optic Neuropathy Related to Graft versus Host Disease Following Allogeneic Bone Marrow Transplantation for Hodgkin Disease.

Graft versus host disease (GvHD) is a common and often troublesome complication of allogeneic bone marrow transplantation. Neurological complications usually involve the peripheral nervous system and muscle, but the central nervous system may be affected. When an optic neuropathy develops, it is often difficult to determine the cause quickly; infective complications and drug toxicity may have arisen, but an inflammatory disorder due to GvHD should also be considered, particularly since treatment with steroids and immune suppression may improve the outcome significantly. This brief case report shows how this may be the case and reviews our current understanding of the pathophysiology and treatment of the disorder within the nervous system.

Neurosarcoidosis-related intracranial haemorrhage: three new cases and a systematic review of the literature.

BACKGROUND AND PURPOSE: Intracranial haemorrhage in neurosarcoidosis (NS-ICH) is rare, poorly understood and the diagnosis of NS may not be immediately apparent. METHODS: The clinical features of three new NS-ICH cases are described including new neuropathological findings and collated with cases from a systematic literature review. CASES: (i) A 41-year-old man with headaches, hypoandrogenism and encephalopathy developed a cerebellar haemorrhage. He had neuropathological confirmation of NS with biopsy-proven angiocentric granulomata and venous disruption. He responded to immunosuppressive therapy. (ii) A 41-year-old man with no history of hypertension was found unconscious. A subsequently fatal pontine haemorrhage was diagnosed. Liver biopsy revealed sarcoid granulomas. (iii) A 36-year-old man with raised intracranial pressure headaches presented with a seizure and a frontal haemorrhage. Hilar lymph node biopsy confirmed sarcoidosis, and he was treated successfully. Systematic review: Twelve other published cases were identified and collated with our cases. Average age was 36 years and M:F = 2.3:1; 46% presented with neurological symptoms and 31% had CNS-isolated disease. Immediate symptoms of ICH were acute/worsening headache or seizures (60%). ICH was supratentorial (62%), infratentorial (31%) or subarachnoid (7%). Forty percent had definite NS, 53% probable NS and 7% possible NS (Zajicek criteria). Antigranulomatous/immunosuppressive therapy regimens varied and 31% died. CONCLUSIONS: This series expands our knowledge of the pathology of NS-ICH, which may be of arterial or venous origin. One-third have isolated NS. Clinicians should consider NS in young-onset ICH because early aggressive antigranulomatous therapy may improve outcome.

Chronic and recurrent meningitis.

Chronic meningitis is defined as the persistence of clinical symptoms and signs of meningitis, with or without abnormal cerebrospinal fluid, for more than four weeks. In as many as one third of cases, no cause is found. In the remainder, infective, neoplastic and so-called aseptic disorders may be identified. Important infective causes include partially treated bacterial (pyogenic), tuberculous, syphilitic, Lyme and fungal meningitis. Sarcoidosis, Behçet's disease, vasculitis and drugs are major non-infective, non-malignant causes. The definitive diagnosis of the cause of chronic meningitis may be made only after extensive investigation. This review describes the clinical features and causes of chronic and recurrent meningitis, and provides an algorithm for investigation and treatment.

Orbital apex lesion due to Aspergillosis presenting in immunocompetent patients without apparent sinus disease.

We present two cases in which Aspergillus infection was identified at a late stage in the clinical evaluation as the cause for a painful, progressive and indolent orbital apex syndrome in the absence of any clinical or radiological sign of sinus involvement. Surgical investigation was undertaken with serious subsequent morbidity. Although treatment is often satisfactory, neurological outcome is without exception poor. A review of the literature has revealed that the risk of such investigations is high, and advice is provided to readers which may allow avoidance of such complications in the future.

Development of an in vitro corrosion/irritation prediction assay using the EpiDerm skin model.

A validation of the in vitro skin corrosion method using the EpiDerm skin model was performed using 12 recommended chemicals. All chemicals were correctly classified by OECD test guideline 431. In order to predict corrosion and/or irritation potential, additional compound exposure times and IL-1alpha measurements were included in a tiered testing approach. Four exposure times were performed followed by MTT (viability) and IL-1alpha measurement. This allowed classification of corrosive chemicals (OECD guideline 431) and those likely to be severe irritants. If the chemical was found to be corrosive or a severe irritant, no further experimental work was performed, otherwise a second experiment was performed using three further exposure times (same endpoints). The second experiment provided information on whether the chemical was likely to be a moderate/mild irritant. If the chemical was negative following both experiments, it was predicted as non-corrosive/non-irritating. A total of 12 chemicals were tested in the irritation or combined assay (five non-irritants, seven irritants). Specificity (% non-irritants concurring with EU classification) was 60% (MTT) and 100% (MTT+IL-1alpha). Sensitivity (% irritants concurring with EU classification) was 86% (MTT) and 86% (MTT+IL-1alpha). Accuracy (% chemicals correctly identified) was 75% (MTT) and 92% (MTT+IL-1alpha).

Optokinetic therapy improves text reading in patients with hemianopic alexia: a controlled trial.

OBJECTIVE: An acquired right-sided homonymous hemianopia can result in slowed left-to-right text reading, called hemianopic alexia (HA). Patients with HA lack essential visual information to help guide ensuing reading fixations. We tested two hypotheses: first, that practice with a visual rehabilitation method that induced small-field optokinetic nystagmus (OKN) would improve reading speeds in patients with HA when compared to a sham visual rehabilitation therapy; second, that this therapy would preferentially affect reading saccades into the blind field. METHODS: Nineteen patients with HA were entered into a two-armed study with two therapy blocks in each arm: one group practiced reading moving text (MT) that scrolled from right to left daily for two 4-week blocks (Group1), while the other had sham therapy (spot the difference) for the first block and then crossed over to MT for the second. RESULTS: Group 1 showed significant improvements in static text reading speed over both therapy blocks (18% improvement), while Group 2 did not significantly improve over the first block (5% improvement) but did when they crossed over to the MT block (23% improvement). MT therapy was associated with a direction-specific effect on saccadic amplitude for rightward but not leftward reading saccades. CONCLUSION: Optokinetic nystagmus inducing therapy preferentially affects reading saccades in the direction of the induced (involuntary) saccadic component. This is the first study to demonstrate the effectiveness of a specific eye movement based therapy in patients with hemianopic alexia (HA) in the context of a therapy-controlled trial. A free Web-based version of the therapy used in this study is available online to suitable patients with HA.

The prevalence of headache in Behçet's syndrome.

OBJECTIVES: Behçet's syndrome is an uncommon systemic disorder that involves the nervous system in 5% of cases. Headache may arise in conjunction with such complications but also appears to occur independently. We sought to define the prevalence of headache in an unselected group of patients with Behçet's syndrome, to characterize the headache syndromes and to identify what treatments are being used. METHODS: A questionnaire was sent to an unselected group of patients through their support group newsletter. RESULTS: The results showed a prevalence of recurrent headache in 82.5% of responders; the majority exhibited symptoms that fulfilled the International Headache Society criteria for migraine, with a higher than normal prevalence of visual or sensory aura of 52%. Using the Migraine Disability Assessment (MIDAS) score for disability in migraine, 62% of responders showed moderate or severe disability. Headache treatment was poor, the majority of sufferers resorting to over-the-counter remedies; preventative treatments had rarely been prescribed. CONCLUSIONS: Recurrent headache is very common in Behçet's syndrome, is poorly treated and is associated with disablement.

Paroxysmal intracranial hypertension.

We present the case of a man who presented with headache and severe papilloedema which was caused not by chronic intracranial hypertension but by paroxysms of raised intracranial pressure, and we speculate what relationship this disorder has to idiopathic intracranial hypertension.

Expression of beta2 adrenoreceptors on peripheral blood mononuclear cells in patients with primary and secondary progressive multiple sclerosis: a longitudinal six month study.

BACKGROUND: Beta(2) adrenoreceptor expression on peripheral blood mononuclear cells is increased in progressive multiple sclerosis. This increase has been correlated with disease activity in relapsing-remitting multiple sclerosis. OBJECTIVE: To determine the beta(2) adrenoreceptor expression in primary and secondary progressive multiple sclerosis in relation to findings on magnetic resonance imaging (MRI) and clinical disease activity. METHODS: 10 patients with multiple sclerosis were studied (five with primary progressive and five with secondary progressive forms of the disease) over a period of six months. Monthly clinical and MRI assessments of the brain and spinal cord were carried out. Beta(2) adrenoreceptor expression was assessed monthly using a ligand binding assay with [(125)I]iodocyanopindolol. Expression of beta(2) adrenoceptors on peripheral blood mononuclear cells was also assessed in five normal controls over a similar period. RESULTS: The mean (SEM) value of beta(2) adrenoreceptor density for the five normal controls was 1346 (183) sites/cell, with affinity Kd of 120 (40) pM. MRI disease activity in primary progressive multiple sclerosis was reported on two occasions and on those occasions the expression of beta(2) adrenoreceptors was increased in excess of 1900 sites/cell; in the remaining 28 observations beta(2) adrenoreceptor expression was within the normal range (800 to 1900 sites/cell). In patients with secondary progressive disease, MRI disease activity was observed on 16 occasions. In these patients expression of beta(2) adrenoreceptors was increased in excess of 2000 sites/cell in all measurements except in one subject who did not show MRI activity throughout the six months period of study. The affinity of the receptors was within the normal range in all cases. CONCLUSIONS: Increased expression of beta(2) adrenoreceptors was correlated with MRI disease activity in two patients with primary progressive multiple sclerosis. In secondary progressive multiple sclerosis, increased expression of beta(2) adrenoreceptors tended not to correlate with MRI disease activity. This may reflect a persistent Th1 immune reaction in the secondary progressive form of the disease.

Chronic relapsing inflammatory optic neuropathy (CRION).

We describe the clinical characteristics and early natural history of a form of inflammatory optic neuropathy which is frequently bilateral and often painful, and is characterized by relapses and remissions. MRI scans of the brain are normal and those of the optic nerves often, but not always, show high signal abnormalities which enhance. The symptoms and signs respond well to corticosteroid treatment, although long-term immuno suppression is often necessary. The syndrome behaves in a way which is typical of the condition known as granulomatous optic neuropathy, but during a median follow-up of 8 (2-26) years in no case has evidence for systemic sarcoidosis been identified. We suggest that the disorder be named chronic relapsing inflammatory optic neuropathy (CRION).

The predictive value of gadolinium enhancement for long term disability in relapsing-remitting multiple sclerosis--preliminary results.

As short-term MRI studies are increasingly being used to monitor disease activity in multiple sclerosis (MS) it is vital to establish if short-term MRI activity is predictive of long term clinical outcome. We followed up after 5 years a group of 10 benign (relapsing-remitting MS with a disease duration > 10 years and EDSS < or = 3) and 10 early relapsing-remitting patients who previously had monthly serial MRI scans for 6 months. In the early relapsing-remitting group median EDSS at entry to the initial serial study was three and in the benign group 2.5. At 5-year follow up, five of these 20 patients had developed a definite deterioration in EDSS. The median number of new enhancing lesions detected originally in the group that had deteriorated was 11 (7-17) compared to 0 (0-5) new enhancing lesions, for those who had not deteriorated (P < 0.05). There was a trend towards a higher baseline T2 lesion load in the group with a definite change in EDSS but this was not significant This study suggests that short-term measurement of the number of gadolinium enhancing lesions may predict long term outcome in relapsing-remitting MS.