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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis.

We performed MRI of brain and spinal cord on 80 patients with multiple sclerosis (MS). Using multi-array coils and fast spin echo, 139 intrinsic lesions were identified in 59 patients (74%). Lesions were more common in the cervical than in the thoracic cord. Cross-sectional areas of the cord, measured from axial images at four levels, showed atrophy in 40%. Clinical disability correlated with cord atrophy but not with cord lesion load. These results show that the use of multi-array coils and fast spin echo allows rapid and sensitive detection of spinal cord lesions in MS and that the cord is involved in the majority of patients. A lack of association between cord lesions and disability may relate to limitations in MR resolution but also suggests that the mechanisms of disability in MS are complex and multifactorial.

Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging.

OBJECTIVE: To assess whether serial serum levels of soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are useful as surrogate markers of disease activity in multiple sclerosis (MS). BACKGROUND: Increased levels of sICAM-1 and sVCAM-1 have been described in cross-sectional, but not longitudinal, studies of patients with MS. Although they appear to correlate with clinical and MRI markers of disease activity, their role as potential surrogate markers remains undefined. METHODS: Serial serum levels of sICAM-1 and sVCAM-1 were measured in patients with MS undergoing monthly gadolinium-enhanced MRI studies of the brain (462 gadolinium-enhanced MRI in 57 patients) and in 12 normal control subjects. Ten patients had primary progressive (PP), 22 relapsing remitting (RR), and 25 secondary progressive (SP) disease. RESULTS: Levels of sICAM-1 and sVCAM-1 were increased intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were elevated in patients with MS compared with normal controls (normal controls median [interquartile range] = 176[119-209] compared with PP = 502[194-1768], RR = 419[158-481], and SP = 352[196-469] ng/mL; p = 0.04). After excluding patients with PP MS, patients with high sICAM-1 levels had a greater number of gadolinium-enhancing lesions per study (1.9[0.9-4.3]) than patients with normal levels (0.4[0-2.7], p = 0.03), and patients with MRI studies with no gadolinium-enhancing lesions had lower associated sICAM-1 levels (200 ng/mL[85-561]) than patients with only persistent (349 ng/mL[82-615]) or new enhancing lesions (497 ng/mL[108-667], p = 0.03). Patients with RR or SP disease that progressed clinically during the study had a greater number of gadolinium-enhancing lesions per MRI study (3.5[0.4-5.5]) than did patients in whom disease did not progress (1.2 [0.3-2.7], p = 0.03). The patients with progressive disease tended to have higher sICAM-1 levels (469 ng/mL [196-1019]) than patients in whom disease did not progress (353 ng/mL [171-469], p = 0.07). Although MS patients tended to have higher sVCAM-1 levels than did normal controls, this finding was not significant. No correlation could be found between levels of sVCAM-1 and gadolinium enhancement on MRI. CONCLUSIONS: Patients with MS have elevated levels of sICAM-1, which correlate with gadolinium enhancement on MRI and possibly short-term disease progression. Soluble ICAM-1, and not sVCAM-1, may therefore be suitable as a long-term surrogate marker of disease activity in MS.

Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis.

Although serial MRI studies of the brain in relapsing-remitting MS have demonstrated frequent asymptomatic disease activity, less is known about the spinal cord. We carried out monthly gadolinium-enhanced brain and spinal cord MRI scans over 1 year in 10 patients with relapsing-remitting MS. Six of the patients had a total of 11 clinical relapses, eight of which involved the spinal cord. A total of 167 active (enhancing or new nonenhancing) lesions in the brain and 19 in the spinal cord were present. Only one active brain lesion was symptomatic compares with six spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. Activity in both the spinal cord and brain was more common around the time of relapse. There was a strong association between the spinal cord and brain MRI activity. We did not detect progressive spinal cord atrophy from measurements of a spinal cord cross-sectional area. We conclude that, in relapsing-remitting MS, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. The lack of ++progressive spinal cord atrophy in these patients, suggesting that significant axonal loss has not occurred, is in keeping with their good recovery after relapse. That brain and spinal cord lesions occur concurrently implies a systemic trigger for disease activity.

Spinal cord MRI using multi-array coils and fast spin echo. I. Technical aspects and findings in healthy adults.

It is time-consuming to detect intrinsic spinal cord lesions in multiple sclerosis (MS) by MRI using conventional surface coils and T2-weighted spin-echo pulse sequences. Multi-array coils and fast spin-echo pulse sequences permit the generation of high-resolution T2-weighted sagittal images of the whole spinal cord in about 5 minutes. Using these advances, we found an area of high signal within the cord in only 1/45 (2%) healthy subjects aged 18 to 72 years, whereas 26% of those who underwent brain imaging had cerebral white matter abnormalities. Degenerative vertebral column changes, especially in the cervical region, were present in 64% and were associated with cord compression in 11%. Cord cross-sectional areas in mm2, measured from axial gradient-echo images, were usually highly reproducible and showed a significant correlation with the subject's height. We conclude that (1) MRI signal abnormalities within the spinal cord may be more specific for MS than cerebral white matter lesions, especially in subjects over 50 years old; (2) asymptomatic degenerative changes in the vertebral column are common, even in younger adults; (3) measurement of cord cross-sectional area should allow accurate quantitation of the degree of atrophy in MS and other spinal cord diseases; and (4) multi-array coils and fast spin echo represent an important advance in MRI of the spinal cord.

The natural history and clinical consequences of aspiration in acute stroke.

Sixty consecutive patients admitted to a teaching hospital with acute stroke were studied prospectively for 3 months to define the natural history and consequences of lung aspiration. Using videofluoroscopy, aspiration was identified in 25 patients (42%) within 72 h of stroke onset, and had resolved in all but three patients (8%) after 3 months. It was closely related to the presence of dysphagia, which itself resolved within 2 weeks in all but the persistent aspirators. Lower respiratory tract infection (LRTI) was more common in aspirating patients (68%) than non-aspirators (6%). The use of intravenous fluids without oral intake did not appear to prevent LRTI in aspirating patients who were also dysphagic. Pneumonia occurred after 2 weeks in the three patients subsequently found to aspirate persistently. Aspiration is a transient phenomenon in most cases of acute stroke; it is associated with a high incidence of LRTI, but mortality in this series was not significantly associated either with respiratory tract infection or aspiration itself.

Late functional deterioration following paralytic poliomyelitis.

Many patients with previous poliomyelitis develop 'post-polio syndrome' (PPS) in which late functional deterioration follows a period of relative stability. The frequency with which PPS can be attributed to clearly defined causes remains uncertain. We reviewed 283 newly-referred patients with previous poliomyelitis seen consecutively over a 4-year period; 239 patients developed symptoms of functional deterioration at a mean of 35 (5-65) years after the paralytic illness. Functional deterioration was associated with orthopaedic disorders in 170 cases, neurological disorders in 35, respiratory disorders in 19 and other disorders in 15. Progressive post-polio muscular atrophy was not observed. Functional deterioration following paralytic polio-myelitis is common, and associated with orthopaedic, neurological, respiratory and general medical factors which are potentially treatable.

The transverse magnetisation decay characteristics of longstanding lesions and normal-appearing white matter in multiple sclerosis.

The characteristics of transverse magnetisation decay of 120 longstanding lesions and 40 regions of normal-appearing white matter have been analysed in 40 patients with multiple sclerosis (MS) and 10 normal controls. Fifty lesions showed a biexponential decay in which two water compartments-one probably intracellular, the other extracellular-could be defined. There was a higher frequency of biexponential lesions in patients with a primary progressive course but no significant difference between benign and secondary progressive groups. Seventy lesions showed a monoexponential decay, of which 31 showed a T2 of greater than 200 ms, implying that these lesions were predominantly composed of extracellular rather than intracellular water. The results imply that an expanded extracellular space within chronic MS brain lesions is a common finding at all levels of disability and disease course. In so far as an expanded extracellular space implies axonal loss, the results suggest that the latter occurs commonly in longstanding MS lesions. The lack of correlation with disability suggests a limited role for the technique in therapeutic monitoring.