Numerical Analysis of Temperature Distribution Profiles of Breast Tissues with Cyst and Tumor of Different sizes and Locations.

Breast cancer causes more deaths among all types of cancers. Efforts have been put to study the change in temperature distribution profile of the breast in presence of an abnormality. By applying Pennes's bio-heat equation, a 2D finite element model is developed for the heat transfer mechanism. Surface temperature gradients due to the presence of abnormalities at various depths and sizes are analyzed. The results show that the presence of a cyst decreases the temperature whereas the occurrence of tumor increases the temperature inside the breast. It is observed that abnormal tissue having a radius less than 1.5cm and depth greater than 5cm, has a negligible effect on the surface temperature profile. The highest change in surface temperature is observed when a cyst or tumor is larger and present near the skin. The simulation results help in the better interpretation of the thermal images and calibration of infrared camera. This study could be helpful in the early diagnosis of breast cancer.

Amyloid-beta-related angiitis: a treatable rapidly progressive dementia.

A 73-year-old woman developed cognitive decline over 1 year. MR scan of the brain showed a focal asymmetrical leukoencephalopathy involving the right frontal, temporal, parietal and occipital lobes. Extensive laboratory investigations found no cause but brain biopsy identified amyloid-beta-related angiitis (ABRA), a potentially treatable cause of rapid-onset dementia. We gave intravenous methylprednisolone and then two courses of intravenous cyclophosphamide, after which her cognitive skills gradually but significantly improved over several months.

A novel assessment and treatment approach to patients with Hashimoto's encephalopathy.

Hashimoto's encephalopathy (HE) is rarely reported with only a few hundred cases published. Diagnosis is made in patients with an appropriate clinical picture and high antithyroperoxidase (anti-TPO) antibodies after infectious, toxic and metabolic causes of encephalopathy have been excluded. There is little objective data on the neurocognitive impairment in patients with HE and their improvement with treatment. We present the case of a 28-year-old woman with HE. Approach to management was novel as objective neuropsychological assessment was used to assess her clinical condition and response to treatment. Intravenous immunoglobulin (IVIg) as the first-line treatment instead of steroids. She responded well. The case illustrates that a different approach is required for the diagnosis and treatment of HE. A new diagnostic criteria is proposed that includes neurocognitive assessment, serum and CSF antibodies, an abnormal EEG and exclusion of other causes of encephalopathy. Furthermore, treatment should be tailored to the patient. LEARNING POINTS: Neurocognitive assessment should be carried out to assess the extent of brain involvement in suspected Hashimoto's encephalopathy pre- and post- treatment.Treatment of Hashimoto's encephalopathy should be tailored to the patient.Unifying diagnostic criteria for Hashimoto's encephalopathy must be established.

Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes.

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.

EAE is not a useful model for demyelinating disease.

Experimental allergic encephalomyelitis (EAE) is the commonest, readily induced, organspecific, autoimmune disorder of laboratory animals of its kind. It is an artificial disorder brought about by the immunisation of susceptible animals with brain antigens in complete Freund׳s adjuvant (CFA). Variations can be induced by altering the nature of the antigen and the conditions involving immunisation. Whilst it is often described as a demyelinating disease, in strict terms it is not, since the primary pathologic process is not demyelination but rather an encephalomyelitis that is immunologically induced. Rather, the prototype demyelinating disease is multiple sclerosis and its variants. In this paper, the central question we ask is whether the data gleaned from the EAE model contributes to our understanding of the pathological events in MS. Towards answering this, we describe the historical development of EAE and its hyperacute form, and discuss the findings studied extensively in the non-human primate which show that ordinary EAE is an exact model for ADEM in the human, and that the hyperacute form of EAE is represented by AHLE in the human. Additionally, we shall comment on the latest research on new variants of EAE, and explain our opinion regarding the use of EAE models in research aiming to understand the pathogenesis of multiple sclerosis.

The UK patient experience of relapse in Multiple Sclerosis treated with first disease modifying therapies.

BACKGROUND: The fixed, progressive disability associated with late Multiple Sclerosis (MS) is known to have a major impact on patients and their families, but the impact of relapse earlier in the disease course is less well documented, particularly from the patient׳s perspective. This study aimed to understand the effects of relapse for people with MS (PwMS), focussing on the years immediately after starting disease modifying therapy (DMT) when experience of a relapse may particularly influence a patient׳s opinions of their disease and its therapy. METHODS: This was a multi-centre, retrospective, observational research study, recruiting patients from 7 UK NHS Hospital Trusts. Consenting patients with relapsing-remitting MS (RRMS), who had started a DMT more than 36 months before screening, were sent a study questionnaire. Data on MS relapses and treatments over 3 years were collected simultaneously from medical records. RESULTS: One hundred and three patients completed the questionnaires. Relapses were under-reported to health care professionals, with 28% of respondents failing to report their most recent attack and 46% declaring they had failed to report an attack in the past. During their most recent relapse, 67% of those in paid employment reported taking time off sick, 48% reduced working hours temporarily, and 41% worked reduced hours and took time off sick. Sixty-six percent required additional support to undertake routine daily tasks during their most recent relapse. A range of effects of relapse which cannot be measured in financial terms were also reported, including effects on physical abilities, mental health and family roles and relationships. CONCLUSION: This contemporary UK-based study provides an insight into the experience of relapse early in the treatment of RRMS from the patient perspective. The comparison of documented patient reported relapses reveals some deficiencies in the recording of relapses which is important to address in view of the reported impact of individual relapses, and emphasises relapse reduction as a worthy treatment aim.

Multiple sclerosis is primarily a neurodegenerative disease.

The precise pathogenesis of multiple sclerosis is unknown. The assumption of a primary immunopathogenesis of the disease is seriously flawed and has failed to deliver an effective therapy for most patients. The progressive degeneration of grey and white matter is integral to the natural history of the disease and is reflected in the atrophy of brain and spinal cord. Demyelination is an essential component of this primary neurodegenerative process rather than the target of a systemic immune response. The primary pathology of multiple sclerosis is a process of neurodegeneration based on the integrity of the blood-brain barrier. Primary progressive multiple sclerosis is the prototype neurodegenerative disease, and the relapsing-remitting form in younger population represents the modifying effect of steroids (vitamin D, sex and stress hormones) on metabolic functions of the central nervous system.

Voltage-gated potassium channelopathy: an expanding spectrum of clinical phenotypes.

Autoimmune voltage-gated potassium channelopathies represent a wide and expanding spectrum of neurological conditions. We present a case demonstrating the phenotypic heterogeneity of antivoltage-gated potassium channels (VGKC)-associated disorders. Such cases may easily be dismissed as functional disorders at first presentation. We propose that there must remain a high index of suspicion for antiVGKC-associated disorders in cases where there are transient neurological disturbances in atypical spatial and temporal distributions.

Swelling and enhancement of the cervical spinal cord: when is a tumour not a tumour?

OBJECTIVE: To describe the management of patients with co-existing cervical spondylotic compression and enhancing intramedullary swelling of uncertain aetiology. We describe the key features, suggest a management plan and review the literature. MATERIAL AND METHODS: A short series of six cases with cervical myelopathy and radiological features of spondylotic compression, swollen cervical cord and intramedullary enhancement is described. Detailed descriptions of clinical features, radiological findings, surgical approaches and outcomes are discussed. All patients underwent cervical decompression via an anterior approach, posterior approach or both. Despite initial concerns that the aetiology might be tumour, no biopsy of cervical cord was required in any of the cases. RESULTS: Symptoms improved in four cases whilst contrast enhancement only improved in two cases following decompression. One patient who failed to improve postoperatively was found to have neurosarcoidosis. No patient became worse after the cervical decompression. CONCLUSION: Swelling of the spinal cord with enhancement and co-existing spondylotic cord compression, in the first instance, should be treated by decompression only. Biopsy to diagnose intrinsic tumour or inflammatory conditions should not be performed unless there is radiological or clinical progression despite adequate decompression.

The sad plight of multiple sclerosis research (low on fact, high on fiction): critical data to support it being a neurocristopathy.

The literature for evidence of autoimmunity in multiple sclerosis (MS) is analysed critically. In contrast to the accepted theory, the human counterpart of the animal model experimental autoimmune demyelinating disease, experimental allergic encephalomyelitis (EAE), is not MS but a different demyelinating disorder, i.e. acute disseminated encephalomyelitis and acute haemorrhagic leucoencephalitis. Extrapolation of EAE research to MS has been guided largely by faith and a blind acceptance rather than sound, scientific rationale. No specific or sensitive immunological test exists that is diagnostic of MS despite the extensive application of modern technology. Immunosuppression has failed to have any consistent effect on prognosis or disease progression. The available data on MS immunotherapy are conflicting, at times contradictory and are based on findings in animals with EAE. They show predominantly a 30% effect in relapsing/remitting MS which suggests powerful placebo effect. Critical analysis of the epidemiological data shows no association with any specific autoimmune diseases, but does suggest that geographic factors and age at development posit an early onset possibly dependent on environmental influences. Certain neurological diseases are, however, found in association with MS, namely hypertrophic peripheral neuropathy, neurofibromatosis-1, cerebral glioma, glioblastoma multiforme and certain familial forms of narcolepsy. These share a common genetic influence possibly from genes on chromosome 17 affecting cell proliferation. A significant number of these disorders are of neural crest origin, the classical example being abnormalities of the Schwann cell. These and other data allow us to propose that MS is a developmental neural crest disorder, i.e. a cristopathy, implicating glial cell dysfunction with diffuse blood-brain barrier breakdown. The data on transcription factor SOX10 mutations in animals may explain these bizarre clinical associations with MS and the phenotypic variability of such alterations (Cossais et al. 2010). Research directed to the area of neural crest associations is likely to be rewarding.

A gene signature for post-infectious chronic fatigue syndrome.

BACKGROUND: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. METHODS: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). RESULTS: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance CONCLUSION: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment.