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.

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.

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.

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.

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 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.

Placental umbilical cord blood transfusion in acute ischaemic stroke.

Stroke is a major cause of neurological disability across all countries in the world. Functional recovery after stroke is limited because of neuronal death and degeneration. Although early reperfusion therapy may improve outcome, thrombolysis does not reverse ischaemic neuronal death and carries the risk of cerebral haemorrhage. Early trials of stem cell therapy in promoting functional recovery after completed stroke remain inconclusive. Based on experimental data, we propose human umbilical cord blood transfusion as a possible therapy for ischaemic cerebral stroke to aid functional recovery.

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.

Fatigue in neurological disorders.

Chronic fatigue is a typical symptom of neurological diseases, and is most disabling in multiple sclerosis, postpoliomyelitis, poststroke, and in chronic fatigue syndrome. Disorders of neuromuscular junction transmission and metabolic diseases cause muscle fatigability, which is characterised by failure to sustain the force of muscle contraction (peripheral fatigue). Fatigue is also seen in diseases that affect the central, peripheral, and autonomic nervous systems (central fatigue). Enhanced perception of effort and limited endurance of sustained physical and mental activities are the main characteristics of central fatigue. Metabolic and structural lesions that disrupt the usual process of activation in pathways interconnecting the basal ganglia, thalamus, limbic system, and higher cortical centre are implicated in the pathophysiological process of central fatigue. A state of pre-existing relative hypocortisolaemia might sensitise the hypothalamic-pituitary-adrenal axis to development of persistent central fatigue after stress. The contributions of physiological, cognitive, and affective changes underlying fatigue are variable, and treatment is largely symptomatic and rehabilitative.

Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that runs a chronic course and disables young people. The disease is more prevalent in the geographic areas that are farthest from the equator. No form of treatment is known to be effective in preventing MS or its disabling complications. A number of epidemiological studies have shown a protective effect of exposure to sunlight during early life and a recent longitudinal study confirmed that vitamin D supplementation reduced life-time prevalence of MS in women. Very little is known regarding the role of vitamin D on the developing brain but experimental data suggest that cerebral white matter is vitamin D responsive and oligodendrocytes in the brain and spinal cord and express vitamin D receptors. It is possible that differentiation and axonal adhesion of oligodendrocytes are influenced by vitamin D level during brain development and a relative lack of vitamin D may increase oligodendroglial apoptosis. The age effect of migration on susceptibility to develop MS could be explained by a role of vitamin D on brain development. In areas of high MS prevalence, dietary supplementation of vitamin D in early life may reduce the incidence of MS. In addition, like folic acid, vitamin D supplementation should also be routinely recommended in pregnancy. Prevention of MS by modifying an important environmental factor (sunlight exposure and vitamin D level) offers a practical and cost-effective way to reduce the burden of the disease in the future generations.

Adjunctive dexamethasone treatment in acute bacterial meningitis.

The initiation of antibiotic treatment on suspicion of bacterial meningitis is important, but it is not enough to improve the prognosis for patients, especially those with pneumococcal meningitis. The mortality and morbidity of pneumococcal meningitis are still devastating, and results of a recent randomised trial have shown evidence in favour of dexamethasone treatment given before or with the first antibiotic dose. Adjuvant dexamethasone is unequivocally recommended in children and adults with haemophilus meningitis or pneumococcal meningitis. The benefit of adjunctive dexamethasone is likely to be greatest in patients who are otherwise healthy and present early with acute bacterial meningitis. Dexamethasone is not currently recommended for the treatment of gram-negative bacillary meningitis and neonatal meningitis. Dexamethasone, before or with the first dose of antibiotic, is likely to be one of the most significant practice changes that will benefit many adults and children with common types of acute bacterial meningitis and has been of proven value in the developed world.

The clinical spectrum, diagnosis, pathogenesis and treatment of Hashimoto's encephalopathy (recurrent acute disseminated encephalomyelitis).

Hashimoto's encephalopathy may present with a wide variety of different neurological symptoms and signs. These include recurrent severe migrainous headache, psychoses, seizures, ataxia, dementia, stupor and coma. We present a personal series of 18 adult patients with Hashimoto's encephalopathy and a review of the literature in this paper. The natural history, laboratory abnormalities and neuroimaging data in these cases favour an immunopathological basis for this syndrome similar to relapsing acute disseminated encephalomyelitis. We suggest that Hashimoto's encephalomyelitis should be considered in the differential diagnosis of seizures, coma, atypical migraine and reversible dementia. Serological screening for anti-thyroid antibody should form part of the initial investigations in all relapsing and reversible encephalopathies.

Exercise lowers pain threshold in chronic fatigue syndrome.

Post-exertional muscle pain is an important reason for disability in patients who are diagnosed to have Chronic Fatigue Syndrome (CFS). We compared changes in pain threshold in five CFS patients with five age and sex matched controls following graded exercise. Pain thresholds, measured in the skin web between thumb and index finger, increased in control subjects with exercise while it decreased in the CFS subjects. Increased perception of pain and/or fatigue after exercise may be indicative of a dysfunction of the central anti-nociceptive mechanism in CFS patients.