Inflammatory pathology markers (activated microglia and reactive astrocytes) in early and late onset Alzheimer disease: a post mortem study.

AIMS: The association between the pathological features of AD and dementia is stronger in younger old persons than in older old persons suggesting that additional factors are involved in the clinical expression of dementia in the oldest old. Cumulative data suggests that neuroinflammation plays a prominent role in Alzheimer's disease (AD) and different studies reported an age-associated dysregulation of the neuroimmune system. Consequently, we sought to characterize the pattern of microglial cell activation and astrogliosis in brain post mortem tissue of pathologically confirmed cases of early and late onset AD (EOAD and LOAD) and determine their relation to age. METHODS: Immunohistochemistry (CD68 and glial fibrillary acidic protein) with morphometric analysis of astroglial profiles in 36 cases of AD and 28 similarly aged controls. RESULTS: Both EOAD and LOAD groups had higher microglial scores in CA1, entorhinal and temporal cortices, and higher astroglial response in CA1, dentate gyrus, entorhinal and temporal cortices, compared to aged matched controls. Additionally, EOAD had higher microglial scores in subiculum, entorhinal and temporal subcortical white matter, and LOAD higher astrogliosis in CA2 region. CONCLUSIONS: Overall, we found that the neuroinflammatory pathological markers in late stage AD human tissue to have a similar pattern in both EOAD and LOAD, though the severity of the pathological markers in the younger group was higher. Understanding the age effect in AD will be important when testing modifying agents that act on the neuroinflammation.

Progressive proximal muscle weakness with subacute onset in an elderly patient: a case report. / Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso.

INTRODUCTION: Statins are some of the most widely prescribed medications. Although statins are generally well tolerated, they can lead to musculoskeletal side effects. Statin-induced necrotizing autoimmune myositis (SINAM) is a rare condition and the prevalence is only 1 per 100,000 people. This disorder is characterized by progressive and severe symmetric muscle weakness, marked elevation of creatine kinase and persistent symptoms despite statin discontinuation. Electromyography commonly shows a nonspecific irritable myopathy pattern indistinguishable from other inflammatory myopathies. Muscle biopsy shows the presence of necrotic fibers, regenerating fibers without significant inflammatory cells and diffuse or focal upregulation of major histocompatibility complex class I expression. The anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies represent a characteristic serological feature of SINAM. CASE REPORT: We present a patient who developed progressive muscle weakness after taking simvastatin for the last seven years. At initial presentation, her creatine kinase level was 2,954 U/L and anti-HMGCR antibodies were positive. The biopsy showed a profound myopathic features with numerous necrotic fibers, some regenerating fibers and perimysial inflammatory cell infiltrate, combined with a diffuse overexpression of major histocompatibility complex class I products. She was diagnosed with SINAM, statin was suspended and a high dose of systemic corticosteroids, intravenous immunoglobulin therapy and methotrexate was started. At three-month follow-up, she had significant improvement in muscle strength and creatine kinase level returned to normal. CONCLUSION: In this case, exclusion of inflammatory myopathies, metabolic muscle disorders and other neurological diseases is necessary for establishing a reliable diagnosis. In SINAM, simply discontinuing statin is often insufficient and aggressive immunosuppression or immunomodulation therapy is needed to achieve disease remission. This case aims to demonstrate that statins can induce serious muscular diseases that require aggressive immunosuppression.

TITLE: Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso.Introducción. Las estatinas son de los medicamentos más recetados. Aunque las estatinas generalmente se toleran bien, pueden provocar efectos secundarios musculoesqueléticos. La miopatía autoinmune necrotizante inducida por estatinas (SINAM) es una afección rara y la prevalencia sólo es de 1 de cada 100.000 personas. Este trastorno se caracteriza por debilidad muscular simétrica progresiva y grave, elevación marcada de la creatincinasa y síntomas persistentes a pesar de la interrupción de la estatina. La electromiografía suele mostrar un patrón de miopatía irritable inespecífico, indistinguible de otras miopatías inflamatorias. La biopsia muscular muestra la presencia de fibras necróticas, fibras en regeneración sin células inflamatorias significativas y una regulación positiva difusa o focal de la expresión del complejo mayor de histocompatibilidad de clase I. Los anticuerpos anti-3-hidroxi-3-metilglutaril-coenzima A (anti-HMG-CoA) reductasa representan un rasgo serológico característico de la SINAM. Caso clínico. Presentamos a un paciente que desarrolló debilidad muscular progresiva después de tomar simvastatina durante los últimos siete años. En la presentación inicial, su nivel de creatincinasa fue de 2.954 U/L y los anticuerpos anti-HMG-CoA reductasa fueron positivos. La biopsia mostró rasgos miopáticos profundos con numerosas fibras necróticas, algunas fibras en regeneración e infiltrado de células inflamatorias perimisial, combinado con una sobreexpresión difusa del complejo mayor de histocompatibilidad de clase I. Se le diagnosticó SINAM, se suspendió la estatina y se inició una dosis alta de corticoides sistémicos, inmunoglobulina intravenosa y metotrexato. Después de tres meses de seguimiento, tuvo una mejora significativa en la fuerza muscular y el nivel de creatincinasa volvió a la normalidad. Conclusiones. En este caso, la exclusión de miopatías inflamatorias, trastornos musculares metabólicos y otras enfermedades neurológicas es necesaria para establecer un diagnóstico fidedigno. En la SINAM, la simple suspensión de las estatinas a menudo es insuficiente, y es necesaria una terapia de inmunosupresión o inmunomodulación agresiva para lograr la remisión de la enfermedad. Este caso tiene como objetivo demostrar que las estatinas pueden inducir enfermedades musculares graves que requieren una inmunosupresión agresiva.

Primary antiphospholipid antibody syndrome presenting with encephalopathy, psychosis and seizures.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events, miscarriages and thrombocytopenia with persistently positive antiphospholipid antibodies.( 1,2 ) APS may be isolated (primary APS) or associated to a connective tissue disease, most often systemic lupus erythematosus (SLE).( 1,2 ) APS usually affects young patients before the fifth decade( 3 ) with stroke being the commonest neurological manifestation.( 4 ) Various other neurological manifestations are being recognized in patients with APS including migraine, epilepsy, multi-infarct dementia and chorea.( 2 ) The pathological process underlying the neurological manifestations remains obscure.( 1,2 ) Herein we report a case of primary APS presenting with a group of unusual neurological manifestations in a 68-year-old woman.

Recurrent Focal myositis: a rare inflammatory myopathy.

Focal myositis is an acute and localized muscle inflammation of unknown aetiology. The clinical diagnosis is often difficult to obtain, since it can be confused with infections, vascular thrombosis or muscle tumours such as sarcomas. This leads to a significant delay in the diagnosis, resulting in the administration of inappropriate and potentially harmful treatments.  We report here a case of recurrent focal myositis in a woman where the diagnosis was only obtained after 6 years, despite multiple hospital admissions. This case reinforces the importance of clinical knowledge and experience to tackle challenging medical scenarios.