Parkinson's disease updates: Addressing the pathophysiology, risk factors, genetics, diagnosis, along with the medical and surgical treatment.

After only Alzheimer's disease (AD), Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. The incidence of this disease increases with age, especially for those above 70 years old. There are many risk factors that are well-established in the contribution to the development of PD, such as age, gender, ethnicity, rapid eye movement sleep disorder, high consumption of dairy products, traumatic brain injury, genetics, and pesticides/herbicides. Interestingly, smoking, consumption of caffeine, and physical activities are the protective factors of PD. A deficiency of dopamine in the substantia nigra of the brainstem is the main pathology. This, subsequently, alters the neurotransmitter, causing an imbalance between excitatory and inhibitory signals. In addition, genetics is also involved in the pathogenesis of the disease. As a result, patients exhibit characteristic motor symptoms such as tremors, stiffness, bradykinesia, and postural instability, along with non-motor symptoms, including dementia, urinary incontinence, sleeping disturbances, and orthostatic hypotension. PD may resemble other diseases; therefore, it is important to pay attention to the diagnosis criteria. Parkinson's disease dementia can share common features with AD; this can include behavioral as well as psychiatric symptoms, in addition to the pathology being protein aggregate accumulation in the brain. For PD management, the administration of pharmacological treatment depends on the motor symptoms experienced by the patients. Non-pharmacological treatment plays a role as adjuvant therapy, while surgical management is indicated in chronic cases. This paper aims to review the etiology, risk factors, protective factors, pathophysiology, signs and symptoms, associated conditions, and management of PD.

Neurological, Extracardiac, and Cardiac Manifestations of Ebstein's Anomaly Along With its Genetics, Diagnostic Techniques, Treatment Updates, and the Future Ahead.

Ebstein's anomaly is a congenital heart defect characterized by the displacement of the tricuspid valve, and its leaflets to be malformed. Due to the defect involving the tricuspid valve, there is a reverse flow of blood into the right-sided atrium, which may lead to cardiac hypertrophy and edema of the lower extremities. There is a decreased flow of blood out of the right heart due to reduced right ventricular contractility and tricuspid regurgitation. Children afflicted with this anomaly usually suffer from atrial septal defect and this is usually diagnosed before birth on a routine ultrasound scan. In neonates, cyanosis can be seen due to right-to-left atrial shunting or as a result of severe congestive heart failure. If the infant has pulmonary hypertension, cyanosis is markedly increased as there will be a limitation in pulmonary blood flow. In adults, arrhythmias, cyanosis, and heart failure are seen. The bundle of Kent leads to the formation of an electrical conduction abnormality between the right ventricle and atrium. This leads to a condition commonly known as Wolff- Parkinson-White syndrome in patients. An enlarged spherical heart is usually present on a chest X-ray. ECG changes of Ebstein's anomaly show taller than usual P waves, PR prolongation, and right bundle branch block. There can be certain neurological and extracardiac manifestations too such as hemiplegia, stroke, dysarthria, etc. During fetal life, specifically at 16 and 20 weeks of gestation, the anomaly can be diagnosed via echocardiography. Prostaglandin infusion (PGE1) is given to maintain pulmonary circulation in neonates if cyanosis is seen. In children and adults with congestive cardiac failure due to this anomaly, medical management includes digoxin, beta-blockers, diuretics, and angiotensin converting enzyme (ACE) inhibitors to improve heart failure. Surgical treatment includes valve reconstruction. In this article, we review the pathophysiology, genetics, diagnosis, management, and prognosis of Ebstein's Anomaly along with a comprehensive discussion on its genetics, neurological manifestations, extracardiac features, and current advancements in treatment.

Clinically Suspected Acute Myocarditis in the First Trimester of Twin Gestation: A Case Report.

Acute myocarditis (AM) in early pregnancy is a rare disease. Its clinical presentation varies from asymptomatic disease to cardiogenic shock and death. A 28-year-old woman, 12 weeks primigravida of a dichorionic and diamniotic pregnancy, was admitted for hyperemesis gravidarum, associated with a common cold-like condition. During hospitalization, she developed new-onset sinus tachycardia and dyspnea. An electrocardiogram revealed sinus tachycardia and diffuse ST-segment elevation. Laboratory tests showed elevated levels of troponin and pro-B-type natriuretic peptide. Pelvic obstetric ultrasound and chest X-ray were normal. Speckle-tracking echocardiography showed mild apical hypokinesia with preserved left ventricular ejection fraction. In view of these findings, AM was suspected, and cardiac magnetic resonance imaging was highly suggestive of AM. The patient had a favorable recovery without cardiovascular or obstetric complications.

Vertebromedullary Topography of the Red-Rumped Agouti (Dasyprocta leporina Linnaeus, 1758).

The agouti is a wild rodent located almost throughout the Brazilian territory, with great scientific importance and high reproductive potential when farmed. In the clinical routine, clinical and surgical procedures are performed on the nervous system of these animals, such as epidural anesthesia and cerebrospinal fluid (CSF) collection; however, data available are limited in literature on the main points of these procedures in this species. In this aspect, the objective was to describe the vertebromedullary topography of the agouti in order to identify and quantify it, with the intention of expanding the information regarding the clinical-surgical procedures in this system. Ten animals were incised longitudinally in the dorsal median line, removing the skin, the musculature, and dorsal fascia of the vertebral column; then, removed the vertebral arches and consequent exposure of the spinal cord and meninges. The morphometry of the animals was done by obtaining the total length, body length, and crown-rump length, as well as the total length of the spinal cord and its segments. The cervical intumescence in the agouti is located between C4-T1 and measures 2.45 cm. The lumbar intumescence is between L5-L7 and is 2.52 cm long. The cauda equina arises from S2 and the filum terminale from S3. As for the medullary cone, it is located between L7-S1 and is 2.52 cm long. The suggested localization for epidural anesthesia or CSF puncture for laboratory tests in agoutis is the lumbosacral space, with the insertion of the needle to be carried out at angle of 90° in the sphinx position. Anat Rec, 303:1472-1477, 2020. © 2019 American Association for Anatomy.

Morfologia da bolsa cloacal de emas, Rhea americana americana Linnaeus, 1758 / Morphology of rhea's cloacal bursa, Rhea americana americana Linnaeus, 1758

A bolsa cloacal é o órgão das aves responsável pela maturação e transferência de linfócitos para outros tecidos. Apesar da importância deste órgão nos mecanismos imunológicos desses animais, são escassas as informações a respeito de sua morfologia em emas. Neste estudo, objetivou-se descrever o desenvolvimento morfológico da bolsa cloacal de emas jovens. Utilizou-se 12 animais de ambos os sexos (6 machos e 6 fêmeas) para a microscopia de luz, eletrônica de transmissão e varredura. Microscopicamente, a bolsa cloacal da ema apresentou, em todas as idades a mucosa interna pregueada composta por lóbulos linfoides de diversos tamanhos, organizados como estrutura alveolar. Em cada prega verificou-se quatro componentes histológicos: as camadas mucosa, submucosa, muscular e adventícia. Esses lóbulos eram compostos de uma zona cortical, uma zona corticomedular e uma zona medular. Verificou-se a existência de linfócitos de tamanhos variados, linfoblastos, capilares sanguíneos, células reticulares epiteliais e macrófagos. Pela microscopia eletrônica de varredura, verificou-se que a superfície da mucosa dos lóbulos bursais apresentaram projeções poligonais, com a presença de curtas microvilosidades em toda a superfície. A comparação nas idades de 0 e 15 semanas de vida demostrou o desenvolvimento dos lóbulos bursais. O padrão morfológico da bolsa cloacal de emas difere do padrão comumente reportado para outras aves tais como pato selvagem, galinha da angola, ganso nativo, peru, codorna japonesa e falcão.(AU)

The cloacal bursa is the bird's organ responsible for maturation and transfer of lymphocytes to other tissues. Despite the importance of this organ in the immunological mechanisms of these animals, information about their morphology in rhea are scarce. We used 12 animals (6 males and 6 females) for light, transmission electron, and scanning microscopy. Microscopically, the cloacal bursa presented the inner mucosa consists of pleated lymphoid lobes of various sizes, organized as alveolar structure, in all ages. In each nail was found four histological components: mucosa, submucosa, muscular and adventitia layers. These lobes were composed of a cortical zone, a corticomedular zone and a medular area. It was verified the existence of varying sizes lymphocytes, lymphoblasts, blood capillaries, epithelial reticular cells and macrophages. By scanning electron microscopy, it was found that the mucous membrane surface of the bursal lobes showed polygonal projections, with the presence of short microvilli membranes throughout the surface. The comparison between 0 and 15 weeks demonstrated the development of the bursal lobes. The morphological pattern of the rhea cloacal bursa differs from standard commonly reported for other birds such as wild duck, Angola's chicken, native goose, turkey, Japanese quail, and Hawk.(AU)

Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial.

AIM: This study aimed to gain a better understanding of the psychological impact of participating in a clinical trial for patients with Pompe disease (Acid Maltase Deficiency). Attitudes and expectations of adult patients with neuromuscular diseases regarding medical trials are as yet unreported. In order to learn about the psychological consequences of participating in a clinical trial, we conducted a prospective assessment of patients with late-onset Pompe Disease, a rare genetic condition, for which no treatment had been available before. This psychological study was carried out as an ancillary study to the randomized double-blind placebo-controlled trial described elsewhere (van der Ploeg et al., 2010). SUBJECTS AND METHODS: We assessed patients (n=8) at inclusion, and at 12 and 18 months for six psychological dimensions: depression (Beck Depression Inventory, BDI), hopelessness (Beck Hopelessness Scale, BHS), anxiety (STAI A-B), quality of life (Whoqol-26), social adjustment (S.A.S-self-report) and locus of control (IPC Levenson). We produced a self-administered questionnaire in order to assess the attitudes, motivations and expectations of patients during the trial. RESULTS: At 12 months, mean social adjustment (SAS-SR, P=0.02) had improved, and at 18 months mean depression score had improved as well (BDI, P=0.03). The quality of life of patients (Whoqol-26) remained unchanged. Throughout the study, patients were more likely to have an internal locus of control than an external one (IPC Levenson). The self-administered questionnaire showed that patients' expectations were disproportionate compared to the medical information they had received starting the trial. For all patients, the first motivation for being enrolled in a clinical trial was "to help research", for half of them the motivation was to "improve their health". Whether patients believed to be part of one group or another (placebo or treatment) depended on their subjective perception of improvement during the trial. CONCLUSION: Given the small sample size, the conclusions of this study are preliminary. However, findings do suggest that there is a positive psychological impact of participating in a treatment trial. Moreover, the patients' reactions upon unblinding have led us to recommend that patients be asked whether they would like their group assignation disclosed to them or not.

Diagnostic value of markers of muscle degeneration in sporadic inclusion body myositis.

Sporadic inclusion body myositis (s-IBM) is characterized histologically by the association of concomitant inflammatory and degenerative processes. We evaluated the sensitivity and specificity of different markers of the degenerative process in order to refine the histological diagnosis. We performed an immunohistochemical study with antibodies directed against ubiquitin, amyloid-beta precursor protein (AbetaPP), amyloid-beta (Abeta), SMI-31, SMI-310, Tar-DNA binding protein-43 (TDP-43) and p62 on s-IBM and control muscle biopsies. Based on conventional stains 36 patients with characteristic clinical features of s-IBM were subclassified as presumed definite s-IBM (d s-IBM, n = 17) or possible s-IBM (p s-IBM, n = 19) according to the presence or absence of vacuolated muscle fibers. Immunohistochemically, TDP-43 and p62 were the most sensitive markers, accumulating in all d s-IBM and in 31% and 37%, respectively, of the p s-IBM cases and thus enabling reclassification of these cases as d s-IBM. We recommend using TDP-43 and p62 antibodies in the histological diagnosis workup of s-IBM. The specificity of these markers has to be further validated in prospective series.

[New classifications and pathophysiology of the inflammatory myopathies]. / Nouvelles classifications et physiopathologie des myopathies inflammatoires.

SCOPE: Review on new classifications of myositis linked with their different pathophysiology. CURRENT SITUATION AND SALIENT POINTS: The classification of myositis refined recently, taking into account clinical (such as isolated muscle involvement or not, association with cancer...), immunological (presence or absence of auto-antibodies) and pathological criteria. This new classification has the ability to separate different clinical and physiopathological entities, having actually different prognosis factors. The most common inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), but also, overlap myositis (defined, among others, by the presence of auto-antibodies), and myositis associated to cancers. These myopathies may be also distinguished by their histological features which also reflect their different underlying pathogeneses. The mechanism of DM is complement-mediated microangiopathy, the inflammatory infiltrate being secondary to ischaemic damage. In PM the muscle fibres are damaged by cytotoxic CD8 T lymphocytes. IBM may be a degenerative disease with accumulation of a variety of proteins within the fibres. The inflammatory infiltrate, which is similar to that seen in PM, may be secondary to accumulated proteins. PERSPECTIVES: These diseases with different pathogeny and prognosis should be treated by specific approaches. That is the reason why we initiated specific clinical trials for respectively inclusion body myositis and overlap myositis.

[Myopericarditis during Horton disease]. / Atteinte myopéricardique au cours de la maladie de Horton.

INTRODUCTION: Myopericarditis is an rare form of Horton disease. We report two new cases. METHOD: Two patients, more than 60-years-old, had developed global cardiac insufficiency with predominant left insufficiency, with physical alteration and biological inflammation. Echocardiography revealed a myopericarditis. Bacteriological explorations were all negative. In the two cases, temporal artery biopsy revealed giant cell arteritis. Treatment with oral corticosteroids improved biological and clinical symptoms. CONCLUSION: Myopericarditis is a rare form of Horton disease. Classical clinical presentation is rarely associated. Temporal artery biopsy is essential in confirming and proposing a specific therapy, in order to prevent cardiovascular ischemic complications.

[Myopathy-lipomatosis associated with A8344G mitochondrial DNA mutation]. / Myopathie-lipomatose par mutation A8344G de l'ADN mitochondrial.

We report the clinical features of two unrelated patients, a 51-year-old woman and a 54-year-old man, presenting proximal myopathy with lipomatosis. In both patients, muscle biopsies showed numerous ragged-red fibers. Molecular analysis were performed with denaturating gradient gel electrophoresis (DGGE) on muscle, blood, hair, buccal and urinary cells. The A8344G mutation of the tRNA-lysine gene of the mitochondrial DNA was detected in all tissues at high levels (more than 80 p cent). None of the patients had a contributive family history, and signs of central nervous system involvement were absent. These observations confirm that lipomatosis may be encountered in mitochondrial disorders and is tightly associated with the A8344G mutation.

Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients.

OBJECTIVE: Polymyositis is a rare inflammatory muscular disease of unknown cause. Corticosteroids and immunosuppressive drugs are the first choice of therapy but are not always effective and may cause serious side effects. Many studies have shown that polyvalent intravenous immunoglobulin (IVIG) may be of interest for the treatment of dermatomyositis. We carried out an open, prospective study to evaluate the efficacy of IVIG in subjects with polymyositis that was refractory to traditional treatments, and we evaluated the benefits of this therapy over a long-term period of followup. METHODS: Thirty-five adult white patients (20 female, 15 male, mean age 43.5 years [SD 16.8]) with chronic, refractory polymyositis were treated with high doses of IVIG, after the patients had received the following traditional treatments: prednisone (n = 35), methotrexate (n = 24), azathioprine (n = 13), cyclophosphamide (n = 4), cyclosporine (n = 7), chlorambucil (n = 1), plasmapheresis (n = 8), lymphopheresis (n = 1), and total body irradiation (n = 1). There had been no changes in the patients' treatment in the 2 months before the initiation of IVIG therapy, and doses were not increased during IVIG treatment. We used preparations of polyvalent human IVIG with increased concentrations of intact IgG. The patients received 1 gm/kg/day for 2 consecutive days per month. The mean course of treatment was 4-6 months. The clinical assessment involved the evaluation of proximal muscle power, muscle disability scale score, and esophageal disorders. The biochemical evaluations carried out before each treatment period were compared by Student's t-test and nonparametric Wilcoxon test. Results were considered to be significant at P = 0.05. RESULTS: In the short-term, significant clinical improvement was noted in 25 of the 35 patients (71.4%). Mean muscle power was estimated before and after IVIG therapy and was found to be significantly improved (P < 0.01). All patients had a significant biochemical response. Mean creatine kinase levels during IVIG therapy decreased significantly before the fourth IVIG perfusion (P < 0.01). Side effects, usually minor, were noted in 6 patients. This benefit allowed the initial prednisone dose to be reduced by >50% in all patients. The mean (+/- SD) followup time for the 25 patients who responded favorably to IVIG treatment was 51.4 +/- 13.1 months. Twelve of these 25 patients remained in full remission following their initial course of IVIG, resulting in complete stoppage of medication in 5 patients or low doses of steroids in 7 patients. The condition of 6 patients remained improved and no other drugs were prescribed, but the patients remained dependent on IVIG infusions. Seven of the 25 patients who responded well to IVIG treatment relapsed at an average of 17.1 months (range 4-23 months) after the discontinuation of IVIG. CONCLUSION: IVIG is an interesting therapy for the treatment of polymyositis, with results showing that the condition of approximately 70% of the patients tested improved. After the discontinuation of the IVIG therapy, the efficacy remained stable in 50% of the patients, with a followup of over 3 years.

Interstitial lung disease in polymyositis and dermatomyositis.

OBJECTIVES: To assess prevalence, characteristics, and long-term outcome of interstitial lung disease (ILD) in polymyositis (PM) and dermatomyositis (DM). To determine predictive variables of ILD course in PM/DM, and to define both clinical and biochemical features associated with ILD onset in PM/DM. METHODS: The medical records of 156 consecutive PM/DM patients in 3 medical centers were reviewed. RESULTS: Thirty-six PM/DM patients (23.1%) developed ILD. We observed that 19.4% of patients with ILD had resolution of pulmonary disorders, whereas 25% experienced ILD deterioration. Morbidity and mortality rates were as high as 13.9% and 36.4%, respectively, in PM/DM patients with ILD. Parameters of PM/DM that related to ILD poor outcome were identified as follows: Hamman-Rich-like pattern, initial diffusing capacity of carbon monoxide <45%, neutrophil alveolitis, and histologic usual interstitial pneumonia. Additionally, for the group with ILD, polyarthritis, higher values of erythrocyte sedimentation rate and C-reactive protein, presence of anti-Jo-1 antibody, and characteristic microangiopathy were significantly more frequent. CONCLUSION: Our series underlines the high frequency of ILD in PM/DM patients, resulting in increased morbidity and mortality rates. It also indicates that PM/DM patients should routinely be screened for ILD, even those patients without anti-Jo-1 antibody, because 69% of our ILD patients were seronegative for the anti-Jo-1 antibody. Our findings further suggest that PM/DM patients presenting with factors predictive of ILD poor outcome may require more aggressive therapy.

Severe perturbations of the blood T cell repertoire in polymyositis, but not dermatomyositis patients.

Polymyositis and dermatomyositis are diseases characterized by muscle weakness and muscle inflammatory infiltrates. Their pathogenesis remains unclear. A central role for endomysial autoaggressive CD8(+) T cells is suspected in polymyositis and for perivascular B cells in dermatomyositis. We compared the T cell repertoire of 10 polymyositis and 10 dermatomyositis patients by immunoscope, a method providing a global assessment of the T cell repertoire and a sensitive detection of clonal T cell expansions. Samples were analyzed qualitatively and quantitatively in the blood (unsorted cells and CD4(+) and CD8(+) cells) and in muscle infiltrates. Dramatic perturbations of the T cell repertoire were observed in the blood of polymyositis but not dermatomyositis patients (p < 0.0005), the latter being undistinguishable from controls. These perturbations were due to oligoclonal expansions of CD8(+) T cells and most blood clonal expansions were also found in muscle. These results indicate that the pathogenesis of polymyositis and dermatomyositis is different and reinforce the view that polymyositis but not dermatomyositis is an autoimmune CD8(+) T cell-mediated disease. Moreover, this method may be helpful for the differential diagnosis of polymyositis and dermatomyositis and for noninvasive follow-up of polymyositis patients.

Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring during highly active antiretroviral therapy: four cases and a review of the literature.

Fourteen cases of gynecomastia occurring during highly active antiretroviral therapy (HAART) have been reported in the literature. To date, no specific therapeutic approach has been proposed, and gynecomastia has usually persisted. We report 4 new cases of HAART-induced gynecomastia that were successfully treated with percutaneous dihydrotestosterone gel.

Macrophagic myofasciitis associated with inclusion body myositis: a report of three cases.

We describe three patients with macrophagic myofasciitis and inclusion body myositis. All patients fulfilled diagnostic criteria for inclusion body myositis and myopathologic criteria for macrophagic myofasciitis. In the three cases macrophagic myofasciitis complicated the evolution of a known and painless inclusion body myositis and was diagnosed in a repeated deltoid biopsy because of the appearance of myalgia during the course of inclusion body myositis in all cases. The unexpected appearance of myalgia during the course of painless inclusion body myositis must arouse the suspicion of an association of another inflammatory muscle disease, macrophagic myofasciitis.