Síndromes Paraneoplásicas Neurológicas

Algumas síndromes neurológicas estão ocasionalmente associadas ao cancro sistémico, na forma de síndrome paraneoplásica. Destas, a degenerescência cerebelosa subaguda, neuronopatia sensitiva, dermatomiosite polimiosite, síndrome miasténica de Eaton-Lambert e neuronopatia motora subaguda tornam obrigatória uma investigação exaustiva, no sentido de identificar o tumor primitivo, devido à sua forte correlação com neoplasia oculta.Os AA apresentam uma revisão sumária destas síndromes, ilustrando as três primeiras com casos clínicos. Faz-se referência aos aspectos imunológicos associados e à sua importância na caracterização destas entidades.

Do You Know This Syndrome?

POEMS syndrome is a unique clinical entity, the diagnosis of which is made when polyneuropathy and monoclonal gammopathy occur together, associated with other changes such as organomegaly, endocrinopathy, skin changes and papilledema. Cutaneous manifestations are heterogeneous, with diffuse cutaneous hyperpigmentation, hemangiomas and hypertrichosis occurring more frequently. We report the case of a 65- year-old female patient with this syndrome, diagnosed after 15 years of disabling peripheral neuropathy.

Epilepsy and Physical Exercise

Epilepsy is one of the commonest neurologic diseases and has always been associated with stigma. In the interest of safety, the activities of persons with epilepsy (PWE) are often restricted. In keeping with this, physical exercise has often been discouraged. The precise nature of a person’s seizures (or whether seizures were provoked or unprovoked) may not have been considered. Although there has been a change in attitude over the last few decades, the exact role of exercise in inducing seizures or aggravating epilepsy still remains a matter of discussion among experts in the field. Based mainly on retrospective, but also on prospective, population and animal-based research, the hypothesis that physical exercise is prejudicial has been slowly replaced by the realization that physical exercise might actually be beneficial for PWE. The benefits are related to improvement of physical and mental health parameters and social integration and reduction in markers of stress, epileptiform activity and the number of seizures. Nowadays, the general consensus is that there should be no restrictions to the practice of physical exercise in people with controlled epilepsy, except for scuba diving, skydiving and other sports at heights. Whilst broader restrictions apply for patients with uncontrolled epilepsy, individual risk assessments taking into account the seizure types, frequency, patterns or triggers may allow PWE to enjoy a wide range of physical activities.

Neuropsychiatric Features of a Cohort of Patients with Systemic Lupus Erythematosus

In order to establish if neuropsychiatric systemic lupus erythematosus (NPSLE) can be identified by any characteristic other than those used to diagnose the neuropsychiatric (NP) disease itself, we retrospectively reviewed 98 systemic lupus erythematosus (SLE) patients followed over a mean period of 10 years. NPSLE was identified in 22 patients. Stroke and generalized seizures were the most frequent NP manifestations. The NPSLE and non-NPSLE groups were similar with regard to demographic characteristics, ACR criteria, serum autoantibodies, and frequency of hypertension and hypercholesterolemia. Of note, compared to the non-NPSLE group, NPSLE was associated with a higher frequency of smoking (78 versus 26%), organ damage (73 versus 34%), and cumulative mortality rate (14 versus 7%). The series of patients was further analysed according to the presence of antiphospholipid syndrome (APS). Significantly, the interval between the onset of NP disease and SLE diagnosis was shorter in the APS(-) (0.3 ± 1 years) than in the APS(+) (5 ± 7 years) groups. Recurrence and/or persistence of NP events were only documented in the APS(-) group. Overall cumulative mortality was highest in NPSLE and in APS(+) patients with inadequate anticoagulation control, identifying an aspect that requires improved vigilance and the development of novel therapeutic modalities.

A Ponta do Iceberg: Manifestações Cutâneas de Patologia Pediátrica com Envolvimento Neurológico

Introdução: Algumas alterações cutâneas podem ser as primeiras manifestações clínicas de diversas entidades nosológicas com atingimento sistémico. O presente trabalho tem como objectivo rever a semiologia dermatológica relevante no contexto das doenças com envolvimento neurológico na infância. Material e Métodos: Revisão dos artigos indexados à MedLine publicados nos últimos 12 anos e com relevância para o tema. Resultados: Os principais grupos nosológicos relevantes para o tema compreendem as genodermatoses (com destaque para as síndromes neurocutâneas), as alterações da pigmentação, as doenças vasculares, as endócrinas, os défices enzimáticos congénitos e os disrafismos espinhais ocultos. Discussão: O reconhecimento da semiologia cutânea específica é importante pois pode permitir um diagnóstico muito mais precoce.

Juvenile Systemic Lupus Erythematosus in Portugal: Clinical and Immunological Patterns of Disease Expression in a Cohort of 56 Patients

Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic, clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent. Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic,clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent.

Drug-Induced Anaphylaxis Survey in Portuguese Allergy Departments

Background and Objective: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. Methods: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. Results: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1. The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. Conclusions: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis.

Hepatic Actinomycosis

Actinomycosis is a rare disorder caused by an anaerobic gram-positive bacillus (Actinomyces), predominantly by the Actinomyces israelii species. Only 20% of cases show an abdominal manifestation, the appendix and ileocecal valve being the most frequent locations. Definitive diagnosis is based on microbiological cultures, microscopy or macroscopy examination. Nevertheless, histological examination of the percutaneous biopsy and blood microbiological cultures are rarely positives. Preoperative diagnosis is hampered by the lack of specific clinical and imaging manifestations, which often mimic malignancy. The rate of preoperative diagnosis is less than 10%, however, the outcome is excellent, with a low mortality rate. The authors describe the case of a patient who was diagnosed with primary hepatic actinomycosis only by a histological examination of the surgical specimen of left hepatectomy extended to segments V and VIII, for suspected malignant lesion. This case demonstrates the difficulties in diagnosing hepatic actinomycosis.

A Nonhealing Ulcer on the Nose. A Case Report

Dermatitis artefacta is a disease characterized by self-inflicted skin lesions as the result or manifestation of psychiatric disorders or specific stress situations. Clinical manifestations range from superficial erosions to deep wounds. Because of its rarity and the polymorphism of the lesions, dermatitis artefacta is often a challenge for the clinicians. This report presents the case of a 62-year-old woman who had an ulcer of the nose lasting for three years caused by digital manipulation. Early recognition of dermatitis artefacta is difficult but avoids unnecessary treatments. A multidisciplinary approach to this entity is necessary to obtain the best results.

The BOLD Effect of Interictal Spike Activity in Childhood Occipital Lobe Epilepsy

Occipital lobe epilepsy (OLE) presents in childhood with different manifestations, age of onset and EEG features that form distinct syndromes. The ictal clinical symptoms are difficult to correlate with onset in particular areas in the occipital lobes, and the EEG recordings have not been able to overcome this limitation. The mapping of epileptogenic cortical regions in OLE remains therefore an important goal in our understanding of these syndromes.

Aortic and Tricuspid Endocarditis in Hemodialysis Patient with Systemic and Pulmonary Embolism

This is a case report of a 43-year-old Caucasian male with end-stage renal disease being treated with hemodialysis and infective endocarditis in the aortic and tricuspid valves. The clinical presentation was dominated by neurologic impairment with cerebral embolism and hemorrhagic components. A thoracoabdominal computerized tomography scan revealed septic pulmonary embolus. The patient underwent empirical antibiotherapy with ceftriaxone, gentamicin and vancomycin, and the therapy was changed to flucloxacilin and gentamicin after the isolation of S. aureus in blood cultures. The multidisciplinary team determined that the patient should undergo valve replacement after the stabilization of the intracranial hemorrhage; however, on the 8th day of hospitalization, the patient entered cardiac arrest due to a massive septic pulmonary embolism and died. Despite the risk of aggravation of the hemorrhagic cerebral lesion, early surgical intervention should be considered in high-risk patients.

Autism Spectrum Disorder Secondary to Enterovirus Encephalitis

Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder.

Pancreatic Involvement by Plasma Cell Neoplasms

INTRODUCTION: Pancreatic involvement by plasma cell neoplasms is an extremely rare event, with only 50 cases described in the literature. They can present as a primary solitary extramedullary plasmacytoma or plasmacytoma secondary to a plasma cell myeloma. Clinical manifestations are due to the presence of a pancreatic mass usually in the pancreas head, which causes extra-biliary obstruction and abdominal pain. METHODS: Abdominal imaging including CT scan or endoscopic ultrasound with fine-needle aspiration tissue sampling is essential for the initial diagnostic procedure. However, immunohistochemical analysis of the biopsy specimen or flow cytometry of the aspirated material is crucial to prove the monoclonality and the final diagnosis of a plasma cell neoplasm. DISCUSSION: Management of these situations include radiotherapy, chemotherapy, surgery or combined therapy. Novel medications including the immunomodulatory drugs or the proteasome inhibitors followed by consolidation with intensive chemotherapy and haematopoietic stem cell transplantation are nowadays used as upfront treatment in the cases associated to a plasma cell myeloma. CONCLUSION: Despite the rarity, plasma cell neoplasms should be considered in the differential diagnosis of obstructive jaundice and pancreatic neoplasms since they are potentially treatable situations.

Dynamics of Epileptic Activity in a Peculiar Case of Childhood Absence Epilepsy and Correlation with Thalamic Levels of GABA

Childhood absence epilepsy (CAE) is a syndrome with well-defined electroclinical features but unknown pathological basis. An increased thalamic tonic GABA inhibition has recently been discovered on animal models (Cope et al., 2009), but its relevance for human CAE is unproven. METHODS: We studied an 11-year-old boy, presenting the typical clinical features of CAE, but spike-wave discharges (SWD) restricted to one hemisphere. RESULTS: High-resolution EEG failed to demonstrate independent contralateral hemisphere epileptic activity. Consistently, simultaneous EEG-fMRI revealed the typical thalamic BOLD activation, associated with caudate and default mode network deactivation, but restricted to the hemisphere with SWD. Cortical BOLD activations were localized on the ipsilateral pars transverse. Magnetic resonance spectroscopy, using MEGA-PRESS, showed that the GABA/creatine ratio was 2.6 times higher in the hemisphere with SWD than in the unaffected one, reflecting a higher GABA concentration. Similar comparisons for the patient's occipital cortex and thalamus of a healthy volunteer yielded asymmetries below 25%. SIGNIFICANCE: In a clinical case of CAE with EEG and fMRI-BOLD manifestations restricted to one hemisphere, we found an associated increase in thalamic GABA concentration consistent with a role for this abnormality in human CAE.