Niemann-Pick disease type C symptomatology: an expert-based clinical description

Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. The estimated disease incidence is 1:120,000 live births, but this likely represents an underestimate, as the disease may be under-diagnosed due to its highly heterogeneous presentation. NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. The aim of this review is to provide non-specialists with an expert-based, detailed description of NP-C signs and symptoms, including how they present in patients and how they can be assessed. Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia). In young infants (<2 years), abnormal saccades may first manifest as slowing and shortening of upward saccades, long before gaze palsy onset. While visceral manifestations tend to predominate during the perinatal and infantile period (2 months–6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (>6 years of age). Psychosis in NP-C is atypical and variably responsive to treatment. Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca®), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.

Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 16 cases

OBJECTIVE: To describe the prevalence, main characteristics, and treatment of severe autoimmune cytopenias [autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenic purpura (AITP)] in patients with chronic hepatitis C virus (HCV) infection. METHODS: Retrospective chart review of patients with chronic HCV infection seen at our institution. Two additional departments contributed eight more patients to assess therapy of HCV-related autoimmune cytopenias. RESULTS: Eight patients (seven AITP, one AIHA) fulfilled the inclusion criteria in our population of 4345 HCV-infected patients. The number of patients with AITP was much greater than would be expected by chance (P<0.0001). Patients with HCV-related AITP were older and demonstrated more immunological markers than a group of 40 controls. Eight additional patients (six AITP, two Evans syndrome) were included. We only assessed the response for AITP patients because of the single case of AIHA. Patients with AITP had a poor response to initial corticosteroids [one complete response (CR), three partial response (PR), and four failures]. Intravenous immunoglobulins led to transient efficacy in three of four patients. In second-line therapy, five of seven patients responded to splenectomy. Rituximab proved effective in increasing platelets in two patients. Of eight patients treated with antiviral therapy (IFN-alpha+/-ribavirin), five responded (three CR, two PR). CONCLUSION: AITP occurs more commonly in patients with chronic HCV infection than would be expected by chance. HCV-positive AITP requires a treatment strategy different from that used in HCV-negative AITP. On the basis of the results from our study and a literature analysis, we propose an algorithm for treatment of severe HCV-related autoimmune cytopenias.

Paracoccidioidomycosis in the state of Maranhão, Brazil: geographical and clinical aspects

INTRODUCTION: The study aimed to show the situation of paracoccidioidomycosis in the state of Maranhão, Brazil. METHODS: This study is a descriptive case series developed in two stages. First, a survey of cases originating from the state of Maranhão at the Instituto de Doenças Tropicais Natan Portela, Piauí (IDTNP) from 1997 to 2007, and second, the clinical description of 29 cases diagnosed in the Centro de Referências em Doenças Infecciosas e Parasitárias, Maranhão (CREDIP) from 2004 to 2010. RESULTS: Two hundred and sixteen cases have been cataloged at the IDTNP. West, east, and central regions of the state of Maranhão recorded 90.3% of cases proving to be important areas for study. The western region, with a prevalence of 10.8/100,000 inhabitants, has a significantly higher proportion of cases than the northern, southern, and eastern regions (p < 0.05). The occurrence was higher in men with 89.3% of cases, and the male-to-female ratio was 8.4:1. The majority of patients were older than 20 years, lived in rural areas, and had farming or soil management as main occupation (73.8%). At CREDIP, 29 cases were diagnosed, of which 26 (89.6%) had multifocal manifestations. Mucous tissues were involved more (75.8%) frequently, followed by lymph nodes, skin, and lungs with 65.5%, 39% and 37.9 %, respectively. The diagnosis was made by combining direct examination, culture, and histopathology. CONCLUSIONS: The study shows the geographical distribution and the epidemiological and clinical aspects of paracoccidioidomycosis, revealing the significance of the disease to the state of Maranhão.

Trans-cultural aspects of social anxiety disorder and related conditions: a Brazilian case series and a review of international clinical studies

Cross-cultural studies have much to teach clinicians and researchers alike about psychopathology in general and about social anxiety disorder (SAD) in particular. Unfortunately, little is known about the degree and the mechanisms through which cultural environment may influence clinical manifestations of SAD. OBJECTIVE: Our objective was to identify culture-related clinical patterns in SAD and related disorders. METHODS: We described socio-demographic and clinical characteristics of a sample of 62 adult outpatients with SAD seen at a university clinic for anxiety and depressive disorders in Rio de Janeiro, Brazil, and compared them with those reported in clinical samples from North America, Europe, Asia and Oceania identified through a systematic review in Medline, PsychINFO, and LILACS. RESULTS: Our comparison of trans-cultural features of SAD lends partial support to Heimberg's (1997) contention that the majority of socio-demographic features and symptoms of this disorder are relatively independent of geographic and cultural differences. CONCLUSION: Patients with SAD were almost universally characterized by: 1) a predominance of males in clinical samples; 2) early onset of the disorder; 3) high educational attainment; and 4) great frequency of comorbidities.

Nondermatomal somatosensory deficits in patients with chronic pain disorder: clinical findings and hypometabolic pattern in FDG-PET

Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18-fluordeoxyglucose positron emission tomography=FDG-PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD-17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a "trigger episode of somatic pain" on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET.

Cruveilhier's legacy to skull base surgery: premise of an evidence-based neuropathology in the 19th century.

OBJECTIVES: Jean Cruveilhier has always been described as a pioneer in pathological anatomy. Almost nothing has been reported concerning his exceptional methodology allying pre-mortem clinical description and syndromic classification of neurological and neurosurgical diseases, and post-mortem meticulous dissections. Cruveilhier's methodology announced the birth of the anatomoclinical method built up by Jean-Martin Charcot and the neurological French school during the 19th century. The aim of our work is to extract the quintessence of Cruveilhier's contributions to skull base pathology through his cogent clinical descriptions coupled with exceptional lithographs of anterior skull base, suprasellar and cerebello-pontine angle tumors. METHODS: We reviewed the masterwork of Jean Cruveilhier on pathological anatomy and we selected the chapters dedicated to central nervous system pathologies, mainly skull base diseases. A systematic review was performed on Pubmed/Medline and Google Scholar using the keywords "Jean Cruveilhier", "Skull base pathology", "Anatomoclinical method". RESULTS: Among his descriptions, Cruveilhier dedicated large chapters to neurosurgical diseases including brain tumors, cerebrovascular pathologies, malformations of the central nervous system, hydrocephalus, brain infections and spinal cord compressions. CONCLUSION: This work emphasizes on the role of Jean Cruveilhier in the birth of the anatomoclinical method particularly in neuroscience during a 19th century rich of epistemological evolutions toward an evidence-based medicine, through the prism of Cruveilhier's contribution to skull base pathology.

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

Familial deletion 18p syndrome: case report

Affiliation: CHU Ste-Justine, Université de Montréal

Peripheral facial palsy in the past: contributions from Avicenna, Nicolaus Friedreich and Charles Bell

Este estudo apresenta documentos de paralisia facial periférica nas artes plásticas no Egito antigo, Grécia e Roma, Idade Média, Renascimento e também dos últimos 4 séculos. Pensamos que a história da paralisia facial periférica acompanha a história da própria espécie humana. São apresentadas as contribuições de Avicenna e Nicolaus Friedreich, e são mostradas controvérsias sobre a descrição original de Charles Bell.

Síndrome de Garcin relacionada a linfoma não-Hodgkin

The complete unilateral cranial nerve paralysis syndrome, or Garcin 's Syndrome, is a rare clinical condition. The purpose of this paper is to describe a case associated with non-Hodgkin s lymphoma. A 41-year-old male patient developed a progressive cranial nerve disorder. On the right hand side, there was impairment of all cranial nerves. We report the clinical and laboratorial findings. Lymph node exeresis revealed a Diffuse Non-Hodgkin s Lymphoma, with diffuse hone marrow infiltration. Cerebrospinal fluid showed pleocytosis, with 100% of immunoblasts. The CT scan showed no tumoral masses on the brain stem. This is the first clinical description of a complete Garcin 's Syndrome caused by diffuse lymphomatous infiltration of the cranial nerves.

DNA-based diagnosis of rare diseases in veterinary medicine: a 4.4 kb deletion of ITGB4 is associated with epidermolysis bullosa in Charolais cattle.

BACKGROUND Rare diseases in livestock animals are traditionally poorly diagnosed. Other than clinical description and pathological examination, the underlying causes have, for the most part, remained unknown. A single case of congenital skin fragility in cattle was observed, necropsy, histological and ultrastructural examinations were carried out and whole genome sequencing was utilized to identify the causative mutation. RESULTS A single purebred female Charolais calf with severe skin lesions was delivered full-term and died spontaneously after birth. The clinical and pathological findings exactly matched the gross description given by previous reports on epitheliogenesis imperfecta and epidermolysis bullosa (EB) in cattle. Histological and ultrastructural changes were consistent with EB junctionalis (EBJ). Genetic analysis revealed a previously unpublished ITGB4 loss-of-function mutation; the affected calf was homozygous for a 4.4 kb deletion involving exons 17 to 22, and the dam carried a single copy of the deletion indicating recessive inheritance. The homozygous mutant genotype did not occur in healthy controls of various breeds but some heterozygous carriers were found among Charolais cattle belonging to the affected herd. The mutant allele was absent in a representative sample of unrelated sires of the German Charolais population. CONCLUSION This is the first time in which a recessively inherited ITGB4 associated EBJ has been reported in cattle. The identification of heterozygous carriers is of importance in avoiding the transmission of this defect in future. Current DNA sequencing methods offer a powerful tool for understanding the genetic background of rare diseases in domestic animals having a reference genome sequence available.

Risco de queda em idosos institucionalizados

Os idosos institucionalizados apresentam risco de queda aumentado, quando comparado com os idosos não institucionalizados. A questão das quedas deve ser encarada como um grave problema de saúde pública, dadas as suas consequências e os custos irreversíveis. Assim, o estudo pretende avaliar o risco de queda em idosos institucionalizados e determinar os fatores que lhe estão associados. Trata-se de um estudo transversal descritivo-correlacional e de natureza quantitativa, que utilizou uma amostra não probabilística por conveniência composta por 136 idosos, com idades que variam entre os 65 anos e os 99 anos de idade, com uma média de idades de 85,98 anos. Os dados foram recolhidos através de um questionário, que procurava obter uma caracterização sociodemográfica, e clínica dos idosos e conhecer a história e circunstâncias das quedas. Foram utilizadas as escalas de Funcionalidade Familiar, Escala de Avaliação da Dependência nos Autocuidados e por último a POMA I (Índice de Tinetti). Os resultados revelam risco de queda bastante considerável, uma vez que se verificou que cerca de 45,6% dos idosos apresenta elevado risco de queda, 16,2% médio risco e 38,2% baixo risco. Verificamos ainda que, ser do sexo feminino e ter um baixo grau de escolaridade são fatores relacionados com o aumento do risco de queda. O mesmo apuramos relativamente ao défice cognitivo, á presença de doenças neurológicas, osteoarticulares, diminuição da acuidade visual e auditiva. Contrariamente, os idosos mais autónomos na deambulação, tomar banho e na toma da medicação são aqueles que apresentam menor risco de queda. Palavras-chave: idosos, risco de queda, institucionalização, capacidade funcional e equilíbrio.

Description of an injury in a human caused by a false tocandira (Dinoponera gigantea, Perty, 1833) with a revision on folkloric, pharmacological and clinical aspects of the giant ants of the genera Paraponera and Dinoponera (sub-family Ponerinae)

The authors observed an injury caused by the sting of a false tocandira ant in the hand of an amateur fisherman and they describe the clinical findings and the evolution of the envenoming, which presented an acute and violent pain, cold sweating, nausea, a vomiting episode, malaise, tachycardia and left axillary's lymphadenopathy. About three hours after the accident, still feeling intense pain in the place of the sting, he presented an episode of great amount of blood in the feces with no history of digestive, hematological or vascular problems. The intense pain decreased after eight hours, but the place stayed moderately painful for about 24 hours. In that moment, he presented small grade of local edema and erythema. The authors still present the folkloric, pharmacological and clinical aspects related to the tocandiras stings, a very interesting family of ants, which presents the largest and more venomous ants of the world.

Brazilian spotted fever: description of a fatal clinical case in the State of Rio de Janeiro

We describe a case of Brazilian spotted fever in a previously healthy young woman who died with petechial rash associated to acute renal and respiratory insufficiency 12 days following fever, headache, myalgia, and diarrhea. Serologic test in a serum sample, using an immunofluorescence assay, revealed reactive IgM/IgG.

HIV/AIDS-related visceral leishmaniasis: a clinical and epidemiological description of visceral leishmaniasis in northern Brazil

Introduction: This study aimed to describe the main features of visceral leishmaniasis (VL), both related to and independent of human immunodeficiency virus (HIV) infection, in patients who were registered in Tocantins, Brazil. Methods: Data from 1,779 new patients with VL, 33 of whom were also infected with HIV, were reviewed. Results: The incidence of VL/HIV coinfection increased from 0.32/100,000 inhabitants in 2007 to 1.08/100,000 inhabitants in 2010. VL occurred predominantly in children aged 10 years or younger, while VL/HIV was more common in patients aged between 18 and 50 years. There were more male patients in the VL/HIV group than in the VL group. Relapse rates were also considerably higher in the VL/HIV (9.1%) group than in the VL group (1.5%). Despite a similar clinical presentation, VL/HIV patients exhibited a higher proportion (24.2%) of concomitant infectious diseases and jaundice. Pentavalent antimonials were used for the initial treatment of VL and VL/HIV infections. However, amphotericin B deoxycholate and liposomal amphotericin B were also widely used in the treatment of VL/HIV coinfection. The mortality rate was higher in the VL/HIV coinfection group (19.4%) than in the VL group (5.4%). Furthermore, the mortality rate due to other causes was significantly higher in the VL/HIV group (12.9%) than in the VL group (0.7%). Conclusions: The study showed that the incidence, clinical characteristics and outcomes among the VL and VL/HIV patients in this state are similar to those from other endemic regions, indicating that both infections are emerging with increasing frequency in Brazil.