Shifting the CARASIL paradigm: report of a non-Asian family and literature review.

BACKGROUND AND PURPOSE: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare form of nonhypertensive cerebral small-vessel disease caused by mutations in the HTRA1 gene. CARASIL is characterized by early adulthood onset of subcortical infarcts, cognitive impairment, alopecia, and spondylosis. Until recently, this disorder was almost exclusively reported in the Asian population. METHODS: Description of the clinical, imaging, and genetic study of 2 siblings with CARASIL, with a brief comparative review of published non-Asian cases of the disease. RESULTS: Both patients exhibited the typical phenotype: cerebral small-vessel disease, spondylosis, and abnormal hair lost. Mutation screening was performed for NOTCH3 and HTRA1 genes. No mutations were found in NOTCH3. The study revealed the presence of a homozygous c.496C>T substitution in HTRA1 in both siblings. CONCLUSION: This report highlights the need of considering this entity in the differential diagnosis of cerebral small-vessel disease in young patients, even in the non-Asian populations.

Valproic acid-induced hyperammonaemic coma and unrecognised portosystemic shunt.

Hyperammonaemic encephalopathy is a rare and potentially fatal complication of valproic acid treatment. The clinical presentation of hyperammonaemic encephalopathy is wide and includes seizures and coma. We present a case of hyperammonaemic coma precipitated by sodium valproate use for symptomatic epilepsy in a patient with unrecognised portosystemic shunt, secondary to earlier alcoholism. The absence of any stigmata of chronic liver disease and laboratory markers of liver dysfunction delayed the recognition of this alcohol-related complication. The portal vein bypass led to a refractory, valproic acid-induced hyperammonaemic coma. The patient fully recovered after dialysis treatment.

Consensus for the Early Identification of Secondary Progressive Multiple Sclerosis in Portugal: a Delphi Panel.

INTRODUCTION: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. MATERIAL AND METHODS: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. RESULTS: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. CONCLUSION: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.

Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Parada cardiorrespiratória após infarto agudo do miocárdio por vasoespasmo coronariano. Relato de caso e revisão da literatura / Cardiorespiratory arrest after acute myocardial infarction due to coronary vasospasm. Case report and literature review

A angina vasoespástica é uma causa incomum de parada cardíaca e arritmias ventriculares. No entanto, os sobreviventes dessas complicações têm um risco aumentado de recorrência, apesar da função ventricular normal e do tratamento médico otimizado. Descrevemos o caso de uma ex-tabagista de 50 anos que teve parada cardiorrespiratória secundária a vasoespasmo coronariano grave.

Vasospastic angina is an uncommon cause of cardiac arrest and ventricular arrhythmias. However, survivors of these complications are at an increased risk of recurrence, despite normal ventricular function and optimized medical therapy. We describe a case of a 50-year-old former smoker who developed cardiorespiratory arrest secondary to severe coronary vasospasm.

Neuroendocrine tumour metastatic brain disease during immunosuppressive treatment for paraneoplastic GABAB receptor antibodies encephalitis: Is immunosuppression always beneficial?

BACKGROUND: Limbic autoimmune encephalitis (LE) should be considered in any patient with acute or subacute neuropsychiatric manifestations, without other common causes of encephalitis. Y-Aminobutyric-acid-B-receptor (anti-GABABR) antibodies are rarely encountered in association with LE. CASE REPORT: A 74-year-old patient presented with a progressive cognitive degradation and generalized tonic-clonic seizures, with positive anti-GABABR. He declined under immunosuppression treatment. Control magnetic resonance revealed brain lesions, which became positive for pulmonary neuroendocrine tumour metastatic disease. CONCLUSION: The occurrence of diversified neurological manifestations of an underling tumour is difficult to manage. We speculate if in some cases, immunosuppression can itself facilitate tumour progression.

Clinicoepidemiological profile of cerebral venous thrombosis in Algarve, Portugal: A retrospective observational study.

BACKGROUND: Cerebral venous thrombosis (CVT) is a very uncommon disorder with a wide variety of clinical manifestations. There are few studies describing the clinical and epidemiological profile of CVT in peripheral or rural areas. Over the last decades, the frequency in which this disease is diagnosed has increased due to greater awareness and availability of noninvasive diagnostic techniques. MATERIALS AND METHODS: A hospital-based retrospective case review of adult (≥15 years) patients with CVT between 2001 and 2012 is described. 31 patients with confirmed imagiological diagnosis of CVT were included. STATISTICAL ANALYSIS USED: Statistical analysis was performed using R version 2.15.2. Incidence rate was computed as number of new cases by time. Confidence interval (CI) was set at 95% and P < 0.05 was considered significant. RESULTS: The average annual incidence was 0.84 (CI: 0.58-1.18) to 0.73 (CI: 0.5-1.02) per 100 000 cases for adult population. There were 23 (74%) women and 8 (26%) men. Predominant initial manifestations were headache, followed by altered mental status and seizures. Median diagnostic delay from onset of illness was 8 days. All patients were treated with unfractionated heparin or low-molecular heparin followed by warfarin. Complete recovery occurred in the majority of cases 22 (78.6%) but two patients died during hospitalization. CONCLUSIONS: Albeit with some particularities, the epidemiology and clinical manifestations we found are comparable to what has been reported in western studies.

Reversible acute parkinsonism and bilateral Basal Ganglia lesions in a diabetic uremic patient.

The syndrome of bilateral basal ganglia lesions in diabetic uremic patients is a rare disorder mostly reported in Asians. There are few reports of the syndrome in Caucasians. It manifests as an acute hyperkinetic or hypokinetic extrapyramidal disorder in association with uniform neuroimaging findings of bilateral symmetrical basal ganglia changes in diabetics undergoing hemodialysis. Its pathophysiology remains largely unknown. Thus, we report a typical case of the syndrome in a Caucasian patient who developed an acute and reversible akinetic rigid parkinsonism secondary to bilateral basal ganglia lesions.

Delayed hypoxic-ischemic leukoencephalopathy.

A 55-year-old female was found unconscious in a ventilated room. She recovered consciousness on the way to the emergency room. Her vital signs were stable. She presented with negativism and poor communication. Physical examination, routine tests, brain CT and electroencephalogram were normal. Urine toxicology was positive for benzodiazepines. Twelve days after, she presented with catatonia and immobility. Additional examinations, including cerebrospinal fluid (CSF) testing and brain CT, were again normal. Risperidone was administered, and psychotherapy intensified. In the third week, the condition worsened, with intense pyramidal signs and decerebration that led to a vegetative state. Brain MRI revealed diffuse leukoencephalopathy. Extensive metabolic and CSF studies were persistently negative. Brain biopsy was compatible with chronic cerebral hypoxia/anoxia. A diagnosis of delayed hypoxic-ischemic leukoencephalopathy was made. Supportive measures were intensified. She was discharged from the hospital after 4 months in a minimally conscious state and was capable of elementary communication and recognising faces.

Helicobacter pylori in dyspeptic children and adults: endoscopic, bacteriologic and histologic correlations

Using different bacteriological (urease test, Gram staining and culture) and histological (Steiner staining and modified Giemsa staining) techniques, we searched for the presence of Helicobacter pylori in the gastric antrum of 200 dyspeptic Brazilian patients (106 females and 94 males aged 19 days to 81 years). The presence of bacteria was then correlated with the endoscopic and histological findings. H. pylori was present in 59.5 of the population studied. In Brazil, colonization occurs early, involving 37 of the dyspeptic population by 20 years of age. The presence of H. pylori in the gastric antrum was strongly associated with duodenal ulcer (P < 0.001) and a normal endoscopic examination did not exclude the possibility of colonization of the gastric antrum by H. pylori. The most sensitive test was the preformed urease test (89). We conclude that more than one diagnostic method should preferably be used for the detection of H. pylori and that the presence of H. pylori is closely correlated with active chronic gastritis (P < 0.001).

Carcinoma papilífero da tireóide: a propósito da variante esclerosante difusa / Thyroid carcinoma: a propos of the diffuse sclerosing variant

O autor descreve os quadros anatomopatológico e clínico-epidemiológico da variante esclerosante difusa do carcinoma papilífero da tireóide, seguidos de proposta diagnóstica quanto aos achados citopatológicos, ao mesmo tempo que demonstra o perfil histoquímico das mucinas neutras e ácidas contidas na substância acinar. Através da imunohistoquímica define a fenotipagem da variante passando a admitir que o infiltrado linfocitário resulta de resposta do hospedeiro aos antígenos tumorais. A análise pela citofotometria evidencia que a variante esclerosante difusa tem em comparaçäo com o carcinoma papilífero comum uma média de maior área nuclear e proporcional aumento de massa relativa de ADN, o que permite considerá-la, ao lado de informaçöes clínicas, como de mau prognóstico. A história natural deste subtipo de carcinoma papilífero sugere terapêutica cirúrgica inicial täo radical quanto possível.

Isolation and characterization of an utero-active compound from Agave americana

Crude extracts of Agave americana contain two utero-active compounds. One of these, tentatively named "Fraction B", has been purified to chromatographic homogeneity. Its pharmacological actions are similar to those of acetylcholine. However its chromatographic and electrophoretic mobilities are different. Some chemical properties of fraction B are compatible with the structure of an acyl derivative of choline different from acetylcholine

Gangrena de Fournier: a propósito de três casos / Fournier's gangrene: report of three cases

A gangrena de Fourier, descrita inicialmente por este autor em 1883, constitui uma condiçäo patológica relativamente rara em dias atuais, mas de elevada morbidade e taxa de mortalidade variando de 7 a 13 por cento. Säo apresentadas três casos desta doença, tratados no Serviço de Urologia do Hospital Universitário Gaffrée e Guinle da Universidade do Rio de Janeiro (UNI-RIO), em um lapso de tempo relativamente curto (entre julho de 1988 e março de 1989). Säo analisados os diferentes aspectos da doença, ressaltando os excelentes resultados obtidos com a terapêutica agressiva antibiótica e cirúrgica, instituída nos três casos

Metástase tumoral de pulmão com invasão cardíaca: relato de um caso e revisão da literatura / Metastatic lung tumor invading the heart: report of one case and review of the literature

Os autores descrevem a evolução clínica de um rapaz de 16 anos com osteossarcoma, primário na perna direita e secundário do pulmão direito com protrusão do tumor para o átrio esquerdo através da veia pulmonar superior direita. O diagnóstico foi realizado durante ecocardiografia como protocolo para detecção de cardiotoxicidade às drogas antineoplásicas. Neste estágio, já havia uma grande metástase pulmonar à direita, irressecável e que foi controlada apenas pela quimioterapia. O paciente desenvolveu sinais clínicos de obstrução do átrio esquerdo e hipertensão arterial pulmonar, sendo submetido a ressecção da protrusão tumoral por cirurgia cardíaca aberta. No entanto, mesmo com prognóstico ruim, sobreviveu por quatro meses mais. A despeito do prognóstico pobre esperado, este tipo de cirurgia não impõe dificuldades técnicas e deveria ser feita sempre que possível tendo em vista a melhora da qualidade de vida que poderá trazer