Distinct movement disorders in contactin-associated-protein-like-2 antibody-associated autoimmune encephalitis.

Autoimmune encephalitis can be classified into antibody-defined subtypes, which can manifest with immunotherapy-responsive movement disorders sometimes mimicking non-inflammatory aetiologies. In the elderly, anti-LGI1 and contactin associated protein like 2 (CASPR2) antibody-associated diseases compose a relevant fraction of autoimmune encephalitis. Patients with LGI1 autoantibodies are known to present with limbic encephalitis and additionally faciobrachial dystonic seizures may occur. However, the clinical spectrum of CASPR2 autoantibody-associated disorders is more diverse including limbic encephalitis, Morvan's syndrome, peripheral nerve hyperexcitability syndrome, ataxia, pain and sleep disorders. Reports on unusual, sometimes isolated and immunotherapy-responsive movement disorders in CASPR2 autoantibody-associated syndromes have caused substantial concern regarding necessity of autoantibody testing in patients with movement disorders. Therefore, we aimed to systematically assess their prevalence and manifestation in patients with CASPR2 autoimmunity. This international, retrospective cohort study included patients with CASPR2 autoimmunity from participating expert centres in Europe. Patients with ataxia and/or movement disorders were analysed in detail using questionnaires and video recordings. We recruited a comparator group with anti-LGI1 encephalitis from the GENERATE network. Characteristics were compared according to serostatus. We identified 164 patients with CASPR2 autoantibodies. Of these, 149 (90.8%) had only CASPR2 and 15 (9.1%) both CASPR2 and LGI1 autoantibodies. Compared to 105 patients with LGI1 encephalitis, patients with CASPR2 autoantibodies more often had movement disorders and/or ataxia (35.6 versus 3.8%; P < 0.001). This was evident in all subgroups: ataxia 22.6 versus 0.0%, myoclonus 14.6 versus 0.0%, tremor 11.0 versus 1.9%, or combinations thereof 9.8 versus 0.0% (all P < 0.001). The small group of patients double-positive for LGI1/CASPR2 autoantibodies (15/164) significantly more frequently had myoclonus, tremor, 'mixed movement disorders', Morvan's syndrome and underlying tumours. We observed distinct movement disorders in CASPR2 autoimmunity (14.6%): episodic ataxia (6.7%), paroxysmal orthostatic segmental myoclonus of the legs (3.7%) and continuous segmental spinal myoclonus (4.3%). These occurred together with further associated symptoms or signs suggestive of CASPR2 autoimmunity. However, 2/164 patients (1.2%) had isolated segmental spinal myoclonus. Movement disorders and ataxia are highly prevalent in CASPR2 autoimmunity. Paroxysmal orthostatic segmental myoclonus of the legs is a novel albeit rare manifestation. Further distinct movement disorders include isolated and combined segmental spinal myoclonus and autoimmune episodic ataxia.

Amyloid-aß Peptide in olfactory mucosa and mesenchymal stromal cells of mild cognitive impairment and Alzheimer's disease patients.

Patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) might develop olfactory dysfunction that correlates with progression of disease. Alteration of olfactory neuroepithelium associated with MCI may be useful as predictor of cognitive decline. Biomarkers with higher sensitivity and specificity would allow to understand the biological progression of the pathology in association with the clinical course of the disease. In this study, magnetic resonance images, apolipoprotein E (ApoE) load, Olfactory Connecticut test and Montreal Cognitive Assessment (MoCA) indices were obtained from noncognitive impaired (NCI), MCI and AD patients. We established a culture of patient-derived olfactory stromal cells from biopsies of olfactory mucosa (OM) to test whether biological properties of mesenchymal stromal cells (MSC) are concurrent with MCI and AD psychophysical pathology. We determined the expression of amyloid Aß peptides in the neuroepithelium of tissue sections from MCI and AD, as well as in cultured cells of OM. Reduced migration and proliferation of stromal (CD90(+) ) cells in MCI and AD with respect to NCI patients was determined. A higher proportion of anosmic MCI and AD cases were concurrent with the ApoE ε4 allele. In summary, dysmetabolism of amyloid was concurrent with migration and proliferation impairment of patient-derived stem cells.

Heterogeneity of cag genotypes of Helicobacter pylori in the esophageal mucosa of dyspeptic patients and its relation to histopathological outcomes.

BACKGROUND: A high prevalence of Helicobacter pylori in the esophageal mucosa of dyspeptic Venezuelan patients has been reported. We aimed to assess the genetic composition of the cag genotypes of H. pylori and its relation to histopathological outcomes in the gastroesophageal mucosa. METHODS: The presence of cagA, cagE, and virB11 cag pathogenicity island (PAI) genes was detected by PCR in 80 of 150 H. pylori-positive dyspeptic patients in both mucosae. Alterations of the gastroesophageal mucosa were assessed by histological techniques. RESULTS: The frequency of intact, partial, and deleted cag-PAI genes in the stomach of dyspeptic patients was found to be 57.5%, 21.3%, and 21.3%, respectively, whereas in the esophagus, frequencies were 33.8%, 33.8%, and 32.5% respectively. The genetic composition in the stomach was 57.5% cagA-positive, 20.0% cagA-negative, 75.0% cagE, and 77.5% virB11, whereas in the esophagus the distribution was 36.3% cagA-positive, 30.0% cagA-negative, 61.3% cagE, and 63.8% virB11. The gene with the largest difference between the two mucosae was cagA, with 58.8% in the stomach and 37.5% in the esophagus; cagE and virB11 were less variable. The correlation among single and/or mixed cag genotypes with histopathological outcomes in both mucosae from the same patient was higher for intact single cag-PAI genotypes, showing severe alterations. CONCLUSIONS: H. pylori may coexist in similar proportions without dominance of one cag genotype, suggesting a heterogeneous distribution in the esophagus. The cagE and virB11 genes can be used as markers of cag-PAI in the esophagus. The single cag-PAI genotype in both mucosae confers an increased risk of developing histological damage.

[Diagnosis of Helicobacter pylori infection by PCR in gastric juice and gastroesophageal biopsies from dyspeptic patients]. / Diagnóstico de la infección por Helicobacter pylori por PCR en jugo gástrico y biopsias gastroesofágicas de pacientes dispéptícos.

Helicobacter pylori is the main bacterial agent implicated in human gastroduodenal inflammatory pathologies; being one of the most common bacterial pathogens, with a high prevalence in Venezuela. The diagnosis of H. pylori infection is performed primarily in gastric biopsies through PCR; however, string-absorbed gastric juice and esophageal biopsies could be also used as alternative specimens to determine the infection. In this study the H. pylori infection was assessed in different specimens of the upper tract digestive of dyspeptic patients, though the detection by PCR of essential genes (glmM and ureA) and genes encoding virulence factors (cagA). Of 104 patients studied, H. pylori was found in 53.8, 69,2 and 58,7% of gastric juice, and gastric and esophageal biopsies, respectively; with predominance of the strains type I (cagA+) in juice and gastric biopsies, and strains type II (cagA-) in esophageal biopsies. The detection of H. pylori in gastric juice and esophageal biopsies showed high sensitivity and specificity, in comparison with the detection in gastric biopsies, suggesting that both types of specimens may be used efficiently for a secure diagnosis of H. pylori infection.

Diagnóstico de la infección por Helicobacter pylori por PCR en jugo gástrico y biopsias gastroesofágicas de pacientes dispépticos / Diagnosis of Helicobacter pylori infection by PCR in gastric juice and gastroesophageal biopsies from dyspeptic patients

Helicobacter pylori es el principal agente bacteriano implicado en lesiones gastroduodenales inflamatorias en humanos y una de las bacterias patógenas más comunes, con una alta prevalencia en Venezuela. El diagnóstico de la infección por H. pylori se realiza frecuentemente en biopsias gástricas mediante PCR; sin embargo, el jugo gástrico y las biopsias esofágicas podrían también ser utilizadas como muestras alternativas para determinar la infección. En el presente trabajo se evalúo la infección por H. pylori en diferentes muestras del tracto digestivo superior de pacientes dispépticos, mediante la detección por PCR de genes esenciales (glmM y ureA) y de virulencia (cagA). De los 104 pacientes estudiados, H. pylori fue encontrado en 53,8; 69,2 y 58,7% de las muestras de jugo gástrico y biopsias gástricas y esofágicas, respectivamente, con una predominancia de cepas tipo I (cagA+) en jugo y biopsias gástricas y cepas tipo II (cagA-) en biopsias esofágicas. La detección de H. pylori en jugo gástrico y biopsias esofágicas mostró una alta sensibilidad y especificidad en relación a la detección en biopsias gástricas, lo cual sugiere que ambos tipos de muestras pueden ser utilizados eficazmente para un diagnóstico seguro de la infección por H. pylori.

Helicobacter pylori is the main bacterial agent implicated in human gastroduodenal inflammatory pathologies; being one of the most common bacterial pathogens, with a high prevalence in Venezuela. The diagnosis of H. pylori infection is performed primarily in gastric biopsies through PCR; however, string-absorbed gastric juice and esophageal biopsies could be also used as alternative specimens to determine the infection. In this study the H. pylori infection was assessed in different specimens of the upper tract digestive of dyspeptic patients, though the detection by PCR of essential genes (glmM and ureA) and genes encoding virulence factors (cagA). Of 104 patients studied, H. pylori was found in 53.8, 69,2 and 58,7% of gastric juice, and gastric and esophageal biopsies, respectively; with predominance of the strains type I (cagA+) in juice and gastric biopsies, and strains type II (cagA-) in esophageal biopsies. The detection of H. pylori in gastric juice and esophageal biopsies showed high sensitivity and specificity, in comparison with the detection in gastric biopsies, suggesting that both types of specimens may be used efficiently for a secure diagnosis of H. pylori infection.