We present a patient with progressive spastic ataxia, with dystonia and anarthria undiagnosed until detailed genetic analysis revealed an MPAN mutation. Highlighting the worldwide MPAN distribution, a 30year history of absent diagnosis and the impact and cost saving of an early but detailed genetic analysis in complex progressive movement disorders, particularly the anarthric NBIA group.
A 39-year-old previously healthy woman presented to the hospital with a nonproductive cough, small-volume hemoptysis, and exertional dyspnea. In addition, she reported a 4-week history of progressive left-sided headache, retro-orbital pain, left ear conductive hearing loss, fever, chills, anorexia, and a 10-lb weight loss. She had no prior sick contacts or history of respiratory tract infections. She did not take any chronic medications or supplements. The patient was a lifelong nonsmoker. She worked as a field consultant in Northern Manitoba communities. While in the hospital, she developed new symptoms of "unquenchable thirst," polydipsia, and polyuria.
A 5 +-day-old male patient was hospitalized due to a significant increase of urine protein for 5 + d. A 36 +4 weeks preterm male infant was found with III° polluted amniotic fluid and excessive placenta, presented with proteinuria, hypoproteinemia, and progressive edema after birth. Two heterozygous mutations of NPHS1 gene, c.3325C>T (p.Arg1109*) and c.2479C>T (p.Arg827*), were found through the whole exon gene detection. The latter has not been reported domestically and the diagnosis of congenitalnephrotic syndrome of the Finnish type (CNF) is definite. The report of c.2479C>T mutation gene will expand the mutation spectrum of CNF gene data in China. Early genetic testing is recommended for cryptogenic congenital nephrotic syndrome (CNS) and early genetic diagnosis of CNF is important for prognostic evaluation, genetic counseling and clinical management.
Department of Clinical Neurology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 11, 3rd floor, Sahlgrenska University Hospital, 413 45, Göteborg, Sweden.
Swedish type Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS-S) is a severe adult-onset leukoencephalopathy with the histopathological hallmark of neuraxonal degeneration with spheroids, described in a large family with a dominant inheritance pattern. The initial stage of the disease is dominated by frontal lobe symptoms that develop into a rapidly advancing encephalopathy with pyramidal, deep sensory, extrapyramidal and optic tract symptoms. Median survival is less than 10?years. Recently, pathogenic mutations in CSF1R were reported in a clinically and histologically similar leukoencephalopathy segregating in several families. Still, the cause of HDLS-S remained elusive since its initial description in 1984, with no CSF1R mutations identified in the family. Here we update the original findings associated with HDLS-S after a systematic and recent assessment of several family members. We also report the results from exome sequencing analyses indicating the p.Cys152Phe variant in the alanyl tRNA synthetase (AARS) gene as the probable cause of this disease. The variant affects an amino acid located in the aminoacylation domain of the protein and does not cause differences in splicing or expression in the brain. Brain pathology in one case after 10?years of disease duration showed the end stage of the disease to be characterized by widespread liquefaction of the white matter leaving only some macrophages and glial cells behind the centrifugally progressing front. These results point to AARS as a candidate gene for rapidly progressing adult-onset CSF1R-negative leukoencephalopathies.
Lipopolysaccharide (endotoxin) from the outer Gram-negative bacterial wall can induce a harmful immunologic response, involving hemodynamic deprivation, and is one important motor driving the septic cascade. The positively charged poly-imine ethylene layer on the oXiris membrane is capable of adsorbing negatively charged endotoxin molecules and removing them from the blood compartment. Endotoxin is detrimental and should be removed from blood.
The adsorbable endotoxin fraction in blood arises from a tight balance between seeding from an infectious focus and removal by an overwhelmed immune system. The net sum of remaining endotoxin in blood is available for an adsorption process in the oXiris filter. Endotoxin data from 2 patients with severe Gram-negative septic shock and endotoxemia in this case series, speaks for a considerable share of the adsorption of the oXiris filter in the endotoxin net removal over time. Key Messages: Analysis of combined in vitro and in vivo data speaks for an effect of the oXiris filter in lowering endotoxin.
Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipeloid and is most frequently associated with exposure to domestic swine. Infection of native and prosthetic joints is a rarely reported manifestation.
We describe a case of E. rhusiopathiae prosthetic joint infection in a woman with a history of exposure to wild animals in the Canadian Arctic. Patient management involved a 1-stage surgical revision exchange with an antibiotic impregnated cement spacer and 6 weeks of intravenous penicillin G followed by 6?weeks of oral amoxicillin. Ten previously reported cases of E. rhusiopathiae joint infection are reviewed. Recent increases in mortality due to infection with this organism among host animal populations in the Canadian Arctic have generated concern regarding a potential increase in human infections. However, whole genome sequencing (WGS) of the organism was unable to identify a zoonotic origin for this case.
Consideration should be given to E. rhusiopathiae as a cause of joint infections if the appropriate epidemiologic and host risk factors exist. Expanded use of WGS in other potential animal hosts and environmental sources may provide important epidemiologic information in determining the source of human infections.
Cold-induced peripheral neuropathy has been described in individuals exposed to severe cold resulting in pain, hypersensitivity to cold, hyperhidrosis, numbness, and skin changes. Nerve conduction studies and thermal detection thresholds are abnormal in symptomatic patients, and intraepidermal nerve fiber density (IENFD) in skin biopsies is reduced.
A 41-year-old male was included as a healthy subject in a study of the spontaneous variability of quantitative sensory testing (QST), nerve conduction studies (NCS), and IENFD. Unexpectedly, IENFD was significantly reduced, whereas the rest of the examination was normal except for reduced vibration detection threshold. The results were confirmed at follow-up examination. The subject had been repeatedly exposed to severe cold resulting in short lasting numbness and paresthesia while living in the eastern part of Greenland and the northern part of Norway.
Loss of intraepidermal nerve fibers caused by exposure to severe cold may be asymptomatic, and their function assessed by thermal detection thresholds may be preserved. This case illustrates that QST and IENFD are complementary tests and that subclinical cold-induced peripheral neuropathy may be prevalent in subjects living in or near polar regions which could have implications for the recruitment of healthy subjects.
An 11-year-old neutered male miniature American Eskimo dog was presented for routine dental cleaning with moderately enlarged submandibular, prescapular, and popliteal lymph nodes. On pre-anesthetic blood analysis a moderate, poorly regenerative anemia and marked lymphocytosis were observed. Although cytologic evaluation of a lymph node aspirate was interpreted as lymphoma, a complete blood cell count, flow cytometric immunotyping of blood leukocytes, and serum electrophoresis identified B-cell chronic lymphocytic leukemia. Chemotherapy with chlorambucil was recommended.
Leucémie lymphocytaire chronique à cellules B chez un chien Eskimo américain miniature. Un chien mâle castré âgé de 11 ans de race Eskimo miniature fut présenté pour nettoyage dentaire de routine avec une hypertrophie modérée des ganglions sous-mandibulaires, pré-scapulaires et poplités. Lors des analyses sanguines pré-anesthésie, une anémie pauvrement régénératrice et une lymphocytose marquée furent observées. Bien que l’évaluation cytologique d’une aspiration d’un des ganglions fut interprétée comme un lymphome, un comptage cellulaire sanguin complet, l’immunotypage des leucocytes sanguins par cytométrie en flux, et une électrophorèse du sérum identifièrent une leucémie lymphocytaire chronique à cellules B. Une chimiothérapie avec du chlorambucil et de la prednisone fut recommandée.(Traduit par Dr Serge Messier).
Studies have shown that our modern electrical lighting environment reduces naturally occurring seasonal variations in sleep-wake rhythms, such as longer sleep during the winter versus summer. However, less is known about how timing and duration of sleep were affected by the seasons in the premodern era, before the invention of electrical lighting. The Swedish researcher Olof Hiorter collected and documented geophysical data every hour during wakefulness in Uppsala, Sweden, between December 1746 and November 1747. In this way, his bed and rise times could be approximated. The data revealed that Hiorter's rise times occurred around 1 hr before sunrise in winter versus 1 hr after sunrise in summer. No such association was observed between the time of sunset and Hiorter's bedtimes. Finally, the time in bed was about 3.5-4 hr shorter in summer compared to winter. This 273-year-old case report suggests that time in bed and rise times of people from the premodern era exhibited seasonal variations.