Effective Treatment of Neurological Symptoms with Normal Doses of Botulinum Neurotoxin in Wilson’s Disease: Six Cases and Literature Review

Background: Recent cell-based and animal experiments have demonstrated an effective reduction in botulinum neurotoxin A (BoNT/A) by copper. Aim: We aimed to analyze whether the successful symptomatic BoNT/A treatment of patients with Wilson’s disease (WD) corresponds with unusually high doses per session. Methods: Among the 156 WD patients regularly seen at the outpatient department of the university hospital in Düsseldorf (Germany), only 6 patients had been treated with BoNT/A during the past 5 years. The laboratory findings, indications for BoNT treatment, preparations, and doses per session were extracted retrospectively from the charts. These parameters were compared with those of 13 other patients described in the literature. Results: BoNT/A injection therapy is a rare (<4%) symptomatic treatment in WD, only necessary in exceptional cases, and is often applied only transiently. In those cases for which dose information was available, the dose per session and indication appear to be within usual limits. Conclusion: Despite the evidence that copper can interfere with the botulinum toxin in preclinical models, patients with WD do not require higher doses of the toxin than other patients with dystonia.

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Neurological Presentation of Severe Dengue in Children From a Colombian Hyperendemic Area

10.21203/rs.3.rs-51332/v1 ◽

2020 ◽

Author(s):

Jaime E. Castellanos ◽

Paula Esteban ◽

Juanita Panqueba-Salgado ◽

Daniela Benavides-del-Castillo ◽

Valentina Pastrana ◽

...

Keyword(s):

Fungal Infections ◽

Hypovolemic Shock ◽

University Hospital ◽

Severe Dengue ◽

Laboratory Findings ◽

Dengue Disease ◽

Neurological Signs ◽

Csf Analysis ◽

Neurological Patients ◽

The University

Abstract Objective: Dengue transmission is sustained in Colombia with increasing prevalence mainly in children. This work was aimed to describe a cases series of children diagnosed with dengue presenting neurological disease in the Huila province of Colombia. Eleven pediatric febrile patients confirmed to dengue disease and presenting neurological signs were studied in the University Hospital of Neiva, Huila province. Clinical and laboratory findings, CSF cytochemical analysis, neurology images, and serology and molecular studies were performed. Results. Viral RNA was detected in all patients’ sera by RT-PCR. Nine out of 11 were primary infections. Tonic-clonic seizures (73%), consciousness alterations (27%), irritability (27%) and ataxia (18%) were the most frequent neurological signs. None of the patients had plasma leakage, hypovolemic shock or liver disease, confirming the encephalitis diagnosis. Diagnostic images did not show abnormal findings neither bacterial or fungal infections were detected in CSF analysis. All patients survived without sequelae except in one patient that presented ataxia for months. In conclusion, we described a group of children with neurological signs during severe dengue disease as the main finding, indicating the importance of include dengue as a differential diagnosis in neurological patients from endemic areas.

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Triage tool for suspected COVID-19 patients in the emergency room: AIFELL score

10.1101/2020.05.09.20096834 ◽

2020 ◽

Author(s):

Ian Levenfus ◽

Enrico Ullmann ◽

Edouard Battegay ◽

Macé M. Schuurmans

Keyword(s):

Time Frame ◽

University Hospital ◽

Emergency Setting ◽

Clinical Experiences ◽

Emergency Rooms ◽

Laboratory Findings ◽

Student’S T ◽

The University ◽

Post Hoc ◽

Short Time

Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital Zurich, we created a triage score with the acronym AIFELL consisting of clinical, radiological and laboratory findings. The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms.

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An inductively coupled plasma mass spectrometry method for relative free copper determination and generation of a paediatric reference interval

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563217744809 ◽

2017 ◽

Vol 55 (4) ◽

pp. 485-490 ◽

Cited By ~ 2

Author(s):

P Wainwright ◽

D Wadey ◽

P Cook

Keyword(s):

Mass Spectrometry ◽

Inductively Coupled Plasma ◽

Wilson’S Disease ◽

Reference Interval ◽

Wilson's Disease ◽

University Hospital ◽

Spectrometry Method ◽

Mass Spectrometry Method ◽

Inductively Coupled ◽

Plasma Mass Spectrometry

Background Diagnosis of Wilson’s disease is currently performed using caeruloplasmin as a first-line screening test; however, this test has well-described limitations. Monitoring of known Wilson’s disease patients often uses 24-h urine collection; however, this is inaccurate in children. Methods for directly measuring plasma free copper have been described, but no reference interval data exist for a paediatric population. Methods An inductively coupled plasma mass spectrometry method for measuring free copper was developed and validated, using ultracentrifugation. A paediatric reference interval was generated using 85 plasma samples from children attending outpatient clinics at University Hospital Southampton. Results Results showed no significant contamination of copper using the ultracentrifugation technique, and validation showed the method was accurate and precise with an analytical coefficient of variation between 5 and 7% depending on the concentration of free copper. Conclusions We describe the use and validation of an ultrafiltration inductively coupled plasma mass spectrometry method for plasma free copper with the first published paediatric reference interval. Free copper could provide much needed assistance for the monitoring of Wilson’s disease in children and also for adults.

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Importance of botulinum toxin in symptomatic treatment of Wilson's disease

Toxicon ◽

10.1016/j.toxicon.2008.04.079 ◽

2008 ◽

Vol 51 ◽

pp. 26

Author(s):

Damásio Joan ◽

Cardoso Márcio Neves ◽

Magalhães Marina

Keyword(s):

Botulinum Toxin ◽

Wilson’S Disease ◽

Symptomatic Treatment ◽

Wilson's Disease

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Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers

Scientific Reports ◽

10.1038/s41598-021-85498-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kenya Kamimura ◽

Takeshi Suda ◽

Yasuo Fukuhara ◽

Shujiro Okuda ◽

Yu Watanabe ◽

...

Keyword(s):

Medical Information ◽

Excision Repair ◽

Predictive Marker ◽

University Hospital ◽

Cisplatin Sensitivity ◽

High Doses ◽

Clinical Trials Registry ◽

The University

AbstractCisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients’ condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).

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Clinical and Laboratoy Characteristics of Parvovirus B19 Infection During 2013/2014 Outbreak in Zagreb, Croatia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.751 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S319-S320

Author(s):

Mia Ajdukovic ◽

Lucija Pejic ◽

Neven Papic ◽

Adriana Vince

Keyword(s):

Clinical Presentation ◽

Parvovirus B19 ◽

Age Groups ◽

Clinical Manifestations ◽

University Hospital ◽

Complication Rates ◽

Laboratory Findings ◽

Mild Anemia ◽

Parvovirus B19 Infection ◽

The University

Abstract Background Human Parvovirus B19 (HPV-B19) occurs worldwide and causes mild, acute exanthematous disease that occurs in a form of cyclic local epidemics. The aim of this study was to analyze clinical features and complication rates of acute HPV-B19 infection in different age groups. Methods We retrospectively reviewed the charts of 718 consecutive patients clinicaly diagnosed with acute HPV-B19 infection who visited outpatient department at the University Hospital for Infectious Diseases in Zagreb, Croatia during 2013–2014 outbreak. In 212 patients (of 298 tested) diagnosis was confirmed by positive IgM antibodies and/or HPV-B19 DNA in peripheral blood. Results Outbreak started in June 2013 and had a peak in April 2014, with highest prevalence in schoolchildren. There were no difference in clinical presentation or laboratory findings between clinicaly and serologicaly diagnosed patients. Biphasic presentation, fever, myalgia, arthralgia, headache and peripheral edema were more frequent in adults, but „slapped cheeks” was found predominantly in children. Complications were more common in adults, most commonly hematological disordes (mild anemia, thrombocytopenia and leukopenia), vasculitis, hepatitis and aseptic meningitis. There were no deaths in our cohort. Conclusion Parvovirus B19 infection has different clinical presentation, laboratory findings and complications in children and adults. Since the diversity of the clinical manifestations in adults may be misleading, the infection in adults should be suspected when disease is prevalent in children. Disclosures `All authors: No reported disclosures.

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Mildly Impaired Foot Control in Long-Term Treated Patients with Wilson’s Disease

Journal of Functional Morphology and Kinesiology ◽

10.3390/jfmk7010005 ◽

2021 ◽

Vol 7 (1) ◽

pp. 5

Author(s):

Sara Samadzadeh ◽

Harald Hefter ◽

Osman Tezayak ◽

Dietmar Rosenthal

Keyword(s):

Gait Speed ◽

Wilson’S Disease ◽

Wilson's Disease ◽

The Body ◽

Gait Disturbance ◽

Control Group ◽

Initial Symptom ◽

Laboratory Findings ◽

Functional Deficit

Abnormal gait is a common initial symptom of Wilson’s disease, which responds well to therapy, but has not been analyzed in detail so far. In a pilot study, a mild gait disturbance could be detected in long-term treated Wilson patients. The question still is what the underlying functional deficit of this gait disturbance is and how this functional deficit correlates with further clinical and laboratory findings. In 30 long-term treated Wilson patients, the vertical component of foot ground reaction forces (GRF-curves) was analyzed during free walking without aid at the preferred gait speed over a distance of 40 m. An Infotronic® gait analysis system, consisting of soft tissue shoes with solid, but flexible plates containing eight force transducers, was used to record the pressure of the feet on the floor. Parameters of the GRF-curves were correlated with clinical scores as well as laboratory findings. The results of Wilson patients were compared to those of an age- and sex-matched control group. In 24 out of 30 Wilson patients and all controls, two peaks could be distinguished: the first “heel-on” and the second “push-off” peak. The heights of these peaks above the midstance valley were significantly reduced in the patients (p < 0.05). The time differences between peaks 1 or 2 and midstance valley were significantly negatively correlated with the total impairment score (p < 0.05). Gait speed was significantly correlated with the height of the “push-off” peak above the midstance valley (p < 0.045). The GRF-curves of free walking, long-term treated patients with Wilson’s disease showed a reduced “push-off” peak as an underlying deficit to push the center of mass of the body to the contralateral side with the forefoot, explaining the reduction in gait speed during walking.

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Atypical case of Wilson's disease with psychotic onset, low 24 hour urine copper and the absence of Kayser-Fleischer rings

Vojnosanitetski pregled ◽

10.2298/vsp130529049k ◽

2014 ◽

Vol 71 (12) ◽

pp. 1155-1158 ◽

Cited By ~ 1

Author(s):

Dragan Krstic ◽

Jadranka Antonijevic ◽

Zeljko Spiric

Keyword(s):

Genetic Analysis ◽

Wilson’S Disease ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Molecular Genetic ◽

Signs And Symptoms ◽

Wilson's Disease ◽

Molecular Genetic Analysis ◽

Laboratory Findings ◽

Atypical Case

Introduction. Wilson's disease is typically manifested in two clinical forms, neurological and hepatic and in rare cases it starts with psychiatric symptoms exclusively. We presented a rare atypical case of Wilson's disease with psychotic onset. Case report. A 22-year-old male patient was initially presented with predominant signs and symptoms of psychiatric disorder and then later with the development of neurological signs and symptoms. Neuroimaging, detected metal deposits in central nervous system (CNS) but not in peripheral organs, while serum analysis excluded pantothenate-kinase associated neurodegeneration (PKAN) and aceruloplasminemia. In favor of the diagnosis of Wilson's disease there were reduced concentrations of copper and ceruloplasmin concentrations and metal deposits in CNS, but other pathognomonic signs and symptoms were absent: in-creased copper in urine, Kayser-Fleischer rings in Descemet?s corneal membrane and deposits of copper in liver. Introduction of penicillamine treatment resulted in improvement in mental and general health of the patient. Molecular genetic analysis definitely confirmed the diagnosis of Wilson's disease. Conclusion. Wilson's disease can remain undetected for a long period of time if masked with dominant or exclusive psychiatric symptoms. If clear clinical symptoms and signs, and unambiguous laboratory findings are not present, it is necessary to perform molecular genetic analysis to confirm the definitive diagnosis.

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Wilson’s disease — hepatocerebral dystrophy

Herald of Pancreatic Club ◽

10.33149/vkp.2018.02.08 ◽

2018 ◽

Vol 40 (2) ◽

pp. 54-60

Author(s):

Y. S. Tsimmerman

Keyword(s):

Clinical Picture ◽

Genetic Basis ◽

Wilson’S Disease ◽

Copper Metabolism ◽

Symptomatic Treatment ◽

Liver Lesion ◽

Wilson's Disease ◽

Extrahepatic Manifestations ◽

Detailed Review ◽

History Of

The article presents a detailed review of modern ideas on Wilson’s disease – hepatocerebral dystrophy. The definition, terminology, history of the study of the disease are stated. Special attention is paid to the analysis of the pathogenesis of hepatocerebral dystrophy, including the genetic basis of its development, the disturbance of copper metabolism. The clinical picture is thoroughly described, taking into account the characteristics of liver lesion and extrahepatic manifestations, diagnostics, classification. Particular attention is paid to the means of pathogenetic and symptomatic treatment.

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Analysis of Running in Wilson’s Disease

Sports ◽

10.3390/sports10010011 ◽

2022 ◽

Vol 10 (1) ◽

pp. 11

Author(s):

Sara Samadzadeh ◽

Harald Hefter ◽

Osman Tezayak ◽

Dietmar Rosenthal

Keyword(s):

Wilson’S Disease ◽

Wilson's Disease ◽

Control Group ◽

Minor Importance ◽

Laboratory Findings ◽

Walking Aids ◽

Reaction Forces ◽

Analysis System ◽

Vertical Ground Reaction Forces

Aim of the study was to analyze the ability of long-term treated patients with Wilson’s disease (WD) to run a distance of 40 m. 30 WD-patients from a single center were consecutively recruited. All patients were able to walk a distance of 40 m without walking aids. Vertical ground reaction forces (GRF-curves) were analyzed by means of an Infotronic® gait analysis system (CDG®) and correlated with clinical and laboratory findings. Results of the WD-patients were compared to those of an age-and sex-matched control group. 25 of the 30 WD-patients were able to run. Patients being unable to run had a significantly (p < 0.03) higher non-motor score. In comparison to the controls speed of running was significantly (p < 0.02) reduced in WD-patients. Their duration of foot contact on the ground lasted significantly (p < 0.05) longer. Running was more irregular in WD and the variability of times to peak of the GRF-curves was significantly (p < 0.05) increased. All running parameters extracted from the GRF-curves of the CDG® did not correlate with severity of WD. Cadence of running was significantly (p < 0.03) negatively correlated with serum liver enzyme levels. Running appears to be rather unimpaired in long-term treated WD, only 16% of the 30 WD-patients were unable to run. This knowledge is highly relevant for the patient management, but because of the missing correlation with severity of WD, analysis of running is of minor importance for monitoring WD-therapy.

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