Severity of metabolic acidosis, state of consciousness, and serum ethanol on admission were the only significant parameters associated with mortality. The type of dialysis or antidote did not appear to affect mortality. Recommendations that were issued for hospital triage of fomepizole administration allowed conservation of valuable antidote in this massive poisoning outbreak for those patients most in need.

Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases.

In our prospective study, age, disease severity and CSF beta-amyloid levels taken together were a risk factor suggesting shorter survival times. Dementia is relatively frequent in ALS and may be a consequence of either FTLD or result from co-existing Alzheimer disease.

We identified a novel FHL1 mutation causing isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.

Information on the prognosis and electrophysiological follow-up of severe thallium poisoning is limited. We report two patients (mother and daughter) who were repeatedly exposed to thallium poisoning experienced hair loss, polyneuropathy, and visual impairment. Nerve conduction studies (NCSs), visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP) changes, and optical neuropathy developed within a few months latency after the first subjective signs. Normal findings of these electrophysiological methods in the first 2 weeks therefore led in one of our patients to exclusion of thallium as the cause of symptoms. Thallium poisoning was, however, later confirmed by toxicological analysis of blood and/or urine and feces in both the patients and in the microscopic hair analysis of the daughter. Both patients were treated with Prussian blue that increased the elimination of thallium in urine and feces. The hair loss was fully reversible. During a 2-year follow-up after the poisoning, polyneuropathy in the lower extremities improved substantially, but residual impairment in both motor and sensory function, NCSs, VEP, and BAEP remained. Additionally, severe asymmetrical vision impairment persists in both women, with central scotomata and impaired color discrimination in both eyes. Substantial improvement of their visual function is unlikely.

Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS.

Genetic polymorphisms influence the metabolism of ethanol and methanol, but the potential effects of genetic predisposition on the clinical course, outcome and short-term health sequelae of acute methanol poisoning are unknown. To evaluate the role of the MEOS system in methanol poisoning, we analysed the effect of three polymorphisms (RsaI -rs2031920; PstIrs3813867; insertion/deletion I/D) within the CYP2E1 enzyme (MEOS system) in 50 adult survivors of methanol poisoning and compared their genotype frequencies with 460 controls. The minor allele frequencies of all three polymorphisms were below 5% in both groups. We did not detect significant differences in the genotype frequencies between survivors of methanol poisoning and controls (p = 0.34 for the RsaI variant; p = 0.59 for the PstI variant and p = 0.21 for the I/D polymorphism). The carriers of at least one minor allele in the CYP2E1 gene had less severe clinical symptoms and better short-term outcome after acute poisoning. Variants within the CYP2E1 gene are likely not significant genetic determinants of acute methanol poisoning (if survivors are analysed), but they may influence the severity of methanol poisoning and its visual/central nervous system (CNS) outcome.Methanol poisoning is a rare condition, occurring mainly as a result of consuming adulterated liquor/spirit.From September 2012 to December 2013, approximately 150 cases of acute methanol poisoning with 48 deaths were registered in the Czech Republic. The cause of these poisonings was the consumption of illegal spirits adulterated with methanol. However, the registered number of intoxicated individuals does not reflect the estimated number of bottles that have toxic contents (according to law enforcement, several thousand bottles may be poisoned), and the poisoning severity in many cases did not correspond to the dose of ingested toxic spirits [1]. Therefore, we suggest that there may be specific genetic backgrounds that are more sensitive (or more resistant) to the toxic effects of methanol and its metabolite formic acid and that may potentially influence the clinical course and outcome of acute methanol poisoning. To date, no study examining the potential role of such genetic (pre)dispositions has been published.Approximately 30% of consumed methanol is excreted unchanged through the respiratory tract, and low amounts of methanol are excreted through sweat or urine [2]. In human beings, methanol is metabolized by the same pathways as ethanol due to its structural similarity to ethanol. The majority of methanol is oxidized by alcohol dehydrogenase [3]; however, this enzyme is monomorphic in poisoned Czech patients (Hubacek, unpublished results).The second largest amount of consumed methanol (approximately 10%) is metabolized by the inducible hepatic MEOS (microsomal ethanol oxidizing system) [4]. The activity of this system is strongly increased in individuals who consume ethanol regularly (long-term ethanol abuse) and with higher ethanol blood concentrations (over 0.5&).The most imp...

BackgroundFrontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP) that may be associated with motor neuron disease (FTLD-MND); involvement of extrapyramidal and other systems has also been reported.Case presentationWe present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite MND. Neuropathological examination revealed hallmarks of FTLD-TDP with major involvement of subcortical and, in particular, mesencephalic structures. These cases differed in onset and progression of clinical manifestations as well as distribution of histopathological changes in the brain and spinal cord. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102 delC.ConclusionsAssociation of a "progressive supranuclear palsy-like" syndrome with marked visuospatial impairment, motor neuron disease and early behavioral disturbances may represent a clinically distinct phenotype of FTLD-TDP. Our observations further support the concept that TDP-43 proteinopathies represent a spectrum of disorders, where preferential localization of pathogenetic inclusions and neuronal cell loss defines clinical phenotypes ranging from frontotemporal dementia with or without motor neuron disease, to corticobasal syndrome and to a progressive supranuclear palsy-like syndrome.