Electrocardiographic findings of methanol toxicity: a cross-sectional study of 356 cases in Iran.

BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.

Serum BDNF Levels Are Reduced in Patients with Disorders of Consciousness and Are Not Modified by Verticalization with Robot-Assisted Lower-Limb Training.

Little is known about plastic changes occurring in the brains of patients with severe disorders of consciousness (DOCs) caused by acute brain injuries at rest and during rehabilitative treatment. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity whose production is powerfully modulated by physical exercise. In this study, we compared serum BDNF levels in 18 patients with unresponsive wakefulness syndrome (UWS) and in a minimally conscious state (MCS) with those in 16 sex- and age-matched healthy controls. In 12 patients, serum BDNF levels before and after verticalization with ErigoPro robot-assisted lower-limb training were compared. Serum BDNF levels were significantly lower in patients (median, 1141 pg/ml; 25th and 75th percentiles, 1016 and 1704 pg/ml) than in controls (median, 2450 pg/ml; 25th and 75th percentiles, 2100 and 2875 pg/ml; p < 0.001). BDNF levels measured before and after verticalization with robot-assisted lower-limb training did not change (p = 0.5). Moreover, BDNF levels did not differ between patients with UWS and MCS (p = 0.2), or between patients with traumatic and nontraumatic brain injuries (p = 0.6). BDNF level correlated positively with the time since brain injury (p = 0.025). In conclusion, serum BDNF levels are reduced in patients with UWS and MCS and cannot be improved by verticalization associated with passive lower-limb training. Additional studies are needed to better understand the mechanisms underlying BDNF reduction in patients with DOCs and to determine the best rehabilitative strategies to promote restorative plastic changes in these patients.

The value of serum uric acid levels to differentiate causes of transient loss of consciousness.

BACKGROUND: Generalized tonic-clonic seizures (GTCS), syncope, and psychogenic nonepileptic seizures (PNES) are common emergent neurological conditions that cause transient disturbances of consciousness; however, it is sometimes difficult to distinguish them. OBJECTIVE: This study aimed to explore the value of serum uric acid levels in differentiating among GTCS, syncope, and PNES by analyzing serum uric acid levels in patients with GTCS, syncope, and PNES. METHODS: A total of 391 patients were retrospectively analyzed. Venous blood was drawn from the patients within 20 min of their arrival to the emergency department; serum uric acid levels were measured using the uricase method. RESULTS: Serum uric acid levels and the percentage of patients with elevated uric acid (elevation percentage) were significantly higher in the group with GTCS (n = 179) than in the groups with syncope (n = 156) (p < 0.001) and PNES (n = 56) (p < 0.001). The result remained the same when the serum uric acid level of male or female patients in the group with GTCS were compared separately with that in the other two groups (all p < 0.001). In the group with GTCS, both the serum uric acid level (p < 0.001) and elevation percentage (p < 0.05) were significantly higher in males than in females. The receiver operating characteristics (ROC) analysis in male patients yielded a serum uric acid value of 428.50 µmol/L with a sensitivity of 0.78 and a specificity of 0.99 as the optimal cutoff value to distinguish GTCS from other events. In female patients, a cutoff value of 338.00 µmol/L had a sensitivity of 0.69 and a specificity of 0.91 to distinguish GTCS from other events. For the group with GTCS, the period of time between the onset of seizure and serum uric acid levels dropping to normal were analyzed in 40 patients. The duration was 44.56 ±â€¯11.46 h for males (n = 23) and 40.37 ±â€¯9.78 h for females (n = 17) with no significant difference (p = 0.325). CONCLUSION: Serum uric acid levels provided certain clinical value for the differentiation of GTCS, syncope, and PNES; however, this requires verification in prospective studies with larger sample sizes.

Electrographic Seizures in Patients with Acute Encephalitis.

INTRODUCTION: Clinical seizures and status epilepticus are frequent complications of encephalitis, can lead to depressed level of consciousness, and are associated with poor outcome. We sought to determine the frequency, risk factors, and clinical impact of electrographic seizures detected with continuing electroencephalography (cEEG) in patients with encephalitis and altered level of consciousness. METHODS: We retrospectively identified all patients with presumed or definite viral or autoimmune encephalitis who underwent cEEG monitoring at Henry Ford Hospital from January 2012 to October 2017. Clinical data and cEEG monitoring reports were abstracted and recorded. The primary outcome was electrographic seizures detected by cEEG. RESULTS: Of 1,735 patients who underwent a minimum of 12 h of cEEG monitoring, we identified 54 with a verified discharge diagnosis of encephalitis. Twenty-two of these patients (41%) had electrographic seizures on cEEG. Compared with encephalitis patients without seizures, electrographic seizures were associated with lower serum sodium levels (137 ± 5 vs 141 ± 7, P = 0.027) and more often were on antiepileptic therapy (100% vs 78%, P = 0.033) on the first day of monitoring. Seizures were also associated with a higher frequency of cortical imaging abnormalities (68% vs 28%, P = 0.005), lateralized periodic discharges (LPDs; 50% vs 16%, P = 0.014), delta background frequency (81% vs 45%, P = 0.010), low or suppressed voltage (96% vs 62%, P = 0.005), and focal slowing (86% vs 47%, P = 0.004). There was no association between electrographic seizures and clinical outcome at discharge. CONCLUSION: Electrographic seizures occur in approximately 40% of patients with acute encephalitis. Low serum sodium, cortical imaging abnormalities, and on cEEG LPDs and background abnormalities are associated factors. The lack of association with short-term outcome suggests that with aggressive treatment, the clinical impact of electrographic seizures in encephalitis can be minimized.

The discriminative value of blood gas analysis parameters in the differential diagnosis of transient disorders of consciousness.

AIM: The differentiation between epileptic and non-epileptic episodes can be challenging. Our aim was to compare lactate, anion gap (AG), bicarbonate and the Denver Seizure Score (DSS) as point-of-care test (POCT) markers for episodes of transient alterations of consciousness. METHODS: The blood serum parameters were drawn at arrival in the emergency department (ED) within 2 h of the episode. After calculating AG and DSS values, the four parameters were compared retrospectively between patients with generalized tonic-clonic seizures (GTCS) (n = 165) and patients with other disorders of consciousness [syncopes (n = 43), and psychogenic non-epileptic seizures (n = 15)]. Additionally, we compared all values among men and women. RESULTS: In GTCS patients, all four parameters differed significantly compared to non-epileptic episode patients (p < 0.001). Serum lactate showed significant additional benefit over the remaining values, with an AUC of 0.947 (95% CI 0.92-0.975) and a high sensitivity and specificity for an optimal cut-off value of 2.45 mmol/l. For DSS, the AUC was 0.857 (95% CI 0.808-0.906; cut-off: 0.35), and for AG 0.836 (95% CI 0.783-0.889; cut-off: 12.45 mmol/l). In the case of serum bicarbonate, the AUC was 0.831 (95% CI 0.775-0.886; cut-off: 22.75 mmol/l). In the sex-dependent comparison, the results were similar. Men showed more significant differences in the compared values than women. CONCLUSIONS: Serum lactate is best suited as POCT marker in the differential diagnosis of epileptic and non-epileptic episodes and is superior to AG, DSS and bicarbonate. The differences among sexes may pose a challenge in their implementation and interpretation.

Alterations of consciousness and mystical-type experiences after acute LSD in humans.

RATIONALE: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking. METHODS: We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 µg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 µg. RESULTS: On the MEQ, 200 µg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 µg compared with 100 µg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 µg. CONCLUSIONS: Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 µg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 µg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

Morfeo Study II: Clinical Course and Complications in Patients With Long-Term Disorders of Consciousness.

BACKGROUND: The life expectancy of patients with disorders of consciousness (DOCs) is ever-increasing, but little is known about their clinical course over late stages. Several issues (premorbid conditions, complications and pressure sores) are to be considered for their effect on clinical outcome, risk of death and recovery of functional performance. Unfortunately, in late stages of long-term rehabilitation, these aspects are still more neglected than in acute and postacute stages. The aim of this study was to investigate the clinical course and the complications of patients in the late stages of DOCs and to explore the relationship between mortality and specific biomarkers. MATERIALS AND METHODS: A total of 112 patients, admitted over 10 years in a dedicated ward, were retrospectively studied. Sociodemographic data, preadmission and inpatient clinical features were collected. Disability Rating Scale scores, complications including pressure sores and blood markers were assessed monthly. Data were analyzed through descriptive statistics and correlations using SPSS. RESULTS: Most patients were men older than 50 years with a nontraumatic etiology and a history of hypertension (42.86%). The most common complication was pneumonia (76.79%). No association was found between sex and mortality or between etiology and mortality (P > 0.05). Mortality correlated significantly with sepsis (ρ = 0.253), albumin (ρ = -0.558), hemoglobin (ρ = -0.354) and white blood cells (ρ = 0.243). Only 42% of patients remained unchanged at Disability Rating Scale evaluation. CONCLUSIONS: These data confirmed that DOCs are not static conditions and they require ongoing monitoring and assessment of clinical status, level of consciousness and laboratory biomarkers.

Hypoglycemia and risk of seizures: a retrospective cross-sectional study.

PURPOSE: Few studies have been dedicated to assess neurological symptoms in relations to hypoglycemia. In this study we investigated the association between different levels of hypoglycemia and the occurrence of epileptic seizures in patients without a prior diagnosis of epilepsy. METHOD: A retrospective cross-sectional study. RESULTS: We identified 388 individuals from a laboratory database in Swedish regional hospital who had been found to have a glucose value of ≤3.5 mM between January and December 2009. Medical records were reviewed. Hypoglycemia was defined at three different categories: 0-2 mM (40 patients), 2.1-3 mM (154 patients) and 3.1-3.5 mM (194 patients). 14 patients had disturbance of consciousness including 3 with seizures. The majority of cases had coma, a generalized tonic-clonic seizure was seen only when s-glucose dropped below 2.0 mM. Two cases with focal seizure were noted, one at s-glucose 2.0 mM, and one at s-glucose 3.3 mM. The absolute risks (95% confidence interval) for having major neurological symptoms at glucose levels of ≤2.0 mM were 0.25 (0.13-0.41), 0.02 (0-0.06) at 2.1-3.0 mM and 0.01 (0-0.03) at 3.1-3.5 mM. CONCLUSION: Coma is the most common neurological symptom related to hypoglycemia. Epileptic seizures are rare and not as common as previously assumed.

[Transplacental or breast milk intoxication to clonidine: a case of neonatal hypotonia and drowsiness]. / Intoxication transplacentaire ou par lait maternel à la clonidine : un cas de somnolence et d'hypotonie néonatale.

We report a case of clonidine poisoning in a breastfed newborn. At 2 days of life, this boy presented a consciousness deficit with drowsiness, hypotonia, and suspected generalized seizures. There were no cardiorespiratory problems outside of progressive central apneas beginning the 5th day. Further initial investigations were normal (extensive biological exams, cranial ultrasonography and transfontanellar Doppler, electroencephalography, and brain MRI study), excluding the main causes of neonatal hypotonia (encephalitis, infection, metabolic disorder). However, new medical questioning revealed maternal daily intake of 0.15 mg clonidine for hypertension during and after pregnancy. Since it was impossible to quantify clonidine quantification in newborn serum and breast milk, a weaning test was performed the 9th day. Twenty-four hours after cessation of breastfeeding, complete regression of symptoms was obtained. Poisoning by clonidine after fetal and neonatal exposure through breast milk is rare but severe enough to simulate a neurological disease. Diagnosis is based on the search for drug use and the cessation of breastfeeding if doubt persists. Recovery of normal examination results is then rapid and complete.

Positive lidocaine toxicology screen after J-Tip for venipuncture.

Venipuncture is common in children, and topical anesthetics are often used to alleviate the pain of the procedure. The J-Tip (National Medical Products, Inc, Irvine, Calif) device has become popular as a rapid and effective means of delivering lidocaine noninvasively. We report a case of a positive lidocaine blood toxicology screen after the use of the J-Tip device in a child pre-venipuncture. A repeat toxicology screen obtained 1 hour later by venipuncture without J-Tip use was negative. This report serves to remind clinicians that topical anesthetics may interfere with toxicology assays, leading to unreliable toxicology results.

Symptoms and course of intoxication with mesuximide--a case report.

We report on a 31-year-old, female patient who presented with somnolence due to an intoxication by the antiepileptic drug, mesuximide (MSM). The serum concentration of its metabolite n-desmethyl-mesuximide (85.7 mg/L) was above the so-called therapeutic range (10-40 mg/L) but below the concentration range that led to an impairment of consciousness in previous cases according to the German SPC (>150 mg/L). The symptoms remitted quickly under hemodialysis. In somnolent patients treated with MSM, the treating physicians should be aware of drug intoxication as a possible etiology. Therefore, the serum concentration should be measured early. Due to the, often, long latency until the results are available, treatment initiation may be necessary based on suspicion.

Determinants of altered sensorium at presentation with diabetic ketoacidosis.

AIM: The aim of this paper was to determine the prevalence of altered sensorium and their determinants in diabetic ketoacidosis (DKA). METHODS: Retrospective review of medical records for diabetic ketoacidosis admissions over a two year period. RESULTS: A total of 94 admissions for DKA in 89 patients were reviewed. Majority of admissions were female related. The mean age of the subjects was 39.1±18.5 years. The prevalence of altered sensorium defined as Glasgow coma scale (GCS) below 15 was 47.9%. In Model 1, systolic blood pressure (SBP) <90 mmHg (odds ratio [OR] 17.5 95% Confidence Interval (CI) 2.1-142.9; P=0.008 and calculated effective serum osmolality >320 mosmol/Kg (OR 3.6 95% CI 1.4-12.2; P=0.043 were independently associated with altered sensorium. In Model 2 where serum osmolality was substituted with uncorrected serum sodium, SBP <90 mmHg OR 19.6 95% CI 2.2-100; P=0.007, uncorrected serum sodium >150 mmol/L OR 18.5 95% CI 2.1-100; P=0.0009 and white cell count >25 x 106/L OR 3.6 95% CI 1.03-13.5; P=0.05 were independently associated with altered sensorium. CONCLUSION: Systolic blood pressure <90 mmHg, calculated effective serum osmolality >320 mosmol/Kg, uncorrected serum sodium >150 mmol/L and white bood count >25 x 106/L were independently associated with altered sensorium.

Hyperammonemia in the pediatric emergency care setting.

UNLABELLED: Hyperammonemia is encountered frequently in acutely ill children presenting for emergency care with altered levels of consciousness (ALOC). Ammonia production, metabolism, and excretion are affected by different variables. Hyperammonemia may be a transient state or may signify more grave etiologies as inborn errors of metabolism. Levels of ammonia are also affected by proper sampling technique, transport, and analysis. OBJECTIVES: To determine the level of ammonia in acutely ill children with ALOC, identify causes of hyperammonemia, and correlate levels with illness severity and morbidity. DESIGN: Observational study. SETTING: Emergency department at Cairo University Specialized Paediatric Hospital. METHODS: Fifty cases of acutely ill pediatric patients with ALOC who presented to the emergency department were included in the study from 2008 through 2009. Emergency department patients (n = 20) with known diseases that may induce hyperammonemia were excluded. Patients were subjected to detailed history taking with emphasis on factors affecting ammonia levels and thorough clinical examination. A cohort group of age- and sex-matched children acted as a control group. RESULTS: The measured blood ammonia level ranged between 13 and 265 µmol/L, with a mean level of 95 µmol/L. Sixty percent of the children with ALOC had ammonia levels of greater than 75 µmol/L, with levels greater than 200 µmol/L seen in 6% of the studied sample. The study demonstrated a highly significant statistical difference between children with ALOC and control groups.There was no correlation between blood ammonia level and age. Correlations of ammonia levels were also conducted in comparison with etiological diagnoses and laboratory parameters with no statistical significance.There was no statistical significance between ammonia level and duration of illness, Sequential Organ Failure Assessment score, or Glasgow Coma Scale score/Morray Scale score. CONCLUSIONS: Clinicians should consider testing children with ALOC for hyperammonemia, provided that a clear understanding of its metabolism and factors controlling it are understood. Proper sampling must be ensured. Mild elevations of ammonia levels are fairly common, but exceedingly high levels should raise concern and may require further evaluation.

[When eating becomes dangerous...]. / Von der Frau, der das Essen nicht bekam.

We report the case of a 59-year-old women with idiopathic insulin auto-immune syndrome, a rare cause of endogenous hyperinsulinemic hypoglycemia. It is characterized by extremely high levels of insulin in the presence of high titers of insulin antibodies despite the absence of previous insulin injections. Early postprandial increase in glucose concentrations due to impaired insulin action resulting from the buffering effect of the antibodies and late postprandial hypoglycemia as a consequence of the dissociation of insulin from the antibodies was observed. A correct diagnosis is important to avoid unnecessary investigations and surgery in these patients who are best treated conservatively - with a good prognosis - by fractionating carbohydrate intake during the day.

[Intoxication with lithium]. / Akzidentelle Lithiumintoxikation.

We report a case of a 75-year-old male patient who presented to the emergency room with arterial hypotension and impaired vigilance. The patient was on lithium therapy due to mood disorder. One month earlier medication with a betablocker, a loop-diuretic and an ACE-inhibitor had been started due to heart failure. Findings at admission included renal insufficiency, pneumonia and a slightly increased serum level of lithium. Three days later his Glasgow Coma Scale Score was 7, he showed gaze deviation, increased muscle tonus and cloni. The patient fully recovered after volume substitution and normalization of his renal function. Diagnosis of chronic intoxication with lithium was made due to the clinical picture and after exclusion of neurological pathologies. The pharmacokinetic characteristics of lithium is described and the risk factors leading to lithium intoxication and treatment of intoxication are discussed.

Severe acute hyperammonemia after brief exposure to valproate.

The authors describe a case of acute hyperammonemia after the addition of valproate to the medication regimen of a patient on multiple psychotropic medications. The patient presented with acute mental-status changes consistent with delirium. With prompt intervention and supportive care, her delirium quickly cleared.

[How often does decreased consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1 and what are its consequences?]. / Jak czesto wystepuje zmniejszona swiadomosc odczuwania hipoglikemii u dzieci i mlodziezy z cukrzyca typu 1 i jakie sa tego nastepstwa?

UNLABELLED: The inability of the patient to recognize the risk of hypoglycemia is a very frequent phenomenon, but it is also often an underestimated complication in diabetes treated with insulin. The results of DCCT trial revealed that intensification in insulin therapy increases three-fold the risk of severe hypoglycaemia. Feeling the state of hypoglycaemia is the basic defensive mechanism in patients with diabetes type 1, making possible to start the self treatment. The decreased consciousness of hypoglycaemia makes limitations to intensive insulin therapy, which main aim is to stop later complications. THE AIM OF THE STUDY was to answer the questions: 1. How often does lack of consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1. 2. What are the possible factors influencing appearance of hypoglycaemia. 3. Is lack of hypoglycaemia consciousness of a risk factor for severe hypoglycaemia. MATERIAL AND METHODS: The study was carried out on 318 patients aged x=13.6 yrs (4-21), suffering from diabetes, mean 6.6 yrs (2-18). The study was retrospective taking into consideration the period from 1.01.1998 to 31.12.2002. RESULTS: In the analysis of the questionnaire assessing the occurrence of hypoglycaemia it was found that 82 patients (25.8%) have problems with feeling the state of hypoglycaemia. We analyzed the influence of time of lasting diabetes and we found that patients with a longer duration of the disease more frequently have problems with feeling hypoglycaemia, 57% patients with lack of hypoglycaemia consciousness have bad metabolic control of the disease. In the analyzed period, 64 incidences of severe hypoglycaemia in 48 patients (30 boys and 18 girls) were found. In patients with lack of consciousness of feeling hypoglycaemia the incidences of severe hypoglycaemia occurred ten times more frequently compared to patients who feel hypoglycaemia. Sleeping makes it impossible to perceive early symptoms of hypoglycaemia: in our patients 51 severe incidences (79.7%) occurred at 1.00-3.00 a.m., 6 (9.3%) occurred at daybreak and 7 (11%) in the evening. CONCLUSIONS: 1. In patients with diabetes type 1 the lack of hypoglycaemia consciousness occurs in about 25%. 2. The lack of hypoglycaemia consciousness is closely connected with time of diabetes duration and with recurrence of hypoglycaemia incidences. 3. Patients with lack of hypoglycaemia consciousness are at greater risk for severe hypoglycemia.