Toxicokinetics of thebaine in those consuming non-food grade poppy seeds as a tea.

INTRODUCTION: Thebaine is an alkaloid in poppy seeds that is neurotoxic to animals. Data on its clinical effects and toxicokinetics in people are minimal. In 2022, poppy seeds high in thebaine entered the Australian food market, and people consuming tea made from these poppy seeds developed poisoning. METHODS: Three patients who drank poppy seed tea and developed neuromuscular toxicity consented for thebaine to be quantitated in serial blood samples. Blood samples were analyzed by liquid chromatography with high-resolution mass spectrometry. RESULTS: Case 1: A man in his 60s presented with drowsiness, vomiting, malaise and myoclonus. He developed metabolic acidosis with hyperlactataemia, acute kidney injury requiring haemodialysis, convulsions, rhabdomyolysis, and was in the hospital for 18 days. The admission thebaine blood concentration was 2.1 mg/L, and the apparent elimination half-life was 14.8 h. Case 2: A man in his 30s presented with myoclonus, rigidity, vomiting, and dizziness. He developed metabolic acidosis with hyperlactataemia, acute kidney injury, and myalgias. The admission thebaine blood concentration was 4.1 mg/L, and the apparent elimination half-life was 11.6 h. Case 3: A man in his 30s presented with myoclonus, rigidity, clonus, diaphoresis, and abdominal pain. The admission thebaine blood concentration was 2.2 mg/L, and the apparent elimination half-life was 8.3 h. DISCUSSION: Neuromuscular toxicity, metabolic acidosis with hyperlactataemia, acute kidney injury, and gastrointestinal symptoms were prominent clinical features in these patients after drinking poppy seed tea. Effects persisted for days, and all survived, despite thebaine concentrations far exceeding those in published forensic reports, although human data are sparse. Compared to rats, the thebaine apparent elimination half-life is much longer in humans who develop symptoms at lower concentrations. CONCLUSIONS: Despite relatively high thebaine blood concentrations and moderate to severe poisoning, outcomes were favourable with early presentations. It is possible that acute kidney injury prolongs the apparent elimination half-life of thebaine.

Case report - Asterixis Post High Frequency Focused-Ultrasound Thalamotomy.

Background: High frequency focused ultrasound is used for treatment of essential tremor. Side effects associated with the procedure may resolve over time. We report a case of negative myoclonus, which has not been reported with this procedure. Case report: A 73-year-old left-handed man underwent focused ultrasound thalamotomy for treatment of essential tremor. Immediately post procedure he was noted to have negative myoclonus in the treated limb. This side effect resolved over the course of 6 months. Discussion: Although asterixis has been associated with thalamic infarcts in the past, this has not yet been reported in the literature with MRgFUS procedure and is a novel observation. Occupational and physical therapy may be considered to address this side effect. It is important to counsel patients about the rare occurrence of this complication of therapy but also its potential for complete resolution over time.

Neurological symptoms improved by hyperbaric oxygen therapy in a post-cardiac arrest patient due to carbon monoxide poisoning: a case report.

Background: Carbon monoxide (CO) poisoning and cardiac arrest can cause neurological complications such as mental deterioration and movement disorders through ischemic brain injury. We report a case in which neurological sequelae after cardiac arrest caused by CO poisoning improved after hyperbaric oxygen (HBO2) therapy. Case report: A 43-year-old male visited the hospital with cardiac arrest due to CO poisoning. He developed neurological sequelae including mental deterioration and myoclonus after recovering spontaneous circulation. Anticonvulsant therapy was used after target temperature management but did not have a positive effect on neurological symptoms. However, after HBO2 therapy the patient's neurological symptoms improved, and he was discharged a month later. Conclusion: HBO2 therapy may be considered when neurological sequelae persist after cardiac arrest due to CO poisoning.

A novel exaggerated "spino-bulbo-spinal like" reflex of lower brainstem origin.

BACKGROUND: Many different oligosynaptic reflexes are known to originate in the lower brainstem which share phenomenological and neurophysiological similarities. OBJECTIVE: To evaluate and discuss the differences and aberrancies among these reflexes, which are hard to discern clinically using neurophysiological investigations with the help of a case report. METHODS: We describe the clinical and neurophysiological assessment of a young man who had a childhood history of opsoclonus-myoclonus syndrome with residual mild ataxia and myoclonic jerks in the distal extremities presenting with subacute onset total body jerks sensitive to sound and touch (in a limited dermatomal distribution), refractory to medications. RESULTS: Based on clinical characteristics and insights gained from neurophysiological testing we could identify a novel reflex of caudal brainstem origin. CONCLUSIONS: The reflex described is likely an exaggerated normal reflex, likely triggered by a dolichoectatic vertebral arterial compression and shares characteristics of different reflexes known to originate in caudal brainstem, which subserve distinctive roles in human postural control.

Effects of transcutaneous acupoint electrical stimulation combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus: A randomized controlled trial.

BACKGROUND: Myoclonus is an undesirable phenomenon that occurs after induction of general anesthesia using etomidate. Opioids such as sufentanil are considered effective pretreatment drugs for myoclonus inhibition, although high doses are required. Transcutaneous acupoint electrical stimulation (TAES), a noninvasive technique involving electrical stimulation of the skin at the acupuncture points, exhibits analgesic effects, promotes anesthetic effects, decreases the dose of anesthetic drugs, and increases endogenous opioid peptide levels. In the present study, we investigated the effects of TAES combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus in patients undergoing elective hysteroscopy. METHODS: In a double-blind manner, 172 patients (American Society of Anesthesiologists class I-II; age, 20-55 years) scheduled to undergo elective hysteroscopy were randomized into the following groups (n = 43 each): control (false TAES followed by saline injection after 30 min), TAES (TAES followed by saline injection after 30 minutes), sufentanil [false TAES followed by low-dose sufentanil (0.1 µg/kg) injection after 30 minutes], and sufentanil plus TAES (TAES followed by low-dose sufentanil injection after 30 minutes). In all groups, general anesthesia was induced by etomidate 0.3 mg/kg after sufentanil or saline injection. The incidence and severity of myoclonus were assessed for 2 minutes after etomidate administration. The visual analogue scale (VAS) scores for pain at 1 hour after surgery were recorded. The heart rate (HR), mean arterial pressure (MAP), and peripheral capillary oxygen saturation (SPO2) were recorded before premedication, after etomidate injection, after uterus expansion, and after recovery from anesthesia. RESULTS: The incidence of myoclonus was highest in the control group (88.3%), followed by TAES (74.4%), sufentanil (60.4%), and TAES plus sufentanil (48.8%) groups. Thus, the incidence was significantly higher in the control and TAES groups than in the sufentanil and TAES plus sufentanil groups. Grade 3 myoclonus occurred in 30.2%, 9.3%, 11.6%, and 9.3% patients in the control, TAES, sufentanil, and TAES plus sufentanil groups, respectively, with significant differences between the control group and the other 3 groups. Furthermore, the postoperative VAS scores for pain were significantly lower in the TAES, sufentanil, and TAES plus sufentanil groups compared with those in the control group. There were no significant differences in any other parameters among groups. CONCLUSION: Our results suggest that TAES combined with low-dose opioids such as sufentanil can decrease the incidence and severity of etomidate-induced myoclonus.

Assessment of the Anticonvulsant Potency of Ursolic Acid in Seizure Threshold Tests in Mice.

Ursolic acid (UA) is a plant derived compound which is also a component of the standard human diet. It possesses a wide range of pharmacological properties, i.e., antioxidant, anti-inflammatory, antimicrobial and antitumor, which have been used in folk medicine for centuries. Moreover, influence of UA on central nervous system-related processes, i.e., pain, anxiety and depression, was proved in experimental studies. UA also revealed anticonvulsant properties in animal models of epilepsy and seizures. The aim of the present study was to investigate the influence of UA on seizure thresholds in three acute seizure models in mice, i.e., the 6 Hz-induced psychomotor seizure threshold test, the maximal electroshock threshold (MEST) test and the timed intravenous pentylenetetrazole (iv PTZ) infusion test. We also examined its effect on the muscular strength (assessed in the grip strength test) and motor coordination (estimated in the chimney test) in mice. UA at doses of 50 and 100 mg/kg significantly increased the seizure thresholds in the 6 Hz and MEST tests. The studied compound did not influence the seizure thresholds in the iv PTZ test. Moreover, UA did not affect the motor coordination and muscular strength in mice. UA displays only a weak anticonvulsant potential which is dependent on the used seizure model.

Electrophysiological Investigations in Orthostatic Myoclonus: Preliminary Findings.

We report the clinical and electrophysiological findings in seven patients with orthostatic myoclonus (OM) associated with gait initiation failure and falls. OM is one of the causes of unsteadiness of stance and gait, and it may develop as a symptom of neurodegenerative disorders. Both positive myoclonic bursts and negative myoclonus may be seen in electrophysiological recordings, and electrophysiological analysis suggests a subcortical origin for OM.

Mioclonías asociadas al tratamiento con ciprofloxacino / Myoclonus associated with Ciprofloxacin therapy

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Positive effects of ceftriaxone on pentylenetetrazol-induced convulsion model in rats.

AIMS: Many drugs have been associated with seizures as a side effect. Although they are defined as safe for nervous system. The effect on proconvulsant activity of beta lactam antibiotics have been also reported. We aimed to investigate whether ceftriaxone has an anticonvulsant effect on PTZ-induced seizures in rats. MATERIALS AND METHODS: 36 male Sprague-Dawley rats, 18 of them for EEG recording and 18 of them are for behavioral studies, were randomly divided in two groups: group A for EEG recordings and group B for behavioral assesment. About 70 mg/kg PTZ was used for behavioral studies after Ceftriaxone administiration. About 35 mg/kg PTZ were used for EEG recording after ceftriaxone administiration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale, first myoclonic jerk onset time, spike percentages, brain MDA and SOD levels were evaluated between the groups. RESULTS: First myoclonic jerk onset time was significantly shorter in saline group than both 200 and 400 mg/kg ceftriaxone groups (p < 0.05). Racine's convulsion scale was significantly lower in 200 and 400 mg/kg ceftriaxone groups than saline group (p < 0.01, p < 0.0001). Both of two ceftriaxone groups have lower spike percentages than the saline group (p < 0.05). Significantly lower MDA levels and higher SOD activity were determined in 200 mg/kg ceftriaxone group compared with the saline group (p < 0.05). CONCLUSION: Our study demonstrated that ceftriaxone has protective effects on PTZ-induced convulsions and on oxidative damage associated with PTZ.

Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives

Fecal microbiota transplantation (FMT) is the infusion of liquid filtrate feces from a healthy donor into the gut of a recipient to cure a specific disease. A fecal suspension can be administered by nasogastric or nasoduodenal tube, colonoscope, enema, or capsule. The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated FMT as an emerging treatment for a wide range of disorders, including Parkinson's disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism. There are many unanswered questions regarding FMT, including donor selection and screening, standardized protocols, long-term safety, and regulatory issues. This article reviews the efficacy and safety of FMT used in treating a variety of diseases, methodology, criteria for donor selection and screening, and various concerns regarding FMT.

[A woman in her forties with cancer, syncope and spasms]. / En kvinne i 40-årene med kreft, synkope og kramper.

A female in her forties with advanced incurable rectal cancer presented to our emergency department after loss of consciousness followed by brief myoclonic jerks in her legs. A cerebral MRI was normal. Her electrocardiogram showed a prolonged QTc interval of 596 milliseconds and hypokalemia was present. She had no family history of congenital long QT syndrome or of cardiovascular disease. She was not on any medication apart from having ingested 100 g caesium carbonate over the previous 11 days as an alternative cancer treatment. Caesium chloride is postulated to increase pH and thereby induce apoptosis in cancer cells. In treatment doses caesium competes with potassium for membrane transport proteins in the cardiac cell membrane and in the reabsorption tubuli of the kidneys. A result is hypokalemia shortly after depolarization during the cardiomyocytes' repolarisation phase or delayed post-depolarisation. Torsade de pointes ventricular arrhythmias, ventricular tachycardia, pump failure and death can follow. A few case reports of adverse effects from caesium ingestion have been published, as well as reports on how caesium is used in animal models to induce ventricular tachycardia, but the hazards of caesium ingestion and its long half-life are not well known in the medical care profession or among patients. As this patient's QTc interval normalised slowly to 413 milliseconds 60 days after stopping caesium ingestion, we consider caesium intoxication and convulsive syncope from a self-terminating ventricular tachycardia as the most probable aetiology. The main message from this case is that alternative medicine can have life-threatening side effects.

The visual system in eyelid myoclonia with absences.

OBJECTIVE: To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]). METHODS: Fifteen patients with eyelid myoclonus with absences (EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE) without ECS, and 16 healthy controls (HC) underwent an electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain morphometry (VBM) protocol. The functional study consisted of 30-second epochs of eyes-open and eyes-closed conditions. The following EEG events were marked and the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking, and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for EMA and IGE). Within-group and between-groups comparisons were performed for fMRI and VBM data as appropriate. RESULTS: In EMA compared to HC and IGE we found: (1) higher blood oxygenation level-dependent (BOLD) signal related to the eye closure over the visual cortex, the posterior thalamus, and the network implicated in the motor control of eye closure, saccades, and eye pursuit movements; and (2) increments in the gray matter concentration at the visual cortex and thalamic pulvinar, whereas decrements were observed at the bilateral frontal eye field area. No BOLD differences were detected when comparing SWD in EMA and IGE. INTERPRETATION: Results demonstrated altered anatomo-functional properties of the visual system in EMA. These abnormalities involve a circuit encompassing the occipital cortex and the cortical/subcortical systems physiologically involved in the motor control of eye closure and eye movements. Our work supports EMA as an epileptic condition with distinctive features and provides a contribution to its classification among epileptic syndromes.

Serial MRI findings in brain anoxia leading to Lance-Adams syndrome: a case report.

Although in literature almost 150 patients with Lance-Adams Syndrome (LAS) have been reported, neuroradiological evaluations were often performed in late stages and there is no serial study evaluating LAS from early stages. We herein report a serial neuroimaging study demonstrating early and transient involvement of cerebellum and thalami in a LAS patient. We may hypothesize that a transient cerebral hypoxia provoked a permanent synaptic rearrangements of the neuronal networks involved in the pathogenesis of post-hypoxic myoclonus in our patient.

[Juvenile myoclonic epilepsy]. / Juvenil myoklonusepilepsi.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a generalised epilepsy with seizure onset in youth. The aim of this review is to present updated knowledge about the etiology, diagnosis and treatment of JME. MATERIAL AND METHOD: The review is based on a judicious selection of original English language articles, meta-analyses, and reviews found in PubMed, and the authors' own experience with the patient group. RESULTS: Seizure onset occurs in adolescence. All have myoclonias, about 90 % have generalized tonic-clonic seizures, and one third have absences. Myoclonic jerks are frequently the debut symptom, while tonic-clonic seizures appear later on. Patients are particularly susceptible to seizures shortly after waking. It is important to ask specifically about myoclonias as most patients do not report jerks spontaneously. The electroencephalograms of 44-81 % of the patients show discharges of 4-6 Hz polyspike waves. Focal EEG abnormalities may be seen in about 30 %. When patients are treated with valproate and seizure-precipitating factors are avoided, especially sleep deprivation, about 80 % become seizure-free. Lamotrigine and levetiracetam are alternative therapies for women of childbearing age. Attempts to taper off the medication after several years of seizure freedom entail a high risk of seizure relapse. INTERPRETATION: As there may be features of focal epilepsy in the seizure semiology and/or the EEGs, it may be difficult to diagnose JME. Thus, many patients are misdiagnosed as having a focal epilepsy and are given antiepileptic drugs that may aggravate the tendency to seizures.

Hiccup: Mystery, Nature and Treatment

Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. The abrupt air rush into lungs elicits a "hic" sound. Hiccup is usually a self-limited disorder; however, when it is prolonged beyond 48 hours, it is considered persistent whereas episodes longer than 2 months are called intractable. A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. Accordingly, any irritant in terms of physical/chemical factors, inflammation, neoplasia invading the arc leads to hiccups. The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. Besides, various drugs (eg, anti-parkinsonism drugs, anesthetic agents, steroids and chemotherapies etc) are the possible etiology. An effective treatment of persistent hiccup may be established upon the correct diagnosis of lesion responsible for the serious event. The pharmacotherapy of hiccup includes chlorpromazine, gabapentin, baclofen, serotonergic agonists, prokinetics and lidocaine. Non-pharmacological approaches such as nerve blockade, pacing, acupuncture and measures to hold breathing are also successful. Finally, alternative medicines and remedies are convenient to treat hiccups with uncertain effect. In conclusions, hiccup is likely to result from lesions involving the hiccup reflex arc. The lesion may need to be localized correctly for ablative treatment in patients with intractable hiccup. Apart from lesion ablation, drugs acting on reflex arc may be effective, while some other conventional measures may also be tried.