Abnormal movements in hospitalized COVID-19 patients: A case series.

BACKGROUND: Abnormal movements in Covid-19 patients have been reported with varying degree of frequency, prompting neurologic consultation and additional diagnostic evaluation. We sought to evaluate the frequency and etiology of abnormal movements among hospitalized Covid-19 patients undergoing neurologic consultation. METHODS: We retrospectively analyzed the first 50 consecutive patients with confirmed Covid-19 hospitalized at our tertiary medical care center who underwent acute inpatient neurology consultation from March 2020 through May 2020. Indication for neurologic consultation and diagnostic studies performed were identified by electronic medical record review. RESULTS: Of the 50 initial consultation requests, 11 (22.0%) patients were evaluated for abnormal movements (nine male and two female). Myoclonus was diagnosed in 6/11 (54.5%) patients. Additionally, two patients were diagnosed with seizures (confirmed on EEG in one), while two additional patients were diagnosed with tremor (physiologic and probable functional). A single case of serotonin syndrome was also identified. CONCLUSION: Abnormal movements observed in hospitalized Covid-19 patients can have a wide range of etiologies and were a frequent initial indication for neurologic consultation. Myoclonus was the most frequent type of abnormal movement observed. Early clinical recognition and directed diagnostic work-up is essential for accurate diagnoses in these patients.

Fatal serotonin syndrome: a systematic review of 56 cases in the literature.

INTRODUCTION: Serotonin syndrome (SS) is a drug-induced potentially life-threatening clinical condition. There is a paucity of data on the risk factors, clinical course, and complications associated with fatal SS. OBJECTIVE: To characterize the epidemiological profile, clinical features, and risk factors associated with fatal SS through a systematic review. METHODS: We performed a systematic review of MEDLINE and Google Scholar for case reports, case series, or cohort studies of fatal SS. RESULTS: Initial database search identified 2326 articles of which 46 (56 patients) were included in the final analysis. The mean age was 42.3 years (range 18-87 years) with female predominance (57%). North America and Europe constitute 80% of the reported fatal SS. The symptoms evolved very rapidly, within 24 h after the administration of serotonergic drugs in 59% of the cases. Fever (61%) was the most common symptom, followed by seizure (36%) and tremors (30%). The mean temperature in the reported cases (25 patients) was 41.6 ± 1.3 °C (range 38.3-43.5 °C). SS was reported to occur with the maintenance dosage of serotonergic agents, after initiation of the drug for the first time, and addition of the drugs for the development of another unrelated illness. Creatine kinase (CK) activities were elevated (>3 times of the upper limit of normal) in eighteen patients, and it was very high (>25,000 IU/L) in four patients. Presence of high grade fever, seizures, and high CK activities may be associated with severe SS. Nine patients (16%) received 5-HT2A antagonists as a therapy. About 50% of patients died within 24 h of the onset of symptoms. CONCLUSIONS: While fatal SS is rare, frequently observed features include hyperthermia, seizures, and high CK activities. Cyproheptadine use appears infrequent for these patients.

Serotonin syndrome in a Parkinson disease patient after intake of an ethanol-containing homeopathic medication.

Serotonin syndrome is due to excess serotonin in the nervous system. We document a case of an elderly Parkinson disease patient who has been neurologically stable on rasagiline and escitalopram for 1 year but developed serotonin syndrome after intake of an ethanol-containing homeopathic medication. The patient presented with seizures, autonomic dysfunction and neuromuscular hyperexcitability. Maintenance medications were discontinued, hydration, sedation and respiratory support were provided with resolution of the symptoms. The combination of escitalopram and ethanol, both metabolized by the cytochrome P450 enzyme system can lead to serotonin syndrome. Our case highlights the importance of drug interactions in patients taking several medications. Additionally, the intake of medicines, may it be conventional or homeopathic medicine, without the guidance of a trained and competent physician, may lead to serious consequences for the patient.

Slow on the Uptake, Progression to Heartbreak.

The prevalence of serotonin syndrome increases over the past several years as more serotonergic medications are being used in clinical practice. It is a potentially lethal condition caused by excessive serotonergic activity. Common causes of serotonin syndrome are the use of prescription medications, illicit drugs, or a combination of substances, leading to an increase in the activity of serotonin in the central and peripheral nervous system. The clinical symptoms range from mild to severe. We report a case of a 25-year-old woman with polysubstance abuse, including cocaine, who presented with confusion, rigidity, high-grade fever, and reduced biventricular function on echocardiogram. Based on the combination of substance used history, clinical presentation, and echocardiogram findings, she was diagnosed with serotonin syndrome complicated by takotsubo cardiomyopathy. She improved after being treated in the intensive care unit and was discharged from the hospital. This patient demonstrates the importance of recognizing and promptly initiating management of serotonin syndrome in order to improve morbidity and mortality.

Serotonin Syndrome Following Terbutaline Administration in a Heart Transplant Patient on Multiple Inotropic Agents: A Case Report.

The significance of serotonin syndrome due to drug-drug interactions has emerged as a prominent consideration when the effects of polypharmacy are reviewed. The emergence of the selective serotonin reuptake inhibitors has most likely fueled the increased reporting of serotonin syndrome in the literature, leading to increased awareness of this phenomenon. However, their presence is not necessarily inclusive to a case and the utilization of agents precipitating an occurrence may be unavoidable. We report a case of serotonin syndrome occurring in a heart transplant patient without the presence of any of the usual suspect agents involved. In the postoperative course, the patient developed cardiogenic shock with vasoplegia requiring continuation of inotropic therapy along with vasopressor support of epinephrine. Oral terbutaline was begun for hemodynamic improvement. The patient's tenuous mental status rapidly deteriorated after addition of the terbutaline, with symptoms consistent with serotonin syndrome. Administration of cyproheptadine, a known reversal agent for serotonin toxicity, rapidly alleviated the adverse symptoms.

Development of severe serotonin syndrome from acute ingestion of vilazodone without co-ingestion.

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) that was introduced to the market in 2011. It has a novel mechanism combining serotonin reuptake and partial agonism of 5HT-1 receptors. It has gained popularity in treating first generation SSRI-resistant depression. There has been little description in the literature of adult overdose. We are describing a 21-year-old female with an intentional overdose of 400 mg of vilazodone. This patient progressively developed worsening serotonin syndrome, which was resistant to aggressive benzodiazepine administration. The patient required sedation with propofol and phenobarbital to control serotonin syndrome. Patient required continued sedation for 36 h post-ingestion, with subsequent extubation and return to normal mental status. We detail an atypical case of a novel SSRI overdose with the treatment regimen used.

Serotonin syndrome masquerading as disease flare in lupus nephritis with end-stage renal disease.

INTRODUCTION: Serotonin syndrome is a potentially life-threatening condition characterized by the triad of mental status changes, autonomic instability, and neuromuscular changes. We report a case of serotonin syndrome masquerading as disease flare in a lupus nephritis patient with end-stage renal disease receiving linezolid for the treatment of infected pseudoaneurysm. CASE REPORT: A 36-year-old female lupus nephritis patient on maintenance hemodialysis for end-stage renal disease had been on multiple antibiotics, including anti-tuberculosis medications, over the past month for infected pseudoaneurysm complicating her arteriovenous fistula. Due to minimal response, she underwent pseudoaneurysmal ligation and given linezolid. Two days later, she developed chest pain, tachycardia, hypertension, tremors, later accompanied by high-grade fever, diarrhea, insomnia, and body weakness. Although fully awake and oriented, she was markedly agitated, mildly icteric, had hyperreflexia and asthenia with proximal muscle strength graded 3/5 in all extremities. Blood counts revealed anemia and thrombocytopenia; ancillary tests showed aspartate aminotransferase markedly higher than alanine aminotransferase, elevated serum lactate dehydrogenase and creatine kinase, and low C3 levels. Intravenous hydrocortisone was started for a suspected lupus flare. On the background of linezolid, isoniazid, and tramadol administration, serotonin syndrome with rhabdomyolysis was strongly considered. Offending drugs were discontinued, resulting in the dramatic improvement of symptoms and improved strength and well-being. The steroid was successfully tapered to 5 mg/day and a week later, she remained afebrile without recurrence of symptoms. CONCLUSION: Serotonin syndrome should be considered in patients on multiple serotonergic agents on the background of end-stage renal disease. Prompt recognition and distinction from lupus activity can significantly impact management decisions.

An atypical case of serotonin syndrome with normal dose of selective serotonin inhibitors: A case report.

RATIONALE: As increasing frequency of serotonergic drug use, SS (serotonin syndrome) occurred more than ever. But clinicians have not enough knowledge and experience about SS as a potentially life-threatening condition. SS is usually caused by the increased serotonin activity in the central nervous system which may due to a serotonergic agent overdose or the concomitant use of 2 or more serotonergic antidepressants. We report a case of SS due to a normal dose of selective serotonin inhibitors (SSRIs) thus to remind clinicians to pay attention to such patients and make an early diagnosis and initiation of therapy in the clinical practice. PATIENT CONCERNS: We report here a 49-year-old man presented with lethargic, less communicative, and insomnia for 20 days while a diagnosis of depression was considered and he was treated with SSRIs. DIAGNOSIS: The patient in our case fulfilled the 3 criteria existed now for diagnosing SS, including the Sternbach criteria, Radomski revised diagnostic criteria, and the Hunter serotonin toxicity criteria. INTERVENTIONS: All the antidepressants were stopped and cyproheptadine with an initial dose of 12 mg a day was started along with supportive care. The patient was also admitted to emergency intensive care unit for further treatment. He was sedated and paralyzed by intravenous Midazolam and Clonazepam along with physical cooling and supportive care. OUTCOMES: All of the patient's symptoms abated gradually and he soon could get off the bed and be communicative. Finally, the patient made a full recovery and he was discharged from the hospital. LESSONS: Our case suggests an atypical clinical course while the medicine the patient takes was not in so much dose. We assumed that there may have been some variation in metabolism of these agents, resulting in increased possibility that led to the subsequent syndrome. Thus, it is essential for clinicians to keep in mind when patients taking serotonergic agents who demonstrate acute change in their mental status. Besides, clinicians should be aware of such patients who seem to be sensitive to SSRIs, who may require a genetic testing before the initiation of SSRI therapy.

Adverse immune reactions and non-immune medications for perioperative use. / Reacciones adversas inmunitarias y no inmunitarias a fármacos de uso perioperatorio.

Reactions to medications can occur through a mechanism mediated by immunoglobulin or otherwise, not both. Drug allergy is a type of adverse reaction to the drug and comprises a range of hypersensitivity reactions mediated by different immunological mechanisms with diverse clinical manifestations. A rate of 3.2 fatal cases of anaphylaxis associated with drugs per 100,000 inhabitants per year is estimated, which seems to be approximately 10 times higher in hospitalized patients. The incidence of perioperative anaphylactic reactions is estimated at 1 in 10,000-20,000 anesthetic procedures. The diagnosis is based on a careful clinical history and physical examination. In some cases, skin tests, progressive challenges and methods to induce tolerance to the medication may be required. In hospitalized patients and at perioperative intervals, muscle relaxants, neuroleptics and morphinomimetics are frequently used and adverse reactions may occur to these drugs. This review shows a general description of the reactions of these medications, emphasizes allergic reactions and analyzes strategies for the diagnosis and treatment of these reactions.

Las reacciones a medicamentos pueden ocurrir por mecanismos mediados o no por imunoglobulina E. La alergia a fármacos es un tipo de interacción adversa y comprende una gama de reacciones de hipersensibilidad mediadas por distintos mecanismos inmunológicos con diversas manifestaciones clínicas. Se estima una tasa anual de 3.2 casos fatales de anafilaxia asociados con los fármacos por cada 100 000 habitantes, que parece ser aproximadamente 10 veces mayor en los pacientes hospitalizados. La incidencia de reacciones anafilácticas perioperatorias se estima en uno de cada 10 000-20 000 procedimientos anestésicos. El diagnóstico se basa en una cuidadosa historia clínica y en el examen físico. En algunos casos pueden requerirse pruebas cutáneas, pruebas de retos progresivos y procedimientos de inducción de tolerancia al medicamento. En los pacientes hospitalizados y en el intervalo perioperatorio frecuentemente se emplean relajantes musculares, neurolépticos y morfinomiméticos, por lo que pueden presentarse respuestas adversas a estos fármacos. En esta revisión se hace énfasis en las reacciones alérgicas a los medicamentos y se abordan estrategias para su diagnóstico y manejo.

[The serotonin syndrome: An updated literature review]. / Le syndrome sérotoninergique : une revue actualisée de la littérature.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.

Linezolid-associated serotonin toxicity after escitalopram discontinuation: concomitant drug considerations.

We report a case of a hospitalised patient who developed probable serotonin toxicity shortly after the initiation of linezolid in whom the selective serotonin reuptake inhibitor (SSRI) escitalopram had been recently discontinued. On day 2 of linezolid administration, the patient reported severe anxiety and was observed to have full body jerking and twitching motions without mental status change. Notably, the patient was concomitantly receiving the antidepressant, trazodone and the benzodiazepine, clonazepam possibly affecting the severity and manifestations of serotonin toxicity. Linezolid was discontinued after 5 days and the patient's symptoms resolved. Serotonin toxicity can present with an array of symptoms and be life threatening if left unrecognised. This report highlights the clinical lessons that discontinuation of an SSRI upon initiation of linezolid does not eliminate the risk of serotonin toxicity and that other concomitant medications may worsen or improve some of the symptoms lending delay and uncertainty to the diagnosis.

Serotonin Syndrome in the Perioperative Setting.

BACKGROUND Serotonin syndrome is a life-threatening condition that can lead to neurologic complications and is associated with the use of serotonergic medications. As the use of antidepressant medications has increased, the incidence of perioperative serotonin syndrome has transitioned from a rare diagnosis to one that should be considered as a differential diagnosis for any patient displaying signs of neuroexcitation. CASE REPORT A 70-year-old man (ASA 2) with a history of vestibular migraines (treated with venlafaxine), gastroesophageal reflux disease, and benign prostatic hyperplasia presented to our institution for photoselective vaporization of the prostate. Upon review of prior anesthetic records, his medical chart was found to list a propofol allergy. In discussion with the patient, he stated the reaction was rigidity. The anesthesiologist and patient agreed this was not an allergy. Thus, the patient was induced with propofol and given ketamine and fentanyl boluses throughout the procedure. During emergence, the patient exhibited myoclonic jerks in the upper and lower extremities. He was given intravenous meperidine for postoperative shivering; minutes after administration, the myoclonic jerks and rigidity worsened. The anesthesia team raised concern about serotonin syndrome. Intravenous midazolam improved the patient's myoclonic jerks and rigidity. CONCLUSIONS Patients with a history of rigidity/movement disorders during the perioperative period may have experienced serotonin toxicity. It is possible, as in our case, for this history to have been labelled as an allergy to a perioperative medication. Clinicians should remain vigilant for patients at risk of developing serotonin syndrome, such as those taking outpatient medications that increase neuronal serotonin.

Hyperpyrexia in a patient with a left ventricular assist device: a diagnosis beyond the obvious.

As the number of patients receiving a left ventricular assist device increases, physicians must always keep in mind that several conditions can present with non-specific symptoms, such as fever, tachypnoea and confusion. We herein report the case of a left ventricular assist device patient who developed a life-threatening condition with acute hyperthermia, confusion and extremities' clonus and muscle spasms. The patient was diagnosed with serotonin syndrome, attributed to the coadministration of 2 commonly prescribed medications (citalopram and omeprazole). This case highlights that a significant proportion of left ventricular assist device patients is treated with serotonergic agents that may predispose them to the appearance of serotonin syndrome, a potentially life-threatening condition.

[Age 89 years, depression, fall with pelvic fracture, severe confusion - serotonin syndrome : Differential diagnosis, importance of CYP450 and economic considerations]. / 89 Jahre, Depression, Sturz mit Beckenfraktur, schwerste Verwirrtheit ­ das serotonerge Syndrom : Differenzialdiagnose, Bedeutung von CYP450 und ökonomische Betrachtungen.

A case study of an 89-year-old patient is reported, who was admitted to hospital because of immobility due to pain. After the cause of the pain could initially be clarified and treated, the further clinical course in this very old woman showed an alarming symptom complex of agitation, confusion and cognitive deterioration, which took on grave forms. The work-up of this case showed a typical constellation of pain and depression in old age; however, the pharmaceutical treatment in this case is not atypical and could lead to a severe serotonin syndrome. The interaction, diagnostics, differential diagnosis, pharmacological, functional, codification and economic aspects of the course of the disease are discussed.