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Brain Communications 2024Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched...
Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation- and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few human studies have been performed. Here, non-invasive magnetic resonance spectroscopy (H and P) was applied to test scan feasibility and assess neurotransmitter balance and energy metabolism in Lafora disease towards a better understanding of pathogenesis. Macromolecule-suppressed gamma-aminobutyric acid (GABA)-edited H magnetic resonance spectroscopy and P magnetic resonance spectroscopy at 3 and 7 tesla, respectively, were performed in 4 Lafora disease patients and a total of 21 healthy controls (12 for the H magnetic resonance spectroscopy and 9 for the PMRS). Spectra were processed using in-house software and fit to extract metabolite concentrations. From the H spectra, we found 33% lower GABA concentrations ( = 0.013), 34% higher glutamate + glutamine concentrations ( = 0.011) and 24% lower -acetylaspartate concentrations ( = 0.0043) in Lafora disease patients compared with controls. From the P spectra, we found 34% higher phosphoethanolamine concentrations ( = 0.016), 23% lower nicotinamide adenine dinucleotide concentrations ( = 0.003), 50% higher uridine diphosphate glucose concentrations ( = 0.004) and 225% higher glucose 6-phosphate concentrations in Lafora disease patients versus controls ( = 0.004). Uridine diphosphate glucose is the substrate of glycogen synthase, and glucose 6-phosphate is its extremely potent allosteric activator. The observed elevated uridine diphosphate glucose and glucose 6-phosphate levels are expected to hyperactivate glycogen synthase and may underlie the generation of polyglucosans in Lafora disease. The increased glutamate + glutamine and reduced GABA indicate altered neurotransmission and energy metabolism, which may contribute to the disease's intractable epilepsy. These results suggest a possible basis of polyglucosan formation and potential contributions to the epilepsy of Lafora disease. If confirmed in larger human and animal model studies, measurements of the dysregulated metabolites by magnetic resonance spectroscopy could be developed into non-invasive biomarkers for clinical trials.
PubMed: 38585668
DOI: 10.1093/braincomms/fcae104 -
BMC Anesthesiology Apr 2024There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine... (Review)
Review
BACKGROUND
There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear.
CASE PRESENTATION
A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine.
CONCLUSIONS
After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.
Topics: Humans; Pregnancy; Female; Adult; Anesthesia, Spinal; Cesarean Section; Status Epilepticus; Bupivacaine; Cardiomyopathies; Rhabdomyolysis; Hyperthermia, Induced
PubMed: 38582882
DOI: 10.1186/s12871-024-02485-x -
Case Reports in Anesthesiology 2024Midazolam is a widely used benzodiazepine due to its rapid onset of action and relatively safe side effect profile. It is used for sedation, anxiolysis, and induction of...
Midazolam is a widely used benzodiazepine due to its rapid onset of action and relatively safe side effect profile. It is used for sedation, anxiolysis, and induction of general anesthesia. However, in <1% of instances, it may cause a paradoxical excitement: agitation, restlessness, myoclonus, stiffening of the limbs, and aggression. We report a case report in which preoperative administration of midazolam caused onset of the aforementioned symptoms that were not attenuated by general anesthesia with dexmedetomidine. This case report aims to create awareness about the rare adverse reactions of midazolam and prepare clinicians to manage these situations.
PubMed: 38567024
DOI: 10.1155/2024/4152422 -
European Journal of Clinical... Jun 2024The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients. (Observational Study)
Observational Study
PURPOSE
The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients.
METHODS
A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis.
RESULTS
The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided.
CONCLUSION
Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy.
Topics: Humans; Neurosyphilis; Male; Prospective Studies; Middle Aged; Female; Adult; Anti-Bacterial Agents; Aged; Risk Factors; Prognosis
PubMed: 38557924
DOI: 10.1007/s10096-024-04810-1 -
JACC. Case Reports Mar 2024Dobutamine is a positive inotropic agent often used in treatment of cardiogenic shock. Although there are well-documented adverse effects, dobutamine-induced myoclonus...
Dobutamine is a positive inotropic agent often used in treatment of cardiogenic shock. Although there are well-documented adverse effects, dobutamine-induced myoclonus is a rarely reported phenomenon. Our case offers a direct and temporally related description of myoclonus, with onset observed within hours of dobutamine initiation and complete resolution within minutes of discontinuation.
PubMed: 38549854
DOI: 10.1016/j.jaccas.2024.102255 -
JAMA Network Open Mar 2024West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is...
IMPORTANCE
West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored.
OBJECTIVE
To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023.
EXPOSURE
Immunosuppresion.
MAIN OUTCOMES AND MEASURES
Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS.
RESULTS
Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64).
CONCLUSIONS AND RELEVANCE
In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.
Topics: Adult; Animals; Humans; Male; Middle Aged; Adolescent; Female; West Nile Fever; Cohort Studies; Retrospective Studies; Mosquito Vectors; West Nile virus
PubMed: 38546642
DOI: 10.1001/jamanetworkopen.2024.4294 -
Journal of Child Neurology Mar 2024Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain...
INTRODUCTION
Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain volumes in pediatric opsoclonus-myoclonus ataxia syndrome patients compared with age- and sex-matched healthy children.
PATIENTS AND METHODS
This longitudinal case-control study included brain magnetic resonance imaging (MRI) scans from consecutive pediatric opsoclonus-myoclonus ataxia syndrome patients (2009-2020) and age- and sex-matched healthy control children. FreeSurfer analysis provided automatic volumetry of the brain. Paired tests were performed on the curvature of growth trajectories, with Bonferroni correction.
RESULTS
A total of 14 opsoclonus-myoclonus ataxia syndrome patients (12 female) and 474 healthy control children (406 female) were included. Curvature of the growth trajectories of the cerebral white and gray matter, cerebellar white and gray matter, and brainstem differed significantly between opsoclonus-myoclonus ataxia syndrome patients and healthy control children (cerebral white matter, = .01; cerebral gray matter, = .01; cerebellar white matter, < .001; cerebellar gray matter, = .049; brainstem, < .01).
DISCUSSION/CONCLUSION
We found abnormal brain maturation in the supratentorial brain, brainstem, and cerebellum in children with opsoclonus-myoclonus ataxia syndrome.
Topics: Humans; Female; Male; Longitudinal Studies; Opsoclonus-Myoclonus Syndrome; Magnetic Resonance Imaging; Brain; Child; Case-Control Studies; Child, Preschool; Adolescent; Organ Size
PubMed: 38544431
DOI: 10.1177/08830738241240181 -
Medicina (Kaunas, Lithuania) Feb 2024Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed... (Review)
Review
Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.
Topics: Humans; Myoclonus; Tremor; Dyskinesias; Brain Diseases; Carbamazepine
PubMed: 38541088
DOI: 10.3390/medicina60030362 -
Children (Basel, Switzerland) Mar 2024Opsoclonus-myoclonus ataxia syndrome (OMAS), also known as Kinsbourne syndrome, is a rare disorder that presents with myoclonus, ataxia, abnormal eye movements,... (Review)
Review
Opsoclonus-myoclonus ataxia syndrome (OMAS), also known as Kinsbourne syndrome, is a rare disorder that presents with myoclonus, ataxia, abnormal eye movements, irritability, and sleep disruptions, often in young children. We report a case of an infant barely 6 months old, with no significant past medical history, who presented to the emergency department with tremors, jerking motions of the head and arms, and rapid eye movements. After an extensive workup, she was found to have a neuroblastoma, which was subsequently surgically removed via thoracotomy. Despite an initial improvement in symptoms post-resection, the patient's symptoms recurred. She was subsequently treated with dexamethasone, intravenous immunoglobulin (IVIG), and rituximab. After treatment, the patient was noted to have mild global developmental delays but was otherwise well. This case report highlights the rare occurrence of OMAS in an infant barely 6 months old at diagnosis. Using the PubMed database, a systematic review was conducted to highlight the clinical presentation, diagnosis, and management of OMAS.
PubMed: 38539402
DOI: 10.3390/children11030367 -
Journal of Movement Disorders Mar 2024Since the release of vaccines against COVID-19, there have been reports of vaccine-related neurologic complications. This study aimed to create a descriptive systematic...
OBJECTIVES
Since the release of vaccines against COVID-19, there have been reports of vaccine-related neurologic complications. This study aimed to create a descriptive systematic review of movement disorders associated with COVID-19 vaccines.
METHODS
We described the demographics, clinical presentation, management, outcomes, and proposed patho-mechanism. A systematic review was performed according to the PRISMA guidelines. A standardized tool was used to assess the quality of the cases.
RESULTS
We have identified 8 articles that met our inclusion criteria consisting of 10 patients who developed movement disorders after vaccination. The majority were males (n = 8), with a median age of 64.5 years. The most common movement disorder was hemichorea. The rest presented with generalized chorea with myoclonus, cervical dystonia, and akathisia. Most cases responded with immunotherapy. The standardized tool used showed that most studies have a low risk of bias.
CONCLUSION
The reported incidence of vaccine-related movement disorders was low in occurrence based on available published cases that were found.
PubMed: 38500249
DOI: 10.14802/jmd.24001