Myoclonus: an update.

PURPOSE OF REVIEW: Myoclonus, a common hyperkinetic movement disorder, can be disabling for patients. It is important to identify and classify myoclonus correctly to ensure appropriate workup and treatment. While the clinical history, examination, and process of classifying myoclonus remain largely unchanged, new causes and triggers for myoclonus are being elucidated, and new genetic causes have been found. Treatment can be challenging, though preliminary data about new options has been promising. RECENT FINDINGS: In this article, we will briefly outline the process of classifying and treating myoclonus. We will then discuss three specific scenarios where myoclonus has been identified: myoclonus associated with SARS-CoV-2 infections, spinal myoclonus following surgery or anesthesia of the spine, and auricular myoclonus. We will also discuss new genetic findings associated with myoclonus-dystonia, and promising results regarding the use of perampanel in treating myoclonus. SUMMARY: The process of describing unique scenarios associated with myoclonus has helped us build our understanding of the causes, genetic background, expected prognosis, and effective treatment of specific types of myoclonus. We hope that further studies on this topic will help tailor treatment.

Negative Myoclonus: Neurophysiological Study and Clinical Impact in Progressive Myoclonus Ataxia.

INTRODUCTION: Negative myoclonus (NM) is an involuntary movement caused by a sudden interruption of muscular activity, resulting in gait problems and falls. OBJECTIVE: To establish frequency, clinical impact, and neurophysiology of NM in progressive myoclonus ataxia (PMA) patients. METHODS: Clinical, neurophysiological, and genetic data of 14 PMA individuals from University Medical Centre Groningen (UMCG) Expertise Center Movement Disorder Groningen were retrospectively collected. Neurophysiological examination included video-electromyography-accelerometry assessment in all patients and electroencephalography (EEG) examination in 13 individuals. Jerk-locked (or silent period-locked) back-averaging and cortico-muscular coherence (CMC) analysis aided the classification of myoclonus. RESULTS: NM was present in 6 (NM+) and absent in 8 (NM-) PMA patients. NM+ individuals have more frequent falls (100% vs. 37.5%) and higher scores on the Gross Motor Function Classification System (GMFCS) (4.3 ±0.74 vs. 2.5 ±1.2) than NM- individuals. Genetic background of NM+ included GOSR2 and SEMA6B, while that of NM- included ATM, KCNC3, NUS1, STPBN2, and GOSR2. NM was frequently preceded by positive myoclonus (PM) and silent-period length was between 88 and 194 ms. EEG epileptiform discharges were associated with NM in 2 cases. PM was classified as cortical in 5 NM+ and 2 NM- through EEG inspection, jerk-locked back-averaging, or CMC analysis. DISCUSSION: Neurophysiological examination is crucial for detecting NM that could be missed on clinical examination due to a preceding PM. Evidence points to a cortical origin of NM, an association with more severe motor phenotype, and suggests the presence of genetic disorders causing either a PMA or progressive myoclonus epilepsy, rather than pure PMA phenotype. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Diaphragmatic myoclonus post cerebellar hemorrhage: a case report.

BACKGROUND: Diaphragmatic myoclonus is a rare motor disorder that affects muscle tone. It is characterized by involuntary movements of the abdominal wall and rhythmic, repetitive contractions of the accessory or respiratory muscles, all of which are innervated by the cervical nerve roots. CASE DESCRIPTION: We reviewed the case of a 57-year-old male patient who underwent surgery for a left cerebellar hemorrhage. He exhibited persistent myoclonus in the palate, jaw, and thoracoabdominal region. Following treatment, there was a significant reduction in flutter amplitude in these areas. CONCLUSION: The clinical rarity and variability of presentations often make diagnosis challenging and delayed. It is believed that this condition stems from abnormal excitation within the central nervous system or neural pathways that involve the phrenic nerve. Another potential mechanism is the direct irritation of the diaphragm. Ultrasound, chest fluoroscopy, and electromyography (EMG) can support the diagnosis. Various pharmacological and surgical treatments have been tried, yet specific treatment guidelines are still lacking.

Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

Cortical neuronal hyperexcitability and synaptic changes in SGCE mutation-positive myoclonus dystonia.

Myoclonus dystonia is a childhood-onset hyperkinetic movement disorder with a combined motor and psychiatric phenotype. It represents one of the few autosomal dominant inherited dystonic disorders and is caused by mutations in the ε-sarcoglycan (SGCE) gene. Work to date suggests that dystonia is caused by disruption of neuronal networks, principally basal ganglia-cerebello-thalamo-cortical circuits. Investigation of cortical involvement has primarily focused on disruption to interneuron inhibitory activity, rather than the excitatory activity of cortical pyramidal neurons. Here, we have sought to examine excitatory cortical glutamatergic activity using two approaches: the CRISPR/Cas9 editing of a human embryonic cell line, generating an SGCE compound heterozygous mutation, and three patient-derived induced pluripotent stem cell lines, each gene edited to generate matched wild-type SGCE control lines. Differentiation towards a cortical neuronal phenotype demonstrated no significant differences in either early- (PAX6, FOXG1) or late-stage (CTIP2, TBR1) neurodevelopmental markers. However, functional characterization using Ca2+ imaging and microelectrode array approaches identified an increase in network activity, while single-cell patch clamp studies found a greater propensity towards action potential generation with larger amplitudes and shorter half-widths associated with SGCE mutations. Bulk RNA sequencing analysis identified gene ontological enrichment for 'neuron projection development', 'synaptic signalling' and 'synaptic transmission'. Examination of dendritic morphology found SGCE mutations to be associated with a significantly higher number of branches and longer branch lengths, together with longer ion-channel dense axon initial segments, particularly towards the latter stages of differentiation (Days 80 and 100). Gene expression and protein quantification of key synaptic proteins (synaptophysin, synapsin and PSD95), AMPA and NMDA receptor subunits found no significant differences between the SGCE mutation and matched wild-type lines. By contrast, significant changes to synaptic adhesion molecule expression were identified, namely higher presynaptic neurexin-1 and lower postsynaptic neuroligin-4 levels in the SGCE mutation carrying lines. Our study demonstrates an increased intrinsic excitability of cortical glutamatergic neuronal cells in the context of SGCE mutations, coupled with a more complex neurite morphology and disruption to synaptic adhesion molecules. These changes potentially represent key components to the development of the hyperkinetic clinical phenotype observed in myoclonus dystonia, as well a central feature to the wider spectrum of dystonic disorders, potentially providing targets for future therapeutic development.

Are the seizures under control or unnoticed? Electroclinical evaluation of epilepsy with eyelid myoclonia.

PURPOSE: In this study, patients with epilepsy with eyelid myoclonia (E-EM) were evaluated according to their EEG findings, seizure outcomes, and their consistency with the final ictal EEG findings. We also investigated the possible prognostic factors. METHODS: Patients with E-EM and at least two years of follow-up in our clinic were included in the study. We analyzed the presence of eyelid myoclonia, absence and myoclonic seizures, and generalized tonic-clonic seizures for the prior two years and then verified with the latest ictal EEG features. Video-EEGs were analyzed according to the background activity, the existence of generalized spike-wave discharge or polyspike-wave complexes, focal spike-wave discharge, photoparoxysmal responses, and fast activity. RESULTS: 21 patients were involved in this study. In six patients, the seizures were undetected on the first EEGs, whereas they were detected on subsequent ones. The seizures were captured on the first EEGs of six patients; however, they disappeared on subsequent ones. Only one patient had seizures detected on every EEG. The consistency of the seizures was variable in eight patients. At the final follow-up, seizures were reported as being under control for more than two years in 12 patients, according to patients and their parents' reports. However, ictal EEG findings were detected in six of these patients. No electroclinical feature was associated with seizure freedom. CONCLUSION: This study provides further evidence that seizure freedom in E-EM patients is overestimated. The patients and their parents may not be aware of the seizures. Therefore, video-EEG monitorization is essential during follow-up.

Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

Early-onset palatal myoclonus in Wernekinck commissure syndrome secondary to caudal paramedian midbrain infarction: A case report and a mini review of the literature.

INTRODUCTION: Wernekinck commissure syndrome (WCS) is an extremely rare midbrain syndrome, which selectively destroys the decussation of the superior cerebellar peduncle and the central tegmental tract, which commonly presents with bilateral cerebellar ataxia, dysarthria, and internuclear ophthalmoplegia. Palatal myoclonus in Wernekinck commissure syndrome is uncommon and often occurs as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. MATERIAL AND METHOD: A patient with WCS, admitted to our hospital from December 2023, was chosen for this study, and the syndrome's clinical manifestations, imaging features, and etiology were retrospectively analyzed based on the literature. A 68-year-old right-handed East Asian man presented with dizziness, slurred speech, difficulty with swallowing and walking, and rhythmic contractions of the soft palate. He had several risk factors for ischemic cerebrovascular diseases (age, sex, dyslipidemia, hypertension and smoking history). Brain magnetic resonance imaging showed hyperintensity of DWI and hypointensity of ADC at the caudal midbrain which was around the paramedian mesencephalic tegmentum anterior to the aqueduct of midbrain. RESULTS: He was diagnosed with Wernekinck commissure syndrome (WCS) secondary to caudal paramedian midbrain infarction. He was started on dual antiplatelet therapy (aspirin and clopidogrel) and intensive statin therapy. Blood pressure and glucose were also adjusted. His symptoms improved rapidly, and he walked steadily and speak clearly after 7 days of treatment. CONCLUSIONS: Palatal myoclonus is known to occur as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. However, Our case suggests that palatal myoclonus can occur in the early stages in WCS.

Flapping Tremor: Unraveling Asterixis-A Narrative 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.

Clinical presentation and evaluation of epilepsy with eyelid myoclonia: Results of an international expert consensus panel.

OBJECTIVE: The objective of this study was to determine areas of consensus among an international panel of experts for the clinical presentation and diagnosis of epilepsy with eyelid myoclonia (EEM; formerly known as Jeavons syndrome) to improve a timely diagnosis. METHODS: An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This international expert panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the diagnosis of EEM. RESULTS: There was a strong consensus that EEM is a female predominant generalized epilepsy syndrome with onset between 3 and 12 years of age and that eyelid myoclonia must be present to make the diagnosis. There was a strong consensus that eyelid myoclonia may go unrecognized for years prior to an epilepsy diagnosis. There was consensus that generalized tonic-clonic and absence seizures are typically or occasionally seen in patients. There was a consensus that atonic or focal seizures should lead to the consideration of reclassification or alternate diagnoses. There was a strong consensus that electroencephalography is required, whereas magnetic resonance imaging is not required for diagnosis. There was a strong consensus to perform genetic testing (either epilepsy gene panel or whole exome sequencing) when one or a combination of factors was present: family history of epilepsy, intellectual disability, or drug-resistant epilepsy. SIGNIFICANCE: This international expert panel identified multiple areas of consensus regarding the presentation and evaluation of EEM. These areas of consensus may be used to inform clinical practice to shorten the time to the appropriate diagnosis.

Familial adult myoclonus epilepsy: Clinical findings, disease course, and comorbidities.

Familial adult myoclonus epilepsy (FAME) is an autosomal dominant condition characterized by the association of myoclonic tremor and epilepsy mainly with onset in adulthood. The clinical course is non-progressive or slowly progressive, as epilepsy is commonly controlled with appropriate antiseizure medication and individuals have a normal life expectancy. However, the myoclonus severity increases with age and leads to some degree of disability in the elderly. Because the non-coding repeat expansions responsible for FAME are not detected by routine genetic tests being used at this time, a clinical diagnosis accompanied by neurophysiological testing remains essential to guide the geneticist on the selection of the specific genetic technique.

Differential diagnosis of familial adult myoclonic epilepsy.

OBJECTIVE: Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses. METHODS: The differential diagnoses and frequent presentations leading to misdiagnosis of FAME were investigated from the available literature and reported based on an expert opinion survey. RESULTS: The phenotypic features of FAME, including generalized tonic-clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug-induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease, whereas, in adulthood, late-onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. Electroencephalography (EEG) may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike-wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder. SIGNIFICANCE: Recognition of FAME will inform prognostic and genetic counseling and diagnosis of the insidious progression, which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow the identification of underlying etiology.

A reliable automatic algorithm to score fragmentary myoclonus.

Excessive fragmentary myoclonus (EFM) is an incidental polysomnographic finding requiring documentation of ≥20 minutes of NREM sleep with ≥5 fragmentary myoclonus (FM) potentials per minute. Manual FM scoring is time-consuming and prone to inter-rater variability. This work aimed to validate an automatic algorithm to score FM in whole-night recordings. One expert scorer manually scored FM in the anterior tibialis muscles in 10 polysomnographies of as many subjects. The algorithm consisted of two steps. First, parameters of the automatic leg movement identification algorithm of the BrainRT software (OSG, Belgium) were modified to identify FM-like activity. Second, a post-processing algorithm was implemented to remove FM activity not meeting sufficient amplitude criteria. The parameter choice and the post-processing were optimised with leave-one-out cross-validation. Agreement with the human scorer was measured with Cohen's kappa (k) and correlation between manual and automatic FM indices in different sleep stages was evaluated. Agreement in identifying patients with EFM was computed. The algorithm showed substantial agreement (average k > 0.62) for all sleep stages, except for W, where a moderate agreement was observed (average k = 0.58). Nonetheless, the agreement between human scorer and the algorithm was similar to previously reported values of inter-rater variability for FM scoring. Correlation coefficients were over 0.96 for all sleep stages. Furthermore, the presence/absence of EFM was correctly identified in 80% of the subjects. In conclusion, this work presents a reliable algorithm for automatic scoring of FM and EFM. Future studies will apply it to objectively and consistently evaluate FM indices and the presence of EFM in large populations.

Reading epilepsy today: A scoping review and meta-analysis of reports of the last three decades.

BACKGROUND AND AIM: Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of the article was to summarize knowledge and recent developments in the field of reading-induced seizures by reviewing all cases for which data were reported within the last three decades. METHODS: A scoping systematic review of demographic, clinical, electroencephalography (EEG) and imaging data of cases with reading-induced seizures reported in PubMed and Web of Science between 1991-01-01 and 2022-08-21 and a meta-analysis of the findings. RESULTS: The review included 101 case reports of epilepsy with reading-induced seizures (EwRIS) from 42 articles. The phenomenon was more prevalent among males (67, 66.3% vs. 34, 33.7%) with an average age of onset of 18.3 ± 7.9 years. When reported, 30.8% of patients had a family history of epilepsy. Orofacial reflex myocloni (ORM) were the most frequent manifestation (68, 67.3% cases), other presentations, mostly in addition to ORM, included visual, sensory or cognitive symptoms, non-orofacial myoclonic seizures, and absence seizures. Within the sample, 75 (74.3%) patients were identified as having primary reading epilepsy (PRE), 13 (12.9%) idiopathic generalised epilepsy (IGE) and 13 (12.9%) focal epilepsies. Advanced EEG and functional imaging data suggest that the basic mechanism of reading-induced seizures is probably similar despite different symptoms and consists of upregulation of the complex cerebral subsystem involved in reading. Ictogenesis and resulting symptomatology may then depend on predominant sensory or proprioceptive stimuli during reading. CONCLUSION: In most cases, reading-induced seizures were confirmed to belong to a particular epilepsy syndrome of PRE. However, there were substantial subgroups with IGE and focal epilepsies. Most likely, reading-induced seizures occur as an abnormal response to extero- or proprioceptive input into an upregulated cortical network subserving reading. Most recent researchers consider EwRIS a system epilepsy.

Early recognition of SGCE-myoclonus-dystonia in children.

AIM: To evaluate early dystonic features in children and adolescents with SGCE-myoclonus-dystonia. METHOD: In this cross-sectional study, 49 patients (26 females and 23 males) with SGCE-myoclonus-dystonia (aged 15y 2mo, SD 12y) with childhood-onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. RESULTS: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby-horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self-reported disability. INTERPRETATION: Children with SGCE-myoclonus-dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. WHAT THIS PAPER ADDS: Most children with SGCE-myoclonus-dystonia got writer's cramp and had walking and running dystonia. Writer's cramp was a key feature and should prompt SGCE genetic investigation. 'Circular shaking leg', 'dragging leg', and 'hobby-horse gait' were recognized as early gait patterns. Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms. Action dystonia rating scales are valid tools to assess severity in children.

Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome).

PURPOSE: To describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome. METHOD: Retrospective analysis from two French tertiary centers. RESULTS: Forty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1-15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1-44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%). CONCLUSION: Patients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy.

Inspiratory laryngeal stridor as the main feature of progressive encephalomyelitis with rigidity and myoclonus: a case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is an acute, potentially life-threatening, yet curable neuro-immunological disease characterized by spasms, muscular rigidity, and brainstem and autonomic dysfunction. The clinical features of glycine receptor (GlyR) antibody-positive PERM may be overlooked, particularly with some unusual symptoms. CASE PRESENTATION: A 52-year-old man was admitted to the hospital for evaluation of tension headache for 20 days and mild dysarthria. These symptoms were followed by panic, profuse sweating, severe dysarthria, dizziness, unsteady gait, and paroxysmal muscle spasms. Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal. The patient's condition steadily deteriorated. He repeatedly presented with rigidity, panic attacks, severe anxiety, paroxysmal inspiratory laryngeal stridor, cyanosis of the lips, and intractable epilepsy. Electromyography showed multiple myoclonic seizures, a single generalized tonic-clonic seizure, and a single generalized tonic seizure. Screening for autoimmune encephalitis antibodies revealed anti-GlyR antibodies in his cerebrospinal fluid. Immunomodulatory pulse therapy with steroids and immunoglobulin resulted in expeditious improvement of the symptoms within 2 weeks, and a follow-up at 5 weeks showed consistent clinical improvement. CONCLUSION: Our case highlights that inspiratory laryngeal stridor is an important symptom of PERM. Our observation widens the spectrum of the clinical presentation of anti-GlyR antibody-positive PERM, where early identification is a key to improving prognosis.

Epilepsy and Sleep in the ATR-X Syndrome.

BACKGROUND: This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome. DESIGN: In this cross-sectional study, 37 participants with ATR-X syndrome aged 1.8 to 44 years were studied using a customized epilepsy questionnaire, review of electroencephalography (EEG) findings, the modified Sleep Questionnaire of Simonds and Parraga and 2-week sleep diary. RESULTS: Eleven participants had a clinical diagnosis of generalized epilepsy (29.7%). Seizure types were generalized tonic-clonic seizures, absences, and myoclonia. Interictal EEG recordings in participants with GTCS showed no epileptic discharges in 78%. Similarly, EEG recordings during myoclonia and absences often demonstrated no epileptic discharges. Sleep problems (difficulty falling or maintaining sleep, and early awakening) were reported in 70%. Participants with reported sleep problems went to bed earlier (p = 0.027) and had a lower sleep efficiency (p < 0.01) than participants without sleep problems, but as a group they both had a sufficient total sleep time (9 hours and 52 minutes vs. 10 hours and 55 minutes). Sixteen participants (43.2) used medication to improve sleep (predominantly melatonin n = 10), being effective in only two. CONCLUSION: One-third of participants with ATR-X syndrome had a clinical diagnosis of epilepsy, but the absence of EEG abnormalities in suspected epileptic seizures questions this diagnosis in these patients. EEG recording during seizure like symptoms is warranted before making an epilepsy diagnosis. Seventy percent experienced sleep problems, although total sleep time was normal in most participants. Long bedtimes might have a negative influence on sleep efficiency.

Status Myoclonus with Post-cardiac-arrest Syndrome: Implications for Prognostication.

BACKGROUND: Status myoclonus (SM) after cardiac arrest (CA) may signify devastating brain injury. We hypothesized that SM correlates with severe neurologic and systemic post-cardiac-arrest syndrome (PCAS). METHODS: Charts of patients admitted with CA to Mayo Clinic Saint Marys Hospital between 2005 and 2019 were retrospectively reviewed. Data included the neurologic examination, ancillary neurologic tests, and systemic markers of PCAS. Nonsustained myoclonus was clinically differentiated from SM. The cerebral performance category score at discharge was assessed; poor outcome was a cerebral performance category score > 2 prior to withdrawal of life-sustaining therapies or death. RESULTS: Of 296 patients included, 276 (93.2%) had out-of-hospital arrest and 202 (68.5%) had a shockable rhythm; the mean time to return of spontaneous circulation was 32 ± 19 min. One hundred seventy-six (59.5%) patients had a poor outcome. One hundred one (34.1%) patients had myoclonus, and 74 (73.2%) had SM. Neurologic predictors of poor outcome were extensor or absent motor response to noxious stimulus (p = 0.02, odds ratio [OR] 3.8, confidence interval [CI] 1.2-12.4), SM (p = 0.01, OR 10.3, CI 1.5-205.4), and burst suppression on EEG (p = 0.01, OR 4.6, CI 1.4-17.4). Of 74 patients with SM, 73 (98.6%) had a poor outcome. A nonshockable rhythm (p < 0.001, OR 4.5, CI 2.6-7.9), respiratory arrest (p < 0.001, OR 3.5, CI 1.7-7.2), chronic kidney disease (p < 0.001, OR 3.1, CI 1.6-6.0), and a pressor requirement (p < 0.001, OR 4.4, CI 1.8-10.6) were associated with SM. No patients with SM, anoxic-ischemic magnetic resonance imaging findings, and absent electroencephalographic reactivity had a good outcome. CONCLUSIONS: Sustained status myoclonus after CPR is observed in patients with other reliable indicators of severe acute brain injury and systemic PCAS. These clinical determinants should be incorporated as part of a comprehensive approach to prognostication after CA.

A Biomarker for Benign Adult Familial Myoclonus Epilepsy: High-Frequency Activities in Giant Somatosensory Evoked Potentials.

BACKGROUND: Benign adult familial myoclonus epilepsy (BAFME) is one of the diseases that cause cortical myoclonus (CM) with giant somatosensory evoked potentials (SEPs). There are no useful diagnostic biomarkers differentiating BAFME from other CM diseases. OBJECTIVE: To establish reliable biomarkers including high-frequency oscillations (HFOs) with giant SEPs for the diagnosis of BAFME. METHODS: This retrospective case study included 49 consecutive CM patients (16 BAFME and 33 other CM patients) who exhibited giant P25 or N35 SEPs. SEPs were processed by a band-pass filter of 400-1000 Hz to analyze HFOs. Clinical and SEP findings were compared between (1) BAFME and other CM groups and (2) patients with presence and absence of P25-HFOs (HFOs superimposed on giant P25). The diagnostic power of each factor for BAFME was calculated. RESULTS: All 16 BAFME patients showed SEP P25-HFOs with significantly higher occurrence (P < 0.0001) compared with that of other CM groups. The presence of P25-HFOs significantly correlated with a BAFME diagnosis (P < 0.0001) and high SEP P25 and N35 amplitudes (P = 0.01 and P < 0.0001, respectively). BAFME was reliably diagnosed using P25-HFOs with high sensitivity (100%), specificity (87.9%), positive predictive value (80%), and negative predictive value (100%), demonstrating its superiority as a diagnostic factor compared to other factors. CONCLUSIONS: P25-HFOs with giant SEPs is a potential biomarker for BAFME diagnosis. P25-HFOs may reflect cortical hyperexcitability partly due to paroxysmal depolarizing shifts in epileptic neuronal activities and higher degrees of rhythmic tremulousness than those in ordinary CM. © 2021 International Parkinson and Movement Disorder Society.