Epilepsy with eyelid myoclonia (Jeavons syndrome): Generalized, focal, or combined generalized and focal epilepsy syndrome?

Epilepsy with eyelid myoclonia (EM) or Jeavons syndrome (JS) is an epileptic syndrome related to the spectrum of genetic generalized epilepsies (GGE). We report two untreated children on which EEGs were performed several hours after a generalized tonic-clonic seizure (GTCS). These showed a unilateral, nearly continuous posterior slowing. This slow-wave activity was associated with contralateral epileptiform activity in one case, while in the second case, it was associated with an ipsilateral activity. However, in the latter child, a few months later an independent focus on the contralateral side was observed. A diagnosis of focal occipital lobe epilepsy was proposed in both cases, and one child underwent a left occipital lobectomy at 3.5 years of age. Despite surgery, absences with EM persisted in this child, and a marked photosensitivity to photic stimulation was observed two years later. The focal slow wave activity of one occipital lobe several hours after a GTCS in these two subjects was in favor of a focal onset preceding the generalization. The EEG evidence for independent left and right posterior focus in these two cases, the persistence of EM, and the development of a marked photosensitivity to photic stimulation in the child who underwent an occipital lobectomy, allow us to suggest that JS is associated with a network of bi-occipital hyperexcitability that rapidly engages bilaterally to produce generalized seizures.

[Response to perampanel in a patient with chronic post-hypoxic myoclonus]. / Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.

INTRODUCTION: Chronic post-hypoxic myoclonus is a condition in which the predominant clinical picture is myoclonus following hypoxic brain damage, usually due to cardiorespiratory arrest. It is a condition that is usually treated with antiepileptic drugs, in most cases with a modest clinical response. CASE REPORT: We report the case of a patient who started with jerking movements, compatible with myoclonus in the four limbs and the face the day after recovering from a cardiorespiratory arrest. An electroencephalogram was performed during which the myoclonias were recorded with no electrical correlates. During admission, and in successive visits after discharge, different antiepileptic treatments were tried for the myoclonias, which were refractory and affected the patient's quality of life. Two years after onset, treatment with perampanel up to a dose of 4 mg was initiated and the patient reported a significant clinical improvement, as evidenced in the visits. CONCLUSIONS: Perampanel may be an effective alternative for the treatment of myoclonias in patients with chronic post-hypoxic myoclonus.

TITLE: Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.Introducción. El mioclono posthipóxico crónico es un cuadro cuya clínica predominante son las mioclonías que acontecen tras un daño cerebral hipóxico, generalmente por parada cardiorrespiratoria. Es una entidad que se trata generalmente con fármacos antiepilépticos, con una modesta respuesta clínica en la mayoría de los casos. Caso clínico. Paciente que comienza con movimientos de sacudidas, compatibles con mioclonías de las cuatro extremidades y faciales al día siguiente de una parada cardiorrespiratoria recuperada. Se realizó un electroencefalograma durante el cual se registraron las mioclonías sin presentar correlato eléctrico. Durante el ingreso, y en sucesivas visitas tras el alta, se probaron diferentes tratamientos antiepilépticos para las mioclonías, que fueron refractarias y comportaron una afectación de la calidad de vida del paciente. Tras dos años de evolución, se inició tratamiento con perampanel hasta una dosis de 4 mg y el paciente refirió una mejoría clínica importante, evidenciada en consultas. Conclusiones. El perampanel puede suponer una alternativa eficaz para el tratamiento de las mioclonías en pacientes con mioclono posthipóxico crónico.

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

A movement disorder specialist gets a taste of his own medicine.

We present a case in which a movement disorder neurologist developed two different hyperkinetic movements due to corticospinal tract hyperexcitability, which resolved completely with surgical removal of an epidural spinal canal tumor. The first-hand description of these movements creates a unique opportunity for enhanced insight into these complex movement phenomena.

Lingual epilepsia partialis continua: a detailed video-EEG and neuroimaging study.

Motor epilepsia partialis continua (EPC) is a frequent and widely described variant of simple focal motor status epilepticus. However, lingual EPC is an unusual epileptic condition. We present a case of lingual EPC secondary to low-grade glioma in which the EEG and neuroimaging features were particularly remarkable. The video-EEG showed lateralized periodic discharges with superimposed rhythmic activity and frequent recurrent focal epileptic seizures. Moreover, brain magnetic resonance imaging showed a right temporo-insular cortico-subcortical lesion which was hyperintense on FLAIR, suggestive of low-grade glioma. In addition, diffusion-weighted imaging and arterial spin labelling series showed restricted diffusion in the right temporo-insular and parietal cortex and increased cerebral flow, respectively. All these findings are in keeping with changes related to persistent focal status epilepticus. Finally, we review the literature and discuss the differential diagnosis of this rare epileptic entity. [Published with video sequence].

A Case of Paraneoplastic Myoclonus Attributed to Non-Small Cell Lung Cancer.

Background: It is well known that myoclonus can be a paraneoplastic manifestation of underlying malignancy. Case Report: A 78-year-old male diagnosed with papillary variant non-small cell lung cancer (NSCLC) presented with tremulousness that rapidly evolved into severe, diffuse myoclonus with prominent palatal involvement requiring intubation. The generalized myoclonus resolved with on levetiracetam, chemotherapy and immune modulation. While low titer positive P/Q type calcium channel autoantibodies were detected, it's etiologic relevance is unclear. Discussion: This case highlights a rare neurologic paraneoplastic presentation of papillary NSCLC. It also illustrates the importance of monitoring airway safety when myoclonus is generalized. Highlights: A new, rare paraneoplastic presentation of papillary variant non-small cell lung adenocarcinoma is described. The patient presented with severe diffuse myoclonus with prominent palatal involvement without encephalitis that responded to a combination of chemotherapy, immune modulation, and levetiracetam. No clear causal antibody was found.

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU.

Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

Spinal myoclonus: a rare presentation of cervical myelopathy.

Myoclonus describes a movement disorder characterised by brief, abrupt and involuntary contractions of muscles or groups of muscles, usually associated with intracranial lesions, with limited evidence linking it to spinal pathologies. The pathophysiology of spinal myoclonus is extensive and multifactorial. Infection, intramedullary and extramedullary space-occupying lesions, trauma, vascular abnormalities, degenerative processes and cervical spondylosis have been implicated with the disease, the latter been associated with cervical stenosis with no reported cases linking it to an underlying cervical disc herniation. Although medical therapy with clonazepam, levetiracetam, valproate, tetrabenazine hydrochloride and spinal block injections has been equivocal, spinal myoclonus secondary to disc herniation requires surgical intervention. This report describes a case of segmental spinal myoclonus, secondary to a herniated cervical intervertebral disc. After corpectomy and a cage-augmented fusion technique, the myoclonic symptoms resolved. To our knowledge, this was the first report to describe the successful management of discogenic spinal myoclonus with spinal surgery.

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.

Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H.

OBJECTIVE: To analyze whether KCNQ2 R201C and R201H variants, which show atypical gain-of-function electrophysiologic properties in vitro, have a distinct clinical presentation and outcome. METHODS: Ten children with heterozygous, de novo KCNQ2 R201C or R201H variants were identified worldwide, using an institutional review board (IRB)-approved KCNQ2 patient registry and database. We reviewed medical records and, where possible, interviewed parents and treating physicians using a structured, detailed phenotype inventory focusing on the neonatal presentation and subsequent course. RESULTS: Nine patients had encephalopathy from birth and presented with prominent startle-like myoclonus, which could be triggered by sound or touch. In seven patients, electroencephalography (EEG) was performed in the neonatal period and showed a burst-suppression pattern. However, myoclonus did not have an EEG correlate. In many patients the paroxysmal movements were misdiagnosed as seizures. Seven patients developed epileptic spasms in infancy. In all patients, EEG showed a slow background and multifocal epileptiform discharges later in life. Other prominent features included respiratory dysfunction (perinatal respiratory failure and/or chronic hypoventilation), hypomyelination, reduced brain volume, and profound developmental delay. One patient had a later onset, and sequencing indicated that a low abundance (~20%) R201C variant had arisen by postzygotic mosaicism. SIGNIFICANCE: Heterozygous KCNQ2 R201C and R201H gain-of-function variants present with profound neonatal encephalopathy in the absence of neonatal seizures. Neonates present with nonepileptic myoclonus that is often misdiagnosed and treated as seizures. Prognosis is poor. This clinical presentation is distinct from the phenotype associated with loss-of-function variants, supporting the value of in vitro functional screening. These findings suggest that gain-of-function and loss-of-function variants need different targeted therapeutic approaches.

Ventral medullary control of rapid eye movement sleep and atonia.

Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep. Motor tone during non-REM (NREM) sleep was unaffected in these same animals. Acute chemogenetic activation of pSOM neurons in rats robustly and selectively suppressed REM sleep but not NREM sleep. Similar lesions targeting the more rostral ventromedial medulla (RVM) did not affect sleep or atonia, while chemogenetic stimulation of the RVM produced wakefulness and reduced sleep. Finally, selective activation of vesicular GABA transporter (VGAT) pSOM neurons in mice produced complete suppression of REM sleep whereas their loss increased EMG spikes during REM sleep. These results reveal a key contribution of the pSOM and specifically the VGAT+ neurons in this region in REM sleep and motor control.

Not everything that shakes is a seizure Role of continuous EEG in the intensive care unit.

Treatment of status epilepticus often requires highly sedative drugs with risk of side effects. Correct diagnosis is mandatory in order to prevent introduction of usefulness treatments. We report a case of suspected myoclonic status epilepticus. A thalamic lesion secondary to an osmotic demyelination syndrome was found to be the likely etiology of the myoclonus. Electrophysiological data (electroencephalography and electromyography) provided evidence for a subcortical origin of myoclonus and use of continuous EEG allowed monitoring of drug withdrawal.

Clinical characteristics and etiology of transient myoclonic state in the elderly.

OBJECTIVES: To clarify clinical picture of transient myoclonic state in elderly patients. METHODS: The Aizawa Hospital database was searched to identify all patients with transient myoclonic state with or without asterixis between April 2006 and June 2013. Medical records, brain images and laboratory data including electroencephalograms and electromyograms were reviewed. RESULTS: We found 26 patients: 10 women and 16 men, and their ages ranged from 56 to 96 years (79.7 ± 9.9 years, mean ± standard deviation). The affected sites of the myoclonic jerks were predominantly the lower face, neck and upper extremities. The myoclonus appeared at conscious resting condition, slightly exaggerated by posturing or action. Asterixis was observed in eight patients. Single myoclonic bursts were 1.70 ± 0.94 s long. The interval of myoclonic bursts was 4.47 ± 2.44 s. Single myoclonic bursts were composed of 9.5 ± 2.5 Hz myoclonic contractions, and single myoclonic contractions were 44.4 ± 12.3 ms in duration. Most of the patients suffered from chronic diseases, but they were basically independent in activity of daily living. Oral administration of clonazepam was effective. CONCLUSIONS: Transient myoclonic state has relatively stereotyped features. The pathophysiology may include some metabolic abnormality on a background of age-related arteriosclerotic changes. Its prognosis is benign, and prompt oral administration of clonazepam abolishes it. Further investigations will be needed to clarify its cause and pathophysiology.

Ictal asystole mimicking seizure deterioration in temporal lobe epilepsy.

We report on a patient with temporal lobe epilepsy, secondary to a left lateral temporal cavernoma, in whom the change in seizure semiology suggested recurrence of secondary generalized seizures. Anticonvulsive medication previously controlled secondary generalized seizures over a period of years but focal seizures continued at a lower rate. Continuous video-EEG monitoring revealed ictal asystole associated with myoclonic syncope and falls during focal seizures arising from the left temporal lobe. After implantation of a cardiac pacemaker, no more falls occurred during the focal seizures. In conclusion, recurrence of seizure-associated falls is typically attributed to recurrence of secondary generalized seizures, however, ictal asystole should be considered in selected epilepsy patients as a differential diagnosis of falls. [Published with video sequence].

Refining the phenotype of Unverricht-Lundborg disease (EPM1): a population-wide Finnish study.

OBJECTIVE: This Finnish nationwide study aimed to refine the clinical phenotype variability and to identify factors that could explain the extensive variability in the clinical severity of the symptoms observed among patients with Unverricht-Lundborg disease (progressive myoclonus epilepsy type 1 [EPM1]) homozygous for the dodecamer expansion mutation in the cystatin B (CSTB) gene. METHODS: The study population consisted of 66 (33 men and 33 women) patients with genetically confirmed EPM1 homozygous for the CSTB expansion mutation for whom the sizes of the expanded alleles were determined. The clinical evaluation included videorecorded Unified Myoclonus Rating Scale and retrospectively collected medical history. The navigated transcranial magnetic stimulation test was used to determine motor threshold (MT) and silent period (SP) of the motor cortex. RESULTS: An earlier age at onset for EPM1 and longer disease duration were associated with more severe action myoclonus, lower performance IQ, increased MT, and prolonged SP. The number of dodecamer repeats in CSTB alleles varied between 38 and 77. On average, the size of the longer expanded alleles of patients was independently associated with MT, but exerted only a modulating effect on age at onset, myoclonus severity, and SP. CONCLUSIONS: As a group, earlier disease onset and longer duration are associated with more severe phenotype. Even though the vast majority of patients with EPM1 have a uniform genetic mutation, the actual size of the longer CSTB expansion mutation allele is likely to have a modulating effect on the age at disease onset, myoclonus severity, and cortical neurophysiology.

Eyelid myoclonia seizures in adults: An alternate look at the syndrome paradox.

OBJECTIVES: Eyelid myoclonia (EM), without or with absences (EMA), is induced by eye closure (ECL)-associated generalized paroxysms of polyspikes and waves. Although considered as an epileptic syndrome, it has been listed as a type of seizure in the recent epilepsy classifications, perhaps because of its clinical heterogeneity. In this study, we aimed to specifically study the clinical and electroencephalogram (EEG) features and the prognosis of long-term followed-up adult patients with EMs and to determine common points between EMAs, idiopathic generalized epilepsies (IGEs), and symptomatic epilepsies. METHODS: Between 1996 and November 2011, 61 adult patients with EMs with or without absences and bilateral EEG paroxysms were retrospectively enrolled in the study and followed up for 1-34 years (mean: 5.8 years). RESULTS: According to patient history, seizure semiology, and EEG findings, we classified the patients having EM seizures into three main groups. In group 1 (n=31), all patients had prominent EMs with or without absences associated with upward rolling of eyeballs. The second group included 20 patients with EM seizures associated with generalized tonic-clonic seizures (GTCSs) and/or massive myoclonias. The third group of 7 patients had varying diagnosis of symptomatic epilepsies. In the first group with pure EMA, the diagnosis was more delayed than in the other groups (p=0.01). In the group with pure EMA, EMs continued in adulthood (p=0.00), and only 24% of patients were seizure-free, which was considered poor prognosis. On EEG, occipital (n=3) and frontal (n=4) focal discharges were found in the group with pure EMA. Interestingly, 2 patients with symptomatic epilepsy with frontal lesions also had EM seizures. CONCLUSION: The patients with pure EMA have many similarities to patients with IGEs. We also demonstrated that EMs could be seen as a seizure type in symptomatic epilepsies. Eyelid myoclonia with absences meets the criteria for an epileptic syndrome with the early onset and long duration of seizures, special seizure type, specific EEG findings, possibility of cognitive impairment, precipitating modalities, photosensitivity, and presence of family history, suggesting a strong genetic background.