Treatment and challenges with antiepileptic drugs in patients with juvenile myoclonic epilepsy.

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges. METHOD: A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007-2018). Additional clinical interviews were performed, and a mixed method approach was applied. RESULTS: Ninety patients with defined JME diagnosis, 54/36 women/men aged 14-39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic-clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life. CONCLUSION: Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME.

The presence of depression and anxiety do not distinguish between functional jerks and cortical myoclonus.

INTRODUCTION: Functional movement disorders are accompanied by a high occurrence of psychopathology and cause serious impairments in quality of life. However, little is known about this in patients with functional jerks and no comparison has been made between patients with functional jerks and organic myoclonus. This case control study compares the occurrence of depression, anxiety and quality of life (HR-QoL) in patients with functional jerks and cortical myoclonus. METHODS: Patients with functional jerks and cortical myoclonus, consecutively recruited, were compared on self-rated anxiety (Beck Anxiety Inventory), depression (Beck Depression Inventory), health-related quality of life (RAND-36), and myoclonus severity (UMRS and CGI-S rating scales). RESULTS: Sixteen patients with functional jerks and 23 with cortical myoclonus were evaluated. There was no significant difference in depression (44% vs. 43%) or anxiety (44% vs. 47%) scores between groups. The HR-QoL was similarly impaired except that functional jerks patients reported significantly more pain (p < 0.05). Only in the functional jerks group myoclonus severity correlated with depression and anxiety. CONCLUSION: Depression and anxiety scores are high and do not discriminate between functional jerks and cortical myoclonus. Quality of life was equally impaired in both sub-groups, but pain was significantly worse in patients with functional jerks.

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Impaired Motor Learning in a Disorder of the Inferior Olive: Is the Cerebellum Confused?

An attractive hypothesis about how the brain learns to keep its motor commands accurate is centered on the idea that the cerebellar cortex associates error signals carried by climbing fibers with simultaneous activity in parallel fibers. Motor learning can be impaired if the error signals are not transmitted, are incorrect, or are misinterpreted by the cerebellar cortex. Learning might also be impaired if the brain is overwhelmed with a sustained barrage of meaningless information unrelated to simultaneously appearing error signals about incorrect performance. We test this concept in subjects with syndrome of oculopalatal tremor (OPT), a rare disease with spontaneous, irregular, roughly pendular oscillations of the eyes thought to reflect an abnormal, synchronous, spontaneous discharge to the cerebellum from the degenerating neurons in the inferior olive. We examined motor learning during a short-term, saccade adaptation paradigm in patients with OPT and found a unique pattern of disturbed adaptation, quite different from the abnormal adaption when the cerebellum is involved directly. Both fast (seconds) and slow (minutes) timescales of learning were impaired. We suggest that the spontaneous, continuous, synchronous output from the inferior olive prevents the cerebellum from receiving the error signals it needs for appropriate motor learning. The important message from this study is that impaired motor adaptation and resultant dysmetria is not the exclusive feature of cerebellar disorders, but it also highlights disorders of the inferior olive and its connections to the cerebellum.

Psychiatric comorbidities in patients from seven families with autosomal dominant cortical tremor, myoclonus, and epilepsy.

OBJECTIVE: The objective of this report was to assess the psychiatric comorbidity in a group of patients affected by autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME). METHODS: Reliable and validated psychodiagnostic scales including the BDI (Beck Depression Inventory), STAI-Y1 and 2 (State-Trait Anxiety Inventory - Y; 1 and 2), MMPI-2 (Minnesota Multiphasic Personality Inventory - 2), and QoLIE-31 (Quality of Life in Epilepsy Inventory - 31) were administered to 20 patients with ADCME, 20 patients with juvenile myoclonic epilepsy (JME), and 20 healthy controls. RESULTS: There was a higher prevalence of mood disorders in patients with ADCME compared to patients with JME and healthy controls, particularly depression (p=0.035 and p=0.017, respectively) and state anxiety (p=0.024 and p=0.019, respectively). Trait anxiety was not different from JME (p=0.102) but higher than healthy controls (p=0.017). The myoclonus score positively correlated with both state (rho: 0.58, p=0.042) and trait anxiety (rho: 0.65, p=0.011). These psychiatric features were also often associated with pathological traits of personality: paranoid (OR: 25.7, p=0.003), psychasthenia (OR: 7.0, p=0.023), schizophrenia (OR: 8.5, p=0.011), and hypomania (OR: 5.5, p=0.022). Finally, in patients with ADCME, decreased quality of life correlated with these psychiatric symptoms. SIGNIFICANCE: Patients with ADCME show a significant psychiatric burden that impairs their quality of life. A comprehensive psychiatric evaluation should be offered at the time of diagnosis to detect these comorbidities and to treat them.

Preliminary neurocognitive outcomes in Jeavons syndrome.

Jeavons syndrome (JS, eyelid myoclonia with absences [EMA]) consists of a triad of symptoms including eyelid myoclonia that may be accompanied by absence seizures, eye closure-induced EEG paroxysms or seizures, and photosensitivity. The age of onset ranges between 2 and 14 years with symptoms peaking between 6 and 8 years of age. Though investigation of the clinical, EEG, and neurological features of JS has occurred, neurocognitive functioning has not been well-delineated despite suggestion that a subtype of the syndrome is characterized in part by cognitive impairment. The purpose of this study was to define neurocognitive functioning in a more detailed manner by examining global IQ and relevant neurocognitive domains (i.e., verbal and nonverbal reasoning, attention, executive functioning, memory) in pediatric patients. The sample (N=6, 4 females) ranged in age from 8 to 15 years (M=11, SD=2.82). All participants completed neuropsychological evaluations. Statistical analyses revealed performance that was below average on measures of global IQ, processing speed and rote, verbal learning coupled with average nonverbal reasoning, and sustained attention. There was also evidence of impaired higher-level verbal reasoning. While global IQ ranged from low average to borderline impaired, no participant could be accurately described as impaired or having intellectual disability (ID) given the consistently average performance noted on some higher-order tasks including nonverbal reasoning.

Periodic eye opening and upward eye deviation accompanied by burst-suppression, as an isolated clinical manifestation of acute post-hypoxic myoclonus.

Various movement disorders have been described following hypoxic-ischaemic brain injury. Here, we present a 72-year-old female patient who developed periodic opening and upward deviation of the eyes as an isolated clinical finding, within 24 hours after cardio-pulmonary arrest. These movements were accompanied by burst-suppression on EEG, and both clinical and electrophysiological findings were suppressed 18 hours after intravenous levetiracetam infusion. The strictly periodic nature of both EEG discharges and eye opening with vertical deviation suggest a cause due to either activation of a subcortical/brainstem pacemaker reciprocally stimulating the cortex, or, alternatively, post-anoxic burst activity of viable cortical neural networks, somehow stimulating the relevant oculomotor nuclei. Together with previous similar cases, our case expands the spectrum of post-resuscitation myoclonus syndromes with the addition of this rare isolated oculopalpebral subtype. [Published with video sequence].

Clinical neurophysiology of psychogenic movement disorders: how to diagnose psychogenic tremor and myoclonus.

Tremor and myoclonus are very common manifestations of psychogenic movement disorders (PMD). In this context, recording of movement disorders aims to provide objective criteria for a positive diagnosis of PMD, independently of the psychological situation. Neurophysiological observations are therefore considered to have a huge impact both on diagnosis and on therapeutic approaches. A specific recording strategy should be employed whenever the medical history or clinical clues raise the eventuality of a PMD. Polymyography coupled to accelerometry is used to demonstrate the major electrophysiological criteria of psychogenic tremor, namely spontaneous variability of tremor frequency and frequency entrainment induced by contralateral rhythmic tasks. Other features, such as paradoxical increase of tremor amplitude with mass loading, co-activation preceding tremor onset and alteration of voluntary contralateral motor performances when tremor is present, are also of interest. The clinical presentation of psychogenic myoclonus is extremely rich and polymorphous and can mimic virtually all forms of cortical, subcortical or spinal myoclonus. Focal, multifocal, axial or generalized jerks can occur. Psychogenic jerks can be sporadic or repetitive, rhythmic or arrhythmic, spontaneous or stimulus-induced. All of these parameters are crucial to determine an individualized neurophysiological strategy. Polymyography is critical to identify a ballistic pattern or a discordant or non-reproducible temporo-spatial organisation of the jerks, but has usually to be completed by other potentially decisive approaches. Reflex psychogenic myoclonus for example displays stimulus-response delays that are too long and variable. Spontaneous psychogenic jerks may be also preceded by a pre-movement potential, detectable by jerk-locked-back-averaging methods.

Psychogenic axial myoclonus: clinical features and long-term outcome.

BACKGROUND: It has been increasingly recognized that the majority of patients with a diagnosis of idiopathic propriospinal myoclonus have either a subsequent clinical course or electrophysiological features indicating that the likely etiology is psychogenic. However, the clinical features of psychogenic axial myoclonus and the long-term outcome have not yet well characterized. PATIENTS AND METHODS: Here we describe clinical findings with representative videos and long term outcomes of 76 patients with an electrophysiologically established diagnosis of psychogenic axial myoclonus. RESULTS: Thirty-seven patients were male. Mean age at onset of symptoms was 40.1 ± 15.1 years. Thirty-two patients (42.1%) presented with isolated axial myoclonus, while 44 patients (57.9%) presented additional features, including involvement of face or limb. In all patients but six (7.9%), the axial myoclonus was in flexion. In more than one-third of patients (42.1%), jerks were multifocal, meaning that there was no clear stereotyped pattern of jerks. Comparison between groups stratified according to the clinical outcome, revealed "delay of diagnosis" as the only predictor of worse outcome. DISCUSSION: We describe here the clinical features and long-term outcome on the largest series of patients with psychogenic axial myoclonus reported in the literature. The description of our series highlights a number of clinical features, which may help neurologists to reach a correct diagnosis on clinical grounds alone. Delay in diagnosis of a psychogenic disorder has a negative effect on long-term outcome.

The eye of the beholder: inter-rater agreement among experts on psychogenic jerky movement disorders.

OBJECTIVE: The current criteria for conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders rely on the assumption that neurological disorders can be distinguished from conversion disorders through clinical assessment. This study aims to assess inter-rater agreement among clinicians with experience in the diagnosis of various hyperkinetic jerky movements, including psychogenic jerks. METHODS: 60 patients with psychogenic jerks, myoclonus or tics were rated by international experts using a standardised survey resembling daily clinical practice. The survey included the following diagnostic steps: a short video offering a visual impression of the patients and their jerky movements, medical history, neurological examination (on video), additional investigations and the findings of a standardised psychiatric interview. The diagnosis and diagnostic certainty were scored after each step. RESULTS: After all clinical information was given, moderate inter-rater agreement was reached (κ=0.56±0.1) with absolute agreement (100%) of experts on the diagnosis in 12 (20%) patients and reasonable agreement (>75%) in 43 (72%) patients. Psychiatric evaluation did not contribute to inter-rater agreement or diagnostic certainty. CONCLUSIONS: Our findings illustrate the fact that experienced movement disorder specialists moderately agree on the clinical diagnosis of jerky movements. Clinical assessment, especially by a team of clinicians in challenging individual cases, might improve diagnostic agreement.

Acquired pendular nystagmus in multiple sclerosis and oculopalatal tremor.

OBJECTIVE: Acquired pendular nystagmus occurs mainly in multiple sclerosis (MS) and focal brainstem lesions. In the later case, it is part of the syndrome of oculopalatal tremor. Even though pathophysiology of acquired pendular nystagmus has been clearly characterized experimentally in both etiologies, there is a persisting ambiguity in clinical literature, which leads one to consider both clinical conditions as a common entity. The objective of our work was to compare in a prospective study clinical features, eye movement recording, and functional consequences of acquired pendular nystagmus in 14 patients with oculopalatal tremor and 20 patients with MS. METHODS: Besides complete neurologic evaluation, evaluation of visual function, 3-dimensional eye movement recording, and functional scores of the Visual Function Questionnaire were recorded. RESULTS: One patient with oculopalatal tremor and 15 patients with MS disclosed signs of optic neuropathy. The nystagmus in the oculopalatal group showed significant larger mean amplitude (8 deg vs 1 deg), higher mean peak velocity (16 deg/s vs 6 deg/s), lower mean frequency (1-3 Hz vs 4-6 Hz), and larger asymmetry and irregularity of ocular oscillations compared to the MS group. The vision-specific health-related quality of life was more deteriorated in the oculopalatal tremor group than in the MS group. CONCLUSIONS: This study emphasizes the need to consider acquired pendular nystagmus in MS and oculopalatal tremor as 2 different clinical entities. This is of particular importance regarding the future evaluation of potential specific effects of pharmacologic agents.

Dreaming experience as a useful diagnostic clue for syncopal episodes.

BACKGROUND: The differential diagnosis between epileptic seizures and syncopes is a common occurrence in clinical practice. The manifestations of seizure and syncope sometimes overlap, and available diagnostic testing often not provides a conclusive answer. Syncope is often preceded by a symptom complex characterized by lightheadedness, generalized muscle weakness, giddiness, visual blurring, tinnitus, and gastrointestinal symptoms. These subjective symptoms are very important in guiding the diagnosis. In our experience, the impression of coming out of a dream after the syncopal episode is a subjective symptom commonly reported by patients, if questioned. METHODS: To verify the occurrence of dreaming experience after syncope and after generalized tonic-clonic seizures (GTCS) and its diagnostic value in differential diagnosis, we asked 100 patients with GTCS and diagnosis of idiopathic generalized epilepsy (Group 1) and 100 patients with a certain diagnosis of syncope (Group 2) whether they have never felt the impression of coming out of a dream after the loss of consciousness (GTCS or syncope, respectively). RESULTS: In Group 1, nobody referred the dreaming experience, whereas in the syncope group, 19% of patients referred this subjective symptom. CONCLUSIONS: Dreaming experience seems to be an additional useful diagnostic clue for syncopal episodes, helping the clinician to differentiate them from seizures.

Is psychopathology part of the phenotypic spectrum of myoclonus-dystonia?: a study of a large Dutch M-D family.

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder frequently caused by mutations in the epsilon-sarcoglycan gene (SGCE, DYT11). In several M-D families, psychiatric symptoms accompanying the motor symptoms have been reported, but a shared genetic etiology remains unclear. OBJECTIVE: To assess neuropsychologic functioning and psychopathology in DYT11 mutation carriers (MC) and their family members using standardized neuropsychologic and psychiatric measures. METHODS: Cognitive and behavioural characteristics of 27 DYT11 MC (14 symptomatic and 13 asymptomatic) and 42 control subjects from 1 large Dutch M-D family were studied. Neuropsychologic tests encompassed memory, language, mental speed, concentration, visuospatial function, and executive functions. Psychiatric assessment addressed qualitative (according to Diagnostic and Statistical Manual-IV criteria) as well as quantitative measures of depression, anxiety, panic attacks, and obsessive-compulsive disorder (OCD), using selfadministered and interview-based scales. RESULTS: No differences were observed on tests of cognitive functioning between DYT11 MC and controls. The frequency of Diagnostic and Statistical Manual-IV diagnoses was higher in the symptomatic DYT11 MC than in controls. The symptomatic DYT11 MC showed more depressive and anxiety symptoms, including panic attacks but no increase of OCD compared with controls. No differences were found between asymptomatic DYT11 MC and controls on any of the psychopathologic tests. CONCLUSIONS: Neither cognitive dysfunction nor OCD seems to be associated with the DYT11 phenotype in this large Dutch pedigree. Depressive and anxiety symptoms are increased in symptomatic, but not in asymptomatic DYT11 MC. Future research has to be carried out to determine whether the psychiatric symptoms are part of or secondary to the DYT11 phenotype.

Neuropsychological findings in patients with Unverricht-Lundborg disease.

The aims of this study were to clarify if patients with Unverricht-Lundborg disease (ULD) have adequate cognitive functioning and to delineate their neuropsychological profile. We evaluated 20 patients with ULD and 20 healthy, matched controls. Mean age of the patients was 35 years, and mean duration of disease, 22 years. Patients underwent a neuropsychological battery exploring intelligence, executive functions, visuospatial and verbal memory, depression, and anxiety. Eleven of 20 subjects with ULD had mild to moderate cognitive impairment. Compared with controls, patients with ULD had lower scores on all short-term memory and executive function tasks. Linear regression analysis disclosed significant associations between impaired performance on some memory tests and duration of disease and between severity of myoclonus and performance on most executive function tests. In conclusion, most patients with ULD seem to be impaired with respect to cognitive abilities. Longitudinal prospective studies are needed to confirm and further expand our findings.

[Movement disorders in stroke]. / Mouvements anormaux et accident vasculaire cérébral.

Dyskinesias are infrequent presentations in acute stroke (1%). They can be found more frequently as delayed presentations after a stroke, but the prevalence is not available from the literature. The full spectrum of hyper- and hypo-akinetic syndromes has been described, but three main pictures are rather specific of an acute stroke: limb shaking, hemichorea-hemiballism and unilateral asterixis. Besides limb shaking, that seems to reflect a transient diffuse ischemia of the frontosubcortical motor pathway, lesions are described at all levels of the frontosubcortical motor circuit including the sensorimotor frontoparietal cortex, the striatum, the pallidum, the thalamic nuclei, the subthalamic nucleus, the substantia nigra, the cerebellum, the brainstem and their interconnecting pathways, as ischemic or hemorrhagic strokes. The preferentially late development of dyskinesia could reflect the return to a more ancestral motor control level, the most functional possible with the remaining configuration of structures, elaborated by brain plasticity after stroke.

Psychogenic propriospinal myoclonus.

We report a case of probable psychogenic propriospinal myoclonus (PSM) in a patient who developed a sudden onset of disabling axial flexor myoclonus following a cosmetic surgical procedure. The electrophysiological findings were consistent with previous reports of PSM. Spontaneous remissions and disappearance of the jerks, sustained for 2 years, following removal of superficial surgical screws support the diagnosis of a psychogenic movement disorder.