Myoclonus:A diagnostic challenge

Myoclonus is een frequent voorkomende hyperkinetische bewegingsstoornis die wordt gekenmerkt door spierschokken (positieve myoclonus) en/of het kortdurend wegvallen van de spiertonus (negatieve myoclonus). De klinische presentatie van myoclonus is heel divers. De schokken kunnen in één of meerdere lichaamsdelen optreden of gegeneraliseerd zijn. Myoclonus kan optreden in het gelaat, de nek, romp en de ledematen. Het kan in rust of juist bij actie optreden en wel of niet stimulusgevoelig zijn. Over het algemeen belemmert myoclonus patiënten ernstig in hun dagelijks functioneren, zoals bij eten/drinken, schrijven en lopen. Myoclonus heeft vele oorzaken, zowel verworden als genetisch. Voor het vaststellen van de onderliggende oorzaak en het bepalen van de juiste behandeling is het belangrijk myoclonus te herkennen en te onderscheiden van andere bewegingsstoornissen zoals bijvoorbeeld tremor en chorea. Na het herkennen kan myoclonus op basis van een anatomische classificatie worden ingedeeld in subtypes, i.e. naar de plaats in het zenuwstelsel waar de schokken ontstaan. Dit zijn corticale (hersenschors), subcorticale (diepe hersenkernen/hersenstam), spinale (ruggenmerg) en perifere (zenuwen/spieren) myoclonus. Daarnaast kunnen schokken ook een uiting zijn van een functionele (psychogene) stoornis. Door myoclonus naar anatomische classificatie te groeperen kan diagnostiek gericht ingezet worden. Dit proefschrift biedt een nieuw diagnostische aanpak voor patiënten met myoclonus. Het beschrijft de uitdagingen en het belang van het nauwkeurig klinisch fenotyperen van zowel motorische als niet-motorische symptomen en de classificatie van het anatomisch myoclonus subtype. Het klinisch neurofysiologisch onderzoek heeft een belangrijke toegevoegde waarde naast de klinische beoordeling in de (sub)classificatie van myoclonus.Myoclonus is a frequently encountered hyperkinetic movement disorder characterized by involuntary jerks, or short interruptions of muscle tone.1 Myoclonus can be anatomically classified into cortical, subcortical, spinal, and peripheral myoclonus2, as well as forming a component of functional movement disorders.3,4 Myoclonus can be present in a large number of both acquired and genetically determined disorders. Accurate diagnosis and classification of its anatomical subtype is important in determining an aetiological differential diagnosis, and guiding therapeutic management. However, clinical diagnosis of myoclonus remains challenging due to its manifestation in a large number of clinical phenotypes, and the number of causative disease causing genes increasing year on year. These challenges and opportunities reinforce the need for a novel and systematic approach to those patients presenting with myoclonus. This thesis provides a new diagnostic approach for patients who present with myoclonus. We describe the challenges and importance of accurate clinical phenotyping, classification of the anatomical myoclonus subtype, and recognition of the frequently accompanying non-motor characteristics. Electrophysiological testing including video-polymyography and advanced techniques (e.g. back-averaging and coherence analysis) proved to play an important contributing role in determining an accurate diagnosis. These, together with the development and wider application of ERD may also demonstrate future applicability in the diagnosis of highly complex hyperkinetic movement disorders, and in particular functional movement disorders

Myoclonus:A diagnostic challenge

Myoclonus is een frequent voorkomende hyperkinetische bewegingsstoornis die wordt gekenmerkt door spierschokken (positieve myoclonus) en/of het kortdurend wegvallen van de spiertonus (negatieve myoclonus). De klinische presentatie van myoclonus is heel divers. De schokken kunnen in één of meerdere lichaamsdelen optreden of gegeneraliseerd zijn. Myoclonus kan optreden in het gelaat, de nek, romp en de ledematen. Het kan in rust of juist bij actie optreden en wel of niet stimulusgevoelig zijn. Over het algemeen belemmert myoclonus patiënten ernstig in hun dagelijks functioneren, zoals bij eten/drinken, schrijven en lopen. Myoclonus heeft vele oorzaken, zowel verworden als genetisch. Voor het vaststellen van de onderliggende oorzaak en het bepalen van de juiste behandeling is het belangrijk myoclonus te herkennen en te onderscheiden van andere bewegingsstoornissen zoals bijvoorbeeld tremor en chorea. Na het herkennen kan myoclonus op basis van een anatomische classificatie worden ingedeeld in subtypes, i.e. naar de plaats in het zenuwstelsel waar de schokken ontstaan. Dit zijn corticale (hersenschors), subcorticale (diepe hersenkernen/hersenstam), spinale (ruggenmerg) en perifere (zenuwen/spieren) myoclonus. Daarnaast kunnen schokken ook een uiting zijn van een functionele (psychogene) stoornis. Door myoclonus naar anatomische classificatie te groeperen kan diagnostiek gericht ingezet worden. Dit proefschrift biedt een nieuw diagnostische aanpak voor patiënten met myoclonus. Het beschrijft de uitdagingen en het belang van het nauwkeurig klinisch fenotyperen van zowel motorische als niet-motorische symptomen en de classificatie van het anatomisch myoclonus subtype. Het klinisch neurofysiologisch onderzoek heeft een belangrijke toegevoegde waarde naast de klinische beoordeling in de (sub)classificatie van myoclonus

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

Improving neurophysiological biomarkers for functional myoclonic movements.

INTRODUCTION: Differentiating between functional jerks (FJ) and organic myoclonus can be challenging. At present, the only advanced diagnostic biomarker to support FJ is the Bereitschaftspotential (BP). However, its sensitivity is limited and its evaluation subjective. Recently, event related desynchronisation in the broad beta range (13-45 Hz) prior to functional generalised axial (propriospinal) myoclonus was reported as a possible complementary diagnostic marker for FJ. Here we study the value of ERD together with a quantified BP in clinical practice. METHODS: Twenty-nine patients with FJ and 16 patients with cortical myoclonus (CM) were included. Jerk-locked back-averaging for determination of the 'classical' and quantified BP, and time-frequency decomposition for the event related desynchronisation (ERD) were performed. Diagnostic gain, sensitivity and specificity were obtained for individual and combined techniques. RESULTS: We detected a classical BP in 14/29, a quantitative BP in 15/29 and an ERD in 18/29 patients. At group level we demonstrate that ERD in the broad beta band preceding a jerk has significantly higher amplitude in FJ compared to CM (respectively -0.14 ± 0.13 and +0.04 ± 0.09 (p < 0.001)). Adding ERD to the classical BP achieved an additional diagnostic gain of 53%. Furthermore, when combining ERD with quantified and classical BP, an additional diagnostic gain of 71% was achieved without loss of specificity. CONCLUSION: Based on the current findings we propose to the use of combined beta ERD assessment and quantitative BP analyses in patients with a clinical suspicion for all types of FJ with a negative classical BP

Distribution and coexistence of myoclonus and dystonia as clinical predictors of SGCE mutation status: a pilot study

Introduction: Myoclonus-dystonia (M-D) is a young onset movement disorder typically involving myoclonus and dystonia of the upper body. A proportion of the cases are caused by mutations to the autosomal dominantly inherited, maternally imprinted, epsilon-sarcoglycan gene (SGCE). Despite several sets of diagnostic criteria, identification of patients most likely to have an SGCE mutation remains difficult. Methods: Forty consecutive patients meeting pre-existing diagnostic clinical criteria for M-D underwent a standardized clinical examination (20 SGCE mutation positive and 20 negative). Each video was reviewed and systematically scored by two assessors blinded to mutation status. In addition, the presence and coexistence of myoclonus and dystonia was recorded in four body regions (neck, arms, legs, and trunk) at rest and with action. Results: Thirty-nine patients were included in the study (one case was excluded owing to insufficient video footage). Based on previously proposed diagnostic criteria, patients were subdivided into 24 "definite," 5 "probable," and 10 "possible" M-D. Motor symptom severity was higher in the SGCE mutation-negative group. Myoclonus and dystonia were most commonly observed in the neck and upper limbs of both groups. Truncal dystonia with action was significantly seen more in the mutation-negative group (p <0.05). Coexistence of myoclonus and dystonia in the same body part with action was more commonly seen in the mutation-negative cohort (p <0.05). Conclusion: Truncal action dystonia and coexistence of myoclonus and dystonia in the same body part with action might suggest the presence of an alternative mutation in patients with M-D

Management of Parkinson’s Disease during pregnancy: Literature review and multi-disciplinary input

Background There are no standardised clinical guidelines for the management of Parkinson’s disease during pregnancy. Increasing maternal age would suggest that the incidence of pregnancy in women diagnosed with Parkinson’s disease is likely to increase. Objective To evaluate the evidence for the treatment of Parkinson’s disease during pregnancy, and to canvass opinion from patients and clinical teams as to the optimum clinical management in this setting. Methods This involved: i) a literature review of available evidence for the use of oral medical therapy for the management of PD during pregnancy, and ii) anonymised survey of patients and clinical teams relating to previous clinical experiences. Results Literature review identified 31 publications (148 pregnancies; 49 Parkinson’s Disease, 2 Parkinsonism, 21 Dopa-Responsive Dystonia, 32 Restless Leg Syndrome, 1 Schizophrenia and 43 unknown indication) detailing treatment with levodopa, and 12 publications with dopamine agonists. Adverse outcomes included seizures and congenital malformations. Survey participation included patients (n=7), neurologists (n=35), PD Nurse Specialists (n=50), obstetricians (n=15) and midwives (n=20) and identified a further 34 cases of pregnancy in women with PD. Common themes for suggested management included: optimisation of motor symptoms, preference for levodopa monotherapy, and normal delivery unless indicated by obstetric causes. Conclusions This study demonstrates the paucity of evidence for decision-making in the medical management of PD during pregnancy. Collaboration is needed to develop a prospective registry, with longitudinal maternal and child health outcome measures, to facilitate consensus management guidelines