Current management of myasthenia gravis in Belgium: a single-center experience.

INTRODUCTION: As new treatments are becoming available for patients with myasthenia gravis (MG), it is worth reflecting on the actual status of MG treatment to determine which patients would most likely benefit from the new treatments. METHODS: We reviewed the clinical files of all MG patients seen at the Department of Neurology of the Antwerp University Hospital during the years 2019, 2020 and 2021. RESULTS: 163 patients were included. Age at diagnosis varied from the first to the eighth decades, with a peak of incidence from 60 to 70 years for both genders, and an additional peak from 20 to 30 years in women. Diplopia and ptosis were by far the most common onset symptom. At maximum disease severity, 24% of the patients still had purely ocular symptoms and 4% needed mechanical ventilation. 97% of the patients received a treatment with pyridostigmine and 68% with corticosteroids, often in combination with immunosuppressants. More than half reported side effects. At the latest visit, 50% of the patients were symptom-free. Also, half of the symptomatic patients were fulltime at work or retired with no or mild limitations in daily living. The remaining patients were working part-time, on sick leave, or retired with severe limitations. DISCUSSION AND CONCLUSION: The majority of MG patients are doing well with currently available treatments, but often at the cost of side effects in the short and in the long term. A significant group is in need of better treatments.

Caspr2 autoantibody-associated Morvan syndrome predating thymoma relapse by 30 months.

Morvan's syndrome (MoS) is a rare autoimmune disorder characterized by central nervous system involvement, autonomic dysfunction and peripheral nerve hyperexcitability. MoS is believed to be caused by autoantibodies targeting contactin-associated protein 2 (Caspr2), a subunit of the neuronal voltage-gated potassium channel (VGKC) complex, usually in association with thymoma, less commonly with other malignancies. This case highlights an exceptional case of severe sleep disturbances and behavioural changes due to MoS, in a patient who would present with and be treated successfully for a second relapse of thymoma 30 months later. Originally he suffered from ocular myasthenia, another autoimmune disorder, which led to diagnosis of his original thymoma and first relapse.

Myasthenia gravis appearing after thymectomy heralding recurrent thymoma.

INTRODUCTION: Thirty to fifty percent of thymoma patients develop myasthenia gravis (MG). In 1.5-28% of cases, MG appears many years after removal of a thymoma. PATIENTS AND METHODS: We present a case report of a 72-year-old female who presented with MG four months after total thymectomy. RESULTS: A 72-year-old female patient presents with MG four months after total thymectomy. Imaging revealed a PET-positive nodule anterior to the superior vena cava. By median sternotomy, the nodule was removed at our hospital. Pathology confirmed a recurrent B2/B3 thymoma with R0 resection. No adjuvant therapy was given. Large population studies show the appearance of new-onset MG associated with recurrent thymoma in 3% of cases. CONCLUSIONS: New-onset MG postthymectomy heralds recurrent disease in 3% of cases. Thorough screening is needed in such patients.

The effect of a single botulinum toxin treatment on somatosensory processing in idiopathic isolated cervical dystonia: an observational study.

BACKGROUND: Patients with idiopathic cervical dystonia (CD) experience involuntary neck muscle contractions, abnormal head position and pain accompanied by dysfunctions in somatosensory processes such as postural control, cervical sensorimotor and perception of visual verticality. First-line treatment is injection with botulinum toxin (BoNT). It remains unclear whether this affects sensorimotor processes. AIM: To investigate the effect of first-line care on deficiencies in somatosensory processes. METHODS: In this observational study, 24 adult patients with idiopathic CD were assessed three times over a treatment period of 12 weeks following a single treatment with BoNT. Disease severity was assessed by a disease-specific questionnaire, rating scale and the visual analogue scale. Seated postural control was assessed with posturography, cervical sensorimotor control was assessed by the joint repositioning error with an eight-camera infrared motion analysis system during a head repositioning accuracy test and perception of visual verticality was assessed with the subjective visual vertical test. RESULTS: Disease symptoms significantly improved following BoNT injections and deteriorated again at 12 weeks. This improvement was not accompanied by improved postural control, cervical sensorimotor control and perception of visual verticality. A trend toward improvement was seen; however, it did not reach the level of the control population. CONCLUSION: The peripheral and central treatment effects of BoNT have little to no effect on postural and cervical sensorimotor control in CD. Further research may explore whether sensory training or specialized exercise therapy improves somatosensory integration and everyday functioning in patients with CD.

Is perception of visual verticality intact in patients with idiopathic cervical dystonia?

Idiopathic cervical dystonia (CD) is a focal dystonia characterized by an abnormal tilted or twisted head position. This abnormal head position could lead to a distorted perception of the visual vertical and spatial orientation. The aim of this cross-sectional study was to investigate whether the perception of the visual vertical is impaired in patients with CD. The subjective visual vertical test (SVV) was measured in 24 patients with CD and 30 controls. The SVV test is conducted in a completely darkened room. A laser bar is projected on an opposing white wall, which is deviated from the earth's gravitational vertical. Participants were seated with their head unrestrained and were instructed to position this bar vertically. The deviations in degrees (°) are corrected for the side of laterocollis in order to measure the E-effect. We found that patients were able to position the laser bar as equally close to the earth's gravitational vertical as controls (+ 0.67° SD ± 2.12 vs + 0.29° SD ± 1.08, p = 0.43). No E-effect was measured. Notwithstanding the abnormal position of the head, the perception of the visual vertical in patients with idiopathic CD is intact, possibly because of central neural compensatory mechanisms.

Cervical sensorimotor control in idiopathic cervical dystonia: A cross-sectional study.

OBJECTIVES: Patients with idiopathic adult-onset cervical dystonia (CD) experience an abnormal head posture and involuntary muscle contractions. Although the exact areas affected in the central nervous system remain uncertain, impaired functions in systems stabilizing the head and neck are apparent such as the somatosensory and sensorimotor integration systems. The aim of the study is to investigate cervical sensorimotor control dysfunction in patients with CD. MATERIAL AND METHODS: Cervical sensorimotor control was assessed by a head repositioning task in 24 patients with CD and 70 asymptomatic controls. Blindfolded participants were asked to reposition their head to a previously memorized neutral head position (NHP) following an active movement (flexion, extension, left, and right rotation). The repositioning error (joint position error, JPE) was registered via 3D motion analysis with an eight-camera infrared system (VICON ® T10). Disease-specific characteristics of all patients were obtained via the Tsui scale, Cervical Dystonia Impact Profile (CDIP-58), and Toronto Western Spasmodic Rating Scale. RESULTS: Patients with CD showed larger JPE than controls (mean difference of 1.5°, p < .006), and systematically 'overshoot', i.e. surpassed the NHP, whereas control subjects 'undershoot', i.e. fall behind the NHP. The JPE did not correlate with disease-specific characteristics. CONCLUSIONS: Cervical sensorimotor control is impaired in patients with CD. As cervical sensorimotor control can be trained, this might be a potential treatment option for therapy, adjuvant to botulinum toxin injections.

Measuring Disability in Patients With Cervical Dystonia According to the International Classification of Functioning, Disability and Health.

Cervical Dystonia (CD) is a rare movement disorder characterized by an abnormal head position. This cross-sectional study describes the health status and severity of disability using an internationally agreed language by applying the International Classification of Functioning, Disability and Health (ICF). Two disease-specific rating scales were administered to 30 patients with CD. By linking the individual answers to the ICF model, the frequency and severity of reported impairments and restrictions were estimated using a count-based method. Results showed that patients most frequently reported impairments linked to "neuromusculoskeletal and movement-related functions" and "mental functions." Most restrictions in activities were related to "interpersonal interactions and relations," "major life areas," and "community, social, and civic life." One third of the reported impairments can be labeled as severe disability. The findings show that CD causes disability in multiple levels of a patients' functioning in life, well beyond the cervical area.

The effectiveness of physiotherapy for cervical dystonia: a systematic literature review.

Cervical dystonia is a form of adult-onset, focal dystonia characterized by involuntary contractions of the neck muscles, leading to a disabling, abnormal head posture. CD has a great impact on the activities of daily living (ADL) and quality of life. Currently, the most widely used and recommended first line treatment is botulinum toxin type A (BoNT/A) injections. Physiotherapy is a potentially useful adjuvant, but little is known about its effectiveness. Consequently, our objective was to investigate the effectiveness of physiotherapy alone or as an adjuvant treatment to BoNT/A injections in cervical dystonia (CD) by means of a systematic literature review. Two online databases, PubMed and Web of Science, were searched for articles describing the effectiveness of physiotherapy treatment for CD. After screening, based on predefined in- and exclusion criteria, 16 studies were retained. Their methodological quality was assessed according to Cochrane guidelines. The methodological quality of most studies was low. Examples of shortcomings are small sample sizes, lack of randomization or blinding, and diversity in therapeutic techniques and outcome measures. Only seven studies were clinical trials; the remaining were either case reports or case series. The reported physiotherapy treatments included EMG biofeedback training, muscular elongation, postural exercises and electrotherapy. Improvements in head position, pain, cervical range of motion, quality of life and ADL have been reported, which is promising. Cautious interpretation on the effectiveness of physiotherapy as an adjuvant therapy is required. Before firm conclusions can be drawn, additional high quality trials are needed.

Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the presynaptic neuromuscular junction, typically occurring in adults as a paraneoplastic syndrome. Only rare cases have been reported in childhood. In most childhood cases, malignancies have not been detected but a propensity to autoimmune disease was noticed. Nevertheless, little is known about genetic factors that may contribute to the susceptibility of an individual to develop LEMS. We report on a 13-year-old girl, known with the Xp11.22-p11.23 duplication syndrome, who presented with severe non-paraneoplastic LEMS. The potential role of this microduplication syndrome in the development of LEMS is explored. Previous literature review of twelve Xp11.2 duplication syndrome patients showed that three of them suffered from various autoimmune diseases. The common duplicated region in those three patients and the presented case comprises 12 disease-associated genes including the FOXP3 (Forkhead Box P3) and WAS (Wiskott-Aldrich syndrome) gene, both implicated in immune function. However, it is unclear whether increased gene dosage of one or both of these genes can cause susceptibility to autoimmune diseases. In conclusion, the presented case emphasizes that autoimmune disease is a recurrent feature of the Xp11.2 duplication syndrome, which should be considered in the follow-up of these patients. The exact mechanism underlying this autoimmune propensity remains to be elucidated.

Childhood chronic inflammatory demyelinating polyneuroradiculopathy--three cases and a review of the literature.

BACKGROUND: Chronic inflammatory demyelinating polyneuroradiculopathy (CIDP) is an autoimmune disease of the peripheral nervous system, causing demyelination and even axonal degeneration. In children, abnormal gait as a first sign of muscle weakness is a frequent reason to seek medical attention. Diagnosis is made on the basis of clinical characteristics, electromyography and nerve conduction studies, and elevated protein in cerebrospinal fluid. AIMS: We present three new cases of CIDP. The literature was reviewed in order to obtain more information on presentation, outcome and treatment strategies world-wide. RESULTS: The course of disease can be relapsing-remitting or chronic-progressive. From case series it is known that first-line immunotherapy (intravenously administered immunoglobulin, corticosteroids or plasmapheresis) is initially of benefit in most children with CIDP. There is little evidence, however, on second-line therapies as azathioprine, cyclosporine A, mycophenolate mofetil, methothrexate, cyclophosphamide and IFN alpha. Although the outcome of children with CIDP is generally regarded to be good, disease related disability can be severe. CONCLUSION: Childhood CIDP is rare. In general and in comparison to adults, children tend to have a more acute progressive onset, with more severe symptoms. Showing a higher tendency towards a relapsing-remitting course, children often show a better and faster improvement after therapy, and a more favorable outcome. Swift recognition of CIDP and empiric start of treatment are considered important to avoid potentially irreversible axonal damage and associated disability. Response to first-line therapies is usually favorable, however recommendations regarding the choice of second-line therapy can only be made on the basis of current practice described in case reports. Safety and efficacy data are insufficient. The cases described show that trial and error are often involved in finding an optimal treatment strategy, especially in those patients refractory to first-line treatment or with a prolonged course. Clinical experience with immunomodulatory treatment is paramount when treating children with CIDP.

Diagnostic utility of stimulated single-fiber electromyography of the orbicularis oculi muscle in patients with suspected ocular myasthenia.

Stimulated single-fiber electromyography (SSFEMG) is a valuable diagnostic tool in cases of myasthenia gravis with limited disease. From 1990 to 2008 SSFEMG in the orbicularis oculi muscle (OO) was performed in a cohort of 456 patients referred with clinical suspicion of myasthenia gravis (MG) and exclusively ocular symptoms. A diagnosis of MG was made on clinical grounds in 103 patients. In this patient cohort, the specificity of SSFEMG for myasthenia was 97%, and the sensitivity was 80%. MG patients with a normal SSFEMG had a benign clinical course. This study confirms a high specificity and sensitivity of SSFEMG when it is performed on patients suspected to have ocular MG. In such patients, a normal SSFEMG of the OO predicts a benign clinical course.

Quality of life after anterior mediastinal mass resection: a prospective study comparing open with robotic-assisted thoracoscopic resection.

OBJECTIVE: To prospectively evaluate quality of life (QoL) evolution after robotic-assisted thoracoscopic or open anterior mediastinal tumour resection with the European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire-C30 and the lung cancer-specific module, LC-13. METHODS: From January 2004 to December 2008, QoL was prospectively recorded in all patients undergoing surgery for mediastinal tumours. A total of 14 patients underwent thoracoscopic resection using the da Vinci robotic system (Intuitive Surgical, Inc., Mountain View, CA, USA), and 22 patients open resection through sternotomy. Questionnaires were administered before surgery and 1, 3, 6 and 12 months, postoperatively, with response rates of 100%, 86.1%, 94.4%; 75.0% and 86.1%, respectively. RESULTS: Both approaches had comparable preoperative patients' characteristics and QoL subscales. Open resection by sternotomy was characterised by a significant decrease in general functioning 1 month after surgery (physical functioning p=0.001, role functioning p=0.001, and social functioning p=0.044). Patients also complained of increased thoracic pain in the first 3 months after surgery (p=0.017). After a da Vinci robotic resection QoL scores approximated baseline preoperative values 1 month after surgery, with the exception of increase in thoracic and shoulder pain the first 3 months after surgery (p=0.028 and 0.029, respectively). CONCLUSIONS: Numerous techniques have been published with different degrees of invasiveness, generating the existing controversy as to which is the best surgical approach for anterior mediastinal tumours. The high burden of decreased physical functioning reported after sternotomy is not seen after a da Vinci robotic-assisted thoracoscopic resection. The initial experience and postoperative QoL data are excellent and, therefore, the da Vinci robot will stay our future technique of choice for the treatment of resectable mediastinal tumours smaller than 4 cm on imaging techniques.

The prognostic value of the EEG in postanoxic coma.

INTRODUCTION: Several studies have been performed to assess the prognostic value of early neurological and neurophysiological findings in patients with postanoxic coma, but they have not led to precise, generally accepted, prognostic rules. This study was performed to assess whether it is possible to create a prognostic outcome table, using a combination of clinical variables and the electroencephalogram (EEG). METHODS: Clinical variables and EEG were registered on admission, at day 1-5, day 6-14, and day 15-42, and were related to the Glasgow outcome scale (GOS) at 30 and 180 days. The EEG abnormalities were categorized using the EEG classification system proposed by Synek (J Clin Neurophysiol 5:161-174, 1988) and Young et al. (Can J Neurol Sci 24:320-325, 1997). These EEG classifications were then further divided into prognostic categories. RESULTS: Age was a significant predictor of outcome. The early recorded clinical variables were the most predictive and the GCS showed a limited prognostic value. The first EEG registration proved to be the most predictive. The Synek-classification was divided into three prognostic categories: "benign," "malignant," and "fatal" and the Young-classification into four: "benign," "intermediate," "malignant," and "fatal." An outcome prediction table is proposed using the Young-classification stratified for age. CONCLUSION: Age is an important variable determining the prognostic value of the EEG and should always be taken into consideration. The prognostic categories, especially when derived from the Young-classification, showed a good prognostic value. Although this is a pilot study, we believe that the revised prognostic categories have a good prognostic value in predicting outcome and are worth further investigation and validation.

Recurrent myasthenia gravis due to a pleural implant 3 years after radical thymectomy.

Although recurrence of a thymoma is rare, pleural dissemination or local relapses have been described. We present a patient who underwent complete thymectomy for a thymoma, type AB according to the World Health Organization classification and stage II according to Masaoka, followed by adjuvant radiotherapy. Three years later, a relapse of the myasthenic symptoms occurred. An isolated pleural implant above the left diaphragm was removed by video-assisted thoracoscopy. Pathology confirmed the recurrence of the thymoma. As this is a rare occurrence, no precise therapeutic guidelines exist. In our case, surgical resection of the recurrence with adjuvant immunomodulating therapy for myasthenia provided good results.

Hereditary spastic paraplegia 3A associated with axonal neuropathy.

OBJECTIVE: To study the frequency and distribution of mutations in SPG3A in a large cohort of patients with hereditary spastic paraplegia. DESIGN: We screened a large cohort of 182 families and isolated cases with pure or complex hereditary spastic paraplegia phenotypes, which were negative for mutations in SPG4. RESULTS: In 12 probands (6.6%), we identified 12 different SPG3A mutations (11 missense and 1 insertion/frameshift) of which 7 were novel and 3 were de novo. We found incomplete penetrance in 1 family (G482V). In most cases, SPG3A mutations were associated with an early age at onset (mean, 3 y); however, in 1 family (R495W mutation), symptoms started later (mean, 14 y) with clear intrafamilial variability (8-28 y). Six patients with an SPG3A mutation (F151S, Q191R, M408T, G469A, R495W) originating from 5 unrelated families presented with a complex form of hereditary spastic paraplegia associated with a neuropathy (17%). Our electrophysiological and pathological findings confirmed an axonal sensory-motor neuropathy. There was no correlation between the genotype and the presence of a neuropathy. CONCLUSIONS: We conclude that mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. SPG3A is more often associated with a neuropathy than previously assumed. Therefore, patients with a bipyramidal syndrome and a neuropathy should be screened for mutations in SPG3A.