Keeping up appearances: Don't frown upon the effects of botulinum toxin injections in facial muscles.

Aesthetic use of low doses of Botulinum toxin (BoNT) injections into the facial muscles has become a leading non-surgical aesthetic treatment worldwide to reduce facial wrinkles, including glabellar lines, forehead lines, and periorbital wrinkles. Within these aesthetic applications, BoNT injections intend to reduce and prevent wrinkles, and the recommended usage of 2 years is often exceeded, which may result in atrophy of the injected muscles. The long-term effects of BoNT injections in the facial muscles and the evidence of diffusion of BoNT to surrounding muscles are obvious pitfalls and challenges for clinical neurophysiologists in differential diagnosing neuromuscular transmission failures. Also, this is further complicated by the risk of developing side effects upon permanent chemical denervation of facial muscles, with less possibility for reinnervation. This review summarizes the known long-term effects of BoNT over time in different facial muscles and the use of objective electrophysiological measures to evaluate these. A better understanding of the long-term effects of BoNT is essential to avoid misdiagnosing other neuromuscular disorders.

Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy.

Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures. Three siblings were found homozygous for a NCDN missense variant, whereas another three unrelated individuals carried different de novo missense variants in NCDN. We assayed the missense variants for their capability to rescue impaired neurite formation in human neuroblastoma (SH-SY5Y) cells depleted of NCDN. Overexpression of wild-type NCDN rescued the neurite-phenotype in contrast to expression of NCDN containing the variants of affected individuals. Two missense variants, associated with severe neurodevelopmental features and epilepsy, were unable to restore mGluR5-induced ERK phosphorylation. Electrophysiological analysis of SH-SY5Y cells depleted of NCDN exhibited altered membrane potential and impaired action potentials at repolarization, suggesting NCDN to be required for normal biophysical properties. Using available transcriptome data from human fetal cortex, we show that NCDN is highly expressed in maturing excitatory neurons. In combination, our data provide evidence that bi-allelic and de novo variants in NCDN cause a clinically variable form of neurodevelopmental delay and epilepsy, highlighting a critical role for NCDN in human brain development.

Botulinum toxin injections associated with suspected myasthenia gravis: An underappreciated cause of MG-like clinical presentation.

INTRODUCTION: The application of botulinum toxin type A (BoNTA) is accelerating, and this includes the uncontrolled cosmetic use of the BoNTA. Diffusion of BoNTA can disturb neuromuscular transmission in several surrounding and distant muscles and result in clinical manifestations similar to myasthenia gravis (MG). CASE PRESENTATIONS: We report two cases of patients referred for neurophysiological evaluation of suspected MG. A 55-year-old female who experienced dysphagia, dysarthria, right-sided ptosis, and neck extensor muscle weakness; and a 46-year-old male who presented with episodic double vision and right-sided ptosis. Both had the history of previous BoNTA use for cosmetic purposes and for the treatment of migraine before the presentation of their symptoms. In both cases examination revealed normal RNS, quite remarkably increased jitter, and signs of denervation and reinnervation in muscles surrounding the injection sites. After extensive neurophysiological evaluations, the primary cause of their symptoms was found to be related to previous BoNTA injections rather than a primary neuromuscular transmission disorder. It could also be concluded that patients do not automatically inform their physicians about cosmetic BoNTA use and they may not be aware of the potential risks associated with BoNTA therapy. CONCLUSIONS: The presented cases illustrate the neurophysiological findings in two patients with suspected MG after the use of BoNTA and emphasize the importance of inquiring about previous BoNTA injections and highlight that it is essential that patients are informed about possible side effects of BoNTA therapy.

Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries.

Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden. METHODS: This cross-sectional study included southern counties in Sweden and Estonia of comparable size. All patients with a confirmed MG diagnosis were asked to answer two questionnaires including demographic and disease-specific data, lifestyle issues, and mental fatigue (Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through the Quantitative Myasthenia Gravis Score (QMG). RESULTS: Thirty-six of 92 identified patients in Estonia and 40 of 70 identified MG patients in Sweden chose to participate in the study. The demographic characteristics and symptoms reported by the patients were similar. QMG score did not differ; however, the Estonian patients scored their current subjective disease severity significantly higher (5.6 ± 2.8) compared to the Swedish patients (3.4 ± 2.3, p = .0005). Estonian patients also had significantly higher FSS scores (5.0 ± 1.7) than Swedish patients (3.5 ± 1.6; p = .001). Swedish patients were more active and performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden, p = .004). CONCLUSIONS: Although, the patients had comparable clinical fatigue, Estonian patients evaluated their health state as being more severe and reported more mental fatigue than Swedish patients. These data indicate large regional differences in disease perception of MG, which is important to consider in international studies.

Repetitive nerve stimulation often fails to detect abnormal decrement in acute severe generalized Myasthenia Gravis.

OBJECTIVE: We assessed the diagnostic pattern of repetitive nerve stimulation (RNS) test and concentric electrode (CNE) jitter analysis between patients with generalized myasthenia gravis (GMG) with acute versus slow onset. METHODS: All examinations that established the diagnosis of GMG at the department of Clinical Neurophysiology, Uppsala University Hospital, were retrospectively analyzed from January 2012 to December 2014. Patients were grouped according to disease duration at neurophysiological evaluation: acute onset (<4weeks) or slow onset (⩾4weeks). RESULTS: We identified 41 patients diagnosed with GMG. Of the nine patients with acute onset GMG (5 women) only one patient had abnormal decrement, whereas of the 32 patients with slow onset (13 women) 26 patients (84%) had abnormal decrement. CNE jitter was abnormal in all. AChR antibody status was comparable (78% versus 84%) whereas the MGFA class was higher in the acute onset group (range: 3A-5) compared to the slow onset group (range: 2A-3B). CONCLUSIONS: RNS test is frequently normal in cases of acute severe GMG, including myasthenic crisis. Performing CNE jitter analysis is therefore of crucial importance for a correct early diagnosis. SIGNIFICANCE: MG patients with acute severe onset of bulbar or generalized fatigue often have normal findings on RNS test in proximal muscles.

123I-ADAM SPET imaging of serotonin transporter in patients with epilepsy and comorbid depression.

BACKGROUND: Purpose of the study was to investigate alterations in midbrain serotonin transporter (SERT) binding in patients with epilepsy and symptoms of depression compared to patients with epilepsy with no symptoms of depression. METHODS: We studied 12 patients with epilepsy (7 patients had focal and 5 had generalized epilepsy syndromes). The presence of self-reported symptoms of depression was assessed using Beck Depression Inventory (BDI) and the Emotional State Questionnaire (EST-Q). The binding potential of the SERT was assessed by performing brain single photon emission tomography (SPET) using the SERT radioligand 2-((2-((dimethylamino)methyl)phenyl)thio)-5-(123)iodophenylamine (123I-ADAM). RESULTS: Seven patients had BDI and EST-Q subscale scores greater than 11 points, which was interpreted as the presence of symptoms of depression. We found that 123I-ADAM binding was not significantly different between patients with epilepsy with and without symptoms of depression. In addition, 123I-ADAM binding did not show a significant correlation to either BDI or EST-Q depression subscale scores and did not differ between patients with focal vs. generalized epilepsy. CONCLUSION: The results of our study failed to demonstrate alterations of SERT binding properties in patients with epilepsy with or without symptoms of depression.

Cognitive profile and depressive symptoms in patients with epilepsy.

BACKGROUND AND OBJECTIVE: The aim of the present study was to describe the cognitive profile of patients with focal and generalized epilepsy syndrome in comparison with healthy control subjects and to investigate whether depression was related to neuropsychological functioning in these patients. MATERIAL AND METHODS: A total of 36 patients with focal epilepsy and 26 patients with generalized epilepsy were compared with the control group of healthy volunteers (n=53). A battery of neuropsychological tests assessing verbal and visual spatial memory and executive functioning was carried out in addition to the completion of the Beck Depression Inventory (BDI). RESULTS: The results indicated that patients with epilepsy performed significantly worse than controls on all verbal memory subscales and verbal fluency domains. The patients with focal epilepsy scored significantly worse than the patients with generalized epilepsy. The BDI scores were significantly correlated with several scores of the cognitive test in both patients' groups but not in the control group. CONCLUSIONS: Our results suggest that patients with epilepsy, especially with focal-onset epilepsy, show cognitive disturbances predominantly in the verbal memory domain. In addition, depression was found to have a negative effect on cognitive functioning in patients with epilepsy.

Epileptic laughter: 2 case reports.

Two cases of gelastic epilepsy in a 6-year-old girl with attacks of mirthful laughter and a 38-year-old male patient with episodes of laughter without any positive emotions are presented. Temporal lobe epilepsy was diagnosed in the first case and possible frontal lobe epilepsy in the second case. It is concluded that that this rare form of epilepsy can be difficult to diagnose and treat, and can clinically be accompanied by urinary incontinence.

Fulminant inflammatory neuropathy mimicking cerebral death.

We report a case of a 44-year-old woman who developed rapidly progressive tetraparesis followed by respiratory failure and abolition of brainstem reflexes. Electrodiagnostic studies excluded the possibility of cerebral death and confirmed the diagnosis of acute motor-sensory axonal neuropathy. The initial fulminant course of the disease was followed by slow recovery to independence in daily activities.

Subjective complaints compared to the results of neuropsychological assessment in patients with epilepsy: The influence of comorbid depression.

The aim of the study was to compare subjective complaints of epilepsy patients with objective results of neuropsychological assessment and to investigate the possible influence of depression on self-reported complaints. 62 patients from the neurology clinic were included in the study. They were asked to fill the subjective complaints questionnaire, Beck Depression Inventory and a series of neuropsychological tests. The results indicated that self-reported cognitive complaints are not strongly associated with objective tests of different cognitive performance measures. We conclude that the discrepancy between subjective and objective cognitive functioning does not only affect the area of memory but a wide range of cognitive domains. Depression is an important factor influencing the level of different subjective complaints.