Congenital factor XI deficiency caused by a novel F11 missense variant: a case report.

Hereditary factor XI (FXI) deficiency is a mild bleeding disorder, rare in the general population but relatively common among Ashkenazi Jews. The human F11 gene comprises 15 exons, spanning over 23 kb of the long arm of chromosome 4 (4q35). Homozygotes or compound heterozygotes typically show severe FXI deficiency, whereas heterozygotes show partial or mild deficiency. However, the genotype-phenotype relationship is difficult to establish, even among individuals within the same family. We report on a female patient with a heterozygous variant in F11 and FXI deficiency (49 IU/dL), who suffers from menorrhagia since menarche and easy bruising. She experienced excessive bleeding during thyroidectomy and after a cesarean section. Her younger sister, who carries the same heterozygous variant in F11 and has mild FXI deficiency (47 IU/dL), has menorrhagia without other bleeding difficulties although she has undergone several surgeries. Their father, who carries the same missense variant, has not experienced any bleeding difficulties (but he has not undergone any surgeries either). The family study revealed that the A428C mutation was inherited from the father. This variant has not previously been described in the literature and is the first F11 variant described in the Croatian population. Our study showed that even when family members have the same germline F11 variant, they still may experience phenotypic variability, making disease prognosis more complex.

Attenuation of ALS progression during pregnancy-lessons to be learned or just a coincidence?

ALS is the most frequent motor neuron disorder in adults with suggested complex relationship regarding gender. Studies investigating ALS and hormones have provided varying results. ALS onset during pregnancy is uncommon and pregnancy after the ALS symptom onset is even rarer. We present three patients with the onset of ALS symptoms before or during pregnancy and propose a putative disease modifying mechanism leading to attenuation of disease progression that we observed during the pregnancies.

Factors Contributing to the Reduction of Pain during Electromyography and Nerve Conduction Studies.

BACKGROUND: Electromyography (EMG) and nerve conduction studies (NCS) are an unpleasant and sometimes painful examinations. Pain can reduce patient's compliance and have a negative effect on the examination results. Different studies report that music affects pain perception by acting as a distractor, by inducing positive emotional valence or through the concept of convergence of different sensory modalities. The aim of this study was to explore the effect of music and different environmental and sociodemographic factors on pain perception during EMG and NCS. SUBJECTS AND METHODS: Sixty patients with suspected neuromuscular disease were randomized into music and control group. Specific questionnaire assessed sociodemographic characteristics, medical history, examination waiting time, examination extent and biometeorological forecast. The numerical rating scale was used for the evaluation of pain. The examiner evaluated patient's compliance after the examination. RESULTS: NCS was less painful for patients in the music group (p=0.03), as well as for more cooperative patients (p=0.011). For patients who previously underwent EMG/NCS, present NCS was more painful (p=0.001), regardless of the music intervention (p=0.019). EMG was more painful for older patients (p=0.041). Patients with lower level of education reported lower pain during NCS (p=0.026). Gender, financial satisfaction, biometeorological forecast, diabetes, depression or malignant disease, use and dosing of analgesics or antidepressants, symptoms, examination waiting time and the examination extent had no effect on pain perception. CONCLUSIONS: Music significantly decreased the perception of pain associated with NCS, but not the EMG portion of the examination. During EMG pain level was not significantly reduced, but the median of pain was still lower. Generally, the pain level during NCS, unlike the one during EMG, was affected by patients' compliance, level of education and painful predetermination. We propose using music during EMG/NCS because it can make the examination more comfortable for the patient and thus contribute to better quality of this examination.

Risdiplam Real World Data - Looking Beyond Motor Neurons and Motor Function Measures.

BACKGROUND: Risdiplam is an orally administered treatment for spinal muscular atrophy which leads to an improvement in motor function as measured by functional motor scales compared with placebo. Although risdiplam has been registered since 2020, real-world data in adults is still scarce. There have been no new safety signals so far, with some results pointing that risdiplam may be effectiveObjective:The objective was to present real-world data of 31 adult patients with spinal muscular atrophy type 2 and type 3 treated with risdiplam in the Republic of CroatiaMethods:Treatment effects were assessed with motor function tests and patient reported outcome measures, including Individualized Neuromuscular Quality of Life questionnaire, and Jaw Functional Limitation Scale. Side effects, as well as subjective improvements and symptoms, were noted. RESULTS: Majority of patients did not report any side effects. During treatment, we have observed clinically meaningful improvements in some patients, with stabilization of motor functions in the remaining patients. The majority of patients with bulbar function impairment experienced bulbar function improvement, all patients reported an increased quality of life with treatment. An unexpected observed treatment effect was weight gain in a third of all patients with some patients reporting an increase in appetite and subjective improvement in digestion. CONCLUSIONS: Risdiplam treatment was well tolerated with subjective and objective positive outcomes registered as measured by functional motor scales and patient-reported outcomes. Since risdiplam is administered orally and acts as a systemic therapy for a multisystemic disorder, effects in systems other than neuromuscular can be expected and should be monitored. Due to systemic nature of the disease patients need multidisciplinary monitoring.

A rare case of parasagittal meningioma causing isolated foot drop: case report and review of the literature.

Foot drop represents a very common reason for a neurologist referral and is often first seen in emergency departments or by a general practitioner. This condition is defined as weakness of ankle dorsiflexion (mainly through tibialis anterior muscle weakness). The most common causes include lower motor neuron lesion, with L4-L5 radiculopathy and peroneal neuropathy being the most frequent ones. Classical diagnostic pathway includes a thorough medical history, detailed neurological examination, radiological studies (MRI of the lumbosacral spine), EMG and nerve conduction studies, and a battery of laboratory tests. The absence of abnormal radiological and neurophysiological findings when searching for the most common causes of foot drop, should raise a red flag and broaden the diagnostic yield for central nervous system pathology (upper motor neuron, UMN) as a possible cause of foot drop. Central causes of isolated foot drop are very rare, with less than 20 cases reported in literature so far, and seven of them being a meningioma. We present a case of a 79-year-old female patient with an isolated foot drop (with no UMN signs on the initial examination) and parasagittal meningioma. Central causes of foot drop should be suspected when foot drop is associated with UMN signs on examination (hyperreflexia of the patellar or ankle jerk and extensor plantar reflex) and when standard diagnostic work-up (MRI of the lumbar spine, EMG and NCS, standard laboratory screening for most common causes of foot drop) is negative or inconclusive. Although very rare, central lesions present a far more serious cause of foot drop and require a more urgent diagnostic work up and a potential neurosurgical referral and treatment. Keeping in mind the possible central causes of foot drop would eliminate unnecessary diagnostic work up and avoid delayed diagnosis and treatment.

Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma.

INTRODUCTION: Avelumab is a programmed death ligand 1-blocking monoclonal antibody used for the treatment of Merkel cell carcinoma (MCC), urothelial carcinoma, and other solid tumors. It acts as an immune checkpoint inhibitor and prolongs survival of MCC patients. Immune-mediated neurological adverse effects are rare and usually respond well to specific therapy. METHODS AND RESULTS: A case of a 70-year-old man with metastatic MCC is described in this study. The patient developed diplopia after the fourth dose of avelumab, which was then discontinued. Seven months later, therapy was reinitiated and followed by a new adverse neurological event: severe demyelinating polyneuropathy combined with ophthalmoplegia refractory to a plethora of immune suppressive/modulatory treatment regimes. DISCUSSION: This report of severe demyelinating polyneuropathy and cranial neuropathy associated with an anti-programmed death ligand 1 drug refractory to immune suppressive/modulatory treatments sheds a new light to evolving spectrum of immune checkpoint inhibitor immune-related neurological adverse events.

Lower number of plasma exchange sessions and glomerular filtration rate decline are associated with second relapses in patients with myasthenia gravis.

The aims were to determine the impact of dysphagia and glomerular filtration rate (GFR) in the prediction of myasthenia relapse and analyse whether different number of plasma exchange sessions could prolong the time before future relapse.This was a retrospective, longitudinal follow-up study with 60 enrolled patients. The patients were followed-up for a total of 50 months.Patients without relapses had significantly higher GFR and higher number of plasma exchange sessions when compared to patients with relapses. Mean time before next myasthenia relapse was significantly longer in patients with GFR ≥ 60 mL/min. Time before next and number of following myasthenia relapses were significantly higher in patients with symptoms of dysphagia.Decline in GFR levels is strongly associated with the presence of dysphagia and independently impacts the onset of myasthenia relapses. Timely initiation of plasmapheresis therapy and adequate hydration of patients with prolonged dysphagia should be one of the treatment goals for clinicians treating this disease.