-
Neurologia I Neurochirurgia Polska Jun 2024Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the...
INTRODUCTION
Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the symptomatic treatment of LEMS.
AIM OF STUDY
To assess the effectiveness and safety of treatment in the real world.
MATERIAL AND METHODS
14 patients with non-neoplastic LEMS treated with amifampridine were enrolled in the study (female 42.9%, mean age 48.8 ± 11.4 years). The patients were assessed using the Quantitative Myasthenia Gravis (QMG) scale, QMG limb domain (LD) score, spirometry, Hand Grip Strength (GRIP) test, and repetitive nerve stimulation study (RNS) at baseline and at the end of follow-up. Diagnostic delay since first symptoms was from seven months up to 22 years. Treatment delay ranged from one to 26 years. The patients were treated and reevaluated after 21.1 ± 12.0 weeks (range 13-48).
RESULTS
All of the patients improved in QMG score. Mean improvement was 5.1 ± 2.0 (range 1-8) points (p < 0.001) and this showed no correlation with the duration of the disease before treatment (p = 0.477). 85.7% of patients (N = 12) improved ≥ 3 points (clinically meaningful) in QMG. 78.6% of the patients improved in QMG LD (mean 2.2 ± 1.6 points (p < 0.001)). Also, forced vital capacity (FVC) improved after treatment (p = 0.031). Mean improvement in GRIP test was 7.0 ± 7.1 kg in the right hand and 5.2 ± 7.5 kg in the left hand (p < 0.001). In RNS before treatment, facilitation ( > 100%) was observed in 78.6% (N = 11) of patients, and was higher before treatment (p < 0.001). Compound muscle action potential (CMAP) amplitude was higher after treatment (p < 0.001). Mean increase of CMAP amplitude was 2.1 ± 1.6 times. In 64.3% (N = 9) of patients lowering of corticosteroid dose was achieved.
CONCLUSIONS
Amifampridine is an effective treatment in non-neoplastic LEMS patients, regardless of disease duration. The treatment is well-tolerated and allows to reduce dose of corticosteroids in the majority of patients.
PubMed: 38935421
DOI: 10.5603/pjnns.99335 -
Neural Regeneration Research Jun 2024Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of...
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
PubMed: 38934395
DOI: 10.4103/NRR.NRR-D-24-00067 -
Sensors (Basel, Switzerland) Jun 2024After a stroke, antagonist muscle activation during agonist command impedes movement. This study compared measurements of antagonist muscle activation using surface...
After a stroke, antagonist muscle activation during agonist command impedes movement. This study compared measurements of antagonist muscle activation using surface bipolar EMG in the gastrocnemius medialis (GM) and high-density (HD) EMG in the GM and soleus (SO) during isometric submaximal and maximal dorsiflexion efforts, with knee flexed and extended, in 12 subjects with chronic hemiparesis. The coefficients of antagonist activation (CAN) of GM and SO were calculated according to the ratio of the RMS amplitude during dorsiflexion effort to the maximal agonist effort for the same muscle. Bipolar CAN (BipCAN) was compared to CAN from channel-specific (CsCAN) and overall (OvCAN) normalizations of HD-EMG. The location of the CAN centroid was explored in GM, and CAN was compared between the medial and lateral portions of SO. Between-EMG system differences in GM were observed in maximal efforts only, between BipCAN and CsCAN with lower values in BipCAN ( < 0.001), and between BipCAN and OvCAN with lower values in OvCAN ( < 0.05). The CAN centroid is located mid-height and medially in GM, while the CAN was similar in medial and lateral SO. In chronic hemiparesis, the estimates of GM hyperactivity differ between bipolar and HD-EMGs, with channel-specific and overall normalizations yielding, respectively, higher and lower CAN values than bipolar EMG. HD-EMG would be the way to develop personalized rehabilitation programs based on individual antagonist activations.
Topics: Humans; Electromyography; Paresis; Male; Female; Muscle, Skeletal; Middle Aged; Aged; Adult; Chronic Disease; Stroke
PubMed: 38931485
DOI: 10.3390/s24123701 -
Medicina (Kaunas, Lithuania) Jun 2024: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the...
: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the Hannover Classification. Microscope-based augmented reality (AR) can be beneficial in cerebellopontine angle and lateral skull base surgery, since these are small areas packed with anatomical structures and the use of this technology enables automatic 3D building of a model without the need for a surgeon to mentally perform this task of transferring 2D images seen on the microscope into imaginary 3D images, which then reduces the possibility of error and provides better orientation in the operative field. : All patients who underwent surgery for resection of ANs in our department were included in this study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. : A total of 43 consecutive patients (25 female, median age 60.5 ± 16 years) who underwent resection of ANs via retrosigmoid osteoclastic craniotomy with the use of intraoperative neuromonitoring (22 right-sided, 14 giant tumors, 10 cystic, 7 with hydrocephalus) by a single surgeon were included in this study, with a median follow up of 41.2 ± 32.2 months. A total of 18 patients underwent subtotal resection, 1 patient partial resection and 24 patients gross total resection. A total of 27 patients underwent resection in sitting position and the rest in semi-sitting position. Out of 37 patients who had no facial nerve deficit prior to surgery, 19 patients were intact following surgery, 7 patients had House Brackmann (HB) Grade II paresis, 3 patients HB III, 7 patients HB IV and 1 patient HB V. Wound healing deficit with cerebrospinal fluid (CSF) leak occurred in 8 patients (18.6%). Operative time was 317.3 ± 99 min. One patient which had recurrence and one further patient with partial resection underwent radiotherapy following surgery. A total of 16 patients (37.2%) underwent resection using fiducial-based navigation and microscope-based AR, all in sitting position. Segmented objects of interest in AR were the sigmoid and transverse sinus, tumor outline, cranial nerves (CN) VII, VIII and V, petrous vein, cochlea and semicircular canals and brain stem. Operative time and clinical outcome did not differ between the AR and the non-AR group. However, use of AR improved orientation in the operative field for craniotomy planning and microsurgical resection by identification of important neurovascular structures. : The single-center experience of resection of ANs showed a high rate of gross total (GTR) and subtotal resection (STR) with low recurrence. Use of AR improves intraoperative orientation and facilitates craniotomy planning and AN resection through early improved identification of important anatomical relations to structures of the inner auditory canal, venous sinuses, petrous vein, brain stem and the course of cranial nerves.
Topics: Humans; Female; Middle Aged; Male; Microsurgery; Neuroma, Acoustic; Aged; Adult; Augmented Reality; Neurosurgical Procedures; Microscopy; Treatment Outcome; Imaging, Three-Dimensional
PubMed: 38929549
DOI: 10.3390/medicina60060932 -
Medicina (Kaunas, Lithuania) May 2024: Mechanical ventilation is often used in intensive care units to assist patients' breathing. This often leads to respiratory muscle weakness and diaphragmatic... (Meta-Analysis)
Meta-Analysis Review
: Mechanical ventilation is often used in intensive care units to assist patients' breathing. This often leads to respiratory muscle weakness and diaphragmatic dysfunction, causing weaning difficulties. Inspiratory muscle training (IMT) has been found to be beneficial in increasing inspiratory muscle strength and facilitating weaning. Over the years, different protocols and devices have been used. : The aim of this systematic review and meta-analysis was to investigate the effectiveness of low-medium (LM-IMT) and high-intensity (H-IMT) threshold inspiratory muscle training in critically ill patients. A systematic literature search was performed for randomized controlled trials (RCTs) in the electronic databases Google Scholar, PubMed, Scopus, and Science Direct. The search involved screening for studies examining the effectiveness of two different intensities of threshold IMT in critically ill patients published the last 10 years. The Physiotherapy Evidence Database (PEDro) scale was chosen as the tool to assess the quality of studies. A meta-analysis was performed where possible. : Fourteen studies were included in the systematic review, with five of them having high methodological quality. : When examining LM-IMT and H-IMT though, neither was able to reach statistically significant improvement in their maximal inspiratory pressure (MIP), while LM-IMT reached it in terms of weaning duration. Additionally, no statistical difference was noticed in the duration of mechanical ventilation. The application of IMT is recommended to ICU patients in order to prevent diaphragmatic dysfunction and facilitate weaning from mechanical ventilation. Therefore, further research as well as additional RCTs regarding different protocols are needed to enhance its effectiveness.
Topics: Humans; Critical Illness; Breathing Exercises; Respiratory Muscles; Respiration, Artificial; Intensive Care Units
PubMed: 38929486
DOI: 10.3390/medicina60060869 -
Animals : An Open Access Journal From... Jun 2024Nutritional secondary hyperparathyroidism (NSH) in dogs is a condition that develops in response to a vitamin D deficiency or an imbalanced calcium-to-phosphorus ratio...
Nutritional secondary hyperparathyroidism (NSH) in dogs is a condition that develops in response to a vitamin D deficiency or an imbalanced calcium-to-phosphorus ratio in dog food. Puppies of large-breed dogs exclusively fed a non-supplemented, boneless raw meat diet are especially susceptible to developing NSH due to their elevated calcium requirement. Reports on NSH in companion animals have been sparse in the last decades due to dog owners having easy access to commercially balanced dog foods. However, with the rising popularity of meat-based raw feeding, this condition has re-emerged. In this case series, four large-breed puppies fed exclusively non-supplemented, boneless raw meat diets presented with complaints of acute onset of pain and paresis. Radiographs and/or computed tomography (CT) scans showed reduced radio density of the skeleton in all four puppies. Two of the dogs had pathological fractures, and these two puppies were euthanized. One was subjected to a post mortem examination, which revealed cortical bone resorption and hypertrophy of the parathyroid glands. The remaining two puppies rapidly improved after receiving pain medication and a commercial, balanced diet. This case series demonstrates a risk of young dogs developing severe neurological deficits when fed a non-supplemented, boneless raw meat diet.
PubMed: 38929402
DOI: 10.3390/ani14121783 -
Diagnostics (Basel, Switzerland) Jun 2024In 2019, mild vestibular function deficiency in elder populations was defined as presbyvestibulopathy (PVP) by the Classification Committee of the Bárány Society. The...
INTRODUCTION
In 2019, mild vestibular function deficiency in elder populations was defined as presbyvestibulopathy (PVP) by the Classification Committee of the Bárány Society. The diagnostic criteria include tests for low-, mid-, and high-frequency vestibular function, represented by caloric testing, rotary chair testing, and head impulse testing, respectively. However, there is still a lack of large-scale reports supporting the relationship between vestibular function tests (VFTs) and aging. In this study, we evaluated whether each test is correlated with aging in the elderly population aged over 50.
METHODS
This study retrospectively enrolled 1043 subjects from a single university hospital database after excluding those with unilateral and bilateral vestibulopathy, central dizziness, and acute dizziness. Enrolled subjects had caloric canal paresis <20%, vHIT lateral canal gain >0.6, vHIT interaural difference <0.3, and age >50 years old.
RESULTS
Significant negative correlations with age were identified in the vHIT ( < 0.001) and rotary chair test (RCT) 1.0 Hz gain ( = 0.030). However, the caloric test ( = 0.739 and 0.745 on the left and right sides, respectively) and RCT 0.12 Hz gain ( = 0.298) did not show a significant correlation with age. A total of 4.83% of subjects aged 70 years or older showed sub-normal vHIT gain that met the criteria of PVP, whereas only 0.50% of subjects aged 60 to 69 did. The prevalence of sub-normal caloric test results, however, was not significantly different between the two age groups (21.55% in the 60-69 age group and 26.59% in the >70 age group).
CONCLUSIONS
The high-frequency range vestibular function seems vulnerable to aging, and this is more discernible at age >70 years. The weak correlation between age and low-frequency vestibular function tests, such as the caloric test and low-frequency rotary chair testing, suggests the need to revisit the diagnostic criteria for PVP.
PubMed: 38928640
DOI: 10.3390/diagnostics14121224 -
International Journal of Molecular... Jun 2024Coenzyme Q10 (CoQ10) plays a key role in many aspects of cellular metabolism. For CoQ10 to function normally, continual interconversion between its oxidised (ubiquinone)... (Review)
Review
Coenzyme Q10 (CoQ10) plays a key role in many aspects of cellular metabolism. For CoQ10 to function normally, continual interconversion between its oxidised (ubiquinone) and reduced (ubiquinol) forms is required. Given the central importance of this ubiquinone-ubiquinol redox cycle, this article reviews what is currently known about this process and the implications for clinical practice. In mitochondria, ubiquinone is reduced to ubiquinol by Complex I or II, Complex III (the Q cycle) re-oxidises ubiquinol to ubiquinone, and extra-mitochondrial oxidoreductase enzymes participate in the ubiquinone-ubiquinol redox cycle. In clinical terms, the outcome of deficiencies in various components associated with the ubiquinone-ubiquinol redox cycle is reviewed, with a particular focus on the potential clinical benefits of CoQ10 and selenium co-supplementation.
Topics: Ubiquinone; Humans; Oxidation-Reduction; Mitochondria; Animals; Selenium; Ataxia; Muscle Weakness; Mitochondrial Diseases
PubMed: 38928470
DOI: 10.3390/ijms25126765 -
International Journal of Molecular... Jun 2024Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder currently affecting the ageing population. Although the aetiology of PD has yet to be...
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder currently affecting the ageing population. Although the aetiology of PD has yet to be fully elucidated, environmental factors such as exposure to the naturally occurring neurotoxin rotenone has been associated with an increased risk of developing PD. Rotenone inhibits mitochondrial respiratory chain (MRC) complex I activity as well as induces dopaminergic neuronal death. The aim of the present study was to investigate the underlying mechanisms of rotenone-induced mitochondrial dysfunction and oxidative stress in an in vitro SH-SY5Y neuronal cell model of PD and to assess the ability of pre-treatment with Coenzyme Q (CoQ) to ameliorate oxidative stress in this model. Spectrophotometric determination of the mitochondrial enzyme activities and fluorescence probe studies of reactive oxygen species (ROS) production was assessed. Significant inhibition of MRC complex I and II-III activities was observed, together with a significant loss of neuronal viability, CoQ status, and ATP synthesis. Additionally, significant increases were observed in intracellular and mitochondrial ROS production. Remarkably, CoQ supplementation was found to reduce ROS formation. These results have indicated mitochondrial dysfunction and increased oxidative stress in a rotenone-induced neuronal cell model of PD that was ameliorated by CoQ supplementation.
Topics: Ubiquinone; Rotenone; Mitochondria; Humans; Oxidative Stress; Reactive Oxygen Species; Neurons; Parkinson Disease; Cell Line, Tumor; Muscle Weakness; Cell Survival; Electron Transport Complex I; Ataxia; Mitochondrial Diseases
PubMed: 38928331
DOI: 10.3390/ijms25126622 -
International Journal of Molecular... Jun 2024Inclusion body myositis (IBM) is a slowly progressive disorder belonging to the idiopathic inflammatory myopathies, and it represents the most common adult-onset...
Inclusion body myositis (IBM) is a slowly progressive disorder belonging to the idiopathic inflammatory myopathies, and it represents the most common adult-onset acquired myopathy. The main clinical features include proximal or distal muscular asymmetric weakness, with major involvement of long finger flexors and knee extensors. The main histological findings are the presence of fiber infiltrations, rimmed vacuoles, and amyloid inclusions. The etiopathogenesis is a challenge because both environmental and genetic factors are implicated in muscle degeneration and a distinction has been made previously between sporadic and hereditary forms. Here, we describe an Italian patient affected with a hereditary form of IBM with onset in his mid-forties. Next-generation sequencing analysis disclosed a heterozygous mutation c.76C>T (p.Pro26Ser) in the PDZ motif of the gene, a mutation already described in a family with a late-onset myopathy and highly heterogenous degree of skeletal muscle weakness. In the proband's muscle biopsy, the expression of ZASP, myotilin, and desmin were increased. In our family, in addition to the earlier age of onset, the clinical picture is even more peculiar given the evidence, in one of the affected family members, of complete ophthalmoplegia in the vertical gaze. These findings help extend our knowledge of the clinical and genetic background associated with inclusion body myopathic disorders.
Topics: Humans; Myositis, Inclusion Body; Male; Pedigree; LIM Domain Proteins; Adaptor Proteins, Signal Transducing; Middle Aged; Muscle, Skeletal; Mutation; Adult
PubMed: 38928252
DOI: 10.3390/ijms25126547