Clinical Reasoning: A 55-Year-Old Woman With Painless Hand Weakness and Atrophy.

Hand weakness is a frequent chief concern in neurology practice. We report a case of a 55-year-old woman presenting with a chronic, gradually worsening right hand weakness and atrophy, selectively affecting the thenar muscles, without any sensory symptoms. She had a history of carpal tunnel syndrome and previously underwent surgical carpal tunnel release. This case delves into the differential diagnosis of hand weakness and atrophy, emphasizing the significance of myotomal innervation in intrinsic hand muscles. Furthermore, it outlines a systematic approach to diagnosing an uncommon cause for a common clinical presentation, offering a comprehensive differential diagnosis, and exploring various possible causes.

Correlation Between Early Serum Myoglobin Levels and the Incidence and Prognosis of Intensive Care Unit-Acquired Weakness (ICU-AW) in Septic Shock Patients: A Comparative Study.

Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation between early serum myoglobin levels in patients with septic shock due to pneumonia, and the incidence of ICU-AW, duration of mechanical ventilation, and prognosis. Patients were classified based on the development of ICU-AW within the first 10 days of ICU admission. We measured serum myoglobin levels upon ICU entry, and analyzed demographic data, APACHE II scores, use of mechanical ventilation, and clinical outcomes, including mortality and duration of mechanical ventilation. The results indicated significantly elevated serum myoglobin levels in the ICU-AW group, correlated with prolonged mechanical ventilation and increased mortality. ROC analysis revealed myoglobin as a promising biomarker for predicting ICU-AW, with an area under the curve of 0.843 (95% CI: 0.819~0.867), demonstrating a sensitivity of 76.00% and specificity of 82.30%. These findings underscored serum myoglobin as a predictive biomarker for early ICU-AW in septic shock patients, highlighting its potential to guide clinical decision-making.

System-level analysis of genes mutated in muscular dystrophies reveals a functional pattern associated with muscle weakness distribution.

Muscular dystrophies (MDs) are inherited genetic diseases causing weakness and degeneration of muscles. The distribution of muscle weakness differs between MDs, involving distal muscles or proximal muscles. While the mutations in most of the MD-associated genes lead to either distal or proximal onset, there are also genes whose mutations can cause both types of onsets. We hypothesized that the genes associated with different MD onsets code proteins with distinct cellular functions. To investigate this, we collected the MD-associated genes and assigned them to three onset groups: genes mutated only in distal onset dystrophies, genes mutated only in proximal onset dystrophies, and genes mutated in both types of onsets. We then systematically evaluated the cellular functions of these gene sets with computational strategies based on functional enrichment analysis and biological network analysis. Our analyses demonstrate that genes mutated in either distal or proximal onset MDs code proteins linked with two distinct sets of cellular processes. Interestingly, these two sets of cellular processes are relevant for the genes that are associated with both onsets. Moreover, the genes associated with both onsets display high centrality and connectivity in the network of muscular dystrophy genes. Our findings support the hypothesis that the proteins associated with distal or proximal onsets have distinct functional characteristics, whereas the proteins associated with both onsets are multifunctional.

Drop Foot With Posterior Tibialis Weakness Treated With Peroneus Longus Transfer in a Child: A Case Report.

CASE: An 8-year-old girl with a history of acute flaccid paralysis presented with chronic valgus drop foot causing tripping and falling. Traditionally surgical correction of this deformity is accomplished by transferring the posterior tibialis tendon to enhance dorsiflexion. The authors describe a new technique which transfers the peroneus longus tendon to the dorsum of the foot in a patient with weakness of the posterior tibialis muscle. The patient's drop foot and gait were improved at the 22-month follow-up. CONCLUSION: Successful transfer of the peroneus longus was accomplished with improved limb clearance during gait and coronal alignment in stance.

Preliminary Study on Effects of Neck Exoskeleton Structural Design in Patients With Amyotrophic Lateral Sclerosis.

Neck muscle weakness due to amyotrophic lateral sclerosis (ALS) can result in dropped head syndrome, adversely impacting the quality of life of those affected. Static neck collars are currently prescribed to hold the head in a fixed upright position. However, these braces are uncomfortable and do not allow any voluntary head-neck movements. By contrast, powered neck exoskeletons have the potential to enable head-neck movements. Our group has recently improved the mechanical structure of a state-of-the-art neck exoskeleton through a weighted optimization. To evaluate the effect of the structural changes, we conducted an experiment in which patients with ALS were asked to perform head-neck tracking tasks while using the two versions of the neck exoskeleton. We found that the neck muscle activation was significantly reduced when assisted by the structurally enhanced design compared to no assistance provided. The improved structure also improved kinematics tracking performance, allowing users to better achieve the desired head poses. In comparison, the previous design did not help reduce the muscle effort required to perform these tasks and even slightly worsened the kinematic tracking performance. It was also found that biomechanical benefits gained from using the structurally improved design were consistent across participants with both mild and severe neck weakness. Furthermore, we observed that participants preferred to use the powered neck exoskeletons to voluntarily move their heads and make eye contact during a conversation task rather than remain in a fixed upright position. Each of these findings highlights the importance of the structural design of neck exoskeletons in achieving desired biomechanical benefits and suggests that neck exoskeletons can be a viable method to improve the daily life of patients with ALS.

Recognizing Myopathy in Patients with Muscle Weakness or Pain.

Muscle weakness and pain can be seen in orthopedic, rheumatologic, cardiac, and musculoskeletal conditions in addition to neurologic disorders. Myopathy, which describes a heterogenous group of hereditary and acquired disorders that affect muscle channels, structure, and metabolism, is one possible cause. This review focuses on essential information to support primary care providers as they assess patients with muscle weakness and pain for myopathy. As with most neurologic disorders, a thorough clinical history and physical examination are essential first steps. These findings will then guide diagnostic testing and facilitate appropriate management or referral for further neuromuscular care.

Acquired hyperkalaemia leading to periodic paralysis: an emergency department perspective.

Hyperkalaemia is one of the common electrolyte imbalances dealt with in the emergency department and is caused by extracellular accumulation of potassium ions above normal limits usually greater than 5.0-5.5 mmol/L. It is found in a total of 1-10% of hospitalised patients usually associated with chronic kidney disease and heart failure. The presentation can range from being asymptomatic to deadly arrhythmias. The appearance of symptoms depends on the rate of change rather than just the numerical values. The rare presentation includes periodic paralysis characterised by the sudden onset of short-term muscle weakness, stiffness or paralysis. Management goals are directed towards reducing potassium levels in emergency settings and later on avoiding the triggers for future attacks. In this case, we present a man in his 50s with the generalised weakness later on diagnosed as hyperkalaemic periodic paralysis secondary to tumour lysis syndrome. Emergency physicians dealing with common electrolyte imbalances should keep a sharp eye on their rare presentation and their precipitating factors and should act accordingly.

Balance function in critical illness survivors and evaluation of psychometric properties of the Mini-BESTest.

Critical illness survivors commonly face impairments, such as intensive care unit-acquired weakness (ICUAW) which is characterized by muscle weakness and sensory deficits. Despite these symptoms indicating potential balance deficits, systematic investigations and validated assessments are lacking. Therefore, we aimed to assess balance function using the Mini-BESTest, evaluate its psychometric properties, and identify associated variables. Balance was assessed post-ICU discharge (V1) and at discharge from inpatient neurorehabilitation (V2) in patients with ≥ 5 days of invasive ventilation. Mini-BESTest measurement characteristics were evaluated in an ambulatory subgroup. A multiple linear regression was conducted. The prospective cohort study comprised 250 patients (34% female, 62 ± 14 years, median ICU stay 55 days). Median Mini-BESTest scores improved significantly from V1 (5 (IQR 0-15)) to V2 (18.5 (10-23)) with a large effect size. Excellent inter-rater and test-retest reliabilities of the Mini-BESTest were observed (ICC = 0.981/0.950). Validity was demonstrated by a very high correlation with the Berg Balance Scale (ρ = 0.90). No floor or ceiling effects were detected. Muscle strength, cognitive function, cerebral disease, critical illness polyneuropathy/myopathy, and depression were significantly associated with balance. Despite significant improvements during the rehabilitation period, balance disorders were prevalent in critical illness survivors. Ongoing therapy is recommended. Due to its excellent psychometric properties, the Mini-BESTest is suitable for use in critical illness survivors.Registration: The study was registered at the German Clinical Trials Register (DRKS00021753, date of registration: 2020-09-03).

Preoperative motor weakness and the impact on patient reported outcomes in lateral lumbar interbody fusion.

This study measures the impact of preoperative motor weakness (MW) on Patient-Reported Outcome Measures (PROMs) in lateral lumbar interbody fusion (LLIF) patients. Retrospectively-sourced data from a prospectively-maintained, single-surgeon database created two cohorts of LLIF patients: patients with/without documented MW. Demographics/perioperative characteristics/PROMs were collected preoperatively and at six-weeks/final follow-up (FF). Studied outcomes were Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), 12-Item Short Form (SF-12) Physical/Mental Component Score (PCS/MCS), Patient Health Questionnaire (PHQ-9), Visual Analog Scale Back/Leg Pain (VAS-BP/LP), and Oswestry Disability Index (ODI). Multivariable linear/logistic regression calculated/compared intercohort minimum clinically important difference (MCID). Mean postoperative follow-up time was 11.5 ± 7.52 months. In total, 214 LLIF patients from December 2010 to May 2023 were included, with 149 having documented MW. In Table 1, self-reported gender was significant between cohorts (p < 0.025). Other significant demographic characteristics were smoker status (p < 0.002), diabetes (p < 0.016), and CCI score (p < 0.011). Table 2 shows notably significant perioperative characteristics: spinal pathology (degenerative spondylolisthesis/foraminal stenosis/herniated nucleus pulposus) (p < 0.005, all), estimated blood loss/length of stay/postoperative day (POD)-zero narcotic consumption (p < 0.001, all). Table 3 outcomes/MCID achievement percentages demonstrated insignificant intercohort differences besides a weakly significant FF ODI score (p < 0.036). MW, a frequently reported symptom in spine surgery, is poorly studied in LLIF patients. Thus, this study evaluates MW impact on PROMs and notes no significant differences. However, one exception regarding FF disability scores was recorded. MW did not affect MCID achievement for our patient population. Therefore, the preliminary findings suggest preoperative MW imparts minimal influence on PROMs/MCID in LLIF patients.

4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease.

Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ10. Poor outcomes result from low absorption and bioavailability of CoQ10 and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ10 supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency.

Correlation between low handgrip strength and metabolic syndrome in older adults: a systematic review.

Muscle weakness has been associated to insulin resistance and metabolic syndrome in the general population. However, it is still unclear whether this association is maintained in older adults. This study investigated correlations between low handgrip strength (HGS) and metabolic syndrome, or some of its components, in older adults through a systematic review of the literature. Searches were conducted in the Virtual Health Library Regional Portal, Scopus, Cochrane, Embase, MEDLINE/ PubMed, SciELO, and Web of Science databases for relevant studiesinvestigating muscle weakness (measured by hand dynamometer) and metabolic syndrome or its components in older adult populations, published up to September 2023. From the 2050 references initially identified, 20 studies, comprising a total of 31,264 older adults of both genders, completely met the inclusion/exclusion criteria. Eighteen studies showed that lower HGS was associated with metabolic syndrome or some of its risk factors, such as abdominal obesity, hyperglycemia, insulin resistance, dyslipidemia, or high blood pressure. Two studies found that older men with high blood pressure had increased HGS. Most studies included in this systematic review revealed a significant correlation between reduced HGS and metabolic syndrome or some of its components, especially abdominal obesity and insulin resistance. We conclude that below-average HGS can be associated with metabolic syndrome in older adults.

Unusual cause of muscle weakness, type II respiratory failure and pulmonary hypertension: a case report of ryanodine receptor type 1(RYR1)-related myopathy.

BACKGROUND: Patients with congenital myopathies may experience respiratory involvement, resulting in restrictive ventilatory dysfunction and respiratory failure. Pulmonary hypertension (PH) associated with this condition has never been reported in congenital ryanodine receptor type 1(RYR1)-related myopathy. CASE PRESENTATION: A 47-year-old woman was admitted with progressively exacerbated chest tightness and difficulty in neck flexion. She was born prematurely at week 28. Her bilateral lower extremities were edematous and muscle strength was grade IV-. Arterial blood gas analysis revealed hypoventilation syndrome and type II respiratory failure, while lung function test showed restrictive ventilation dysfunction, which were both worse in the supine position. PH was confirmed by right heart catheterization (RHC), without evidence of left heart disease, congenital heart disease, or pulmonary artery obstruction. Polysomnography indicated nocturnal hypoventilation. The ultrasound revealed reduced mobility of bilateral diaphragm. The level of creatine kinase was mildly elevated. Magnetic resonance imaging showed myositis of bilateral thigh muscle. Muscle biopsy of the left biceps brachii suggested muscle malnutrition and congenital muscle disease. Gene testing revealed a missense mutation in the RYR1 gene (exon33 c.C4816T). Finally, she was diagnosed with RYR1-related myopathy and received long-term non-invasive ventilation (NIV) treatment. Her symptoms and cardiopulmonary function have been greatly improved after 10 months. CONCLUSIONS: We report a case of RYR1-related myopathy exhibiting hypoventilation syndrome, type II respiratory failure and PH associated with restrictive ventilator dysfunction. Pulmonologists should keep congenital myopathies in mind in the differential diagnosis of type II respiratory failure, especially in patients with short stature and muscle weakness.

An 11-month-old boy with tuberculous meningitis presenting as progressive limb weakness, fever, developmental retardation, and loss of consciousness: a case report.

BACKGROUND: Tuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported. CASE PRESENTATION: An 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5-6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging. CONCLUSION: Over half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome.

Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients' health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient's functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited. METHODS: This two-stage qualitative study used semi-structured interviews in patients aged 45-80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30-80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction. RESULTS: In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results. CONCLUSION: The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies. TRIAL NUMBER: GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473 .

Associations of Handgrip Strength Weakness and Asymmetry with Lower Cognitive Function: Results from the National Health and Nutrition Examination Survey (2011-2014).

Background: The joint associations of handgrip strength (HGS) weakness and asymmetry with cognitive decline remain understudied in older adults. Objective: To investigate the associations between HGS weakness, asymmetry, and lower cognitive function in a nationally representative sample of older Americans. Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey 2011-2014. Weakness was defined as HGS <26 kg for men and <16 kg for women. Asymmetry was determined by calculating the ratio of dominant to non-dominant HGS. Participants with an HGS ratio <0.90 or >1.10 were classified as having any HGS asymmetry. Those with an HGS ratio >1.10 exhibited dominant HGS asymmetry, while those with an HGS ratio <0.90 displayed nondominant HGS asymmetry, respectively. Lower cognitive functioning was defined as global cognitive composite scores more than 1 standard deviation below the mean. Covariate-adjusted logistic regression models were used to analyze the associations between HGS asymmetry/weakness and lower cognitive functioning. Results: Compared to individuals with non-weak and symmetric HGS, those with any HGS asymmetry alone and weakness alone had 1.017 (95% confidence interval [CI]: 0.707-1.463) and 1.391 (95% CI: 0.542-3.571) greater odds for cognitive decline, while co-occurrence of both HGS asymmetry and weakness was associated with 3.724 (95% CI: 1.711-8.107) greater odds for lower cognitive function after controlling for confounders. Cnclusions: Individuals exhibiting both diminished and asymmetrical HGS demonstrated an elevated susceptibility to cognitive impairment, thereby implying that the inclusion of HGS asymmetry assessment in conjunction with weakness evaluation may enhance the accuracy of prognosticating cognitive decline.