-
Biomolecules Oct 2023Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.
Topics: Animals; Humans; Amyotrophic Lateral Sclerosis; Motor Neurons; Muscle, Skeletal; Muscular Atrophy; Paralysis
PubMed: 38002264
DOI: 10.3390/biom13111582 -
BMJ Case Reports Apr 2022A woman in her 70s was admitted to hospital with worsening shortness of breath and no prior respiratory history of note. This patient's shortness of breath was...
A woman in her 70s was admitted to hospital with worsening shortness of breath and no prior respiratory history of note. This patient's shortness of breath was posture-dependent; symptoms were markedly worse and oxygen saturations were lower on sitting upright than in recumbency. Her shortness of breath had started several weeks prior to admission and had slowly worsened. Chest X-ray revealed a raised right hemidiaphragm. Further investigation revealed a patent foramen ovale, which was managed with percutaneous closure. This is one of several cases that demonstrate right-to-left shunting through a septal defect secondary to right hemidiaphragmatic paralysis. However, previous reports have not provided a clear guide for management of these cases. We suggest where patients are admitted with new onset breathlessness and platypnoea-orthodeoxia, a septal defect should be suspected. In this report, we have suggested a flowchart for the investigation and management of platypnoea-orthodeoxia syndrome.
Topics: Dyspnea; Female; Foramen Ovale, Patent; Heart Septal Defects; Humans; Hypoxia; Paralysis
PubMed: 35383098
DOI: 10.1136/bcr-2021-248502 -
JAMA Facial Plastic Surgery Jul 2018When able to identify facial paralysis, members of society regard individuals with facial paralysis differently. They perceive a decrease in attractiveness, more... (Observational Study)
Observational Study
IMPORTANCE
When able to identify facial paralysis, members of society regard individuals with facial paralysis differently. They perceive a decrease in attractiveness, more negative affect, and lower quality of life. However, the ability of lay people in society to accurately identify the presence of facial paralysis has not yet been defined.
OBJECTIVE
To determine societal members' ability to (1) identify paralysis in varying degrees of paralysis severity and (2) localize the defect on the face.
DESIGN, SETTING, AND PARTICIPANTS
A prospective observational study conducted in an academic tertiary referral center using a group of 380 casual observers was carried out.
MAIN OUTCOMES AND MEASURES
Surveys were designed containing smiling and repose images of normal faces and faces with unilateral facial paralysis of 3 severity levels (low, medium, and high) as categorized by House-Brackmann (HB) grade. The photographs were then shown to casual observers in a web-based survey. After reviewing both normal faces and faces with varying degrees of paralysis, they then indicated (1) whether paralysis was present and (2) if so, where the paralysis was on the face.
RESULTS
A total of 380 participants (267 [70.3%] women and 113 [29.7%] men with a mean [SD] age of 29 [12] years) successfully completed the survey, viewing 2860 facial photographs in aggregate. The accuracy rate of identifying paralysis increased from low-grade through high-grade paralysis. Facial paralysis was identified in 249 (34.6%) of 719 facial photographs with low-grade paralysis, 448 (63.2%) of 709 with medium-grade paralysis, and 696 (96.7%) of 720 with high-grade paralysis (χ2 = 912.6, P < .001); 6.2% (44/731) of normal faces were incorrectly identified as having paralysis (χ2 = 912.6, P < .001). Participants correctly localized paralysis in 157 (63.0%) of 249 low-grade photographs, 307 (68.5%) of 448 medium-grade photographs, and 554 (79.6%) of 696 high-grade photographs (χ2 = 32.5, P < .001). In general, participants tended to identify facial paralysis more accurately in smiling vs repose faces (48.6% vs 20.6%, 92.4% vs 33.7%, and 96.7% vs 96.6% in low-, medium-, and high-grade paralysis, respectively) (χ2 = 62.2, P < .001; χ2 = 262.6, P < .001; χ2 = 0.0, P = .96, respectively).
CONCLUSIONS AND RELEVANCE
The ability of individuals to identify the presence of facial paralysis increased as paralysis severity increased. Further, smiling increased accurate identification. However, even when individuals can identify paralysis, they are not necessarily able to accurately localize the paralysis on a face. This may speak to a phenomenon in which perception of a facial defect comes from a holistic interpretation of a face, rather than a clinically accurate specification of the defect location. These findings are important in the future counseling of patients.
LEVEL OF EVIDENCE
NA.
Topics: Adult; Affect; Beauty; Facial Paralysis; Female; Humans; Male; Photography; Prospective Studies; Quality of Life; Smiling; Social Perception
PubMed: 29423522
DOI: 10.1001/jamafacial.2017.2402 -
Journal of Virology May 2023In 2014, 2016, and 2018, the United States experienced unprecedented spikes in pediatric cases of acute flaccid myelitis (AFM), which is a poliomyelitis-like paralytic...
In 2014, 2016, and 2018, the United States experienced unprecedented spikes in pediatric cases of acute flaccid myelitis (AFM), which is a poliomyelitis-like paralytic illness. Accumulating clinical, immunological, and epidemiological evidence has identified enterovirus D68 (EV-D68) as a major causative agent of these biennial AFM outbreaks. There are currently no available FDA-approved antivirals that are effective against EV-D68, and the treatment for EV-D68-associated AFM is primarily supportive. Telaprevir is an food and drug administration (FDA)-approved protease inhibitor that irreversibly binds the EV-D68 2A protease and inhibits EV-D68 replication . Here, we utilize a murine model of EV-D68 associated AFM to show that early telaprevir treatment improves paralysis outcomes in Swiss Webster (SW) mice. Telaprevir reduces both viral titer and apoptotic activity in both muscles and spinal cords at early disease time points, which results in improved AFM outcomes in infected mice. Following intramuscular inoculation in mice, EV-D68 infection results in a stereotypic pattern of weakness that is reflected by the loss of the innervating motor neuron population, in sequential order, of the ipsilateral (injected) hindlimb, the contralateral hindlimb, and then the forelimbs. Telaprevir treatment preserved motor neuron populations and reduced weakness in limbs beyond the injected hindlimb. The effects of telaprevir were not seen when the treatment was delayed, and toxicity limited doses beyond 35 mg/kg. These studies are a proof of principle, provide the first evidence of benefit of an FDA-approved antiviral drug with which to treat AFM, and emphasize both the need to develop better tolerated therapies that remain efficacious when administered after viral infections and the development of clinical symptoms. Recent outbreaks of EV-D68 in 2014, 2016, and 2018 have resulted in over 600 cases of a paralytic illness that is known as AFM. AFM is a predominantly pediatric disease with no FDA-approved treatment, and many patients show minimal recovery from limb weakness. Telaprevir is an FDA-approved antiviral that has been shown to inhibit EV-D68 . Here, we demonstrate that a telaprevir treatment that is given concurrently with an EV-D68 infection improves AFM outcomes in mice by reducing apoptosis and viral titers at early time points. Telaprevir also protected motor neurons and improved paralysis outcomes in limbs beyond the site of viral inoculation. This study improves understanding of EV-D68 pathogenesis in the mouse model of AFM. This study serves as a proof of principle for the first FDA-approved drug that has been shown to improve AFM outcomes and have efficacy against EV-D68 as well as underlines the importance of the continued development of EV-D68 antivirals.
Topics: Animals; United States; Mice; Enterovirus D, Human; Disease Models, Animal; Paralysis; Central Nervous System Viral Diseases; Enterovirus Infections; Antiviral Agents
PubMed: 37154751
DOI: 10.1128/jvi.00156-23 -
Medical Science Monitor : International... Mar 2020Todd's paralysis, a neurological abnormality characterized by temporary limb weakness or hemiplegia, typically occurs following a seizure, without enduring consequences.... (Review)
Review
Todd's paralysis, a neurological abnormality characterized by temporary limb weakness or hemiplegia, typically occurs following a seizure, without enduring consequences. Since limb weakness or hemiplegia can also be a common symptom of an acute ischemic stroke, it is often difficult to diagnose Todd's paralysis in individuals experiencing an acute ischemic stroke if they do not have a pre-existing history of epilepsy. Given that there is a limited understanding of Todd's paralysis, this review discusses the history, prevalence, clinical manifestations, duration, etiology, and diagnosis of Todd's paralysis. A few factors that may help clinicians distinguish Todd's paralysis from other clinical indications are as follows: (1) Todd's paralysis is commonly observed after partial seizures or generalized tonic-clonic seizures. (2) The incidence of Todd's paralysis is greater if the epilepsy is associated with old age or stroke history. (3) The duration of Todd's paralysis can range from minutes to days, depending on the type of seizure or whether the patient has experienced cortical structural damage. (4) The etiology of Todd's paralysis is associated with cerebral perfusion abnormality after seizures. Further research is needed to explore factors that distinguish Todd's paralysis from other indications that may lead to limb weakness in order to improve the diagnosis of Todd's paralysis.
Topics: Epilepsy; Humans; Paralysis; Seizures; Stroke
PubMed: 32134903
DOI: 10.12659/MSM.920751 -
The American Journal of Emergency... Aug 2022Unilateral paralysis is an alarming symptom with broad differential diagnoses, including stroke, Todd's paralysis, myelopathy, and peripheral neuropathy. Hypokalemic... (Review)
Review
Unilateral paralysis is an alarming symptom with broad differential diagnoses, including stroke, Todd's paralysis, myelopathy, and peripheral neuropathy. Hypokalemic paralysis (HP), a neuromuscular disorder associated with muscle dysfunction, is caused by hypokalemia and manifests as symmetric proximal extremity muscle weakness. Unilateral paralysis has rarely been reported in the literature. Once hypokalemia is corrected, HP is usually reversible. Delayed diagnosis and treatment may result in fatal consequences. Here, we report an atypical case of unilateral weakness along with a review of the literature on unilateral HP.
Topics: Humans; Hypokalemia; Hypokalemic Periodic Paralysis; Muscle Weakness; Paralysis; Stroke
PubMed: 35527097
DOI: 10.1016/j.ajem.2022.04.042 -
Journal of Neurology Nov 2023To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology. (Review)
Review
OBJECTIVE
To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology.
METHODS
Following PRISMA statement recommendations, 338 abstracts were screened independently by two authors. Inclusion criteria were research articles of human patients affected by BFP, either central or peripheral; English, Italian, French or Spanish language; availability of the abstract, while exclusion criteria were topics unrelated to FP, and mention of unilateral or congenital FP. Only full-text articles reporting the diagnostic work-up, the management, and the prognosis of the BFP considered for further specific data analysis.
RESULTS
A total of 143 articles were included, resulting a total of 326 patients with a mean age of 36 years. The most common type of the paralysis was peripheral (91.7%), and the autoimmune disease was the most frequent aetiology (31.3%). The mean time of onset after first symptoms was 12 days and most patients presented with a grade higher than III. Associated symptoms in idiopathic BFP were mostly non-specific. The most frequently positive laboratory exams were cerebrospinal fluid analysis, autoimmune screening and peripheral blood smear, and the most performed imaging was MRI. Most patients (74%) underwent exclusive medical treatment, while a minority were selected for a surgical or combined approach. Finally, in more than half of cases a complete bilateral recovery (60.3%) was achieved.
CONCLUSIONS
BFP is a disabling condition. If a correct diagnosis is formulated, possibilities to recover are elevated and directly correlated to the administration of an adequate treatment.
Topics: Humans; Adult; Facial Paralysis; Facial Nerve Diseases; Causality; Magnetic Resonance Imaging
PubMed: 37523065
DOI: 10.1007/s00415-023-11897-7 -
Toxins Apr 2017Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base... (Review)
Review
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits ( spp.) and taipans ( spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species ( spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.
Topics: Animals; Antivenins; Humans; Neuromuscular Junction; Neurotoxins; Paralysis; Snake Bites; Snake Venoms
PubMed: 28422078
DOI: 10.3390/toxins9040143 -
Journal of Internal Medicine Jul 2017The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our... (Review)
Review
The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our overall health. Scientists and engineers have been working for decades to tap into this network and 'crack the neural code' by decoding neural signals and learning how to 'speak' the language of the nervous system. Progress has been made in developing neural decoding methods to decipher brain activity and bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and for diagnosing brain-related diseases such as Parkinson's and Alzheimer's disease. In a recent first-in-human study involving paralysis, a paralysed male study participant regained movement in his hand, years after his injury, through the use of a bioelectronic neural bypass. This work combined neural decoding and neurostimulation methods to translate and re-route signals around damaged neural pathways within the central nervous system. By extending these methods to decipher neural messages in the peripheral nervous system, status information from our bodily functions and specific organs could be gained. This, one day, could allow real-time diagnostics to be performed to give us a deeper insight into a patient's condition, or potentially even predict disease or allow early diagnosis. The future of bioelectronic medicine is extremely bright and is wide open as new diagnostic and treatment options are developed for patients around the world.
Topics: Biosensing Techniques; Biotechnology; Brain; Electric Stimulation Therapy; Electronics, Medical; Forecasting; Humans; Neurons; Paralysis; Synaptic Transmission
PubMed: 28419590
DOI: 10.1111/joim.12610 -
Journal of Neuroengineering and... Nov 2023Individuals with a locked-in state live with severe whole-body paralysis that limits their ability to communicate with family and loved ones. Recent advances in... (Review)
Review
Individuals with a locked-in state live with severe whole-body paralysis that limits their ability to communicate with family and loved ones. Recent advances in brain-computer interface (BCI) technology have presented a potential alternative for these people to communicate by detecting neural activity associated with attempted hand or speech movements and translating the decoded intended movements to a control signal for a computer. A technique that could potentially enrich the communication capacity of BCIs is functional electrical stimulation (FES) of paralyzed limbs and face to restore body and facial movements of paralyzed individuals, allowing to add body language and facial expression to communication BCI utterances. Here, we review the current state of the art of existing BCI and FES work in people with paralysis of body and face and propose that a combined BCI-FES approach, which has already proved successful in several applications in stroke and spinal cord injury, can provide a novel promising mode of communication for locked-in individuals.
Topics: Humans; Brain-Computer Interfaces; User-Computer Interface; Locked-In Syndrome; Paralysis; Electric Stimulation; Brain
PubMed: 37980536
DOI: 10.1186/s12984-023-01272-y