Limb Weakness Research Articles

Chronic inflammatory demyelinating polyneuropathy associated with active systemic lupus erythematous: Anifrolumab as a potentially successful add-on therapy to intravenous immunoglobulins.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy, rarely reported as being associated with systemic lupus erythematous (SLE). We report the case of 53-year-old women with a long history of SLE, diagnosed with CIDP during a lupus flare beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. She received treatment with steroids, intravenous immunoglobulins and anifrolumab and showed clinical and immunological improvement. It is important to take into account the presence of peripheral neurological disorders in patients with SLE, considering CIDP as an uncommon manifestation. Controlling severe active disease is an imperative issue to manage this neurological manifestation which has a serious impact on health-related quality of life and physical function.

Linking LRP12 CGG repeat expansion to inherited peripheral neuropathy

BackgroundThe causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on...

Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency

Case presentationA girl aged 2 years and 5 months presented to the hospital with chief complaints of intermittent fever and weakness of the left limb for more than 1 month. The child had transient urticaria appearing on her face for 5 days. The inflammatory biomarkers were significantly increased. Brain MRI showed multiple ischemic lesions in the brain’s small vessels. The patient exhibited significant systemic inflammation and multiple vasculitis. Whole-exome sequencing showed c.1358A>G p. (Tyr453Cys) and c.1082-7T>A compound heterozygous variants in the adenosine deaminase 2 (ADA2) gene, of which the c.1082-7T>A variant has not been reported yet in previous literature. Peripheral blood mRNA reverse transcription-Sanger sequencing confirmed that this variant affected mRNA splicing, resulting in a frameshift with premature stop codon c.1083_1103del p. (Leu362Glnfs*45). Peripheral blood test suggested a significant decrease in ADA2 activity. Eventually, the patient was diagnosed with deficiency of adenosine deaminase 2 (DADA2). Her condition improved after treatment with etanercept. She had no more fevers, and no hemiplegia attacks were observed during the 3 years of follow-up.ConclusionFever and hemiplegia were the main manifestations in this patient, without typical rashes. DADA2 was finally confirmed by enzymology and genetic testing, and we believe this is the first reported case of the c.1082-7T>A intronic variant in DADA2, and the RNA studies conducted in this case have been pivotal in assessing its pathogenicity.

Tuberculous longitudinal extensive transverse myelitis: 2 cases and literature review

Context This study aimed to investigate the characteristics, diagnosis, and management of tuberculous longitudinally extensive transverse myelitis (TB-LETM), a rare manifestation of tuberculosis. Findings We analyzed two rare cases of TB-LETM and discussed their clinical manifestations and imaging findings in the context of the relevant literature. Patient 1, a 23-year-old female, presented with quadriplegia and dysuria, and spinal magnetic resonance imaging (MRI) revealed lesions extending from C1 to T3. Patient 2, an 18-year-old female, reported acute-onset numbness and weakness in both lower limbs, with MRI showing lesions from T1 to T4, along with multiple intracranial leptomeningeal enhancements. Both patients had elevated cerebrospinal fluid (CSF) cell counts and protein levels, and positive blood T-cell spot test (T-SPOT.TB), but no microbiological evidence of Mycobacterium tuberculosis was found. Diagnosis was based on clinical presentation, medical history, chest computed tomography (CT) findings, and CSF analysis. Over the past decade, 14 cases of TB-LETM have been reported. Common symptoms include fever, acute paralysis, sensory deficits in the lower limbs, and dysuria. Elevated CSF protein, lymphocytosis, and decreased glucose levels are essential for differentiating TB-LETM from autoimmune disorders. Conclusion Longitudinally extensive transverse myelitis (LETM), especially when involving the cervical and thoracic cords, should be considered a potential manifestation of tuberculosis infection. Analysis of cerebrospinal fluid, MRI findings, and T-SPOT testing can provide crucial diagnostic insights. A combination of anti-tuberculosis therapy and corticosteroids has proven clinically effective in managing this condition.

Analysis of a Case of Immune-Related Myocarditis Combined with Myasthenia Gravis and Liver Injury Induced by Tislelizumab

Immune checkpoint inhibitors (ICIs) have demonstrated significant advantages and potential in tumor immunotherapy, but immune-related adverse events (irAEs) are becoming increasingly important safety issues. This article analyzes and discusses a case of a patient with esophageal cancer who developed bilateral lower limb weakness, bilateral ptosis, loss of appetite, nausea, and vomiting after four cycles of treatment with tislelizumab. The patient was considered to have immune-related myocarditis, myasthenia gravis, and liver injury involving multiple organs caused by tislelizumab treatment. As multi-organ damage caused by tislelizumab is rarely reported domestically and internationally, this article will analyze and discuss domestic and foreign literature, hoping to provide some help to clinicians who subsequently use tislelizumab.

Progression from outpatient referral to spinal surgery in an Australian cohort with degenerative spinal disease.

Degenerative spine disease (DSD) encompasses a range of conditions with increasing prevalence and a significant burden of disease. Patients with DSD are often referred to a neurosurgery clinic with lengthy waiting times from referral to consultation. The reported proportion of referred patients who undergo spinal surgery varies from 20.05% to 54% in heterogenous study populations from predominantly North American and European study populations. These rates do not correlate with institutional data in the Australian public hospital system and there is limited Australian data in the literature. This retrospective study aimed to quantify the proportion of patients referred to a neurosurgery clinic who progressed to elective spinal surgery and explore predictors for surgery based on referral contents. All patients referred for DSD to a single tertiary centre between 1/1/16 and 31/12/22 were included. Referrals for spinal pathology due to trauma, infection or tumour were excluded. Patient demographics, clinical presentation and imaging findings contained in the outpatient referral were recorded. Outcomes, including progression to surgery, were also recorded. Univariate and multivariate analysis was performed to determine predictive factors for surgery. Of 5189 referrals, only 471 (9.1%) underwent surgery. Only 4.7% had surgery at our institution with the remaining 4.4% undergoing surgery elsewhere. Referrals from neurologists, rheumatologists and referrals specifying limb weakness or sensory change, were more likely to progress to surgery, although these predictors were only present in 0.7 - 3.9% of referrals. Axial pain negatively predicted surgery. To our knowledge, this is the only study in an Australian population to analyse the outcome of DSD referrals to neurosurgery clinic, based on referral contents alone. The vast majority of patients do not require surgery. Though there are a few predictive factors, progression to surgery cannot reliably be predicted from the referral, highlighting the opportunity to improve patient outcomes and healthcare utilisation for patients with DSD.

MANAGEMENT OF TRAUMATIC QUADRIPARESIS (ABHIGHĀTAJA SARVĀṄGA VĀTA) WITH PAÑCAKARMA THERAPIES - A CASE STUDY

Globally, 15 million people are living with spinal injuries. Spinal injury Percentage of total Neurological disorders disease burden in India is 1.9.The following is a case managed in Dept of Pañchakarma, S.V. Ayurvedic Hospital, Tirupati, depicting the success of various Pañchakarma therapies. A 65-year-old male patient with a chief complaint of loss of sensations from below the neck and weakness in both upper and lower limbs, giving the history of a road traffic accident in the year 2015 and underwent Microscopic anterior cervical C3 - C4 discectomy and fusion surgery after the accident. He has been treated with Sarvāṅga Abhyaṅga and Nāḍī swedam for 3 days, Mātrāvasti with Nirguṇḍītailam for 7 days, Kālavasti with Vājigandhādiyoga for Āsthāpana and Nirguṇḍī tailam for Anuvāsana for 16 days. The ASIA scale score recorded at the outset was 78/324, Which improved to 205/324 after the completion of therapies. The patient ultimately regained his sensations and had moderate improvement in motor power of muscles, which was reflected in the ASIA scale. Sarvāṅga Abhyaṅga and Nāḍī swedam administered initially have been considered as the first-line therapies in the management of vitiated Vāta. The Mātrāvasti administered afterwards has tremendous Vātahara property. The Vājigandhādi yoga, which has been explained in Vaṅgasena for the management of Gṛdhrasīvāta, is tried here in Kālavasti format. The abovestated Pañchakarma therapies have shown significant amelioration in both sensory and motor deficits. More over they proved safe during the entire length of course.

Late-onset CSF1R-related Disorder: A Case Report.

CSF1R-related disorder, a catastrophic neurodegenerative disease, arises from genetic mutations in the colony-stimulating CSF1R. Initial misdiagnosis is common, as demonstrated by this case involving a 52-year-old female who presented with symptoms of limb numbness and weakness. Differential diagnosis first indicated Parkinsonism, lacunar infarction, and cervical spondylosis. Subsequently, however, this patient's clinical presentation evolved to include bradykinesia, cognitive decline, and a spectrum of neurological manifestations. A Pan-V2 assay revealed a heterozygous mutation in the CSF1R gene. Craniocerebral MRI showed cerebral infarctions, lacunar infarctions, and leukoaraiosis. Despite symptomatic treatments, our patient's clinical status continued to decline until her family chose to discontinue further medical interventions. This case underscores the diagnostic complexities of early detection of CSF1R-related disorders. It emphasizes the importance of including leukodystrophy in such differential diagnoses and the need for prompt genetic screening in patients who present with progressive leukoencephalopathy, especially when cerebrospinal fluid analysis is unremarkable.

Navigating Complexity in Pediatric NMOSD: Unusual Symptoms and Adverse Reactions: A Case Report

Background and Clinical Significance: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune demyelinating disorder of the central nervous system, characterized by the presence of aquaporin-4 (AQP4) antibodies and a high relapse rate. We provide information about the diagnosis, unusual symptoms, and treatment of a paediatric patient with NMOSD. Case Presentation: A 14-year-old girl was hospitalized for weakness and paraesthesia of the lower limbs (LL). The patient underwent detailed investigations and was diagnosed with NMOSD and cryptogenic organizing pneumonia. Initial treatment with methylprednisolone and prednisone yielded a favourable response. Therapy with mycophenolate was initiated. However, the patient experienced two more relapses, prompting the use of rituximab therapy with a favourable outcome and a two-year relapse-free follow-up period. Conclusions: Patients with NMOSD may have multisystemic inflammation, including organs outside the central nervous system. Our case report highlights a case of NMOSD, pulmonary involvement, and unusual adverse reactions to rituximab.

Associative brain-computer interface training increases wrist extensor corticospinal excitability in patients with subacute stroke.

In a recently developed associative rehabilitative brain-computer interface (BCI) system, electroencephalography (EEG) is used to identify the most active phase of the motor cortex during attempted movement and deliver precisely timed peripheral stimulation during training. This approach has been demonstrated to facilitate corticospinal excitability and functional recovery in patients with lower limb weakness following stroke. The current study expands those findings by investigating changes in corticospinal excitability following the associative BCI intervention in patients with post stroke with upper limb weakness. In a randomized controlled trial, 24 patients with subacute stroke, subdivided into an intervention group and a "sham" control group, performed 30 wrist extensions. The intervention comprised 30 pairings of single peripheral nerve stimulation at the motor threshold, timed so that the generated afferent volley arrived at the motor cortex during the peak negativity of the movement-related cortical potential (MRCP), which was identified with EEG. The sham group underwent the same intervention, though the intensity of the nerve stimulation was below the perception threshold. Immediately after training, patients in the associative group exhibited significantly larger amplitudes of muscular-evoked potentials, compared with pretraining measurements in response to transcranial magnetic stimulation. These changes persisted for at least 30 min and were not observed in the sham group. We demonstrate that motor-evoked potential amplitudes increased significantly following paired associative BCI training targeting upper limb muscles in patients with subacute stroke, which is in line with results from lower limb studies.NEW & NOTEWORTHY We have demonstrated that a single training session with an associative brain-computer interface increased corticospinal excitability in patients suffering from upper limb weakness following stroke. This is the first time such an effect is described in the upper limb, which paves the way for effect augmentation of existing upper limb rehabilitation protocols.

Drug-Induced Cauda Equina Syndrome in an 8-Year-Old Boy With Acute Lymphoblastic Leukemia: An Uncommon Case Report.

Intrathecal methotrexate can cause cauda equina syndrome in pediatric ALL patients, as demonstrated in this rare case of an 8-year-old boy. Symptoms included progressive limb weakness and urinary retention. Early recognition, prompt discontinuation of the offending agent, and multidisciplinary management are crucial. Vigilant neurological monitoring is essential for pediatric acute lymphoblastic leukemia patients receiving intrathecal chemotherapy.

Diffuse large B-cell lymphoma presenting as acute lumbosacral plexopathy with persistent lower back pain and fatigability

ABSTRACT Various types of lymphoma can involve the lumbosacral plexus, mainly diffuse large B-cell lymphoma, in which cancer-related persistent fatigue and fatigability (a new concept that assesses fatigue to specific activities) can occur. We report a rare case of acute right L2-S1 lumbosacral plexopathy secondary to diffuse large B-cell lymphoma, presenting with persistent lower back pain and pronounced fatigability. A 49-year-old male with controlled primary hypothyroidism experienced progressive lower back pain extending to the right lower limb, accompanied by dysesthesias and significant fatigue exacerbated by physical activities. Clinical examination revealed asymmetrical lower limb weakness, an absent right ankle reflex, and a positive straight leg raise test indicative of lumbosacral plexopathy. Comprehensive serological and imaging evaluations, including MRI and 18F-FDG PET-CT, identified lumbosacral spine lesions and widespread lymphomatous involvement. Immunohistochemical analysis confirmed the presence of CD20+, CD10+, bcl2+, bcl6+, and MUM1+ cells, establishing a diagnosis of diffuse large B-cell lymphoma. This case underscores the importance of considering lymphomatous lumbosacral plexopathy in the differential diagnosis of fatigability and lower back pain to prevent misdiagnosis and ensure timely, appropriate treatment. Further studies are suggested to explore the implications of lymphoma on neuropathy and chronic fatigability among survivors.

Anti-sulfatide antibody-positive Guillain–Barré syndrome in adults following off-craniotomy for cerebellar contusion: A case report

Rationale: Gullain–Barré syndrome (GBS) is a rare autoimmune condition primarily presenting with symmetrical progressive limb weakness. It is frequently associated with sensory and autonomic symptoms and autonomic disturbances and often manifests seropositivity for anti-ganglioside antibodies. Infections are considered major precipitants; however, GBS post-craniotomy for severe traumatic brain injury is a rarity. Patient concerns: A 79-year-old female underwent craniotomy for a cerebellar contusion sustained from severe traumatic brain injury, leading to quadriplegia, autonomic dysfunction, dilated pupils, and respiratory failure. However, the patient’s GBS manifested slightly differently. Her limb weakness was asymmetric and progressed from 1 upper limb to the other. Diagnoses: The diagnosis of GBS was confirmed based on clinical presentation, cerebrospinal fluid analysis showing albuminocytologic dissociation, and the detection of anti-sulfatide antibodies in serum. Interventions: The patient received intravenous immunoglobulin (IVIG) therapy at 2 g/kg daily, along with supportive measures including mechanical ventilation and rehabilitation. Outcomes: The patient demonstrated significant improvement within 5 days of IVIG treatment, achieving near-complete functional recovery with grade 4 muscle strength at discharge 6 weeks post-intervention. Lessons: This case highlights the need to consider GBS in postoperative patients with acute limb weakness, even in atypical presentations. Early recognition and timely IVIG treatment are critical for favorable outcomes.

Over-supplement of vitamin D may cause delirium, abdominal distension, and muscle weakness in the elderly: A case report and literature review

Rationale: Vitamin D deficiency is common among the elderly due to limited sunlight exposure, increasing osteoporosis risk. Over-supplementation poses risks, especially with caregiver involvement. Patient concerns: Rising vitamin D overdose cases underscore the need for better education on safe intake and monitoring practices to prevent toxicity, particularly hypercalcemia from excessive doses. Diagnoses: This case report details the clinical presentation and management of a woman who exhibited progressive lower limb weakness, delirium, and abdominal distension over a 3-day period. Initial assessments ruled out intracranial hemorrhage but revealed significant electrolyte imbalances, including hyponatremia, hypokalemia, hypomagnesemia, and severe hypercalcemia. Upon further inquiry, it was discovered that the patient had consumed an excessive amount of liquid Vitamin D3 over the preceding 3 weeks, surpassing the threshold for vitamin D intoxication. Interventions: Intravenous fluid hydration was initiated to promote calcium excretion. Bisphosphonates and calcitonin were administered to reduce serum calcium levels. Electrolyte imbalances, including hyponatremia, hypokalemia, and hypomagnesemia, were corrected. Continuous monitoring and supportive care were provided in the geriatric ward. Outcomes: After these treatments, the patient’s electrolyte levels stabilized, and her symptoms, such as confusion and muscle weakness, gradually improved, leading to a full recovery. Lessons: This case underscores the importance of recognizing hypercalcemia, particularly in the elderly, where symptoms may manifest nonspecifically. Additionally, it highlights the potential risks associated with medication errors and inadvertent overdoses, particularly in situations involving elderly spousal caregivers.

Hereditary Spastic Paraplegia Linked to Abnormal Splicing From an AIMP1 Missense Variant.

Hereditary spastic paraplegias (HSP) are a diverse group of neurodegenerative diseases characterized by lower limb spasticity and weakness. To date, over 80 genes have been associated with HSP, but many families remain without a molecular diagnosis. In this study, linkage analysis and whole-exome sequencing (WES) were performed to identify the causal gene in a HSP family with autosomal recessive inheritance. Multipoint linkage analysis revealed a maximum significant multipoint LOD score of 4.6 on chromosome 4. WES analysis focused on this region led to the identification of a homozygous missense variant in AIMP1 (c.223G>A). Minigene assays showed that the presumed missense variant in AIMP1 caused loss of the exon 3 donor splice site. Ultimately, this led to the use of an alternative splice site within the intron and the insertion of a premature stop codon. The identification of a novel AIMP1 causal variant contributes to the growing list of HSP genes. Furthermore, it shows that, considering also previous reported cases, disruption of AIMP1 causes a spectrum of disorders ranging from intellectual disability to more complex neurodegenerative diseases.

Rare but relevant: Nitrous oxide and peripheral neurotoxicity, what do we know?

Nitrous oxide (N2O), used medically as an anaesthetic, has gained popularity as a recreational drug, with rising prevalence particularly among young adults. While its reinforcing and addictive potential remains debated, N2O is proven to be neurotoxic, especially with prolonged, heavy use, which is often unexpected for users. The neurotoxicological mechanism underlying N2O-induced neurotoxicity involves inactivation of vitamin B12 (cobalamin), which disrupts methionine synthesis, essential for maintaining the myelin sheath. This can result in demyelinating diseases, including generalized demyelinating polyneuropathy (GDP). Clinical incidence of N2O-induced peripheral neuropathy is largely unknown, although some research suggests it is not uncommon. Treatment includes immediate cessation of N2O use and vitamin B12 supplementation. Although this treatment often reverses damage, residual symptoms such as limb weakness may persist. Additionally, genetic and dietary factors, such as vitamin B12 deficiency, may heighten individual vulnerability for N2O's detrimental effects.

Effect of Multisensory Exercise Training on Sensation and Balance in Patients with Diabetic Neuropathy – A Pilot Study

Background: Diabetic peripheral neuropathy, is a common manifestation of peripheral nervous system in diabetes due to elevated glucose level. Symptoms include painful lower limbs, altered sensation, reduce reflexes and weakness of lower limb resulting in impairment in balance and gait. As treatment various interventions are used such as balance training, strength training, aerobic exercise, sensory motor training. Aim of study: This study was to assess the effect of multisensory exercise training on sensation and balance in patients with diabetic neuropathy. Methodology: This study was conducted in various OPDs and diabetic center of Surat. 10 diabetic neuropathic patients were randomly assigned in to 2 groups; 5 patients were allocated in group A (conventional & multisensory training) and 5 patients were allocated in group B (conventional therapy). Patients in both groups were treated for 3 days per week for 4 weeks. Conventional physiotherapy was given for 3 days in a week at home for 4 weeks. Sensation and balance were assessed by using Semmes-Weinstein Monofilaments and berg balance scale respectively. Data were recorded at baseline and after 4 weeks of training. Result: The result showed there was no significant difference in effect of multisensory exercise on sensation and there was significant improvement in balance in patients with diabetic neuropathy. Conclusion: The result of study indicate that 4 weeks of multisensory exercise program was improving balance in patients with diabetic neuropathy as compare to conventional therapy. Key words: Multisensory exercise, Sensation, Balance, Diabetic neuropathy

Spinal cord cyst of the 14-year-old boy. Case report.

Spinal cord cysts in children are rare but can causevarious symptoms depending on their size andlocation. We present a 14 -14-year-old boy whopresented weakness of the lower right limb with gaitabnormality, posterior cord ataxia, and difficultygetting up from a sitting position and rising from asquatting position. Magnetic resonance imaging ofthe thoracic spine showed the presence of a largefluid area (110 mm x 30 mm x 17mm) locatedintracanalicularly, extradurally, from Th 9 to L1,posterior to the spinal cord, displacing the spinalcord forward and to the right. After consultation with a neurosurgeon, the patient was transferred to thePediatric Neurosurgery Department of the Instituteof Pediatric Medicine in Warsaw for furthertreatment. Surgery was performed to remove thespinal cord cyst. Histopathological examinationexcluded a neoplastic process. After 4 days in thehospital, the patient was discharged in goodcondition. The motor function improved over severaldays.

Onasemnogene Abeparvovec is Safe in Hemolytic Disease of the Newborn: A Case Report.

Spinal muscular atrophy (SMA) is a rare autosomal recessive genetic disease caused by Survival Motor Protein 1 (SMN1) gene mutations. Classically divided into three types, SMA is characterized by hypotonia, weakness, and tongue fasciculation in the first 6 months of life in type 1, inability to walk and limb weakness in type 2, and failure to run with proximal weakness in type 3 SMA. With the advent of newborn screening, treating presymptomatic patients with Onasemnogene abeparvovec (OA) is the treatment of choice in some centers worldwide. The incidence of jaundice is high in this age group, with no recommendation to guide the use of OA in newborns with jaundice. To our knowledge, treating an SMA patient with alloimmune hemolytic disease of the newborn (HDN), a relatively common disease in the newborn period, has never been reported in the past. We report our experience with dosing a presymptomatic child with SMA who had neonatal jaundice and hemolytic anemia due to hemolytic disease of the newborn who tolerated the treatment well. To our knowledge, this is the first case to report the safety of this novel treatment for an SMA patient with alloimmune HDN.

Catastrophic antiphospholipid syndrome of pregnancy with acute massive cerebral infarction: A case report.

Catastrophic antiphospholipid syndrome (CAPS) is the most serious type of antiphospholipid antibody syndrome (APS) and can be easily confused with other disorders, such as hemolytic uremic syndrome, disseminated intravascular coagulation and thrombocytopenia syndromes. Timely diagnosis of CAPS poses considerable challenges due to its rarity and the fact that clinicians often lack knowledge of the disease. A 21-year-old patient was 32 weeks and 5 days pregnant when she presented to the hospital with a 7-hour history of sudden onset of left-sided limb weakness with no apparent cause. Lupus anticoagulant and/or anticardiolipin antibodies were positive. Head magnetic resonance imaging + magnetic resonance angiography + diffusion weighted imaging: right temporo-occipital insula, right basal ganglia and bilateral radial corona-hemispheric center showed multiple acute-phase cerebral infarction changes and right middle cerebral artery occlusion. Catastrophic antiphospholipid syndrome. By intracranial artery thrombectomy and anticoagulation with low-molecular heparin. The patient's left limb muscle strength recovered to grade 5. A healthy baby boy was delivered by cesarean section. Both mother and child are safe. The rarity of CAPS is such that misdiagnosis often occurs, culminating in serious complications and even death, emphasizing the need for early recognition, timely diagnosis and immediate treatment. In CAPS that improves with treatment, monitoring and prevention of recurrence is also essential.