A case report of spastic diplegic cerebral palsy in a late preterm child with hypoplastic left heart syndrome.

Background: Congenital heart disease (CHD) is the most common birth defect, affecting 1% of children who are born in the United States each year. Children with hypoplastic left heart syndrome, a type of critical CHD, are at high risk for neurodevelopmental disabilities, which are conditions that can affect motor, language, and cognitive development. In children with critical CHD, the severity and prevalence of their motor delays is most pronounced in infancy. Case Description: We present a case of a former late preterm male with hypoplastic left heart syndrome and history of hypoxic ischemic encephalopathy, who was diagnosed with spastic diplegic cerebral palsy in the setting of periventricular leukomalacia. Like many children with critical CHD, this child had gross motor delays and tone abnormalities in infancy. However, unlike many children with CHD, he continued to have neurologic differences that prompted additional evaluation through a Cardiac Neurodevelopmental Program. He was diagnosed with spastic diplegic cerebral palsy based upon clinical history and physical examination. Ancillary testing showed periventricular leukomalacia on brain magnetic resonance imaging (MRI); this finding was consistent with his clinical diagnosis. Conclusions: This is an interesting case report of spastic diplegic cerebral palsy in a late preterm infant with critical CHD. When making a diagnosis of cerebral palsy, it is important to consider the etiology of the motor impairment. Selective vulnerability may have played a factor in this child's condition. The most vulnerable part of the neonatal brain is the periventricular white matter; cerebral hypoxia can lead to periventricular leukomalacia. Children with CHD have brain dysmaturity beginning in-utero. Thus, it is possible that this child's brain dysmaturity may have increased his susceptibility to periventricular leukomalacia. Because most children with CHD have gross motor delays in infancy, it may be challenging to make a definitive diagnosis of cerebral palsy in an infant with critical CHD. Children with cerebral palsy have early motor delays that persist throughout life. It is the identification of persistent motor impairments through repeat evaluations that enabled this child's cerebral palsy diagnosis. This illustrates the importance of developmental surveillance in children with critical CHD.

Functional evaluation of novel variants of B4GALNT1 in a patient with hereditary spastic paraplegia and the general population.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurological disorders that are characterized by progressive spasticity and weakness in the lower limbs. SPG26 is a complicated form of HSP, which includes not only weakness in the lower limbs, but also cognitive impairment, developmental delay, cerebellar ataxia, dysarthria, and peripheral neuropathy, and is caused by biallelic mutations in the B4GALNT1 (beta-1,4-N-acetylgalactosaminyltransferase 1) gene. The B4GALNT1 gene encodes ganglioside GM2/GD2 synthase (GM2S), which catalyzes the transfer of N-acetylgalactosamine to lactosylceramide, GM3, and GD3 to generate GA2, GM2, and GD2, respectively. The present study attempted to characterize a novel B4GALNT1 variant (NM_001478.5:c.937G>A p.Asp313Asn) detected in a patient with progressive multi-system neurodegeneration as well as deleterious variants found in the general population in Japan. Peripheral blood T cells from our patient lacked the ability for activation-induced ganglioside expression assessed by cell surface cholera toxin binding. Structural predictions suggested that the amino acid substitution, p.Asp313Asn, impaired binding to the donor substrate UDP-GalNAc. An in vitro enzyme assay demonstrated that the variant protein did not exhibit GM2S activity, leading to the diagnosis of HSP26. This is the first case diagnosed with SPG26 in Japan. We then extracted 10 novel missense variants of B4GALNT1 from the whole-genome reference panel jMorp (8.3KJPN) of the Tohoku medical megabank organization, which were predicted to be deleterious by Polyphen-2 and SIFT programs. We performed a functional evaluation of these variants and demonstrated that many showed perturbed subcellular localization. Five of these variants exhibited no or significantly decreased GM2S activity with less than 10% activity of the wild-type protein, indicating that they are carrier variants for HSP26. These results provide the basis for molecular analyses of B4GALNT1 variants present in the Japanese population and will help improve the molecular diagnosis of patients suspected of having HSP.

[Applied anatomy study and preliminary clinical application of hyper selective neurectomy of triceps branches combined with partial neurotomy of S 2 nerve root to relieve spastic equinus foot].

Objective: To observe the possibility of hyper selective neurectomy (HSN) of triceps branches combined with partial neurotomy of S 2 nerve root for relieving spastic equinus foot. Methods: Anatomical studies were performed on 12 adult cadaveric specimens. The S 2 nerve root and its branches were exposed through the posterior approach. Located the site where S 2 joined the sciatic nerve and measured the distance to the median line and the vertical distance to the posterior superior iliac spine plane, and the S 2 nerve root here was confirmed to have given off branches of the pelvic splanchnic nerve, the pudendal nerve, and the posterior femoral cutaneous nerve. Between February 2023 and November 2023, 4 patients with spastic equinus foot were treated with HSN of muscle branches of soleus, gastrocnemius medial head and lateral head, and cut the branch where S 2 joined the sciatic nerve. There were 3 males and 1 female, the age ranged from 5 to 46 years, with a median of 26 years. The causes included traumatic brain injury in 2 cases, cerebral hemorrhage in 1 case, and cerebral palsy in 1 case. The disease duration ranged from 15 to 84 months, with a median of 40 months. The triceps muscle tone measured by modified Ashworth scale (MAC) before operation was grade 3 in 2 cases and grade 4 in 2 cases. The muscle strength measured by Daniels-Worthingham manual muscle test (MMT) was grade 2 in 1 case, grade 3 in 1 case, and 2 cases could not be accurately measured due to grade 4 muscle tone. The Holden walking function grading was used to evaluate lower limb function and all 4 patients were grade 2. After operation, triceps muscle tone, muscle strength, and lower limb function were evaluated by the above grading. Results: The distance between the location where S 2 joined the sciatic nerve and median line was (5.71±0.53) cm and the vertical distance between the location and posterior superior iliac spine plane was (6.66±0.86) cm. Before joining the sciatic nerve, the S 2 nerve root had given off branches of the pelvic splanchnic nerve, the pudendal nerve, and the posterior femoral cutaneous nerve. All the 4 patients successfully completed the operation, and the follow-up time was 4-13 months, with a median of 7.5 months. At last follow-up, the muscle tone of the patients decreased by 2-3 grades when compared with that before operation, and the muscle strength did not decrease when compared with that before operation. Holden walking function grading improved by 1-2 grades, and there was no postoperative hypoesthesia in the lower limbs. Conclusion: HSN of triceps branches combined with partial neurotomy of S 2 nerve root can relieve spastic equinus foot without damaging other sacral plexus nerves.

Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy.

BACKGROUND: Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology. OBJECTIVES: To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause. METHODS: Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing. RESULTS: Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed. CONCLUSIONS: RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Preclinical alternative drug discovery programs for monogenic rare diseases. The case of hereditary spastic paraplegias.

Patients diagnosed with rare diseases and their and families search desperately to organize drug discovery campaigns. Alternative models that differ from default paradigms offer real opportunities. There are, however, no clear guidelines for the development of such models, which reduces success rates and raises costs. We address the main challenges in making the discovery of new preclinical treatments more accessible, using rare hereditary paraplegia as a paradigmatic case. First, we discuss the necessary expertise, and the patients' clinical and genetic data. Then, we revisit gene therapy, de novo drug development, and drug repurposing, discussing their applicability. Moreover, we explore a pool of recommended in silico tools for pathogenic variant and protein structure prediction, virtual screening, and experimental validation methods, discussing their strengths and weaknesses. Finally, we focus on successful case applications.

Esophageal Per-Oral Endoscopic Myotomy (E-POEM): Future Directions and Perspectives.

PURPOSE OF REVIEW: POEM is a mature procedure endorsed by societal guidelines as a first line therapy for achalasia and spastic esophageal disorders. Nonetheless, several questions remain, including expanding indications for POEM, periprocedural evaluation and management, and the optimal POEM technique to enhance clinical success while mitigating risk for reflux. RECENT FINDINGS: There is uncertainty regarding several technical aspects of the POEM myotomy; though aggregating evidence supports the use of real-time impedance planimetry to guide the myotomy. While post-POEM reflux remains a concerning long term sequela, there is an increasing focus on the potential role of endoscopic anti-reflux interventions. Lastly, with the widespread adoption of POEM, we continue to witness ongoing efforts to standardize post-procedural care and training in this procedure. POEM is no longer a novel but rather established procedure. Yet, this technique has continued to evolve, with the aim of optimizing treatment success while reducing adverse events and risk for post-procedural reflux.

Thickened Retinal Nerve Fiber Layer Without Hypermyelination in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Purpose: To report the retinal findings in a patient with autosomal recessive spastic ataxia of Charlevoix-Saguenay. Methods: A case was evaluated. Results: A 16-year-old male patient with a known diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay was referred for evaluation of retinal hypermyelination given its frequent association with the condition. The patient was asymptomatic with a best-corrected visual acuity of 20/20. Optical coherence tomography of the peripapillary retinal nerve fiber layer (RNFL) showed bilateral thickening in each eye (average thicknesses: 180 µm, right eye; 177 µm, left eye). An examination showed no myelinization of the RNFL. Conclusions: Most studies to date describe RNFL thickening secondary to hypermyelination as a characteristic finding in autosomal recessive spastic ataxia of Charlevoix-Saguenay. This case provides evidence that this thickening may be a result of hypertrophy rather than hypermyelination. Further investigation is needed to define the pathophysiologic cause of RNFL thickening in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Two case reports of coronary spastic angina accompanied by the menstrual cycle.

Background: Coronary spastic angina (CSA) in premenopausal women is not frequent but has also been suggested to be associated with oestrogen decline during the menstrual cycle and sometimes becomes refractory and difficult to control. We experienced two premenopausal women with CSA that showed the involvement of the menstrual cycle. Case summary: Case 1: 41-year-old-woman had ST-segment elevation and chest pain during urosepsis, just 2 days after the onset of menstruation. The acetylcholine stress test was performed according to the menstrual cycle, and multiple coronary spasms were induced. Case 2: 40-year-old-woman had refractory chest pain as a symptom of premenstrual syndrome (PMS). Coronary angiography on drugs at the maximum dose revealed spontaneous multiple coronary spasms. Blood levels of oestrogen were normal, suggesting that hormonal change may be involved, and the introduction of low-dose pills made free from angina and the reduction of drug dose. Discussion: In premenopausal female angina pectoris, oestrogen may play a role; it is important to ask about the menstrual cycle and history of PMS. Besides, the timing of catheterization in premenopausal women with suspected CSA should be considered. Low-dose pills may be effective in some cases, and active medical collaboration with other departments such as gynaecology is desirable.　.

Novel de novo SPAST mutation in a Han Chinese SPG4 patient: a case report.

Spastic paraplegia type 4 (SPG4), the predominant form of Autosomal Dominant Hereditary spastic paraplegia (AD-HSP), is characterized by variants in the SPAST gene. This study reports a unique case of a late-onset SPG4 in a Han Chinese male, manifesting primarily as gait disturbances from lower extremity spasticity. Uncovered through whole-genome sequencing, a previously undocumented frameshift variant, c.1545dupA in exon 14 of the SPAST gene, was identified. Notably, this variant was absent in asymptomatic parents with confirmed paternity and maternity status, suggesting a de novo variant occurrence. This discovery emphasizes the potential of de novo variants to exhibit a late-onset pure pattern, extending the SPG4 variant spectrum, and consideration of such variants should be given in HSP patients with a negative family history.

Effect of Foot Posture on Limits of Stability in Children With Spastic Diplegic Cerebral Palsy.

Cerebral palsy (CP) is a neurological condition that affects musculoskeletal system causing altered balance control, which is governed by constant adjustments by muscular activity and joint positioning. Since the foot is the platform upon which we stand and balance, it is important to study and characterize foot posture abnormalities in CP to better understand their possible effect on multidirectional limits of stability (MDLS) in standing. Our aim was to find relation between foot posture and MDLS in diplegic children. Thirty diplegics (13 pes-planus and 17 pes-cavus) between the age of 6 to 14, gross motor function classification system (GMFCS) levels I and II, whose parents consented were included in this study. Diplegics unable to stand unsupported for < 2 minutes, undergone lower-limb surgeries in 6 months, having visual impairments were excluded. Foot posture was assessed with arch index, MDLS were measured by GEAMASTER stabilometer. There was significant positive correlation between foot posture and limits of stability. Diplegic children having pes-planus have better MDLS as compared with pes-cavus.

Botulinum toxin type A injection combined with biofeedback in the treatment of spastic pelvic floor syndrome.

BACKGROUND: Spastic pelvic floor syndrome (SPFS) is a refractory pelvic floor disease characterized by abnormal (uncoordinated) contractions of the external anal sphincter and puborectalis muscle during defecation, resulting in rectal emptation and obstructive constipation. The clinical manifestations of SPFS are mainly characterized by difficult defecation, often accompanied by a sense of anal blockage and drooping. Manual defecation is usually needed during defecation. From physical examination, it is commonly observed that the patient's anal muscle tension is high, and it is difficult or even impossible to enter with his fingers. AIM: To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome. METHODS: Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome. All patients underwent pelvic floor surface electromyography assessment, anorectal dynamics examination, botulinum toxin type A injection 100 U intramuscular injection, and two cycles of biofeedback therapy. RESULTS: After the botulinum toxin A injection combined with two cycles of biofeedback therapy, the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery (P < 0.05). Moreover, the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery (P < 0.05). CONCLUSION: Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome. Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively. However, randomized controlled trials are needed.

Pure Hereditary Spastic Paraplegia in a Patient With a Novel Heterozygous KIDINS220 Gene Mutation.

This case presents a somewhat unique and different phenotype of hereditary spastic paraplegia from previously reported kinase D-interacting substrate of 220 kDa (KIDINS220) gene mutation-related disease. We report a unique putative causative heterozygous mutation in KIDINS220 in a pure hereditary spastic paraplegia (HSP) patient expanding the HSP group further. We also deliberate on how our case was different from prior KIDINS220-related pathologies including spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, and the observation of KIDINS220 and aquaporin-4 (AQP4) downregulation in the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. These findings warrant further investigations of the biology of KIDINS220. With the advent of new gene editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), variants such as ours provide an opportunity for targeted precision medicine.

Comparison of Single Session Auditory Versus Visual Feedback on Performance and Postural Balance in Hemiplegic Children With Cerebral Palsy.

BACKGROUND:  Cerebral palsy (CP) is a pediatric disorder characterized by a motor impairment resulting from a permanent, non-progressive lesion in the brain. Cerebral palsy is marked by movement and postural control impairments, which greatly affect body structure, function, daily activities, and participation. OBJECTIVE: To compare the single-session auditory versus visual feedback on performance and postural balance in children with hemiplegic cerebral palsy. METHOD: The study was a crossover clinical trial involving a group of 25 patients diagnosed with CP hemiplegia, aged between 6 and 12 years, including both genders. Each patient underwent conventional balance therapy followed by either auditory feedback or visual feedback intervention. After a 48-hour wash-out period, they received conventional balance therapy again before undergoing the alternative intervention initially assigned. The Modified Ashworth scale (MAS), pediatric balance scale (PBS), timed one-leg stance, time up and go test (TUG), and center of pressure (CoP) displacements were assessed as the outcome measures before and after the interventions. RESULTS: Based on the one-leg stand test, TUG, and CoP displacement outcome measures results, both interventions improved balance time, speed of movement, and postural stability in children with hemiplegic spastic cerebral palsy (P < 0.05). Moreover, after a single session of the intervention, the visual feedback group demonstrated a significantly greater improvement in the TUG test, one-leg stand test, and CoP displacement compared to the auditory group (P < 0.05). CONCLUSIONS: The results of the study suggest that combining auditory or visual feedback with conventional balance therapy is effective in treating children with hemiplegic spastic cerebral palsy; furthermore, the utilization of visual feedback would be more effective. Further research is needed to determine the long-term effects of visual and auditory feedback on the assessed outcome measures.

Two Sibling Cases of Spastic Paraplegia-45 with a Novel Pathogenic Variant in NT5C2 Gene: Concomitant RYR1 Gene in One Sibling.

Introduction: Hereditary spastic paraplegia (SPG) is a genetically and clinically heterogeneous group of rare neurodegenerative disorders. SPG45 is the AR inherited type of complicated SPG, which is due to a mutation in the NT5C2 gene. Case Presentation: Two sisters, aged 8 and 4, exhibited delayed motor development since early childhood. They also experienced learning difficulties, dysarthric speech, ataxia, nystagmus, strabismus, and spasticity in their extremities. Additionally, brisk deep tendon reflexes were observed in their upper and lower limbs, and they exhibited positive pathological reflexes. Whole-exome sequencing identified a previously unidentified homozygous mutation in the NT5C2 gene, leading to the diagnosis of SPG45 in both siblings. A mutation in the RYR1 gene associated with malignant hyperthermia was also detected in one of the siblings, necessitating ongoing monitoring. Discussion/Conclusion: To the best of our knowledge, we report the first case of a patient with coexistence of the NT5C2 gene and the RYR1 gene.

A coactivation strategy in anticipatory postural adjustments during voluntary unilateral arm movement while standing in individuals with bilateral spastic cerebral palsy.

Individuals with bilateral spastic cerebral palsy (BSCP) reportedly has problems with anticipatory postural adjustments (APAs) while standing. However, the use of coactivation strategy in APAs in individuals with BSCP has conflicting evidence. Hence, this study aimed to investigate postural muscle activities in BSCP during unilateral arm flexion task in which postural perturbations occur in the sagittal, frontal, and horizontal planes. We included 10 individuals with BSCP with level II on the Gross Motor Function Classification System (BSCP group) and 10 individuals without disability (control group). The participants stood on a force platform and rapidly flexed a shoulder from 0° to 90° at their own timing. Surface electromyograms were recorded from the rectus femoris, medial hamstring, tibialis anterior, and medial gastrocnemius. The control group showed a mixture of anticipatory activation and inhibition of postural muscles, whereas the BSCP group predominantly exhibited anticipatory activation with slight anticipatory inhibition. Compared with the control group, the BSCP group tended to activate the ipsilateral and contralateral postural muscles and the agonist-antagonist muscle pairs. The BSCP group had a larger disturbance in postural equilibrium, quantified by the peak displacement of center of pressure during the unilateral arm flexion, than those without disability. Individuals with BSCP may use coactivation strategy, mainly the anticipatory activation of postural muscle activity, during a task that requires a selective postural muscle activity to maintain stable posture.

Reduction of sacsin levels in peripheral blood mononuclear cells as a diagnostic tool for spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disease caused by biallelic variants in the SACS gene encoding for sacsin. More than 200 pathogenic variants have been identified to date, most of which are missense. It is likely that the prevalence of autosomal recessive spastic ataxia of Charlevoix-Saguenay is underestimated due to the lack of an efficient diagnostic tool able to validate variants of uncertain significance. We have previously shown that sacsin is almost absent in fibroblasts of patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay regardless of the type of SACS variant, because sacsin carrying missense variants is cotranslationally degraded. In this work, we aimed to establish the pathogenicity of SACS variants by quantifying sacsin protein in blood samples, with relevant implications for autosomal recessive spastic ataxia of Charlevoix-Saguenay diagnosis. We developed a protocol to assess sacsin protein levels by western blot using small amounts of peripheral blood mononuclear cells, which can be propagated in culture and cryopreserved. The study involves eight patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (including a novel case) carrying variants of different types and positions along the SACS gene and two parents who are carriers of heterozygous missense variants. We show that patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (carrying either missense or truncating variants) almost completely lacked sacsin in peripheral blood mononuclear cells. Moreover, both carriers of a SACS missense variant showed 50% reduction in sacsin protein levels compared to controls. We also describe a patient with uniparental isodisomy carrying a homozygous nonsense variant near the 3' end of the SACS gene. This resulted in a stable sacsin protein lacking the last 202 amino acids, probably due to escape of nonsense-mediated decay of mRNA. In conclusion, we have optimized a minimally invasive diagnostic tool for autosomal recessive spastic ataxia of Charlevoix-Saguenay in blood samples based on sacsin protein level assessment. Indeed, our results provide definite evidence that sacsin carrying missense pathogenic variants undergoes cotranslational degradation. The quantitative reduction in sacsin levels in the case of missense variants of uncertain significance allows defining them as pathogenic variants, something which cannot be predicted bioinformatically with high certainty.

Role of Interleukin-17 cytokine family in human T-cell lymphotropic virus type 1 (HTLV-1) infection and associated diseases.

BACKGROUND: Human T-lymphotropic virus (HTLV-1) is a neglected virus with worldwide distribution of over 10 million people and is the cause of two main associated diseases Adult T cell Leukemia-Lymphoma (ATLL), and HTLV-1-associated Myelopathy/Tropical Spastic paraparesis (HAM/TSP). The IL-17 cytokine family plays a crucial role in the host immunity against HTLV-1 and the development of associated disease. A systematic review was conducted to analyze all research reporting on the levels or expression of the IL-17 HTLV-1 infection and associated diseases. METHODS: The literature search was conducted in electronic databases including PubMed/Medline and Web of Sciences until January 31st, 2024, followed by the PRISMA guidelines. RESULTS: Our search revealed 20 eligible articles to be included in our study. The total number of cases studied was 1420, of which 386 were carriers without any symptoms, and were 176 ATLL and 237 HAM/TSP. The IL-17 cytokine family production or mRNA expression was higher in HAM/TSP patients but showed a trend toward reduction in the case of ATLL. CONCLUSIONS: Our results showed that while The IL-17 cytokine family plays a significant role in the immunopathogenesis of disease and clinical status of patients with inflammatory disorders such as HAM/TSP, IL-17 production is diminished and the RORC/IL-17 signaling pathway is downregulated during ATLL. Our data suggest that boosting the RORC/IL-17 signaling pathway in ATLL and using anti-IL-17 agents in HAM/TSP and other HTLV-related inflammatory conditions might benefit patients and improve their outcomes.

Intramedullary Spinal Epidermoid Cyst-A Rare Cause of Spastic Paraparesis.

Spinal intramedullary epidermoids are rare intramedullary lesions of the spinal cord. They may be congenital or acquired with the congenital type often associated with spinal dysraphism and other spinal anomalies. The clinical presentation depends on the level of the involvement of the spinal cord. Management of these lesions is surgical excision. We report a case of intramedullary spinal epidermoid who presented with spastic paraparesis.

Novel Machine Learning Analysis Algorithm of DNA Methylation Patterns Identifies Cerebral Palsy with Concurrent Epilepsy.

Background: Spastic cerebral palsy, the most common pediatric-onset disabling condition with an estimated prevalence of 0.2% in children, is a complex condition characterized by stiff movement, muscle contractures, and abnormal gait that can diminish quality of life. Spastic CP accounts for approximately 83% of all CP cases and frequently co-occurs with other complex conditions, like epilepsy. An estimated 42% of spastic CP cases have co-occurring epilepsy. Unfortunately, CP is often difficult to diagnose. Although most children with CP are born with it or acquire it immediately after birth, many are not identified until after 19 months of age with CP diagnosis often not confirmed until 5 years of age. New bioinformatic approaches to identify CP earlier are needed. Recent studies indicate that altered DNA methylation patterns associated with CP may have diagnostic value. The potential confounding effects of co-occurrent epilepsy on these patterns are not known. We evaluated machine learning classification of CP patients with or without co-occurring epilepsy. Results: Whole blood samples were collected from 30 study participants diagnosed with epilepsy (n=4), spastic CP (n=10), both (n=8), or neither (n=8). A novel Support-Vector-Machine learning algorithm was developed to identify methylation loci that have ability to classify CP from controls in the presence or absence of epilepsy. This algorithm was also employed to measure classification ability of identified methylation loci. After preprocessing of data, isolation of important methylation loci was performed in a binary comparison between CP and controls, as well as in a 4-way scheme, encapsulating epilepsy diagnoses. The classification ability was similarly assessed. CP Classification performance was evaluated with and without inclusion of epilepsy as a feature. Median F1 scores were 0.67 in 4-class comparison, and 1.0 in the binary classification, outperforming Linear-Discriminant-Analysis (0.57 and 0.86, respectively). Conclusion: This novel algorithm was able to classify study participants with spastic CP and/or epilepsy from controls with significant performance. The algorithm shows promise for rapid identification in methylation data of diagnostic methylation loci. In this model, Support Vector Machines outperformed Linear Discriminant Analysis in classification. In the evaluation of epigenetics-based diagnostics for CP, epilepsy may not be a significant confounding factor.

Diving deep: zebrafish models in motor neuron degeneration research.

In the dynamic landscape of biomedical science, the pursuit of effective treatments for motor neuron disorders like hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) remains a key priority. Central to this endeavor is the development of robust animal models, with the zebrafish emerging as a prime candidate. Exhibiting embryonic transparency, a swift life cycle, and significant genetic and neuroanatomical congruencies with humans, zebrafish offer substantial potential for research. Despite the difference in locomotion-zebrafish undulate while humans use limbs, the zebrafish presents relevant phenotypic parallels to human motor control disorders, providing valuable insights into neurodegenerative diseases. This review explores the zebrafish's inherent traits and how they facilitate profound insights into the complex behavioral and cellular phenotypes associated with these disorders. Furthermore, we examine recent advancements in high-throughput drug screening using the zebrafish model, a promising avenue for identifying therapeutically potent compounds.