Lower Extremity Weakness Research Articles

CLRM-02 CALCIFIED SPINAL MENINGIOMAS: A SYSTEMATIC REVIEW OF CLINICAL CHARACTERISTICS, TREATMENT STRATEGIES, AND OUTCOMES

Abstract Calcified meningiomas involving the spine are rare but can pose significant surgical challenges. We systematically reviewed the literature on calcified spinal meningiomas. PubMed, EMBASE, Web-of-Science, and Scopus databases were searched to include studies reporting clinical data of patients with calcified spinal meningioma. Included articles were analyzed for symptoms, imaging, spine level of the tumor, tumor location relative to the spinal cord, calcification status, treatment regimen, recurrence, progression-free survival, and outcomes. A total of 35 articles encompassing 94 patients were included. Most patients were female (90.4%), presenting with lower extremity weakness (44%) and/or lower extremity paresthesia (38.1%). Most calcified spinal meningiomas occurred in the thoracic spine (82%) and on the dorsal (33.3%) or ventral (27.2%) side relative to the spinal cord. Most tumors were intradural (87.2%). Histologically, most calcified spinal meningiomas were WHO grade I (97.4%) and psammomatous (50.7%). Most tumors demonstrated macroscopic calcification (48.9%). Most patients underwent gross total resection (91.5%) through a posterior approach (100%). Two patients (2.1%) received adjunctive radiotherapy. The most common treatment related complication was CSF leakage. Post-operatively, most patients demonstrated symptomatic improvement (75.5%) and 2 (2.1%) had local tumor recurrence. Calcified spinal meningiomas are uncommon but benign entities. These neoplasms tend to adhere to surrounding tissues and nerves and, thus, can be surgically challenging to remove. In most patients, safe gross total resection remains the standard of care, but accurate surgical planning is necessary to reduce the risks of postoperative complications.

Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ10 deficiency: Hypomorphic variants and two distinct disease entities.

Primary coenzyme Q10 (CoQ10) deficiency is a group of inborn errors of metabolism caused by defects in CoQ10 biosynthesis. Biallelic pathogenic variants in COQ7, encoding mitochondrial 5-demethoxyubiquinone hydroxylase, have been reported in nine patients from seven families. We identified five new patients with COQ7-related primary CoQ10 deficiency, performed clinical assessment of the patients, and studied the functional effects of current and previously reported COQ7 variants and potential treatment options. The main clinical features included a neonatal-onset presentation with severe neuromuscular, cardiorespiratory and renal involvement and a late-onset disease presenting with progressive neuropathy, lower extremity weakness, abnormal gait, and variable developmental delay. Baker's yeast orthologue of COQ7, CAT5, is required for growth on oxidative carbon sources and cat5Δ strain demonstrates oxidative growth defect. Expression of wild-type CAT5 could completely rescue the defect; however, yeast CAT5 harboring equivalent human pathogenic variants could not. Interestingly, cat5Δ yeast harboring p.Arg57Gln (equivalent to human p.Arg54Gln), p.Arg112Trp (equivalent to p.Arg107Trp), p.Ile69Asn (equivalent to p.Ile66Asn) and combination of p.Lys108Met and p.Leu116Pro (equivalent to the complex allele p.[Thr103Met;Leu111Pro]) partially rescued the growth defects, indicating these variants are hypomorphic alleles. Supplementation with 2,4 dihydroxybenzoic acid (2,4-diHB) rescued the growth defect of both the leaky and severe mutants. Overexpression of COQ8 and 2,4-diHB supplementation synergistically restored oxidative growth and respiratory defect. Overall, we define two distinct disease presentations of COQ7-related disorder with emerging genotype-phenotype correlation and validate the use of the yeast model for functional studies of COQ7 variants.

Progression to fusion after lumbar laminectomy for degenerative lumbar spondylolisthesis: Rate and risk-factors. A national database study

ObjectiveLumbar laminectomy is often utilized in the treatment of degenerative lumbar spondylolisthesis. Risk factors that contribute to reoperation rates, in particular to progression to fusion, are poorly understood. We aimed to identify rate and risk factors of lumbar fusion surgery following lumbar laminectomy for the treatment of degenerative lumbar spinal spondylolisthesis. MethodsOur sample was obtained from the national MarketScan Commercial Claims and Encounters Database. We reviewed patients undergoing lumbar laminectomy for stable degenerative lumbar spondylolisthesis (Grade-1) at one or two levels between January 2007 and December 2016. ResultsA total of 33,681 patients were included. By 2 years after the index operation, 2.48 % of patients had required lumbar fusion surgery. Female sex was associated with lower odds (OR 0.8, 95 %CI 0.7–0.9) of reoperation for fusion. Diabetes (OR 1.2, 95 %CI 1.1–1.4), rheumatoid arthritis (OR 1.5, 95 %CI 1.2–1.7) and clinical presentation with LBP (OR 2.1, 95 %CI 1.6–2.9), lower extremity weakness (OR 1.4, 95 %CI 1.1–1.5), as well as occurrence of a postoperative neurological complications (OR 2.0, 95 %CI 1.1–3.4) increased the odds ratio for requiring fusion surgery within two years after lumbar laminectomy. ConclusionIn this large cross-sectional sample of a national claims database consisting of lumbar laminectomy patients for the treatment of spondylolisthesis, approximately 2.5 % required subsequent lumbar fusion. Several modifiable risk factors for fusion progression were identified, which may guide clinicians in shared decision-making and to help identify patients with elevated post-operative risk providing potential leverage point for prevention.

Dysfunctional neuro-muscular mechanisms explain gradual gait changes in prodromal spastic paraplegia

BackgroundIn Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperreflexia, muscle weakness, and spasticity of lower extremities. Even before the manifestation of spastic gait, in the prodromal phase, axonal degeneration leads to subtle gait changes. These gait changes - depicted by digital gait recording - are related to disease severity in prodromal and early-to-moderate manifest SPG4 participants.MethodsWe hypothesize that dysfunctional neuro-muscular mechanisms such as hyperreflexia and muscle weakness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 participants. We test our hypothesis in computer simulation with a neuro-muscular model of human walking. We introduce neuro-muscular dysfunction by gradually increasing sensory-motor reflex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force.ResultsBy increasing hyperreflexia of plantarflexor and dorsiflexor muscles, we found gradual muscular and kinematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 participants.ConclusionsPredicting kinematic changes of prodromal and early-to-moderate manifest SPG4 participants by gradual alterations of sensory-motor reflex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions.

Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q

Pathogenic variants in SPART cause Troyer syndrome, characterized by lower extremity spasticity and weakness, short stature and cognitive impairment, and a severe mitochondrial impairment. Herein, we report the identification of a role of Spartin in nuclear-encoded mitochondrial proteins. SPART biallelic missense variants were detected in a 5-year-old boy with short stature, developmental delay and muscle weakness with impaired walking distance. Patient-derived fibroblasts showed an altered mitochondrial network, decreased mitochondrial respiration, increased mitochondrial reactive oxygen species and altered Ca 2+ versus control cells. We investigated the mitochondrial import of nuclear-encoded proteins in these fibroblasts and in another cell model carrying a SPART loss-of-function mutation. In both cell models the mitochondrial import was impaired, leading to a significant decrease in different proteins, including two key enzymes involved in CoQ10 (CoQ) synthesis, COQ7 and COQ9, with a severe reduction in CoQ content, versus control cells. CoQ supplementation restored cellular ATP levels to the same extent shown by the re-expression of wild-type SPART, suggesting CoQ treatment as a promising therapeutic approach for patients carrying mutations in SPART .

Type 3 bone-disc-bone osteotomy (grade 4+ osteotomy) combined with presurgical halo-pelvic traction: a safe and effective solution to correct severe angular-like kyphoscoliosis.

Treatment of severe angular-like kyphoscoliosis is a technically demanding surgical challenge and requires high-risk spinal osteotomy, such as vertebral column resection. Preoperative halo-pelvic traction is commonly used to decrease the curve magnitude. However, few studies have utilized the potent method of bone-disc-bone osteotomy, which could theoretically provide correction up to 60°. This study aimed to evaluate the safety and effectiveness of type 3 bone-disc-bone osteotomy combined with presurgical halo-pelvic traction to correct severe angular-like kyphoscoliosis. This was a retrospective cohort study. Patients with severe angular-like kyphoscoliosis who underwent presurgical halo-pelvic traction and type 3 bone-disc-bone osteotomy from January 2017 to December 2019 were consecutively reviewed. Patient demographics and clinical data were recorded. The coronal and sagittal Cobb angles were measured preoperation, post-traction, post-operation, and at the final follow-up. Complications were also recorded. Patients' health-related quality of life was evaluated by the Scoliosis Research Society 22 (SRS-22) questionnaire. Paired Student's t test and one-way analysis of variance were used for comparisons among different groups. Thirty patients (18 females and 12 males) with an average age of 20.2 years (range, 13-33 years) were included. The mean preoperative coronal and sagittal Cobb angles were 123.1°±16.4° (range, 90°-155°) and 120.3°±19.9° (range, 90°-156°), respectively. After 2.9±0.7 months (range, 2-4 months) of halo-pelvic traction, the coronal and sagittal Cobb angles decreased significantly to 81.9°±13.2° and 76.0°±12.6°, respectively. Postoperatively, the scoliotic and kyphotic angles further decreased to 42.4°±12.2° and 33.9°±8.8°, respectively. After a mean follow-up of 2.93±1.05 years, the correction rates were maintained at 64.3%±10.6% and 70.5%±6.3%, respectively. Nine patients experienced positive evoked potential events during surgery. Common complications after surgery included transient lower extremity weakness, pneumonia, and pleural effusion. The self-image scores were significantly improved from 2.66±0.27 to 3.36±0.23 compared to preoperation. This study proposes a novel strategy to correct severe angular-like spinal deformities. The combination of presurgical halo-pelvic traction and type 3 bone-disc-bone osteotomy (grade 4+ osteotomy) achieves substantial correction and satisfactory aesthetic outcomes without serious complications.

Tanı Konulmamış Nöromüsküler Hastalığı Olan Gebenin Acil Sezaryen için Anestezi Yönetimi

A 30 year-old ASA II pregnant woman with an undiagnosed neuromuscular disease at 41 weeks of gestation was admitted to our hospital. Neurological examination is normal except lower extremity weakness that has been ongoing for the last 10 years. In this case report, we aimed to discuss general anesthesia management for emergency cesarean section of this particular pregnant woman.

A Case of Pediatric Guillain-Barré Syndrome After Respiratory Syncytial Virus Infection

We report a two-year-old girl whose progressive lower extremity weakness was masked by a respiratory presentation, only to be identified as having Guillain-Barré syndrome in the context of respiratory syncytial virus bronchiolitis. This case adds to the expanding literature of postinfectious demyelinating disorders in very young children, which seem to be unrelated to particular antigenic triggers.

ErZhiFormula prevents UV-induced skin photoaging by Nrf2/HO-1/NQO1 signaling: An in vitro and in vivo studies.

ErZhiFormula (EZF) is a classical traditional Chinese medicinal formulation. It can be used to treat liver and kidney yin deficiency, dizziness, lumbar debility, insomnia, nocturnal emission, lower extremity weakness, and other aging-related diseases. However, the protective effect of EZF in skin photoaging and its potential mechanism has not been clarified. This study aims to explore the role of EZF in the skin photoaging mechanism induced by UV radiation. Ultra Performance Liquid Chromatography (UPLC) was used to identify the fingerprint of EZF. The mice were irradiated with UVA and UVB to establish the photoaging model in vivo. Human immortalized keratinocytes (HaCaT) were irradiated with UVB to establish the photoaging model in vitro. The activity of cells was detected by CCK-8 and LDH kits, the level of reactive oxygen species was detected by DCF fluorescent probe, and the apoptosis was detected by PE annexin V and 7-Amino-Actinomycin (7-AAD) staining. Comet assay was used to detect cell DNA damage. The antioxidant enzyme levels in cell and mouse serum were detected by antioxidant kit, and Western blot was used to detect protein expression. We found that EZF contain many active ingredients, including salidroside, specnuezhenide, isoquercitrin, etc. EZF can improve the photoaging of HaCaT cells and mouse skin caused by UV radiation. The results of animal experiments are consistent with those of cell experiments. Combined with Western blot analysis, we found that EZF finally played an anti-skin photoaging role by regulating the Nrf2/HO-1/NQO1 pathway. EZF can protect skin from UV-induced photoaging by regulating the Nrf2/HO-1/NQO1 signal pathway. EZF may become a traditional Chinese medicine with the potential to prevent skin photoaging.

Case 2: Lower Extremity Pain and Weakness in a Child with Autism Spectrum Disorder

Case 2: Lower Extremity Pain and Weakness in a Child with Autism Spectrum Disorder

ID: 218987 Utilization of Neuromodulation for Failed Back Surgery Syndrome in Setting of Recurrent Infections

A 70-year-old female with a past medical history significant for recurrent skin infections, fibromyalgia, Ehlers Danlos Syndrome, and chronic back pain secondary to T12 compression fracture, multilevel spondylosis, and stenosis s/p L2-S1 laminectomy/fusion presented to the ED for significant worsening of her chronic back pain. One-week prior, patient was seen by her primary care physician for a left forearm abscess, underwent incision and drainage in the office, and was discharged on oral antibiotics. One month later, patient began experiencing intractable back pain with associated bilateral lower extremity weakness and subsequently went to the ED. Manual muscle testing of her lower extremities was 3/5 throughout, with no other red flag signs or symptoms. A thoraco-lumbar MRI revealed a T9-T10 epidural collection suggestive of an epidural abscess with cord compression, in addition to a chronic T12 compression fracture. She underwent a T9-T10 laminectomy, with her post-operative course being uneventful. She was discharged to subacute rehab to complete a course of intravenous antibiotics. She was told to follow up for kyphoplasty after her infection clears. One month post-operatively patient continued to have radicular symptoms bilaterally and continued back pain and returned to the ED. An MRI of her thoraco-lumbar spine revealed worsening of T12 compression fracture, T10-T11 vertebral disc herniation with adjacent enhancing fluid collection in the right ventral epidural space suspicious for abscess vs extruded disc material.

P.037 Neurofascin-155 IgG in acute-onset inflammatory polyneuropathy: possible predictor of relapse and recovery

Background: IgG4 autoantibodies to neurofascin-155 (NF-155) have been described in a subset of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). While reports suggest an acute onset is more likely than in antibody negative CIDP, little literature exists around the subsequent course of NF-155 positive cases that originally presented with an acute inflammatory demyelinating polyneuropathy (AIDP) phenotype. Methods: Two male patients, ages 51 and 59, presented with similar, <2 week histories of lower extremity weakness. Patients were diagnosed with AIDP and treated with IVIG. Following initial improvement, both patients relapsed. One patient was treated with IVIG and steroids with subsequent improvement; however, he was unable to be weaned from steroids without experiencing recurrence of symptoms. The other patient was not retreated. Testing for NF-155 IgG was sent. Results: The first patient ultimately required Rituximab for stable improvement, the other improved spontaneously. Both patients later had positive tests for NF-155 IgG4 antibodies. Conclusions: Both of our NF-155 positive cases had initial AIDP-like presentations, followed by a relapsing course and excellent eventual recovery. This result, along with limited other available cases, suggest that in patients with an AIDP-like presentation, NF-155 IgG4 autoantibodies could be a marker of disease recurrence, but do not necessarily predict a poor outcome.

Cachexia, chorea, and pain in chronic nonbacterial osteitis and inflammatory bowel disease: a case report

BackgroundInflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118–1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3–19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228–1237, 2014).Case presentationA 13-year-old Caucasian boy presented with 1 month of progressive lower-extremity pain, weakness, and weight loss. His physical examination was notable for cachexia, lower-extremity weakness, and chorea. Labs revealed normocytic anemia and systemic inflammation. Imaging revealed symmetric abnormal marrow signal in the pelvis and upper femurs. Pathologic examination of the bone revealed chronic inflammation consistent with chronic nonbacterial osteitis. Endoscopy revealed colonic inflammation consistent with inflammatory bowel disease.ConclusionsChildren and adolescents with musculoskeletal pain lasting more than 2 weeks with systemic signs or symptoms like weight loss should prompt evaluation for systemic inflammatory disorders such as chronic nonbacterial osteitis, which can occur in isolation or associated with inflammatory bowel disease. This patient also had a nonspecific neurologic abnormality, chorea, which resolved with treatment of underlying inflammatory disorder. These extraintestinal manifestations may be concurrent with or precede intestinal inflammation, requiring a high index of suspicion when investigating nonspecific systemic inflammation.

Recurrent Ischemic Stroke In Elderly With Polycythemia Vera: Case Report

<p><strong>Background</strong>: Myeloproliferative disorders can rise a risk of thrombotic events. Ischemic stroke is one of presenting symptoms can be found in such patients. These coexisting conditions can burden patients with more severe complications.</p><p><strong>Objectives</strong>: To discuss a case of polycythemia vera with multiple episodes of ischemic stroke.</p><p><strong>Case description</strong>: The patient was a 70-year-old female with chief complaint of sudden rotatory dizziness with moderate to severe intensity. Nausea, vomiting, slurred speech, and facial muscle weakness were also reported. Onset of symptoms started 3 hours before hospital admission. Medical history including previous ischemic stroke in 2020 and 2015 with remaining right extremity weakness. Physical examination showed weakness, hypertension. Nystagmus horizontal bidirectional and upper motor neuron lesion of left CN VII and XII, weakness in right upper and lower extremities were observed. Physiological reflexes were increased, and pathological reflex was found. Head CT showed hypodense lesion led to her ischemic stroke diagnosis. Blood test showed increased hemoglobin count, leukocytosis but normal platelet count. Increased cell numbers and variations of size, morphology and distribution were found in peripheral smear. This finding was also supported with bone marrow examination which showed hypercellularity, panmyelosis with dysplasia of all hematopoietic lineage. Patient was diagnosed with polycythemia vera and treated accordingly.</p><p><strong>Conclusion</strong>: Further examination of hematology, such as peripheral smear or bone marrow examination should be considered in patients with recurrent episodes of stroke to rule in underlying myeloproliferative disorders.Appropriate treatment and routine hematology<strong> </strong>follow up are in need to increase awareness of future thrombotic events or leukemic transformations.</p>

1031 OSA management with RME device in pediatric patient with GBS on IVIg and non surgical candidate due to immunomodulated status

Abstract Introduction Adenotonsillectomy is considered the standard of care in pediatric populations diagnosed with OSA and adenotonsillar hypertrophy. For non-surgical and specific populations, Rapid maxillary expansion, a technique that consists in increasing the transverse diameter of the hard palate with the use of a fixed orthodontic appliance, has recently been used, with evidence of improvement of signs and symptoms of the disease, AHI normalization, and overall PSG parameters improvement. Report of case(s) Patient with a history of Chronic inflammatory demyelinating polyradiculoneuropathy and Guillain Barre syndrome, diagnosed at 8 years of age, posterior to gastrointestinal viral infection. MRI of the lumbosacral spine showed inflammatory changes at the cauda equina, conus and epiconus consistent with GBS. She also has CIDP, first diagnosed by Electromyography. The same year she had witnessed snoring and apneic episodes and underwent a PSG which showed an AHI of 2/hr. On Physical exam, she had tonsils 2+ and was referred to an ENT specialist for tonsillectomy. A repeat PSG at the age of 9 years revealed an AHI of 1.6/hour with no central apnea/hypopnea. At that time, due to clinical worsening of her neurologic symptoms, with ataxia and lower extremity weakness, she was started on a course of IVIg therapy. Due to IVIg treatment, she was not a candidate for tonsillectomy. In view of excessive daytime sleepiness, concentration difficulties at school and not being a candidate for tonsillectomy, she was referred for Rapid Maxillary Expansion. She has had maxillary expanders since the age of 9 and is now asymptomatic and her snoring has remarkably improved. She is now in the process of being fitted with braces and her lower extremity weakness has also improved with IVIg. Complete resolution of sleep apnea symptoms after rapid maxillary expansion without tonsillectomy. Conclusion Although tonsillectomy has been the gold standard for the treatment of OSA in the pediatric population, patients who are not surgical candidates for tonsillectomy can undergo orthodontic treatment and benefit from the outcomes. As reported in our unique case, the patient became completely symptom-free. Support (if any)

Abstract #1406447: A Case of Severe Hypercalcemia After Recovery from Rhabdomyolysis that was Refractory to Hemodialysis

Rhabdomyolysis (RBD) is severe skeletal muscle injury which often results in acute kidney injury (AKI) and significant electrolytes abnormalities. We herein describe a case of severe hypercalcemia that occurred during the recovery phase of RBD that was successfully treated with intravenous (IV) pamidronate. A 58-year-old male with history of cirrhosis, IgA nephropathy and chronic kidney disease presented with lower extremity weakness and was found to have AKI due to statin-induced RBD. Creatinine Kinase (CK) was > 30000 U/L [30-200], BUN 78 mg/dl [ 6-22], Creatinine 5.78 mg/dl [ 0.77-1.25], corrected Calcium (Ca) 7.0 mg/dl [8.6- 10.2], Ionized Ca 2.5 mg/dl [4.5- 5.3], Phosphorus 6.7 mg/dl [2.3-4.7], 25-OH Vitamin D 4.8 ng/ml [30 -80] and Parathyroid hormone (PTH) 333 ng/ml [8.7-77.1]. The patient received IV calcium gluconate, vitamin D supplementation and hemodialysis (HD) and was started on calcitriol 0.25 mg three times a week. He was discharged on calcitriol, calcium acetate and vitamin D with a corrected Ca of 9.1 mg/dl. One week later, the patient was readmitted with confusion and a corrected Ca of 15.3 mg/dl, phosphorus of 7 mg/dl, CK of 131 U/L, 25- OH vitamin D 10 ng/ml, PTH 11.4 ng/ml. Additional workup for hypercalcemia was unremarkable. His hypercalcemia persisted despite HD with low calcium baths, gentle IV hydration, and IV furosemide. Calcitonin 4 units/kg was initiated but his Ca remained 12.4mg/dl after 48 hours. IV pamidronate 30 mg was given and within 5 days, his Ca level was 9.4 mg/dl, reaching a nadir of 8.9 mg/dl. RBD is commonly associated with hypocalcemia in the acute phase. Hypercalcemia can also occur in the recovery phase, but few reports exist and the appropriate management has not been established. As in our case, overtreatment of hypocalcemia may exacerbate hypercalcemia. The pathophysiology of the hypercalcemia may be due to mobilization of Ca from injured muscles and soft tissue deposits. Secondary hyperparathyroidism can also contribute to a hypercalcemic response. Hypercalcemia due to RBD is usually self-limited but more severe cases can occur. Few have reported on the use of bisphosphonates for this condition. In our case, multiple treatments were not successful in lowering calcium. Despite concerns that bisphosphonates may not successfully lower calcium, since hypercalcemia was not mediated by bone turnover, calcium decreased after bisphosphonate therapy and no adverse effects were experienced. Therefore, bisphosphonate therapy can be considered in refractory post-rhabdomyolysis hypercalcemia.

Novel Presentation of a Mosaic STAT5B Gain-of-Function Variant

Somatic gain-of-function (GOF) variants in STAT5B have been described in leukemias and lymphomas, and more recently in three patients presenting with nonclonal eosinophilia, atopic dermatitis, diarrhea, and urticaria. Here, we describe a 7-year-old middle-Eastern female presenting with autoimmune adrenal insufficiency and lower extremity weakness. Diagnostic studies revealed CNS demyelination and demyelinating polyneuropathy of the motor nerves. CBC was notable for leukocytosis with eosinophilia, with peak AEC at 3100 cells/cumm. Immunophenotyping demonstrated normal IgG and subclasses and IgA, elevated IgM (233.1 mg/dL), and mildly elevated IgE (135 IU/ml). T cell lymphocytosis was noted on flow cytometry. Extensive infectious and autoantibody testing was unremarkable, and flow cytometry and cytology from CSF, blood, and bone marrow were not concerning for malignancy. She was treated with IV methylprednisolone and steroid taper, followed by rituximab and IVIG. Additional imaging demonstrated an enlarged thymus thought to represent rebound thymic hyperplasia, and splenomegaly. Trio whole exome sequencing performed on a buccal sample was notable for a de novo STAT5B c.1883C>G (p.Thr628Ser) variant present in 13/111 (–12%) of sequencing reads. This STAT5B variant has been reported in T cell prolymphocytic leukemia and studies have shown this variant confers GOF. Clinical evaluation for the STAT5B variant detected mosaicism in buccal swab DNA and near 50% variant allele frequency (VAF) in blood and bone marrow. We then assessed the VAF in various cells on a research basis. The VAF in buccal DNA was 7–9%, 46–48% in whole blood, and 48% in the bone marrow. Cell sorting for CD4+ and CD8+ T cells revealed a VAF of 46–48%. A similar VAF was observed in CD56+ cells (48%) and CD14+ cells (–50%). A fibroblast line was generated from a skin punch biopsy, and the variant allele was absent, suggesting somatic origin. Preliminary data from peripheral blood flow cytometric analysis demonstrated a slight increase in Treg cells, and Th2 skewing of Tregs as implied by cell surface markers. Assessment of pSTAT5 at baseline and after cytokine stimulation suggest increased responsiveness. The patient was started on tofacitinib, a JAK inhibitor primarily targeting JAK1/JAK3. She improved clinically, weaned on steroids, and is being evaluated for HSCT.

Scurvy presenting with difficulties to walk and weakness in pediatric patients; 2 case reports. (P11-9.009)

<h3>Objective:</h3> Vitamin deficiency should be considered during differential diagnosis of neurological symptoms in patients presenting with subacute progressive gait instability and weakness. <h3>Background:</h3> Despite the perception that scurvy is a rare disorder (1,2), clinicians should have a high index of suspicion in patients at risk for nutritional deficiencies including picky eater, behavioral or sensory issues. <h3>Design/Methods:</h3> We report 2 patients of ascorbic acid deficiency who presented with subacute progressive gait instability and weakness. <h3>Results:</h3> Case 1 is a 12-year-old male with autism spectrum disorder who presented with 3 weeks of progressive bilateral lower extremity weakness resulting in wheelchair dependence. Cranial nerves, deep tendon reflexes, and sensory exam were normal. Motor exam notable for proximal &gt; distal lower extremity weakness. Skin and mucosal examination revealed gingival bleeding and corkscrew hair. Detailed dietary history revealed a severely restricted diet. He was found also to have low vitamin D. Patient treated empirically with vitamin C supplementation resulted in marked improvement within 24 hours, so no additional work up was recommended. Ascorbic acid level was extremely low confirming the diagnosis. Case 2 is a 4-year-old with history of mild hypotonia who presented with subacute progressive lower extremities weakness exacerbated by physical activity. Cranial nerves, deep tendon reflexes, and sensory exam were normal. Motor exam notable for proximal &gt; distal lower extremity weakness, waddling gait, and positive Gowers maneuver. Dietary history revealed restricted diet for the last 3 months. CK normal. Supplementation with Vitamin C resulted in minimal symptoms improvement so additional neuroimaging was recommended such as magnetic resonance imaging (MRI) of brain, spine and thigh/leg as well as lumbar puncture (LP) all unremarkable. Ascorbic acid level was low confirming the diagnosis. <h3>Conclusions:</h3> Dietary restriction and subacute progressive weakness should raise concern for nutritional myopathies. Refusal to bear weight is a frequent presentation of ascorbic acid deficiency (3). <b>Disclosure:</b> Dr. Railean has nothing to disclose. Dr. Martindale has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Tourette Association of America. The institution of Dr. Martindale has received research support from Tourette Association of America.

Rare Case of Neurosarcoidosis presenting as Isolated Longitudinal Extensive Transverse Myelitis (LETM). (P9-5.006)

<h3>Objective:</h3> NA <h3>Background:</h3> Neurosarcoidosis is seen in only 5–16% of the patients with sarcoidosis. Incidence of longitudinal extensive transverse myelitis (LETM) in neurosarcoidosis is even rarer. <h3>Design/Methods:</h3> 37-year-old male with history of recurrent LETM and seizure disorder was admitted for worsening lower extremity weakness and unresponsiveness. History was significant for transverse myelitis diagnosed 8 months ago after presenting with lower extremity weakness and urinary incontinence. MRI of the spine at that time revealed focus of abnormal T2 signal in upper thoracic spinal cord extending from the mid T3 level inferiorly through the T5–6 level, with associated cord expansion. <h3>Results:</h3> Repeat MRI of the spine and brain showed progression of disease in the spine with nodular leptomeningeal enhancement most prominent within the posterior fossa. Extensive workup including neuromyeltitis optica, paraneoplastic panel, anti-aquaporin Ab and Anti-MOG Ab testing was negative. Patient was treated with steroids and plasmapheresis treatment (PLEX). PLEX treatments were held due to concern for infection. He was switched to steroid taper and biweekly Rituximab infusion. Rituximab infusions were stopped due to side effects and patient was trialed on mycophenolate mofetil. However, patient was transitioned back to steroid taper and rituximab infusion after worsening of symptoms. Patient eventually underwent meningeal biopsy which showed granulomatous leptomeningitis and parenchymal microglial activation. With strong suspicion for Neurosarcoidosis now based on accumulated evidence the patient was restarted on IV methylprednisolone and subsequent steroid taper. Improvement of his symptoms with partial recovery of strength was noted. Patient was subsequently transitioned to Leflunomide, infliximab infusions and steroid taper. Follow up MRI of the brain and spinal cord showing improvement in areas of enhancement. <h3>Conclusions:</h3> Our patient presented with neurosarcoidosis manifesting as LETM with no prior diagnosis of sarcoidosis or evidence of system involvement on further thorough workup. The diagnosis was challenging confirmed after a neural biopsy given absence of non-neurological manifestations. <b>Disclosure:</b> Dr. Khosa has nothing to disclose. Dr. Anandaram has nothing to disclose. Dr. Khosa has nothing to disclose. Dr. Buttar has nothing to disclose.

Caspr2 Antibody-Mediated Ataxia, Parkinsonism, and Epilepsy: A Case for Escalating Immunotherapy. (P13-11.007)

<h3>Objective:</h3> To report a rare presentation of anti-Caspr2 syndrome treated successfully with rituximab. <h3>Background:</h3> Anti-Caspr2 syndrome has a variety of clinical phenotypes including encephalopathy, seizure, psychiatric disturbances, respiratory failure, dysautonomia, peripheral nerve dysfunction, as well as ataxia of a constant or episodic nature.¹ In many of the cases with ataxia, there is associated limbic encephalitis.² Anti-Caspr2 syndrome with ataxia, parkinsonism and seizure has only been reported once in the literature.³ This symptomatology can be easily mistaken for an atypical parkinsonism like cerebellar multiple systems atrophy, or spinocerebellar ataxia type 2 but this treatable cause is an important consideration. <h3>Design/Methods:</h3> To report a case of anti-Caspr2 syndrome presenting with pure ataxia, then progressing to parkinsonism, and epilepsy; its successful treatment; and accompanying video examinations. <h3>Results:</h3> A 71 year-old man was referred for 8 months of progressive, generalized ataxia and dysarthria. Immune-mediated ataxia was considered given the subacute course with rapid progression. He was found to have a Caspr2 antibody titer of 1:100. Evaluation for malignancy was unremarkable. Lumbar puncture revealed Caspr2 antibody positivity. The patient was treated with 4 days of intravenous steroids and immunoglobulins with significant improvement. He relapsed four months later with lower extremity weakness and ataxia. Despite maintenance intravenous immunoglobulin, his ataxia continued to progress. He then developed focal seizures with impaired awareness and left sided parkinsonism. He was started on rituximab immunotherapy for ongoing disease activity. His ataxia and parkinsonism significantly improved to near-baseline with continued stability 6 months later. <h3>Conclusions:</h3> This case illustrates an example of an autoimmune-mediated cerebellar ataxia of subacute onset with progression to parkinsonism and epilepsy. Special consideration for anti-Caspr2 syndrome should be taken in cases of progressive ataxia with accompanying neurologic features of parkinsonism and seizure. Escalation to rituximab can be considered for patients who continue to progress despite preliminary immunotherapy. <b>Disclosure:</b> Dr. Sugar has nothing to disclose. Dr. Witek has nothing to disclose.