Gait Ataxia Research Articles

Neuropsychiatric Disorders Revealing Autoimmune Polyendocrine Syndrome Type 3: Case Report

Multiple autoimmune syndrome is a rare pathological condition because it associates at least three different autoimmune diseases in the same patient. We discuss through this case and with a review of the literature MAS type 3 and its association with neuroanemic syndrome which remains exceptional. This is a 47-year-old patient, followed for vitiligo and a depressive syndrome, admitted for an ataxic gait lasting a month, in whom the neurological examination revealed a combined sclerosis syndrome of the spinal cord associated with a static cerebellar syndrome. Dermatological examination revealed diffuse acrofacial vitiligo. The biological assessment revealed Biermer's anemia and autoimmune thyroiditis. The clinical evolution was favorable under treatment. The discovery of Biermer's disease in a woman should prompt the search for arguments for one or other associated autoimmune diseases.

SAT489 Grave’s Disease Secondary To Alemtuzumabuse

Abstract Disclosure: M.S. Gong: None. D. Lee: None. R. Arceo-Mendoza: None. Introduction: We present a case of alemtuzumab-induced autoimmune thyroid disease in a patient with Multiple Sclerosis (MS). Clinical Case: A 42/F was evaluated by endocrine inpatient service for hyperthyroidism. She presented with tremors, dyspnea, and ataxic gait. She has known MS and was treated with Alemtuzumab (ALZ) in 2018 and in 2019, with her initial infusion being 4 years prior to this admission. Lab tests on admission showed TSH of <0.01 uIU/mL with elevated Free T3 and Free T4 of 1987 pg/dL (NV:171-371 pg/dL) and 3.9 ng/dL (NV:0.7-1.5 ng/dL) respectively. Her Thyroid Stimulating Immunoglobulin and TSH receptor binding antibody were elevated. Baseline TSH prior to starting ALZ and a follow up TSH in 2020 were in the normal range. She denies personal or family history of thyroid disease. Hospital course was further compounded by ongoing leukopenia, with a WBC of 2.3 and ANC of 1.1. Initiation of thionamide therapy was discussed however patient declined to start methimazole when risk of agranulocytosis, albeit low, was explained. She had opted to proceed with RAI therapy for definitive management but then changed her mind. We were just initially able to treat her with prednisone, beta blocker and cholestyramine with close biochemical monitoring as an outpatient. Her Grave’s hyperthyroidism was refractory to medical management hence she was eventually admitted again for medical optimization and surgical evaluation. Her hospital course upon readmission was complicated by worsening hemoptysis and a diagnosis of pulmonary embolism. At this point, it was decided she is not a good surgical candidate for thyroid surgery given comorbidities. She eventually agreed to start methimazole after undergoing bone marrow biopsy for worsening leukopenia and cleared by hematology to start the antithyroid drug. At this time, she remains to be on methimazole as an outpatient. Clinical course however, is unfortunately complicated by patient’s ongoing poor compliance to clinic follow up. Clinical Lesson: ALZ is an anti-CD52 monoclonal Ab which induces depletion of B and T lymphocytes causing lymphopenia and immunosuppression. It is an effective treatment for MS but is linked to a number of autoimmune adverse event. Thyroid autoimmune dysfunction may occur in 20-30% of patients, and Grave’s disease accounts for 60-70% of cases. The ALZ product label recommends TFT monitoring every 3 months for at least 48 months after the last infusion. Our patient presented with Grave’s disease in 4 years following initial ALZ administration. To our knowledge, there is no published case with reported ALZ-induced Grave’s disease with this length of interval since infusion. Our case highlights not only the importance of pretreatment screening but continued vigilance and close thyroid function monitoring in patients treated with ALZ even several years after therapy. Presentation Date: Saturday, June 17, 2023

SAT220 Rare Case Of Pembrolizumab Induced Primary Hypoparathyroidism

Abstract Disclosure: S.G. Goud: None. A. Siddiqui: None. M. Alkhathlan: None. C.Y. Fan: None. Introduction: Immune checkpoint inhibitors such as pembrolizumab (Keytruda) used in the treatment of various cancers are associated with immune mediated endocrinopathies, among which thyroid dysfunction and pituitary hypophysitis are common, whereas hypoparathyroidism is rare. We report a case of primary hypoparathyroidism and hypocalcemia with pembrolizumab. Clinical Case: 58-year-old male with metastatic urothelial cell carcinoma, status post neoadjuvant chemotherapy with gemcitabine and cisplatin in 2017, followed by radical cystectomy with recurrence of metastasis in 2018, who was started on Keytruda every three weeks. After 10 months, he developed immune mediated hypothyroidism treated with levothyroxine. After 33 months on Keytruda, he developed hematochezia with constipation and intermittent abdominal pain. Colonoscopy showed findings consistent with autoimmune colitis; Keytruda was held and colitis was treated with tapering steroids. Surveillance imaging showed stable disease, so Keytruda continued to be held. After 7 months of holding Keytruda, on routine blood work he had a critically low calcium level of 5.5 mg/dl (8.4-10.2 mg/dl) with tingling and numbness in his hands, muscle spasms, generalized weakness, and fatigue for the past few weeks. On exam there was no Trousseau’s sign, Chvostek's sign, or gait ataxia. Hemodynamically stable. Labs showed lowest corrected calcium of 5.5, normal renal function, low vitamin D of 8 ng/ml (30-100 ng/ml), elevated phosphorus of 6.3 mg/dl (2.5-4.5 mg/dl), and normal magnesium. PTH was frankly low at 12.7 pg/ml (15-65 pg/ml), indicating primary hypoparathyroidism. ACTH stimulation test was normal. Retrospective review of the labs from oncology office records showed gradual, progressive hypocalcemia for a few months prior to presentation, with calcium levels ranging between 6.7 to 7.7 mg/dl. Of note, calcium prior to pembrolizumab was normal at 9.4 mg/dl. He was treated with IV calcium gluconate and then transitioned to calcium carbonate (CaCO3) 500 mg TID, calcitriol 0.5 mg BID, and Vit D 50,000 IU twice weekly. Hydrochlorothiazide (HCTZ) added as calcium remained low. After three days calcium improved to 7 mg/dl range and he was discharged. Calcium levels checked periodically after discharge ranged from 8 to 9 mg/dl (8.4-10.2 mg/dl), and phosphorus levels normalized. CaCO3 dose was adjusted accordingly, Vit D was changed to 50,000 IU weekly based on a level of 71 ng/dl after 3 months, and HCTZ was discontinued after 6 months. PTH was still low at 9.7 pg/ml (15-65 pg/ml) 6 months after discharge, off pembrolizumab for over a year. Calcium sensing receptor (CaSR) activating antibody was not checked in our case. Conclusion: It is important clinicians be aware of the risk for hypocalcemia and its unpredictable presentation to help with timely recognition and management. Presentation: Saturday, June 17, 2023

SAT624 Neurosarcoidosis Presenting With Panhypopituitarism

Abstract Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None. Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N<38), ACE 6 U/l (N <2.5), WBC 10 (N<5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH <5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of <2.8 pmol/l( N>13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N <295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions. Presentation: Saturday, June 17, 2023

Vestibular Pathology as Early Finding of Friedreich's Ataxia in a 16 Years Old Woman.

Friedreich's ataxia is degenerative disease frequently starting around puberty and it's characterized by a progressive gait ataxia, limb weakness, apparition of Babinsky sign, loss of deep tendon reflex, dysarthria and skeletal deformities. The development of vestibular pathology is common but not completely understood. A 16 years old woman with early vestibular defects in relation to a latter Friedreich's ataxia diagnosis is reported.

Neurological Outcome and Respiratory Insufficiency in Intramedullary Tumors of the Upper Cervical Spine.

Background and Objectives: Intramedullary spinal cord tumors (IMSCT) are rare entities. A location in the upper cervical spine as a highly eloquent region carries the risk of postoperative neurological deficits, such as tetraparesis or respiratory dysfunction. Evidence for respiratory dysfunction is scarce. This study aimed to describe these highly eloquent tumors' early and late postoperative clinical course. Materials and Methods: This is a single-center retrospective cohort study. We included 35 patients with IMSCT at levels of the craniocervical junction to C4 who underwent surgical treatment between 2008 and 2022. The authors analyzed the patients' preoperative status, tumor- and surgery-specific characteristics, and follow-up functional status. Results: The study cohort included twenty-two patients with grade II ependymoma (62.9%), two low-grade astrocytomas (5.7%), two glioblastomas (5.7%), six hemangioblastomas (17.1%), two metastases (5.7%), and one patient with partially intramedullary schwannoma (2.9%). Gross total resection was achieved in 76% of patients. Early dorsal column-related symptoms (gait ataxia and sensory loss) and motor deterioration occurred in 64% and 44% of patients. At a follow-up of 3.27 ± 3.83 years, 43% and 33% of patients still exhibited postoperative sensory and motor deterioration, respectively. The median McCormick Scale grade was 2 in the preoperative and late postoperative periods, respectively. Only three patients (8.6%) developed respiratory dysfunction, of whom, two patients, both with malignant IMSCT, required prolonged invasive ventilation. Conclusions: More than 60% of the patients with IMSCT in the upper cervical cord developed new neurological deficits in the immediate postoperative period, and more than 40% are permanent. However, these deficits are not disabling in most cases since most patients maintain functional independence as observed by unchanged low McCormick scores. The rate of respiratory insufficiency is relatively low and seems to be influenced by the rapid neurological deterioration in high-grade tumors.

Novel CWF19L1 mutations in patients with spinocerebellar ataxia, autosomal recessive 17.

Spinocerebellar ataxia, autosomal recessive-17 (SCAR17) is a rare hereditary ataxia characterized by ataxic gait, cerebellar signs and occasionally accompanied by intellectual disability and seizures. Pathogenic mutations in the CWF19L1 gene that code for CWF19 like cell cycle control factor 1 cause SCAR17. We report here two unrelated families with the clinical characteristics of global developmental delay, cerebellar ataxia, pyramidal signs, and seizures. Cerebellar atrophy, and T2/FLAIR hypointense transverse pontine stripes were observed in brain imaging. Exome sequencing identified novel homozygous mutations including a splice acceptor site variant c.1375-2 A > G on intron 12 in a male patient and a single nucleotide variant c.452 T > G on exon 5 resulting in a missense variant p.Ile151Ser in the female patient from two unrelated families, respectively. Sanger sequencing confirmed the segregation of these variants in the family members with autosomal recessive inheritance. Transcript analysis of the splice site variant revealed activation of a novel cryptic splice acceptor site on exon 13 resulting in an alternative transcription with a loss of nine nucleotides on exon 13. Translation of this transcript predicted an in-frame deletion of three amino acids p.(459_461del). We also observed a novel exon 13 skipping which results in premature termination of the protein product. Our study expands the phenotype, radiological features, and genotypes known in SCAR17.

Novel homozygous frameshift variant in the ATCAY gene in an Iranian patient with Cayman cerebellar ataxia; expanding the neuroimaging and clinical features: a case report

BackgroundPathogenic variants in the ATCAY gene are associated with a rare autosomal recessive disorder called Cayman cerebellar ataxia. Affected individuals display psychomotor retardation, cerebellar dysfunction, nystagmus, intention tremor, ataxic gait and dysarthric in some cases.Case presentationWhole exome sequencing was performed for a 21-month-old girl suffering from developmental delay specifically in motor and language aspects, hypotonia, nystagmus, pes planus and strabismus. The detected variant in the patient was confirmed by family segregation analysis by Sanger sequencing in both of her parents. Previously three homozygous variants in the ATCAY gene (missense, splice site and frameshift deletion) have been reported in patients with Cayman cerebellar ataxia. Here we report the fourth homozygous variant and the second homozygous frameshift deletion in this gene to be associated with autosomal recessive Cayman cerebellar ataxia.ConclusionThe identification of this novel homozygous frameshift deletion in the ATCAY gene expands our understanding of the genetic landscape underlying Cayman cerebellar ataxia. Furthermore, the occurrence of this variant in Iran, in addition to Pakistan, signifies the importance of considering genotypic and phenotypic factors beyond ethnicity when studying this disorder. These findings contribute to the ongoing efforts to unravel the molecular basis of Cayman cerebellar ataxia and improve diagnostic approaches and potential therapeutic interventions.

Multi-infarct stroke secondary to reactive thrombocytosis in a patient with iron deficiency anaemia: A case report

A 47-year-old woman who presented to the hospital with left sided weakness, left sided paraesthesia, ataxic gait, headache, nausea and vomiting was found to have multiple infarct strokes. Her past medical history was significant for iron deficiency anaemia secondary to menorrhagia. Her haemoglobin level on arrival at the hospital was 7.3 gm/dl. Her symptoms improved after blood transfusions and iron infusion. She had low cardiovascular risk factors and her stroke work up was negative. So, it was assumed that her stroke was likely related to reactive thrombocytosis secondary to iron deficiency anaemia.

Gait disorders induced by photothrombotic cerebellar stroke in mice

Patients with cerebellar stroke display relatively mild ataxic gaits. These motor deficits often improve dramatically; however, the neural mechanisms of this improvement have yet to be elucidated. Previous studies in mouse models of gait ataxia, such as ho15J mice and cbln1-null mice, have shown that they have a dysfunction of parallel fiber-Purkinje cell synapses in the cerebellum. However, the effects of cerebellar stroke on the locomotor kinematics of wild-type mice are currently unknown. Here, we performed a kinematic analysis of gait ataxia caused by a photothrombotic stroke in the medial, vermal, and intermediate regions of the cerebellum of wild-type mice. We used the data and observations from this analysis to develop a model that will allow locomotive prognosis and indicate potential treatment regimens following a cerebellar stroke. Our analysis showed that mice performed poorly in a ladder rung test after a stroke. During walking on a treadmill, the mice with induced cerebellar stroke had an increased duty ratio of the hindlimb caused by shortened duration of the swing phase. Overall, our findings suggest that photothrombotic cerebellar infarction and kinematic gait analyses will provide a useful model for quantification of different types of acute management of cerebellar stroke in rodents.

P06.19.A BEYOND T CELL TOXICITY - INTRATHECAL CXCL13 ELEVATION INDICATES B-CELL INVOLVEMENT IN NEUROLOGICAL IMMUNE-RELATED ADVERSE EVENTS FOLLOWING IMMUNE CHECKPOINT INHIBITION: 2 CASE OBSERVATIONS AND COMPREHENSIVE REVIEW

Abstract BACKGROUND Neurological immune-related adverse events (nirAE) can occur following cancer treatment with immune checkpoint inhibitors (ICI). Mainly attributed to autoreactive T-cells, nirAE usually respond to first line therapy with high-dose steroids (GC). Severe or fatal outcomes are rare & most frequently reported in clinically overlapping syndromes with accumulating evidence of B cell autoimmunity. MATERIAL AND METHODS We present 2 patients who developed grade 3-4 nirAE with evidence suggestive for B cell involvement. RESULTS Case 1: A 75y female with metastatic melanoma developed double vision & general weakness 2 weeks after the 1st cycle of ipilimumab & nivolumab. Diagnostic workup showed pleocytosis (27 cells/µl) with elevated CXCL13 (316 pg/ml) in cerebrospinal fluid (CSF). Increases of creatine kinase, troponin T, elevated levels of anti-acetylcholine receptor antibodies & positive anti-titin antibodies led to the diagnosis of myocarditis & myositis/myasthenia gravis overlap syndrome. The patient received pulsed high-dose GC with tapering. CSF flow cytometry revealed intrathecal recruitment of CXCL13-responsive B cell helper T cells of a predominant inflammatory phenotype & a highly increased pathological CD4/CD8 T cell ratio in peripheral blood. Clinically non-responding to GC, the patient received additional therapy with immunoglobulins (IVIG). 2 weeks later she was readmitted due to generalized myopathy with dropped head & received a second cycle of high-dose GC since she refused plasmapheresis. Further escalation with rituximab could not be realized because the patient rapidly deteriorated & deceased. Case 2: A 75y female with metastatic invasive enteric adenocarcinoma of the lung developed gait ataxia & ataxia of the lower limbs 5 months after pembrolizumab therapy. CSF analysis showed a pleocytosis (248 cells/µl) with plasma cells, pronounced CXCL13 elevation (>488 pg/ml) & positive screening for anti-neuronal cerebellar antibodies, suggesting ICI-mediated cerebellitis. The patient received high-dose GC & IVIG for 5 days each, was discharged but readmitted 5 months later due to subacute onset of spastic paraparesis. Magnetic resonance imaging of the spine revealed thoracic myelopathy & CSF showed mild pleocytosis (5 cells/µl), intrathecal immunoglobulin synthesis & mild CXCL13 elevation (33 pg/ml). The patient completed a second cycle of steroids followed by rituximab targeting B-cell involvement & currently 4 months later is clinically stable. CONCLUSION Intrathecal CXCL13 may serve as diagnostic tool of B cell involvement, here supported by intrathecal immunoglobulin synthesis, presence of plasma cells and/or severely altered immune cell compositions. Early treatment escalation with B cell depleting agents such as rituximab may help prevent fatal clinical courses.

Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety, and tolerability of dimethyl fumarate in Friedreich Ataxia (DMF-FA-201).

Friedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder that causes gait and limb ataxia, dysarthria, and impaired vibratory sense, with cardiomyopathy being the predominant cause of death. There is no approved therapy, which results in the use of symptomatic treatments and the chronic support of physiotherapy. Dimethyl fumarate (DMF) is a fumaric acid ester used for the treatment of psoriasis and Multiple Sclerosis (MS). It induces Nrf2 in vitro and in vivo, and it increases frataxin in FRDA patient lymphoblasts, in mouse models, and in MS treated patients. The aim of our study is to investigate if DMF can increase the expression of the FXN gene and frataxin protein and ameliorate in-vivo detectable measures of mitochondrial dysfunction in FRDA. The study is composed of a screening visit and two sequential 12-week phases: a core phase and an extension phase. During the first phase (core), patients will be randomly assigned to either the DMF or a placebo group in a 1:1 ratio. During the first week, patients will receive a total daily dose of 240 mg of DMF or placebo; from the second week of treatment, the dose will be increased to two 120 mg tablets BID for a total daily dose of 480 mg. During the second phase (extension), all patients will be treated with DMF. EudraCT number 2021-006274-23. The primary endpoint will be a change in FXN gene expression level after 12 weeks of treatment. Secondary endpoints will be frataxin protein level, cardiopulmonary exercise test outputs, echocardiographic measures, Nrf2 pathway and mitochondrial biogenesis gene expression, safety, clinical scales, and quality of life scales. This is the first study aimed at exploring the ability of DMF, an already available treatment for MS and psoriasis, to correct the biological deficits of FRDA and potentially improve mitochondrial respiration in-vivo.

An alcoholic with gait ataxia and global confusion

N/A

Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia.

Dominantly inherited GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene have recently been shown to cause spinocerebellar ataxia 27B (SCA27B). We aimed to study the frequency and phenotype of SCA27B in a cohort of patients with unsolved late-onset cerebellar ataxia (LOCA). We also assessed the frequency of SCA27B relative to other genetically defined LOCAs. We recruited a consecutive series of 107 patients with LOCA, of whom 64 remained genetically undiagnosed. We screened these 64 patients for the FGF14 GAA repeat expansion. We next analysed the frequency of SCA27B relative to other genetically defined forms of LOCA in the cohort of 107 patients. Eighteen of 64 patients (28%) carried an FGF14 (GAA)≥250 expansion. The median (range) age at onset was 62.5 (39-72) years. The most common clinical features included gait ataxia (100%) and mild cerebellar dysarthria (67%). In addition, episodic symptoms and downbeat nystagmus were present in 39% (7/18) and 37% (6/16) of patients, respectively. SCA27B was the most common cause of LOCA in our cohort (17%, 18/107). Among patients with genetically defined LOCA, SCA27B was the main cause of pure ataxia, RFC1-related disease of ataxia with neuropathy, and SPG7 of ataxia with spasticity. We showed that SCA27B is the most common cause of LOCA in our cohort. Our results support the use of FGF14 GAA repeat expansion screening as a first-tier genetic test in patients with LOCA.

Laser interstitial thermal therapy in pediatric cerebellar epilepsy.

Cerebellar lesional epilepsy is rare, commonly manifesting in early life and posing diagnostic and treatment challenges. Seizure semiology may be subtle, with repetitive eye blinking, face twitching, and irregular breathing, while EEG commonly remains unremarkable. Pharmacoresistance is the rule, and surgical intervention is the only treatment with the potential for cure. Novel minimally invasive techniques, such as laser interstitial thermal therapy (LITT), are emerging for surgically less accessible, deep-seated epileptogenic lesions. We report the case of a patient who presented with peculiar eye and face movements occurring episodically and stereotypically since the first weeks of life and was later diagnosed with cerebellar epilepsy related to a hamartoma. Refractory daily seizures, unresponsive to antiseizure medication, were followed by increasingly prominent gait ataxia and delayed speech development. Staged LITT was performed in two consecutive sessions at 3 and 4 years, leading to seizure cessation, neurological improvement, and developmental gains over a postsurgical follow-up period of 8 months. Our case highlights cerebellar lesional epilepsy as a rare but important differential diagnosis in children with paroxysmal disorders predominantly involving the face. Furthermore, we illustrate the radiological correlates of neurocognitive deficit related to the cerebellar lesion, manifesting as cerebello-cerebral diaschisis. Most importantly, our observations showcase LITT as a safe and effective therapeutic approach in cerebellar lesional epilepsy and an attractive alternative to open brain surgery, especially for deep-seated lesions in the pediatric population.

A case of severe paraneoplastic glutamic acid decarboxylase antibody‐spectrum disorder with improvement through prior immunotherapy before surgical intervention

AbstractBackgroundInitially associated with stiff‐person syndrome, antibodies to glutamic acid decarboxylase (GAD) antibodies are now recognized as indicators of GAD antibody‐spectrum disorders (GAD‐SD), which encompass cerebellar ataxia, autoimmune epilepsy and limbic encephalitis. Paraneoplastic neurological syndromes associated with GAD‐SD are rare, and optimal timing of surgical intervention and impact on neurological symptoms remain poorly understood.Case PresentationWe present the case of a 65‐year‐old woman who developed overlapping symptoms of cerebellar ataxia and stiff‐person syndrome detected through high‐titer GAD antibodies in both serum and cerebrospinal fluid, alongside the presence of a thymoma. Due to severe dysphagia and gait ataxia that rendered her bedridden on admission, surgical intervention was initially deferred. Instead, she received immunotherapies including intravenous methylprednisolone and intravenous immunoglobulin, which remarkably improved neurological symptoms. However, a decline in symptoms occurred on tapering oral prednisolone. Subsequently, a thoracoscopic thymectomy was carried out 27 months after symptom onset, leading to further neurological improvement and successful reduction of prednisolone.ConclusionIn paraneoplastic GAD‐SD cases with severe symptoms at presentation, prioritizing immunotherapy and considering surgical intervention once the symptoms have stabilized might be advantageous.

Intradural Extramedullary Tumors and Associated Syndromes.

Most intradural tumors are located within the intradural extramedullary compartment, and the most common tumors are schwannomas and meningiomas. Other less common neoplasms include neurofibroma, solitary fibrous tumor, myxopapillary ependymoma, lymphoma, metastatic leptomeningeal disease, malignant peripheral nerve sheath tumor, and paraganglioma. Patients usually present with gait ataxia, radicular pain, and motor and sensory deficits due to chronic compressive myelopathy or radiculopathy. MRI is the modality of choice for detecting and evaluating intradural extramedullary spinal tumors. This imaging technique helps narrow the differential diagnosis and therefore decide treatment.

A Rare Low-Grade Glioma with Stevens Jonson’s Syndrome - Case Report

Introduction: The brain has a complicated structure within the body, but the CNS develops during growth and development in three stages: cytogenesis, histogenesis, and organogenesis, which determine the CNS's final makeup and shape. Organogenesis occurs in children when neural and extra-neural tissues mingle, causing a growing lesion inside the skull. Nearly 20% of the second-most prevalent group of paediatric neoplasms after leukaemia either a benign or malignant primary brain tumour may exist. The majority of infratentorial and close-to-midline brain tumours result in hydrocephalus. Astrocytomas, ependymomas, craniopharyngiomas, and malignant gliomas are the most prevalent supratentorial tumours. Additionally, toxic epidermal necrolysis (TEN) and Stevens Johnson's syndrome (SJS) are now thought to be variations of the same hypertension illness. These conditions affect 1 to 3 million children each year. The degree of epidermal detachment determines the classification; a transitional SJS with less than 10% and 30% epidermal detachment is most frequently confused with Kawasaki illnesses. Case presentation: 9-year-old male child came with complaints of ataxic gait in the past 7 days and vomiting in the past 20 days. As narrated by the father patient was well 7 days back then the patient had difficulty walking due to an ataxic gait, the patient fell on the ground and had a head injury and had no vomiting, fever, loss of consciousness, and no altered sensorium. The patient had 4 episodes of vomiting yesterday and 2 episodes today morning, non-bilious, non-projectile, and containing sputum, patient had a headache that was progressive, intermittent no blurring of vision, not fever but vomiting. The patient then came for further management. Conclusion: The second most prevalent type of paediatric neoplasm after leukaemia, organogenesis in the kid occurs when neural and extra neural tissue combines to form a growing lesion inside the skull either a benign or malignant primary brain tumour may exist. The majority of infratentorial and close-to-midline brain tumours result in hydrocephalus. Additionally, toxic epidermal necrolysis (TEN) and Stevens Johnson's syndrome (SJS) are now thought to be variations of the same hypertension illness. With the development of newer diagnostic methods like MRI, CT, SPECT, PET, and newer electroencephalography techniques as well as evoked potential, it is now possible to accurately diagnose and delineate a variety of neurological alignments. The incidence of these conditions ranges from 1 to 3 million per child lower the risk of morbidity.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'.

Wernicke Encephalopathy in a Pediatric Patient with Avoidant Restrictive Food Intake Disorder: A Rare Presentation of Thiamine Deficiency.

BACKGROUND Wernicke encephalopathy is traditionally associated with chronic alcoholism, nutritional imbalance, prolonged intravenous feeding, hyperemesis, anorexia nervosa, and malabsorption syndromes. We report a case of Wernicke's encephalopathy in a 12-year-old girl with avoidant restrictive food intake disorder. CASE REPORT The patient had lost 45.4 kg of body weight due to self-imposed changes to her diet, before presenting with decreased oral intake for 2-3 weeks, intermittent nausea, crampy epigastric pain, and post-prandial emesis. Her weight on admission was 78.2 kg. She received intravenous fluids of dextrose 5% with normal saline while she initially attempted to eat, but the post-prandial emesis persisted. She developed a fear of vomiting, which led to even more severe food intake restriction. After a week, she began to report double vision and blurred peripheral vision, with physical findings of nystagmus and an ataxic gait. She was empirically started on thiamine after negative neurology workup, with improvement of her gait, blurry vision, and nystagmus. Thiamine deficiency was later confirmed. CONCLUSIONS In patients with large amounts of weight loss presenting with neurological symptoms, Wernicke's encephalopathy must be considered in the differential diagnosis. Avoidant restrictive food intake disorder is rarely reported to cause Wernicke's encephalopathy. To the best of our knowledge, this is the first pediatric case demonstrating that Wernicke encephalopathy can occur in this type of eating disorder and not just in anorexia nervosa.