Sensory Ataxia Research Articles

Morphological analysis of autophagy in axonal degeneration in gracile axonal dystrophy mice.

Gracile axonal dystrophy (gad) mutant mice present with autosomal recessive inherited sensory ataxia in the early stages, followed by age-dependent motor ataxia. This phenotype is caused by a mutation in the ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) gene and leads to a lack of expression of UCH-L1 protein, which is related with the autophagy pathway and the ubiquitin-proteasome system (UPS). To elucidate the pathophysiology of abnormal protein accumulation in gad mice, we focused on macroautophagy. Using electron microscopy, we detected a double-membrane structure, which was characteristic of autophagosomes, in gad mice. In addition, on immunohistochemistry to investigate the expression levels of autophagy-related proteins in the gracile nuclei of the gad mouse, we found upregulation of LC3 and p62 but not LAMP-2A. These results suggested that a lack of UCH-L1 expression might induce the formation of autophagosomes, but the resulting autophagy flux might be disturbed.

Drug and Toxin-Induced Cerebellar Ataxias

Ataxia is the inability to coordinate voluntary movement and can present with a variety of symptoms involving dyscoordination of gait and extremity movement, slurred speech, and abnormal eye movements. Ataxia can be divided into either cerebellar or sensory. Cerebellar ataxia originates from damage to the cerebellum or its connecting tracts, while sensory ataxia is a result of damage to the afferent sensory pathways such as the dorsal column and large myelinated proprioceptive fibers

Imbalance and gait impairment in Parkinson's disease: discussing postural instability and ataxia.

Gait and balance difficulties pose significant clinical challenges in Parkinson's disease (PD). The impairment of physiological mechanisms responsible for maintaining natural orthostatism plays a central role in the pathophysiology of postural instability observed in PD. In addition to the well-known rigidity and abnormalities in muscles and joints, various brain regions involved in the regulation of posture, balance, and gait, such as the basal ganglia, cerebellum, and brainstem regions like the pontine peduncle nucleus, are affected in individuals with PD. The recognition of the cerebellum's role in PD has been increasingly acknowledged. Cortical areas and their connections are associated with freezing of gait, a type of frontal lobe ataxia commonly observed in PD. Furthermore, impairments in the peripheral nervous system, including those caused by levodopatherapy, can contribute to gait impairment and imbalance in PD patients. Consequently, individuals with PD may exhibit frontal ataxia, sensory ataxia, and even cerebellar ataxia as underlying causes of gait disturbances and imbalance, starting from the early stages of the disease. The complex interplay between dysfunctional brain regions, impaired cortical connections, and peripheral nervous system abnormalities contributes to the multifaceted nature of gait and balance difficulties in PD. Understanding the intricate mechanisms is crucial for the development of effective therapeutic approaches targeting these specific deficits in PD.

Pathology of human organic mercury poisoning: Lessons from an autopsy case

We had an opportunity to perform a general autopsy of a case with chronic organic mercury toxicosis in 2017. He had been engaged in synthesizing a variety of organic mercury compounds throughout the four years from 1966 and developed chronic organic mercury poisoning in 1969. Almost forty years on, he still remained to complain of persistent paresthesia at finger tips and tongue, and of narrowed visual field. Neurological examinations clarified a rise of two-point discrimination thresholds, a systemic increase of touch thresholds, constriction of the visual field caused by general visual depression, and sensorineural hearing loss while primary modalities of his somatic, visual, and auditory sensations were preserved. These symptoms and signs are characteristic of human organic mercury poisoning. Furthermore, he had difficulty in processing a lot of visual and auditory information at a time. His two-point discrimination thresholds and systemic elevation of touch thresholds were comparable to those of mild organic mercury poisoning cases. He had slight sensory ataxia, but not cerebellar ataxia. Brain [18F]-2-fluorodeoxyglucose positron emission tomography analysis exhibited marked hypometabolism at bilateral postcentral gyrus, striate cortex, and superior temporal gyrus, but not the cerebellum. Histopathological studies revealed considerable decrease of granular neurons and neuronal networks in bilateral primary somatosensory, visual, and auditory cortices. Those characteristic brain lesions fairly explain increase of thresholds of somatic, visual, and auditory sensations, and degradation of integrating sensory information. It is noted that damages to the peripheral nervous system and the cerebellum were not detected and that his intellectual faculties were preserved.

Acute‐onset distal dominant neuropathy after severe acute respiratory syndrome coronavirus 2 vaccination in a male patient with recent dengue infection: A case report

AbstractObjectiveGuillain–Barré Syndrome (GBS) is an autoimmune degenerative disease commonly presenting with acute progressive sensorimotor paralysis, sometimes associated with dysautonomia, facial diplegia and severe respiratory distress. Gastroenteritis due to Campylobacter jejuni and respiratory infection secondary to Epstein–Barr virus usually precede GBS; however, vaccination or recent dengue infection as temporal causes are rarely reported.Case PresentationHere, we present a 20‐year‐old man, who complained of a 5‐day history of a progressively worsening tingling sensation isolated in the hands and feet, and unilateral Bell's palsy on the left side of his face, which occurred 2 weeks after his severe acute respiratory syndrome coronavirus 2 vaccination and 6 weeks from his recent hospitalization from Dengue fever. Except for the left complete unilateral facial paralysis, weakness in the intrinsic hands and feet muscles, and sensory ataxia, the rest of his physical examination was unremarkable. On work‐up, the findings of albuminocytological dissociation and distal sensorimotor demyelinating polyneuropathy in the nerve conduction study supported the diagnosis of GBS.ConclusionThe enhanced immune response from a recent dengue infection and severe acute respiratory syndrome coronavirus 2 vaccination might increase the risk of GBS. The predominantly distal GBS phenotype has rarely been reported in the literature, adding to the peculiarity of this case.

Prospective Study of Acalabrutinib with Rituximab in Patients with Symptomatic Anti-MAG Mediated IgM Peripheral Neuropathy

Background: Peripheral neuropathy (PN) occurs in 20-25% of patients with an IgM paraprotein and up to 50% of these patients have an anti-myelin associated glycoprotein (MAG) antibody which is frequently associated with sensory ataxia and distal limb weakness negatively affecting function and quality of life. While rituximab is active, its activity is limited as a monotherapy and often associated with an IgM flare that can potentiate PN. BTK-inhibitors can block rituximab-associated IgM flare and are proven to markedly reduce serum IgM in Waldenström's Macroglobulinemia (WM). We therefore initiated this trial to evaluate a novel treatment for anti-MAG PN. Methods: We initiateda prospective, single-arm phase II study of acalabrutinib and rituximab (NCT05065554). Patients with an anti-MAG antibody with an IgM monoclonal gammopathy or WM; and a predominantly sensory demyelinating PN with a modified Rankin score of ≥1 with progressive symptoms or a score of ≥2 are eligible. Treatment consists of continuous oral acalabrutinib (100 mg twice daily) with rituximab weekly in cycles 1 and 4. Each cycle is 28 days. The primary endpoint is to evaluate the hematologic response rate. The key secondary endpoint is to evaluate the proportion of patients that achieve improvement or stability in PN based on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) patient-reported disability scale. Additional secondary neurologic endpoints include the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, MRC distal sum score, INCAT sensory sum score, and a neuropathy-specific quality of life scale (IN-QOL). We hypothesize that 75% of participants (H1) will have a hematologic response versus a null (H0) of 50% or lower. With 33 evaluable patients, there will be 82% power to detect a significant difference with an alpha (2-sided) of 0.04. Results: Eight patients, including 4 females, have enrolled as of July 1, 2023. The median age is 70 years (range 65-76), and median ECOG is 1. Median I-RODS score at baseline was 41 (range 23-48; 48 = no disability). All patients have an IgM kappa paraprotein with median baseline serum IgM of 975 mg/dL (range 226-2137), kappa free light chain of 28 mg/L (range 16-47), and M-spike of 0.6 g/dL (range 0.17-1.1). Anti-MAG antibody titer range is 1:70,000 to 1:819,200 IU/L. Bone marrow biopsy showed no disease in 4 patients, a clonal plasma cell population in 1 patient, and lymphoplasmacytic infiltrate in 3 patients. No adenopathy or splenomegaly were detected on baseline CT scans. Six patients (75%) are MYD88 mutated and none CXCR4 mutated. Five patients had prior rituximab therapy and two received prior IVIG. With a median time on treatment of 175 days (range 28-510), the overall response rate among 7 evaluable patients using IWWM-11 criteria was 86%. Categorical responses include 2 very good partial responses (≥90% decrease in IgM, or normalization of IgM with persistent IgM monoclonal protein); 1 partial response (≥50% but <90% decrease in IgM); 3 minor responses (≥25% but <50% decrease in IgM) and 1 stable disease. Four of 7 patients (57%) had improvement in the I-RODS score. Median improvement was 0.5 points (range -4 to 11). One patient was removed from the trial after 28 days due to grade 3 elevation in ALT. Two other reversible grade 3 adverse events occurred including rituximab related infusion reaction and syncope unrelated to treatment. Conclusions: The combination of acalabrutinib and rituximab has demonstrated activity in this first prospective study that is evaluating BTK-inhibition with CD20 directed therapy in patients with IgM related anti-MAG PN. Hematologic responses occurred in 86% of patients and 57% had an improvement in the I-RODS score. Treatment is well tolerated. Additional data from more detailed neurologic assessments are forthcoming. The trial continues to enroll patients. Our findings provide a framework to develop novel, more effective treatment options for anti-MAG PN.

Frontal ataxia: historical aspects and clinical definition.

Frontal ataxia, originally described by Bruns, is characterized by the presence of signs of frontal lobe dysfunction, such as perseveration, paratonia, frontal release signs, cognitive changes, and urinary difficulty, associated with imbalance, slow gait, broad-based, the presence of postural instability and falls, retropulsion, and bradykinesia in the lower limbs. The goal of the present study is to recall the historical aspects of this condition, to draw attention to the importance of this clinical finding for the differential diagnosis of ataxias and to review the main semiological differences between primary ataxias (frontal, cerebellar, and sensory ataxia).

Neurologic orphan diseases: Emerging innovations and role for genetic treatments.

Orphan diseases are rare diseases that affect less than 200000 individuals within the United States. Most orphan diseases are of neurologic and genetic origin. With the current advances in technology, more funding has been devoted to developing therapeutic agents for patients with these conditions. In our review, we highlight emerging options for patients with neurologic orphan diseases, specifically including diseases resulting in muscular deterioration, epilepsy, seizures, neurodegenerative movement disorders, inhibited cognitive development, neuron deterioration, and tumors. After extensive literature review, gene therapy offers a promising route for the treatment of neurologic orphan diseases. The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases. Additionally, the use of adeno-associated viral vectors has shown improvement in survival, motor function, and developmental milestones, while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients. Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes. Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth, proliferation, and angiogenesis. Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.

Intraoperative stimulation mapping of thalamocortical tracts in asleep and awake settings: novel electrophysiological, anatomical, and tractographic paradigms.

Despite the disabling deficits of motor apraxia and sensory ataxia resulting from intraoperative injury of the superior thalamocortical tracts (TCTs), region-specific electrophysiological localization is currently lacking. Herein, the authors describe a novel TCT mapping paradigm. Three patients, 1 asleep and 2 awake, underwent glioma resection affecting primarily the somatosensory cortex and underlying TCT. Stimulation was performed at the median, ulnar, and posterior tibial nerves. Parameters comprised single anodal pulses (duration 200-500 μsec, 2.1-4.7 Hz) with a current ranging from 10 to 25 mA. Recordings were captured with a bipolar stimulation probe, avoiding the classic collision technique. Positive localization sites were used to tractographically reconstruct the TCT in the third case. Employing one electrophysiological paradigm, the TCT was localized subcortically in all 3 cases by using a bipolar probe, peak range of 19.6-29.2 msec, trough of 23.3-34.8 msec, stimulation range of 10-25 mA. In the last case, tractographic reconstruction of the TCT validated a highly accurate TCT localization within a specific region of the posterior limb of the internal capsule. The authors describe the first electrophysiological technique for intraoperative localization and protection of the TCT in both asleep and awake craniotomies with tractographic validation, while avoiding the collision paradigm. None of the above paradigms have been previously reported. More data are required to further validate this technique.

Benefit of high-dose oral riboflavin therapy in riboflavin transporter deficiency.

Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation is beneficial in short-term reports, but the quantum of benefit in various clinical domains is not well understood. A PubMed search was conducted, which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow-up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed. Seventy-six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%) and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy dependent. Riboflavin supplementation is a lifesaving intervention for patients with RTD and results in a profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease-modifying therapies.

DNM1L variant presenting as adolescent-onset sensory neuronopathy, spasticity, dystonia, and ataxia.

DMN1L encodes for dynamin-like protein 1 (DLP1) which plays a key role in perixosomal and mitochondrial fission. Individuals with heterozygous variants in DNM1L present with a wide range of neurologic symptoms, including encephalopathy, epilepsy, and motor deficits. Here we report on a woman presenting with adolescence onset of sensory neuronopathy, spasticity, dystonia, and ataxia. Trio genome sequencing identified a heterozygous variant in DNM1L (NM_012062.3 c.121G>A/p.Val41Met) which was thought to be pathogenic. This case describes the latest known symptomatic onset of DMN1L-related disease described in literature. We highlight our approach to a challenging diagnostic workup and interpretation of a specific variant that has not been previously reported. Furthermore, the case highlights the diagnostic importance of utilizing genomic sequencing and research studies for patients with rare disease.

Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review.

Periaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F). In this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported PRX-related CMT cases and summarized the clinical manifestations and genetic features of PRX-related CMTs. The hit rate for biallelic PRX variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and PRX variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous system involvement. The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms. Consistent with observations in other countries and ethnic groups, PRX-related CMT is rare in China. The clinical spectrum is wider than previously anticipated.

CANVAS, a sensory neuronopathy to look for in ataxia

Sensory neuronopathies name the degeneration of peripheral sensory neurons in dorsal root ganglia. Among the genetic causes, CANVAS could be the most frequent. CANVAS is a clinical entity associating cerebellar ataxia, sensory neuronopathy and vestibular areflexia due to biallelic expansions in RFC1. This study reports the 18 individuals with sensory neuronopathy tested for RFC1 expansion in our center. The clinical picture showed that chronic cough was a frequent sign beginning before the onset of other symptoms. CANVAS is an underestimated cause of late-onset sensory and cerebellar ataxia that needs to be tested for widely now that the molecular cause is known.

CO110 Hospitalizations, Clinical Characteristics and Mortality in Adults with Adrenomyeloneuropathy (AMN): A Retrospective Study

Adrenomyeloneuropathy (AMN) is a rare neurodegenerative X-linked disease caused by mutations in ABCD1 that cause progressive myeloneuropathy, spastic paraparesis, sensory ataxia, loss of mobility, incontinence, and sexual dysfunction. This study sought to examine for the first time hospitalizations, clinical characteristics, and mortality in adults with AMN in the US.

EE373 The Economic Impact of Adrenomyeloneuropathy (AMN) on Direct Medical Costs in Commercially Insured US Adults: A Retrospective Study

Adrenomyeloneuropathy (AMN) is the most common manifestation of X-linked adrenoleukodystrophy (X-ALD), a rare neurodegenerative disease caused by mutations in ABCD1, featuring progressive myeloneuropathy, spastic paraparesis, sensory ataxia, loss of mobility, incontinence, and sexual dysfunction. Presentation, onset and clinical manifestations vary between men and women. This study sought to quantify for the first time the impact of AMN on healthcare costs in commercially insured adults, both male and female, in the US.

Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues. DAAO-TGCdh5 transgenic mice express DAAO under control of the putatively endothelial-specific Cdh5 promoter. When we provide these mice with D-alanine, they rapidly develop sensory ataxia caused by oxidative stress and mitochondrial dysfunction in neurons within dorsal root ganglia and nodose ganglia innervating the heart. DAAO-TGCdh5 mice also develop cardiac hypertrophy after chronic chemogenetic oxidative stress. This combination of ataxia, mitochondrial dysfunction, and cardiac hypertrophy is similar to findings in patients with Friedreich’s ataxia. Our observations indicate that neurovascular oxidative stress is sufficient to cause sensory ataxia and cardiac hypertrophy. Studies of DAAO-TGCdh5 mice could provide mechanistic insights into Friedreich’s ataxia.

Topographic Consideration on the Occurrence of Ipsilesional Facial Paresis in Lateral Medullary Infarction

Introduction: The purpose of this study was to identify course of the corticobulbar tract and factors associated with the occurrence of facial paresis (FP) in lateral medullary infarction (LMI). Methods: Patients diagnosed with LMI who were admitted to tertiary hospital were retrospectively investigated and divided into two groups based on the presence of FP. FP was defined as grade 2 or more by the House-Brackmann scale. Differences between the two groups were analyzed with respect to anatomical location of the lesions, demographic data (age, sex), risk factors (diabetes, hypertension, smoking, prior stroke, atrial fibrillation, and other cardiac risk factors for stroke), large vessel involvement on magnetic resonance angiography, other symptoms and signs (sensory symptoms, gait ataxia, limb ataxia, dizziness, Horner syndrome, hoarseness, dysphagia, dysarthria, nystagmus, nausea/vomiting, headache, neck pain, diplopia, and hiccup). Results: Among 44 LMI patients, 15 patients (34%) had FP, and all of them had ipsilesional central-type FP. The FP group tended to involve upper (p < 0.0001) and relative ventral (p = 0.019) part of the lateral medulla. Horizontally large lesion was also related to the presence of FP (p = 0.044). Dysphagia (p = 0.001), dysarthria (p = 0.003), and hiccups (p = 0.034) were more likely to be accompanied by FP. Otherwise, there were no significant differences. Conclusion: The results of present study indicate that the corticobulbar fibers innervating the lower face decussate at the upper level of the medulla and ascend through the dorsolateral medulla, where the concentration of the fibers is densest near the nucleus ambiguus.

Post‐COVID‐19 vaccination Guillain–Barré syndrome with sensory ataxia, gaze‐evoked nystagmus, mental‐status change and positive pathological reflex

AbstractBackgroundVarious neurological disorders have been reported after vaccination against coronavirus disease 2019, one of which is Guillain–Barré Syndrome (GBS).Case PresentationWe report a case of a 73‐year‐old woman who developed GBS and extra‐GBS manifestations 19 days after the second dose of BNT162b2 mRNA vaccine. She presented lower limb predominant muscle weakness and loss of tendon reflexes. Nerve conduction study showed acute motor and sensory axonal neuropathy. In addition, she developed notable deep sensory ataxia, and showed positive pathological reflex, gaze‐evoked nystagmus and altered consciousness, which suggested brainstem involvement.ConclusionsThis is the first coronavirus disease 2019 vaccine‐related GBS complicated with such central nervous system manifestations.

Energy Expenditure Index Correlates with Motor and Sensory Impairments and Disease Severity in Adrenomyeloneuropathy (P12-9.008)

<h3>Objective:</h3> This study aimed to assess whether energy expenditure index (EEI) after the fast walking in individuals with adrenomyeloneuropathy (AMN) is associated with perceived exertion, impaired gait, postural sway, spasticity, and disease severity. <h3>Background:</h3> AMN is a progressive X-linked peroxisomal disorder presenting during adulthood. AMN is long tract disorder involving dorsal columns and corticospinal tracts, characterized by sensory ataxia, spastic paraparesis and bowel/bladder dysfunction. The ratio of heart rate (HR) per meter walk is a valid scale to represent energy consumption during walking and is known as the EEI. <h3>Design/Methods:</h3> We conducted a cross-sectional analysis of baseline data collected from a clinical trial in adults with AMN. Perceived exertion was quantified in patients using the modified Borg scale (MBS). Gait parameters were measured by 3D motion capture at fast walking and postural sway was assessed in four static standing positions. The Ashworth scale and expanded disability status scale (EDSS) were used to evaluate spasticity and disease severity, respectively. The analysis was performed using multiple linear regressions adjusted for age and weight of participants. <h3>Results:</h3> Fifty-seven individuals (35 females and 22 males) with recorded resting HR and walking HR after the fast walking were included. EEI was significantly associated with MBS in both females (R²: 0.44, P-value: 0.0001) and males (R²: 0.68, P-value: 0.0001). Among females, EEI was correlated with cadence (R²: 0.35, P-value: 0.0001), stride length (R²: 0.32, P-value: 0.0003), double support time (R²: 0.29, P-value: 0.006), spasticity (R²: 0.22, P-value: 0.004), and pyramidal EDSS (R²: 0.18, P-value: 0.009). EEI was associated with pyramidal EDSS (R²: 0.39, P-value: 0.001), spasticity (R²: 0.39, P-value: 0.001), and cadence (R²: 0.27, P-value: 0.003) among males. <h3>Conclusions:</h3> AMN symptoms correlate with increased effort with mobility, and EEI may be a mean to measure the impact of the severity of AMN symptoms on patients’ quality of life. <b>Disclosure:</b> Mr. Amanat has nothing to disclose. Christopher Joseph has nothing to disclose. Jennifer Keller has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Encompass Health. Jennifer Keller has received publishing royalties from a publication relating to health care. Dr. Raymond has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Bluebird bio. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Travere. Dr. Raymond has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with Dept of HHS. Dr. Turk has received intellectual property interests from a discovery or technology relating to health care. Dr. Turk has received publishing royalties from a publication relating to health care. Dr. Fatemi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bluebirdbio. Dr. Fatemi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for RCO law. The institution of Dr. Fatemi has received research support from Minoryx. The institution of Dr. Fatemi has received research support from Viking Therapeutics. The institution of Dr. Fatemi has received research support from Swanbio Therapeutics . The institution of Dr. Fatemi has received research support from Autobahn Therapeutics. The institution of Dr. Fatemi has received research support from Nuvelution. The institution of Dr. Fatemi has received research support from NIH. The institution of Dr. Fatemi has received research support from A Cure for Ellie Foundation. The institution of Dr. Fatemi has received research support from Brian’s Hope Foundation . Dr. Fatemi has received intellectual property interests from a discovery or technology relating to health care. Dr. Fatemi has a non-compensated relationship as a Director (Board member) with ALDConnect that is relevant to AAN interests or activities. The institution of Dr. Fine has received research support from NIH.

Ixekizumab-associated transverse myelopathy in a patient with psoriatic arthritis (P14-3.017)

<h3>Objective:</h3> We present the case of a woman with acute-onset myelopathy who presented with sensory symptoms and ataxia. We discuss her diagnosis of monoclonal antibody-induced short-segment transverse myelopathy and the potential mechanisms mediating this adverse reaction. <h3>Background:</h3> Monoclonal antibodies have provided novel therapeutic avenues for several disorders in oncology, rheumatology, and neurology. These treatments, however, have been noted to carry a rapidly growing host of adverse reactions, many of which involve the nervous system. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 57-year-old right-handed woman with psoriatic arthritis on monthly ixekizumab injections (a humanized monoclonal antibody directed against interleukin 17A) was admitted for a two-day history of progressive dysesthesias, which ascended from her feet to the lower abdomen. Her neurologic examination showed patellar and ankle hyperreflexia with large-fiber modality length-dependent sensory loss and preserved small-fiber modalities. The workup was notable for normal B12, homocysteine, copper, and zinc levels. No abnormal protein bands were identified on serum protein electrophoresis. A lumbar puncture yielded a bland CSF with two white cells, glucose of 65, protein of 43.5, and 0 oligoclonal bands. Serum ANA was positive with homogeneous with a 1:320 titer, reflecting to positive dsDNA and Scl70. A broad infectious workup was negative for HSV, VZV, CMV West Nile virus, Lyme, syphilis, HIV, and HTLV-2. MRI of the neuraxis was remarkable for a short-segment T2 hyperintense lesion of the dorsal column spanning T7–9. In the context of unrevealing etiological work-up, she was diagnosed with ixekizumab-induced transverse myelopathy and the biologic drug was stopped. She continued to improve during the following year without recurring CNS symptoms. <h3>Conclusions:</h3> We report the first case of ixekizumab-induced thoracic transverse myelopathy which we stipulate may result from dysregulation of the T-helper pathways given the antagonism of IL-17A. As shown by this clinical presentation, neurologists need to be aware of the adverse reactions of monoclonal antibodies. <b>Disclosure:</b> Dr. Rosso has nothing to disclose. Dr. Milano has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Jackson kelly. Dr. Gleichgerrcht has nothing to disclose.