Normal Brain Imaging Research Articles

Role of nonpharmacological concussion management in children: systematic review of randomized controlled trials.

Concussion is a global public health problem that affects many children worldwide. Most patients present with postconcussion syndrome and normal brain imaging find- ings. Despite the high incidence of concussion in children, published research on nonpharmacological management is lacking and much more often concerns pharmacological interventions. This systematic review aimed to evaluate the role of nonpharmacological interventions in managing concussion based on randomized controlled trials. The PubMed, Scopus, Web of Science, and Cochrane data- bases were extensively searched for articles published between January 2013 and July 2023. A modified patient intervention, comparison, and outcome framework was used to construct the search strategy and eligibility criteria. Risk of bias was assessed using the Risk of Bias-2 tool. A total of 16 studies conducted between January 2013 and July 2023 were analyzed. Three studies were conducted in an acute care setting (<24-hour postinjury) involving rest, computer time, and doing nothing, while the other 13 studies were conducted in a chronic care setting (>24-hour postinjury) and included aerobic exercise, collaborative care intervention, cervical spine rehabilitation, education by physiotherapists, a hyperbaric oxygen therapy protocol, family intervention therapy, virtual reality, traditional occupational therapy, virtual rehabilitation, oculomotor control exercises, vestibular rehabilitation, coordination exercises, and balance exercises. This systematic review highlights the importance of nonpharmacological therapy in pediatric concussion cases. Active rehabilitation may yield promising outcomes. Another interesting approach may be useful in pediatric concussion management. How- ever, this systematic review shows a lack of high-quality literature supporting nonpharmacological pediatric con- cussion treatments.

Associations between elevated uric acid and brain imaging abnormalities in pediatric patients with methylmalonic acidemia under 5 years of age

Methylmalonic acidemia (MMA) is the most common inborn organic acidemia, presenting multisystemic complications. Uric acid may have neurotoxic or neuroprotective effects due to its antioxidant or pro-inflammatory properties; however, its role in MMA brain injury remains unclear. We examined the correlation between the serum uric acid levels and brain imaging features of MMA. Data were collected from a cross-sectional study of 216 patients with MMA and 216 healthy matched controls aged 0–5 years in China. Serum uric acid levels were measured, and magnetic resonance imaging and computed tomography findings were retrieved from hospital records. Overall, 74.1% patients had brain abnormalities. Patients in the MMA group with abnormal brain imaging had higher serum uric acid levels than those in the MMA normal brain imaging and control groups. The area under the curve of serum uric acid was 0.74, 0.91, and 0.93 for MMA diagnosis with abnormal brain images, basal ganglia changes, and globus pallidus changes, respectively. Higher serum uric acid levels were independently associated with abnormal brain images. Children aged < 5 years with abnormal brain images in MMA exhibit elevated serum uric acid levels, serving as an effective auxiliary diagnostic indicator and independent risk factor for brain tissue injury.

A homozygous nonsense variant in the alternatively spliced VLDLR exon 4 causes a neurodevelopmental disorder without features of VLDLR cerebellar hypoplasia.

VLDLR cerebellar hypoplasia is characterized by intellectual disability, non-progressive cerebellar ataxia, and seizures. The characteristic MRI findings include hypoplasia of the inferior portion of the cerebellar vermis and hemispheres, simplified cortical gyration, and a small brain stem. Biallelic VLDLR pathogenic variants cause loss-of-function of the encoded very low-density lipoprotein receptor. VLDLR exons 4 and 16 are alternatively spliced, resulting in the expression of four transcript variants, including two exon 4-lacking mRNAs expressed in the human brain. Previously reported VLDLR pathogenic variants affect all four transcript variants. Here we report on two sisters with facial dysmorphism, microcephaly, intellectual disability, and normal brain imaging. Exome sequencing in one patient identified the homozygous VLDLR nonsense variant c.376C>T; p.(Gln126*) in exon 4; her similarly affected sister also carried the homozygous variant and parents were heterozygous carriers. VLDLR transcript analysis identified mRNAs with and without exon 4 in patient fibroblasts, while exon 4-containing VLDLR mRNAs were predominantly detected in control fibroblasts. We found significantly reduced VLDLR mRNA levels in patient compared to control cells, likely caused by nonsense-mediated mRNA decay of exon 4-containing VLDLR transcripts. Expression of neuronal VLDLR isoforms produced from exon 4-lacking transcripts may have protected both patients from developing the cerebellar hypoplasia phenotype.

The clinical utility of a circulating tumor cell based cerebrospinal fluid assay in the diagnosis and molecular analysis of leptomeningeal disease in patients with metastatic non-small cell lung cancer.

8644 Background: Leptomeningeal disease (LMD) is associated with significant morbidity and mortality for metastatic non-small cell lung cancer (mNSCLC). The standard of care for diagnosing LMD remains magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology, but these have limited sensitivity. CSF-based liquid biopsy is an emerging strategy for dynamic assessments of CSF-derived tumor cells to monitor intracranial responses and CNS clonal evolution during treatment and at progression. However, data for the feasibility and utility of this approach is limited. We describe our clinical experience to evaluate the use of molecular analysis on CSF-derived circulating tumor cells (CTCs) for mNSCLC. Methods: Patients with mNSCLC who had a lumbar puncture for CSF collection as part of routine clinical care to rule out LMD were included in the study. CSF was evaluated for CTCs and cell-free DNA (cfDNA) with a commercially available assay (CNSide) and subsequent molecular profiling was performed to detect actionable mutations. Patients were analyzed for LMD with CSF cytology and MRI imaging. Molecular testing results from sequencing of tumor tissue and plasma cell tumor DNA were available for all patients. Other than copy number amplification detection for MET, the CSF assay allowed for analysis of MET and HER2 expression via fluorescent in situ hybridization (FISH). Results: The study included 22 patients with mNSCLC (77% female; median age 60 years; 95% adenocarcinoma). Sensitizing EGFR mutations were found in 78% of patients and 18% had an atypical EGFR mutation at initial diagnosis. LMD was diagnosed using the CSF CTC assay in thirteen of the 22 patients (59%) patients. CSF cytology was negative for LMD in five of 13 cases (38%) and furthermore, 2 of these cases (15%) had normal MRI brain imaging. There were sufficient CTCs to perform molecular profiling on seven of the 13 patients (54%). The concordance with tissue NGS was 100% and the driver mutation was identified in all 7 patients with the CSF CTC assay. MET expression and HER2 expression via FISH were noted in 11 patients (50%) and 4 patients (18%) respectively. Conclusions: In this single institution study, we detected a higher sensitivity to diagnose LMD with CNSide. This CSF assay identified 38% of LMD cases which were missed by standard CSF cytology and of note, 15% of the cases found with LMD were missed by both CSF cytology and MRI. In addition, CSF molecular testing using this assay demonstrated high concordance with tissue-based molecular testing. The study illustrates that multigene molecular analysis of CSF CTCs can be a useful tool for diagnosis, monitoring of response to therapy, as well as for the identification of therapeutic targets specific to the CSF especially for patients with oncogene-driven mNSCLC.

Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients: Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.

Correlation between early computed tomography findings and neurological outcome in pediatric traumatic brain injury patients

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. Head computed tomography (CT) is frequently utilized for evaluating trauma-related characteristics, selecting treatment options, and monitoring complications in the early stages. This study assessed the relationship between cranial CT findings and early and late neurological outcomes in pediatric TBI patients admitted to the pediatric intensive care unit (PICU). The study included children aged 1 month to 18 years who were admitted to the PICU due to TBI between 2014 and 2020. Sociodemographic data, clinical characteristics, and cranial CT findings were analyzed. Patients were categorized based on their Glasgow Coma Scale (GCS) score. Of the 129 patients, 83 (64%) were male, and 46 (36%) were female, with a mean age of 6.8 years. Falls (n = 51, 39.5%) and in-vehicle traffic accidents (n = 35, 27.1%) were the most common trauma types observed. Normal brain imaging findings were found in 62.7% of the patients, while 37.3% exhibited intracranial pathology. Hemorrhage was the most frequent CT finding. Severe TBI (n = 26, p = 0.032) and mortality (n = 9, p = 0.017) were more prevalent in traffic accidents. The overall mortality rate in the study population was 10.1%. In children with TBI, cranial CT imaging serves as an essential initial method for patients with neurological manifestations. Particularly, a GCS score of ≤ 8, multiple hemorrhages, diffuse cerebral edema, and intraventricular bleeding are associated with sequelae and mortality.

Optic Nerve Sheath MR Imaging Measurements in Patients with Orthostatic Headaches and Normal Findings on Conventional Imaging Predict the Presence of an Underlying CSF-Venous Fistula.

Spontaneous spinal CSF leaks typically cause orthostatic headache, but their detection may require specialized and invasive spinal imaging. We undertook a study to determine the value of simple optic nerve sheath MR imaging measurements in predicting the likelihood of finding a CSF-venous fistula, a type of leak that cannot be detected with routine spine MR imaging or CT myelography, among patients with orthostatic headache and normal conventional brain and spine imaging findings. This cohort study included a consecutive group of patients with orthostatic headache and normal conventional brain and spine imaging findings who underwent digital subtraction myelography under general anesthesia to look for spinal CSF-venous fistulas. The study group consisted of 93 patients (71 women and 22 men; mean age, 47.5 years; range, 17-84 years). Digital subtraction myelography demonstrated a CSF-venous fistula in 15 patients. The mean age of these 8 women and 7 men was 56 years (range, 23-83 years). The mean optic nerve sheath diameter was 4.0 mm, and the mean perioptic subarachnoid space was 0.5 mm in patients with a CSF-venous fistula compared with 4.9 and 1.2 mm, respectively, in patients without a fistula (P < .001). Optimal cutoff values were found at 4.4 mm for optic nerve sheath diameter and 1.0 mm for the perioptic subarachnoid space. Fistulas were detected in about 50% of patients with optic nerve sheath diameter or perioptic subarachnoid space measurements below these cutoff values compared with <2% of patients with optic nerve sheath diameter or perioptic subarachnoid space measurements above these cutoff values. Following surgical ligation of the fistula, optic nerve sheath diameter increased from 4.0 to 5.3 mm and the perioptic subarachnoid space increased from 0.5 to 1.2 mm (P < .001). Concerns about a spinal CSF leak should not be dismissed in patients with orthostatic headache when conventional imaging findings are normal, and simple optic nerve sheath MR imaging measurements can help decide if more imaging needs to be performed in this patient population.

Brain imaging abnormalities in children with dysphagia with aspiration: A retrospective study.

Head imaging is often performed in children with persistent dysphagia with aspiration to evaluate for Chiari malformations that may be associated with dysphagia. Unfortunately, the frequency of Chiari malformations or other head imaging abnormalities in children who aspirate is unknown. The goal of this study is to determine the frequency of head imaging abnormalities in children with evidence of aspiration or penetration on video fluoroscopic swallow study (VFSS). Tertiary Children's Hospital. We performed retrospective analysis of children with a diagnosis of aspiration evaluated at our center from January 2010 through April 2021. In this study, we included children with VFSS confirmedaspiration or penetration, brain magnetic resonance imaging (MRI) performed at our center, and without known genetic, congenital craniofacial, or neurologic abnormalities. Of the 977 patients evaluated in our system during that time with a diagnosis of aspiration, 185 children met the inclusion criteria. Eight children were diagnosed with Chiari malformations (4.3%) and 94 head MRIs were abnormal (51.4%). There was no difference in VFSS findings (frequency of aspiration, penetration, penetration-aspiration score, or recommended thickness of liquid) in children with a Chiari malformation versus other abnormalities or normal brain imaging. The majority of other non-Chiari brain imaging abnormalities were nonspecific. There was no difference in VFSS findings in children with abnormal MRI findings versus normal MRI. Brain imaging abnormalities are common in children who aspirate. Intervenable lesions are rare. Further studies are required to determine patients that will most likely benefit from brain imaging.

Herpes Simplex Virus Type 2 Encephalitis in an Immunocompetent Adult: A Diagnostic Challenge

Herpetic encephalitis is the most common cause of fatal sporadic encephalitis. Beyond the neonatal period, herpes simplex virus type 1 (HSV-1) is the etiologic agent in nearly all cases, with &lt; 10% of cases attributable to HSV-2. Nevertheless, neurological infections caused by HSV-2 are responsible for significant morbidity and mortality. Therefore, it must be diagnosed and treated at an early stage. It is classically characterized by a triad of fever, headache, and behavioral changes. The association of these symptoms, laboratory tests, and imaging is fundamental for the early diagnosis and immediate treatment of this pathology to prevent its progression from being fatal. We report a rare case of HSV-2 encephalitis in a previously healthy 61-year-old man, free of genital lesions, who presented with altered mental status, fever, altered cerebrospinal fluid (CFS) with lymphocytic pleocytosis, normal brain imaging, and an initially negative CFS polymerase chain reaction for HSV-1 and HSV-2.

Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management

ObjectivesPatients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines. MethodsIn this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or “stroke mimic” (SM: normal brain imaging or evoking a migraine). ResultsThirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found. DiscussionAcute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy. ConclusionAcute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.

Neurobiological perspective on the development of executive functions.

Executive functions are a set of top-down cognitive processes necessary for emotional self-regulation and goal-directed behaviour supporting, among others, academic abilities. Premature infants are at high risk for subsequent cognitive, psychosocial, or behavioural problems even in the absence of medical complications and in spite of normal brain imaging. Given that this is a sensitive period of brain growth and maturation, these factors may place preterm infants at high risk for executive function dysfunction, disrupted long-term development, and lower academic achievements. Therefore, careful attention to interventions at this age is essential for intact executive functions and academic development.

Neurological and imaging phenotypes of adults with untreated phenylketonuria: new cases and literature review.

Phenylketonuria (PKU) is the most prevalent congenital disease of amino acid metabolism. Neurological manifestations usually complicate PKU in untreated adult patients. This study describes neurological and imaging phenotypes of adult patients with untreated PKU. We investigated a cohort of 320 unrelated adult patients with suspected genetic leukoencephalopathies using whole-exome sequencing (WES). We analyzed the phenotypic features of adult PKU patients in our cohort and summarized cases reported in the literature. We identified 10 patients in our cohort and 12 patients in the literature, who presented with neurological manifestations and were diagnosed with PKU in adulthood. Approximately 60% of these patients had onset of clinical features in adulthood. The most common neurological symptoms of patients presenting in adulthood were cognitive disturbance and spastic paralysis, followed by vision loss, cerebellar ataxia, weakness of limbs, and seizure. This differed from that of patients presenting with PKU features in childhood, who consistently had mental retardation with various neurological complications emerging during a broad age range. Imaging findings were similar between patients presenting with clinical features in childhood compared with adulthood, comprising symmetric periventricular white matter hyperintense on T2-weighted imaging and diffusion-weighted imaging predominantly in the parietal and occipital lobes. Also, normal brain imaging and diffuse leukoencephalopathies were observed in both patient groups. PKU with clinical features presenting in adulthood is an atypical subtype and should be considered during diagnosis of adults with neurological symptoms and leukoencephalopathy. DWI seems to be most helpful to distinguish patients with PKU. Additionally, we demonstrate that PKU constitutes a part (3.1%) of adult genetic leukoencephalopathies.

Preexisting Cerebrovascular Disease in Pregnancy: a Case Series on Pregnancy Outcomes (S3.004)

<h3>Objective:</h3> To characterize adverse pregnancy outcomes (APO) in patients with preexisting cerebrovascular disease (CVD). <h3>Background:</h3> Detailed data are lacking regarding APO in pregnant patients with CVD, limiting neurologists’ ability to counsel patients. <h3>Design/Methods:</h3> We reviewed medical records of 35 patients with CVD evaluated in a neuro-obstetrics subspecialty clinic embedded within a high risk maternal-fetal medicine practice between August 2019 and December 2021. Patients were referred for neurological evaluation during or prior to pregnancy. We described subsequent maternal and fetal APO, including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), pre term birth (PTB), fetal growth restriction (FGR), and small for gestational age infant (SGA), as well as delivery mode, postpartum readmissions and recurrent acute CVD. <h3>Results:</h3> A total of 35 patients were included (6 TIA, 14 ischemic stroke, 1 subarachnoid hemorrhage, 1 intracerebral hemorrhage, 5 cerebral venous thrombosis, 3 unruptured aneurysm, 2 arteriovenous malformation, 1 cervical artery dissection, 2 reversible cerebral vasoconstriction syndrome [RCVS]). Average age at delivery was 33 years, and most patients (91%) had vascular risk factors including obesity (23%), chronic hypertension (20%), diabetes mellitus (11%), history of prior APO (26%), and migraine (57%). All patients with prior TIA, ischemic stroke, or cerebral venous thrombosis received antithrombotics during pregnancy. Overall, APO occurred in 44% of pregnancies, and included PTB (28%), HDP (19%), GDM (14%), FGR (8%), and SGA (8%). Cesarean deliveries occurred in 42% of pregnancies, all for obstetric indications. Two patients were readmitted postpartum, one for neurological symptoms (headache) with normal brain imaging, and one for an obstetrical complication. One patient experienced recurrent postpartum CVD (RCVS), without readmission. <h3>Conclusions:</h3> In patients with CVD history, APO were common but recurrent acute CVD was rare. Patients with prior CVD may be at high risk for APO due to underlying vascular risk factors rather than specific CVD diagnosis. <b>Disclosure:</b> Ms. Wyckoff has nothing to disclose. Dr. Mammadli has nothing to disclose. Dr. Booker has nothing to disclose. Dr. D’Alton has a non-compensated relationship as a Advisory Board with Merck for Mothers that is relevant to AAN interests or activities. Dr. LaSala has nothing to disclose. Stephanie Purisch has nothing to disclose. Prof. Valeri has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for McLean Hospital. Prof. Valeri has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA. The institution of Prof. Valeri has received research support from National Institute of Health. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edwards Scientific. Dr. Willey has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for RECARDIO. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of the American College of Cardiology. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Uptodate. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as a Review chapter author, MKSAP 16-20 with American College of Physicians. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Argionis and Associates LLC. The institution of Dr. Miller has received research support from National Institutes of Health.

A Rare Case of Rheumatoid Meningitis (P9-5.024)

<h3>Objective:</h3> To increase awareness of this rare and underrecognized form of aseptic meningitis. <h3>Background:</h3> Rheumatoid meningitis (RM) is a rare disorder that is historically difficult to diagnose given its diverse range of reported clinical presentations and lack of clear pathognomonic findings. RM is typically a diagnosis of exclusion, made only after ruling out alternative infectious and malignant disease. Common laboratory findings include elevated rheumatoid factor (RF) and anti-citrullinated peptide (anti-CCP) antibody. MRI may show leptomeningeal or pachymeningeal involvement, primarily in a frontoparietal location pattern. CSF analysis typically reveals a pleocytosis with a moderate elevation in protein level. Treatment generally consists of high dose steroids followed by immunotherapy. <h3>Design/Methods:</h3> A 69-year-old male with a history of longstanding rheumatoid arthritis on immunosuppressive therapy with methotrexate and recent addition of abatacept presented to our tertiary referral center with progressive neurologic deficits. He initially developed sudden, bilateral sensorineural hearing loss and dizziness with reported normal brain imaging. Six months later, he developed seizures and rapid functional decline with severe cognitive impairment. <h3>Results:</h3> An MRI brain revealed multifocal leptomeningeal and pachymeningeal enhancement with a relatively unremarkable appearance of the subjacent parenchyma, primarily focused in the right frontoparietal region. CSF studies were remarkable for a mild pleocytosis and a moderate elevation in CSF protein. RF was markedly elevated at 227 IU/mL as was anti-CCP antibody at &gt;200 units. Extensive serum and CSF infectious and oncologic testing were negative. He was treated with 5 days of IV methylprednisolone with a rapid improvement in his cognition. Alternative immunosuppressive therapy for RA with methotrexate and rituximab has resulted in sustained functional stability. <h3>Conclusions:</h3> While rare, RM should be considered in the differential of a patient with aseptic meningitis of unclear etiology, with or without a history of rheumatoid arthritis. Early detection and treatment are essential to the prevention of long-lasting sequela of the disease. <b>Disclosure:</b> Dr. Schmoll has nothing to disclose. Dr. Rodenbeck has nothing to disclose. Dr. Graner has nothing to disclose.

Photosensitive occipital lobe epilepsy: Delineation of an under-recognized reflex epilepsy syndrome according to the new ILAE criteria and long-term follow-up.

Photosensitive occipital lobe epilepsy (POLE) should be suspected in patients with occipital lobe seizures triggered by photic stimuli, who have normal motor-mental development and brain imaging. We aimed to examine the clinical, electrophysiological, and prognostic features of POLE, which is a rare and under-investigated syndrome. Archives from two tertiary epilepsy centers were retrospectively scanned and patients with normal neurological examination and cranial imaging were identified with POLE if they had: (1) seizures consistently triggered by photic stimuli; (2) non-motor seizures with visual symptoms; and (3) photosensitivity documented on EEG. The clinical and electrophysiological features and prognostic factors were evaluated for patients who had follow-up ≥5 years. We identified 29 patients diagnosed with POLE with a mean age of 20.1± 7.6 years. In one-third of the patients, POLE syndrome overlapped with genetic generalized epilepsy (GGE). The overlap group had higher rates of febrile seizure history and self-induction; when compared to pure POLE patients, their EEGs showed more frequent interictal generalized epileptic discharges and posterior multiple spikes during intermittent photic stimulation. During long-term follow-up, the remission rate for POLE was 80%, but EEG photosensitivity persisted in three quarters of patients despite clinical remission, and more than half had relapsed after clinical remission. This first long-term follow-up study, utilizing newly suggested criteria of the International League Against Epilepsy, showed that POLE syndrome shows a notable overlap with GGE but also has distinctive features. POLE has a good prognosis; however, relapses are common, and photosensitivity persists as an EEG finding in the majority of patients.

An atypically mild case of ethylmalonic encephalopathy with pathogenic ETHE1 variant

Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia evolving to dystonia, petechiae, orthostatic acrocyanosis, diarrhea, and elevated ethylmalonic acid in urine. In this case report, we describe a patient with only mild speech and gross motor delays, subtle biochemical abnormalities, and normal brain imaging found to be homozygous for a pathogenic ETHE1 variant (c.586G>A) via whole exome sequencing. This case highlights the clinical heterogeneity of ETHE1 mutations and the utility of whole-exome sequencing in diagnosing mild cases of EE.

HIDING IN PLAIN SIGHT: ANTI-NMDAR- ENCEPHALITIS IN A 30-YEAR-OLD MALE- A CASE REPORT

The most common type of autoimmune encephalitis is anti-NMDAR-encephalitis. It is characterized by IgG an­tibodies against the GluN1 subunit of the NMDA receptor, leading to marked neuropsychiatric and behavioural symptoms that progress in a subacute manner to seizures, speech abnormalities, and a depressed level of con­sciousness. In this case report, the clinical course of a 30-year-old man who first received treatment for viral encephalitis after exhibiting normal symptoms is described. CSF showed lymphocytic pleocytosis with normal brain imaging. The EEG demonstrated diffuse slowing and encephalopathy. An autoimmunity encephalitis workup was done after exhaustive investigations for metabolic and infectious causes came back negative. A diagnosis of anti-NMDAR encephalitis was made after antibodies were found in the CSF.

A case of papilledema with TB meningitis with bilateral abducent nerve palsy – A diagnostic challenge

Tuberculous meningitis (TBM) contributes around 5% among extrapulmonary tuberculosis (TB) and it is devastating with significant morbidity and mortality. It is associated with high frequency of neurologic sequelae and mortality. TBM has a subacute presentation with non-specific clinical signs making difficulty in early diagnosis. We report a case presenting with only ocular symptoms and no typical signs of meningitis with normal brain imaging. Real time PCR and other nucleic acid amplification methods are increasingly used for detection of mycobacterium TB from cerebrospinal fluid. When recognized early and treated promptly with appropriate anti-tuberculous medication, prognosis is good.

Retrospective Analysis of Clinical Feature in Trigeminal Neuralgia

BACKGROUND: Trigeminal neuralgia (TN) is usually established using characteristic clinical features such as sudden, severe, and unilateral facial pain. Studies about diverse clinical features and epidemiologic data of TN have been reported previously; however, most of the previous studies have evaluated in and focused on Caucasian and Western populations. OBJECTIVES: The purpose of this study was to evaluate diverse clinical features, currently applied types of treatment, and brain imaging studies in patients with TN in a Korean population. STUDY DESIGN: Retrospective analysis. SETTING: An interventional pain management practice in South Korea. METHODS: Patients with a primary diagnosis of TN were identified using Clinical Data Warehouse v 2.5 (CDW, Planit Healthcare, Seoul, Korea) using the key words “trigeminal neuralgia and G50.0 (International classification of disease 10 code).” RESULTS: TN occurred predominantly between the fifth and seventh decades of life, with female predominance. The V3 division and unilateral right-side involvement were the most common affected region. An electric shock like sensation and the intraoral side (teeth and gingiva) were the most common pain description and location, respectively. Normal brain imaging studies and vascular compression on the trigeminal nerve were observed in 92 (64.7%) and 36 (25%) patients, respectively. The superior cerebellar artery was the most common offending vessel (19;13.3%). Monotherapy with carbamazepine alone was the most common (91;37.7%), whereas radiofrequency thermoablation was the most common invasive treatment. LIMITATIONS: The results of this study were based on data on TN patients from a single center. The generalizability of the findings to the Korean population is thus limited. CONCLUSION: There is little difference between Korean and other Asian patients with TN in their demographic and clinical characteristics. KEY WORDS: Brain imaging, clinical feature, electric shock-like sensation, intraoral side, trigeminal neuralgia, vascular compression

Spectrum of Growth Hormone Disorders in Children: A Case Series of 5 Cases

Growth Hormone Deficiency (GHD) is one of the most important treatable endocrine causes of short stature. A problem anywhere in the Growth Hormone (GH) - Insulin-Like Growth Factor-1 (IGF-1) axis can lead to short stature. Childhood GH deficiency can be congenital, acquired, or idiopathic. Hereby, the authors present a case series consisting of five cases of short stature, aimed to provide an overview of the spectrum of GH-related disorders. All five patients presented to the Paediatric Endocrinology Outpatient Department of a tertiary care Institute with complaints of not gaining height. The patients in present case series had significant short stature (Z score for height &lt;-3 SD (Standard Deviation) in each case). These patients were suspected of having GH deficiency based on clinical presentation and investigations. After a proper diagnostic work-up and GH stimulation tests, cases 1 to 4 were found to have GH deficiency. The 5th case was suspected of having Laron Syndrome based on high GH levels and low IGF-1. There were subtle differences in the spectrum of GH deficiency. The 1st case had Multiple Pituitary Hormone Deficiency (MPHD). Cases 2 to 4 had Isolated Growth Hormone Deficiency (IGHD). Case 2 had findings of pituitary stalk interruption on brain imaging. We found a genetic association in the 3rd case, while the 4th case had almost normal brain imaging. Cases 1 to 4 received GH therapy, and all showed appreciable height gain. These subtle differences can sometimes make the diagnosis difficult, and often a different approach to treatment is required.