Progressive Neurological Symptoms Research Articles

Bridging the gap between neuroimaging and neurosurgery: a case of epidural arteriovenous fistula with an intradural presentation. Illustrative case.

Epidural arteriovenous fistulas (eAVFs) are rare vascular malformations often mistaken for their intradural counterparts due to similar angiographic features. Differentiation between epidural and intradural vascular lesions is crucial as it impacts surgical planning and prognosis. Despite advancements in diagnostic imaging, these entities can be misinterpreted and challenge management. The authors report the case of a 68-year-old male suspected to have a type I dural arteriovenous fistula based on magnetic resonance angiography and angiographic evaluation. He presented with progressive myelopathy and multiple neurological symptoms exacerbated by recent trauma. A superselective angiogram of the right T10 segmental artery suggested an intradural arteriovenous fistula; however, intraoperatively, the lesion was epidural. The arterialized venous structures were obliterated, and the patient reported significant postoperative symptomatic improvement. This case highlights the critical importance of comprehensive imaging and cautious interpretation in the diagnosis of spinal vascular malformations. It also underscores the need for a multidisciplinary approach to ensure accurate diagnosis and effective treatment. Surgeons must be prepared for intraoperative findings that diverge from preoperative imaging to adapt surgical strategies accordingly. Furthermore, this case contributes to the evolving understanding of eAVFs, suggesting that revised imaging protocols may be required to better distinguish epidural from intradural vascular abnormalities. https://thejns.org/doi/10.3171/CASE24331.

6674 Non-Progressive Diabetes Leading to Neurologic Diagnosis

Abstract Disclosure: F.L. Thelmo: None. M. Murugesh: None. B. Simon: None. Introduction: The autoantibody GAD (anti-glutamic acid decarboxylase) is highly associated with Type 1 diabetes (T1DM) and Latent Autoimmune Diabetes in Adulthood (LADA). If GAD is detected before the onset of overt diabetes, typically 80% of patients with abnormal glucose tolerance progress to insulin deficiency and the need for insulin treatment after 5 years.[1] Stiff Person Syndrome (SPS) is also associated with GAD antibodies, but in SPS, the GAD antibodies are believed to be different epitopes that target GABA production in neuromuscular pathways. We present a case of presumed LADA that did not progress for 30 years, with progressive neurologic symptoms leading to a diagnosis of SPS in later adulthood.Case: A 52-year-old female presented for evaluation of T1DM and worsening neuropathies. She had a long history of prediabetes, with mildly elevated glucose values noted on labs since her early twenties. There was no family history of T1DM or autoimmune conditions. Six years ago, she sought endocrine evaluation. HgbA1c values were 6.1 to 6.6%. Intermittent use of continuous glucose monitoring (CGM) revealed post-prandial hyperglycemia up to 180mg/dL, occasionally (but rarely) exceeding 200mg/dL. She recalls being told that she had positive antibodies (unclear which ones tested) and given a diagnosis of T1DM. She declined insulin and maintained glycemic control with carbohydrate restriction and exercise; there were no episodes of diabetic ketoacidosis. She then developed neurologic symptoms: fullness, tightness and bloating in the abdomen (diagnosed with gastroparesis on scanning) and after a COVID 19 booster in 2021, muscle spasms in the legs and back with worsening abdominal tightness. At the time of her current presentation, A1C was 6.4%, glycated albumin was 14.4% (prediabetes range 13.6 - 15.5%) and CGM time in range was 99%. A non-fasting C-peptide was 3.6 ng/mL (1.1- 4.4ng/mL) with glucose of 119 mg/dL. Repeat antibody testing revealed undetectable IA-2 and ZnT8 antibodies, but GAD was grossly elevated at 1,015.3 U/mL. Given the unusually high GAD titer, SPS was suspected, and this diagnosis was confirmed on referral to neurology. The patient was advised to liberalize diet and will be monitored with HgbA1c and serial C-peptide levels to assess progression in the future. Discussion: While high GAD antibody levels are associated with progression to insulin dependence in adults with LADA, in SPS the GAD titers tend to be even higher2. The presence of only one auto-antibody for T1DM (and not multiple), long-standing non-progressive hyperglycemia, and normal C-peptide pointed away from autoimmune diabetes being the etiology for mild glucose intolerance in this patient. If neurologic symptoms are present, high GAD should prompt the evaluation for other syndromes associated with GAD antibody epitopes such as SPS. Presentation: 6/2/2024

8386 The Evolving Face of The Great Masquerader - Panhypopituitarism Associated with Neurosyphilis

Abstract Disclosure: M. Yabe: None. Z. Lin: None. F. Joseph: None. G. Philip: None. R. Silver: None. L. Callejas: None. J. Giunta: None. Untreated syphilis is on the rise in the United States. The CDC reported syphilis cases in newborns have increased 10-fold over a decade in November 2023, signifying the emergence of untreated infections. Pituitary involvement in syphilis is a very rare phenomenon, and endocrinological investigation is often overlooked. This will be the second reported case of neurosyphilis with pituitary involvement in a non-HIV infected patient. A 45-year-old female with no significant past medical history was admitted to the hospital with progressive neurological symptoms of intermittent left-side headache, hearing loss with tinnitus, and gait instability. Postcontrast MRI Brain revealed multifocal leptomeningeal enhancement involving supratentorial and infratentorial regions. Thickening of the enhanced pituitary infundibulum was also noted. Subsequent RPR titer showed 1:16 and lumbar puncture revealed CSF-VDRL titer 1:32, with pleocytosis 83 cells/uL, CSF-glucose 19 mg/dL, and CSF-protein 370 mg/dL. The patient completed Penicillin G 4 million/units intravenous every 4 hours for 14 days, with repeat MRI showing significant interval decrease in previously described extensive supratentorial and infratentorial leptomeningeal enhancement. However, there is no record of her sexual partner receiving treatment. The patient was readmitted one year later after a fall while displaying dysmetria. MRI Brain with contrast revealed a small subacute infarct along the right frontal corona radiata and pituitary gland measuring up to 1.2 cm in craniocaudal dimension compared to 0.4 cm on the prior exam. This prompted evaluation of pituitary hormones: FSH 0.8 IU/L, LH <0.3 IU/L, and ACTH 6.3 pg/mL, with normal serum growth hormone and prolactin levels. Further investigation revealed morning cortisol 2.5 ug/dL, thyrotropin < 0.2 uIU/mL, and free thyroxine 0.63 ng/dL. Radiological evidence is suspicious of inflammatory etiology of the pituitary gland. The patient was discharged with endocrinology follow-up and plan to perform a pituitary gland biopsy as an outpatient for confirmatory result. The association of neurosyphilis and hypophysitis leading to panhypopituitarism in a non-HIV infected patient was first reported in 2015. Since then, there remains limited research regarding their association due to rarity of pituitary involvement in neurosyphilis. With untreated syphilis on the rise and increased availability of MRI, clinicians should expect to encounter more cases of neurosyphilis with pituitary involvement in the future. Early detection of panhypopituitarism in those with positive CSF-VDRL titer could lead to better clinical outcomes. It is paramount that these cases are documented to emphasize pituitary involvement in neurosyphilis and encourage a low threshold to initiate endocrinological testing in the future. Presentation: 6/3/2024

HGGL-01 GLIOBLASTOMA MULTIFORM INVOLVING MULTIPLE BRAIN REGIONS ASSOCIATED WITH MUTATIONS IN EXON 4 OF ISOCITRATE DEHYDROGENASE 1 COMPLICATED BY ACUTE KIDNEY FAILURE: A CASE REPORT

Abstract Glioblastoma multiform (GBM), WHO grade 4, is the most aggressive primary brain tumor in adults associated with poor prognosis. We present a case of a 43-year-old female, Muyira, diagnosed with GBM involving multiple brain regions and harboring mutations in exon 4 of isocitrate dehydrogenase 1, who subsequently developed acute kidney failure. The patient initially presented with progressive neurological symptoms, including headache and cognitive decline. Multiplanar multiecho MRI of the brain was performed with IV contrast in orthogonal plane and revealed a moderate sized multilobulated heterogeneously and predominantly peripherally enhancing mass lesion with irregular margins and central non enhancing areas of necrosis arising from the right corona radiata, insular cortex, external capsule, lentiform nucleus, temporal, and frontal white matter with blood products. Perilesional edema was seen. Effacement of sulcal spaces. Right sylvian fissure, compression over right ventricle and midline shift of 8mm toward left side. There was dilatation of the left lateral ventricle with periventricular cerebrospinal fluid ooze. Uncal herniation was right side. On MR spectroscopy large choline, creatinine levels were seen in the lesion with reduced N-acetyl aspartate levels as compared to the normal parenchyma. Findings were suggestive of neoplastic lesion mostly high-grade glioma. Polymerase chain reaction sequencing confirmed the presence of missense mutation R132H in exon 4 of isocitrate dehydrogenase 1 gene. Despite maximal safe surgical resection, the patient developed acute kidney failure secondary to the nephrotoxic effects of gadolinium. Management of both the primary brain tumor and renal complication necessitated a multidisciplinary approach involving neurosurgery, oncology, nephrology, and supportive care. Despite aggressive interventions, the patient’s condition deteriorated, highlighting the challenges in managing concurrent life-threatening conditions in patients with advanced GBM.

Deposition of Gadolinium in the Central and Peripheral Nervous Systems and Its Effects on Sensory, Cognitive, and Athletic Implications after Multiple Injections of Gadolinium-Based Contrast Agents in Rats.

After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.

Easily misdiagnosed X-linked adrenoleukodystrophy

BackgroundAddison’s disease and X-linked adrenoleukodystrophy (X-ALD) (Addison’s-only) are two diseases that need to be identified. Addison’s disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison’s-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison’s disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD.MethodsWe retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics.ResultsTwo patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison’s disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394–2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison’s-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum.ConclusionsPatients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison’s disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison’s-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.

Therapeutic Efficacy of Ultrasound-Guided Selective Nerve Block on Chronic Cervical Radiculopathy.

Background and Objectives: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral disc herniation, degenerative changes, or trauma. While conservative treatments are initially preferred, persistent or severe cases may require surgical intervention. Ultrasound-guided selective nerve root block (SNRB) has emerged as a promising intervention for alleviating symptoms and potentially obviating the need for surgery. This study evaluates the therapeutic efficacy of ultrasound-guided SNRB in managing chronic CR, aiming to determine its potential in symptom relief and delaying or avoiding surgical procedures. Materials and Methods: A retrospective analysis was conducted on 720 outpatients treated for CR between October 2019 and March 2022. After excluding patients with traumatic CR, previous surgeries, malignancies, progressive neurological symptoms requiring immediate surgery, or inadequate conservative treatment, 92 patients who had experienced cervical radicular pain for more than three months and had failed to improve after more than six weeks of conservative treatment with VAS scores ≥ 5 were included. The patients underwent single or multiple ultrasound-guided SNRB procedures, involving the injection of dexamethasone and lidocaine under real-time ultrasound guidance. Symptom severity was assessed at the baseline, and at 4, 8, and 12 weeks post-procedure using the Visual Analog Scale (VAS). The data collected included age, sex, presence of neck and/or radicular pain, physical examination findings, recurrence of symptoms, improvement in symptoms, and whether surgical intervention was ultimately required. Statistical analyses were performed to identify the factors associated with symptom improvement or recurrence. Results: Significant symptom improvement was observed in 69 (75.0%) participants post-SNRB, with 55 (79.7%) showing improvement at 4 weeks, 11 (15.9%) at 8 weeks, and 3 (4.4%) at 12 weeks. Symptom recurrence, defined by an increase in VAS score accompanied by a pain flare lasting at least 24 h after a pain-free interval of at least one month, was noted in 48 (52.2%) patients. The presence of combined neck and radicular pain was a significant predictor of recurrence (p = 0.008). No significant associations were found between symptom relief and factors such as age, gender, initial pain severity, or MRI findings. Conclusions: Ultrasound-guided SNRB effectively manages chronic CR, providing substantial symptom relief and potentially reducing the need for surgical intervention. This technique offers a promising conservative treatment option, especially given its real-time visualization advantages and minimal radiation exposure.

Modified pedicle subtraction osteotomy for osteoporotic vertebral compression fractures: a retrospective study of 104 patients.

Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. 104 patients who underwent posterior osteotomy(Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO)after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ±13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0± 552.2ml vs. 987.0± 638.5ml, P = 0.038), time of operation (244.1± 63.0min vs. 292.4± 87.6min, P = 0.025) were favorable in Modified PSO group compared to control group. To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.

Real-world use of a CSF circulating tumor cell assay in the diagnosis and management of leptomeningeal metastasis.

2029 Background: The diagnosis of leptomeningeal metastasis (LM) can be challenging due to variability in clinical symptoms, radiographic, and cerebrospinal fluid (CSF) findings. The National Comprehensive Cancer Network (NCCN) guidelines recommend assessment of circulating tumor DNA (ctDNA) to increase sensitivity of tumor cell detection and assess the response to treatment. We hypothesize that the real-world use of an assay for the direct detection and enumeration of circulating tumor cells (CTCs) in the CSF is clinically useful for accurate diagnosis of LM, particularly in an early stage of disease. Methods: We report a series of 55 patients treated at our institution with a cancer diagnosis and either neurological symptoms or radiographic findings that suggested LM. All patients underwent a lumbar puncture, assessment for CSF CTCs, and conventional hospital-based cytology testing between 6/1/2020 and 8/1/2023. Survival data cutoff was 12/31/2023. Patient outcomes are reported. Results: 55 patients were tested, and 30 patients were found to be positive for CTCs and diagnosed with LM. Only 10 patients were concurrently positive for CTCs and cytology at our institution, whereas 20 patients with positive CTCs had a negative or ambiguous cytology. No patients with a negative CTC result (25 patients) were subsequently diagnosed with LM, whereas 4 patients with a positive CTC result remained without progressive neurological symptoms. 5 patients diagnosed with LM were alive at the time of data cutoff. The histologic breakdown for LM was: breast (11), non-small cell lung cancer (NSCLC) (16), gastrointestinal (GI) (3). Median overall survival (OS) was longer in patients with a positive CTC and negative cytology result compared to patients with concurrent positive CTC and cytology (172 vs. 63 days, p = 0.06). Median OS was also longer in breast cancer LM compared to NSCLC LM (235 vs. 63 days, p = 0.008). Most patients diagnosed with LM received therapies including Ommaya reservoir placement, intrathecal chemotherapy, and/or radiation. Conclusions: The use of a CSF circulating tumor cell assay aided the diagnosis of LM and led to timely initiation of treatment. A negative result of the CTC assay was associated with ruling out LM. Diagnosis of LM with the CTC assay and negative cytology was associated with longer survival, possibly due to earlier treatment initiation, and not solely a lead time bias. Breast cancer LM patients had improved survival compared to NSCLC and GI cancer patients, possibly due to more effective treatment options.

Endovascular Rescue of Previously Treated Carotid Aneurysm: Higher Radial Force 48-Wire Flow Diverter for Salvage of Collapsed 64-Wire Device With Braid Deformation: 2-Dimensional Operative Video.

Aneurysm treatment presents various therapeutic options. Flow diverters (FD) stents are a revolutionizing endovascular technique for previously untreatable aneurysms.1 FD stents have documented success rates up to 95% and complication rates as low as 2.3%.2 This modality has proven its effectiveness and safety, but it is critical to consider potential complications. Complications include vascular-related problems such as perforation, occlusion, cerebral hyperperfusion, stent thrombosis, restenosis, and embolic events.3 To date, there is no standardized definition for braid collapse and fish-mouthing; however, braid collapse has been reported to occur at a rate of 1% and the latter at a rate of 3%.4 This technical video presents a case of a 51-year-old woman initially treated with a Surpass Evolve flow diverter (Stryker) for a right ophthalmic aneurysm. Secondary to device malapposition and collapse, she developed recurrent ischemic progressive neurologic impairment symptoms. The braid collapse was treated using a Pipeline Embolization device 3.25 × 20 mm (Medtronic) because this device exhibited a larger partial compressive force when compared with the 64-wire device.5 The procedure was uneventful and significantly improved the patient's neurologic symptoms. This technical video illustrates rescue stenting as a salvage intervention for FD collapse cases. The patient gave informed consent for surgery. Institutional review board approval was deemed unnecessary.

Neuronopathic Gaucher disease: Rare in the West, common in the East.

Gaucher disease (GD) stands as one of the most prevalent lysosomal disorders, yet neuronopathic GD (nGD) is an uncommon subset characterized by a wide array of clinical manifestations that complicate diagnosis, particularly when neurological symptoms are understated. nGD may manifest as the acute neuronopathic type, or GD type 2 (GD2), either prenatally or within the first weeks to months of life, whereas GD type 3 (GD3) symptoms may emerge at any point during childhood or occasionally in adolescence. The clinical presentation encompasses severe systemic involvement to mild visceral disease, often coupled with a spectrum of progressive neurological signs and symptoms such as cognitive impairment, ataxia, seizures, myoclonus, varying degrees of brainstem dysfunction presenting with stridor, apneic episodes, and/or impaired swallowing. This manuscript aims to provide a comprehensive review of the incidence, distinctive presentations, and diverse clinical phenotypes of nGD across various countries and regions. It will explore the natural history of the neurodegenerative process in GD, shedding light on its various manifestations during infancy and childhood, and offer insights into the diagnostic journey, the challenges faced in the clinical management, and current and investigative therapeutic approaches for GD's neurological variants.

Primary intradural Extraosseous Ewing’s sarcoma of the cauda equina: A case report and literature review

Intradural Extraosseous Ewing sarcoma (IEES) is an infrequent occurrence. We report a case of a 66-year-old male who presented with a 2-month history of low back pain and bilateral S1 sciatica, with acute sphincter dysfunction. Imaging studies revealed an intradural extramedullary lesion in the cauda equina spanning from level L4 to S1. The patient underwent partial removal of the intradural lesion. Histopathological examination showed the presence of small round cells, which were consistent with Ewing Sarcoma. The patient was then treated with targeted radiation therapy and chemotherapy.The rarity of IEES in this specific location underscores the significance of evaluating and managing patients with intradural spinal tumors with careful consideration of this diagnosis. To further investigate this condition, we conducted a thorough review of the literature on IEES involving the lumbar spine and cauda equina. Our analysis revealed that patients with this condition frequently exhibit rapidly progressive neurological symptoms likely attributed to hemorrhagic transformation. This characteristic may serve as a distinguishing factor from other lesion types, particularly benign ones. Our study provides a comprehensive summary that can offer direction for clinical management in comparable uncommon and novel cases.

“Neuropsychiatric manifestation of hyponatremia: a case report”

Introduction “Electrolyte abnormalities are commonly encountered in daily clinical practice, and their diagnosis relies on routine laboratory results. Electrolyte disturbances can affect the brain among many other organs and tissues and must be promptly recognized, as they can lead to serious and potentially life-threatening complications if neglected or not appropriately treated. Neurological manifestations reflect the severity of acute neuronal dysfunction and thus require urgent treatment. Acute and/or severe electrolyte imbalances can manifest with rapidly progressive neurological symptoms, seizures, and psychiatric manifestations. They are more frequently observed in patients with sodium disorders (especially hyponatremia), hypocalcemia, and hypomagnesemia.ObjectivesWere the psychiatric manifestations secondary to hyponatremia or epilepsy? Or is it a comorbidity? What are the risk factors? And what is the appropriate course of action for this type of patient?”MethodsWe present, through a clinical case, the situation of a 64-year-old patient who experienced status epilepticus secondary to hyponatremia, requiring hospitalization in the neurology department. Subsequently, she developed psychiatric manifestations with a marked change in behavior. She began experiencing symptoms of anxiety and depressive mood, headaches, somatic complaints, and social isolation. Her condition gradually worsened, necessitating hospitalization in the psychiatry department 3 years later.ResultsThe patient was placed on Carbamazepine by her neurologist, and since then, she has not experienced epileptic seizures. Her follow-up electrolyte panel initially showed slight disturbances before normalizing. Psychiatric manifestations were concurrent with these somatic symptoms and worsened over time. During her psychiatric hospitalization three years later, after a thorough evaluation, she was prescribed Sertraline ans Risperidone in combination with Carbamazepine, resulting in a significant improvement in her condition.ConclusionsIn summary, this case illustrates the critical impact of electrolyte abnormalities on both neurological and psychiatric health, especially in older patients. Understanding risk factors associated with electrolyte imbalances is crucial for effective diagnosis and management, particularly in the elderly. This underscores the importance of a multidisciplinary approach to address the potential serious consequences of electrolyte disturbances on overall patient well-being.Disclosure of InterestNone Declared

Changes in &lt;i&gt;DNMT1&lt;/i&gt; expression as a marker of epigenetic regulation disturbanses in multiple sclerosis patients

BACKGROUND: Multiple sclerosis is a chronic neurodegenerative autoimmune disease characterized by the presence of foci of inflammation and demyelination in the central nervous system. The initiation of pathological processes in multiple sclerosis is caused by a complex interaction of genetic factors, unfavorable environmental factors and epigenetic influences. Progressive neurological symptoms caused by axonal conduction disorders, axonal death and neurodestruction lead to a significant decreased patients’ quality of life and disability. The search for a new markers to improve diagnostic and therapeutic methods, including taking into account the genetic background and epigenetic interactions, is an urgent task.&#x0D; AIM: The work was aimed to study the changes in DNMT1 mRNA expression in multiple sclerosis patients with different disease duration, to analyze methylation of DNMT1 promoter, and compare the changes in the level of DNMT1 expression with the homocysteine content in the blood, and the presence of polymorphic variants in genes coding the key folate cycle enzymes.&#x0D; MATERIALS AND METHODS: The level of DNMT1 mRNA expression in peripheral mononuclear blood cells was assessed by reversed transcription followed by polymerase chain reaction. Fluorescent polymerase chain reaction followed by methyl-sensitive analysis of high-resolution melting curves was used to analyze methylation of the DNMT1 promoter. The content of homocysteine in the blood was determined by chemiluminescence immunoassay. The real-time polymerase chain reaction was used for genotyping by polymorphism of folate cycle genes; the fluorescent probes with the LNA modifications were used to discriminate alleles.&#x0D; RESULTS: It has been shown that in multiple sclerosis patients, including those at the onset of the disease, the level of DNMT1 mRNA expression is significantly lower than in the control group. No relationship was found between the decrease in DNMT1 expression and the level of promoter methylation. Strong positive relationship between the level of DNMT1 mRNA expression and homocysteine content in patients with multiple sclerosis and the combined effects of the genotypes of MTR A2756G and MTHFR C677T polymorphism on the expression of DNMT1 have been shown. These findings suggest that genetically determined features of folate metabolism may contribute to the disruption of epigenetic regulation in multiple sclerosis.&#x0D; CONCLUSIONS: The obtained results indicate the promise of research aimed to identifying the factors causing epigenetic changes in multiple sclerosis. Studying the mechanisms of the folate cycle genes polymorphic variants contribution to the pathogenesis of multiple sclerosis could be one of the possible ways to improve diagnostic and therapeutic approaches.

Navigating Diagnostic Dilemmas in Subacute Subdural Hemorrhage: A Case Report

In this case report a 64-year-old male patient with recent past medical history of head injury complicated by zygomatic arc fracture and mild subarachnoid hemorrhage is studied. He had been presented to the Emergency Department because of progressive neurological symptoms and neurological deficits in the physical examination that could have been indicating subcacute subdural hemorrhage. However, the patient was reluctant to undergo diagnostic imaging due to concerns about radiation exposure. After several explanations, a CT scan was done, which revealed a bilateral subacute subdural hematoma. Neurosurgical management was initiated and intravenous corticosteroid therapy was administered to reduce local edema. The challenge of this case is based on the subtlety of symptoms that might cause patients to delay seeking medical attention. Additionally, patient reluctance to undergo diagnostic tests can complicate management, emphasizing the importance of patient education and therapeutic alliance. Multidisciplinary management involving Neurology and Neurosurgery is crucial for optimal patient care in such cases. This report underscores the significance of effective communication and collaborative decision-making between healthcare providers and patients to ensure timely and appropriate management of complex medical conditions.

The spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects

BackgroundTBL1XR1 encodes a F-box-like/WD40 repeat-containing protein that plays a role in transcription mediated by nuclear receptors and is a known genetic cause of neurodevelopmental disease of childhood (OMIM# 608628). Yet the developmental trajectory and progression of neurologic symptoms over time remains poorly understood.MethodsWe developed and distributed a survey to two closed Facebook groups devoted to families of patients with TBL1XR1-related disorder. The survey consisted of 14 subsections focused upon the developmental trajectories of cognitive, behavioral, motor, and other neurological abnormalities. Data were collected and managed using REDCap electronic data capture tools.ResultsCaregivers of 41 patients with a TBL1XR1-related disorder completed the cross-sectional survey. All reported variants affecting a single amino acid, including missense mutations and in-frame deletions, were found in the WD40 repeat regions of Tbl1xr1. These are domains considered important for protein–protein interactions that may plausibly underlie disease pathology. The majority of patients were diagnosed with a neurologic condition before they received their genetic diagnosis. Language appeared most significantly affected with only a minority of the cohort achieving more advanced milestones in this domain.ConclusionTBL1XR1-related disorder encompasses a spectrum of clinical presentations, marked by early developmental delay ranging in severity, with a subset of patients experiencing developmental regression in later childhood.

Case report of leukoencephalopathy with predominant brainstem and spinal cord involvement and lactate elevation behind the mask of multiple sclerosis

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare or underdiagnosed autosomal-recessive mitochondrial disease that sometimes mimics progressive multiple sclerosis (MS). Difficulties in diagnosing LBSL are due to the possibility of the onset of the disease in adulthood, and the nonspecific clinical picture in the form of slowly progressive neurological symptoms (pyramidal, cerebellar, sensory and cognitive impairments) without the involvement of other organs and systems characteristic of mitochondrial pathology. However, a notable feature of LBSL is its pathognomonic magnetic resonance imaging of the white matter of the brain and spinal cord, which allows a reliable diagnosis when certain criteria are met. Currently, there are no drugs registered for the specific treatment of LBSL, however, correct diagnosis is necessary to complete the epidemiological data, and to prevent the prescription of drugs with side effects that worsen the quality of life of patients. The number of clinical publications about LBSL is small, both in Russian and foreign publications, and therefore each identified case is of great interest. The article presents a brief review of the literature and a case report of a patient with the adult-onset LBSL, who received disease modifying therapy of multiple sclerosis for a long time. The patient’s main problems were progressive lower paraparesis and ataxia. To make clinicians more aware, we have reviewed the difficulties in differential diagnosis between LBSL and MS, we provided detailed medical history, neurological status, and magnetic resonance imaging findings.

Natural history of Chiari I malformation with syrinx and dilatation of the central canal in the pediatric population: the CHEO experience.

Given that syrinx is often considered an indication of surgery in children with Chiari I malformation (CM1), understanding of the natural history of these patients is very challenging. In this study, we investigate the natural history of children with CM1 that have syrinx and/or prominence of the central canal on presentation. All pediatric Chiari I patients who had syrinx and/or prominence of the central canal who underwent MR imaging of the head and spine from 2007 to 2020 were reviewed. Patients were divided into 3 groups (early surgery, delayed surgery, and conservative management). We focused on those patients who did not initially undergo surgery and had at least 1year of clinical follow-up. We assessed if there were any radiological features that would correlate with need for delayed surgical intervention. Thirty-seven patients met the inclusion criteria. Twenty-one patients were female and 16 were male. The mean age at presentation was 8.7 (5.8 SD). Fourteen (38%) patients had early surgical intervention, with a mean of 2.5months after initial presentation, 8 (16%) had delayed surgery due to new or progressive neurological symptoms and 46% of patients did not require intervention during follow-up. The length of tonsillar herniation and the position of the obex were associated with the need of surgery in patients who were initially treated conservatively. In pediatric patients with CM1 with syringomyelia and prominence of the central canal, conservative treatment is initially appropriate when symptoms are absent or mild. Close follow-up of patients with CM1 and dilatation of the central canal who have an obex position below the foramen magnum and greater tonsillar herniation is suggested, as these patients show a trend towards clinical deterioration over time and may require earlier surgical intervention.

Intrathecal chemotherapy for leptomeningeal metastases in patients with breast cancer

To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer. Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity). The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months. Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.

Novel HexA splice site mutations in a patient with late atypical onset Tay-Sachs disease: importance of combined NGS and biochemical analysis.

Tay-Sachs disease (TSD) is a rare genetic disorder with diverse clinical manifestations, often leading to underdiagnosis due to symptom similarities with other neurological conditions. In this study, we aimed to identify the genetic mutations underlying late-onset TSD in a 27-year-old patient with progressive neurological symptoms. Whole-exome sequencing revealed two hexA gene mutations associated with TSD: a previously known variant, c.805G > A (p.Gly269Ser), and a novel splice-site mutation, c.346 + 2dupT. Through clinical assessments, genetic analysis, and functional investigations-including RNA sequencing and enzymatic activity assays-we confirmed the pathogenicity of the novel mutation. Our findings highlight the efficacy of advanced genomic technologies in diagnosing intricate genetic disorders and emphasize the significance of functional validation to confirm the effects of mutations. Identifying compound heterozygous mutations in the hexA gene also provides insight into Mendelian inheritance patterns. This case highlights the diagnostic challenges posed by overlapping clinical phenotypes and emphasizes the need for increased genetic awareness among clinicians. Accurate diagnosis of TSD has significant implications for patients and their families, allowing for informed genetic counseling and guiding clinical management decisions. While current treatment options are limited, timely and accurate diagnosis holds promise for future research and therapeutic interventions. This study highlights the value of a multidisciplinary approach in exploring the molecular basis of complex genetic diseases and informing clinical decisions.