Onset Of Neurological Symptoms Research Articles

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.

Postpartum Bilateral Nerve Palsy: A Harbinger for Preeclampsia?

Objective: To report a case of postpartum bilateral facial weakness that preceded the diagnosis of preeclampsia. Introduction: Bell’s palsy is a neuromuscular disorder that can cause paralysis or weakness of the face. It is the most common cause of unilateral facial weakness; however, bilateral weakness is rare. Bell’s palsy is one of the most common neuromuscular disorders observed in pregnancy, though the link between the two is not entirely clear. Proposed etiologies include reactivation of human herpes viruses, immune mediated inflammatory demyelination of the facial nerve, and microangiopathy as a result of systemic hypertension. There have been several case reports and studies suggesting a correlation between preeclampsia and Bell’s palsy. We present a rare case of postpartum bilateral Bell’s palsy in the setting of preeclampsia. Design: Case report. Results: Our patient is a 24 year-old G6P4116 Caucasian woman with no significant past medical history who presented with bilateral facial weakness and headache. She was postpartum day four from a spontaneous vaginal delivery of dichorionic diamniotic twins at 35 weeks at an outside hospital. She denied any elevated blood pressures during her pregnancy. Initially, on postpartum day two she had reported a severe headache that initially affected her occipital region bilaterally before migrating to her ears and forehead. At this time the patient was normotensive and was discharged home on analgesics. On postpartum day three, she returned to another emergency department with a worsening, severe headache. She was sent home with a diagnosis of anxiety. On postpartum day four, her symptoms persisted and she came to the emergency department at our facility. During our initial evaluation, her blood pressure was 170/98. She was admitted for severe preeclampsia and given IV magnesium and nifedipine. However, her headache persisted and she developed bilateral facial weakness, neck pain, and swelling. She reported that she was unable to move her face and had difficulty smiling. Her face was expressionless. She denied nausea, vomiting, dysphagia, double vision, gait disturbances, hearing loss, fever, shortness of breath, numbness, or tingling. She denied recent travel, sick contacts, or animal or tick bites. She was evaluated by neurology and her initial physical exam revealed intact cranial nerves, though the patient appeared to have difficulty squeezing her eyes shut and smiling. Periorbital edema was noted. Facial symmetry and sensation were intact bilaterally. She had difficulty saying the letter “P.” Her MRIs of both brain and cervical spine, chest x-ray, and lumbar puncture were all normal. Our working diagnoses included bilateral Bell’s palsy, Guillain-Barré and Miller-Fischer syndromes. The antibody panel drawn for Miller-Fischer syndrome subsequently resulted as negative. Our patient received three days of IVIG and was discharged on a week supply of prednisone 60mg with a taper thereafter. At discharge, she had severe bilateral facial droop. She was unable to puff out her cheeks or raise her eyebrows. Neurology recommended outpatient follow up. One month after discharge she had residual right sided facial droop, but the deficits of the left side of her face had mostly resolved. Discussion: Current literature suggests a correlation between preeclampsia and Bell’s palsy. There is some thought that elevated blood pressure leads to facial nerve compression secondary to edema or microemboli. One report suggested that the onset of Bell’s palsy antepartum or postpartum may be a predictor of preeclampsia. An English language PUBMED search revealed six case reports on bilateral Bell’s palsy in either the pregnant or postpartum state. Cases reported occurred in either the third trimester or within the first week postpartum. This was consistent with the onset of our patient’s symptoms during her first week postpartum. In one case, neurological symptoms preceded preeclampsia. Our patient complained of headaches and neck pain prior to having elevated blood pressures. Three of these cases included twin gestations, as did our case. Outcomes varied, with some patients seeing complete resolution of symptoms within weeks to others having recurring symptoms over a year. Providers should consider the relationship between preeclampsia and Bell’s palsy when treating pregnant or postpartum patients with new onset neurological symptoms. Pregnant and postpartum patients are at greater than three times increased risk for Bell’s palsy and have more severe symptoms and longer recovery times compared to the average population. It is important that obstetricians and gynecologists assess for signs of preeclampsia in pregnant or postpartum patients with concerns for Bell’s palsy, as well as refer patients for a complete neurological workup. Ultimately, more research is needed to further understand the relationship between preeclampsia and Bell’s palsy.

Postpartum Bilateral Nerve Palsy: A Harbinger for Preeclampsia?

Objective: To report a case of postpartum bilateral facial weakness that preceded the diagnosis of preeclampsia. Introduction: Bell’s palsy is a neuromuscular disorder that can cause paralysis or weakness of the face. It is the most common cause of unilateral facial weakness; however, bilateral weakness is rare. Bell’s palsy is one of the most common neuromuscular disorders observed in pregnancy, though the link between the two is not entirely clear. Proposed etiologies include reactivation of human herpes viruses, immune mediated inflammatory demyelination of the facial nerve, and microangiopathy as a result of systemic hypertension. There have been several case reports and studies suggesting a correlation between preeclampsia and Bell’s palsy. We present a rare case of postpartum bilateral Bell’s palsy in the setting of preeclampsia. Design: Case report. Results: Our patient is a 24 year-old G6P4116 Caucasian woman with no significant past medical history who presented with bilateral facial weakness and headache. She was postpartum day four from a spontaneous vaginal delivery of dichorionic diamniotic twins at 35 weeks at an outside hospital. She denied any elevated blood pressures during her pregnancy. Initially, on postpartum day two she had reported a severe headache that initially affected her occipital region bilaterally before migrating to her ears and forehead. At this time the patient was normotensive and was discharged home on analgesics. On postpartum day three, she returned to another emergency department with a worsening, severe headache. She was sent home with a diagnosis of anxiety. On postpartum day four, her symptoms persisted and she came to the emergency department at our facility. During our initial evaluation, her blood pressure was 170/98. She was admitted for severe preeclampsia and given IV magnesium and nifedipine. However, her headache persisted and she developed bilateral facial weakness, neck pain, and swelling. She reported that she was unable to move her face and had difficulty smiling. Her face was expressionless. She denied nausea, vomiting, dysphagia, double vision, gait disturbances, hearing loss, fever, shortness of breath, numbness, or tingling. She denied recent travel, sick contacts, or animal or tick bites. She was evaluated by neurology and her initial physical exam revealed intact cranial nerves, though the patient appeared to have difficulty squeezing her eyes shut and smiling. Periorbital edema was noted. Facial symmetry and sensation were intact bilaterally. She had difficulty saying the letter “P.” Her MRIs of both brain and cervical spine, chest x-ray, and lumbar puncture were all normal. Our working diagnoses included bilateral Bell’s palsy, Guillain-Barré and Miller-Fischer syndromes. The antibody panel drawn for Miller-Fischer syndrome subsequently resulted as negative. Our patient received three days of IVIG and was discharged on a week supply of prednisone 60mg with a taper thereafter. At discharge, she had severe bilateral facial droop. She was unable to puff out her cheeks or raise her eyebrows. Neurology recommended outpatient follow up. One month after discharge she had residual right sided facial droop, but the deficits of the left side of her face had mostly resolved. Discussion: Current literature suggests a correlation between preeclampsia and Bell’s palsy. There is some thought that elevated blood pressure leads to facial nerve compression secondary to edema or microemboli. One report suggested that the onset of Bell’s palsy antepartum or postpartum may be a predictor of preeclampsia. An English language PUBMED search revealed six case reports on bilateral Bell’s palsy in either the pregnant or postpartum state. Cases reported occurred in either the third trimester or within the first week postpartum. This was consistent with the onset of our patient’s symptoms during her first week postpartum. In one case, neurological symptoms preceded preeclampsia. Our patient complained of headaches and neck pain prior to having elevated blood pressures. Three of these cases included twin gestations, as did our case. Outcomes varied, with some patients seeing complete resolution of symptoms within weeks to others having recurring symptoms over a year. Providers should consider the relationship between preeclampsia and Bell’s palsy when treating pregnant or postpartum patients with new onset neurological symptoms. Pregnant and postpartum patients are at greater than three times increased risk for Bell’s palsy and have more severe symptoms and longer recovery times compared to the average population. It is important that obstetricians and gynecologists assess for signs of preeclampsia in pregnant or postpartum patients with concerns for Bell’s palsy, as well as refer patients for a complete neurological workup. Ultimately, more research is needed to further understand the relationship between preeclampsia and Bell’s palsy.

Closing the Gap: The Incidence of Complications in Minimally Invasive Tubular, Endoscopic, and Robotic-Assisted Procedures Transforaminal Lumbar Interbody Fusion

Background ContextThe aim of the current study was to compare the incidence of postoperative complications between MIS tubular, endoscopic and Robot-assisted TLIF techniques. MethodsConsecutive patients who underwent single or multi-level TLIF between 2020 and 2022. Pre-operative and post-operative patient reported outcomes (VAS Leg and ODI), demographic, and intra-operative variables were recorded. One way ANOVA with Bartlett’s equal-variance and Pearson chi-squared tests were used. ResultsThe current study included a total of 170 TLIF patients: 107 (63%) tubular, 42 (25%) endoscopic, and 21 (12%) robot-assisted. All three TLIF techniques had similar complication rates: tubular 6 (5.6%), endoscopic 2 (4.8%), and robot-assisted 1 (4.8%) all occurring within the first two weeks. Tubular TLIF reported the lowest incidence of new onset neurological symptoms, primarily radiculitis or numbness/tingling, at two weeks postoperatively (p<0.05) with 21 (20%) tubular, 17 (41%) endoscopic, and 9 (43%) robot-assisted patients. There were two revisions in the robot-assisted group, while tubular and endoscopic each had one within one year. There was no statistical difference in pre- or postoperative PROs between the TLIF groups. ConclusionsThe current study demonstrated that tubular, endoscopic, and robot-assisted TLIF procedures had similar complication rates. The tubular MIS TLIF reported less new neurological symptoms compared to endoscopic and robot-assisted TLIF procedures at two weeks postoperative, with all groups declining in symptom persistency at later time intervals. Average VAS scores continuously improved up to one year postoperatively amongst all groups.

Parenchymal Neuro-Behçet's disease or Comorbid Behçet's disease with multiple sclerosis: A discriminative analysis of a complex clinical entity

BackgroundPatients with Behçet's disease (BD) may rarely manifest with cerebral white matter lesions resembling multiple sclerosis (MS). This may result in misdiagnosis due to diagnostic difficulties between parenchymal neuro-BD (pNBD) and MS. This study aims to elucidate the distinguishing features of patients with comorbid BD and MS (BD+MS) in comparison to those with pNBD and MS alone by focusing on clinical and laboratory features. We also aimed to identify the distinctive characteristics of BD+MS patients by comparing them to patients with pNBD and MS. MethodsThe methodology of this study involved a retrospective analysis of patient records followed in the Department of Neurology at the Istanbul Faculty of Medicine, Istanbul University. The study population included patients diagnosed with pNBD, MS, and a comorbid condition of BD and MS (BD+MS). We assessed clinical, radiological, and laboratory data, including disease onset, annual relapse rates, Expanded Disability Status Scale (EDSS) progression, and cerebrospinal fluid examination. Several parameters were examined between the pNBD, MS, and BD+MS patient groups to find similarities and differences between subgroups. ResultsOur study included 1,764 patients: 172 with pNBD, 1,574 with MS, and 18 with BD+MS. A predominance of females was noted in the BD+MS (72%, p < 0.001) and MS (69 %, p < 0.001) groups compared to pNBD (30 %). The median age at the onset of neurological symptoms was 35.5 (IQR: 16.8) years for BD+MS, 34.6 (13.6) years for pNBD, and 27.6 (13.3) years for MS (BD+MS vs. MS; p = 0.3, pNBD vs. MS, p = 0.7). Additionally, the number of attacks was notably different, with BD+MS patients experiencing a median of 3.5 (2.0) attacks compared to 3.0 (3.0) for MS patients and only 1.0 (1.0) for pNBD patients, suggesting a more active disease course in the MS and BD+MS groups compared to pNBD (p < 0.001). The median annualized relapse rate for BD+MS was 0.3 (0.2), which was lower than the rate of 0.4 (0.4) in MS (p = 0.048) and equivalent to the rate of 0.2 (0.3) in pNBD (p = 0.2). The time to the first relapse was similar to those with BD+MS and MS, but considerably shorter than in individuals with pNBD (p < 0.0001). The cerebrospinal fluid (CSF) analysis showed no significant differences in neutrophil and lymphocyte counts between BD+MS and MS patients but elevated levels in pNBD patients (p < 0.05). CSF protein levels were consistent across all groups (p = 0.1 and p = 0.7). Oligoclonal bands were detected in all patients with BD+MS, in the majority of MS patients (83.6 %), and a small percentage of pNBD patients (19.7 %), showing a notable distinction between the BD+MS and pNBD groups (p < 0.001). ConclusionOur study underscores the need for a skeptical approach in diagnosing and treating patients with BD who exhibit symptomatic MS-like MRI lesions. Our findings suggest that BD+MS is a distinct clinical entity, warranting specific diagnostic and treatment approaches. Our findings highlight that BD patients with MS-like lesions meeting MS diagnostic criteria should be managed as patients with comorbid MS and BD rather than pNBD.

Abstract PO5-20-06: Paraneoplastic cerebellar degeneration in anti-Yo antibody and HER2-positive metastatic breast carcinoma

Abstract Paraneoplastic cerebellar degeneration (PCD) in the context of breast carcinoma affects less than 1% of patients. In most cases, breast cancer diagnosis follows several months or even years after the onset of neurological symptoms. The first association between PCD and occult gynecologic cancers (breast or ovarian) was identified in 1938 with the discovery of antibodies directed against cytoplasmic antigens of Purkinje cells (“anti-Yo antibodies”). Since then, evidence has grown significantly to support anti-Yo antibodies as excellent diagnostic markers of PCD with underlying gynecologic and breast carcinoma. This case study evaluates a 57-year-old female who initially presented with headache and subacute cerebellar ataxia. Her symptoms progressed over a period of three months with multiple falls, onset of speech difficulties, and diplopia. She also reported 30-pound weight loss, which she attributed to dieting and starting semaglutide. Magnetic resonance imaging (MRI) of the brain and spine were unremarkable and autoimmune workup was normal. Cerebral spinal fluid (CSF) and serum studies demonstrated positive anti-Yo antibodies. Computed tomography (CT) of the abdomen and pelvis showed an enlarged left axillary lymph node concerning for metastatic disease with a 1.2cm focus of asymmetric density in the central inferior left breast parenchyma. Diagnostic mammogram one year prior was reportedly normal. Ataxia symptoms improved after a course of empiric intravenous immunoglobulins and steroids. Ultrasound-guided biopsy of the left axillary lymph node revealed metastatic mammary carcinoma: estrogen and progesterone receptor negative and human epidermal growth factor receptor 2 (HER2)-positive, cT0N2aM0, ypTxN1aM0, stage IIIa (AJCC 8th edition). She underwent further metastatic workup, including repeat CSF studies and MRI. MRI of the spine was remarkable for multiple hemangiomas throughout the cervical, thoracic, and lumbar spine, with subsequent unremarkable bone scan. MRI of the abdomen was remarkable for right hepatic lobe hemangioma and a right adrenal nodule. CSF studies showed no sign of metastases. After multidisciplinary discussion, TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) neoadjuvant therapy was initiated and repeat imaging demonstrated favorable treatment response with a shrinking axillary mass; no primary breast mass was identified. The patient underwent left sentinel lymph node biopsy with a positive frozen section intraoperative for invasive cancer, therefore proceeded with left axillary lymph node dissection. She was offered a mastectomy but elected for only axillary surgery. Pathology revealed 1 of 14 lymph nodes were positive for metastatic ductal carcinoma. She remains in a rehabilitation center and her ataxia is improving, but her functional status remains below baseline. She is undergoing radiation to whole breast and regional lymph nodes. With this case, we aim to continue to build upon the limited base of the exceedingly rare presentation of breast cancer-associated paraneoplastic syndrome. In addition, several studies and case reports have demonstrated a strong correlation between HER2 overexpression and anti-Yo associated PCD. As we continue to diagnose and monitor breast cancer patients, we could consider starting to screen for anti-Yo antibodies in HER2-positive patients to gain insight into a patient’s prognosis and development of PCD. Citation Format: You Kim, Alison Coogan, Andrea Madrigrano. Paraneoplastic cerebellar degeneration in anti-Yo antibody and HER2-positive metastatic breast carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-06.

Familial hemiplegic migraine in Indian children-a tertiary center experience.

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1-18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks.

Brain magnetic resonance imaging findings in children with neurological complications of coronavirus disease 2019 (Omicron variant): a multicenter retrospective observational study.

An increasing rate of encephalopathy associated with coronavirus disease 2019 (COVID-19) has been observed among children. However, the literature on neuroimaging data in children with COVID-19 is limited. To analyze brain magnetic resonance imaging (MRI) of pediatric COVID-19 patients with neurological complications. This multicenter retrospective observational study analyzed clinical (n=102, 100%) and neuroimaging (n=93, 91.2%) data of 102 children with COVID-19 infections and comorbid acute neurological symptoms. These children were hospitalized at five pediatric intensive care units (PICUs) in China between December 1, 2022, and January 31, 2023. All patients were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as detected via reverse transcriptase polymerase chain reaction. About 75.7% of the children were infected with the Omicron variant BF.7 strain. Brain MRI was performed 1-12 days following the onset of neurological symptoms, which revealed acute neuroimaging findings in 74.2% (69/93) of cases, including evidence of acute necrotizing encephalopathy (33/69, 47.8%), encephalitis (31/69, 44.9%), reversible splenial lesion syndrome (3/69, 4.3%), reversible posterior leukoencephalopathy (1/69, 1.4%), and hippocampal atrophy (1/69, 1.4%). Overall, these data highlighted five neuroimaging patterns associated with the outbreak of the SARS-CoV-2 Omicron variant, with acute necrotizing encephalopathy being the most common of these neuroimaging findings. Rarely, the brain MRI of these pediatric COVID-19 patients also demonstrate hippocampal atrophy.

Successful treatment of unilateral facial nerve palsy in a pediatric patient with syringobulbia and Chiari malformation type I: illustrative case.

Unlike syringomyelia, syringobulbia is not commonly observed in pediatric patients with Chiari malformation type I (CMI). Previous series have reported the incidence of syringobulbia as between 3% and 4% in these patients. Presentation is typically chronic, with the slow onset of neurological symptoms and cranial nerve (CN) palsies resulting from lower brainstem involvement. The authors report the first case of a pediatric patient with simultaneous CMI, syringobulbia, and unilateral CN VII palsy. A 7-year-old male presented with right facial weakness in addition to headaches, ataxia, urinary incontinence, and falls. Magnetic resonance imaging revealed CMI with a syrinx of the cervicothoracic spine and syringobulbia. Posterior fossa decompression with duraplasty was performed without complications, and the patient was discharged home on postoperation day 5. At the 3-week follow-up, the patient's neurological deficits had largely subsided. At the 3-month follow-up, his CN VII palsy and syringobulbia had completely resolved. Pediatric CMI patients with syringomyelia are at risk for developing syringobulbia and brainstem deficits, including unilateral facial palsy. However, craniocervical decompression can prove successful in treating such deficits.

Binocular Diplopia in Miller Fisher Syndrome Pediatric Patient: A Rare Case Report

Introduction : Miller Fisher Syndrome (MFS) is a rare variant of Guillain-Barré syndrome that usually presents with ataxia, areflexia and ophthalmoplegia. It is more common among patients in their 40s and number of cases in pediatric patients is significantly smaller. Our objective is to report a rare case of diplopia in Miller Fisher.&#x0D; Case Illustration : An 11 years old boy came with complaint of double vision and history of gaze restriction. Patient had history of inpatient admission due to acute progressive generalized limb weakness and walking difficulty followed by respiratory failure. Patient also had history of chewing and swallowing difficulty. Inpatient treatment included intravenous immunoglobulin (IVIG) for 5 days which resultedin clinical improvement. Electromyography examination done while hospitalization showed normal results. Orthoptic examination revealed 15 degrees exotropia of left eye with 30 prism dioptres (PD) at near and far distance. Worth four dot test resulted in cross diplopia with no abnormality in head CT scan. After 2 months follow-up with push-up pencil exercise, patient showed improvement of symptoms.&#x0D; Discussion : MFS is a clinical diagnosis that can be assessed by clinical triad of ataxia, areflexia and ophthalmoplegia. Diagnosis can be supported by ancillary test such as cerebrospinal fluid analysis, electrophysiologic studies or antibody anti-GQ1b . Treatment of MFS are mainly for supportive care with respiratory support and immunotherapy if needed in severe cases.&#x0D; Conclusion : The outcome of MFS is usually good with a complete recovery. The improvements generally begin within two to four weeks after the onset of neurological symptoms and complete within six months.

Factors predicting functional outcome after rtPA for patients with acute ischemic stroke

BackgroundAccurate outcome prediction for patients with acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rtPA) treatment is essential for optimizing patients’ management. We aimed to identify factors associated with unfavorable outcomes following intravenous rtPA treatment. This study was carried out on 162 patients who presented with acute ischemic stroke within 4.5 h from onset of neurological symptoms and were eligible for intravenous rtPA. After exclusion of 48 patients, 114 patients were finally eligible for follow-up. After complete medical and neurological history, complete medical and neurological examination and brain image (CT and or MRI brain) were collected from the patients. patients eligible were included in the study. NIHS scale was assessed for all patients at time of admission, after 24 h, and follow-up for 3 months.ResultsAfter a 90-day follow-up period for 114 patients with acute ischemic stroke after rtPA, 35.8% had good outcome (MRS; 0–2), 18.5% had partial outcome (MRS; 3–4) and 12.5% had poor outcome (MRS; 5–6). Atrial fibrillation (AF), PH of stroke, stroke severity, and severity of symptom (NIHSS) score were significantly (P: 0.004, 0.001, 0.007 and 0.001) correlated with poor outcome after rtPA. Similarly, old age, high blood pressure at time of presentation, hypertension, and dyslipidemia were showed to carry poor outcome.ConclusionsAF, high NIHSS score, PH of stroke, previous stroke, hypertension, dyslipidemia, and high blood pressure on presentation were significantly correlated with poor functional outcome.

Myeloid and lymphoid expression of C9orf72 regulates IL-17A signaling in mice.

A mutation in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Patients with ALS or FTD often develop autoimmunity and inflammation that precedes or coincides with the onset of neurological symptoms, but the underlying mechanisms are poorly understood. Here, we knocked out murine C9orf72 in seven hematopoietic progenitor compartments by conditional mutagenesis and found that myeloid lineage C9orf72 prevents splenomegaly, loss of tolerance, and premature mortality. Furthermore, we demonstrated that C9orf72 plays a role in lymphoid cells to prevent interleukin-17A (IL-17A) production and neutrophilia. Mass cytometry identified early and sustained elevation of the costimulatory molecule CD80 expressed on C9orf72-deficient mouse macrophages, monocytes, and microglia. Enrichment of CD80 was similarly observed in human spinal cord microglia from patients with C9ORF72-mediated ALS compared with non-ALS controls. Single-cell RNA sequencing of murine spinal cord, brain cortex, and spleen demonstrated coordinated induction of gene modules related to antigen processing and presentation and antiviral immunity in C9orf72-deficient endothelial cells, microglia, and macrophages. Mechanistically, C9ORF72 repressed the trafficking of CD80 to the cell surface in response to Toll-like receptor agonists, interferon-γ, and IL-17A. Deletion of Il17a in C9orf72-deficient mice prevented CD80 enrichment in the spinal cord, reduced neutrophilia, and reduced gut T helper type 17 cells. Last, systemic delivery of an IL-17A neutralizing antibody augmented motor performance and suppressed neuroinflammation in C9orf72-deficient mice. Altogether, we show that C9orf72 orchestrates myeloid costimulatory potency and provide support for IL-17A as a therapeutic target for neuroinflammation associated with ALS or FTD.

New onset tremor in patients with COVID-19: can be a possible link with parkinsonism?

Aims: SARS-CoV-2 is a highly pathogenic member of the coronavirus family. We notice that some patients who were following in outpatient service have a new onset tremor. Our aim to describe these patients and interpreting new onset tremor after Covid-19 that possible link with parkinsonism. Methods: Forty-two patients with tremor who applied to Alanya Alaaddin Keykubat University Hospital neurology outpatient clinic between the 2021-2022 years were included the study. The data related to demographic characteristics, reasons for application of outpatient neurology clinic, pre-diagnosis and treatment were collected retrospectively. Results: The patients had a viral infection up to 3 months before the diagnosis of tremor was examined from the hospital system. It was determined that a total of 7 patients had viral infections due to upper respiratory infections and these were confirmed by polymerase chain reaction (PCR). Since two of these patients had concomitant thyroid dysfunction, one had diabetes and one had a history of acute cerebrovascular disorder, they were not included in the study. Covid-19 results were found to be positive wit PCR in 3 patients with a diagnosis of new onset tremor. It was determined in the neurology outpatient clinic notes of the patients that their complaints started after Covid-19. Conclusion: We haven’t enough data about Covid-19 yet but it should be included in the differential diagnosis of patients with new onset neurological symptoms, especially in epidemic situations.. Extensive clinical, neurological, and electrophysiological investigations of the patients may help to understand the virus's role in causing neurological manifestations

Spatial Tumor Heterogeneity in a Young Female with Lung Adenocarcinoma and Brain Metastasis

Small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are the two different forms of lung cancer, the latter subtype accounts for approximately 85% of cases. Lung cancer is estimated to be the main cause of all cancer deaths, accounting for nearly 1,800,000 deaths globally in 2020. In this clinical case, we describe a female patient with non-specific symptoms over an approximate duration of one and a half years. Metastatic lung adenocarcinoma was diagnosed after the onset of severe neurological symptoms, brain surgery, and historical analysis of the large pathological brain mass. Following this, the tumor in the lung, which was small in size and the sole metabolically active site of the disease, was surgically removed. The recurrence in the brain and the onset of new neurological symptoms occurred rapidly—within three months, necessitating a second operation. Histological examination of the primary tumor and metastasis unveiled significant disparities–the primary tumor was moderately differentiated with PD-L1 expression (programmed death-ligand 1) within the range of 1 to 49%, while metastasis was poorly differentiated and PD-L1 negative, both absent of EGFR mutations (epidermal growth factor receptor) and ALK fusion (anaplastic lymphoma kinase). Following two brain operations, the patient underwent three-dimensional conformal radiation therapy (3DCRT). Subsequently, the initiation of systemic therapy was postponed by a two-month interval due to the activation of chronic hepatitis C virus infection. This case study contributes to the growing body of knowledge aimed at enhancing our grasp of tumor heterogeneity and dynamics of progression.

Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease

IntroductionThe standard of care for patients with infantile-onset Pompe disease (IOPD) is enzyme replacement therapy (ERT), which does not cross the blood brain barrier. While neuromuscular manifestations of IOPD are well-described, central nervous system (CNS) manifestations of this disorder are far less characterized. Here we describe severe CNS-related neurological manifestations including seizures and encephalopathy in six individuals with IOPD. MethodWe identified six children with IOPD who developed CNS manifestations such as seizures and/or encephalopathy. We studied their brain magnetic resonance imaging scans (MRIs) and graded the severity of white matter hyperintensities (WMHI) using the Fazekas scale scoring system as previously published. Longitudinal cognitive measures were available from 4/6 children. ResultsAll six IOPD patients (4 males/2 females) had been treated with ERT for 12–15 years. Seizures and/or encephalopathy were noted at a median age at onset of 11.9 years (range 9–15 years). All were noted to have extensive WMHI in the brain MRIs and very high Fazekas scores which preceded the onset of neurological symptoms. Longitudinal IQ scores from four of these children suggested developmental plateauing. DiscussionAmong a subset of IOPD patients on long-term ERT, CNS manifestations including hyperreflexia, encephalopathy and seizures may become prominent, and there is likely an association between these symptoms and significant WMHI on MRI. Further study is needed to identify risk factors for CNS deterioration among children with IOPD and develop interventions to prevent neurological decline.

Pediatric neuroblastoma with intraspinal extension: the role of surgical management.

Neuroblastoma with spinal involvement accounts for up to 30% of pediatric spinal tumors and can cause profound neurological deficits. Chemotherapy is the preferred treatment option, but in select patients resection may be indicated. The goal of this study was to identify preoperative factors that led to early surgical intervention, with a specific emphasis on identifying differences on long-term neurological function and spinal deformity in the recent treatment era. A retrospective chart review was performed on all children diagnosed with neuroblastoma at a single institution from 2007 to 2020. Patient demographics, symptoms (motor deficit and sphincter dysfunction), and tumor characteristics (e.g., 123I metaiodobenzylguanidine [MIBG] avidity, MYCN amplification, chromosomal abnormality, pathology, catecholamine secretion, and stage) were recorded. Spine involvement included neural or vertebral extension, spinal cord compression, and/or T2 signal change on MRI. Survival, neurological status (motor deficit, sphincter dysfunction), and spine deformity at last follow-up were compared using univariate and multivariate analyses. The variables that contributed to neurological and deformity outcome were assessed with binomial logistic and linear regression models using R software. Seventy-seven of the 160 patients with neuroblastoma had spinal neuroblastoma, meaning either bone metastases alone (n = 43) or intraspinal extension with or without neurological deficit (n= 34). Most patients with spinal neuroblastoma were treated with chemotherapy and/or radiation therapy (97% and 57%, respectively). Resection of the spinal tumor was performed in 14 (18%) patients, all of whom also received chemotherapy. Between the surgical and nonsurgical patients, no baseline demographic differences were found. However, surgical patients were more likely to present with either motor deficits (50% vs 5%, p = 0.0011) or bladder/bowel dysfunction (14% vs 0%, p 0.035), and a shorter median time to onset of neurological symptoms (33 vs 80 days, p = 0.0096). Surgical patients also had a significantly shorter median overall survival (33.0 vs 54 months, p = 0.014). Of the 14 patients who underwent spine surgery, 2 patients underwent surgery at the time of diagnosis while the remaining 12 underwent initial chemotherapy followed later by resection. The 2 patients who underwent initial surgery had excellent outcomes, with neither long-term motor or bowel/bladder deficits nor spinal deformity. Surgical patients had shorter overall survival. However, the 2 patients with radiographic evidence of cord compression and acute neurological symptom onset who underwent initial, immediate surgery within 3 days of diagnosis had fewer long-term neurological deficits than surgical patients who underwent initial trials of chemotherapy. Thus, acute decompression may provide benefit in carefully selected patients with acute neurological deficits and cord compression on imaging.

Association between perioperative neuraxial local anesthetic neurotoxicity and arachnoiditis: a narrative review of published reports.

Arachnoiditis is a rare but devastating disorder caused by various insults, one of which is purported to be local anesthetic neurotoxicity following neuraxial blockade. However, the relationship between local anesthetics administered into the neuraxis and the development of arachnoiditis has not been clearly elucidated. We aimed to summarize the existing complex body of literature and characterize both the essential features and strength of any association between neuraxial local anesthetic neurotoxicity and arachnoiditis with a view toward mitigating risk, enhancing prevention, and refining informed consent discussions. We reviewed all published reports of arachnoiditis attributed to local anesthetic neurotoxicity following perioperative neuraxial anesthesia. This narrative review was based on a systematic search methodology, which included articles published up until December 2022. Thirty-eight articles were included, comprising 130 patients, over one-half of which were published prior to this century and inconsistent with modern practice. Neuraxial techniques included 78 epidurals, 48 spinals, and 5 combined spinal-epidurals, mostly for obstetrics. Reporting of essential procedural data was generally incomplete. Overall, at least 57% of patients experienced complicated needle/catheter insertion, including paresthesia, pain, or multiple attempts, irrespective of technique. The onset of neurological symptoms ranged from immediate to 8 years after neuraxial blockade, while the pathophysiology of arachnoiditis, if described, was heterogeneous. The existing literature attributing arachnoiditis to local anesthetic neurotoxicity is largely outdated, incomplete, and/or confounded by other potential causes, and thus insufficient to characterize the features and strength of any association.

Clinical and genetic spectrum of RNF216-related disorder: a new case and literature review

BackgroundCases of RNF216-related disorder have been reported sporadically. However, the clinical and genetic spectrum of this disorder has not been fully studied.MethodsWe identified an individual with a novel causative RNF216...

Magnetic resonance imaging in assessing the staging of intracerebral hemorrhages in children

The purpose of the study was to evaluate the possibilities of MRI in determining the stage of hemorrhagic stroke (HS) depending on structural and perifocal changes in children.Materials and methods. The study included 46 patients (including 19 boys and 27 girls) aged from the 29th day of life to 18 years, with a clinical picture of cerebrovascular accident and the presence of HS in the brain substance (BS) during an MRI study. For statistical analysis, patients were divided into two groups: group 1 – patients examined in the first 48 hours from the onset of neurological symptoms (21 people), group 2 – after 48 hours (26 people). Comparison in two groups was carried out according to MR signs: the presence of perifocal cytotoxic edema, the presence of perifocal hemorrhagic impregnation, the presence of a cytoplasmic rim. Intergroup comparisons on a qualitative basis were carried out using Fisher's exact test.Results. As a result of the study, differential diagnostic criteria for the stages of HS in children were determined by analyzing the MRI semiotics of hematoma in combination with the symptom complex of perifocal changes (CPC) in the form of perifocal cytotoxic edema, perifocal hemorrhagic impregnation and cytoplasmic rim. Statistically significant differences in the frequency of occurrence of signs of perifocal cytotoxic edema and perifocal hemorrhagic impregnation in the groups were found. The presence of perifocal cytotoxic edema was statistically significant (p = 0.027) more common in group 1 (47% (n = 10), 95% CI 26–69) than in group 2 (16% (n = 4), 95% CI 5–36). The presence of perifocal hemorrhagic soaking was statistically significantly (p = 0.003) more common in group 1 (81% (n = 17), 95% CI 57–93) than in group 2 (36% (n = 9), 95% CI 18–57). In addition, a statistically significant (p = 0.005) difference was found in the incidence of CPC, which was observed in group 1 (28% (n = 6), CI 12–52) and was not observed in group 2 (0%, (n = 0), 95% CI 0–17).Conclusions. The use of T2, T1, FLAIR, SWI and DWI modes (b = 1000) in combination with ADC in the protocol of MRI examination of children is mandatory, and only a comparison of the characteristics of the MR signal from a hematoma in combination with an analysis of perifocal changes allows us to differentiate the stage of hemorrhage. HS in the acute and early subacute stages has a similar MRI semiotics, therefore, it is necessary to assess the complex of perifocal changes, which allows to differentiate these stages, as it is determined in patients examined in the first 48 hours (p &lt; 0.05) and is not observed after two days. SWI analysis makes it possible to differentiate the late subacute stage of hematoma from chronic due to different characteristics of the MR signal, and also allows you to establish the presence of perifocal hemorrhagic impregnation, which contributes to the differential diagnosis of hemorrhage in the early stages of the pathological process.

Paralisi periferica bilateale del VII nervo cranico da infezione da virus di Epstein-Barr

Following a primary Epstein-Barr virus infection, a 4- years-old boy develops bilateral peripheral VII cranial nerve palsy. Ruled out the other bilateral facial palsy’s causes (first of all borreliosis), the cause of the paralysis is recognized in the Epstein-Barr virus infection. We start a steroid therapy associated with physiotherapy treatment for functional rehabilitation. Bilateral peripheral facial palsy is a rare condition. Un- like unilateral palsy, which is idiopathic in about half of the cases, bilateral palsy is idiopathic in only 20% of cas- es. Both in the case of unilateral and bilateral involve- ment, Borrelia burgdorferi infection stands out among the recognized causes in first place. Another bilateral facial palsy’s cause is Epstein-Barr virus infection, because of its important neurotropism, which causes palsy with a still unclear mechanism. About 2 months after the onset of neurological symptoms our boy is gradually recovering facial nerve functions.