Neurological Comorbidities Research Articles

Human Fetal Brain Magnetic Resonance Imaging (MRI) Tells Future Emergence of Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which can result from a range of observed symptoms pertaining to social, emotional, and cognitive processing difficulties especially regarding communication of their own feelings, opinions, and thoughts with others. Although a diagnosis received by 1 in 68 children in the United States, a cause for autism is still unknown. Both genetic and environmental factors during prenatal and postnatal development are believed to account for the emergence of ASD. It is known that early treatment improves language and cognitive abilities later. However, currently, the earliest diagnosis of ASD can be made only around 18 months of age. It is critical to be aware of an altered initial brain anatomy in ASD for better predicting what aspects of brain function will likely preferentially and precociously deteriorate, which would allow for potentially earlier/better prevention and treatment. We hypothesized that prospective ASD patients will show region‐specific abnormalities in developmental stages. We have used retrospective clinical brain MRI of the fetuses who were diagnosed as ASD in later age to obtain earliest MRI‐based regional volumetric biomarkers. Thirty‐nine fetuses (mean age 24.87 ± 5.05 gestational week [GW]) were included in this study (9 prospective ASD patients, 20 neurotypical controls, 6 non‐ASD controls with neurological comorbidities observed in the prospective ASD patients, and 4 non‐ASD controls with non‐neurological comorbidities observed in the prospective ASD patients. After preprocessing, the images were segmented automatically with an atlas‐based automated anatomical labeling method. A set of three‐factor ANOVA was performed for lobar and regional comparisons of the segmented brain regions. The insula/insular lobe showed statistically significantly larger volume in ASD than that in all three control groups in the lobar comparison. In the regional comparison, the ASD group had statistically significantly larger amygdala, hippocampal commissure, and insula compared to the non‐ASD controls with neurological and non‐neurological comorbidities. Our results suggest that an increased volume of the insula/insular lobe may be a strong prenatal MRI biomarker that could predict the emergence of ASD later in life. The larger amygdala and hippocampal commissure could be additional biomarkers for identifying such prospective ASD patients.

MP48-07 THE NEUROTOXICITY OF ANDROGEN DEPRIVATION THERAPY: A PHARMACOVIGILANCE STUDY

You have accessJournal of UrologyCME1 May 2022MP48-07 THE NEUROTOXICITY OF ANDROGEN DEPRIVATION THERAPY: A PHARMACOVIGILANCE STUDY Logan Briggs, Stephen Reese, Peter Herzog, David-Dan Nguyen, Muhieddine Labban, Khalid Alkhatib, Quoc-Dien Trinh, and Alicia K. Morgans Logan BriggsLogan Briggs More articles by this author , Stephen ReeseStephen Reese More articles by this author , Peter HerzogPeter Herzog More articles by this author , David-Dan NguyenDavid-Dan Nguyen More articles by this author , Muhieddine LabbanMuhieddine Labban More articles by this author , Khalid AlkhatibKhalid Alkhatib More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , and Alicia K. MorgansAlicia K. Morgans More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002619.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is conflicting evidence regarding whether androgen deprivation therapy (ADT) is associated with neurotoxicity. Thus, we aim to characterize the association between different types of ADT and cognitive impairment or dementia in a real-world pharmacovigilance data set. METHODS: VigiBase, the World Health Organization’s international pharmacovigilance database, was queried for reports of cognitive impairment or dementia (together termed neurocognitive impairment) among men who took ADT from 1968 to 2021. Disproportionality analysis was performed to compare rates of neurocognitive impairment with different types of ADT versus other Vigibase drugs. Differences were assessed using reporting odds ratio (ROR) with 95% confidence intervals (95% CI) and lambda values (Q ≥1.0 was considered statistically significant). RESULTS: Odds of neurocognitive impairment were significantly elevated with first-generation (ROR 1.47, 95% CI 1.34-1.62, Q=1.35) and next-generation ADT (ROR 2.40, 95% CI 2.28-2.54, Q=2.26). Odds of neurocognitive impairment were significantly elevated with enzalutamide (ROR 2.89, 95% CI 2.73-3.05, Q=2.70) and numerically increased with apalutamide (ROR 3.31, 95% CI 1.57-7.00, Q=0.98), but were decreased with abiraterone (ROR 0.68, 95% CI 0.55-0.84, Q=0.57). CONCLUSIONS: This study demonstrates that ADT has elevated odds of neurocognitive impairment in a real-world data set. Risk of neurotoxicity was higher with next-generation than first-generation ADT, and higher with enzalutamide than abiraterone. Due to limitations inherent to disproportionality analysis (measuring associations, not risk) and incomplete data prohibiting the ability to control for factors such as age or use of secondary drugs, results should be considered exploratory in nature. This data may contribute to clinical decision-making for men with prostate cancer eligible for ADT, especially those with neurologic comorbidities. Source of Funding: LGB reports research funding from the Office of Scholarly Engagement at Harvard Medical School © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e822 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Logan Briggs More articles by this author Stephen Reese More articles by this author Peter Herzog More articles by this author David-Dan Nguyen More articles by this author Muhieddine Labban More articles by this author Khalid Alkhatib More articles by this author Quoc-Dien Trinh More articles by this author Alicia K. Morgans More articles by this author Expand All Advertisement PDF DownloadLoading ...

Association of Traumatic Brain Injury With the Risk of Developing Chronic Cardiovascular, Endocrine, Neurological, and Psychiatric Disorders

Increased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular and endocrine comorbidity risk after TBI in individuals without these comorbidities and associations with post-TBI mortality have received little attention. To assess the incidence of cardiovascular, endocrine, neurological, and psychiatric comorbidities in patients with mild TBI (mTBI) or moderate to severe TBI (msTBI) and analyze associations between post-TBI comorbidities and mortality. This prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center to select patients without any prior clinical comorbidities who experienced TBI from 2000 to 2015. Using the same data registry, individuals without head injuries, the unexposed group, and without target comorbidities were selected and age-, sex-, and race-frequency-matched to TBI subgroups. Patients were followed-up for up to 10 years. Data were analyzed in 2021. Mild or moderate to severe head trauma. Cardiovascular, endocrine, neurologic, and psychiatric conditions were defined based on International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Associations between TBI and comorbidities, as well as associations between the comorbidities and mortality, were analyzed. A total of 4351 patients with mTBI (median [IQR] age, 45 [29-57] years), 4351 patients with msTBI (median [IQR] age, 47 [30-58] years), and 4351 unexposed individuals (median [IQR] age, 46 [30-58] years) were included in analyses. In each group, 45% of participants were women. mTBI and msTBI were significantly associated with higher risks of cardiovascular, endocrine, neurologic, and psychiatric disorders compared with unexposed individuals. In particular, hypertension risk was increased in both mTBI (HR, 2.5; 95% CI, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9) groups. Diabetes risk was increased in both mTBI (HR, 1.9; 95% CI, 1.4-2.7) and msTBI (HR, 1.9; 95% CI, 1.4-2.6) groups, and risk of ischemic stroke or transient ischemic attack was also increased in mTBI (HR, 2.2; 95% CI, 1.4-3.3) and msTBI (HR, 3.6; 95% CI, 2.4-5.3) groups. All comorbidities in the TBI subgroups emerged within a median (IQR) of 3.49 (1.76-5.96) years after injury. Risks for post-TBI comorbidities were also higher in patients aged 18 to 40 years compared with age-matched unexposed individuals: hypertension risk was increased in the mTBI (HR, 5.9; 95% CI, 3.9-9.1) and msTBI (HR, 3.9; 95% CI, 2.5-6.1) groups, while hyperlipidemia (HR, 2.3; 95% CI, 1.5-3.4) and diabetes (HR, 4.6; 95% CI, 2.1-9.9) were increased in the mTBI group. Individuals with msTBI, compared with unexposed patients, had higher risk of mortality (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001); postinjury hypertension (HR, 1.3; 95% CI, 1.1-1.7), coronary artery disease (HR, 2.2; 95% CI, 1.6-3.0), and adrenal insufficiency (HR, 6.2; 95% CI, 2.8-13.0) were also associated with higher mortality. These findings suggest that TBI of any severity was associated with a higher risk of chronic cardiovascular, endocrine, and neurological comorbidities in patients without baseline diagnoses. Medical comorbidities were observed in relatively young patients with TBI. Comorbidities occurring after TBI were associated with higher mortality. These findings suggest the need for a targeted screening program for multisystem diseases after TBI, particularly chronic cardiometabolic diseases.

Mechanism of injury and special considerations as predictive of serious injury: A systematic review.

ObjectivesThe Centers for Disease Control and Prevention's field triage guidelines (FTG) are routinely used by emergency medical services personnel for triaging injured patients. The most recent (2011) FTG contains physiologic, anatomic, mechanism, and special consideration steps. Our objective was to systematically review the criteria in the mechanism and special consideration steps that might be predictive of serious injury or need for a trauma center.MethodsWe conducted a systematic review of the predictive utility of mechanism and special consideration criteria for predicting serious injury. A research librarian searched in Ovid Medline, EMBASE, and the Cochrane databases for studies published between January 2011 and February 2021. Eligible studies were identified using a priori inclusion and exclusion criteria. Studies were excluded if they lacked an outcome for serious injury, such as measures of resource use, injury severity scores, mortality, or composite measures using a combination of outcomes. Given the heterogeneity in populations, measures, and outcomes, results were synthesized qualitatively focusing on positive likelihood ratios (LR+) whenever these could be calculated from presented data or adjusted odds ratios (aOR).ResultsWe reviewed 2418 abstracts and 315 full‐text publications and identified 42 relevant studies. The factors most predictive of serious injury across multiple studies were death in the same vehicle (LR+ 2.2–7.4), ejection (aOR 3.2–266.2), extrication (LR+ 1.1–6.6), lack of seat belt use (aOR 4.4–11.3), high speeds (aOR 2.0–2.9), concerning crash variables identified by vehicle telemetry systems (LR+ 4.7–22.2), falls from height (LR+ 2.4–5.9), and axial load or diving (aOR 2.5–17.6). Minor or inconsistent predictors of serious injury were vehicle intrusion (LR+ 0.8–7.2), cardiopulmonary or neurologic comorbidities (LR+ 0.8–3.1), older age (LR+ 0.6–6.8), or anticoagulant use (LR+ 1.1–1.8).ConclusionsSelect mechanism and special consideration criteria contribute positively to appropriate field triage of potentially injured patients.

Neurocognitive impairment associated with traditional and novel androgen receptor signaling inhibitors ± androgen deprivation therapy: a pharmacovigilance study.

Conflicting evidence exists regarding whether hormone therapy for prostate cancer is associated with neurotoxicity. Thus, we aim to characterize the association between different types of hormone therapy and neurocognitive impairment in a real-world pharmacovigilance database. We queried VigiBase, the World Health Organization's international pharmacovigilance database, for reports of neurocognitive impairment among men who took hormone therapy from 1968 to 2021. We performed disproportionality analysis comparing rates of neurocognitive impairment with different types of hormone therapy versus other VigiBase drugs. Traditional hormonal therapy was defined as androgen deprivation therapy (ADT: gonadotropin-releasing-hormone agonists or antagonists) or first-generation androgen receptor (AR) antagonists. Novel AR signaling inhibitors (ARSIs) were defined as ARSIs with or without ADT. Differences were assessed using reporting odds ratio (ROR) with 95% confidence intervals (CI) and Empirical Bayes Estimator (EBE) values ≥1.0 signifying statistical significance. Odds of neurocognitive impairment were significantly elevated with traditional hormone therapy (ROR 1.47, 95% CI 1.34-1.62, EBE = 1.35) and novel ARSIs (ROR 2.40, 95% CI 2.28-2.54, EBE = 2.26). Odds of neurocognitive impairment were significantly elevated with enzalutamide (ROR 2.89, 95% CI 2.73-3.05, EBE = 2.70) and numerically increased with apalutamide (ROR 3.31, 95% CI 1.57-7.00, EBE = 0.98), but were decreased with abiraterone (ROR 0.68, 95% CI 0.55-0.84, EBE = 0.57). This study demonstrates elevated odds of neurocognitive impairment with hormone therapy in a real-world data set. Neurotoxicity risk was higher with novel ARSIs than traditional agents, and higher with enzalutamide than abiraterone. Due to limitations inherent to disproportionality analysis (measuring associations, not risk) and incomplete data prohibiting the ability to control for factors such as age or use of secondary drugs (e.g., concurrent use of novel ARSIs with ADT), results are exploratory in nature. The amalgamation of these and other conflicting data may contribute to clinical decision-making for men with prostate cancer eligible for treatment with these therapies, especially those with significant neurologic comorbidities.

Bridging structural and functional biomarkers in functional movement disorder using network mapping.

Background There are gaps in our neurobiological understanding of functional movement disorder (FMD).ObjectivesWe investigated gray matter volumetric profiles in FMD, and related findings to resting‐state functional connectivity (rsFC) profiles using Human Connectome Project data.MethodsVolumetric differences between 53 FMD patients and 50 controls were examined, as well as relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping was also used to probe whether FMD‐related structural alterations preferentially impacted brain areas with dense rsFC.ResultsCompared to controls without neurological comorbidities (albeit with mild depression and anxiety as a group), the FMD cohort did not show any volumetric differences. Across patients with FMD, individual differences in symptom severity negatively correlated with right supramarginal and bilateral superior temporal gyri volumes. These findings remained significant adjusting for FMD subtype or antidepressant use, but did not remain statistically significant adjusting for depression and anxiety scores. Symptom severity‐related structural alterations mapped onto regions with dense rsFC—identifying several disease epicenters in default mode, ventral attention, and salience networks.ConclusionsThis study supports that FMD is a multinetwork disorder with an important role for the temporoparietal junction and its related connectivity in the pathophysiology of this condition. More research is needed to explore the intersection of functional neurological symptoms and mood.

Referral trajectories in patients with vertigo, dizziness and balance disorders and their impact on health-related quality of life and functioning: results from the longitudinal multicenter study MobilE-TRA

BackgroundDue to reported barriers in the management of patients with vertigo, dizziness and balance problems (VDB), referral trajectories starting from primary care might be determined by other factors than medical necessity. The objective of this paper was to examine the impact of disease-related and other determinants on referral trajectories of older patients with VDB and to investigate, how these trajectories affect the patients’ functioning and health-related quality of life (HRQoL).MethodsData originate from the longitudinal multicenter study MobilE-TRA, conducted in two German federal states. Referrals to neurologists or ear-nose-throat (ENT) specialists were considered. Referral patterns were visualized using a state sequence analysis. Predictors of referral trajectories were examined using a multinomial logistic regression model. Linear mixed models were calculated to assess the impact of referral patterns on the patients’ HRQoL and functioning.ResultsWe identified three patterns of referral trajectories: primary care physician (PCP) only, PCP and neurologist, and PCP and ENT. Chances of referral to a neurologist were higher for patients with a neurological comorbidity (OR = 3.22, 95%-CI [1.003; 10.327]) and lower for patients from Saxony (OR = 0.08, 95%-CI [0.013; 0.419]). Patients with a PCP and neurologist referral pattern had a lower HRQoL and lower functioning at baseline assessment. Patients with unspecific diagnoses also had lower functioning.ConclusionReferral trajectories were determined by present comorbidities and the regional healthcare characteristics. Referral trajectories affected patients’ HRQoL. Unspecific VDB diagnoses seem to increase the risk of ineffective management and consequently impaired functioning.

Management of Psychiatric and Neurological Comorbidities in Epilepsy

People with epilepsy often have between 30 and 50% of their patients with neuropsychiatric disorders. The major neurological comorbidities linked with epilepsy, such as migraine, dementia, traumatic brain injury, and autism spectrum disorder, have relative effects on some of the psychiatric disorders, such as mood and anxiety disorders. The current research objective was to report the usage of pharmacologic drugs in the treatment of a neuropsychiatric disorder in epilepsy. A total of 630 patients of different aged groups (9-18 years, between 19-64 years and Elderly &gt; 65 years) were included in our research. The study was carried out at Qazi Hussain Ahmed Medical Complex Nowshera from September 2021 to Jan 2022. Epilepsy patients in rural areas had a substantially lower incidence of neuropsychiatric disorders than those in urban areas, and most of the patients were men. The most often used Anti epilepsy drugs (AEDs) for treating epilepsy were lamotrigine, valproate, and levetiracetam, which were used by 50% of participants. Carbamazepine was only used by adults and was least frequently utilized by older people. In order to effectively manage neuro-psychiatric comorbidities in epilepsy, it is important to consider both possible iatrogenic and therapeutic consequences.

A complex systems view on the current hypotheses of epilepsy pharmacoresistance.

Drug‐resistant epilepsy remains to this day as a highly prevalent condition affecting around one‐third of patients with epilepsy, despite all the research and the development of several new antiseizure medications (ASMs) over the last decades. Epilepsies are multifactorial complex diseases, commonly associated with psychiatric, neurological, and somatic comorbidities. Thus, to solve the puzzling problem of pharmacoresistance, the diagnosis and modeling of epilepsy and comorbidities need to change toward a complex system approach. In this review, we have summarized the sequence of events for the definition of epilepsies and comorbidities, the search for mechanisms, and the major hypotheses of pharmacoresistance, drawing attention to some of the many converging aspects between the proposed mechanisms, their supporting evidence, and comorbidities‐related alterations. The use of systems biology applied to epileptology may lead to the discovery of new targets and the development of new ASMs, as may advance our understanding of the epilepsies and their comorbidities, providing much deeper insight on multidrug pharmacoresistance.

Current Advances in the Management of Adult Craniopharyngiomas.

Craniopharyngiomas (CPs) are slow growing, histologically benign intracranial tumors located in the sellar–suprasellar region. Although known to have low mortality, their location and relationship to the adjacent neural structures results in patients having significant neurologic, endocrine, and visual comorbidities. The invasive nature of this tumor makes complete resection a challenge and contributes to its recurrence. Additionally, these tumors are bimodally distributed, being treated with surgery, and are followed by other adjuncts, such as focused radiation therapy, e.g., Gamma knife. Advances in surgical techniques, imaging tools, and instrumentations have resulted in the evolution of surgery using endoscopic techniques, with residual components being treated by radiotherapy to target the residual tumor. Advances in molecular biology have elucidated the main pathways involved in tumor development and recurrence, but presently, no other treatments are offered to patients, besides surgery, radiation, and endocrine management, as the disease and tumor evolve. We review the contemporary management of these tumors, from the evolution of surgical treatments, utilizing standard open microscopic approaches to the more recent endoscopic surgery, and discuss the current recommendations for care of these patients. We discuss the developments in radiation therapy, such as radiosurgery, being used as treatment strategies for craniopharyngioma, highlighting their beneficial effects on tumor resections while decreasing the rates of adverse outcomes. We also outline the recent chemotherapy modalities, which help control tumor growth, and the immune landscape on craniopharyngiomas that allow the development of novel immunotherapies.

Childhood-Onset Hereditary Spastic Paraplegia (HSP): A Case Series and Review of Literature

BackgroundHereditary spastic paraplegia (HSP) encompasses several rare genetic disorders characterized by progressive lower extremity spasticity and weakness caused by corticospinal tract degeneration. Published literature on genetically confirmed pediatric HSP cases is limited. MethodsWe conducted a retrospective review of childhood-onset HSP cases followed in the neuromuscular clinics at Children's and Emory Healthcare in Atlanta. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, genetic test results, comorbidities, and treatment were recorded. ResultsSixteen patients with HSP (eight males, eight females) with a mean age 19 years ± 15.7 years were included. Ten patients (66%) presented with gait difficulty. Seven (44%) were ambulatory at the last clinic follow-up visit with an average disease duration of 7.4 years. Genetically confirmed etiologies included SPAST (3 patients), MARS (2), KIF1A (2), KIF5A (1), SACS (1), SPG7 (1), REEP1 (1), PNPT1 (1), MT-ATP6 (1), and ATL1 (1). Symptom onset to genetic confirmation on an average was 8.2 years. Sensory motor axonal polyneuropathy was found in seven patients, and two exhibited cerebellar atrophy on magnetic resonance imaging (MRI) of the brain. Neurological comorbidities included developmental delay (n = 9), autism (n = 5), epilepsy (n = 3), and attention-deficit/hyperactivity disorder (n = 2). ConclusionsIn our study, a significant proportion (70%) of subjects with childhood-onset HSP had comorbid neurocognitive deficits, polyneuropathy with or without neuroimaging abnormalities, and rare genetic etiology. Genetic diagnosis was established either through inherited genetic neuropathy panel or whole-exome sequencing, which supports the utility of whole-exome sequencing in aiding in HSP diagnosis.

Factors associated with seizure severity among children with epilepsy in Northern Nigeria.

To describe how seizure severity in children with epilepsy may be affected by certain socio-demographic and clinical variables. A cross-sectional study. At the Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Sixty children and adolescents who were being followed up for seizure disorder at the child neurology clinic. Information on socio-demographic characteristics was obtained with a questionnaire, details of neurological co-morbidities were extracted from the participants' records, and seizure severity was assessed with the National Hospital Seizure Severity Score 3 tool. Chi-square test was used to establish the relationship between categorical variables, while the Independent t-test was used in describing the differences between means. Simple linear regression was calculated to assess the predictability of seizure severity. The median age was ten years (IQR = 6-13 years), with a male dominance (1.5:1). The Seizure Severity Score (SSS) ranged between 3 and 24 units, with a mean of 12.22 ± 4.29 units. The only characteristic that had a significant association with SSS on bivariate analysis was the "presence of co-morbidities" (p=0.019). A simple linear regression revealed that the presence of a neurological co-morbidity predicted an increase in the SSS by 2.67 units. [R2 = 0.091, F (1, 58)= 5.837, p = 0.019. β = 2.67, t= 2.42, p= 0.019.]. This study shows that neurological co-morbidities predict worsening seizure severity. This knowledge may influence prognostication and the charting of a treatment trajectory. No external funding.

360 CyberKnife Radiosurgery Versus Radiofrequency Thermocoagulation in Patients with Trigeminal Neuralgia With or Without Multiple Sclerosis: A Single-Center Comparison

INTRODUCTION: Treatment of refractory trigeminal neuralgia (TN), especially in patients with Multiple Sclerosis (MS), remains challenging. Single-fraction Cyberknife radiosurgery (CK) and retrogasserian thermocoagulation (TC) are possible therapeutic options. Comparative studies regarding treatment efficacy and outcome in patients with refractory TN treated with CK or TC, with additional consideration to MS, are scarce. METHODS: Clinical and radiographic data of patients with TN treated with single-fraction CK or TC at a single academic institution were analyzed. Pain level was evaluated using the Barrow Neurological Institute (BNIp) pain scale pre-intervention and 3, 6, 12 months and last follow-up (LFU) post-interventionally. Subgroup analysis was performed in patients with MS. RESULTS: 113 patients were treated with 161 treatments. Median age of the cohort was 61.1 (31.1–98.4) years. There were no significant differences between the cohorts regarding age, side, branch distribution and pre-procedural BNIp. Median follow-up time was 44.3 (3.0–135.9) months. After CK, improved outcome was reported in 59.1%, 57.9%, 66.7%, and 67.3% at 3, 6, 12 months and LFU, while after TC, improved outcome was reported in 85.0%, 77.4%, 70.8% and 55.9%. Patients were more likely to benefit initially and at 3 months follow-up from a TC procedure (p&lt;.0001), but improved outcome at LFU was more pronounced in the CK cohort (p=.077). Repeated treatments were significantly more common in the TC cohort (p=.02). MS was the most frequent neurological co-morbidity. Exclusive analysis of the MS subgroup revealed similar results regarding pain improvement at 3-months follow-up (TC: 95.5% vs. CK: 54.0%; p&lt;.001) and at LFU, (TC: 72% vs. 86.0%; p=.009). Incidence of new-onset hypesthesia was not significantly different in both cohorts (p=.550). CONCLUSION: Both therapies present safe and efficient treatment strategies for patients with refractory TN. Initial BNIp improvement was significantly better in patients treated with TC, while longterm effects were more pronounced in the CK cohort. This was also true for patients with MS.

Case Report: Atonic PNES Capture in fMRI

Psychogenic Non-Epileptic Seizures (PNES) are a misunderstood and disabling pathology, characterized by a paroxysmal occurrence of clinical signs without the epileptic activity. Resting-state functional MRI (fMRI) studies in patients with PNES have shown abnormal functional connectivity of the resting-state networks, especially in the limbic and motor systems, and in the precuneus. However, the transient nature of PNES episodes prevents us from elucidating the underlying mechanisms of seizures. Here, we report the case of a patient who presented an atonic episode of PNES during a 3T fMRI session. The patient is a 23-year-old woman, suffering from post-traumatic stress disorder, with no neurological comorbidities. The preprocessing of the fMRI images involved realignment, co-registration, segmentation, normalization, denoising (PhysIO toolbox), and smoothing. The time boundary of the seizure was defined according to the patient's reports, and the seizure period was contrasted with the resting state period before the seizure. A whole-brain analysis showed significant activations (left inferior temporal gyrus, left temporo-occipital junction) and deactivations (right precuneus, right superior parietal lobule, right postcentral gyrus, bilateral lingual gyri, inferior occipital gyri, and cerebellar lobules; right insula in a sub-thresholded analysis). Activations and deactivations occurred in four cerebral networks: emotional processing, agency, self-perception, and dissociation. To our knowledge, this report is the first published case of functional MRI during PNES. These results could confirm the emotional and dissociative hypothesis of the physiopathology of PNES and highlight future targets for neuromodulation.

Cerebral Palsy: An Overview of Etiology, Types and Comorbidities

Cerebral Palsy (CP) is the most frequent cause of childhood disability. CP occurs in 1 out of every 345 children in the United States. CP is primarily a motor disease that is the result of an insult to the brain that occurs during the prenatal or early postnatal period when the brain is still developing. CP is not a single disease but a physical description of motor impairments that originate from multiple etiologies. This article briefly discusses the etiologies, classification and management of the neurologic medical comorbidities that are associated with CP. Proactive management can assist in minimizing morbidity and maximizing outcomes and improving quality of life.

Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability

BackgroundAlternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability.Case presentationClinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature.ConclusionsHemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.

Population-Based Study of Nonelective Postpartum Readmissions in Women With Stroke, Migraine, Multiple Sclerosis, and Myasthenia Gravis.

To compare maternal obstetric complications and nonelective readmissions in women with common neurologic comorbidities (WWN) vs women without neurologic disorders. We performed a retrospective cohort study of index characteristics and acute postpartum, nonelective rehospitalizations from the 2015-2017 National Readmissions Database using ICD-10 codes. Wald χ2 testing compared baseline demographic, hospital, and clinical characteristics and postpartum complications between WWN (including previous stroke, migraine, multiple sclerosis [MS], and myasthenia gravis [MG]) and controls. Multivariable logistic regression models examined odds of postpartum complications and nonelective readmissions within 30 and 90 days for each neurologic comorbidity compared to controls (α = 0.05). A total of 7,612 women with previous stroke, 83,430 women with migraine, 6,760 women with MS, 843 women with MG, and 8,136,335 controls met the criteria for index admission after viable infant delivery. WWN were more likely than controls to have inpatient diagnoses of edema, proteinuria, or hypertensive disorders and to have received maternal care for poor fetal growth. The adjusted odds of a Centers for Disease Control and Prevention severe maternal morbidity indicator were greater for women with previous stroke (adjusted odds ratio [AOR] 8.53, 95% CI 7.24-10.06), migraine (AOR 2.04, 95% CI 1.85-2.26), and MG (AOR 4.45, 95% CI 2.45-8.08) (all p < 0.0001). Readmission rates at 30 and 90 days for WWN were higher than for controls (30 days: previous stroke 2.9%, migraine 1.7%, MS 1.8%, MG 4.3%, controls 1.1%; 90 days: previous stroke 3.7%, migraine 2.5%, MS 5.1%, MG 6.0%, controls 1.6%). Women with MG had the highest adjusted odds of readmission (30 days: AOR 3.96, 95% CI 2.37-6.65, p < 0.0001; 90 days: AOR 3.30, 95% CI 1.88-5.78, p < 0.0001). WWN may be at higher risk of severe maternal morbidity at the time of index delivery and postpartum readmission. More real-world evidence is needed to develop research infrastructure and create efficacious interventions to optimize maternal-fetal outcomes in WWN, especially for women with previous stroke or MG.

Cortical thickness in default mode network hubs correlates with clinical features of dissociative seizures

BackgroundDissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. MethodsForty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons. ResultsGroups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations. ConclusionsIn patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry.

Non convulsive refractory status epilepticus induced by thiocolchicoside (TCC) intrathecal injection: A case report

TCC is a semisynthetic molecule widely used in clinical settings as a pain killer and myorelaxant. Several neurological side effects have been reported in association with TCC treatment including somnolence, confusion and seizure, the latter in a lower percentage of patients. Some previous reports described seizure onset after TCC intake in adulthood. However, major epileptological complication, namely status epilepticus, has never been previously reported in association with TCC treatment. In our report, we describe a case of acute refractory non‐convulsive status epilepticus (NCSE) in the context of a TCC‐induced acute toxic encephalopathy (ATE) in a woman without any previous neurological or physical comorbidities.

Incidence of neurological and psychiatric comorbidity over time: a population-based cohort study in Ontario, Canada.

Comprehensive, population-based investigations of the extent and temporality of associations between common neurological and psychiatric disorders are scarce. This retrospective cohort study used linked health administrative data for Ontarians aged 40-85years on 1 April 2002, to estimate the adjusted rate of incident dementia, Parkinson's disease (PD), stroke or mood/anxiety disorder (over 14years) according to the presence and time since diagnosis of a prior disorder. Sex differences in the cumulative incidence of a later disorder were also examined. The cohort included 5,283,546 Ontarians (mean age 56.2 ± 12.1years, 52% female). The rate of dementia was significantly higher for those with prior PD (adjusted hazard ratio [adjHR] 4.05, 95% confidence interval [CI] 3.99-4.11); stroke (adjHR 2.49, CI 2.47-2.52) and psychiatric disorder (adjHR 1.79, CI 1.78-1.80). The rate of PD was significantly higher for those with prior dementia (adjHR 2.23, CI 2.17-2.30) and psychiatric disorder (adjHR 1.77, CI 1.74-1.81). The rate of stroke was significantly higher among those with prior dementia (adjHR 1.56, CI 1.53-1.58). Prior dementia (adjHR 2.36, CI 2.33-2.39), PD (adjHR 1.80, CI 1.75-1.85) and stroke (adjHR 1.47, CI 1.45-1.49) were associated with a higher rate of an incident psychiatric disorder. Generally, associations were strongest in the 6months following a prior diagnosis and demonstrated a J-shape relationship over time. Significant sex differences were evident in the absolute risks for several disorders. The observed nature of bidirectional associations between these neurological and psychiatric disorders indicates opportunities for earlier diagnosis and interventions to improve patient care.