Comorbid Neurological Disorders Research Articles

COMPARATIVE EFFECT OF MIME THERAPY WITH SENSORY EXERCISES VERSUS CONVENTIONAL THERAPY AMONG BELLS PALSY PATIENTS

Background: Bell’s palsy is an acute peripheral facial paralysis involving the seventh cranial nerve, often presenting with facial asymmetry and loss of motor function. Rehabilitation is essential for restoring function, with interventions ranging from conventional physiotherapy to advanced therapies like mime therapy combined with sensory exercises. These approaches aim to improve facial symmetry, emotional expression, and motor control, offering holistic management for patients with mild to moderate facial nerve dysfunction. Objective: To evaluate the effects of mime therapy combined with sensory exercises versus conventional physiotherapy in patients with Bell’s palsy. Methods: This randomized clinical trial included 40 patients aged 18 to 65 years, recruited from Jinnah Hospital and Mayo Hospital, Lahore, using purposive sampling. Participants had unilateral facial nerve dysfunction classified as Grades II-IV on the House-Brackmann scale, with symptoms lasting less than six months. Patients with severe dysfunction (Grades V-VI) or comorbid neurological disorders were excluded. Group A received mime therapy combined with sensory exercises, while Group B underwent conventional physiotherapy. Both groups received therapy for ten weeks, with four sessions per week. Facial function was assessed pre- and post-treatment using the Sunnybrook Score and the House-Brackmann grading system. Data analysis was performed using SPSS version 22. Results: Group A demonstrated a significant improvement in Sunnybrook scores, increasing from 46.0 ± 5.0 to 70.2 ± 6.5 (p = 0.015), with a paired difference of 24.2 ± 3.0 (p < 0.001). Group B showed moderate improvement in House-Brackmann grades, increasing from 45.0 ± 4.8 to 60.1 ± 6.2 (p = 0.028), with a paired difference of 15.1 ± 2.1 (p < 0.001). Between-group analysis highlighted superior outcomes in Group A compared to Group B. Conclusion: Mime therapy combined with sensory exercises demonstrated significantly better outcomes in facial symmetry, motor function, and functional recovery compared to conventional therapy, making it a more effective rehabilitation approach for Bell’s palsy.

Extracutaneous Lesions in Patients with Focal Scleroderma of Craniofacial Localization: a Retrospective Cross-Sectional Study

Background. Focal scleroderma is rare, acquired disease characterized by inflammation, sclerosis, skin and underlying tissues atrophy, with no lesions to internal organs. However, craniofacial localized scleroderma (CLS) can lead to neurological, ophthalmic, and maxillofacial changes. Extracutaneous lesions at limited scleroderma remain poorly studied despite its high prevalence. Objective. The aim of the study is to characterize brain anomalies revealed at neuroimaging and to analyze their incidence in pediatric patients with focal scleroderma, as well as to describe comorbid neurological and ophthalmic disorders. Methods. Descriptive retrospective cross-sectional study included 33 pediatric patients who underwent hospital treatment at dermatology and allergology department of National Medical Research Center of Children’s Health with diagnosis of focal scleroderma from 2016 to 2024. All patients were examined by neurologist and ophthalmologist during hospitalization, as well as magnetic resonance imaging (MRI) was performed. The incidence of neurological, ophthalmic, and radiological signs was evaluated in the studied patients as well as their correlations within the data analysis. Results. 33 pediatric patients from 3 to 17 years old were studied. The number of boys and girls was not significantly different (p=0.46). MRI neuroimaging changes were revealed in 17 of 33 patients (51.5%). 12 patients (36.4%) had isolated disorders, 5 (15.1%) — multiple (two or more types) according to MRI data. Neurological disorders were reported in 8 out of 33 patients (24%). Ophthalmic disorders — in 10 out of 33 (30.3%). The study has revealed correlation indicating that the presence of epilepsy in CLS is associated with changes in the brain structure according to MRI (hyperintensive signal at T2-weighted image and FLAIR) (p=0,022). Also, such changes as hypointense signal during T2-VI are correlated with tension headache (p=0.03). No correlation between ophthalmic changes and neuroimaging changes was revealed. Conclusion. Significant number of pediatric patients with CLS have wide range of ophthalmic and neurological manifestations, including neuroimaging abnormalities. Precise and timely diagnosis of these symptoms is crucial for determining treatment intervention.

Diagnosis of chronic migraine and comorbid neurological disorders in real-life clinical practice

Chronic migraine (CM) is a neurological disorder whose diagnosis requires not only knowledge of its diagnostic criteria, but also the physician's ability to differentiate between various forms of primary and secondary headache (HA), as well as to recognize comorbid neurological disorders that aggravate the course of CM. Timely and correct diagnosis of CM and comorbid disorders allows to prescribe effective treatment to a patient and convert the migraine from a chronic to an episodic form. The diagnostics of CM and comorbid neurological disorders has not been sufficiently investigated in our country, which formed the basis for this study.Objective: to evaluate the quality of diagnostics of CM and comorbid neurological disorders in real-life neurological practice.Material and methods. The study included 200 patients with CM (63 men and 137 women, mean age 33.1±7.1 years) admitted to A.Ya. Kozhevnikov Clinic of Nervous Diseases (CND) of Sechenov University, complaining of frequent headaches. They had previously been examined and treated by neurologists in other medical institutions on an outpatient and/or inpatient basis. A clinical interview was conducted with all patients to establish a diagnosis and analyze their previous treatment, and a psychometric test was performed to assess symptoms of anxiety and depression.Results. Only 6% of patients had been previously diagnosed with CM, the remaining 94% were incorrectly diagnosed with secondary HA. All patients had previously been prescribed additional examinations, mainly neuroimaging of the brain and ultrasound of the cerebral vessels, although there were no "red flags". None of the patients had been previously assessed for their emotional state, while almost all patients had high situational anxiety (n=190; 95%) and high personal anxiety (n = 180; 90%), there were symptoms of depression (n=190; 95%) of varying severity. Comorbid neurological disorders (medication overuse HA), insomnia, musculoskeletal pain etc.) were diagnosed in 91.5% of patients in CND and in only in 8% of patients in other medical centers.Conclusion. In real-life clinical practice, CM and comorbid neurological disorders are inadequately diagnosed and excessive and unjustified additional examinations are prescribed.

FEATURES OF NEUROLOGICAL DISORDERS IN CHILDREN WITH SPEECH DEVELOPMENTAL DISORDERS

Problems of speech pathology in children attract the attention of doctors, speech therapists and psychologists due to the high prevalence of these disorders and the importance of speech function in the mental development of the child. The result of impaired speech development is the difficulty or impossibility of a child’s education in a comprehensive school. In this regard, the formation of speech in children is a necessary factor for social adaptation and learning. Despite the numerous studies, there are no exact criteria for the early diagnosis of speech development disorders, questions of etiology and pathogenesis have not been resolved, methods for predicting the course and rehabilitation of children with speech development delays require further development, and the features of speech development delays for various variants of comorbid neurological disorders [4]. Delayed speech development in children, if adequate therapeutic and rehabilitation measures are not carried out in a timely manner, may in the future lead to a decrease in the intellectual potential of the nation. KEYWORDS: delayed speech development, neurological disorders.

Assessment of potentially inappropriate medications among long-stay older adult patients with serious mental illnesses: findings from a low-resource setting

Abstract Background Potentially inappropriate medications (PIMs) are defined as drugs whose adverse effects outweigh the benefits or when more efficacious alternatives are present. This study aims to assess the overall prevalence of PIMs according to Beers 2019 and 2023 among older adult patients with serious mental illnesses (such as schizophrenia), and factors associated with PIMs while examining the difference between the two versions. Method This cross-sectional study included chronic patients aged 65 years and above, hospitalized at the Psychiatric Hospital of the Cross (Lebanon), and taking at least one medication daily. Sociodemographic characteristics, medications, and clinical information were obtained from patients’ medical records. SPSS version 26 was used for data analysis. Descriptive statistics were used to describe independent variables, while bivariate analysis was used to assess associations between PIM use and different factors. A two-tailed p value < 0.05 was considered statistically significant. Results Ninety-seven patients were included with a mean age of 71.21 (± 4.63) years. 52.6% were female. 44.3% were on polypharmacy (5–9 medications). 97.9% had at least one PIM according to both versions with the majority being anticholinergics (84.5%). Polypharmacy was significantly correlated to PIM use. Hospital stay length and the presence of comorbid neurological disorders were negatively associated with PIM use. Conclusion PIMs were extremely prevalent among hospitalized psychiatric older adult patients. Raising awareness among physicians on the Beers criteria or making them mandatory could help diminish PIM use among this vulnerable population.

A - 160 Cognition over Time in Chronic sTBI with Non-Neurologic Comorbidities in Residential NeuroRehab.

Traumatic brain injury has been associated with increased risk of many comorbid neurologic and non-neurologic disorders (Masel & DeWitt, 2010). There is scant literature, however, to describe serial assessment of cognitive changes associated with comorbid non-neurologic disorders and sequelae in patients with chronic, severe traumatic brain injury (sTBI). A 60-year-old, right-handed, White male sustained an sTBI at age 15 secondary to a motor vehicle collision and subsequently developed behavioral and substance use problems, before being placed in a long-term residential neurorehabilitation program. He later developed kidney disease, believed to be the result of long-term use of anti-epileptic drugs (AEDs) that were prescribed to control seizures that developed following his brain injury. He continued to experience seizures, despite taking AEDs. Staff at his residential program reported concerns of declines in cognition and daily functioning over the past three years. Compared to results from two previous evaluations performed approximately four and six years prior, he demonstrated reductions in attention and working memory, processing speed, executive functioning, auditory and reading comprehension, and functional living skills. Expressive language, memory, and visuospatial skills were generally consistent with previous evaluations. Due to significant reductions across multiple cognitive domains, and multiple potential contributing factors, including ongoing seizures, late-stage kidney disease, and a possible superimposed neurodegenerative disorder, it was recommended that the patient continue to undergo serial neurocognitive testing to monitor for further decline and provide etiological clarification. The results were used by his therapists, residential program staff, and neurology providers to inform his treatment planning and care.

Розлади аутистичного спектра: фактори ризику, особливості діагностики й терапії

У статті обговорюються сучасні уявлення про взаємодію генного поліморфізму й факторів середовища при маніфестації розладів аутистичного спектра (РАС). Наведено скринінговий інструментарій для оцінки розвитку дитини й попередньої діагностики РАС, порядок остаточної діагностики лікарями-спеціалістами. Висвітлені особливості перебігу РАС при коморбідних психічних розладах і загальних медичних станах. У статті подана модель лікування розладів загального розвитку, розроблена в Українському науково-дослідному інституті соціальної і судової психіатрії та наркології, висвітлені особливості застосування психосоціальних інтервенцій, терапії лікарськими засобами коморбідних психічних і неврологічних розладів.

Особливості коморбідних патологій при мігрені без аури у дітей і вплив її лікування на перебіг хвороби

Актуальність. Мігрень — первинна форма головного болю з високою варіабельністю і непередбачуваною частотою нападів, що часто супроводжується різноманітними коморбідними станами, які впливають на клінічний перебіг захворювання і ускладнюють його лікування. Мета: оцінити частоту і структуру провідних неврологічних коморбідних порушень при мігрені без аури у дітей і оцінити динаміку частоти атак після їх лікування. Матеріали та методи. Сформовано дві групи залежно від форми захворювання: 1-ша група (основ­на) — мігрень без аури (МБА), 2-га група (порівняння) — мігрень з аурою (МЗА). Групу МБА становили 142 пацієнта. Групу МЗА становили 96 пацієнтів. Результати. При МБА неврологічні коморбідні порушення зустрічаються в 77,5 % (110 випадків), що в 2,5 раза частіше, ніж при МЗА — 31,2 % (30 випадків) (pФішера < 0,001). У всіх випадках коморбідних порушень виявлено астенічний синдром (ізольовано або в поєднанні з іншими порушеннями), їх лікування (нефармакологічне і фармакологічне) істотно вплинуло на перебіг МБА зі зменшенням частоти атак. Висновки. Корекція коморбідних неврологічних порушень при МБА у дітей зменшує кількість нападів (за три контрольних місяці), що обґрунтовує доцільність даного підходу при лікуванні МБА в педіатричній популяції.

The burden of neurological comorbidities in six autoimmune bullous diseases: a population-based study.

Apart from bullous pemphigoid (BP), the association of other autoimmune bullous diseases (AIBDs) with neurological conditions is poorly understood. To estimate the association between a wide array of AIBDs and neurological conditions. A retrospective cross-sectional study recruited patients with BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These patients were compared with their age- and sex-matched control subjects with regard to the lifetime prevalence of Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy and multiple sclerosis (MS). Logistic regression was used to calculate OR for specified neurological disorders. The current study included 1743, 251, 106, 126, 860 and 103 patients diagnosed with BP, MMP, EBA, PG, PV and PF, respectively. These patients were compared with 10141, 1386, 606, 933, 5142 and 588 matched controls, respectively. Out of the investigated neurological conditions, PD associated with BP (OR, 2.71; 95% CI, 2.19-3.35); AD with BP (OR, 2.11; 95% CI, 1.73-2.57), MMP (OR, 2.37; 95% CI, 1.03-5.47), EBA (OR, 6.00; 95% CI, 1.90-18.97) and PV (OR, 2.24; 95% CI, 1.40-3.60); stroke with BP (OR, 1.84; 95% CI, 1.55-2.19) and EBA (OR, 2.79; 95% CI, 1.11-7.01); and epilepsy with BP (OR, 2.18; 95% CI, 1.72-2.77) and PV (OR, 1.80; 95% CI, 1.19-2.73). MS did not significantly cluster with any of the six AIBDs. In addition to BP, EBA and PV were found to cluster with neurological comorbidities. Patients with these AIBDs with compatible symptoms may be carefully assessed for comorbid neurological disorders.

Tumour brain: Pretreatment cognitive and affective disorders caused by peripheral cancers.

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood-brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis.

Functional motor phenotypes: to lump or to split?

IntroductionFunctional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms.ObjectiveTo compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities.MethodsConsecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted.ResultsA total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors.ConclusionsOur data support the evidence of a large overlap between FMD phenotypes.

Bidirectional Relations Among Depression, Migraine, and Epilepsy: Do They Have an Impact on Their Response to Treatment?

The evaluation and treatment of patients with epilepsy is not limited to the type of epilepsy, but it must incorporate the common comorbid neurologic, psychiatric, and medical disorders, as the latter can bare an impact on the course and response to treatment of the seizure disorder and vice versa. In this article we review the bidirectional relations among epilepsy and two of its most common comorbidities, mood disorders and migraine and examine the implications of these relations on the selection of therapies of these three disorders and their response to treatment. We also review the most salient common pathogenic mechanisms that may explain such relations.

Migraine Symptoms Improvement During the COVID-19 Lockdown in a Cohort of Children and Adolescents.

Background: Pediatric migraine is among the most common primary or comorbid neurologic disorders in children. Psychological stressors are widely acknowledged as potential triggers involved in recurring episodes of pediatric migraine. As the COVID-19 emergency may have affected the levels of stress perceived by children and adolescents with migraine, the present study was aimed to understand the effect of COVID-19 emergency on symptoms intensity and frequency in pediatric patients.Methods: A cohort of 142 child and adolescent patients with a diagnosis of migraine was enrolled at the Child Neurology and Psychiatry Unit of the IRCCS Mondino Foundation in Pavia (Italy). Socio-demographic and clinical characteristics were obtained from medical records. An on-line survey was used to collect information on COVID-19 exposure, stress response to the lockdown period, anxious symptoms during COVID-19 emergency, as well as migraine symptoms intensity and frequency before and during the lockdown.Results: The great majority were outpatients (n = 125, 88.0%), 52 (36.6%) had migraine with aura, whereas, 90 (63.4%) had migraine without aura. All the patients reporting worsening symptoms progression before COVID-19, had reduced intensity during the lockdown (χ2 = 31.05, p < 0.0001). Symptoms frequency reduction was observed in 50% of patients presenting worsening symptoms before the lockdown, 45% of those who were stable, and 12% of those who were already improving. All patients who had resolved symptoms before COVID-19 were stable during the lockdown (χ2 = 38.66, p < 0.0001). Anxious symptomatology was significantly associated with greater migraine symptoms frequency (χ2 = 19.69, p < 0.001). Repeating the analysis separately for individuals with and without aura did not affect the findings and significant associations were confirmed for both the patients' subgroups.Discussion: A significant reduction of migraine symptoms intensity and frequency was observed in pediatric patients during the COVID-19 lockdown phase in northern Italy. The improvement in both intensity and frequency of the migraine symptoms was especially significant in patients who were stable or worsening before the lockdown. The reduction of symptoms severity during a period of reduced environmental challenges and pressures further highlights the need of providing effective training in stress regulation and coping for these patients.

Retinal pathology occurs in stiff-person syndrome.

To evaluate whether structural and functional changes occur in the afferent visual system of patients with stiff-person syndrome (SPS) and whether these changes correlate with disease burden, given the high concentration of γ-aminobutyric acid receptors, which are generally thought to be involved in SPS pathogenesis, in the retina. In this single-center, cross-sectional study, patients with SPS and healthy controls (HCs) underwent optical coherence tomography (OCT), with a subset undergoing high- and low-contrast visual acuity (VA) assessments. Burden of disease was assessed via the number of body regions affected. Individuals with uncontrolled hypertension or comorbid neurologic or ophthalmologic disorders were excluded. Statistical analyses were performed using mixed-effects linear regression models. Thirty-five patients with SPS and 40 age- and sex-matched HCs underwent OCT. A subset of 23 patients with SPS and 28 HCs underwent VA assessments. Relative to HCs, patients with SPS had lower ganglion cell + inner plexiform layer (GCIPL) thicknesses (SPS: 74.36 µm [SD 5.7]; HCs: 76.33 µm [SD 4.2]; p = 0.005), inner nuclear layer thicknesses (SPS: 44.37 µm [SD 2.7]; HCs: 45.18 µm [SD 2.2]; p = 0.042), and 100% (SPS: 53 [SD 9.6]; HCs: 57.5 [SD 6.1]; p = 0.005), 2.5% (SPS: 24.35 [SD 10.1]; HCs: 30.16 [SD 7.7]; p = 0.006), and 1.25% contrast (SPS: 16.41 [SD 10.6]; HCs: 20.84 [SD 8.6]; p = 0.034) letter acuity scores. GCIPL thicknesses correlated with the number of body regions affected in SPS (decrease of 1.25 µm [95% confidence interval, -2.2 to -0.3 µm; p = 0.008] per additional body region affected). Retinal neuronal pathology can occur in SPS. OCT may have utility as a biomarker of disease burden in SPS.

Association Between Pemphigus and Neurologic Diseases

ImportanceThe association between pemphigus and neurologic diseases was not evaluated systematically in the past. In a recent uncontrolled cross-sectional study, Parkinson disease was found to be significantly associated with pemphigus; in the same study, epilepsy had a nonsignificant association with pemphigus. Several case reports have suggested that pemphigus coexists with multiple sclerosis and dementia.ObjectiveTo estimate the association between pemphigus and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple sclerosis), using one of the largest cohorts of patients with pemphigus.Design, Setting, and ParticipantsA retrospective population-based cross-sectional study was performed between January 1, 2004, and December 31, 2014, using the database of Clalit Health Services, the largest public health care organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. A total of 1985 patients with a new diagnosis of pemphigus and 9874 controls were included in the study.Main Outcomes and MeasuresThe proportion of dementia, epilepsy, Parkinson disease, and multiple sclerosis was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control participants. Logistic regression was used to calculate odds ratios (ORs) for dementia, epilepsy, Parkinson disease, and multiple sclerosis. The association was examined after a sensitivity analysis that included only patients treated with long-term, pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab) and after adjustment for several confounding factors.ResultsWhen comparing the 1985 cases (1188 women and 797 men; mean [SD] age, 72.1 [18.5] years) with the 9874 controls (5912 women and 3962 men; mean [SD] age, 72.1 [18.5] years), dementia was seen in 622 cases (31.3%) vs 1856 controls (18.8%), with an OR of 1.97 (95% CI, 1.77-2.20). Epilepsy was present in 74 cases (3.7%) vs 210 controls (2.1%), with an OR of 1.78 (95% CI, 1.36-2.33). Parkinson disease was seen in 175 cases (8.8%) vs 437 controls (4.4%), with an OR of 2.09 (95% CI, 1.74-2.51). Multiple sclerosis was present in 2 cases (0.1%) vs 6 controls (0.01%), with an OR of 1.65 (95% CI, 0.34-8.22). Study findings were robust to sensitivity analysis that included patients receiving pemphigus-specific treatments. Estimates were not altered significantly after controlling for comorbidities and overuse of health care.Conclusions and RelevanceAn association was observed between pemphigus and specific neurologic diseases, including dementia, Parkinson disease, and epilepsy. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid neurologic disorders and receive appropriate treatment.

Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family

The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scaffolds influencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption. The known Ankyrin and tetratricopeptide repeat (TPR) domains have been modeled. The newly predicted N-terminal ATPase domain may function as a regulated molecular switch for downstream signaling. Several putative conserved protein binding motifs allowed to extend the TANC interaction network. Interestingly, we highlighted connections with different signaling pathways converging to modulate neuronal activity. Beyond a known role for TANC family members in the glutamate receptor pathway, they seem linked to planar cell polarity signaling, Hippo pathway, and cilium assembly. This suggests an important role in neuron projection, extension and differentiation.

Neurobehavioral comorbidities of epilepsy: Role of inflammation.

Epilepsy is associated with a high incidence of comorbid neurologic and psychiatric disorders. This review focuses on the association of epilepsy with autism spectrum disorder (ASD) and depression. There is high concordance of these behavioral pathologies with epilepsy. We review data that unambiguously reveal that epilepsy, ASD, and depression are associated with elevated brain inflammatory markers and that these may interact with serotoninergic pathways. Interference with inflammatory pathways or actions can reduce the severity of seizures, depression, and ASD-like behavior. Inflammation in the brain can be induced by seizure activity as well as by behavioral, environmental, and physiologic stressors. Furthermore, induction of inflammation at an early time point during gestation and in early neonatal life can precipitate both an ASD-like phenotype as well as a more excitable brain. It appears likely that priming of the brain due to early inflammation could provide a means by which subsequent inflammatory processes associated with epilepsy, ASD, and depression may lead to comorbidity.

Modeling brain lentiviral infections during antiretroviral therapy in AIDS.

Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain. Based on previous reports quantifying total viral DNA levels in brain from HIV-1 and SIV infections, estimates of integrated proviral DNA burden were made, which were used to calibrate the mathematical model predicting viral accrual in brain macrophages from primary infection. The annual rate at which susceptible brain macrophages become HIV-1 infected was estimated to be 2.90×10-7-4.87×10-6 per year for cART-treated HIV/AIDS patients without comorbid neurological disorders. The transmission rate for SIV infection among untreated macaques was estimated to be 5.30×10-6-1.37×10-5 per year. An improvement in cART effectiveness (1.6-48%) would suppress HIV-1 infection in patients without neurological disorders. Among patients with advanced disease, a substantial improvement in cART effectiveness (70%) would eradicate HIV-1 provirus from the brain within 3-32 (interquartile range 3-9) years in patients without neurological disorders, whereas 4-51 (interquartile range 4-16) years of efficacious cART would be required for HIV/AIDS patients with comorbid neurological disorders. HIV-1 and SIV provirus burdens in the brain increase over time. A moderately efficacious antiretroviral therapy regimen could eradicate HIV-1 infection in the brain that was dependent on brain macrophage lifespan and the presence of neurological comorbidity.

Kidney-brain crosstalk in the acute and chronic setting.

Patients with kidney disease often exhibit multiple organ dysfunction that is caused, in part, by marked connectivity between the kidney and other organs and tissues. Substantial crosstalk occurs between the kidney and the brain, as indicated by the frequent presentation of neurological disorders, such as cerebrovascular disease, cognitive impairment, and neuropathy during the natural history of chronic kidney disease. The underlying pathophysiology of such comorbid neurological disorders in kidney disease is governed by shared anatomic and vasoregulatory systems and humoral and non-humoral bidirectional pathways that affect both the kidney and the brain. During acute kidney injury, the brain and kidney might interact through the amplification of cytokine-induced damage, extravasation of leukocytes, oxidative stress, and dysregulation of sodium, potassium, and water channels. The advent of dialysis and renal transplantation programmes has led to a reduction in the rate of neurological complications associated with uraemia, but a new set of complications have arisen as a consequence of the effects of dialysis on the central nervous system over the short and long term. This Review discusses the clinical complications of acute and chronic renal failure from a neurologic perspective, and highlights current understanding of the underlying pathophysiologies.

The choice of the antihypertensive drug in special conditions: evidence-based data in co-morbid neurology diseases (part 5)

Hypertension is a risk factor for some neurological disorders (like stroke, transient ischemic attack, cognitive dysfunction, including the most severe forms, such as dementia). In other diseases of neurology system systemic hypertension might either contribute to the progression of the disease, or decrease the treatment efficiency. Thus, the management of hypertension in a patient with co-morbid neurological disorder is a complex task requiring the comprehensive approach and the joint efforts of both cardiologist and neurologist. This will result in the best control of hypertension and the most efficient risk reduction. The current guidelines on diagnostics, management and prevention of hypertension (by the Joint National Committee of the USA, European Society of Cardiology / European Society of Hypertension, American Society of Hypertension / International Society of Hypertension, and national guidelines by Russian Society of Cardiology) consider some issues of the management of a hypertensive patient with concomitant neurology disorder (mainly, stroke, and transient ischemic attack). The paper shows the evidence-based data on the hypertension management in co-existent neurodegenerative diseases, cognitive dysfunction, neuromuscular diseases, epilepsy, migraine etc.