Standardized Neurological Examination Research Articles

Conversion Rate of Essential Tremor to Essential Tremor-Parkinson’s Disease: Data from a Prospective, Longitudinal Study (S42.010)

<h3>Objective:</h3> We quantified the conversion rate from essential tremor (ET) to ET with Parkinson’s disease (ETPD) in a prospective, longitudinal cohort study of ET cases. We compared the observed rate to that reported in the epidemiological literature. <h3>Background:</h3> There has been a longstanding dialogue as to whether ET increases the risk of developing PD. While there are relevant cross-sectional data, there are almost no longitudinal, prospective data. <h3>Design/Methods:</h3> We enrolled ET cases in a prospective, longitudinal study. A senior movement disorders neurologist evaluated standardized neurological examinations every 18 months. <h3>Results:</h3> 193 ET cases (mean age = 78.1 ± 9.6 years, range = 55 – 96) had a mean follow-up duration of 4.1 years. Seven (3.6%) converted from ET to ETPD. The incidence of PD among ET cases was 7/792.9 person years [py] (i.e., 882.8/100,000 py). A meta-analysis of the incidence (per 100,000 py) of PD in 14 studies from 13 countries across 4 continents reported an incidence of PD = 61.21 (males, ≥40 years) and 37.55 (females, ≥40 years). The incidence/100,000 py in males peaked in the 80 – 89 year old age group (258.47) and in females in the 80 – 89 year old age group (103.48 py). The above published values are 3.4 – 23.5 times lower than the value we observed for ET. <h3>Conclusions:</h3> The incidence of PD in an ET cohort is substantially higher than that reported in historical, population-based control groups across numerous countries. Additional prospective, longitudinal data are needed to further explore this association. <b>Disclosure:</b> Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health. Dr. Berry has nothing to disclose. Dr. Ghanem has nothing to disclose. Dr. Cosentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Association for Frontotemporal Dementia. Dr. Cosentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SAGE Pharmaceuticals.

Bradykinesia in Neurodegenerative Disorders: A Blinded Video Analysis of Pathology-Proven Cases.

Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies. We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies. Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration. Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05). Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dopaminergic connectivity reconfiguration in the dementia with Lewy bodies continuum

IntroductionThe impairment of nigrostriatal dopaminergic network is a core feature of dementia with Lewy bodies (DLB). The involvement and reconfiguration of extranigrostriatal dopaminergic circuitries in the DLB continuum is still theme of debate. We aim to investigate in vivo the dynamic changes of local and long-distance dopaminergic networks across DLB continuum. MethodsForty-nine patients (including 29 with dementia and 20 prodromal cases) and fifty-two controls entered the study. Each subject underwent a standardized clinical and neurological examination and performed Brain SPECT to measuring brain dopamine transporter (DAT) density. Spatially normalized images underwent the occipital-adjusted specific binding to obtain parametric data. The ANCOVA was applied to assess 123I-FP-CIT differences between pDLB, overt-DLB and CG, considering age, gender, and motor impairment as variables of no interest. Between-nodes correlation analysis measured molecular connectivity within the ventral and dorsal dopaminergic networks. ResultsProdromal DLB and DLB patients showed comparable nigrostriatal deficits in basal ganglia regions compared with CG. Molecular connectivity analyses revealed extensive connectivity losses, more in ventral than in dorsal dopaminergic network in DLB dementia. Conversely, the prodromal group showed increased connectivity compared to CG, mostly putamen-thalamus-cortical and striatal-cortical connectivity. ConclusionsThis study indicates a comparable basal ganglia deficit in nigrostriatal projections in DLB continuum and supports a different reorganization of extra-striatal dopaminergic connectivity in the prodromal phases of DLB. The shift from an increased to a decreased bilateral putamen-thalamus-cortex connectivity might be a hallmark of transition from prodromal to dementia DLB stages.

The association of early regulatory problems with behavioral problems and cognitive functioning in adulthood: two cohorts in two countries.

Regulatory problems (RPs; excessive crying, sleeping, or feeding difficulties) that co-occur (i.e., multiple) or are persistent have been associated with cognitive and behavioral problems in childhood. However, it remains unknown if multiple or persistent RPs are associated with cognitive and behavioral problems in adulthood. This large prospective longitudinal study (N=759) was conducted in two cohorts in Germany (N=342) and Finland (N=417). RPs were assessed at 5, 20, and 56 months via the same standardized parental interviews and neurological examinations. In young adulthood, questionnaires were used to assess behavioral problems. Cognitive functioning was assessed with IQ tests. We examined the effects of multiple or persistent RPs on the outcomes via analysis of covariance tests and logistic regression controlled for the influence of cohort. Of 163 participants with RPs, 89 had multiple and 77 had persistent RPs. Adults who had early multiple or persistent RPs (N=151) reported more internalizing (p=.001), externalizing (p=.020), and total behavioral problems (p=.001), and, specifically, more depressive (p=.012), somatic (p=.005), avoidant personality (p < .001), and antisocial personality problems (p=.006) than those who never had RPs (N=596). Participants with multiple or persistent RPs were more likely to receive any ADHD diagnoses (p=.017), particularly of hyperactive/impulsive subtype (p=.032). In contrast, there were no associations between multiple or persistent RPs and IQ scores in young adulthood. The results indicate long-lasting associations between multiple or persistent RPs and behavioral problems. Thus, screening for early RPs could help to identify children who are at risk for later behavioral problems.

Cerebral toxoplasmosis with neurological co-infection in people living with AIDS/HIV: results of a prospective cohort in São Paulo, Brazil

Concomitant neurological diseases in people living with HIV/AIDS (PLWHA) is a challenging subject that has been insufficiently evaluated by prospective clinical studies. The goal of the present study was to identify the clinical characteristics and outcomes of PLWHA with cerebral toxoplasmosis and neurological co-infections. We conducted a prospective observational cohort study at a tertiary teaching center in São Paulo, Brazil, from January to July 2017. Hospitalized PLWHA aged ≥ 18 years with cerebral toxoplasmosis were consecutively enrolled. A standardized neurological examination was performed at admission and weekly until discharge or death. Diagnosis and treatment followed institutional routines; neuroradiology, molecular diagnosis, neurosurgery, and the intensive care unit (ICU) were available. The main outcomes were neurological coinfections and in-hospital death. We included 44 (4.3%) cases among 1,032 hospitalized patients. The median age was 44 (interquartile range [IQR]: 35-50) years, and 50% (n = 22) of the patients were male. The median CD4+ T lymphocyte count was of 50 (IQR: 15-94) cells/mm3. Multiple lesions on computed tomography were present in 59% of the cases. Neurological coinfections were diagnosed in 20% (n = 9) of the cases, and cytomegalovirus was the most common etiology (encephalitis: n = 3; polyradiculopathy: n = 2). Longer hospital stays (30 versus 62 days; p = 0.021) and a higher rate of ICU admissions (14% versus 44%; p = 0.045) were observed among PLWHA with neurological coinfections in comparison to those without them. The rate of in-hospital mortality was of 13.6% (n = 6) (coinfection group: 33%; no coinfection group: 8.6%; p = 0.054). Neurological c-infections were common among PLWHA with cerebral toxoplasmosis, and cytomegalovirus was the main copathogen. The group of PLWHA with neurological co-infections underwent longer hospital stays and more frequent intensive care unit admissions. Additionally, this group of patients tended to have higher in-hospital mortality rate.

Assessment of excessive daytime sleepiness in cirrhotic patients

Background. It is known that alterations of the sleep-wake cycle are present from the early stages of hepatic encephalopathy (starting with grade I on the West Haven criteria). However, minimal hepatic encephalopathy (which is not included in the West Haven criteria) defines the earliest form of HE, with no obvious clinical manifestations, but with subtle alterations in cognitive domains such as attention, visuo-spatial perception, psychomotor speed and response inhibition. Aim. To determine if liver cirrhosis in otherwise asymptomatic individuals (without clinically manifest hepatic encephalopathy) is associated with an increased risk of altered sleep rhythm or excessive daytime sleepiness. Additionally, to determine if this risk is correlated with liver disease severity or other clinical and biological parameters. Material and methods. Cross-sectional study involving 25 adult patients with liver cirrhosis. Patients were evaluated through a standard neurological examination and with the Epworth Sleepiness Scale. Liver disease severity was measured using the MELD and Child-Pugh scores. Blood ammonia levels were also measured. Results. Mean age of the patients was 50±12 years-old. There was a predominance of males (68%, n=17). Mean MELD score was 17±7 points. Mean Child-Pugh score was 8±2 points. Mean blood ammonia level was 34±17 μg/dL. Subjective daytime somnolence was reported by 24% of patients (n=6). Mean ESS score was 6±5 points. No correlation was noted between the ESS scores and liver disease severity as measured by the Child-Pugh and MELD scores. Only three patients (12%) scored over 10 points on the ESS (none of them obese) and were consequently diagnosed with excessive daytime sleepiness (EDS). This proportion falls into the accepted prevalence of EDS in the general population. Conclusions. In our study, liver cirrhosis was not associated with a higher prevalence of excessive daytime sleepiness than in the general population.

Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients

Background: Cognitive decline is inadequately captured by the standard neurological examination. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are biomarkers of neuronal damage and astrocytic reactivity that may offer an accessible measure of the multiple sclerosis (MS) pathology linked to cognitive decline. Objective: To investigate the association of sNfL and sGFAP with cognitive decline in MS patients at high risk for progressive pathology. Methods: We included 94 MS patients with sustained Expanded Disability Status Score (EDSS) ⩾ 3, available serum samples and cognitive assessment performed by symbol digit modalities test (SDMT) over a median of 3.1 years. The visit for sGFAP/sNfL quantification was at confirmed EDSS ⩾ 3. Linear regression analysis on log-transformed sGFAP/sNfL assessed the association with current and future SDMT. Analyses were adjusted for age, sex, EDSS, treatment group, and recent relapse. Results: sNfL was significantly associated with concurrent SDMT (adjusted change in mean SDMT = −4.5; 95% confidence interval (CI): −8.7, −0.2; p = 0.039) and predicted decline in SDMT (adjusted change in slope: −1.14; 95% CI: −1.83, −0.44; p = 0.001), particularly in active patients. sGFAP was not associated with concurrent or future SDMT. Conclusions: Higher levels of sNfL were associated with cognitive impairment and predicted cognitive decline in MS patients at high risk for having an underlying progressive pathology.

Neurological soft signs in adolescents are associated with brain structure.

Neurological soft signs (NSS) are minor deviations in motor performance. During childhood and adolescence, NSS are examined for functional motor phenotyping to describe development, to screen for comorbidities, and to identify developmental vulnerabilities. Here, we investigate underlying brain structure alterations in association with NSS in physically trained adolescents. Male adolescent athletes (n = 136, 13-16 years) underwent a standardized neurological examination including 28 tests grouped into 6 functional clusters. Non-optimal performance in at least 1 cluster was rated as NSS (NSS+ group). Participants underwent T1- and diffusion-weighted magnetic resonance imaging. Cortical volume, thickness, and local gyrification were calculated using Freesurfer. Measures of white matter microstructure (Free-water (FW), FW-corrected fractional anisotropy (FAt), axial and radial diffusivity (ADt, RDt)) were calculated using tract-based spatial statistics. General linear models with age and handedness as covariates were applied to assess differences between NSS+ and NSS- group. We found higher gyrification in a large cluster spanning the left superior frontal and parietal areas, and widespread lower FAt and higher RDt compared with the NSS- group. This study shows that NSS in adolescents are associated with brain structure alterations. Underlying mechanisms may include alterations in synaptic pruning and axon myelination, which are hallmark processes of brain maturation.

Inflammation-Related microRNAs-146a and -155 Are Upregulated in Mild Cognitive Impairment Subjects Among Older Age Population in Montenegro.

Pathological and clinical features of Alzheimer's disease (AD) are in temporal discrepancy and currently accepted clinical tests provide the diagnosis decades after the initial pathophysiological events. In order to enable a more timely detection of AD, research efforts are directed to identification of biomarkers of the early symptomatic stage. Neuroinflammatory signaling pathways and inflammation-related microRNAs (miRNAs) could possibly have a crucial role in AD, making them promising potential biomarkers. We examined the expression of circulatory miRNAs with a documented role in AD pathophysiology: miR-29a/b, miR-101, miR-125b, miR-146a, and miR-155 in the plasma of AD patients (AD, n = 12), people with mild cognitive impairment (MCI, n = 9), and normocognitive group (CTRL, n = 18). We hypothesized that these miRNA expression levels could correlate with the level of participants' cognitive decline. The study participants completed the standardized interview, neurological examination, neuropsychological assessment, and biochemical analyses. miRNA expression levels were assessed by RT-PCR. Neurological and laboratory findings could not account for MCI, but miR-146a and -155 were upregulated in the MCI group compared to the control. miR-146a, known to mediate early neuroinflammatory AD events, was also upregulated in the MCI compared to AD group. ROC curve analysis for miRNA-146a showed 77.8% sensitivity and 94.4% specificity and 66.7% sensitivity and 88.9% specificity for miR-155. Determination of circulatory inflamma-miRs-146a and -155 expression, together with neuropsychological screening, could become a non-invasive tool for detecting individuals with an increased risk for AD, but research on a larger cohort is warranted.

Prevalence of Dementia and Main Subtypes in Mexico: The Study on Aging and Dementia in Mexico (SADEM).

Dementia is a priority public health issue due to its high prevalence worldwide and its economic, social, and health impact. However, there are few reports in Mexico based on formal tests and with a clinical approach based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). This study estimates the prevalence of the main types of dementia among elderly people living in the community in Mexico City. A population-based, two-step study was conducted, including 6,204 elderly individuals aged 60 or above with in-home assessment. All participants were screened for cognitive impairment; those who presented some cognitive problem underwent a standardized neurological examination. Each diagnosis was based on the criteria for dementia in the DSM-5, and the final consensus diagnosis of dementia was determined by an expert panel. The global estimated prevalence of dementia in the Mexican population was 7.8% met the criteria for Alzheimer's disease, 4.3% for vascular dementia, and 2.1% for mixed dementia. The prevalence of dementia was higher in women than in men (15.3% versus 12.5%, respectively). These results provide evidence to propose strategies for Latin American countries where dementia represents a challenge due to the heterogeneity of the populations and socioeconomic disparities, requiring early diagnosis and at the first levels of care.

Eye movement disorders in inborn errors of metabolism: A quantitative analysis of 37 patients.

Inborn errors of metabolism are genetic disorders that need to be recognized as early as possible because treatment may be available. In late‐onset forms, core symptoms are movement disorders, psychiatric symptoms, and cognitive impairment. Eye movement disorders are considered to be frequent too, although specific knowledge is lacking. We describe and analyze eye movements in patients with an inborn error of metabolism, and see whether they can serve as an additional clue in the diagnosis of particularly late‐onset inborn errors of metabolism. Demographics, disease characteristics, and treatment data were collected. All patients underwent a standardized videotaped neurological examination and a video‐oculography. Videos are included. We included 37 patients with 15 different inborn errors of metabolism, including 18 patients with a late‐onset form. With the exception of vertical supranuclear gaze palsy in Niemann‐Pick type C and external ophthalmolplegia in Kearns‐Sayre syndrome, no relation was found between the type of eye movement disorder and the underlying metabolic disorder. Movement disorders were present in 29 patients (78%), psychiatric symptoms in 14 (38%), and cognitive deficits in 26 patients (70%). In 87% of the patients with late‐onset disease, eye movement disorders were combined with one or more of these core symptoms. To conclude, eye movement disorders are present in different types of inborn errors of metabolism, but are often not specific to the underlying disorder. However, the combination of eye movement disorders with movement disorders, psychiatric symptoms, or cognitive deficits can serve as a diagnostic clue for an underlying late‐onset inborn error of metabolism.

Clinical assessment of patients with chronic disorders of consciousness by different medical specialists

Introduction. Clinical assessment of consciousness in patients coming out of a coma remains a topic of discussion. Monitoring these patients over time is challenging not only because of the slow fluctuations in their neurological status, but also because doctors are not fully aware of the classification of chronic disorders of consciousness (CDC), and how to use the Coma Recovery Scale-revised (CRS-R), which was specifically developed for this group of patients. In practice, most doctors use standard neurological examination to assess consciousness rather than the CRS-R. We have hypothesized that this approach leads to contradictory and poorly standardized results. Materials and methods. We investigated the level of inter-expert reliability in pairs of three medical specialists: neurologists, neurosurgeons and neurocritical care specialists (working in neurocritical care units) in the clinical assessment of consciousness. Their examination findings were compared to the CRS-R scores. Results. The inter-expert reliability was poor in all three specializations when using clinical examination to determine the degree of impaired consciousness in patients with CDC. An average level of IER (Cohen's kappa = 0.46) was found only in the neurosurgeonCRS-R pair. Conclusion. A scale with detailed criteria is different to a standard clinical examination and has a higher level of IER. Moving from subjective evaluation to a standardized CRS-R will enable medical specialists to determine a patients rehabilitation potential and predict disease progression more accurately. Educational programmes, including virtual platforms, should be developed to encompass most of the medical community.

Differences in the Distribution of the General Movements Classification Between Neonatal Risk Groups in the Children's Hospital Zurich: An Observational Study

Neonatal infants are at increased risk for motor development disorders. To compare General Movements (GMs) classification between three neonatal risk groups, correlate the GMs Assessment (GMA) with a standardized developmental neurological examination (SDNE) and determine risk factors for abnormal GMs. Monocentric observational study with three risk groups (children with operated congenital heart disease (CHD) n=26, with operated congenital gastrointestinal malformations (CGM) n=17 and with fetal operated myelomeningocele (MMC) n=12 who underwent inpatient video-based examination. GMA was evaluated according to Hadders-Algra classification and divided into 4 categories: normal optimal (NO), normal suboptimal (NS), mildly abnormal (MA), definitely abnormal (DA). The distribution was as follows: CHD 80.8% NS, 19.2% MA, CGM 5.9% NO, 64.7% NS, 29.4% MA, MMC upper extremities 100% NS, lower extremities 33.3% NS, 33.3% MA and 33.3% DA (group comparison Kruskal-Wallis 10.729, p=0.003). GMA correlated significantly with SDNE (Spearman r s=0.869, p<0.001). Binary logistic regression analysis showed that only gestational age (Chi2=11.93, p<0.001) correlated with abnormal GMs. The majority of children showed normal GMs. Children with MMC and those with lower gestational age showed an increased risk of abnormal GMs. The GMA and SDNE represent complementary "bedside tools" to detect early motor abnormalities.

Review of the Role of Intraoperative Neurophysiological Monitoring in Spinal Surgery With a Focus on the True and False Positives and a Clinical Correlation.

Spinal surgery is a technically challenging endeavor with potentially devastating complications. Intraoperative neurophysiological monitoring (IONM) is a method of preventing and identifying damage to the spinal cord. The aim of our study was to examine the clinical utility of IONM in spinal surgeries performed at our institution and what effect, if any, subsequent interventions had on postoperative patient outcomes. This is a retrospective cohort study of 169 patients who underwent spinal surgery with IONM at 2 institutions between 2013 and 2018. Signal changes detected were recorded as well as the surgeon's response to these changes. Neurological status was recorded using a standard neurological examination and characterized as per the McCormick Neurological Scale. Patients were followed up for 12 months after surgery. A total of 169 spinal surgery cases with concurrent use of spinal cord monitoring were carried out in our institution between 2013 and 2018. The youngest patient was 14 years old, and the oldest was 92 years old (mean, 51.9 ± 19.6 years). There were 100 female patients and 69 male patients. Most patients (n = 124) had no signal changes. Signal changes were observed in 26.6% of the cases (n = 45). Most of these signal changes were rectified through repositioning of the patient (n = 24). The other 21 patients saw no improvement in their signals before the end of their procedures; however, these 21 patients had no postoperative deficits (grade I). This brought the false positive rate to 38% (21/55); the false negative rate was 1.8% (3/169). This study showed similar outcomes in patients whether IONM signals were recovered or not. The false positive and false negative rates were high. Our study helps to raise awareness about IONM's strengths and weaknesses to inform future clinical practice. We recommend prioritizing clinical judgment in spinal surgery cases and using IONM with caution.

The Phenomenology of Primary Orthostatic Tremor.

ABSTRACTBackgroundThe presence and prevalence of several neurological signs in patients with primary orthostatic tremor have not been systematically studied.ObjectivesTo assess the prevalence of clinical features of primary orthostatic tremor.MethodsVideo‐based assessment by four raters of standardized neurological examination of 11 patients with primary orthostatic tremor.ResultsOn standing, bent knees (7/11), hem sign (6/10), and a broad base of support (6/11) were the three most prevalent signs. Examination of gait revealed abnormal tandem gait (9/11) and bent knees (6/11) as the most prevalent clinical signs. In the arms, none of the patients displayed bradykinesia, ataxia, or dystonia. In the legs, ataxia was absent in all patients and bradykinesia was present in only one patient.ConclusionsAbnormal tandem gait, bent knees, hem sign, and broad base on standing are the most prevalent clinical signs in primary orthostatic tremor. We did not encounter clear extrapyramidal or unequivocal cerebellar signs.

Clinical evaluation versus magnetic resonance imaging findings in patients with radicular arm pain-A pragmatic study.

ObjectivesCervical nerve root compression can lead to radiculopathy in the arm. Some studies have reported low accuracy in determining the responsible nerve root in both cervical and lumbar regions. This prospective, observational, pragmatic study aimed to determine the accuracy of the clinical evaluation relative to magnetic resonance imaging (MRI) findings in patients with arm radiculopathy.MethodsPatients with neck pain and neck‐related arm pain referred to a spine unit underwent a standard clinical neurological examination and cervical spine MRI. The clinical examination required a judgment of the most likely cervical root involved, including the side. The Interobserver reproducibility was tested. Using MRI, the most likely nerve root involved according to radiology was assessed.ResultsEighty‐three patients met the inclusion criteria. The Interobserver reproducibility between clinical evaluators was 58%, with a modest κ coefficient (0.33, 95% confidence interval [CI]: 0.18–0.47) classified only as "fair agreement.” Only 31% (95% CI: 22–42) of the 83 patients exhibited full agreement regarding the suspected cervical root as assessed via the clinical evaluation and MRI. In another 28% (95% CI: 18–39), the clinical evaluation identified an adjacent level to that identified on MRI.ConclusionsIn cervical radiculopathy, the clinical‐neurological examination diagnosed the same in 31% or an adjacent cervical root in 28% of the patients in relation to the most affected cervical root on MRI.

IDF21-0671 Identification of neurophysiological abnormalities in nerve in patients with type 1 diabetes

Background: The progression of neuropathy is a continuum from subclinical neuropathy detectable with electrophysiological tests to clinically evident one recognizable on neurological examination. Although there has been considerable research of peripheral neuropathy in type 1 diabetes, still there is controversy regarding the pattern of nerve involvement in diabetic neuropathy. Detection of the pattern of nerve involvement can help to establish a protocol for screening of diabetic peripheral neuropathy (DPN) in its subclinical stage. Aim: The aim of this study was to describe the pattern of nerve involvement in type 1 diabetic patients with subclinical neuropathy using nerve conduction studies. Method: 65 patients with type 1 diabetes, ages from 18 to 55 years, and 34 controls without diabetes matched to the patient group were included into the study. All patients and controls underwent a standard neurological examination (NSS and NDS (the variant used in Belarus) score) and bilateral nerve conduction study (NCS) of the sensory and motor lower limb nerves using NeuroSoft machine. Interpretation of the results was based on the following normal reference ranges: n. Peroneus superficialis A> 10μV, v> 45 m/s; n Suralis A> 5 μV, v> 45 m / s; n Peroneus profundus A> 3mV, v> 40 m/s; n Tibialis A> 3.5mV, v> 40m/s. Data was analysed using IBM SPSS statistics v 20.0. Results: Clinically evident DPN was detected in 14 patients with type 1 diabetes from 65 examined. The use of NCS allowed to identify the subclinical stage of polyneuropathy (abnormalities in at least two of the electrophysiological parameters) additionally in 35 patients who had no symptoms and clinical signs of DPN. In all the patients of the control group, the NCS parameters were in the reference range. Regarding abnormal NCS parameters in patients with subclinical diabetic neuropathy (conduction velocity vs. amplitude of the compound action potential), amplitudes reduction for the n. Peroneus superficialis and n. Peroneus profundus predominated. Median of the amplitude for n. Peroneus superficialis in patients with subclinical diabetic polyneuropathy was 7.22 [5.25; 8.54] μV vs. 12.4 [10.57; 16.2] μV in the control group, p <0.001; for n. Peroneus profundus 2.21 [1.68; 2.68]mV vs. 3.15 [3.04; 3.42]mV in the control group, p <0.001. Significant differences in the amplitudes for n.Suralis and n.Tibialis has not been identified. Nerve conduction velocity (NCV) in both groups – in patients with the subclinical diabetic polyneuropathy and the control group – was within the reference range. However, the medians of NCV for n. Suralis and n. Tibialis were significantly lower in the group of patients with neuropathy compared with the controls – 47.08 [44.35; 50.13]m/s vs. 51.3 [47.6; 59.05]m/s, p = 0.025 and 44.8 [42.15; 48.2]m/s vs. 49.35 [48.30; 53.45]m/s, p = 0.004, respectively. Conclusion: In patients with type 1 diabetes with a subclinical stage of diabetic polyneuropathy the most frequent neurophysiological abnormalities were reduced amplitudes (the axonal damage) for sensory and motor fibers of n. Peroneus.

Diffusion restriction in the corticospinal tract and the corpus callosum of term neonates with hypoxic-ischemic encephalopathy.

Diffusion-weighted imaging performed shortly after brain injury has been shown to facilitate visualization of acute corticospinal tract injury known as "pre-Wallerian degeneration." The aim of this study was to determine whether diffusion restriction in the corticospinal tract and corpus callosum occurs within the first 2weeks after birth in neonates with neonatal hypoxic-ischemic encephalopathy. We enrolled a consecutive series of 66 infants diagnosed with hypoxic-ischemic encephalopathy who underwent MRI. We evaluated diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values to assess the presence of restricted diffusion in the corticospinal tract and corpus callosum. Next, we compared ADC values in the corticospinal tract and in the splenium and genu of the corpus callosum of infants with abnormal pattern on MRI with those of control infants, who showed a normal pattern on MRI. We attempted to follow all infants with hypoxic-ischemic encephalopathy until 18months of age and assess them using a standardized neurologic examination. After exclusions, we recruited 25 infants with abnormal MRI and 20 with normal MRI (controls). Among these 45 neonates, pre-Wallerian degeneration was visualized in the corticospinal tract in 10 neonates and in the corpus callosum in 12. The ADC values in the corticospinal tract in the first week were significantly lower than they were in the second week. Infants with pre-Wallerian degeneration in the corticospinal tract showed an unfavorable outcome. Pre-Wallerian degeneration was visualized in the corticospinal tract and corpus callosum and was associated with extensive brain injury caused by hypoxic-ischemic encephalopathy. The changes in signal were observed to evolve over time within the first 2weeks. The clinical outcome of infants having pre-Wallerian degeneration in the corticospinal tract was unfavorable.

Hypoxic Ischemic Encephalopathy (HIE) in Term and Preterm Infants.

Hypoxic-ischemic syndrome (HIS) and Hypoxic-ischemic encephalopathy (HIE) are conditions that affect term and premature babies, with different pathophysiology and different brain disorders. HIE appears in 1-6 / 1000 live births and 26/1000 live births in developing countries. 15-20% die in the early neonatal period, while surviving babies have severe neurological impairment, including cerebral palsy, epilepsy, visual and hearing impairment, cognitive impairment, intellectual, behavioural, and social disorders. The hypoxic-ischemic event occurs before, during or after birth. The reasons may be related to the mother, the way of birth, the placenta, and the newborn. The criteria for diagnosis of HIE include a combination of perinatal factors, the need for resuscitation, standard neurological examinations, neurophysiological monitoring, neuroimaging methods and biochemical markers. The most effective treatment for HIE is hypothermia in combination with pharmacological therapy. HIE and HIS are problem that still persist in developing countries due to inadequate obstetric care, neonatal resuscitation, and hypothermia. Current and emerging research for HIE examines new markers for early recognition, treatment, and appropriate neuroprotection of high-risk term and premature infants.

Modified Sensory Testing in Non-verbal Patients Receiving Novel Intrathecal Therapies for Neurological Disorders.

Several neurological disorders may be amenable to treatment with gene-targeting therapies such as antisense oligonucleotides (ASOs) or viral vector-based gene therapy. The US FDA has approved several of these treatments; many others are in clinical trials. Preclinical toxicity studies of ASO candidates have identified dose-dependent neurotoxicity patterns. These include degeneration of dorsal root ganglia, the cell bodies of peripheral sensory neurons. Quantitative sensory testing (QST) refers to a series of standardized mechanical and/or thermal measures that complement clinical neurologic examination in detecting sensory dysfunction. QST primarily relies on patient self-report or task performance (i.e., button-pushing). This brief report illustrates individualized pragmatic approaches to QST in non-verbal subjects receiving early phase investigational intrathecal drug therapies as a component of clinical trial safety protocols. Three children with neurodevelopmental disorders that include Neuronal Ceroid Lipofuscinosis Type 7, Ataxia-Telangiectasia, and Epilepsy of Infancy with Migrating Focal Seizures are presented. These case studies discuss individualized testing protocols, accounting for disease presentation, cognitive and motor function. We outline specific considerations for developing assessments for detecting changes in sensory processing in diverse patient groups and safety monitoring trials of early phase investigational intrathecal drug therapies. QST may complement information obtained from the standard neurologic examination, electrophysiologic studies, skin biopsies, and imaging. QST has limitations and challenges, especially in non-verbal subjects, as shown in the three cases discussed in this report. Future directions call for collaborative efforts to generate sensory datasets and share data registries in the pediatric neurology field.