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Background: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies. Objective: In this study, we performed a Delphi consensus exercise to identify the key screening tests to inform the development of a digital neurological examination tool for epidemiological research. Methods: Twelve panellists (six experts in neurological examination, five experts in data collection—two were also experts in the neurological examination, and three experts in participant experience) of different nationalities joined the Delphi exercise. Experts in the neurological examination provided a selection of items that allow ruling out neurological impairment and can be performed by trained health workers. The items were then rated by them and other experts in terms of their feasibility and acceptability. Results: Ten tests and seven anamnestic questions were included in the final set of screening items for the digital neurological examination. Three tests and five anamnestic questions were excluded from the final selection due to their low ratings on feasibility. Conclusion: This work identifies the key feasible and acceptable screening tests and anamnestic questions to build an electronic tool for performing the neurological examination, in the absence of a neurologist. [ABSTRACT FROM AUTHOR]

Background: Identifying the cause of non-traumatic coma in the emergency department is challenging. The clinical neurological examination is the most readily available tool to detect focal neurological deficits as indicators for cerebral causes of coma. Previously proposed clinical pathways have granted the interpretation of clinical findings a pivotal role in the diagnostic work-up. We aimed to identify the actual diagnostic reliability of the neurological examination with regard to identifying acute brain damage. Methods: Eight hundred and fifty-three patients with coma of unknown etiology (CUE) were examined neurologically in the emergency department following a predefined routine. Coma-explaining pathologies were identified retrospectively and grouped into primary brain pathology with proof of acute brain damage and other causes without proof of acute structural pathology. Sensitivity, specificity and percentage of correct predictions of different examination protocols were calculated using contingency tables and binary logistic regression models. Results: The full neurological examination was 74% sensitive and 60% specific to detect acute structural brain damage underlying CUE. Sensitivity and specificity were higher in non-sedated patients (87/61%) compared to sedated patients (64%/59%). A shortened four-item examination protocol focusing on pupils, gaze and pyramidal tract signs was only slightly less sensitive (67%) and more specific (65%). Conclusions: Due to limited diagnostic reliability of the physical examination, the absence of focal neurological signs in acutely comatose patients should not defer from a complete work-up including brain imaging. In an emergency, a concise neurological examination should thus serve as one part of a multimodal diagnostic approach to CUE. [ABSTRACT FROM AUTHOR]

Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 ± 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance. [ABSTRACT FROM AUTHOR]

Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) predicts poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and available in most hospitals, it is worthwhile to know how neurological signs are associated with SEP results. The aim of this study was to investigate whether specific clinical neurological signs are associated with either an absent or a present median nerve SEP in patients after CPR. Data from the previously published multicenter prospective cohort study PROPAC (prognosis in postanoxic coma, 2000-2003) were used. Neurological examination, consisting of Glasgow Coma Score (GCS) and brain stem reflexes, and SEP were performed 24, 48, and 72 h after CPR. Positive predictive values for predicting absent and present SEP, as well as diagnostic accuracy were calculated. Data of 407 patients were included. Of the 781 SEPs performed, N20 s were present in 401, bilaterally absent in 299, and 81 SEPs were technically undeterminable. The highest positive predictive values (0.63-0.91) for an absent SEP were found for absent pupillary light responses. The highest positive predictive values (0.71-0.83) for a present SEP were found for motor scores of withdrawal to painful stimuli or better. Multivariate analyses showed a fair diagnostic accuracy (0.78) for neurological examination in predicting an absent or present SEP at 48 or 72 h after CPR. This study shows that neurological examination cannot reliably predict absent or present cortical N20 responses in median nerve SEPs in patients after CPR. [ABSTRACT FROM AUTHOR]

The article reports on the case of a 58-year-old woman who suffered from muscle pain in particular of the femoral muscles after exercise. Outcomes of ultrasound examination indicated an echolucent and echogenic thickening of the vessel wall in the right vertebral artery. It also revealed that were no signs of atherosclerosis. The case demonstrates the close temporal relationship of a cervical artery dissection to a trivial mechanical trauma.

Background: We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. Materials and methods: We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. Results: 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. Conclusions: Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS. [ABSTRACT FROM AUTHOR]

Objectives: Neurological symptoms associated with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccination were discovered in the context of billions of administered vaccine doses. The clinical manifestations often resemble post Coronavirus Disease 2019 (post-COVID-19) syndrome (PCS) features and may be considered as post-COVID-19 vaccine syndrome (PVS). Data regarding frequency, severity and pathophysiological mechanisms are scarce. Methods: We assessed routine clinical examinations in 50 patients reporting new-onset neurological symptoms after SARS-CoV-2 vaccination, including neurological examination, laboratory and electrophysiology tests, as well as self-report questionnaires measuring fatigue, depressive symptoms, anxiety, risk of somatic symptom disorder, and health-related quality of life. Patients were included when symptoms occurred after confirmed COVID-19 vaccination and without prior SARS-CoV-2 infection, and if no alternative diagnosis was found to explain the symptoms. Results: The most frequently reported symptoms were paraesthesia (56%), fatigue (46%) and cognitive impairment (36%). Neurological, routine laboratory, and electrophysiological examinations did not yield distinct pathological findings. Neuropsychological testing of a subgroup revealed deficits in attention, executive function and memory. Discussion: The spectrum of clinical manifestations post-vaccination poses a substantial overlap with PCS symptoms. As no pathological findings were obtained in routine diagnostics, uncertainty remains about the underlying pathophysiological mechanisms and requires further investigation beyond routine work-up. [ABSTRACT FROM AUTHOR]

In addition, 2 (13.3%) patients presented with minimal muscle weakness at neurological examination: patient V:14 showing mild (MRC 4/5) distal and neck flexor muscle weakness since the age of 32 years and patient IV:19 displaying minimal (MRC 4.5/5) weakness of left foot dorsiflexion, at the age of 53 years. Although remarkable distal muscle weakness was detected in 13/15 patients, relevant scapular and/or pelvic muscle weakness was observed in around 60% of the cases during the disease course. This disease is characterized by adult presentation between the fourth and the seventh decade of life with distal lower and less frequently upper limb muscle weakness in most of the cases, suggesting that I PLIN4 i gene expansion should be investigated in all patients presenting a distal myopathy, particularly in those showing rimmed vacuoles at muscle biopsy. We included 15 affected patients presenting, at mean age of 46.1 ± 10.1 years (range 30-66), with lower and/or upper limb distal muscle weakness in 12/14 (85.7%) of them, mostly in lower limbs; only 2/14 (14.3%) patients reported scapular or pelvic weakness at onset, respectively. [Extracted from the article]

Simple clinical scores to predict large vessel occlusion (LVO) in acute ischemic stroke would be helpful to triage patients in the prehospital phase. We assessed the ability of various combinations of National Institutes of Health Stroke Scale (NIHSS) subitems and published stroke scales (i.e., RACE scale, 3I-SS, sNIHSS-8, sNIHSS-5, sNIHSS-1, mNIHSS, a-NIHSS items profiles A-E, CPSS1, CPSS2, and CPSSS) to predict LVO on CT or MR arteriography in 1085 consecutive patients (39.4 % women, mean age 67.7 years) with anterior circulation strokes within 6 h of symptom onset. 657 patients (61 %) had an occlusion of the internal carotid artery or the M1/M2 segment of the middle cerebral artery. Best cut-off value of the total NIHSS score to predict LVO was 7 (PPV 84.2 %, sensitivity 81.0 %, specificity 76.6 %, NPV 72.4 %, ACC 79.3 %). Receiver operating characteristic curves of various combinations of NIHSS subitems and published scores were equally or less predictive to show LVO than the total NIHSS score. At intersection of sensitivity and specificity curves in all scores, at least 1/5 of patients with LVO were missed. Best odds ratios for LVO among NIHSS subitems were best gaze (9.6, 95 %-CI 6.765-13.632), visual fields (7.0, 95 %-CI 3.981-12.370), motor arms (7.6, 95 %-CI 5.589-10.204), and aphasia/neglect (7.1, 95 %-CI 5.352-9.492). There is a significant correlation between clinical scores based on the NIHSS score and LVO on arteriography. However, if clinically relevant thresholds are applied to the scores, a sizable number of LVOs are missed. Therefore, clinical scores cannot replace vessel imaging. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment in people with MS (PwMS) has primarily been investigated using conventional imaging markers or fluid biomarkers of neurodegeneration separately. However, the single use of these markers do only partially explain the large heterogeneity found in PwMS. Objective: To investigate the use of multimodal (bio)markers: i.e., serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and conventional imaging markers in predicting cognitive functioning in PwMS. Methods: Eighty-two PwMS (56 females, disease duration = 14 ± 9 years) underwent neuropsychological and neurological examination, structural magnetic resonance imaging, blood sampling and lumbar puncture. PwMS were classified as cognitively impaired (CI) if scoring ≥ 1.5SD below normative scores on ≥ 20% of test scores. Otherwise, PwMS were defined as cognitively preserved (CP). Association between fluid and imaging (bio)markers were investigated, as well as binary logistics regression to predict cognitive status. Finally, a multimodal marker was calculated using statistically important predictors of cognitive status. Results: Only higher NfL levels (in serum and CSF) correlated with worse processing speed (r = − 0.286, p = 0.012 and r = − 0.364, p = 0.007, respectively). sNfL added unique variance in the prediction of cognitive status on top of grey matter volume (NGMV), p = 0.002). A multimodal marker of NGMV and sNfL yielded most promising results in predicting cognitive status (sensitivity = 85%, specificity = 58%). Conclusion: Fluid and imaging (bio)markers reflect different aspects of neurodegeneration and cannot be used interchangeably as markers for cognitive functioning in PwMS. The use of a multimodal marker, i.e., the combination of grey matter volume and sNfL, seems most promising for detecting cognitive deficits in MS. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a 32-year-old woman with coeliac disease, who was diagnosed with worsening visual evoked responses (VER) and positive aquaporin-4 antibodies.

Objective: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. Methods: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. Results: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081–21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. Conclusions: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis. [ABSTRACT FROM AUTHOR]

Background: Disease and treatment-associated immune system abnormalities may confer higher risk of Coronavirus disease 2019 (COVID-19) to people with multiple sclerosis (PwMS). We assessed modifiable risk factors associated with COVID-19 in PwMS. Methods: Among patients referring to our MS Center, we retrospectively collected epidemiological, clinical and laboratory data of PwMS with confirmed COVID-19 between March 2020 and March 2021 (MS-COVID, n = 149). We pursued a 1:2 matching of a control group by collecting data of PwMS without history of previous COVID-19 (MS-NCOVID, n = 292). MS-COVID and MS-NCOVID were matched for age, expanded disability status scale (EDSS) and line of treatment. We compared neurological examination, premorbid vitamin D levels, anthropometric variables, life-style habits, working activity, and living environment between the two groups. Logistic regression and Bayesian network analyses were used to evaluate the association with COVID-19. Results: MS-COVID and MS-NCOVID were similar in terms of age, sex, disease duration, EDSS, clinical phenotype and treatment. At multiple logistic regression, higher levels of vitamin D (OR 0.93, p < 0.0001) and active smoking status (OR 0.27, p < 0.0001) emerged as protective factors against COVID-19. In contrast, higher number of cohabitants (OR 1.26, p = 0.02) and works requiring direct external contact (OR 2.61, p = 0.0002) or in the healthcare sector (OR 3.73, p = 0.0019) resulted risk factors for COVID-19. Bayesian network analysis showed that patients working in the healthcare sector, and therefore exposed to increased risk of COVID-19, were usually non-smokers, possibly explaining the protective association between active smoking and COVID-19. Conclusions: Higher Vitamin D levels and teleworking may prevent unnecessary risk of infection in PwMS. [ABSTRACT FROM AUTHOR]

Background: There is no evidence-based therapy for non-arteritic central retinal artery occlusion (NA-CRAO). Intravenous thrombolysis (IVT) with alteplase in a time window < 4.5 h may lead to a favorable outcome. Purpose of this study was to investigate the feasibility, efficacy and safety of IVT in patients classified as functionally blind. Methods: We conducted a retrospective observational study of NA-CRAO-patients. All patients underwent an ophthalmological and neurological examination including cerebral magnetic resonance imaging (MRI) for assessment of additional stroke lesions. Patients were treated either conservatively or with IVT within 4.5 h. Visual acuity (VA) was evaluated in logMAR and a categorical analysis was performed. Results: Thirty-seven patients were included in the study, 21 patients in the conservative treatment group (CTG) and 16 patients in the IVT group. The median logMAR visual acuity at admission and discharge was similar in both groups. The medium symptom to treatment time in the IVT group was 158.0 min. 3 patients (19%) of the IVT group showed a favorable outcome, all CTG patients remained at the level of functional blindness. No serious adverse events were observed after IVT. MRI showed additional acute stroke in over one-third of the patients (n = 14). Conclusions: Early intravenous thrombolysis therapy according to the current stroke protocol n a time window up to 4.5 h after the onset of symptoms was feasible and might be a potential treatment option for NA-CRAO. Patients with NA-CRAO are at very high risk of ischemic stroke and MRI should be done in all patients for optimized treatment and secondary stroke prevention. A prospective randomized study is required. [ABSTRACT FROM AUTHOR]

2 Brain magnetic resonance imaging shows diffuse medullary and spinal atrophy (arrows) which can be seen in A, C the age of 49 and B, D age of 61 While there was no evidence of new acute brain lesions attributable to his vertigo symptoms, his vertigo could not be credited to a previous spinal cord injury. Neurological examination showed spontaneous direction-changing nystagmus, in which the duration of nystagmus in each direction was not periodic, nor was the duration of the null-point duration seen between nystagmus in each direction, which was consistent with aperiodic alternating nystagmus (right horizontal 15 s-null point 10 s-left beating nystagmus 135 s-null point 15 s-right beating nystagmus 75 s-left beating nystagmus 100 s-null point 15 s-right beating nystagmus 70 s-left beating nystagmus 70 s) (Fig. While rotatory chair tests were not performed in this patient, and caloric or video head impulse tests were within normal range, we believe that potential for combined vestibular nuclei/velocity storage disfunction likely coexists in this patient, given that both medullary and cerebellar involvement are possible in AOAD. Presuming that the patient's clinical presentation was related to trauma, MRI and electrophysiological findings were considered to be related to traumatic spinal cord injury. [Extracted from the article]

Background and objective: People with functional motor disorder (FMD) report triggers—sensory or motor-induced stimuli that exacerbate or initiate paroxysmal occurrences of their movement disorder. These are a distinct phenomenon from precipitating factors occurring at the initial onset of the disorder. We aimed to assess triggers in FMD and understand their relevance to paroxysmal variability often seen in FMD. Methods: We enrolled consecutive outpatients with a definite diagnosis of FMD. Each patient underwent a detailed clinical evaluation also including the presence of trigger factors and video-recordings both during neurological examination and physiotherapy treatment. Patients were classified as having "triggers" (T-FMD) or "not having triggers" (NoT-FMD) as well as "paroxysmal" compared to "persistent with paroxysmal variability". Results: The study sample was 100 patients (82% female) with FMD; the mean age at onset was 41 years. Triggers were observed in 88% of patients and in 65 of these the FMD was pure paroxysmal. The most common triggers were movement or physical exercise, followed by emotional, visual, touch, and auditory stimuli; 39 (44%) were isolated and 49 (56%) were combined triggers. Among the T-FMD patients, FMD were paroxysmal in 74% (n = 65) and persistent with paroxysmal variability in 26% (n = 23). The T-FMD patients were younger (p = 0.016) and had a gait disorder (p = 0.035) more frequently than the NoT-FMD patients. Discussion: Triggers are frequent in FMD and may have diverse overlapping clinical presentations. In this sample, FMD was most often paroxysmal, suggesting the value of noting triggers as clinical clues in the diagnosis and rehabilitation of FMD. [ABSTRACT FROM AUTHOR]

Background: The new essential tremor (ET)-plus nomenclature was proposed by the 2018 Tremor Consensus Criteria. However, few studies have adopted this usage and the clinical differences between ET and ET-plus remains unclear. To address this issue, we reclassified and compared the characteristics of ET and ET-plus patients in a large Chinese tremor cohort. Methods: In this cross-sectional observational study, 766 patients originally diagnosed with ET underwent neurological examination. Scale ratings were used to evaluate motor and non-motor symptoms, and quality of life (QoL). We then reclassified the ET cohort and compared demographic and clinical characteristics between ET and ET-plus patients. A logistic regression analysis was used to explore whether the presence of neurological soft signs in ET-plus was associated with tremor severity or QoL. Results: Among 665 clinically confirmed ET syndrome patients, 274 were ET and 391 were ET-plus. The most prevalent neurological soft sign was resting tremor. ET-plus patients were older, had older age at onset and longer disease duration. ET-plus patients recorded higher scores in tremor severity evaluations and lower in cognitive evaluations, whereas a higher proportion of patients presented with depression or anxiety symptoms. Resting tremor and questionable cerebellar signs were associated with tremor severity. Cognitive impairment was associated with worse QoL. Conclusions: ET-plus patients were older, had longer disease durations, worse tremor manifestations, and more distinct non-motor symptoms. Certain additional soft signs of ET-plus were associated with tremor severity or worse QoL. ET-plus patients may include advanced ET patients with additional neurological soft signs presenting along with disease progression. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. Methods: Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. Results: Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (β = 0.01, p < 0.001) and Q-albumin (β = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (β = 0.57, p = 0.014), impaired motor function (β = 0.36, p = 0.008), increasing disease activity (β = 0.04, p = 0.008), and organ damage (β = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. Conclusion: Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE. [ABSTRACT FROM AUTHOR]

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline. [ABSTRACT FROM AUTHOR]

Central and peripheral nervous system involvement during acute COVID-19 is well known. Although many patients report some subjective symptoms months after the infection, the exact incidence of neurological and cognitive sequelae of COVID-19 remains to be determined. The aim of this study is to investigate if objective neurological or cognitive impairment is detectable four months after SARS-CoV-2 infection, in a group of patients who had mild–moderate COVID-19. A cohort of 120 health care workers previously affected by COVID-19 was examined 4 months after the diagnosis by means of neurological and extensive cognitive evaluation and compared to a group of 30 health care workers who did not have COVID-19 and were similar for age and co morbidities. At 4 month follow-up, 118/120 COVID-19 cases had normal neurological examination, two patients had neurological deficits. COVID-19 patients did not show general cognitive impairment at MMSE. In COVID-19 cases the number of impaired neuropsychological tests was not significantly different from non COVID-19 cases (mean 1.69 and 1 respectively, Mann–Whitney p = n.s.), as well as all the mean tests' scores. Anxiety, stress and depression scores resulted to be significantly higher in COVID-19 than in non COVID-19 cases. The results do not support the presence of neurological deficits or cognitive impairment in this selected population of mild–moderate COVID-19 patients four months after the diagnosis. Severe emotional disorders in patients who had COVID-19 in the past are confirmed. [ABSTRACT FROM AUTHOR]

Dysarthria may be classified as flaccid, spastic, ataxic, hypokinetic, choreatic, dystonic, or mixed. We hypothesized that in routine neurological practice the reliability and accuracy of perceptual analysis alone in the classification of dysarthria is low and that this classification is mainly based on the clinical context rather than on the perception of speech. We therefore studied the accuracy and the inter- observer agreement in the classification of dysarthrias on the basis of perceptual analysis alone. Seventy two neurologists and neurological trainees classified recorded speech samples of 100 patients as flaccid, spastic, ataxic, extrapyramidal, or mixed dysarthria, or as not dysarthric. All observers were blinded to the patients’ final diagnosis, which was based on all clinical features and investigations. In the analysis the observers were arranged in eight groups of nine observers, or four paired groups with similar levels of clinical experience. Together, the observers in a given group rated all 100 recordings. The accuracy of the classification was poor (35 % were classified correctly) and the inter-observer agreement between paired groups low (κ 0.16 to 0.32). The level of experience in neurology did not have a significant influence. Neurological trainees as well as experienced neurologists have great difficulty in identifying specific types of dysarthria on the basis of perceptual analysis alone. In clinical practice this probably means that most neurologists will classify dysarthria in the context of other features from neurological examination or ancillary investigations. [ABSTRACT FROM AUTHOR]

Context Polyneuropathy is a common disease and is more prevalent (at least 3 %) in elderly people. However, routine neurological examination of healthy elderly people may show distal sensory loss and absent tendon reflexes,which can obscure the distinction from polyneuropathy. Objective To investigate the relation between age and the prevalence of distal sensory loss, absent tendon reflexes, or muscle weakness, and to ascertain above which age these neurological signs could be considered as normal in ageing. Data sources PubMed, Embase, the Cochrane Library, and Current Contents from 1960 until 2004. Reference lists of relevant studies were searched for additional studies, reviews or textbooks. Study selection studies reporting on neurological signs upon routine neurological examination in generally healthy adult persons were considered for inclusion. Two reviewers independently assessed study eligibility and performed study inclusion. Of 629 studies initially identified, 50 (8 %) met the inclusion criteria. Data extraction Two reviewers independently performed data extraction and assessed study quality based on study design and the rigour by which confounding co-morbidity was excluded. Data synthesis The 50 included studies comprised a total of 9,996 adult persons. Assuming heterogeneity between studies, the prevalence data from different studies were pooled for separate age groups with a random-effects model. In healthy persons older than 60 years the prevalence of absent vibration sense at the big toes (29 % [95 % CI 18 % to 38%]) or ankles (15 % [95 % CI 11 % to 20%]), and absent ankle reflexes (23 % [95 % CI 16 % to 30 %]) was increased. Conclusions Self-declared healthy adult persons younger than 60 years do not have neurological signs. After the age of 60 absent vibration sense at the big toes or ankles, and absent ankle reflexes are more prevalent, although the majority does not have these neurological signs. It seems more appropriate to apply different diagnostic criteria for polyneuropathy in adult persons younger and older than 60 years. [ABSTRACT FROM AUTHOR]

Objective: To explore the use of digital biomarkers to distinguish healthy controls (HC) from subjects with a radiologically isolated syndrome (RIS). Methods: We developed a smartphone application called MS Screen Test (MSST) to explore several dimensions of the neurological exam such as finger tapping speed, agility, hand synchronization, low contrast vision and cognition during a short evaluation. This app was tested on a cohort of healthy volunteers including a subset of subjects who underwent two evaluations on the same day to assess reproducibility. In a second step, the app was tested on a cohort of RIS subjects. Performances of RIS subjects were compared with age and genre-matched HC. Results: HC underwent two consecutive evaluations on MSST. The analysis showed good reproducibility for all measures. Then 21 RIS subjects were compared to 32 matched HC. Compared to HC, we found that RIS subjects had a lower finger tapping speed on the dominant hand (5.6 versus 6.5 taps per second; p = 0.005), a longer inter hand interval during the hand synchronization task (14.4 versus 11.3 ms; p = 0.03) and significantly poorer scores on the low contrast vision and cognition tests. Conclusion: MSST only requires a smartphone to obtain digital biomarkers relative to several dimensions of the neurological examination. Our results highlighted subtle differences between HC and RIS subjects. We plan to evaluate this tool in MS patients, which will allow us to get a much larger sample of subjects, to determine whether digital biomarkers can predict disease course. [ABSTRACT FROM AUTHOR]

Background: Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. Methods: Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. Results: Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. Conclusions: In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity. [ABSTRACT FROM AUTHOR]

Background: There is scarce data as to the association between physical activity and the volumes of subcortical brain regions in people with multiple sclerosis (PwMS). Objective: To compare the volumetric measures of subcortical brain structures in physically active and insufficiently active PwMS. Methods: This cross‐sectional study comprised 153 PwMS (39.3 ± 12.0 years, 68.0% female) who had undergone a complete neurological examination, computerized cognitive evaluation and brain MRI (using a high‐resolution scanner). MRI volumetric analysis was based on the FreeSurfer image analysis suite. Regions of interest included the hippocampus, amygdala, brain stem, basal ganglia, thalamus, accumbens nucleus, putamen, caudate and pallidum. Two MRI metrics, total volume (mm3) and estimated percentile of the subcortical region according to adjusted normative population, were calculated for each individual and brain region. Based on scores obtained from the Godin Leisure-Time Exercise Questionnaire, the cohort was subsequently divided into two groups, physically active (n = 77) and insufficiently active (n = 76). Results: The left hippocampus estimated percentile point significantly differentiated between active and insufficiently active PwMS (48.5 (S.D. = 32.2) vs. 36.4 (S.D. = 29.8); p = 0.004), even after controlling for disability (p = 0.011) and cognition (p = 0.021). The right hippocampal estimated percentile point was also significantly different between groups (46.7 (S.D. = 30.6) vs. 34.6 (S.D. = 30.8); p = 0.004). Subcortical volume of the right hippocampus explained 19.4% of the variance between the groups (p = 0.008), even after controlling for disability (p = 0.013) and cognition (p = 0.020). Conclusions: Our results provide evidence that PwMS who regularly participate in leisure-time physical activities maintain their hippocampal volume, regardless of their disability and cognitive capabilities. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the frequency and the clinical correlations of pseudobulbar affect (PBA) in a population-based incident cohort of ALS patients. Incident ALS cases, diagnosed in 2011 and 2012, according to El Escorial criteria were enrolled from a prospective population-based registry in Apulia, Southern Italy. Neurological status was assessed using a standard neurological examination and the revised ALS Functional Rating Scale (ALSFRSr). The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate the presence and severity of PBA. Total scores range from 7 to 35. A score ≥13 was used to identify the presence of PBA. One-hundred thirty-two sporadic incident ALS cases were enrolled. Median disease duration was 20 months (range 2-143), median onset-diagnosis interval (ODI) 12 months (range 2-131), median ALSFRSr at baseline 36/48 (range 2-47) and median ALSFRSr bulbar sub-score 10/12 (range 0-12). Neurological examination revealed presence of PBA in 34/132 patients (26 %). Pathological CNS-LS score was found in 45/132 patients (34 %). Median total CNS-LS score was 9/35 (range 7-29). The subgroup with pathological CNS-LS was characterized by a short disease duration from symptom onset, ODI, time to diffusion to a second region, time to generalization and ALSFRSr bulbar sub-score, bulbar onset, 'definite' diagnostic category, bulbar upper motor-neuron involvement and presence of PBA at neurological examination. In population-based setting, one-third of ALS patients present PBA at diagnosis. The presence of PBA is associated with bulbar UMN involvement and markers of a more severe phenotype. [ABSTRACT FROM AUTHOR]

Background: Positional manoeuvres are an important part of the neurological examination, particularly in patients with vertigo where the presence and characteristics of provoked nystagmus can help differentiate central from peripheral neurological disorders. Methods: Case series of functional positional eye and eyelid movements. Results: We report four patients with functional eye and eyelid movements provoked during positional manoeuvres. The range of abnormalities observed included positional convergence spasm, brief functional saccadic oscillations, and excessive positional blinking mimicking upbeat nystagmus. The functional movements described were present on a background of pre-existing peripheral or central nystagmus, or positional vertigo. Conclusion: Functional positional eye and eyelid movements may co-exist with organic nystagmus that renders an accurate interpretation of the manoeuvre more challenging. A thorough understanding of the clinical features that differentiate these two categories of eye/eyelid movements makes the analysis easier, thus preventing misdiagnosis and avoiding unnecessary investigations. [ABSTRACT FROM AUTHOR]

Background and purpose: Focal epilepsy of unknown cause (FEUC) is an under-investigated topic despite its remarkable frequency. We aimed to report the long-term follow-up findings along with the drug-response, 5 year remission rates and diagnostic changes to give an insight about the heterogeneous characteristics of FEUC. Methods: Demographic, clinical, neurophysiological and imaging data of 196 patients diagnosed as FEUC according to ILAE criteria, with a minimum 5-year follow-up were evaluated in a tertiary epilepsy center. The drug resistance, 5 years of remission and relapse rates were investigated and the subgroups were compared statistically. Results: The rate of drug resistance was 21.8% and status epilepticus (p < 0.001), abnormal neurological examination (p = 0.020), seizure onset before 10 years (p = 0.004) and a high initial seizure frequency (p = 0.006) were significant predictors of drug resistance. The rates of terminal 5-year remission, 5-year remission ever and relapse were 39.9%, 44.26% and 24.04%, respectively. There were 13 patients (6.6%) with a changed final diagnosis. Drug resistance (p = 0.004), pathological EEG (p = 0.034) and status epilepticus (p = 0.021) were negative variables for achieving remission. The lobar localization of seizures was not a predictor of remission or relapse. Onset after 10 years of age had a higher probability of achieving a 5-year remission according to Kaplan–Meier curves (p < 0.001). Conclusions: Focal epilepsy of unknown cause has a benign electroclinical subgroup with favorable long-term course, lower drug resistance and higher 5 years of terminal remission and remission ever rates, when appropriately treated. Our findings might be valuable in terms of counseling and management of patients with FEUC at the first referral to epilepsy clinics. [ABSTRACT FROM AUTHOR]

Background/aims: To validate the use of the Test Your Memory (TYM) test in dementias other than Alzheimer's disease, and to compare the TYM test to two other short cognitive tests. Methods: One hundred and fifty-seven patients with dementia other than typical Alzheimer's disease were recruited from a specialist memory clinic. Patients completed the TYM test, the revised Addenbrooke's Cognitive Examination (ACE-R) and Mini-Mental State Examination (MMSE), plus neurological examination, clinical diagnostics and multi-disciplinary team review. Their TYM scores were compared to age-matched controls and an Alzheimer's disease cohort. Results: Patients scored an average of 34.4/50 on the TYM test compared to 46.0/50 in age-matched controls. Using the threshold of 42/50, the TYM test detected 80% of non-Alzheimer dementias. The area under the ROC curve was 0.89 with a PPV of 0.80 and a NPV of 0.84. The TYM test performed better than the ACE-R (using the threshold of 83) which detected 69% of cases and the MMSE (using a threshold of 24) which detected only 27%. Conclusions: The TYM test is a useful test in the detection of non-Alzheimer dementia. The TYM test performs much better than the MMSE at detecting non-Alzheimer dementias. [ABSTRACT FROM AUTHOR]

Objective: To determine the optimal observation period (OBP) in adults with a clinical diagnosis of brain death (BD) using electroencephalography (EEG) or computerized tomography angiography (CTA). Methods: We conducted a retrospective observational analysis of adult patients with a diagnosis of BD from January 2000 to February 2017. The optimal OBP was defined as the minimum time interval from the first complete clinical neurological examination (CNE) that ensures that neither a second CNE nor any ancillary test (AT) performed after this period would fail to confirm BD. Results: The study sample included 447 patients. In the supratentorial group, the first AT confirmed BD in 389 cases (98%), but in 8 (2%) cases the complementary test was incongruent. In this group, 8 of 245 patients in whom the first AT was carried out within the first 2 h after a complete CNE had a non-confirmatory test of BD versus none of 152 in whom the first AT was delayed more than 2 h (3.0% vs 0.0%; p = 0.026). In the infratentorial group, we found a higher probability of obtaining a first non-confirmatory AT of BD (34% vs 2%; p = 0.0001) and an OBP greater than 32.5 h was necessary to confirm a BD diagnosis. Conclusions: We found important differences in the confirmation of BD diagnosis between primary supratentorial and infratentorial lesion, and identified an optimal OBP of 2 h in patients with supratentorial lesions. By contrast, in primary posterior fossa/infratentorial lesions, the determination of an optimal OPB remains less accurate and hence more challenging. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a B-cell-mediated disease with autoimmunity towards the astrocyte water channel aquaporin-4 (AQP-4) in the central nervous system.Objective: To assess the long-term safety and efficacy in NMOSD patients receiving maintenance therapy with B-cell-depleting agent rituximab for more than 2 years.Method: NMOSD patients were included prospectively from 2014 to 2018 and received continuous cycles of rituximab infusions biannually. Incidence of adverse events (AE), serious AEs (SAE), and infusion-related AEs were evaluated through monthly phone calls and neurological examination every 4 months.Results: A total of 44 NMOSD patients were included, of those 30 were treatment naive (68%). The mean age was 37.2 years with 79.5% females. With overall observation period of 31.6 ± 7.3 months (24-48 months), tolerability was assessed as satisfactory in most cases. We observed infusion reactions (mostly mild) in 31.8% of patients and 31.8% never experienced any AEs after a mean 5.1 cycles of rituximab therapy. Rituximab was also beneficial in terms of improvement in relapse rate (from 0.26 ± 0.54 to 0, P = 0.003) and Expanded Disability Status Scale (from 4.1 ± 1.8 to 3.1 ± 1.8, P < 0.001). Stratification according to AQP4-IgG serostatus showed no difference between groups.Conclusion: Rituximab treatment is well tolerated, safe, and efficacious with a minor risk of mild infusion reactions for NMOSD patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the frequency, clinical and radiological features, and efficacy of clinical evaluation and perfusion-weighted imaging (PWI) for the prediction of final stroke in patients with DWI/MRI-negative posterior circulation stroke (PCS) presenting acute dizziness/vertigo. From our comprehensive prospective stroke registry of acute ischemic stroke during a 7-year period, we identified 1846 consecutive patients with PCS, 850 of whom presented with acute dizziness/vertigo. Of these 850 patients, initial DWI-MRI was negative in 35 (4.1%). In these 35 patients, dizziness/vertigo was acute prolonged in 31 and recurrent transient in 4. Focal neurological signs or profound imbalance were present in 16/35 or 18/34, respectively. Spontaneous nystagmus was absent in 21/35; the HINTS protocol (head impulse, nystagmus, and test-of-skew) was not applicable to them. In 12/26 patients, PWI was positive and the same time as DWI was negative. The usual site of lesion was the lateral medulla (n = 18). Twenty-nine patients (83%) had small strokes, while 19 (54%) had large vessel strokes. The sensitivity of systematic clinical evaluation adopting neurological examination, HINTS plus, and assessment of equilibrium was 83%, for prediction of final stroke and 100% when combined with PWI. An integrated approach using systematic neurological and neuro-otological examinations combined with PWI accurately diagnoses PCS presenting with acute dizziness/vertigo. Although most patients with acute vertigo and MRI-negative PCS have small brainstem strokes, about a half have large vessel stroke with greater risk of progression requiring prompt treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze pain, both nociceptive and neuropathic, in patients with post-polio syndrome (PPS) and relate the pain to age at the initial polio infection, age at examination, to gender and disability. The study was conducted in a university hospital department. Patients with PPS were interviewed at their regular visits about pain, its character, intensity and localization. A clinical examination, including a thorough neurological examination, was performed. Data included age at time of polio infection, age at time of examination and gender. Pain intensity was measured with the VAS-scale and walking capability by the WISCI-scale. One hundred sixty-three (88 women, 75 men) patients were included in the study. Pain was present in 109 (67%). Pain was more frequently reported by women (82%) than by men (49%). 96 patients experienced nociceptive pain, 10 patients both neuropathic and nociceptive pain and three experienced pure neuropathic pain. Half of the patients with pain experienced pain in more than one body region. When neuropathic pain was present, another additional neurological disorder was diagnosed. Pain was more often found in younger patients (around 70%) than in older patients (around 50%). In summary pain is common in patients with PPS and most patients experienced nociceptive pain. Women have pain more often than men. Older patients experience pain more seldom than younger patients. Age at time of primary polio infection is important for the development of pain. When neuropathic pain is present, it is important to proceed with neurological examination to find an adequate diagnosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship between electrophysiological recordings and clinical as well as radiological findings in patients suggestive to suffer from a lumbar spinal stenosis (LSS). We hypothesise that the electrophysiological recordings, especially SSEP, indicate a lumbar nerve involvement that is complementary to the neurological examination and can provide confirmatory information in less obvious clinical cases. In a prospective cohort study, 54 patients scheduled for surgery due to LSS were enrolled in an unmasked, uncontrolled trial. All patients were assessed by neurological examination, electrophysiological recordings, and magnetic resonance imaging (MRI) of the lumbar spine. The electrophysiological recordings focused on spinal lumbar nerve involvement. About 88% suffered from a multisegmental LSS and 91% of patients respectively complained of chronic lower back pain and/or leg pain for more than 3 months, combined with a restriction in walking distance. The neurological examination revealed only a few patients with sensory and/or motor deficits while 87% of patients showed pathological electrophysiological recordings (abnormal tibial SSEP in 78% of patients, abnormal H-reflex in 52% of patients). Whereas the clinical examination, even in severe LSS, showed no specific sensory-motor deficit, the electrophysiological recordings indicated that the majority of patients had a neurogenic disorder within the lumbar spine. By the pattern of bilateral pathological tibial SSEP and pathological reflexes associated with normal peripheral nerve conduction, LSS can be separated from a demyelinating polyneuropathy and mono-radiculopathy. The applied electrophysiological recordings, especially SSEP, can confirm a neurogenic claudication due to cauda equina involvement and help to differentiate neurogenic from vascular claudication or musculo-skeletal disorders of the lower limbs. Therefore, electro-physiological recordings provide additional information to the neurological examination when the clinical relevance of a radiologically-suspected LSS needs to be confirmed. [ABSTRACT FROM AUTHOR]

Objectives:. (a) To determine the prevalence of unexplained symptoms among newly referred patients in a Dutch academic outpatient clinic for general neurology; (b) To identify factors that can serve as characteristics and possibly as screening instruments for unexplained symptoms in this population. Methods:. Observational study, consisting of self-assessment questionnaires. Patients and resident neurologists completed self-designed questionnaires, which included questions about possible features of unexplained symptoms. Patients also completed the Hospital Anxiety and Depression Scale (HADS), evaluating the existence of anxiety and depressive symptoms. Diagnosis of unexplained symptoms was based on the final classification of the patient’s symptoms as non-organic, after assessment by a senior neurologist. In the analysis, separate predicting factors and groups of factors were adjusted for age, sex and HADS-score, and analysed as possible characteristics of unexplained symptoms. Results:. 35% of the patients (208 total, 174 completed questionnaires) were considered to suffer from unexplained symptoms.Young age (p < 0.001) and female sex (p = 0.007) were significantly associated with unexplained symptoms, high HADS-scores were not (p = 0.10). Characteristics associated with unexplained symptoms were the resident’s preliminary impression of symptoms being non-organic, after reading of the referral letter [OR 96.8, 95% confidence interval (95 %-CI) 29.7–315, PPV 82%, NPV 96%] and after the first encounter (OR 305, 95 %-CI 37.3–2494.6, PPV 83%, NPV 98%), but before the actual history taking and neurological examination. The only other non-demographic characteristic of unexplained symptoms was a visit in order to obtain a second opinion (OR 2.43, 95 %-CI 1.15–5.10). Clustering of these factors, however, did not have sufficient predictive power to result in an accurate screening instrument. Conclusions:. Unexplained symptoms are common in the neurology outpatient clinic and are to some extent predicted by the physician’s preliminary judgement of symptoms. However, history taking and neurological examination remain indispensable for the detection of less obvious organic disorders. [ABSTRACT FROM AUTHOR]

Introduction: The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood.Methods: In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. Each patient underwent a neurological examination every 6 months and a 3T MRI at the beginning of the treatment and after 24 months. The accumulation of new cortical lesions (CLs) and the progression of regional GM atrophy were compared between the two groups.Results: At the end of the study (T24), the percentage of patients with new CLs (13.5 vs. 89%, p < 0.001) and the percentage of GM volume change was lower in the treated group (p < 0.001). The regional analysis revealed that the treated group had also less volume loss in thalamus, caudatus, globus pallidus, cingulate cortex, and hippocampus (p < 0.001), as well as in, cerebellum, superior frontal gyrus, and insular-long gyrus (p < 0.05). Patients with no evidence of disease activity were 60% in the treated group and 10% in the untreated group (p < 0.001).Conclusions: These results suggest a possible protective effect of fingolimod on focal and diffuse GM damage. [ABSTRACT FROM AUTHOR]

Background: Friedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking.Methods: Genetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed.Results: 20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 aged > 50).Conclusions: FRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function. [ABSTRACT FROM AUTHOR]

Introduction: Tremor is the most frequent and disabling neurological side effect under Calcineurin inhibitor-induced immunosuppression, but no studies have defined its phenomenology, severity, distribution, the impact on quality of life, as well as of other neurological symptoms associated.Methods: 126 consecutive kidney-transplanted patients, under treatment with Cyclosporin A, Tacrolimus and non-Calcineurin inhibitors, within therapeutic range, were enrolled. Participants underwent a deep neurological examination by two blinded to the treatment raters, and a blood sampling to assess plasmatic immunosuppressant level and nephrological function tests. Tremor and cerebellar signs were scored according to the Fahn-Tolosa-Marin and the SARA scale. Parkinsonism was excluded applying the UPDRS (part III).Results: Tremor was more common and severe in the Tacrolimus group, similar to impairment in ADL. Regardless of treatment, tremor involved both upper and lower limbs and was activated by action, but in about 50% of cases presented in action and rest condition. Plasmatic level of Tacrolimus was higher in patients with tremor than in those without, while cholesterol was significantly lower. Cerebellar and neuropathic signs were overall mild and were not significantly different across the three groups comparing patients with and without tremor.Conclusions: Non-Calcineurin inhibitors such as Sirolimus have the lowest propensity to induce tremor and with a milder severity, while Calcineurin inhibitors, especially Tacrolimus, the highest, and regardless of the formulation. Plasmatic concentration of Tacrolimus was higher in tremulous patients; further research needs to validate the role of cholesterol plasmatic concentration in predicting the occurrence of tremor in patients on Tacrolimus. [ABSTRACT FROM AUTHOR]

Postpartum lower limb motor and/or sensory deficit is an uncommon obstetrical complication. We aimed to identify its incidence, etiology, and precipitating factors, as well as the neurological prognosis by retrospectively analyzing the successive neurological evaluations, electrophysiological, and MRI data from all the consecutive patients with postpartum motor and/or sensory deficits of the lower limbs referred from the Lariboisière Obstetrical Department to the Lariboisière Neurophysiology Department, from January 2012 to June 2016, as well as data concerning labor and morphological characteristics of mother and baby. Thirteen patients (0.11% of the parturient women in the Lariboisière hospital) were included. Eight (62%) had lumbosacral plexopathy. Symptoms followed a first vaginal delivery in 10/13 patients (77%), in patients who were mostly overweight (mean patient BMI before pregnancy 25.6 ± 3.2 kg/m). Labor duration was slightly longer than average (mean labor duration 8.9 ± 2.9 h). No other potentially precipitating factor was identified. Recovery was good in all patients, 7/11 (64%) made a rapid full recovery (mean recovery time 5 ± 2.5 weeks excluding one patient who had a normal neurological examination at 2 weeks but still complained of foot weakness that fully recovered in 1 year), and a minority (4/11, 36%) still complained of minor symptoms at time of follow-up, but showed marked improvement. New mothers presenting postpartum lower limb nerve injury should, therefore, be reassured. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a 64-year-old man with complaints of frequent falls and disequilibrium. HIs neurological examination revealed dysarthria with lack of prosody. His further examination revealed bradykinesia without rigidity or motor paresis and early presence of cerebellar ataxia.

Corpus callosum abnormality (CCA) outcomes are quite unpredictable and variable, from asymptomatic forms to mild or severe neurodevelopment disorders. The aim of this study was to examine clinical outcomes in CCA patients. The study included 61 children and adolescents in whom brain magnetic resonance imaging (MRI) scans showed CCA, isolated or associated to other central nervous system lesions. All patients underwent anamnesis, physical and neurological examination, routine laboratory tests, electroencephalogram (EEG), and MRI scans. In all participants, the intelligence quotient (IQ) was determined. We divided the participants into two subgroups: the first subgroup included patients with an isolated CCA, and the second subgroup included patients with CCA associated with extra-callosal brain lesions (complex CCA). We found that CCA were associated with elevated frequency to intellectual disability (ID), other neurodevelopment disorders, epilepsy, and isolated EEG anomalies. Mild ID ( p = 0.003) was more frequent in the isolated subgroup, while epilepsy ( p = 0.036) and pre-perinatal risk factors ( p = 0.023) were more frequent in the complex CCA subgroup. Although the role of the CC in the interhemispheric communication is known, neurological and neurodevelopment outcomes of CCA are extremely variable and unpredictable. The presence of extra-callosal brain anomalies is one of the major prognostic factor, and probably, they have an important impact on the clinical outcome. [ABSTRACT FROM AUTHOR]

Our aim was to characterize the nature and extent of pathological changes in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS) using novel diffusion kurtosis imaging-derived white matter tract integrity (WMTI) metrics and to investigate the association between these WMTI metrics and clinical parameters. Thirty-two patients with relapsing-remitting MS and 19 age- and gender-matched healthy controls underwent MRI and neurological examination. Maps of mean diffusivity, fractional anisotropy and WMTI metrics (intra-axonal diffusivity, axonal water fraction, tortuosity and axial and radial extra-axonal diffusivity) were created. Tract-based spatial statistics analysis was performed to assess for differences in the NAWM between patients and controls. A region of interest analysis of the corpus callosum was also performed to assess for group differences and to evaluate correlations between WMTI metrics and measures of disease severity. Mean diffusivity and radial extra-axonal diffusivity were significantly increased while fractional anisotropy, axonal water fraction, intra-axonal diffusivity and tortuosity were decreased in MS patients compared with controls ( p values ranging from <0.001 to <0.05). Axonal water fraction in the corpus callosum was significantly associated with the expanded disability status scale score ( ρ = −0.39, p = 0.035). With the exception of the axial extra-axonal diffusivity, all metrics were correlated with the symbol digits modality test score ( p values ranging from 0.001 to <0.05). WMTI metrics are thus sensitive to changes in the NAWM of MS patients and might provide a more pathologically specific, clinically meaningful and practical complement to standard diffusion tensor imaging-derived metrics. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the nerve ultrasound characteristics in genetically distinct inherited neuropathies, the value of the modified ultrasound pattern sum score (mUPSS) to differentiate between the subtypes and the correlation of ultrasound with nerve conduction studies (NCS), disease duration and severity. All patients underwent a standardized neurological examination, ultrasound, and NCS. In addition, genetic testing was performed. Consequently, mUPSS was applied, which is a sum-score of cross-sectional areas (CSA) at predefined anatomical points in different nerves. 31 patients were included (10xCharcot-Marie-Tooth (CMT)1a, 3xCMT1b, 3xCMTX, 9xCMT2, 6xHNPP [Hereditary neuropathy with liability to pressure palsies]). Generalized, homogeneous nerve enlargement and significantly increased UPS scores emphasized the diagnosis of demyelinating neuropathy, particularly CMT1a and CMT1b. The amount of enlargement did not depend on disease duration, symptom severity, height and weight. In CMTX the nerves were enlarged, as well, however, only in the roots and lower limbs, most prominent in men. In CMT2 no significant enlargement was detectable. In HNPP the CSA values were increased at entrapped sites, and not elsewhere. However, a distinction from CMT1, which also showed enlarged CSA values at entrapment sites, was only possible by calculating the entrapment ratios and entrapment score. The mUPSS allowed distinction between CMT1a (increased UPS scores, entrapment ratios <1.0) and HNPP (low UPS scores, entrapment ratios >1.4), while CMT1b and CMTX showed intermediate UPS types and entrapment ratios <1.0. Although based on few cases, ultrasound revealed consistent and homogeneous nerve alteration in certain inherited neuropathies. The modified UPSS is a quantitative tool, which may provide useful information for diagnosis, differentiation and follow-up evaluation in addition to NCS and molecular testing. [ABSTRACT FROM AUTHOR]

Walking limitation is a key component of disability in patients with multiple sclerosis (MS), but the information on daily walking activity and disability over time is limited. To determine, (1) the agreement between the standard measurements of MS-related disability [expanded disability status scale (EDSS), functional systems (FS) and ambulation index (AI)] obtained by conventional and remote evaluation using a multimedia platform; (2) the usefulness of monitoring 6-min walk test (6MWT) and average daily walking activity (aDWA) to better characterize patients disability. Twenty-five patients (EDSS score 1.0-6.5) were evaluated every 3 months for the first year, and aDWA repeated at year 2. Remote visits included the recording of a video with self-performed neurological examination and specific multimedia questionnaires. aDWA was measured by a triaxial accelerometer. All but two patients completed the study. Modest agreement between conventional and multimedia EDSS was found for EDSS ≤ 4.0 (kappa = 0.2) and good for EDSS ≥ 4.5 (kappa = 0.6). For the overall sample, pyramidal, cerebellar and brainstem FS showed the greatest agreement (kappa = 0.7). SR-AI showed a modest agreement for EDSS ≤ 4.0 and good for EDSS ≥ 4.5 (kappa = 0.3 and 0.6, respectively). There was a strong correlation between conventional and 6MWT measured by accelerometer ( r = 0.76). The aDWA correlated strongly with the EDSS ( r = −0.86) and a cut-off point of 3279.3 steps/day discriminated patients with ambulatory impairment. There was a significant decline in aDWA over 2 years in patients with ambulatory impairment that were not observed by standard measurements of disability. MS clinical monitoring by telemedicine is feasible, but the observed lower agreement in less disabled patients emphasizes the need to optimize the assessment methodology. Accelerometers capture changes that may indicate deterioration over time. [ABSTRACT FROM AUTHOR]

Telemedicine is a growing field in many medical specialties. Within clinical neurosciences one of its largest applications is in acute stroke care. However, little is known about its value and effect in general neurology, despite stroke. In a retrospective survey of 1500 teleconsultations over a time period of 12 months from October 2008 to September 2009, from a large telestroke network in Germany, we evaluated 352 cases with a non-stroke diagnosis. Duration and methods of teleconsultation as well as neurological consultations at bedside and discharge diagnosis were analyzed and compared to stroke cases. Discharge diagnosis was not identical to teleconsultation diagnosis in 48.9 % of all non-stroke cases compared to 12.5 % of all stroke cases. Duration of teleconsultation was 26.5 min in non-stroke cases compared to 14.3 min for stroke cases. In non-stroke cases other parts of the neurological examination were added to the pure administration of a stroke scale. There were no significant differences between non-stroke cases with correct and incorrect consultation diagnoses concerning in-hospital mortality (4.6 vs. 5.0 %) and length of hospital stay (8.3 vs. 7.6 days). We conclude that diagnostic accuracy and protocol routine is not as exact in non-stroke cases compared to acute stroke cases. Other neurologic conditions may need different algorithms for a telemedicine service. Thus experience from a telestroke service cannot be transferred to other neurologic conditions on a routine basis. [ABSTRACT FROM AUTHOR]

The introduction of highly active anti-retroviral therapy (HAART) led to a radical change in the natural history of HIV infection and of the associated neurological opportunistic infections. However, the mortality of central nervous system (CNS) complications and opportunistic infections is still high in untreated HIV-infected individuals or in patients unaware of their HIV infection. We describe the outcome of HIV-infected patients followed at a single center for AIDS-related neurological syndromes in the 16 years following the introduction of HAART, and compare the findings with those in patients admitted up to 1996. We have conducted a retrospective study of patients with HIV infection or AIDS (based on WHO criteria and classified according to the 1993 CDC criteria) admitted during 20 years (January 1992 to March 2012) to the Infectious Diseases Unit of the University of Verona for the presence of focal or widespread CNS lesion on neuroimaging. Clinical history, CD4 cell count, HIV-RNA level, neurological examination, imaging, cerebrospinal fluid examination and eventual cerebral biopsy results were reviewed as well as the final neurological diagnosis and the treatment. The survival time from the clinical onset of the neurologic syndrome to death was calculated for each patient who died. A statistical analysis was performed comparing data collected up to and after 1996, i.e., before and after HAART introduction. Among 1043 patients with HIV infection or AIDS admitted to the Infectious Diseases Unit of the University of Verona between January 1992 and March 2012, 114 had a CNS lesion. The following diseases were observed: neurotoxoplasmosis (NT), progressive multifocal leukoencephalopathy), primary central nervous system lymphoma (PCNSL), the severe form of HIV-associated neurocognitive disorder, cryptococcal encephalitis (CE) and lesions of undetermined origin. The follow-up period was 4 weeks to 72 months both in the pre-HAART and HAART era. Cerebral lesions were detected in 53/243 patients (21.8 %) in the pre-HAART era and in 61/801 patients (7.6 %) in the HAART era ( p < 0.001). Most patients who developed a neurological complication in the HAART period (40/59, 67.8 %) were untreated or did not know to be HIV-infected; in particular, 27.9 % of patients with a CNS lesion in the HAART era were unaware of their HIV infection vs 13.2 % in the pre-HAART era ( p < 0.05). Some patients were not virologically suppressed (14/59, 23.7 %) or were immunological non-responders (undetectable viral load, with CD4 count <200 cells/μL; 4/59, 6.8 %). Other statistically significant data were the mean age at the onset of neurological complications (32.6 ± 5.4 years in the pre-HAART, 40.3 ± 9.5 in the HAART group, p < 0.001) and the mean CD4 cell count at the onset of illness (median of 38 cells/µL (2-215) in the pre-HAART, 77 cells/µL (2-752) in the HAART group; p < 0.001). In the HAART era a reduction of PCNSL and NT was observed. Our results, while confirming a decrease in the incidence of opportunistic infections of the CNS in the HAART era, show that late presentation of patients with HIV infection remains an important issue in our catchment area. [ABSTRACT FROM AUTHOR]

The aim of this study is to describe the frequency of isolated, subtle, neurological abnormalities (ISNAs) in a large population of neurologically and cognitively healthy subjects and to compare ISNAs to various types of MRI-detected cerebrovascular lesions and subcortical brain atrophy in different age classes. 907 subjects were selected from a large, prospective hospital-based study. At baseline neurological examination, 17 ISNAs were selected. Primitive reflexes were the most common ISNAs (35.8 %), while dysphagia was the most rarely encountered (0.3 %). Measures of small vessel disease, i.e., deep and subcortical white matter hyperintensity and lacunar infarcts as well as subcortical atrophy, were variously associated with ISNAs. In the adult group, the ISNAs were associated with hypertriglyceridemia, TIA, and subcortical lacunar infarcts, while in the elderly-old group they were associated with arterial hypertension, subcortical white matter hyperintensity, and subcortical atrophy. An increased risk of ISNAs was associated with lacunae and white matter hyperintensity in the parietal region. This study shows that white matter hyperintensity, lacunae, and subcortical atrophy are associated with an increased risk of ISNAs in cognitively and neurologically healthy aging subjects. ISNAs are not benign signs. Therefore, adults and elderly people presenting with ISNAs should have access to accurate history and diagnosis to prevent progression of small vessel disease and future neurological and cognitive disabilities. [ABSTRACT FROM AUTHOR]

The article describes a case of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) in a 35 year-old Pakistani woman who experienced acute leg weakness. Topics discussed include the patient's novel mutation and its impact on protease activity, an overview of her medical history, and details of the findings of her neurological examination.

We report the case of Niemann-Pick disease type C with extensive phenotypic heterogeneity in two monozygotic twins. One of the twins presented with a history of obsessive-compulsive disorder and slowly progressive inferior limb clumsiness, dysphagia and dysarthria. Neurological examination revealed a broad-based ataxic gait, limb dysmetria, downward vertical gaze palsy, brisk lower limb reflexes and ankle clonus, while neuropsychological assessment revealed global cognitive deficits in multiple domains. Complete neurological and neuropsychological evaluation in the asymptomatic monozygotic twin brother only revealed mild neurological impairment. In the hypothesis of Niemann-Pick disease type C, Filipin test, measurement of plasma oxysterols levels and genetic analysis were carried out in both twins. Filipin staining showed massive intracellular accumulation of non-esterified cholesterol, plasma oxysterols levels were elevated and genetic analysis revealed a homozygous c.2662 C > T (p.P888S) mutation in the NPC1 gene (18q11.2) in both twins. 18F-FDG-PET imaging with single-subject analysis revealed a reduced frontal and temporal glucose metabolism, which correlated with disease progression. This case supports the phenotypic variability of Mendelian inherited disorders in monozygotic twins, likely due to epigenetic differences and post-zygotic mutagenesis. [ABSTRACT FROM AUTHOR]

Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear. [ABSTRACT FROM AUTHOR]