Reliability of subsequent memory effects in children and adults: The good,the bad,and the hopeful

Functional MRI (fMRI) is a key tool for investigating neural underpinnings of cognitive development. Yet, in recent years, the reliability of fMRI effects has come into question and with it, the feasibility of using task-based fMRI to identify developmental changes related to cognition. Here, we investigated the reliability of task-based fMRI activations with a widely used subsequent memory paradigm using two developmental samples: a cross-sectional sample (n = 85, age 8–25 years) and a test-retest sample (n = 24, one-month follow up, age 8–20 years). In the large cross-sectional sample, we found good to excellent group-level reliability when assessing activation patterns related to the encoding task and subsequent memory effects. In the test-retest sample, while group-level reliability was excellent, the consistency of activation patterns within individuals was low, particularly for subsequent memory effects. We observed consistent activation patterns in frontal, parietal, and occipital cortices, but comparatively lower test-retest reliability in subcortical regions and the hippocampus. Together, these findings highlight the limitations of interpreting task-based fMRI effects and the importance of incorporating reliability analyses in developmental studies. Leveraging larger and densely collected longitudinal data may help contribute to increased reproducibility and the accumulation of knowledge in developmental sciences.     

Contralateral and ipsilateral responses in primary somatosensory cortex following electrical median nerve stimulation--an fMRI study.

OBJECTIVE: Ten healthy adult subjects were examined using functional magnetic resonance imaging (fMRI) to investigate responses in the contralateral and ipsilateral primary somatosensory cortex (SI) following electrical stimulation of the median nerve. METHODS: The right and left median nerves were stimulated alternately at the wrist in the different sessions. First, the location of the response in contralateral SI was identified following median nerve stimulation, and then, a spherical search volume with a 10mm radius centered on the region of the contralateral response was determined. Whether or not fMRI activation occurred within this sphere following ipsilateral stimulation was examined using a 3T MR imager. RESULTS: A response in contralateral SI was observed in 8 of the 10 subjects in right and left hemisphere. Responses in ipsilateral SI were observed in 6 of 8 subjects in right hemisphere, and the region of the response tended to be posterior to the contralateral region. On the other hand, in left hemisphere, the ipsilateral responses were found in three. CONCLUSIONS: In the present study, not only contralateral SI but also ipsilateral SI was activated following median nerve. The location of the ipsilateral activation was significantly more posterior than the contralateral one in right hemisphere. SIGNIFICANCE: The region of activation in ipsilateral SI was located in the posterior portion of post central gyrus, corresponding to around BA2 and 5 in human.     

Occipital blood‐brain barrier permeability is an independent predictor of visual outcome in type 2 diabetes,irrespective of the retinal barrier: A longitudinal study

Blood‐brain barrier (BBB) permeability in type 2 diabetic patients has been previously shown to be altered in certain brain regions such as the basal ganglia and the hippocampus. Because of the histological and functional similarities between the BBB) and the blood‐retinal barrier (BRB), we aimed to investigate how the permeability of both barriers predicts visual outcome. We included 2 control groups (acute unilateral stroke patients, n = 9; type 2 diabetics without BRB leakage n = 10) and a case study group of type 2 diabetics with established BRB leakage (n = 17). We evaluated sex, age, disease duration, metabolic impairment, retinopathy grade and BBB permeability as predictors of visual acuity at baseline, 12  and 24 months in the type 2 diabetics without BRB leakage group and the case study group. We have also explored differences in BBB permeability in the occipital lobe and frontal lobe in the 3 different groups. K^trans (volume transfer coefficient) and V_p (fractional plasma volume) were estimated. The BBB permeability parameter V_p was higher in the case study group compared to the unaffected hemisphere of the stroke patient control group, suggesting vascular dynamics were changed in the occipital lobe of type 2 diabetics with established BRB leakage. These patients showed a significant correlation between glycated hemoglobin (HbA1C) levels and occipital and frontal K^trans. We report for the first time that occipital BBB permeability is an independent predictor of visual acuity at baseline, as well as at 12 and 24 months, in type 2 diabetics with established BRB leakage. Our results suggest that occipital BBB permeability might be an independent biomarker for visual impairment in patients with established BRB leakage.     

Finger movement functions remain in the ipsilesional hemisphere and compensation by the contralesional hemisphere might not be expected after hemispherotomy -pre- and post-hemispherotomy evaluations in 8 cases-

BackgroundWe hypothesized that fine finger motor functions are controlled by the ipsilesional hemisphere, and that gross motor functions are compensated for by the contralesional hemisphere after brain injury in humans. The purpose of this study was to compare finger movements before and after hemispherotomy that defunctionated the ipsilesional hemisphere for patients with hemispherical lesions.MethodsWe statistically compared Brunnstrom stage of the fingers, arm (upper extremity), and leg (lower extremity) before and after hemispherotomy. Inclusion criteria for this study were: 1) hemispherotomy for hemispherical epilepsy; 2) a ≥ 6-month history of hemiparesis; 3) post-operative follow-up ≥ 6 months; 4) complete freedom from seizures without aura; and 5) application of our protocol for hemispherotomy.ResultsAmong 36 patients who underwent multi-lobe disconnection surgeries, 8 patients (2 girls, 6 boys) met the study criteria. Mean age at surgery was 6.38 years (range, 2–12 years; median, 6 years; standard deviation, 3.5 years). Paresis of the fingers was significantly exacerbated (p = 0.011) compared to pre-operatively, whereas that of the upper limbs (p = 0.07) and lower limbs (p = 0.103) was not.ConclusionFinger movement functions tend to remain in the ipsilesional hemisphere after brain injury, whereas gross motor movement functions such as those of the arms and legs are compensated for by the contralesional hemisphere in humans.     

Pediatric Nerve Biopsy Diagnostic and Treatment Utility in Tertiary Care Referral

BackgroundPediatric neuropathies are both unique and similar to their adult counterparts, with genetic varieties thought to be more common. The objective of this work was to assess the utility of nerve biopsy in children at a tertiary referral center in light of availability of current genetic testing.MethodsWe retrospectively reviewed the clinical, nerve biopsy, and genetic testing findings of 316 pediatric (age ≤18 years) patients.ResultsMedian age at diagnosis was 9.8 years (4 days to 18 years). Nerve biopsy was nontargeted in 198 (182 whole sural, seven superficial peroneal, and nine other), targeted in 21 (14 fascicular sciatic and seven brachial plexus), and unknown in 97 cases. Prebiopsy localizations and diagnoses were diverse, most commonly with length-dependent localizations (n = 150). Median follow-up was 6 months (0 to 480 months). A distinctive histopathologic diagnosis was made in 106 cases (33%), including inflammatory or immune (n = 30), neoplastic (n = 19), hereditary (n = 41), vasculitis (n = 10), and other (n = 6). Nerve biopsy confirmed the suspected diagnosis in 91 (29%) individuals and changed or refined the initial diagnosis in 182 (58%). Treatment modifications as a result of biopsy occurred in 80 (25%) cases; 59 (19% of the entire cohort) with clinical improvements noted, most commonly by immunotherapy (n = 30). Low diagnostic yield occurred in “hypotonic infants” without nerve conduction abnormalities. Pain at the biopsy site beyond 1 month was rare (n = 3; 1%). Forty-four patients underwent genetic testing. Among demyelinating varieties, mutations were identified in five of 11 (46%) cases compared with only six of 33 (18%) cases of axonal varieties.ConclusionPediatric nerve biopsy provides diagnostic information that frequently alters treatment recommendations. Furthermore, it leads to clinical improvements, especially in inflammatory immune neuropathies. For suspected inherited varieties, genetic testing has the highest diagnostic yield in demyelinating phenotypes.     

Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin‐1β

Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro‐inflammatory cytokine interleukin (IL)‐1β has not been established in TAI. An IL‐1β‐neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham‐injured controls (n = 20) and untreated, naive mice (n = 9). The anti‐IL‐1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 μg/brain tissue) at 24 h post‐injury in both cFPI (n = 5) and sham‐injured (n = 3) mice, with lower concentrations at 72 h post‐injury (up to ~18 μg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post‐injury, and the Morris water maze (MWM) at 14–21 days post‐injury. Following TAI, the IL‐1β‐neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL‐1β‐neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL‐1β is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI.     

Cortical Aquaporin-4 in relation to brain oedema and neurological function of cortical cryo-injured mice

To estimate the spatial and temporal expression of Aquaporin-4 (AQP-4) in a murine model of automated cerebral cryoinjury and correlate AQP-4 expression with development of brain oedema and neurological function. AQP-4 levels were determined quantitatively by Western blots at site of injury and at sites adjacent to and distant from injury in brains of cryoinjured (experimental) (n = 18), sham injured (n = 18) & normal mice at 24, 48, 72 h post injury. AQP-4 expression was correlated with percentage water content of brain, Neurological Severity Score (NSS) and rotarod scores. We found a 1.4-fold increase in expression of AQP-4 at the site of injury and at sites distant from injury at 24 h when compared to normal mice (p = 0.05). The increase in expression of AQP-4 24 h post injury was significantly higher in experimental group at the site of injury and at the site adjacent to the injury in the ipsilateral hemisphere when compared to the sham injured mice (p = 0.05). At 24 h post injury the median NSS score in the experimental group was 9 (interquartile range 7.25–10) and that in the sham group was 0.5 (interquartile range 0.0–1.0) (p < 0.001).At 48 and 72 h, AQP-4 expression remained elevated in the experimental group when compared to normal brain, but the levels were not significantly different from that in sham group. AQP-4 expression was significantly elevated in the ipsilateral hemisphere in the first 24 h following cerebral cortical injury in mice and this could be correlated with worsening of neurological function. Over the next 48 h, there was a trend towards decrease in AQP-4 expression that was associated with partial recovery of neurological function.     

A clinic-based cluster analysis in patients with moderate-severe obstructive sleep apnea (OSA) in Chile

RationalePatients commonly report differences in either clinical or symptomatic profiles, despite having the same severity of obstructive sleep apnea (OSA).ObjectiveTo identify clinical and symptomatic phenotypes and to evaluate cardiovascular mortality in each phenotype.MethodsData from 1370 participants (788 with moderate-severe OSA and 582 controls as a reference group) were extracted using the SantOSA database. Sixteen variables were analyzed using latent class analysis to define clinical subtypes. The association between subtypes and cardiovascular mortality was evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards model. Adjusted hazard ratios (HRs) with confidence intervals (CIs) were modified by cardiovascular confounders.ResultsThe median observation period was 5.2 years. We found four clusters: cluster #1: symptomatic men with major comorbidities (n = 252); cluster #2: symptomatic women with comorbidities (n = 154); cluster #3: asymptomatic men with comorbidities (n = 143); and cluster #4: symptomatic young men without major comorbidities (n = 239). In cluster #1, mortality was 4.76% and was independently associated with age (HR 1.12; CI 1.07–1.17), type 2 diabetes mellitus (HR 3.37; CI 1.29–8.78) and coronary heart disease (HR 3.85; CI 1.27–11.56); in cluster #2, mortality was 3.89% and was independently associated with age (HR 1.12; CI 1.06–1.19) and the oxygen desaturation index (ODI, HR 1.02; CI 1.01–1.04); and in cluster #3, mortality was 3.49% (HR 3.50; CI 1.03–11.90) and was independently associated with age (HR 1.19; CI 1.10–1.29). In cluster #4, mortality was 1.25% and showed nonsignificant associations.ConclusionIn patients with moderate-severe OSA, we described four phenotypes of patients according to clinical features with different risks of cardiovascular mortality.Study registerISRCTN62293645.     

Cardiac Troponin-I: A Predictor of Prognosis in Subarachnoid Hemorrhage

Background  Release of cardiac biomarkers is reported in patients with subarachnoid hemorrhage (SAH). Data addressing the impact of cardiac injury on outcome in these patients is sparse. This study was conducted to ascertain the association of elevation of serum cardiac Troponin-I (cTnI) with mortality and neurological outcome in patients with SAH. Methods  Medical records of all patients admitted with a diagnosis of SAH and at least one measured cTnI were reviewed. Demographic and clinical variables including admission neurological status were collected. Conservative and non-parametric statistics were used to assess association between cTnI and death or neurological outcome at discharge. Results  The study group comprised of 83 patients with a mean age of 59 years. There was a female (60%) and African-American (60%) preponderance. At admission, the median Glasgow Coma Scale (GCS) was 9, and 47% had a severe Hunt–Hess grade (HHG) of ≥4. Elevation of cTnI was found in 31 (37%) patients and was associated with worse baseline Fisher grade (p=0.01) and neurological status: GCS score (p=0.006) and HHG (p=0.007). Patients with abnormal cTnI were more likely to die (55% vs.27%; odds ratio 1.3–8.4, p = 0.01) and had a worse GCS score (p = 0.008) and HHG (p = 0.004) on discharge. On multivariate analysis, peak cTnI (p = 0.04) and admission GCS score of <12 (p = 0.02) were independent predictors of death at discharge. Conclusion  Patients with subarachnoid hemorrhage and elevated cTnI are found to have worse neurological status at admission. These patients have a worse neurological outcome and in-hospital mortality.     

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis

ObjectiveIt may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM.MethodsThis prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5–16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18–75).ResultsIn total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02).ConclusionPediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.     

Changes in long term peripheral nerve biophysical properties in childhood cancer survivors following neurotoxic chemotherapy

ObjectiveIn the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS.MethodsDetailed cross-sectional neurophysiological examination, using median nerve axonal excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment).ResultsCisplatin treated CCS (n = 16) demonstrated multiple sensory axonal excitability changes including increased threshold (P < 0.05), alterations in depolarising and hyperpolarising threshold electrotonus (P < 0.05) and reduction in resting and minimum IV slope (P < 0.01). Vincristine treated CCS (n = 73) were comparable to controls, except for prolonged distal motor latency (P = 0.001). No differences were seen in the non-neurotoxic chemotherapy group (n = 14). Abnormalities were more evident in the cisplatin subgroup with greater clinical neuropathy manifestations.ConclusionPersistent long term changes in axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis.SignificanceThis study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.     

Diagnosis and Outcomes of Late-Onset Wilson's Disease: A National Registry-Based Study

Background

Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms.

Objective

The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD.

Methods

Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up.

Results

Forty-five patients were identified (median age: 49, range: 40–64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser–Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis.

Conclusions

In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

An fMRI marker for peripheral nerve regeneration

Final outcome after surgical repair of peripheral nerve transections varies. Here, we present the first longitudinal functional magnetic resonance imaging (fMRI) observation of cortical somatosensory reorganization patterns after surgery. A 43-year-old man presented with isolated complete transection of the right median nerve and underwent immediate epineural end-to-end coaptation. Applying standardized vibrotactile median nerve stimulation, 3 T brain activation maps were evaluated at 1, 7, 15 weeks and 1 year after surgery. Initially, the affected hemisphere showed no primary activation but increased frontoparietal activity. After 1 year, primary activation had recovered, and frontoparietal activity was decreased relative to the nonaffected hemisphere. Based on these longitudinal fMRI patterns, we propose a new marker for restoration of somatosensory function, which may not be provided by electrophysiological methods.     

Medullary hemangioblastoma: 34 patients at a single institution

This study aimed to elucidate the surgical experience of medullary hemangioblastoma (MH) at a single institution. We reviewed 34 consecutive patients with MH operated on between January 2005 and June 2012 in the neurosurgery department of the Beijing Tiantan Hospital. There were 14 men and 20 women. The patients were aged from 17 to 60 years with an average age of 38 years. Tumors were cystic in 12 patients (Type A), and solid in 22 patients. The solid tumors were of a small size in six patients (<3 cm, Type B), large in 12 (3.1–5 cm, Type C), and giant in four (>5 cm, Type D). Radical tumor removal was achieved in all patients. Tracheotomy was performed in 10 patients (one Type B patient, seven Type C, two Type D) postoperatively. Pneumonia secondary to lower cranial nerve palsy occurred in six patients (all Type C). Complications including intracranial infection (n = 5), gastrointestinal bleeding (n = 2), and intracranial hematoma (n = 1) also occurred in this group. Follow-up (range, 2–82 months; mean, 30 months) was available in all patients. At follow-up, 29 patients (85.3%) had a good outcome. Twenty-eight of these (82.4%) had an excellent outcome postoperatively (Karnofsky Performance Status ⩾80). Although transient surgical complications are possible especially for large solid tumors, total surgical resection can be performed with favorable long-term outcomes with meticulous microsurgical technique and understanding of the vascular pattern of the tumor. Postoperative management of MH is as important as the operation.     

Infectious mononucleosis as a risk factor for depression: A nationwide cohort study

BackgroundInfectious mononucleosis is a clinical diagnosis characterized by fever, sore throat, lymph node enlargement and often prolonged fatigue, most commonly caused by Epstein-Barr virus infection. Previous studies have indicated that infectious mononucleosis can be followed by depression; however, large-scale studies are lacking. We used nationwide registry data to investigate the association between infectious mononucleosis and subsequent depression in this first large-scale study.MethodsProspective cohort study using nationwide Danish registers covering all 1,440,590 singletons born (1977–2005) in Denmark by Danish born parents (21,830,542 person-years’ follow-up until 2016); where 12,510 individuals had a hospital contact with infectious mononucleosis. The main outcome measures were a diagnosis of major depressive disorder (ICD-8: 296.09, 298.09, 300.4; ICD-10: F32) requiring hospital contact.ResultsInfectious mononucleosis was associated with a 40% increased hazard ratio (HR) for a subsequent depression diagnosis in the fully adjusted model (HR: 1.40, 95% CI: 1.26–1.56;n = 358), when compared to unexposed individuals. The increased risk of being diagnosed with depression was significant to the periods one to four years after the infectious mononucleosis diagnosis (HR: 1.40, 95% CI: 1.17–1.67;n = 121) and ≥ five years (HR: 1.40, 95% CI: 1.22–1.61;n = 207). We did not find any differences according to age (p = 0.61) nor sex (p = 0.30).ConclusionIn this largest study to date, infectious mononucleosis in childhood or adolescence was associated with an increased risk of a subsequent depression. Our findings have important clinical implications and identifies youth with infectious mononucleosis as a group at high risk of later depression in young adulthood.     

Clinical outcomes after revascularization for pediatric moyamoya disease and syndrome: A single-center series

Moyamoya is a progressive cerebrovascular arteriopathy that affects children of any age. The goal of this study was to determine imaging and clinical outcomes as well as complication rates in a pediatric cohort undergoing either a combined direct/indirect or indirect-only revascularization approach. Patients with moyamoya disease or syndrome ≤ 18 years of age at the time of initial surgery were identified, and clinical data were collected retrospectively. Over a 12-year period, 26 patients underwent revascularization procedures on 49 hemispheres with a median follow-up of 2.6 years from surgery. Median age at surgery was 7.3 years (range 1.4–18.0 years). Thirty-three hemispheres (67.3%) underwent combined revascularization with a direct bypass and encephalomyosynangiosis, and sixteen hemispheres (32.7%) underwent indirect-only revascularization. The rate of 30-day perioperative complication was 10.2%, and the rate of postoperative clinical stroke by end of follow-up was 10.2% by hemisphere. There was a 5.7% rate of intraoperative bypass failure requiring conversion to an indirect revascularization approach. On follow-up imaging, 96.9% of direct bypasses remained patent. On multivariate analysis, higher preoperative Pediatric Stroke Outcome Measure (PSOM) scores were associated with lower rates of good clinical outcome on follow-up (unit OR 0.03; p = 0.03). Patients with age < 5.4 years had lower rates of good clinical outcome on follow-up. In this North American cohort, both combined direct/indirect and indirect only revascularization techniques were feasible. However, younger children < 5.4 years of age have worse outcomes than older children, similar to east Asian cohorts.     

Retinal layer thickness predicts disability accumulation in early relapsing multiple sclerosis

Background and purpose

This study was undertaken to investigate baseline peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness for prediction of disability accumulation in early relapsing multiple sclerosis (RMS).

Methods

From a prospective observational study, we included patients with newly diagnosed RMS and obtained spectral-domain optical coherence tomography scan within 90 days after RMS diagnosis. Impact of pRNFL and GCIPL thickness for prediction of disability accumulation (confirmed Expanded Disability Status Scale [EDSS] score ≥ 3.0) was tested by multivariate (adjusted hazard ratio [HR] with 95% confidence interval [CI]) Cox regression models.

Results

We analyzed 231 MS patients (mean age = 30.3 years, SD = 8.1, 74% female) during a median observation period of 61 months (range = 12–93). Mean pRNFL thickness was 92.6 μm (SD = 12.1), and mean GCIPL thickness was 81.4 μm (SD = 11.8). EDSS ≥ 3 was reached by 28 patients (12.1%) after a median 49 months (range = 9–92). EDSS ≥ 3 was predicted with GCIPL < 77 μm (HR = 2.7, 95% CI = 1.6–4.2, p < 0.001) and pRNFL thickness ≤ 88 μm (HR = 2.0, 95% CI = 1.4–3.3, p < 0.001). Higher age (HR = 1.4 per 10 years, p < 0.001), incomplete remission of first clinical attack (HR = 2.2, p < 0.001), ≥10 magnetic resonance imaging (MRI) lesions (HR = 2.0, p < 0.001), and infratentorial MRI lesions (HR = 1.9, p < 0.001) were associated with increased risk of disability accumulation, whereas highly effective disease-modifying treatment was protective (HR = 0.6, p < 0.001). Type of first clinical attack and presence of oligoclonal bands were not significantly associated.

Conclusions

Retinal layer thickness (GCIPL more than pRNFL) is a useful predictor of future disability accumulation in RMS, independently adding to established markers.     

Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial

Objective

This study compares efficacy and safety of divalproate extended release (DVA‐ER) and amitriptyline (AMT) in migraine .

Materials and methods

Three hundred migraineurs having >4 attacks monthly were randomized into DVA‐ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events.

Results

The median age was 32 years, and 241 were women. 150 patients each received DVA‐ER and AMT. At 3 months, 74.7% in DVA‐ER and 62% patients in AMT group improved in headache frequency (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA‐ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA‐ER group.

Conclusion

Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis.     

BOLD fMRI signal in stroke patients and its importance for prognosis in the subacute disease period – Preliminary report

Functional magnetic resonance imaging (fMRI) allows for the assessment of neuronal activity through the blood-level-dependent signal. The purpose of study was to evaluate the pattern of brain activity in fMRI in patients with ischemic stroke and to assess the potential relationship between the activity pattern and the neurological/functional status.

New evidence for preserved somatosensory pathways in complete spinal cord injury: A fMRI study

Trauma to the spinal cord rarely results in complete division of the cord with surviving nerves sometimes remaining silent or failing to function normally. The term motor or sensory discomplete has been used to describe this important but unclassified subgroup of complete SCI. Importantly, silent motor or sensory pathways may contribute to aversive symptoms (spasticity, pain) or improved treatment success. To demonstrate more objectively the presence of subclinical preserved somatosensory pathways in clinically complete SCI, a cross‐sectional study using functional MRI (fMRI) was undertaken. The presence of brain activation following innocuous brushing of an insensate region below‐injury (great toe) was analyzed in 23 people (19 males (83%), mean ± SD age 43 ± 13 years) with clinically complete (AIS A) SCI with (n = 13) and without (n = 10) below‐level neuropathic pain and 21 people without SCI or pain (15 males (71%); mean ± SD age 41 ± 14 years). Location appropriate, significant fMRI brain activation was detected in 48% (n = 11/23) of subjects with clinically complete SCI from below‐injury stimulation. No association was found between the presence of subclinical sensory pathways transmitting innocuous mechanical stimuli (dorsal column medical lemniscal) and below‐level neuropathic pain (χ² = 0.034, P = 0.9). The high prevalence of sensory discomplete injuries (～50% complete SCI) strengthens the case to explore inclusion of this category into the international SCI taxonomy (ISNCSCI). This would ensure more widespread inclusion of discomplete SCI in ongoing pain and motor recovery research. Neurophysiological tests such as fMRI may play a role in this process. Hum Brain Mapp 39:588–598, 2018. © 2017 Wiley Periodicals, Inc.