Serum and CSF PDGF‐AA and FGF‐2 in relapsing‐remitting multiple sclerosis: a case–control study

Background and purpose: Fibroblast growth factor‐2 (FGF‐2) and platelet‐derived growth factor‐A (PDGF‐AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF‐2 and PDGF‐AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing‐remitting multiple sclerosis (RR‐MS) and compared these values with control subjects. Methods: Twenty‐three patients with RR‐MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann–Whitney U‐test and Spearman’s rank correlation were used for analysis. P values of <0.05 were considered significant. Results: Age and sex distribution were similar in both groups. Serum values of FGF‐2 were higher in relapse phase compared with remission phase, with a trend toward significance (P = 0.052). CSF PDGF‐AA showed significant negative correlation with disease duration (correlation coefficient = ?0.58, P = 0.004). Serum levels of PDGF did not differ between two phases significantly. There was no difference in serum and CSF values of these factors between patients and controls. When we compared patients with prolonged disease with controls, a significant difference between the CSF levels of PDGF‐AA was observed (mean ± SEM 2.78 ± 0.8 in controls vs. 0.55 ± 0.29 in patients with MS ≥ 2 years, P < 0.05). Conclusion: Our study was the first to show that CSF PDGF‐AA is related to disease duration. Supporting previous findings we showed that serum and CSF levels of these factors are weak indicators of disease severity.     

One‐year follow‐up study of neuropathic pain in chronic inflammatory demyelinating polyradiculoneuropathy

We sought to gather information about frequency and features of neuropathic pain (NeP) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients and to investigate course of NeP during 1‐year follow‐up. Study included 105 patients diagnosed with CIDP. Patients with diabetes (N = 26) were excluded. NeP was diagnosed by the official guidelines and painDETECT questionnaire (PD‐Q). Medical Research Council Sum Score (MRC‐SS), INCAT disability and sensory scores, and Beck Depression Inventory were also measured. PD‐Q showed presence of NeP in 16 (20%) of 79 CIDP patients and their mean pain was moderate (5.1 ± 3.0 of 10). Diagnostic delay in CIDP patients with NeP was prolonged compared to CIDP patients without NeP (21 ± 28 vs 9 ± 12 months, P < .05). Slowly progressive course of the disease was more frequent in patients with NeP (81% vs 52%, P < .05). Patients with NeP had worse INCAT sensory score (P < .01), INCAT disability score (P < .05), MRC‐SS, as well as worse disease outcome at time of testing (P < .05). Depression was more common in patients with NeP (69% vs 17%, P < .01). During 1‐year follow‐up, majority of our CIDP patients had good control of NeP with gabapentinoids or amitriptyline. NeP was common in our cohort of non‐diabetic CIDP patients. It was associated with worse functional disability, worse sensory deficit, and depression. Special attention should be paid to CIDP patients with NeP because they request additional symptomatic therapy that appeared efficacious in our cohort.     

Muscular adaptations and insulin‐like growth factor‐1 responses to resistance training are stretch‐mediated

Introduction: Modulation of muscle characteristics was attempted through altering muscle stretch during resistance training. We hypothesized that stretch would enhance muscle responses. Methods: Participants trained for 8 weeks, loading the quadriceps in a shortened (SL, 0–50° knee flexion; n = 10) or lengthened (LL, 40–90°; n = 11) position, followed by 4 weeks of detraining. Controls (CON; n = 10) were untrained. Quadriceps strength, vastus lateralis architecture, anatomical cross‐sectional area (aCSA), and serum insulin‐like growth factor‐1 (IGF‐1) were measured at weeks 0, 8, 10, and 12. Results: Increases in fascicle length (29 ± 4% vs. 14 ± 4%), distal aCSA (53 ± 12% vs. 18 ± 8%), strength (26 ± 6% vs. 7 ± 3%), and IGF‐1 (31 ± 6% vs. 7 ± 6%) were greater in LL compared with SL muscles (P < 0.05). No changes occurred in CON. Detraining decrements in strength and aCSA were greater in SL than LL muscles (P < 0.05). Conclusions: Enhanced muscle in vivo (and somewhat IGF‐1) adaptations to resistance training are concurrent with muscle stretch, which warrants its inclusion within training. Muscle Nerve 49 : 108–119, 2014     

Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot‐Marie‐Tooth disease 1A

Diaphragm weakness in Charcot‐Marie‐Tooth disease 1A (CMT1A) is usually associated with severe disease manifestation. This study comprehensively investigated phrenic nerve conductivity, inspiratory and expiratory muscle function in ambulatory CMT1A patients. Nineteen adults with CMT1A (13 females, 47 ± 12 years) underwent spiromanometry, diaphragm ultrasound, and magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots, with recording of diaphragm compound muscle action potentials (dCMAP, n = 15), transdiaphragmatic and gastric pressures (twPdi and twPgas, n = 12). Diaphragm motor evoked potentials (dMEP, n = 15) were recorded following cortical magnetic stimulation. Patients had not been selected for respiratory complaints. Disease severity was assessed using the CMT Neuropathy Scale version 2 (CMT‐NSv2). Healthy control subjects were matched for age, sex, and body mass index. The following parameters were significantly lower in CMT1A patients than in controls (all P < .05): forced vital capacity (91 ± 16 vs 110 ± 15% predicted), maximum inspiratory pressure (68 ± 22 vs 88 ± 29 cmH₂O), maximum expiratory pressure (91 ± 23 vs 123 ± 24 cmH₂O), and peak cough flow (377 ± 135 vs 492 ± 130 L/min). In CMT1A patients, dMEP and dCMAP were delayed. Patients vs controls showed lower diaphragm excursion (5 ± 2 vs 8 ± 2 cm), diaphragm thickening ratio (DTR, 1.9 [1.6‐2.2] vs 2.5 [2.1‐3.1]), and twPdi (8 ± 6 vs 19 ± 7 cmH₂O; all P < .05). DTR inversely correlated with the CMT‐NSv2 score (r = ?.59, P = .02). There was no group difference in twPgas following abdominal muscle stimulation. Ambulatory CMT1A patients may show phrenic nerve involvement and reduced respiratory muscle strength. Respiratory muscle weakness can be attributed to diaphragm dysfunction alone. It relates to neurological impairment and likely reflects a disease continuum.     

Interleukin‐6 and silent cerebral infarction in hemodialysis patients: a cross‐sectional study

Background: In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of interleukin‐6 (IL‐6) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased IL‐6 levels correlate with the occurrence of SCI in HD patients. Methods: Using cranial magnetic resonance imaging findings, we divided 50 Japanese patients undergoing HD into two groups: with SCI (60 ± 7 years, mean ± SD, n = 27) and without SCI (60 ± 6 years, n = 23). We compared the gender, body mass index, metabolic profiles, IL‐6 levels, and smoking habits between the two groups. Results: We made the following observations: (i) The prevalence of diabetes or hypertension did not differ between the two groups, (ii) the level of IL‐6 was higher in the with‐SCI group than in the without‐SCI group (P < 0.0001), (iii) the proportion of smokers was higher in the with‐SCI group (P < 0.05), (iv) plasma level of high‐density lipoprotein cholesterol was lower, whilst uric acid level was higher, in the with‐SCI group (P < 0.05 and P < 0.05, respectively), and (v) multiple logistic regression analysis identified IL‐6 levels as being significantly associated with the presence of SCI (odds ratio 3.13, 95% CI = 1.42–7.89, P < 0.0001). Conclusions: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that IL‐6 is significantly associated with the presence of SCI in HD patients.     

Limitations in daily activities and general perception of quality of life: Long term follow‐up in patients with anti‐myelin‐glycoprotein antibody polyneuropathy

In this study, we assessed the modifications over time of daily activities and quality of life (QoL) in 32 subjects with anti‐myelin‐glycoprotein (MAG) antibody neuropathy. A widespread panel including clinical scores and patient‐reported questionnaires, in compliance of the terms by the International Classification of Functioning, Disability, and Health (ICF) of the World Health Organization (WHO), was employed at enrollment (T0) and at follow‐up evaluation (T1) after a mean interval of 15.4 ± 5.7 months. The Sensory Modality Sum score (SMS) at four limbs showed a significant worsening over time (mean score 27.2 ± 3.9 at T0 vs 25.7 ± 3 at T1 at upper limbs, P = .03; 20.5 ± 4.8 at T0 vs 18.6 ± 5.9 at T1 at lower limbs, P = .04). The Visual Analogue Scale (VAS) for pain significantly worsened at upper limbs at T1 (mean values 0.84 ± 1.95 at T0 vs 1.78 ± 2.6 at T1, P = .03). All the other tests did not show significant differences between T0 and T1. In the subgroup who underwent rituximab (15/32 treated before T0, 3/32 patients treated between T0 and T1 with median interval of 1 year), no significant differences were observed between T0 and T1. Despite the quite long follow‐up, statistical significance was not achieved either for the limited number of patients or for the lack of sensitive outcome measures. In our cohort, the significant worsening of the SMS and VAS after a median of 14 months can be considered as a reliable expression of the natural history of the disease, and suggest that these scales might represent possible outcome measures in anti‐MAG antibody neuropathy.     

Lack of caspase‐3 attenuates immobilization‐induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

Introduction: Immobilization by casting induces disuse muscle atrophy (DMA). Methods: Using wild type (WT) and caspase‐3 knockout (KO) mice, we evaluated the effect of caspase‐3 on muscle mass, apoptosis, and inflammation during DMA. Results: Caspase‐3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase‐3 decreased immobilization‐induced increased apoptotic myonuclei (3.2‐fold) and macrophage infiltration (2.2‐fold) in soleus muscle and attenuated increased monocyte chemoattractant protein‐1 mRNA expression (2‐fold in KO vs. 18‐fold in WT) in gastrocnemius. Conclusions: Caspase‐3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. Muscle Nerve 47: 711–721, 2013     

Assessment of musculo‐articular and muscle stiffness in young and older men

Introduction: The aim of this cross‐sectional study was to concurrently assess musculo‐articular stiffness (MAS) and muscle stiffness (MS) of the knee extensors in younger and older individuals. Methods: Fourteen young (22.1 ± 3.0 years old) and 12 older (65.4 ± 5.7 years old) men were tested for maximal voluntary contraction (MVC), rate of torque development (RTD), muscle thickness, MAS, and MS of knee extensors. Results: MVC, RTD, and muscle thickness were higher in the younger group (288.6 vs. 194.3 Nm, 1319.5 vs. 787.0 Nm s^?1, 23.1 vs. 17.7 mm, respectively, P < 0.05). MAS normalized to the load supported (30% of MVC) was not different between groups (87.9 vs. 88.5 Nm^?1kg^?1), whereas the older group exhibited a higher level of normalized MS (23.2 vs. 18.6 Nm^?1kg^?1, P < 0.05). Conclusions: Determinants of MS have been highlighted along with their role in elevated MS. The unaltered level of MAS, which is functionally important in an aging population, might be achieved through a decrease in tendon stiffness. Muscle Nerve 46: 559–565, 2012     

Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled,randomized, double‐blind,cross‐over study

S90049, a novel sublingual formulation of the non‐ergoline D₂‐D₃ agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (?13 ± 12 versus ?7 ± 9 respectively; estimated difference ?5.2, 95% Confidence Interval (CI)[?10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (?21.2 ± 10.1) and apomorphine (?23.6 ± 14.1) (estimated difference: 4.0 95% CI [?2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society     

Differences between acute‐onset chronic inflammatory demyelinating polyneuropathy and acute inflammatory demyelinating polyneuropathy in adult patients

Acute inflammatory demyelinating polyneuropathy (AIDP) and acute‐onset chronic inflammatory demyelinating polyneuropathy (A‐CIDP) are conditions presenting overlapping clinical features during early stages (first 4 weeks), although the latter may progress after 8 weeks. The aim of this study was to identify predictive factors contributing to their differential diagnosis. Clinical records of adult patients with AIDP or A‐CIDP diagnosed at our institution between January 2006 and July 2017 were retrospectively reviewed. Demographic characteristics, clinical manifestations, cerebrospinal‐fluid (CSF) findings, treatment and clinical evolution were analyzed. Nerve conduction studies were performed in all patients with at least 12 months follow‐up. A total of 91 patients were included (AIDP, n = 77; A‐CIDP, n = 14). The median age was 55.5 years in patients with A‐CIDP vs 43 years in AIDP (P = .07). The history of diabetes mellitus was more frequent in A‐CIDP (29% vs 8%, P = .04). No significant differences between groups were observed with respect to: human immunodeficiency virus (HIV) status, presence of auto‐immune disorder or oncologic disease. Cranial, motor and autonomic nerve involvement rates were similar in both groups. Patients in the A‐CIDP group showed higher frequency of proprioceptive disturbances (83% vs 28%; P < .001), sensory ataxia (46% vs 16%; P = .01), and the use of combined immunotherapy with corticoids (29% vs 3%; P = .005). There were no significant differences in CSF findings, intensive care unit (ICU) admission, or mortality rates. During the first 8 weeks both entities are practically indistinguishable. Alterations in proprioception could suggest A‐CIDP. Searching for markers that allow early differentiation could favor the onset of corticotherapy without delay.     

Analysis of video‐polysomnographic sleep findings in dementia with Lewy bodies

Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video‐polysomnographic (video‐PSG) investigations. We describe video‐PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video‐PSG monitoring. Twenty‐nine nondemented patients with Parkinson's disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal‐related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini–Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor‐behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment. © 2013 International Parkinson and Movement Disorder Society     

Anger in Parkinson's disease: A case‐control study

Cognitive‐psychiatric features of Parkinson's disease (PD) are common and they may be as disabling as the motor features of the disease. PD has been associated with stoic and inflexible personality traits. While many features of personality have been studied in PD, a systematic study of anger trait and anger expression in PD has not been performed. We used the Spanish adapted version of the state–trait anger Expression Inventory‐2 (STAXI‐2), comprised of six scales and an anger expression index, to measure anger trait and anger expression. There were 126 PD patients with depressive symptoms and 126 age‐ and gender‐matched controls. PD patients had lower levels of state anger (15.8 ± 3.1 vs. 17.9 ± 5.3, P < 0.001), trait anger (19.2 ± 5.3 vs. 20.7 ± 6.0, P < 0.05), anger expression‐out (9.0 ± 2.5 vs. 10.5 ± 3.0, P < 0.001), and anger expression index (26.1 ± 8.8 vs. 29.6 ± 9.4, P = 0.002); and higher levels in anger expression‐in (14.0 ± 3.4 vs. 12.2 ± 3.2, P < 0.001), anger control‐out (18.6 ± 5.0 vs. 16.1 ± 5.0, P < 0.001), and anger control‐in (14.3 ± 4.7 vs. 13.0 ± 4.5, P < 0.05) than controls. These differences persisted in analyses adjusting for age, gender, and depressive symptoms. Conclusions: PD patients showed lower levels of external expression of anger and higher levels of control of anger. Our results demonstrate another dimension to the stoic personality trait seen in PD. © 2007 Movement Disorder Society     

High prevalence of anti-α-crystallin antibodies in multiple sclerosis: correlation with severity and activity of disease

INTRODUCTION: The presence of T-cell reactivity to alphaB-crystallin in patients with multiple sclerosis (MS) has suggested that this small molecular weight heat shock protein (Hsp) may be an autoantigen in MS. MATERIAL AND METHODS: We have tested the serum of patients with clinically definite MS (n=30), other inflammatory neurological disease (n=22), non-inflammatory neurological disease (n=42) and healthy individuals (n=23) for systemic humoral responses to bovine alphaB-crystallin, to the homologous chaperone protein, alphaA-crystallin, and to another small Hsp, Hsp 27. RESULTS: Sixty-three percent of MS patients exhibited immunoreactivity to alpha-crystallin and this was present in all 4 of 4 non-ambulatory patients with MS. In contrast, serum concentrations in MS patients of antibodies to the small Hsp, Hsp27, and to myelin basic protein were negligible (P<0.001). Serum anti-alpha-crystallin immune responses were detected in significantly lower percentages of patients with other inflammatory neurological diseases (32%, P<0.025), and with non-inflammatory neurological diseases (12%, P<0.001). None of the healthy control individuals showed anti-alpha-crystallin reactivity. The concentration of anti-alpha-crystallin antibodies in patients with MS correlated with severe disease (P<0.05) and with active disease (P<0.025). CONCLUSION: Our observations support the notion that anti-alpha-crystallin autoimmune responses may contribute to pathogenicity in MS and may represent a mechanism of how recurrent attacks of MS develop subsequent to an isolated demyelinating episode.     

Randomized,placebo‐controlled trial of incobotulinumtoxina for upper‐limb post‐stroke spasticity

Introduction: Efficacy and safety of incobotulinumtoxinA in post‐stroke upper‐limb spasticity were studied. Methods: Subjects randomized 2:1 to incobotulinumtoxinA (fixed dose 400 U) or placebo, with fixed doses for the primary target clinical pattern (PTCP; flexed elbow, 200 U; flexed wrist, 150 U; clenched fist, 100 U). Doses for non‐primary patterns were flexible within predefined ranges. Results: At week 4, incobotulinumtoxinA led to larger improvements in PTCP Ashworth scale (AS) scores than placebo [least‐squares mean change ± standard error: –0.9 ± 0.06 (n = 171) vs. –0.5 ± 0.08 (n = 88); P < 0.001], and more subjects were PTCP AS responders (≥1‐point improvement) with incobotulinumtoxinA (69.6%) than with placebo (37.5%; P < 0.001). Investigator's Global Impression of Change confirmed superiority of incobotulinumtoxinA vs. placebo (P = 0.003). IncobotulinumtoxinA was associated with functional improvements, as demonstrated in responder rates for Disability Assessment Scale principal target at week 4 (P = 0.007). Adverse events were mainly mild/moderate, and were reported by 22.4% (incobotulinumtoxinA) and 16.8% (placebo) of subjects. Conclusions: IncobotulinumtoxinA significantly improved upper‐limb spasticity and associated disability, and was well‐tolerated. Muscle Nerve 53: 415–421, 2016     

Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia

Fan X, Borba CPC, Copeland P, Hayden D, Freudenreich O, Goff DC, Henderson DC. Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia. Objective: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine‐treated patients with schizophrenia. Method: In an 8‐week randomized, double‐blind, placebo‐controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole‐body dual‐energy X‐ray absorptiometry (DXA). Results: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. ?0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low‐density lipoprotein (LDL) levels (?15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (?376 ± 632 vs. ?36 ± 301 nm , P = 0.035). Further, there was a significant reduction in the lean mass (?1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole‐body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. Conclusion: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine‐treated patients with schizophrenia.     

Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks

Objective: Long‐term antidepressant (AD) treatment for depression in bipolar disorder (BPD) patients is highly prevalent, but its benefits and risks remain uncertain, encouraging this meta‐analysis of available research. Method: We reviewed randomized controlled trials for BPD involving ≥6 months of treatment with AD ± mood stabilizer (MS) vs. placebo ± MS, using meta‐analyses to compare reported risks of new depression vs. mania. Results: In seven trials (350 BPD patients) involving 12 contrasts, long‐term treatments that included ADs yielded 27% lower risk of new depression vs. MS‐only or no treatment [pooled relative risk, RR = 0.73; 95% CI 0.55–0.97; number‐needed‐to‐treat (NNT) = 11], but 72% greater risk for new mania [RR = 1.72; 95% CI 1.23–2.41; number‐needed‐to‐harm (NNH) = 7]. Compared with giving an MS‐alone, adding an AD yielded neither major protection from depression (RR = 0.84; 95% CI 0.56–1.27; NNT = 16) nor substantial increase in risk of mania (RR = 1.37; 95% CI 0.81–2.33; NNH = 16). Conclusion: Long‐term adjunctive AD treatment was not superior to MS‐alone in BPD, further encouraging reliance on MSs as the cornerstone of prophylaxis.     

Blink R1 latency utility in diagnosis and treatment assessment of polyradiculoneuropathy‐organomegaly‐endocrinopathy‐monoclonal protein‐skin changes and chronic inflammatory demyelinating polyradiculoneuropathy

Introduction: In polyradiculoneuropathy‐organomegaly‐endocrinopathy‐monoclonal protein‐skin changes (POEMS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), limb nerve conduction studies (NCSs) are limited in identifying demyelination and in detecting treatment effects in severely affected patients. Blink R1 latency may improve these assessments. Methods: POEMS and CIDP patients who had undergone NCS and blink reflex were identified. Correlations among R1 latency, limb NCS, and neuropathy impairment scores (NIS) were compared. Results: Among 182 patients (124 POEMS, 58 CIDP) who were identified, R1 prolongation (>13 ms) occurred in 64.3% (65.3% POEMS, 62.1% CIDP). R1 prolongation correlated with more severely affected NCS in both POEMS (ulnar CMAP 2.6 mV vs. 4.5 mV, P = 0.001) and CIDP (2.0 mV vs. 6.1 mV, P < 0.001). In severely affected patients (ulnar CMAP ≤0.5 mV [10%:18/182]), R1 (>13 ms) helped establish demyelination. In 31 patients (16 POEMS, 15 CIDP), the R1 latency changes were concordant with NIS changes in 94% of patients with POEMS and 60% of patients with CIDP. Discussion: Blink R1 latencies are valuable in defining demyelination and detecting improvement in severely affected POEMS and CIDP patients. Muscle Nerve 57 : E8–E13, 2018     

Relapsing Neuromyelitis Optica: demographic and clinical features in Iranian patients

Background: Neuromyelitis Optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system with distinguishing features from multiple sclerosis (MS). NMO has an unknown etiology with poor prognosis in which anti‐aquaporin‐4 receptor IgG seems to play a major role. The purpose of this study is to represent a clinical and demographic data of NMO in Iranian population. Methods: Of 1800 patients attending our MS clinic, 44 patients with NMO were recruited from 2006 to 2009. Results: Female to male ratio was 3:1 and the disease affected women in younger ages than men (P = 0.04). The median expanded disability status scale score was 3 and the mean duration of symptoms was 4.53 ± 3.41 (median = 4) years with annual relapse rate of 1.13 year/patient. The most frequent symptoms at presentation were optic neuritis 22 (50%) and transverse myelitis 14 (31.8%). Out of 12 patients whose titer of NMO‐IgG was measured, four (30.7%) patients were seropositive. Twenty‐eight patients (63%) received azathioprine for a mean duration of 16.84 ± 27.91 months with significantly lower annual relapse rate (0.4 year/patient). Conclusions: Iranian patients as a Caucasian population living in Asia seem to have the same clinical features in comparison with the reported studies from Western countries. Although the duration of follow‐up was not too long, but they may possibly have a more benign course.     

Rate and acceleration of whole‐brain atrophy in premanifest and early Huntington's disease

Huntington's disease (HD) produces progressive and ultimately widespread impairment of brain function. Neostriatal atrophy alone cannot account for whole‐brain losses seen postmortem, and the mutant huntingtin protein and its neuropathologic sequelae are evident throughout the brain. Whole‐brain atrophy quantification encompasses the totality of mutant huntingtin's effects on brain volume and may be useful in tracking progression in trials. We studied whole‐brain atrophy in HD using a 2‐year follow‐up design, with three annual MRI scans. We recruited 20 control subjects, 21 premanifest mutation carriers, and 40 patients with early HD and used the brain boundary shift integral to study rate and acceleration of atrophy. Among subjects with an acceptable quality 2‐year scan pair, age‐ and gender‐standardized mean brain atrophy rate was greater (P < 0.001) in the patients with HD (n = 21; 0.88%/yr; 95% confidence interval: 0.62–1.13%/yr) than that in controls (n = 13; 0.16%/yr; 0.00–0.32%/yr). In the 12 patients with early HD in whom acceleration could be directly assessed there was evidence (P= 0.048) of acceleration year‐on‐year (mean acceleration = 0.69% yr^?2; 95% confidence interval: 0.01% yr^?2 to 1.37% yr^?2), although this was not formally significantly different from that in controls (n = 7, P = 0.055). Statistically significantly increased atrophy rates and acceleration were not seen overall in the premanifest group, who were on average 18 years from predicted disease onset. We conclude that the study of whole‐brain atrophy has the potential to inform our understanding of the neurobiology of HD and warrants further study as one means of assessing the outcomes of future clinical trials. © 2009 Movement Disorder Society     

Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy

Introduction: We investigated the effects of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Eighteen CIDP patients treated with subcutaneous immunoglobulin performed 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run‐in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO₂‐max) and maximal combined isokinetic muscle strength (cIKS) of knee and elbow flexion/extension. Results: VO₂‐max and muscle strength were unchanged during run‐in (?4.9% ± 10.3%, P = 0.80 and ?3.7% ± 10.1%, P = 0.17, respectively). Aerobic exercise increased VO₂‐max by 11.0% ± 14.7% (P = 0.02). Resistance exercise resulted in an increase of 13.8% ± 16.0% (P = 0.0004) in cIKS. Discussion: Aerobic exercise training and resistance exercise training improve fitness and strength in CIDP patients. Muscle Nerve 57 : 70–76, 2018