cover image European Journal of Neurology

European Journal of Neurology

2019 - Volume 26
Issue 8 | August 2019
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Article first published online:
09 Jul 2019 | DOI: 10.1111/ene.13714

Original Article

Background and purpose

Sporadic Creutzfeldt–Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease caused by an abnormal isoform of the human prion protein. Structural magnetic resonance imaging in patients with pathologically confirmed sCJD was compared with cognitively normal individuals to identify a cortical thickness signature of sCJD.

Methods

This retrospective cross‐sectional study compared patients with autopsy‐confirmed sCJD with dementia ( = 11) with age‐ and sex‐matched cognitively normal individuals ( = 22). We identified regions of interest (ROIs) in which cortical thickness was most affected by sCJD. Within patients with sCJD, the relationship between ROI cortical thickness and clinical measures (disease duration, cerebrospinal fluid tau and diffusion‐weighted imaging abnormalities) was evaluated.

Results

Compared with cognitively normal individuals, patients with sCJD had significantly reduced cortical thickness in multiple ROIs, including the fusiform gyrus, precentral gyrus, precuneus and superior temporal gyrus bilaterally; the caudal middle frontal gyrus, superior frontal gyrus, postcentral gyrus, inferior temporal gyrus and transverse temporal gyrus in the left hemisphere; and the superior parietal lobule in the right hemisphere. Only one patient with sCJD had co‐pathology consistent with Alzheimer's disease. Reduced cortical thickness did not correlate with disease duration, presence of diffusion restriction or elevated cerebrospinal fluid tau.

Conclusion

Cortical signature changes in sCJD may reflect brain changes not captured by standard clinical measures. This information may be used with clinical measures to inform the progression of sCJD and patterns of prion protein spread throughout the brain. These results may have implications for prediction of symptomatic progression and plausibly for development of therapeutic strategies.

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Authors:
J. Navid, G. S. Day, J. Strain, R. J. Perrin, R. C. Bucelli, A. Dincer, J. K. Wisch, D. Soleimani‐Meigooni, J. C. Morris, T. L. S. Benzinger and B. M. Ances
Article first published online:
25 Mar 2019 | DOI: 10.1111/ene.13930

Original Article

Background and purpose

Acute endovascular reperfusion treatment (aERT) of stroke patients with large‐vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of aERT in daily clinical routine are warranted and, in this study, we present national data from Denmark during 2011–2017.

Methods

National data for Denmark from 2011 to 2017 on all aERT procedures in patients with acute ischaemic stroke and computed tomography angiography/magnetic resonance angiography‐verified large‐vessel occlusion were derived from the Danish Stroke Registry, a national clinical quality registry to which reporting is mandatory for all hospitals treating stroke patients. Outcome (modified Rankin Scale score) after 3 months, including time of death, was assessed prospectively based on clinical examination or the Danish Civil Registration System.

Results

During the 7 years of observation, a total of 1720 patients were treated with aERT. The annual number of procedures increased from 128 in 2011 to 409 in 2017. The median age was 70 years, 58% were males and median National Institutes of Health Stroke Scale score at baseline was 16. Median time from symptom onset to groin puncture was 238 min with a decreasing trend during the years. Successful recanalization was reported in 1306 (76%) patients. At 3‐month follow‐up, an modified Rankin Scale score of 0–2 was reported in 46% of patients, whereas 14% of patients had died.

Conclusion

Routine data on aERT in acute ischaemic stroke in Denmark from 2011 to 2017 suggest that the procedure is safe and efficacious.

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Authors:
T. Truelsen, K. Hansen, G. Andersen, L. Sørensen, C. Madsen, A. Diaz, T. Stavngaard, H. H. Hundborg, J. Højgaard, N. Hjort, H. K. Iversen, S. P. Johnsen and C. Z. Simonsen
Article first published online:
19 Mar 2019 | DOI: 10.1111/ene.13931

Short Communication

Background and purpose

Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been identified in both children and adults with demyelination, with a strong association with bilateral or recurrent optic neuritis (ON). However, the full clinical spectrum of this newly described condition is unknown. We sought to describe non‐ON inflammatory ophthalmological presentations such as uveitis and optic perineuritis in the context of MOG antibody seropositivity.

Methods

Using a live cell‐based assay analysed by flow cytometry, we identified seropositive patients referred for MOG antibody testing in Australasia between 2014 and 2017. We identified four MOG antibody‐positive patients with non‐ON inflammatory ophthalmological presentations and present their detailed clinical information in this case series.

Results

Three patients had uveitis either in association with, or remote from, ON. One patient had optic perineuritis and peripheral ulcerative keratitis. We describe the presentation, examination, investigation findings and clinical course of these four patients.

Conclusions

Recognition of these novel clinical associations may expand the clinical spectrum of MOG antibody‐associated presentations. An expedited diagnosis may guide the management of these complex patients.

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Authors:
S. Ramanathan, C. Fraser, S. R. Curnow, M. Ghaly, R. J. Leventer, J. Lechner‐Scott, A. Henderson, S. Reddel, R. C. Dale and F. Brilot
Article first published online:
05 Mar 2019 | DOI: 10.1111/ene.13932

Letter to the Editor

Concerning to Schirinzi ., Natural history of a cohort of 1 variant female carriers

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Authors:
Laura B. Jardim, Vanessa B. Leotti, Ursula Matte and Carmen R. Vargas
Article first published online:
09 May 2019 | DOI: 10.1111/ene.13934

Original Article

Background

Healthy circadian rhythmicity has been suggested to relate to a better state of brain‐injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC).

Methods

Going beyond earlier studies, a systems‐level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale ‐ Revised (CRS‐R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients’ behavioural repertoire (CRS‐R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BT), i.e. when cognitive performance is expected to peak.

Results

The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS‐R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre‐specified time of occurrence of BT.

Conclusions

In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain‐injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre‐assessed) BT (≈4 pm in healthy individuals) as this is when patients should be most responsive.

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Authors:
C. Blume, M. Angerer, M. Raml, R. del Giudice, N. Santhi, G. Pichler, A. B. Kunz, M. Scarpatetti, E. Trinka and M. Schabus
Article first published online:
19 Mar 2019 | DOI: 10.1111/ene.13935

Original Article

Background and purpose

Breakthrough disease on first‐line injectables in relapsing‐remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS.

Methods

Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder‐adjusted Cox proportional hazard models.

Results

A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2–5.6) for RTX and 3.4 (95% CI, 1.3–9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01–0.38) for RTX and 1.0 (95% CI, 0.6–1.7) for FGL vs. NTZ.

Conclusions

In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.

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Authors:
M. Boremalm, A. Juto, M. Axelsson, L. Novakova, T. Frisell, A. Svenningsson, J. Lycke, F. Piehl and J. Salzer
Article first published online:
12 Mar 2019 | DOI: 10.1111/ene.13936

Original Article

Background and purpose

Diffuse white matter (WM) injury is prominent in primary‐progressive multiple sclerosis (PP‐MS) pathology and is a potential biomarker of disease progression. Diffusion kurtosis imaging allows the quantification of non‐Gaussian water diffusion, providing metrics with high WM pathological specificity. The aim of this study was to characterize the pathological changes occurring in the normal‐appearing WM of patients with PP‐MS at baseline and at 1‐year follow‐up and to assess their impact on disability and short‐term disease progression.

Methods

A total of 26 patients with PP‐MS and 20 healthy controls were prospectively enrolled. Diffusion kurtosis imaging single‐shot echo‐planar imaging (EPI) was acquired on a 3‐T scanner (Philips Achieva, Best, The Netherlands) (voxel size, 2 × 2 × 2 mm, 30 directions for each ‐value = 1000, 2000 s/mm and one  = 0 s/mm). A two‐compartment biophysical model of WM tract integrity was used to derive spatial maps of axonal water fraction (AWF), intra‐axonal diffusivity, extra‐axonal axial and radial diffusivities (, ) and tortuosity from the following WM tracts: corpus callosum (CC), corticospinal tract (CST) and posterior thalamic radiation (PTR).

Results

At baseline, patients with PP‐MS showed a widespread decrease of AWF, tortuosity and and an increase of in CC, CST and PTR ( ranging from 0.001 to 0.036). At 1‐year follow‐up, a significant AWF decrease was detected in the body of CC ( = 0.048), PTR ( = 0.008) and CST ( = 0.044). Baseline AWF values in CST significantly discriminated progressed from non‐progressed patients ( = 0.021; area under the curve, 0.854).

Conclusion

Based on its change over time and its relationship with disease progression, among the analyzed metrics, AWF seems the most sensitive metric of WM tissue damage in PP‐MS and therefore it could be considered as a marker for monitoring disease progression.

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Authors:
M. Margoni, M. Petracca, S. Schiavi, M. Fabian, A. Miller, F. D. Lublin and M. Inglese
Article first published online:
25 Mar 2019 | DOI: 10.1111/ene.13937

Original Article

Background and purpose

The aim of this study was to retrospectively investigate clinical and neuroimaging characteristics in the largest sample size of patients with corpus callosum infarction to date and then to follow up these patients for 1 year to clarify the prognosis of this rare stroke entity.

Methods

A total of 127 patients with acute callosal infarction out of 5584 acute ischaemic stroke patients were included in this study. The recruited patients were divided into a pure callosal infarction group and a complex callosal infarction group (coupled with other infarct locations simultaneously), and clinical and neuroimaging features were analyzed. Some of the patients were followed up for 1 year to evaluate recurrence rate and mortality.

Results

The incidence of acute callosal infarction was 2.3%. Most patients presented with advanced neurological dysfunction with or without mild to moderate motor or sensory disorders on admission. The negative rate of computed tomography scan was still 76.4% even at >24 h after onset. Large‐artery atherosclerosis was the most common etiological type. Compared with complex callosal infarction, the pure callosal infarction group had more mental disorders ( = 0.030). Compared with common basal ganglia infarction, the pure callosal infarction group had better short‐term recovery ( = 0.016) but higher 1‐year mortality ( = 0.037). Age and mental disorders were independent risk factors for death in callosal infarction.

Conclusions

Callosal infarction is a white matter stroke that occurs with low incidence. Elderly patients with vascular risk factors showed sudden mental or cognitive disorders and callosal infarction could not be excluded. More attention should be paid to the early diagnosis and secondary prevention of callosal infarction because of its poor long‐term outcome.

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Authors:
X. Sun, J. Li, C. Fan, H. Zhang, Y. Si, X. Fang, Y. Guo, J. H. Zhang, T. Wu, S. Ding and X. Bi
Article first published online:
11 Apr 2019 | DOI: 10.1111/ene.13942

Original Article

Background and purpose

Oxidative stress plays an important role in acute ischaemic stroke. However, the association of oxidative lipoprotein markers, including oxidized low‐density lipoprotein (oxLDL), oxLDL:high‐density lipoprotein (HDL) and oxLDL:low‐density lipoprotein (LDL), with functional outcome of minor stroke or transient ischaemic attack (TIA) remains unclear. We aimed to investigate the association between oxidative lipoprotein markers and poor functional outcome in patients with minor stroke or TIA.

Methods

All patients with minor stroke or TIA were recruited from the Clopidogrel in High‐Risk Patients With Acute Non‐Disabling Cerebrovascular Events (CHANCE) trial. The poor functional outcome included modified Rankin Scale (mRS) score 2–6 and 3–6 at 90‐day and 12‐month follow‐up. Multivariate logistic regression was used to investigate the associations of oxLDL, oxLDL:HDL and oxLDL:LDL with poor functional outcome.

Results

Among 3019 patients included in this study, the median (interquartile range) oxLDL, oxLDL:HDL and oxLDL:LDL were 13.96 (6.65–28.81), 4.52 (2.08–9.32) and 11.73 (5.27–24.85) μg/dL, respectively. After adjusted for confounding factors, patients in the highest oxLDL quartile had a higher proportion of mRS score 2–6 at 90 days [hazard ratio (HR), 1.78; 95% confidence interval (CI), 1.26–2.52] and 12 months (HR, 1.42; 95% CI, 1.01–1.99), and mRS score 3–6 at 90 days (HR, 1.98; 95% CI, 1.29–3.04) and 12 months (HR, 1.77; 95% CI, 1.09–2.89) when compared with the lowest oxLDL quartile ( < 0.05). Similar results were found for oxLDL:HDL and oxLDL:LDL.

Conclusions

Higher levels of oxidative lipoprotein markers are independent predictors of poor functional outcome in patients with minor stroke or TIA at 90 days and 12 months.

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Authors:
A. Wang, X. Zhang, S. Li, X. Zhao, L. Liu, S. C. Johnston, X. Meng, J. Lin, Y. Zuo, H. Li, Y. Wang and Y. Wang
Article first published online:
15 Mar 2019 | DOI: 10.1111/ene.13943

Original Article

Background and purpose

Patients with stroke mimics (SM), i.e. conditions with stroke‐like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions.

Methods

We included IVT‐treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003–2017, examined with magnetic resonance imaging 22–36 h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS‐MOST), Second European Co‐operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3 months.

Results

Of 10 436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5–10) vs. 8 (5–14),  < 0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% ( < 0.001), SICH NINDS in 0.5% vs. 3.9% ( < 0.001), SICH ECASS II in 0.2% vs. 2.1% ( = 0.007) and SICH SITS‐MOST in 0% vs. 0.5% ( = 0.28). Modified Rankin Scale score 0–1 at 3 months was present in 84.1% vs. 57.7% ( < 0.001) and death within 3 months in 2.6% vs. 5.4% ( = 0.028) of mimics and stroke patients, respectively.

Conclusions

This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.

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Authors:
B. Keselman, C. Cooray, G. Vanhooren, P. Bassi, D. Consoli, P. Nichelli, A. Peeters, D. Sanak, A. Zini, N. Wahlgren, N. Ahmed and M. V. Mazya
Article first published online:
25 Mar 2019 | DOI: 10.1111/ene.13944

Original Article

Background and purpose

Several diagnostic biomarkers are currently available for clinical use in early‐onset cognitive impairment. The decision on which biomarker is used in each patient depends on several factors such as its predictive value or tolerability.

Methods

There were a total of 40 subjects with early‐onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non‐neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid‐positron emission tomography (PET) and F‐fluorodeoxyglucose‐PET were performed. Neurologists provided pre‐ and post‐biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure.

Results

Cerebrospinal fluid biomarkers and amyloid‐PET increased diagnostic confidence in AD (77.4%–86.2% after CSF, 92.4% after amyloid‐PET, < 0.01) and non‐neurodegenerative conditions (53.6%–75% after CSF, 95% after amyloid‐PET, < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated.

Conclusions

Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early‐onset cognitive impairment.

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Authors:
N. Falgàs, A. Tort‐Merino, M. Balasa, S. Borrego‐Écija, M. Castellví, J. Olives, B. Bosch, G. Férnandez‐Villullas, A. Antonell, J. M. Augé, F. Lomeña, A. Perissinotti, N. Bargalló, R. Sánchez‐Valle and A. Lladó
Article first published online:
28 Mar 2019 | DOI: 10.1111/ene.13945

Original Article

Background and purpose

Tirofiban is used off‐label in clinical practice for acute ischaemic stroke (AIS). However, it is unknown whether tirofiban increases the bleeding risk or improves the outcome of endovascular treatment (EVT) in AIS. This study evaluated the efficacy and safety of tirofiban in combination with EVT for AIS.

Methods

Consecutive patients with AIS receiving EVT were included in the prospective stroke registry from 2015 to 2018. The efficacy outcomes were modified Rankin Scale (mRS) score at 3 months and National Institutes of Health Stroke Scale (NIHSS) score at 24 h. The safety outcomes were symptomatic intracerebral hemorrhage (sICH), any in‐hospital intracerebral hemorrhage, in‐hospital death and 3‐month death.

Results

Of 211 patients, 82 (38.9%) received tirofiban. A total of 39 (48.1%) with tirofiban and 44 (36.1%) without tirofiban had mRS score 0–2 [adjusted odds ratio (OR), 2.41; 95% confidence interval (CI), 1.11–5.23, = 0.026]. NIHSS score at 24 h was lower in the tirofiban group (9.5 vs. 12.0, adjusted = 0.032). Five (6.1%) patients with tirofiban and 16 (12.4%) without tirofiban had sICH (adjusted OR, 0.54; 95% CI, 0.16–1.83, = 0.32). In‐hospital intracerebral hemorrhage occurred in 10 (12.2%) patients with tirofiban and 41 (31.8%) without tirofiban (adjusted OR, 0.32; 95% CI, 0.13–0.76, = 0.01). In‐hospital death occurred in 7 (8.5%) patients with tirofiban and 16 (12.4%) without tirofiban (adjusted OR, 0.69; 95% CI, 0.22–2.13, = 0.52). A total of 13 (15.9%) patients with tirofiban and 22 (17.1%) without tirofiban were dead at 3 months (adjusted OR, 0.98; 95% CI, 0.40–2.40, = 0.96).

Conclusions

Tirofiban in combination with EVT was associated with a lower mRS score at 3 months and NIHSS score at 24 h. It was not associated with a higher rate of sICH, in‐hospital death and death at 3 months.

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Authors:
X. Pan, D. Zheng, Y. Zheng, P. W. L. Chan, Y. Lin, J. Zou, J. Zhou and J. Yang
Article first published online:
19 Mar 2019 | DOI: 10.1111/ene.13946

Letter to the Editor

Response to Jardim and colleagues regarding comments on ‘Natural history of a cohort of variant female carriers’

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Authors:
T. Schirinzi, G. Vasco, E. S. Bertini and M. Cappa
Article first published online:
06 May 2019 | DOI: 10.1111/ene.13947

Original Article

Background and purpose

Bowel symptoms are well documented in mitochondrial disease. However, data concerning other pelvic organs is limited. A large case–control study has therefore been undertaken to determine the presence of lower urinary tract symptoms (LUTS) and sexual dysfunction in adults with genetically confirmed mitochondrial disease.

Methods

Adults with genetically confirmed mitochondrial disease and control subjects were recruited from a specialist mitochondrial clinic. The presence and severity of LUTS and their impact on quality of life, in addition to sexual dysfunction and bowel symptoms, were captured using four validated questionnaires. Subgroup analysis was undertaken in patients harbouring the m.3243A>G mitochondrial DNA mutation. A subset of patients underwent urodynamic studies to further characterize their LUTS.

Results

Data from 58 patients and 19 controls (gender and age matched) were collected. Adults with mitochondrial disease had significantly more overactive bladder (81.5% vs. 56.3%,  = 0.039) and low stream (34.5% vs. 5.3%,  = 0.013) urinary symptoms than controls. Urodynamic studies in 10 patients confirmed that bladder storage symptoms predominate. Despite high rates of LUTS, none of the patient group was receiving treatment. Female patients and those harbouring the m.3243A>G mutation experienced significantly more sexual dysfunction than controls (53.1% vs. 11.1%,  = 0.026, and 66.7% vs. 26.3%,  = 0.011, respectively).

Conclusions

Lower urinary tract symptoms are common but undertreated in adult mitochondrial disease, and female patients and those harbouring the m.3243A>G mutation experience sexual dysfunction. Given their impact on quality of life, screening for and treating LUTS and sexual dysfunction in adults with mitochondrial disease are strongly recommended.

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Authors:
O. V. Poole, T. Uchiyama, I. Skorupinska, M. Skorupinska, L. Germain, D. Kozyra, S. Holmes, N. James, E. Bugiardini, C. Woodward, R. Quinlivan, A. Emmanuel, M. G. Hanna, J. N. Panicker and R. D. S. Pitceathly
Article first published online:
30 Apr 2019 | DOI: 10.1111/ene.13952

Original Article

Background and purpose

Conduction block is a pathognomonic feature of immune‐mediated neuropathies. The aim of this study was to advance understanding of pathophysiology and conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN).

Methods

A multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments.

Results

Of 49 CIDP and 14 MMN patients, 25% and 79% had median nerve forearm block, respectively. Clinical scores were similar in CIDP patients with and without block. CIDP patients with median nerve block demonstrated markedly elevated thresholds and greater threshold changes in threshold electrotonus, whilst those without did not differ from healthy controls in electrotonus parameters. In contrast, MMN patients exhibited marked increases in superexcitability. Nerve size was similar in both CIDP groups at the site of axonal excitability. However, CIDP patients with block demonstrated more frequent paranodal serum binding to teased rat nerve fibres. In keeping with these findings, mathematical modelling of nerve excitability recordings in CIDP patients with block support the role of paranodal dysfunction and enhanced leakage of current between the node and internode. In contrast, changes in MMN probably resulted from a reduction in ion channel density along axons.

Conclusions

The underlying pathologies in CIDP and MMN are distinct. Conduction block in CIDP is associated with paranodal dysfunction which may be antibody‐mediated in a subset of patients. In contrast, MMN is characterized by channel dysfunction downstream from the site of block.

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Authors:
N. Garg, S. B. Park, J. Howells, S. Vucic, C. Yiannikas, E. K. Mathey, T. Nguyen, Y. Noto, M. H. Barnett, A. V. Krishnan, J. Spies, H. Bostock, J. D. Pollard and M. C. Kiernan
Article first published online:
26 Apr 2019 | DOI: 10.1111/ene.13953

Original Article

Background and purpose

The expanded repeat length in negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non‐causative CAG repeats on the AAO of SCA patients. However, studies on Chinese SCA1 patients regarding candidate modifier factors involved in the variability in AAO are rare.

Methods

In all, 152 Chinese SCA1 patients who were genotyped for and nine other (CAG)‐containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)‐containing genes.

Results

Our results verified the negative effect of the expanded allele in by regression analysis. Some (CAG)‐containing genes including , and modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ,,,,, and normal alleles in were detected.

Conclusion

By using interaction analyses, , and were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.

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Authors:
P. Wang, Z. Chen, Y. Peng, L. Cao, X. Li, C. Wang, H. Yang, H. Peng, Y. Shi, X. Zhou, T. Li, L. Feng, C. Wu, R. Qiu, K. Xia, B. Tang and H. Jiang
Article first published online:
15 Apr 2019 | DOI: 10.1111/ene.13954

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Article first published online:
09 Jul 2019 | DOI: 10.1111/ene.14014