Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability

Background and Objectives:There is limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbidities, longitudinal impairments, and disabilities.Methods:Test-confirmed patients with SFN in Olmsted, Minnesota and adjacent counties were compared 3:1 to matched controls (January 1st, 1998-December 31st, 2017).Results:Ninety-four patients with SFN were identified, incidence 1.3/100,000/year increasing over the study period, prevalence 13.3/100,000. Average follow-up was 6.1 years (0.7-43 years), mean onset age 54 years (range 14–83). Female (67%), obesity (BMI mean 30.4 versus 28.5), insomnia (86% versus 54%), analgesic-opioid prescriptions (72% versus 46%), hypertriglyceridemia (180 mg/dl mean versus 147 mg/dl) and diabetes mellitus (DM) (51% versus 22%, p<0.001) were more common (OR 3.8-9.0, all p<0.03). Patients with SFN did not self-identify as disabled with median mRS of 1.0 (range 0-6) versus controls 0.0 (0-6), p=0.04. Higher Charlson comorbidities (median 6, range 3-9) occurred versus controls (median 3, range 1-9) p<0.001. Myocardial infarctions occurred in 46% versus 27% of controls (p<0.0001). Classifications included: idiopathic (70%); DM (15%); Sjögrens (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry (1%); lupus (1%); post viral (1%); Lewy body (1%) and multifactorial (5%). Foot ulcers occurred in 17, with 71% having DM. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3, change/year 0.08 (range 0-2.0). Median Neuropathy Impairment Score (NIS) was 2 at onset (range 0 to 8), change/year +1.0 (range -7.9 to +23.3). NIS and CASS change >+1 point/year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled DM, and Lewy body. Death from symptom onset was higher in patients with SFN 19% versus controls 12%, p<0.001, 50% secondary to DM complications.Discussion:Isolated SFN is uncommon but increasing in incidence. Most patients do not develop major neurological impairments and disability but have multiple comorbidities, including cardiovascular ischemic events, and increased mortality from SFN onsets. Development of large fiber involvements and DM are common over time. Targeted testing facilitates interventional therapies for DM but also rheumatologic and rare genetic forms.

Microsurgical Repair of Severed Thoracic Spinal Cord and Clinical Outcome: Technical Case Report

This report describes a case of successful repair of severed thoracic spine in a young man who presented with a penetrating stab injury to spine resulting in Brown-Séquard syndrome. Surgical technique and post-operative management is discussed.A 34-year-old fit and well healthy man was admitted with a history of stab injury to the thoracic spine at thoracic T2/3 level with ASIA impairment score (AIS) score D with an incomplete spinal cord affecting his left lower limb with complete paralysis and right lower limb paresis with impaired sensation below T6 level to L5. Neuroimaging confirmed a penetrating knife injury traversing the T2/3 level causing hemi-section of the spinal cord confirmed intraoperatively. He underwent an urgent exploratory surgery of his spine and a T2/3 laminectomy was performed to aid removal of the knife. The dura was noted to be contused and severed spinal cord was noted to be severed with associated cord oedema. A microsurgical repair of the severed cord was performed with duroplasty followed by intense neuro-rehabilitation. On a three month follow up his AIS score is E with lower limb power is 5/5 bilaterally and he is able to mobilise independently up to 8-10 steps without any supportive aid and with crutches he is independently functional and mobile.This is the first documented case of microsurgical repair of severed thoracic spinal cord secondary to traumatic knife injury. In the management of such scenario, apart from the removal of foreign body, repair of the cord with duroplasty should be carefully considered. The role of spinal neuroplasticity in healing following timely repair of the spinal cord along with intense rehabilitation remains the key. This had resulted in a good clinical and functional outcome with in a 12 month period.

Cerebral Visual Impairment in CDKL5 Deficiency Disorder Correlates With Developmental Achievement

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder is a rare neurodevelopmental disorder characterized by infantile-onset refractory epilepsy, profound developmental delays, and cerebral visual impairment. Although there is evidence that the presence of cerebral visual impairment in CDKL5 deficiency disorder is common, the potential impact of cerebral visual impairment severity on developmental attainment has not been explored directly. Focusing on a cohort of 46 children with CDKL5 deficiency disorder, examination features indicative of cerebral visual impairment were quantified and compared to developmental achievement. The derived cerebral visual impairment severity score was inversely correlated with developmental attainment, bolstering the supposition that cerebral visual impairment severity may provide a useful early biomarker of disease severity and prognosis. This study demonstrates the utility of a cerebral visual impairment score to better capture the range of cerebral visual impairment severity in the CDKL5 deficiency disorder population and further elucidates the interaction between cerebral visual impairment and developmental outcomes.

Responder analysis for neuropathic impairment and quality-of-life assessment in patients with hereditary transthyretin amyloidosis with polyneuropathy in the NEURO-TTR study

Objective Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare disease characterized by rapid neuropathic progression. In pivotal studies of gene-silencing treatments, the modified Neuropathy Impairment Score + 7 tests (mNIS + 7) and Norfolk-Quality of Life (QOL)-Diabetic Neuropathy (DN) questionnaire assessed treatment impact on neuropathic progression. Establishing responder definition (RD) thresholds for these measures would enable evaluation of clinically meaningful treatment benefit. Methods mNIS + 7 and Norfolk-QOL-DN were administered at baseline and week 65 to 165 adults with ATTRv-PN receiving inotersen (n = 106) or placebo (n = 59) in the NEURO-TTR study. Anchor-based approaches for estimating RD thresholds were used for Norfolk QOL-DN, while distribution-based approaches were used for both measures. Responders were patients with a score change < RD, indicating improvement or stabilization (i.e., no clinically meaningful progression). Odds ratios (ORs) and Fisher’s exact tests compared proportions of responders by treatment. Results The mean RD estimates were 12.2 points and 8.8 points for mNIS + 7 and Norfolk QOL-DN, respectively. The proportions of patients whose change in score indicated improvement or stabilization were statistically significantly larger for inotersen than placebo for all estimated RD thresholds for mNIS + 7 (64–86% responders for inotersen vs. 27–46% for placebo, ORs = 3.8–7.2, ps < 0.001) and Norfolk QOL-DN (66–81% vs. 35–56%, ORs = 2.4–3.6, ps < 0.05). Discussion Establishing RD thresholds for these instruments enables evaluation of clinically relevant and individual-level treatment benefit on neuropathic progression. Across RDs estimated using multiple methods, a higher proportion of patients receiving inotersen than placebo showed improved or stabilized neuropathic progression at week 65. Trial registration ClinicalTrials.gov Identifier: NCT01737398; Date of registration: November 29, 2012.

POS1486-HPR DAILY ACTIVITY IMPAIRMENT IS MEDIATED BY BOTH ORAL DRYNESS AND ORAL HEALTH RELATED QUALITY OF LIFE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

Background:Both oral functions and oral health-related quality of life (OHRQoL) are poorly affected by low salivary flow rate in patients with primary Sjögren’s syndrome (pSS).Objectives:The aim of the study was to evaluate the effects of oral dryness and OHRQoL on daily life in patients with primary Sjögren’s syndrome (pSS).Methods:In this cross-sectional study, 86 patients with pSS (M/F: 5/81; mean age: 52.4 ± 11.6 years) were included. The data were collected by clinical examination and a questionnaire regarding patient-reported outcome measures (PROMs). Patient filled PROMs regarding Oral Health Impact Profile-14 (OHIP-14) for OHRQoL, Work Productivity and Activity Impairment scale (WPAI) for Daily life and the EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) for their symptoms. Unstimulated whole saliva flow rates (U-WSFR) of patients were calculated as ml/min. Increases in PROMs and decreases in U-WSFR reflected poor conditions. After preliminary analysis, a mediation analysis was used to evaluate the relations among variables.Results:WPAI-Daily activity impairment score was higher in patients with low U-WSFR (≤0,1 ml/min) than the others (67±29,8 vs 52,5±28,6) (p=0.042). Both U-WSFR (0,43±0,57 ml/min) and ESSPRI-Dryness score (6.31 ± 2.71) were correlated with scores of OHIP-14 (25,96±17,13)(r:- 0,38 p=0.000; r: 0,37 p=0.000) and WPAI-Daily activity impairment (57,96±29,71)(r: -0,36 p=0.004; r: 0,53 p=0.000). Moreover, scores of ESSPRI-Pain (5,16±3,12) and ESSPRI-Fatigue (5,41±2,97) were also related to WPAI-Daily activity impairment score (r: 0,41 p=0.001; r:0,49 p=0.000, respectively).In the mediation analysis, WPAI-Daily activity impairment score (57.9 ± 29.7) was directly mediated by ESSPRI-Dryness score (p=0.0010) and indirectly mediated by OHIP-14 score (25.9 ± 17.1) (p=0.0357). After mediation analysis, a bootstrap analysis with 5000 replications was applied to estimate the mediation effect to generate 95% CI. Percentile bootstrap of OHIP-14 score was found to be an effective mediator for Daily activity impairment based on 5000 bootstrap samples.Conclusion:Both oral dryness and poor OHRQoL in patients with pSS affected daily activity impairment. Therefore, the patients’ needs for improving oral health were critical components of treatment plans to improve the daily activity of SjS patients.Disclosure of Interests:None declared

Clinical Outcome of Single-Stage Decompression and Posterior Stabilization in Thoracolumbar Spinal Tuberculosis

Background Thoracolumbar spine constitutes the most common site for spinal tuberculosis. Though the treatment of spinal tuberculosis is antitubercular drugs initially, the patient with neurologic weakness warrants definitive surgical procedure of decompression and stabilization. Even though many investigators have reported favorable results with anterior decompression and stabilization surgery, due to the increased morbidity and complications, the posterior-only approach with decompression and stabilization has evolved as the operation of choice in recent time. Methods All patients aged between 18 and 70 years with clinically and radiologically proven symptomatic thoracolumbar spinal tuberculosis who failed with conservative treatment for 4 weeks or developed neurologic weakness between the treatments are included in this study. All patients were offered decompression and posterior stabilization with transpedicular screws and rods after explaining the above procedure. Clinical outcome was measured by modified Frankel grading; AIS (American Spinal Injury Association impairment score) grade impairment score; and pain assessment done with visual analog scale (VAS) pre- and postoperatively and at 3, 6, and 9 months of interval. Results The postoperative pain relief, neurologic improvement as per modified Frankel grade, AIS grade, and improvement in erythrocyte sedimentation rate and C-reactive protein were significant as compared with the preoperative status. The surgical interventions thus prove to have adequate relief to the patient and arresting the disease progression. The surgical outcome has very minimal intra- and postoperative complications. Conclusion Single-stage decompression and posterior stabilization in thoracolumbar spinal tuberculosis is safe, effective, and results in good clinical outcome. The advantages of surgery include thorough debridement, decompression, and achievement of spinal stabilization.

Golimumab improves work productivity in patients suffering from moderate to severe ulcerative colitis: results of a prospective study over 24 months

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with recurrent episodes of debilitating symptoms negatively affecting work productivity and health-related quality of life (HRQoL). The use of biologics in UC treatment improves work and HRQoL but prospective long-term data concerning the treatment with TNFα inhibitor golimumab in UC patients are still rare. Therefore, our study aimed to evaluate the change in work productivity, capacity for daily activities and HRQoL in UC patients treated with golimumab in Germany. Methods Using the Work Productivity and Activity Impairment questionnaire, the change in work productivity and in capacity for daily activities after 3 months and over the whole observational period of 24 months were assessed (both primary endpoints). Disease-specific and health-related quality of life (QoL) were analyzed with the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short-Form 12 Health Survey Questionnaire (SF-12), and the Partial Mayo Score (secondary endpoints). Further, disease-related hospitalization rates were assessed. Results This prospective non-interventional study included 286 patients. Thereof, 212 patients were employed at baseline (modified intention to treat analysis set employed at baseline, mITTe). 61.3% of the mITTe patients had moderate and 17.0% had severe UC. Three months after initiation of golimumab therapy, total work productivity impairment (TWPI) score and activity impairment score improved significantly from baseline with a mean change of − 17.3% (p < 0.0001) and − 14.4% (p < 0.0001), respectively. Results persisted over 24 months (mean change TWPI score: − 24.5%, mean change activity impairment score: − 30.0%). Disease- and health-related QoL also improved significantly under golimumab treatment as indicated by increased IBDQ [mean change: 28.0 (SD: ± 36.1, month 3), 42.1 (SD: ± 39.5, month 24)] and SF-12 scores [PCS-12: 45.9 (SD: ± 8.5), MCS-12: 4.9 (SD: ± 10.6, month 3), PCS-12: 5.9 (SD: ± 9.0), MCS-12: 6.4 (SD: ± 11.1, month 24)]. Disease-related hospitalization rate decreased from 16.0% (BL) to 4.3% at month 24 and the mean number of missed working days due to UC decreased from 8.2 (SD: 17.6, BL) to 0.7 (SD: 2.1) after golimumab induction. Conclusions Golimumab leads to notable long-term improvements in work productivity, daily activity, HRQoL, and disease-related hospitalization rates in patients with moderate to severe UC. Trial registration: PEI (Paul-Ehrlich-Institute, Langen, Germany) Registration Nr: NIS#255 (https://www.pei.de/SharedDocs/awb/nis-0201-0300/0255.html)

Symptom burden in multimorbidity: a population-based combined questionnaire and registry study from Denmark

ObjectivePatients with multimorbidity may carry a large symptom burden. Symptoms are often what drive patients to seek healthcare and they also assist doctors with diagnosis. We examined whether symptom burden is additive in people with multimorbidity compared with people with a single morbidity.DesignThis is a longitudinal cohort study drawing on questionnaire and Danish national registry data. Multimorbidity was defined as having diagnoses from at least two out of ten morbidity groups. Associations between morbidity groups and symptom burden were estimated with multivariable models.ParticipantsIn 2012, 47 452 participants from the Danish Symptom Cohort answered a questionnaire about symptoms (36 symptoms in total), including whether symptoms were affecting their daily activities (impairment score) and their worries about present symptoms (worry score) (the highest score among the 36 symptoms on a 0–4 scale).Main outcome measureThe primary outcome was symptom burden.ResultsParticipants without morbidity reported 4.77 symptoms (out of 36 possible). Participants with one, two or three morbidities reported more symptoms than patients without morbidity (0.95 (CI 0.86 to 1.03), 1.87 (CI 1.73 to 2.01) and 2.89 (CI 2.66 to 3.12), respectively). Furthermore, they reported a higher impairment score (0.36 (0.32 to 0.39), 0.65 (0.60 to 0.70) and 1.06 (0.98 to 1.14)) and a higher worry score (0.34 (0.31 to 0.37), 0.62 (0.57 to 0.66) and 1.02 (0.94 to 1.10)) than participants without morbidity. In 45 possible combinations of multimorbidity (participants with two morbidities), interaction effects were additive in 37, 41 and 36 combinations for the number of symptoms, impairment score and worry score, respectively.ConclusionParticipants without morbidity reported a substantial number of symptoms. Having a single morbidity or multimorbidity resulted in approximately one extra symptom for each extra morbidity. In most combinations of multimorbidity, symptom burden was additive.

Lumbosacral Radiculoplexus Neuropathy: Neurological Outcomes and Survival in a Population-based Study

Objective:To determine whether community Lumbosacral Radiculoplexus Neuropathy (LRPN) patients have milder neuropathy than referral patients, we characterize the outcomes and survival of population-based compared to referral-based LRPN cohorts .Background:Previously, we found that the incidence of LRPN is 4.16/100,000/year, a frequency greater than other inflammatory neuropathies. The survival of LRPN is uncharacterized.Materials/Methods:62 episodes in 59 LRPN patients were identified over 16 years (2000-2015). Clinical findings were compared to previous referral-based LRPN cohorts. Survival data were compared to age-gender matched controls.Results:At LRPN diagnosis, median age was 70 years, median neuropathy impairment score (NIS) 22 points, 92% had pain, 95% weakness, 23% were wheelchair-bound and median modified Rankin scale (mRS) was 3 (1-4). At last follow-up, median NIS improved to 17 points (p<0.001) with 56% having ≥4 points improvement, 16% were wheelchair-bound, and median mRS was 2. Compared to referral-based LRPN cohorts, community LRPN had less impairment, less bilateral disease (37% vs 92%) and less wheelchair usage (23% vs 49%). LRPN survival was 86% at 5 years and 55% at 10 years. Compared to age-gender matched controls, LRPN patients had 76% increased risk of death (p=0.016). In multivariate analysis, diabetes mellitus, age, stroke, chronic kidney disease, peripheral artery disease, and coronary artery disease were significant mortality risk factors but LRPN was not.Conclusions:LRPN is a painful, paralytic, asymmetric, monophasic, sometimes bilateral pan-plexopathy that improves over time but leaves patients with impairment. Although having LRPN increases mortality, this increase is probably due to comorbidities (diabetes mellitus) rather than LRPN itself.

Sagittal bending of the optic nerve at the entrance from the intracranial to the optic canal and ipsilateral visual acuity in patients with sellar and suprasellar lesions

OBJECTIVEVisual acuity impairment due to sellar and suprasellar tumors is not fully understood. The relationship between these tumors and disturbance of visual function was examined using preoperative MRI.METHODSThis study reviewed 93 consecutive patients with sellar and suprasellar tumors. Best-corrected visual acuity (BCVA) and visual impairment score (VIS) were used for estimation of visual impairments. Preoperative MR images were examined to obtain several values for estimation of chiasmatic compression. Additionally, the optic nerve–canal bending angle (ONCBA) was newly defined as the external angle formed by the optic nerve in the optic canal and the optic nerve in the intracranial subarachnoid space at the junction, using preoperative sagittal T2-weighted MR images.RESULTSThe mean ONCBA was about the same on the right (44° ± 25°) and the left (44° ± 24°). Sagittal ONCBA was defined as large (> 45°) and moderate (≤ 45°) on each side. Preoperative VIS was found to be significantly worse if the right or left ONCBA (or both) was large (right side: ONCBA large [median 20, IQR 8–30] > ONCBA moderate [median 10, IQR 3–17], p = 0.003, Mann-Whitney U-test; left side: ONCBA large [median 22, IQR 9–30] > ONCBA moderate [median 10, IQR 2–16], p = 0.001). A large ONCBA showed a significant relationship with unfavorable ipsilateral BCVA (> logMAR, 0; right side, p = 0.001, left side, p = 0.001, chi-square test). The ONCBA had a positive correlation with ipsilateral BCVA (right: r = 0.297, p = 0.031; left: r = 0.451, p = 0.000, Pearson’s correlation coefficient). Preoperative BCVA was significantly lower on the same side in the large ONCBA group compared with the moderate ONCBA group (right side: large ONCBA 0.169 ± 0.333 [logMAR, mean ± standard deviation] vs moderate ONCBA 0.045 ± 0.359, p = 0.026, Student t-test; left side: large ONCBA 0.245 ± 0.346 vs moderate ONCBA 0.025 ± 0.333, p = 0.000). This visual acuity impairment improved after resection of the tumors.CONCLUSIONSSagittal bending of the optic nerve at the entrance from the intracranial subarachnoid space to the optic canal may be related to ipsilateral deterioration of visual acuity in sellar and suprasellar lesions. Sagittal T2-weighted MRI is recommended for preoperative estimation of the optic nerve bending.