Metabolic syndrome is common in adults with 5q-spinal muscular atrophy and impacts quality of life and fatigue.

INTRODUCTION/AIMS: Spinal muscular atrophy (SMA) is a multisystem disorder. We assessed metabolic syndrome (MetS) prevalence in adults with SMA and its association with motor function, quality of life (QoL), fatigue, and depression. METHODS: MetS was diagnosed using 2009 consensus criteria. Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), and 36-Item Short Form Health Survey (SF-36) were recorded and correlations between muscle function, depression, fatigue, QoL, and MetS were analyzed. RESULTS: We included 36 individuals (18 males; mean age: 38.7 ± 14.6 years). MetS was present in 25.0%. The most common component of MetS was central obesity (69.7%). Nearly half of the SMA individuals exhibited at least one abnormal lipid level result. Individuals with MetS more frequently were SMA type 3 (77.8% vs. 37.0%, p = .02) and had higher levels of fatigue (48.4 ± 6.7 vs. 39.5 ± 11.6, p = .03) than those without MetS. No associations of the presence of MetS with ambulatory status or HFMSE/RULM scores were observed. SMA individuals with MetS scored significantly lower in mental and social domains of QoL and total SF-36 score (p = .04). We observed weak to moderate correlations between the presence of MetS and SMA type, presence of comorbidities, QoL, and fatigue. DISCUSSION: The frequency of MetS was modestly higher among adults with SMA than in the general population, particularly in SMA type 3. MetS was associated with reduced QoL and increased fatigue. Larger studies are needed to fully understand the significance of MetS in adults with SMA.

Risdiplam therapy in adults with 5q-SMA: observational study on motor function and treatment satisfaction.

BACKGROUND: We aimed to describe the experience of a single neuromuscular center in Germany in treating adult spinal muscular atrophy (SMA) patients with risdiplam and to analyze motor function and treatment satisfaction during a follow-up period up to 20 months. METHODS: Fourteen patients with type 2 or 3 SMA (seven with SMA type 2, six with SMA type 3; age range: 18-51) were included. The Revised Upper Limb Module (RULM) and the Hammersmith Functional Motor Scale Expanded (HFMSE) were recorded at baseline and at follow-up (month 4, 8, 12, 16, 20). Treatment adverse events were collected at every follow-up visit. Patients' treatment satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: Half of the patients reached the 20-month follow-up. Based on the HFMSE score, no patients had clinically meaningful improvement. Twelve remained stable (92.3%), two showed transient clinically meaningful deterioration (15.4%) and one experienced lasting clinically meaningful deterioration (7.7%). Based on the RULM scores, seven patients were either stable or demonstrated clinically meaningful improvement (53.8%) and six showed clinically meaningful deterioration (46.2%). There was no treatment withdrawal during the follow-up. The most common adverse events were skin rash/increased skin sensitivity to sunlight (n = 3), diarrhea (n = 3), aphthous ulcer (n = 3) and abdominal pain (n = 2). Most patients stated to be at least "satisfied" with the medication. CONCLUSIONS: Risdiplam was well tolerated. Half of the patients remained stable or improved after risdiplam initiation. Larger and multicentric studies are needed to better understand the long-term effects of risdiplam in adult SMA.

Psychometric longitudinal evaluation of the Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) in patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: We studied the performance of a 15-item, health-related quality-of-life polyneuropathy scale in a longitudinal study of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Sixty-one patients with CIDP completed the Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) scale and Patient Impression of Change (PIC) at baseline and follow-up visits. Clinicians completed Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores at baseline and follow-up visits. Conventional and modern psychometric analyses were performed on the completed forms. RESULTS: CAPPRI was psychometrically stable between visits without significant difference in response pattern between visits 1 and 2 (paired t-test P = .72). There was strong correlation between changes in INCAT and changes in CAPPRI scores between two visits (rho = 0.6, P < .001). In addition, we showed robust CAPPRI effect sizes between PIC categories. CONCLUSIONS: We demonstrated psychometric stability and construct longitudinal validity of CAPPRI.

Neuropathic pain in patients with Charcot-Marie-Tooth type 1A.

BACKGROUND: Only several studies analyzed the characteristics of neuropathic pain (NeP) more extensively in patients with Charcot-Marie-Tooth type 1A (CMT1A). Therefore, we sought to determine the frequency and features of NeP in CMT1A patients and to assess the association between NeP and sociodemographic and clinical characteristics of patients with CMT1A. METHODS: Our research included 51 genetically diagnosed CMT1A patients. The International Association for the Study of Pain (IASP) criteria were used for diagnosis of NeP. PainDETECT questionnaire (PD-Q) was used to assess NeP features. The Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale (ONLS) score, and Beck Depression Inventory were also used. RESULTS: NeP was present in 15 (29.4%) patients with CMT1A. The average intensity of pain was 5.7 ± 2.2 out of 10. The most sensitive neuropathic symptoms were numbness, then tingling, and burning sensations, while the most specific symptom was allodynia. Patients with NeP more frequently reported pain in the back (p < 0.01) and the trunk (p < 0.05). Patients with NeP had more pronounced disability of the upper extremities and overall disability, as assessed by the ONLS score (p < 0.05). Depression was more frequent in patients with NeP compared with patients without NeP (66.7 to 13.9%, p < 0.01). CONCLUSION: NeP was present in almost one-third of the patients with CMT1A and it was moderate on average. Presence of NeP was associated with worse functional disability and depression.

Chronic Acquired Polyneuropathy Patient Reported Index (CAPPRI) in chronic inflammatory demyelinating polyradiculoneuropathy.

To date there are only two validations on the Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) questionnaire, both originated from the North America. We sought to translate and validate CAPPRI for use in Serbian patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We included 109 CIDP patients. CAPPRI, short form (36) health survey (SF-36), Medical Research Council Sum Score (MRC-SS), Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used. Serbian CAPPRI questionnaire was understandable and the language was appropriate and simple. Calculation demonstrated good person (0.9) and item (0.9) reliability with adequate item (4.1), and person (2.9) separation indices. There was a minor floor effect (13.8%), and no ceiling effect. All items had good fit, except items 2 (pain), 5 (sleeping), and 14 (eating) to some degree. Category responses were well ordered and organized, except item 14 (eating). The CAPPRI score did not vary regarding gender, age, or education. Patients with worse scores on MRC-SS, INCAT sensory score, INCAT disability score, FSS, and BDI had worse scores on CAPPRI (P < .01). The CAPPRI score showed strong correlation with the SF-36 score (rho = -0.76, P < .01). The Serbian version of the CAPPRI is reliable and valid patient-reported index for patients with CIDP, able to differentiate between levels of impairment and disability in this disease.

Validation of the Serbian version of inflammatory Rasch-built overall disability scale in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

Inflammatory Rasch-built overall disability scale (I-RODS) seems to be a valid activity measure for use in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our aim was to translate and validate the I-RODS for use in CIDP patients from Serbia. Study comprised 83 patients diagnosed with CIDP. I-RODS was translated and cross-culturally validated using the standard guidelines. Following scales were also administered: Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Krupp's Fatigue Severity Scale, Beck Depression Inventory, Visual Analogue Scale for pain, and health survey-36 (SF-36) as a quality of life measure. According to the I-RODS, significant proportion of our patients reported that "running" (51%), "dancing" (41%), and "standing for hours" (40%) were impossible tasks to perform, while "teeth brushing" (94%), "eating" (88%), and "reading a newspaper/book" (82%) were noted as the easiest items. Patients with more muscle weakness (lower MRC sum score) and more severe INCAT sensory score had lower I-RODS score (P < .01). Also, patients with fatigue, depression and pain had lower I-RODS scores (P < .01). I-RODS score correlated with the INCAT disability score (P < 0.01) was 78 ± 19 compared to 51 ± 30 in patients with INCAT >1 (P < .01). I-RODS score correlated with the total SF-36 score (rho = +0.73, P < .01), as well as with all SF-36 domain scores. Serbian version of the I-RODS seems to be a valid activity measure for use in CIDP patients. I-RODS was able to assess different levels of disability, it was in association with impairment measures, INCAT disability scale and quality of life. Further studies are needed to assess its responsiveness.

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.

Employment status of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

It has been previously shown that patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are unemployed or retired have worse quality of life. The aim of this study was to assess predictors of early retirement in CIDP. One hundred five patients with CIDP were included. Following measures were used: questionnaire on employment status, Medical Research Council Sum Score, INCAT disability score, Beck Depression Inventory, and Krupp's Fatigue Severity Scale. At the moment of testing, 2% of patients were students, 15% were employed, 9% were unemployed due to CIDP, 9% were unemployed but not due to CIDP, 28% were retired early due to disability caused by CIDP, and finally 37% were in old-age pension. Mean age when patients retired due to CIDP was 50 ± 8 years. Mean time from CIDP onset to retirement was 2.7 ± 2.3 years. Older age at onset, lower education, and more severe weakness at the time of diagnosis were significant predictors of early retirement due to CIDP. Retired patients were 12 times more likely to suffer from depression, compared to employed patients (OR = 12.2, 95% CI = 1.41-100, P < 0.01), and eight times more likely to have fatigue (OR = 8.2, 95% CI = 1.89-35.82, P < 0.01). Older patients with lower education and more severe weakness at the time of diagnosis were most likely retired due to CIDP. Early retirement was associated with depression and fatigue. Therefore, maintaining employment should be an important aim in the management of CIDP patients.

Neuromuscular disease-specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease-specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (ß = 0.35, p < 0.01), higher INCAT disability score at time of testing (ß = 0.29, p < 0.01), and being unemployed/retired (ß = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.

Three-Year Follow-Up Study in Patients with Guillain-Barré Syndrome.

A majority of patients with Guillain-Barré syndrome (GBS) have tendency of a good recovery. Our aim was to evaluate the outcome of the disease 1 and 3 years after GBS symptom onset. METHODS: During 2014, GBS was diagnosed in 82 patients in seven tertiary healthcare centers. Neurological follow-up was conducted in 57 (70%) patients after 1 year, and in 54 (66%) after 3 years. Functional disability was estimated according to the GBS disability scale (GDS), with a score of 0-3 indicating mild disability and a score of 4-6 indicating severe disability during acute phase, whereas a score >1 indicated poor recovery on follow-ups. Visual analog scale was used to assess sensory symptoms and musculoskelatal pain, and Krupp's Fatigue Severity Scale was used to asses fatigue. RESULTS: Poor functional outcome was found in 39% of GBS patients at year 1 and 30% at year 3. Paresthesias/dysesthesias were detected in 60% of patients after 1 year and 43% after 3 years. Musculoskeletal pain was present in 40% of patients at year 1 and 33% at year 3. Significant fatigue after 1 year was found in 21% of subjects and after 3 years in 7%. Parameters associated with poor functional outcome after 1 year were age >55 years (p=0.05), severe disability at admission (p1 indique une récupération difficile au moment des suivis. L'échelle visuelle analogue (EVA) a aussi été utilisée pour évaluer leurs symptômes sensoriels et leurs douleurs musculo-squelettiques. Enfin, l'échelle de gravité de la fatigue de Krupp a été utilisée pour évaluer leur degré de fatigue. Résultats: La première année, on a observé une piètre amélioration des capacités fonctionnelles chez 39% des patients atteints du SGB; pour la troisième année, cette proportion était de 30%. Au bout d'un an, on a aussi détecté la présence de paresthésie/dysesthésie chez 60% des patients; pour la troisième année, cette proportion était de 43%. Des douleurs musculo-squelettiques ont été rapportées chez 40% des patients après un an; deux ans plus tard, ce pourcentage chutait à 33%. Enfin, un état de fatigue important a été noté chez 21% des patients au bout d'un an; ce pourcentage n'était plus que de 7% au bout de trois ans. Les paramètres associés à une piètre amélioration des capacités fonctionnelles au bout d'un an étaient l'âge (>55 ans; p=0,05) ainsi qu'une incapacité sévère au moment de leur admission (p<0,05) et de leur congé (p<0,01). Au bout de trois ans, une piètre amélioration des capacités fonctionnelles était associée au sexe masculin (p<0,05) et à une incapacité sévère au moment d'obtenir un congé (p=0,06). CONCLUSIONS: Un an et trois ans après l'apparition des premiers symptômes du SGB, un nombre important de patients donnaient à voir des séquelles neurologiques, ce qui incluait une forme ou une autre d'incapacité fonctionnelle, des symptômes sensoriels, des douleurs et un état de fatigue.

Diabetes mellitus may affect short-term outcome of Guillain-Barré syndrome.

We sought to determine influence of diabetes mellitus on Guillain-Barré syndrome (GBS) course and short-term prognosis. Among the 257 GBS patients included in this retrospective study, diabetes mellitus was present in 17%. The degree of disability at admission and on discharge was assessed according to the GBS Disability Scale (mild disability = 0-3, severe disability = 4-6). Even after correction for age, diabetes mellitus was significantly associated with more severe disability at nadir (odds ratio, OR = 3.4, p < 0.05) and on discharge (OR = 2.0, p < 0.05). Linear regression analysis with multiple factors included showed that age and presence of diabetes were significant predictors of severe disability at nadir (adjusted R2 = 0.21, p < 0.05), and on discharge (adjusted R2 = 0.19, p < 0.05). The presence of diabetes mellitus affects short-term prognosis of GBS, independent of age.

Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy.

OBJECTIVE: To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN). METHODS: This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients (n = 24) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden's index), and correlations with demographic characteristics were calculated. RESULTS: Neurofilament concentrations were significantly higher in MND compared to MMN (p < 0.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman's rho 0.68, p < 0.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were ≥ 44.15 pg/mL (serum NfL) and ≥ 715.5 pg/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease. CONCLUSION: Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis.

Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% of all ALS cases is the accumulation of phosphorylated trans-activation response (TAR) DNA-binding protein 43 protein (pTDP-43) aggregates in the cytoplasm of neurons and glial cells within the central nervous system. Traditionally, it was believed that the accumulation of TDP-43 aggregates and subsequent neurodegeneration primarily occurs in motor neurons. However, contemporary evidence suggests that as the disease progresses, other systems and brain regions are also affected. Despite this, there has been a limited number of clinical studies assessing the non-motor symptoms in ALS patients. These studies often employ various outcome measures, resulting in a wide range of reported frequencies of non-motor symptoms in ALS patients. The importance of assessing the non-motor symptoms reflects in a fact that they have a significant impact on patients' quality of life, yet they frequently go underdiagnosed and unreported during clinical evaluations. This review aims to provide an up-to-date overview of the current knowledge concerning non-motor symptoms in ALS. Furthermore, we address their diagnosis and treatment in everyday clinical practice.

An observational cohort study on pulmonary function in adult patients with 5q-spinal muscular atrophy under nusinersen therapy.

BACKGROUND: Few studies assessed the effect of nusinersen on respiratory function in adult patients with spinal muscular atrophy (SMA). The aim of this single-center study was to analyze pulmonary function and its association with muscle function and quality of life (QoL) in adult patients with 5q-SMA under nusinersen. METHODS: We recorded forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF) during nusinersen treatment in 38 adult SMA patients. Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 36-Item Short Form Health Survey (SF-36) questionnaire and Fatigue Severity Scale (FSS) were recorded and correlations between muscle function, QoL, fatigue and respiratory parameters were analyzed. RESULTS: No differences were detected between mean FVC, FEV1, PEF at different timepoints versus baseline. Ambulatory patients showed significant improvement in mean PEF at month 30, compared to non-ambulatory patients (+ 0.8 ± 0.5 vs. - 0.0 ± 0.5, p < 0.05). Patients with fatigue at baseline showed significant improvement in mean PEF at month 10, compared to patients without fatigue at baseline (+ 0.6 ± 0.9 vs. - 0.4 ± 0.5, p < 0.05). Physical domains of SF-36 positively correlated with the change in FVC and FEV1. FSS negatively correlated with the change in mean PEF. CONCLUSION: Mean pulmonary function remained stable during nusinersen treatment over a period of up to 30 months. Improvement in pulmonary function was associated with improvement in motor function, fatigue and QoL, early after nusinersen initiation.

Analysis of 1840 Equine Intraocular Fluid Samples for the Presence of Anti-Leptospira Antibodies and Leptospiral DNA and the Correlation to Ophthalmologic Findings in Terms of Equine Recurrent Uveitis (ERU)-A Retrospective Study.

In the equine clinic of the LMU in Munich, therapeutic vitrectomies have been routinely performed in horses for three decades. The vitreous samples obtained during vitrectomies were usually tested for anti-Leptospira antibodies and for more than 20 years also by PCR for leptospiral DNA. If the indication for surgery was ophthalmologically inconclusive, an aqueous humor was collected preoperatively and examined for evidence of leptospiral infection. In this study, medical records from 2002 to 2017 were analyzed. Records for 1387 eyes affected by equine recurrent uveitis (ERU) and 237 eyes affected by another type of uveitis met the inclusion criteria. A total of 216 samples from healthy eyes were used as controls. In 83% of intraocular samples from ERU eyes, antibody titers of 1:100 or higher were detectable by microscopic agglutination test (MAT). Similarly, 83% of intraocular samples had anti-Leptospira antibodies detected by ELISA. In 72% of the intraocular specimens, leptospiral DNA was detectable by PCR. No antibodies were detectable in the samples from eyes with another type of uveitis or in the samples from healthy eyes. A PCR was positive in only one sample from a healthy eye. These results with a very high number of intraocular specimens demonstrate the great importance of an intraocular leptospiral infection for ERU. It can be concluded that for a reliable diagnosis of intraocular leptospiral infection or to reliably exclude an infection multiple tests should be applied.

Employment status of patients with Charcot-Marie-Tooth type 1A.

Previous studies showed that being unemployed is associated with lower quality of life in patients with Charcot-Marie-Tooth type 1A (CMT1A). The aim of this study was to assess the differences between CMT1A patients capable of working and CMT1A patients incapable of working due to CMT1A. Forty-four patients with genetically confirmed CMT1A were included. Medical Research Council (MRC) Sum Score, Charcot-Marie-Tooth Neuropathy Score (CMTNS), CMT Examination Score (CMTES), Overall Neuropathy Limitations Scale (ONLS), Beck Depression Inventory (BDI), Krupp's Fatigue Severity Scale (FSS), and Falls Efficacy Score (FES) were used. Whole cohort was divided into two groups: 1. CMT1A patients capable of working (employed and unemployed not due to CMT) and 2. CMT1A patients incapable of working due to CMT1A (unemployed due to CMT and retired due to CMT). At time of testing, 38.6% patients were employed, 13.6% were unemployed due to CMT, 6.8% were unemployed but not due to CMT, and 40.9% were retired early due to disability caused by CMT. Patients retired due to CMT1A at the age of 43 ± 10 years. ONLS total score and physical work appeared as significant independent predictors of being incapable of working due to CMT1A. Patients incapable of working were almost four times more likely to have fatigue (OR = 3.7, 95% CI 1.0-13.1, p < 0.05) and 11 times more likely to have fear of falling (OR = 11.0, 95% CI 2.0-59.7, p < 0.01). Patients with more severe functional disability and physical type of job were most likely incapable of working due to CMT1A. Incapability of working was associated with fatigue and fear of falling.

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A.

Introduction: Charcot-Marie-Tooth type 1A (CMT1A) comprises ~50% of all CMT cases. CMT1A is a slowly progressive motor and sensory neuropathy that leads to significant disability. We aimed to investigate the quality of life (QoL) in Serbian patients with CMT1A and to assess sociodemographic and clinical features associated with their QoL. Material and Methods: Forty-five genetically confirmed patients with CMT1A were included -60% women [age 50.4 ± 12.6 years, disease duration 22 (12.5-31.5) years]. SF-36, Medical Research Council (MRC) Sum Score, CMT Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS), Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used in the study. Results: Regarding SF-36, Mental Health and Social Functioning were the scales with the best achievements, whereas Role Physical was the worst domain. Worse QoL in patients with CMT1A was associated with elder age (rho = -0.34, p < 0.05), longer disease duration (rho = -0.31, p < 0.05), more pronounced muscle weakness measured by MRC-SS (rho = 0.43, p < 0.01), presence of tremor (p < 0.05), worse CMTES (rho = -0.68, p < 0.01), more severe disability in upper (rho = -0.70, p < 0.01) and lower limbs (rho = -0.61, p < 0.01) measured by ONLS scores, use of walking aids (p < 0.01), and with depression (p < 0.01) and fatigue (p < 0.01). Worse scores on CMTES (beta = -0.43, p < 0.01), BDI (beta = -0.39, p < 0.01), and FSS (beta = -0.36, p < 0.01) were significant independent predictors of worse QoL in patients with CMT1A (adjusted R 2 = 0.77, p < 0.001). Conclusion: Besides impairment made directly by CMT1A itself, QoL in these patients was also strongly affected by the presence of depression and fatigue. Since CMT1A is still not a curable disease, it is of interest to identify factors associated with QoL that are amenable to treatment.

Quality of life in hereditary neuropathy with liability to pressure palsies is as impaired as in Charcot-Marie-Tooth disease type 1A.

To date, only one study assessed quality of life (QoL) in patients with hereditary neuropathy with liability to pressure palsies (HNPP). We aimed to fill in this gap by investigating QoL in a cohort of patients with HNPP compared to Charcot-Marie-Tooth type 1A (CMT1A) patients, as well as to analyze sociodemographic and clinical features associated with QoL in HNPP. Eighteen genetically confirmed HNPP patients were age-and gender-matched with 18 CMT1A patients. SF-36 questionnaire was used to assess QoL. Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale Score (ONLS), Falls Efficacy Score (FES), Visual Analog Pain Scale, Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) were also used in our study. Although HNPP patients were less clinically impaired, no difference was observed in these two cohorts regarding SF-36 scores. Worse QoL in HNPP patients was associated with lower education (p < 0.01), physical work (p < 0.05), higher number of clinically affected nerves during the disease course (p < 0.01), worse MRC-SS score (p < 0.01), worse ONLS score (p < 0.01), and with more severe pain (p < 0.01), depression (p < 0.01), and fatigue (p < 0.01). Worse pain at the moment of testing appeared as a significant independent predictor of worse QoL in HNPP patients (ß = - 0.93, p < 0.001). QoL was similarly impaired in patients with HNPP and patients with CMT1A. We identified different factors associated with QoL in HNPP, and many of these factors are amenable to treatment which is of special interest in these still incurable disease.

Quality of life in patients with polyneuropathy associated with different types of monoclonal gammopathy of undetermined significance.

Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS-PNP) has a chronic and slowly progressive course but can lead to significant disability and reduced quality of life (QoL). The aim of this study was to analyze QoL in MGUS-PNP patients and to determine its predictors. Our study included 51 patients diagnosed with MGUS-PNP (23.5% with IgM, 66.7% IgG or IgA, 7.8% undetermined paraprotein, 2.0% light chains). QoL was assessed using the SF-36 questionnaire. The Medical Research Council Sum Score (MRC-SS), INCAT disability and sensory scores, ataxia score, Krupp's Fatigue Severity Scale and Beck's Depression Inventory were also used. Total SF-36 score was 50.0 ± 21.4 and no difference was observed between IgM and IgG/IgA MGUS-PNP. Physical composite score was worse than mental (44.4 ± 21.4 vs. 54.5 ± 20.9). Following factors showed correlation with SF-36 total score in univariate analysis: INCAT disability score, MRC-SS, INCAT sensory score, level of ataxia, fatigue and depression (p < 0.01). Significant predictors of worse SF-36 total score in our MGUS-PNP patients were depression (ß = - 0.46, p < 0.01), fatigue (ß = - 0.32, p < 0.01) and INCAT disability score (ß = - 0.27, p < 0.01). QoL in MGUS-PNP is equally affected in patients with different types of paraprotein. MGUS-PNP patients with more severe functional disability, fatigue and depression need special attention of clinicians since they could be at higher risk to have worse QoL. This should be taken into account when treating subjects with MGUS-PNP.

Yield of the PMP22 deletion analysis in patients with compression neuropathies.

INTRODUCTION: Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare neuromuscular disorder, mostly caused by PMP22 deletion. AIM: To determine a yield of the genetic analysis of PMP22 gene deletion in patients with compression neuropathies. METHOD: We included 112 patients with clinical suspicion of HNPP diagnosis. Nerve conduction studies (NCS) were performed for motor and sensory nerves bilaterally. Number of the PMP22 gene copies was determined using a real-time polymerase chain reaction (RT-PCR). RESULTS: PMP22 deletion was found in 34 (30.3%) patients. Patients with genetically confirmed HNPP had 12 years earlier disease onset compared to other patients with compression neuropathies (p < 0.01), more nerves affected during lifespan (5.5 ± 3.5 vs. 3.0 ± 2.0, p < 0.01) and at the time of referral (2.7 ± 2.5 vs. 2.0 ± 1.9, p < 0.05). HNPP patients had positive family history more frequently (p < 0.01). Foot deformities (pes cavus and hammertoe), symmetric muscle atrophy in lower legs and absent muscle reflexes in lower limbs were more common in HNPP patients. NCS abnormalities were also more common in HNPP group. Multiple linear regression analysis identified positive family history (ß = + 0.35, p < 0.01) and decreased sensory conduction velocity in at least three sensory nerves (ß = + 0.40, p < 0.01) as independent predictors of the PMP22 deletion. CONCLUSION: Among patients with compression neuropathies, those with a positive family history, earlier symptom onset and NCS abnormalities had a higher chance to have PMP22 deletion.