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P967: Two novel HSJ1 mutations in a cohort of distal hereditary motor neuropathy patients
Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
117, range 65–182) were significantly lower than control MUNIX (mean 215, range 131–391) and MPS (mean 329, range 165–503) (p<0.01). Similarly in CIDP patients both MUNIX (mean 64, range 19–139) and MPS (mean 98, range 15–223) were lower than controls (p<0.01). In CIDP patients MUSIX (mean 90, range 61–136) and sMUP (mean 50, range 29–69) were significantly higher than control MUSIX (mean 58, range: 40–89) and sMUP (mean 35, range 22–61) (p<0.05). In contrast, no significant difference was found for MUSIX (mean 65, range 48–104) and sMUP (mean 40, range 18–58) in AIDP patients compared to controls (p>0.05). When AIDP and CIDP groups were combined a sensitivity of 84.62% for MPS and 69.23% for MUNIX were estimated. Conclusions: Decreased MPS and MUNIX suggest presence of axonal loss both in AIDP and CIDP. Increased motor unit size in CIDP patients indicates compensatory reinnervation. Moreover, MPS is shown to be a more sensitive MUNE method than MUNIX in inflammatory demyelinating neuropathies.
P967 Two novel HSJ1 mutations in a cohort of distal hereditary motor neuropathy patients 1
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B. Gess , A. Schirmacher , M. Auer-Grumbach , J. Senderek , P. Young 1 University Hospital Muenster, Sleep Medicine and Neuromuscular Disorders, Muenster, Germany; 2 University Hospital Vienna, Neurology, Vienna, Austria; 3 Friedrich-Baur-Institute, Munich, Germany Distal hereditary motor neuropathies (dHMN) form a rare group of hereditary neuropathies characterized by distal motor symptoms. HSJ1 was recently found as the causative gene of a recessive dHMN in a Moroccan Jewish kindred. In this study, we undertook genetic testing for mutations in the HSJ1 gene in a cohort of dHMN patients from Germany and Austria. We found four patients, two each in two families, with HSJ1 mutations. Both HSJ1 mutations were novel and homozygous. One mutation was a splice-site-, the other a missense-mutation. The splice-site mutation was shown to lead to inclusion of an intron into the transcript, causing reduced expression of HSJ1 protein in patient fibroblast cultures. Patients showed distal-symmetric pareses of the legs and the hands. Nerve conduction studies showed axonal neuropathy with signs of acute and chronic denervation in electromyography. In one family, there was mild sensory involvement in clinical and electrophysiological testing. Taken together, we show a low frequency of HSJ1 mutations and present two novel mutations in our cohort of dHMN patients.
P968 Motor unit number estimation in diabetes mellitus patients with and without polyneuropathy M.-M. Kallestrup 1,2 , S. Paramanathan 1 , H. Andersen 2 , A. Fuglsang-Frederiksen 1 , H. Tankisi 1 1 Aarhus University Hospital, Dept. of Clinical Neurophysiology, Aarhus, Denmark; 2 Aarhus University Hospital, Dept. of Neurology, Aarhus, Denmark Question: What is the utility of Motor Unit Number Estimation (MUNE) methods in quantifying the degree of axonal loss in Diabetes Mellitus patients with and without polyneuropathy? Methods: Twenty-two Type I and Type II diabetic patients were prospectively included. Patients were divided into neuropathic (10) (mean age: 66, range: 47-78) and non-neuropathic group (12) (mean age: 64, range: 41-78), based on clinical examination and nerve conduction studies in dominant median motor and sensory, bilateral peroneal and tibial motor and bilateral sural nerves. Multipoint Stimulation MUNE (MPS) and Motor Unit Number Index (MUNIX) examinations on Abductor Pollicis Brevis by stimulating the median nerve were conducted. Motor unit size was calculated as surface motor unit potential (sMUP) and Motor unit size index (Musix). The results were compared with twenty untrained healthy control subjects (mean age: 46.7, range: 23-67). Results: In neuropathic patients MUNIX (mean: 122, range: 34-308) and MPS were (mean: 100, range: 63-262) significantly lower than control MUNIX (mean: 215, range: 131-391) and MPS (mean: 329, range: 162-503) (p<0.05). Similarly, in non-neuropathic diabetic patients, MUNIX (mean: 147, range: 65-306) and MPS (mean: 147, range: 61-304) were lower than controls (p<0.01). sMUP was significantly higher both in neuropathic (mean: 71, range: 38-120) and non-neuropathic (mean: 64, range: 39-130) patients than controls (mean: 35, range: 22-61) (p<0.05). In contrast, there
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was no difference in Musix between controls (mean: 58, range: 40-89) and neuropathic (mean: 67, range: 34-122) or non-neuropathic (mean: 65, range: 43-112) diabetic patients (p>0.05). Conclusions: Decreased MPS and Munix values together with increased sMUP suggest presence of axonal loss not only in neuropathic but also in non-neuropathic diabetic patients which probably could not be determined by routine NCSs due to compensatory reinnervation. However, further studies should be conducted with larger patient groups and older control subjects.
P969 New evidence suggesting high fasting glycemia as a cause of peripheral neuropathy in non-diabetic subjects B.I. Tiftikcioglu 1 , T. Duksal 1 , S. Bilgin 1 , S. Kose 2 , Y. Zorlu 1 Tepecik Research and Education Hospital, Neurology, Izmir, Turkey; 2 Tepecik Research and Education Hospital, Infectious Diseases and Clinical Microbiology, Izmir, Turkey
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Question: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have been referred to as “pre-diabetes” and represent an increased risk for diabetes. Although several groups have mentioned the necessity of evaluation of patients with IGT for neuropathy, IFG patients have not been studied yet. Microvascular inflammation is one of the major pathogenetic mechanisms in diabetic peripheral neuropathy (DPN). However, the relationship between inflammation and nerve conduction studies (NCS) abnormalities has not been studied extensively. We aimed to investigate the associations between the serum biomarkers of inflammation and endothelial dysfunction and the most distal sensory NCSs in the very early phases of diabetes, namely IFG and IGT. Methods: NCSs including sural, medial dorsal cutaneous (MDC), dorsal sural (DS) and medial plantar (MP) sensory nerves, were performed on 44 controls, 25 IFG and 25 IGT patients. Symptoms and examination were scored using Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS). Serum vWF and sE-selectin levels were analyzed for endothelial dysfunction, inflammation was assessed through an IL-6 assay. Results: Compared with controls, IL-6 levels were higher in IFG and IGT; vWF and sE-selectin levels were higher in IGT (p<0.001). Compared with IFG patients, levels of all biomarkers were higher in IGT (p<0.05). Increase in IL-6 levels was related to increase in NSS and NDS. Both IFG and IGT patients showed significant abnormalities in MDC, DS and MP sensory NCSs, even in patients with preserved sural NCSs. Increase in biomarkers of inflammation and endothelial dysfunction were correlated with various NCS abnormalities in MDC, DS, and MP sensory NCSs (p<0.05). Conclusions: Our results indicate that neuropathy might begin in individuals as early as IFG stage. This is confirmed by both clinically, through increased NSS and NDS, and electrophysiologically, through impaired NCSs of the most distal sensory nerves. Besides, the marked elevation in IL-6 indicates the on-going inflammation process in IFG patients. Abnormalities in the most distal sensory NCSs were associated with biomarkers of inflammation and endothelial dysfunction. Our findings highlight the importance of evaluating individuals with IFG, as well as IGT, in terms of peripheral neuropathy.
P970 Distinctive patterns of sonographic nerve enlargement in CharcotMarie-Tooth type 1A and hereditary neuropathy with pressure palsies S. Goedee, G. Brekelmans, L. van den Berg, L. Visser UMC Utrecht, Neurology, Utrecht, Netherlands Objective: We systematically investigated main arm and leg nerves in CMT-1A and HNPP patients to determine whether nerve sonography is able to discriminate between HNPP and CMT-1A. Background: Sonographic detection of morphologic abnormalities in polyneuropathies is a relatively new research area. The most prominently encountered pathological features are nerve enlargement, increased fascicle size, hypo-echogenicity and intraneural vascularization. There are only a few case reports and case series, mentioning nerve enlargement in CMT and HNPP patients. However, no systematic investigation has been performed yet. Methods: We recruited 9 patients fulfilling the international criteria on CMT-1A and 9 with DNA proven HNPP. Medical Research Council sumscore was determined. A standardized sonographic protocol was applied.
117, range 65–182) were significantly lower than control MUNIX (mean 215, range 131–391) and MPS (mean 329, range 165–503) (p<0.01). Similarly in CIDP patients both MUNIX (mean 64, range 19–139) and MPS (mean 98, range 15–223) were lower than controls (p<0.01). In CIDP patients MUSIX (mean 90, range 61–136) and sMUP (mean 50, range 29–69) were significantly higher than control MUSIX (mean 58, range: 40–89) and sMUP (mean 35, range 22–61) (p<0.05). In contrast, no significant difference was found for MUSIX (mean 65, range 48–104) and sMUP (mean 40, range 18–58) in AIDP patients compared to controls (p>0.05). When AIDP and CIDP groups were combined a sensitivity of 84.62% for MPS and 69.23% for MUNIX were estimated. Conclusions: Decreased MPS and MUNIX suggest presence of axonal loss both in AIDP and CIDP. Increased motor unit size in CIDP patients indicates compensatory reinnervation. Moreover, MPS is shown to be a more sensitive MUNE method than MUNIX in inflammatory demyelinating neuropathies.
P967 Two novel HSJ1 mutations in a cohort of distal hereditary motor neuropathy patients 1
1
2
3
1
B. Gess , A. Schirmacher , M. Auer-Grumbach , J. Senderek , P. Young 1 University Hospital Muenster, Sleep Medicine and Neuromuscular Disorders, Muenster, Germany; 2 University Hospital Vienna, Neurology, Vienna, Austria; 3 Friedrich-Baur-Institute, Munich, Germany Distal hereditary motor neuropathies (dHMN) form a rare group of hereditary neuropathies characterized by distal motor symptoms. HSJ1 was recently found as the causative gene of a recessive dHMN in a Moroccan Jewish kindred. In this study, we undertook genetic testing for mutations in the HSJ1 gene in a cohort of dHMN patients from Germany and Austria. We found four patients, two each in two families, with HSJ1 mutations. Both HSJ1 mutations were novel and homozygous. One mutation was a splice-site-, the other a missense-mutation. The splice-site mutation was shown to lead to inclusion of an intron into the transcript, causing reduced expression of HSJ1 protein in patient fibroblast cultures. Patients showed distal-symmetric pareses of the legs and the hands. Nerve conduction studies showed axonal neuropathy with signs of acute and chronic denervation in electromyography. In one family, there was mild sensory involvement in clinical and electrophysiological testing. Taken together, we show a low frequency of HSJ1 mutations and present two novel mutations in our cohort of dHMN patients.
P968 Motor unit number estimation in diabetes mellitus patients with and without polyneuropathy M.-M. Kallestrup 1,2 , S. Paramanathan 1 , H. Andersen 2 , A. Fuglsang-Frederiksen 1 , H. Tankisi 1 1 Aarhus University Hospital, Dept. of Clinical Neurophysiology, Aarhus, Denmark; 2 Aarhus University Hospital, Dept. of Neurology, Aarhus, Denmark Question: What is the utility of Motor Unit Number Estimation (MUNE) methods in quantifying the degree of axonal loss in Diabetes Mellitus patients with and without polyneuropathy? Methods: Twenty-two Type I and Type II diabetic patients were prospectively included. Patients were divided into neuropathic (10) (mean age: 66, range: 47-78) and non-neuropathic group (12) (mean age: 64, range: 41-78), based on clinical examination and nerve conduction studies in dominant median motor and sensory, bilateral peroneal and tibial motor and bilateral sural nerves. Multipoint Stimulation MUNE (MPS) and Motor Unit Number Index (MUNIX) examinations on Abductor Pollicis Brevis by stimulating the median nerve were conducted. Motor unit size was calculated as surface motor unit potential (sMUP) and Motor unit size index (Musix). The results were compared with twenty untrained healthy control subjects (mean age: 46.7, range: 23-67). Results: In neuropathic patients MUNIX (mean: 122, range: 34-308) and MPS were (mean: 100, range: 63-262) significantly lower than control MUNIX (mean: 215, range: 131-391) and MPS (mean: 329, range: 162-503) (p<0.05). Similarly, in non-neuropathic diabetic patients, MUNIX (mean: 147, range: 65-306) and MPS (mean: 147, range: 61-304) were lower than controls (p<0.01). sMUP was significantly higher both in neuropathic (mean: 71, range: 38-120) and non-neuropathic (mean: 64, range: 39-130) patients than controls (mean: 35, range: 22-61) (p<0.05). In contrast, there
S305
was no difference in Musix between controls (mean: 58, range: 40-89) and neuropathic (mean: 67, range: 34-122) or non-neuropathic (mean: 65, range: 43-112) diabetic patients (p>0.05). Conclusions: Decreased MPS and Munix values together with increased sMUP suggest presence of axonal loss not only in neuropathic but also in non-neuropathic diabetic patients which probably could not be determined by routine NCSs due to compensatory reinnervation. However, further studies should be conducted with larger patient groups and older control subjects.
P969 New evidence suggesting high fasting glycemia as a cause of peripheral neuropathy in non-diabetic subjects B.I. Tiftikcioglu 1 , T. Duksal 1 , S. Bilgin 1 , S. Kose 2 , Y. Zorlu 1 Tepecik Research and Education Hospital, Neurology, Izmir, Turkey; 2 Tepecik Research and Education Hospital, Infectious Diseases and Clinical Microbiology, Izmir, Turkey
1
Question: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have been referred to as “pre-diabetes” and represent an increased risk for diabetes. Although several groups have mentioned the necessity of evaluation of patients with IGT for neuropathy, IFG patients have not been studied yet. Microvascular inflammation is one of the major pathogenetic mechanisms in diabetic peripheral neuropathy (DPN). However, the relationship between inflammation and nerve conduction studies (NCS) abnormalities has not been studied extensively. We aimed to investigate the associations between the serum biomarkers of inflammation and endothelial dysfunction and the most distal sensory NCSs in the very early phases of diabetes, namely IFG and IGT. Methods: NCSs including sural, medial dorsal cutaneous (MDC), dorsal sural (DS) and medial plantar (MP) sensory nerves, were performed on 44 controls, 25 IFG and 25 IGT patients. Symptoms and examination were scored using Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS). Serum vWF and sE-selectin levels were analyzed for endothelial dysfunction, inflammation was assessed through an IL-6 assay. Results: Compared with controls, IL-6 levels were higher in IFG and IGT; vWF and sE-selectin levels were higher in IGT (p<0.001). Compared with IFG patients, levels of all biomarkers were higher in IGT (p<0.05). Increase in IL-6 levels was related to increase in NSS and NDS. Both IFG and IGT patients showed significant abnormalities in MDC, DS and MP sensory NCSs, even in patients with preserved sural NCSs. Increase in biomarkers of inflammation and endothelial dysfunction were correlated with various NCS abnormalities in MDC, DS, and MP sensory NCSs (p<0.05). Conclusions: Our results indicate that neuropathy might begin in individuals as early as IFG stage. This is confirmed by both clinically, through increased NSS and NDS, and electrophysiologically, through impaired NCSs of the most distal sensory nerves. Besides, the marked elevation in IL-6 indicates the on-going inflammation process in IFG patients. Abnormalities in the most distal sensory NCSs were associated with biomarkers of inflammation and endothelial dysfunction. Our findings highlight the importance of evaluating individuals with IFG, as well as IGT, in terms of peripheral neuropathy.
P970 Distinctive patterns of sonographic nerve enlargement in CharcotMarie-Tooth type 1A and hereditary neuropathy with pressure palsies S. Goedee, G. Brekelmans, L. van den Berg, L. Visser UMC Utrecht, Neurology, Utrecht, Netherlands Objective: We systematically investigated main arm and leg nerves in CMT-1A and HNPP patients to determine whether nerve sonography is able to discriminate between HNPP and CMT-1A. Background: Sonographic detection of morphologic abnormalities in polyneuropathies is a relatively new research area. The most prominently encountered pathological features are nerve enlargement, increased fascicle size, hypo-echogenicity and intraneural vascularization. There are only a few case reports and case series, mentioning nerve enlargement in CMT and HNPP patients. However, no systematic investigation has been performed yet. Methods: We recruited 9 patients fulfilling the international criteria on CMT-1A and 9 with DNA proven HNPP. Medical Research Council sumscore was determined. A standardized sonographic protocol was applied.