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P614: Micromutations in PMP22 gene in patients with severe inherited neuropathies: report of a family
Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
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P612 Small and large fibre neuropathy in patients with diabetes type 1 compared with type 2: a follow-up study S. Løseth 1,2 , E. Stålberg 3 , S. Lindal 4 , R. Jorde 5 , S.I. Mellgren 6 University of Tromsø, Tromsø, Norway; 2 University Hospital of North Norway, Department of Clinical Neurophysiology, Tromsø, Norway; 3 Uppsala University Hospital, Department of Clinical Neurophysiology, Uppsala, Sweden; 4 University Hospital of North Norway, Department of Pathology, Tromsø, Norway; 5 University Hospital of North Norway, Department of Internal Medicine, Tromsø, Norway; 6 University Hospital of North Norway, Department of Neurology, Tromsø, Norway 1
Question: Are there differences in the spectrum of large and small fibre involvement in patients with diabetes type 1 versus those with type 2? Methods: Fifty-nine patients (35 type 1 and 24 type 2 diabetes) were included in a follow-up study after 5 years. Nerve conduction studies (NCS), quantitative sensory testing (QST) at the distal calf and skin biopsy for quantification of intraepidermal nerve fibre density (IENFD) in addition to symptom scoring and clinical evaluations were performed. Z-scores were calculated to adjust for the physiologic effects of age, height and gender. Results: Patients with type 1 diabetes were younger with longer disease duration; they had higher HbA1c and lower BMI. Neuropathic symptoms tended to be more frequent in type 2 (54% versus 37%; ns). Comparing data to the baseline study, the overall NCS score was more abnormal after 5 years in both type 1 (p=0.006) and type 2 diabetes (p=0.02). IENFD became significantly lower only in those with type 2 (reduction from 7.9±4.8 to 4.3±2.8 fibres/mm, p=0.006). Cold perception threshold was higher in type 2 at follow-up compared to baseline (p=0.049). Between the two types of diabetes the difference of progression of abnormalities was only significant for the IENFD (more progression in type 2, p=0.048). Conclusions: A 5 year follow-up study in diabetics showed progression of large fibre neuropathy in both type 1 and type 2. Small fibre neuropathy seems to progress more rapidly in those with type 2.
P613 Detection of early neuropathy in type 2 diabetes mellitus R. Remli 1 , S.A. Md Rani 1 , W.N.N. Wan Yahya 1 , R. Sahathevan 1 , Z. Md Zain 2 , N. Mohamed Ibrahim 1 , R. Azman Ali 1 , H.J. Tan 1 1 National University of Malaysia, Medical Department, Kuala Lumpur, Malaysia; 2 National University of Malaysia, Community Health Department, Kuala Lumpur, Malaysia Question: To determine the frequency and predictors of asymptomatic lower limb neuropathy amongst type 2 diabetic patients in University Kebangsaan Malaysia Medical Centre (UKMMC). Methods: This was a cross sectional study which recruited diabetic patients in UKM Medical Centra who did not have any neuropathy symptoms. All patients who obtained a score of “0” in diabetic neuropathy symptoms score (unsteadiness in walking, neuropathic pain, paraesthesia, numbness [1] (Table 1).
Figure 1. The frequency of nerve conduction parameters abnormalities in motor and sensory nerves.
All patients were subjected to a neurological examination to ascertain their and nerve conduction studies. Result: Ninety diabetic patients who were asymptomatic for neuropathy were recruited. Of these, 81 patients (90%) had abnormal NCS and 9 patients (10%) had normal NCS. From 81 asymptomatic neuropathy patients, 14 (15.6%) had pure motor neuropathy, 12 (12.2%) had pure sensory neuropathy and 56 (62%) had mixed sensorimotor neuropathy (Fig. 1). Duration of diabetes, age of diabetic patients and presence of retinopathy were found to be significantly associated with the presence of asymptomatic neuropathy. Using multivariate analysis only the duration of diabetes more than 4 years was found to be an independent risk factor for neuropathy (Table 2). Conclusion: The frequency of asymptomatic neuropathy in type 2 DM in this study was high. This study highlights the importance of the NCS in determining the presence of asymptomatic neuropathy in type 2 diabetes mellitus patients. The early detection of DPN in type 2 DM patients who had diabetes for more than 4 years may reduce the detrimental consequences associated with it. Reference: [1] Meijer JWG, Smit AJ, Sonderent EV et al. Symptoms scoring system to diagnose distal polyneuropathy in diabetes: the Diabetic Neuropathy Symptom Score. Diabetic Medicine. Vol 19; 11: 962-965.
P614 Micromutations in PMP22 gene in patients with severe inherited neuropathies: report of a family M. Alcantara 1 , D. Portugal 2 , L.F. Oliveira 3 , M. Venturini 2 1 Sarah Rehabilitation Hospitals, Neurophysiology, Fortaleza, Brazil; 2 Sarah Rehabilitation Hospitals, Neurology, Fortaleza, Brazil; 3 Sarah Rehabilitation Hospitals, Pediatrics, Fortaleza, Brazil Question: Charcot-Marie-Tooth (CMT) 1A is commonly caused by the duplication of peripheral myelin protein 22 gene (PMP22dupl). Micromutations of PMP22 are rare causes of CMT and may lead to variable clinical phenotypes, ranging from mild disease to severe demyelinating neuropathy. Methods: We report an unusual presentation of CMT disease and its possible association with single nucleotide polymorphisms (SNPs) in coding exons of PMP22. Results: Two siblings, brother and sister, age 4 and 7 years respectively, born of non-consanguineous parents, presented with claw hands, diffuse weakness and atrophy, pes cavus and steppage gait. Their father had mild distal weakness and ulnar and peroneal motor nerve conduction velocities (MNCVs) were unobtainable. Nerve conduction studies in the whole pedigree showed an asymmetrical motor-sensory neuropathy, worse in upper limbs and more severe in the offspring. One striking difference among the siblings was the preservation or median sensory nerves in the sister and the severe compromise of all upper limb nerves in the brother. Possible conduction blocks of motor nerves were present only in siblings. Two SNPs were detected in PMP22 sequencing in siblings (IVS3-17G>A and IVS4+33C>T) and one in the father (IVS3-17G>A). Mutations in EGR2, MPZ and PMPdupl/deletion were absent. Conclusions: Atypical forms of CMT disease might be related to de novo micromutations in PMP22. Particularly severe autosomal dominant demyelinating neuropathies can appear and even bring about an anticipation phenomenum. Further studies are necessary to ascribe the value of SNPs
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Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
Abstract P614 – Figure 1. Nerve conduction studies recorded from the father.
Abstract P614 – Figure 2. Nerve conduction studies recorded from the siblings.
in this context and sequencing of the gene is necessary when common mutations are absent.
P615 Polyneuropathy in HyperCKemia K. Abeler, S. Løseth, H. Lilleng, S.I. Bekkelund University hospital of North Norway, Clinical neurophysiology, Tromsø, Norway Question: Creatine kinase (CK) is a commonly used biomarker of neuromuscular disease. It is usually considered a marker of myopathy, but hyperCKemia is also described in polyneuropathy especially in amyotrophic lateral sclerosis and postpolio syndrome. We aimed to assess whether the prevalence of polyneuropathy is increased in persons with elevated CK compared to persons with normal CK. Methods: Individuals with persistent hyperCKemia (n=121) and age and gender matched controls (n=129) were identified in a population study (n=12,828). They were examined with neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG). The neurophysiological diagnosis of polyneuropathy was based on NCS-criteria according to Dyck and neuropathic EMG pattern. Results: We identified 63 persons with polyneuropathy according to our neurophysiological definition. Prevalence of polyneuropathy was higher in the hyperCKemia group (n=39, 32.8%) compared to the control group (n=24, 18.6%) (p=0.013). NCS of the tibial nerve showed decreased compound motor action potential (p<0.0001), decreased motor conduction velocity (p=0.002) and increased F-wave latency (p=0.003). EMG showed significantly increased average motor unit potential amplitude in three of four muscles. Conclusion: Polyneuropathy was more common in persons with persistent hyperCKemia in our population sample. This finding indicates that even mild to moderate polyneuropathy may lead to some instability of the muscle cell membrane and leakage of Creatine Kinase.
P616 Neurophysiology and ultrasound in diagnosis of isolated peripheral nerve tumors. Literature revision and personal experience D. Coraci 1 , V. Santilli 1 , C. Erra 2 , P. De Franco 3 , L. Padua 2,3 Sapienza University, Board of Physical Medicine and Rehabilitation, Rome, Italy; 2 Università Cattolica del Sacro Cuore, Institute of Neurology, Rome, Italy; 3 Don Gnocchi ONLUS Foundation, Milan, Italy
1
Question: Primary nerve tumors can affect any peripheral nerve and can be benign, malignant, symptomatic, or asymptomatic. In this pathology, neurophysiologic examination presents an important role to define the possible lack of function of the nerve. However, sometimes, this evaluation cannot give all the information to make diagnosis. On the other hand, ultrasonography allows us to visualize the peripheral nerves and underline the morphologic changes in nerve structure. Our work shows the usefulness of the association of neurophysiology and ultrasound. Methods: We present a literature revision of the use of ultrasound in peripheral nerve tumor study and a collection of 10 cases where the combined use of clinic, neurophysiology and ultrasound guided the diagnostic process of nerve tumors. Results: All the patients presented a clinic pattern of nerve involvement and everyone was evaluated with neurophysiology which confirmed a mononeuropathy, but without the possibility of a sure diagnosis. The following ultrasound evaluation allowed to visualize a focal lesion, compatible with a nerve tumor. Conclusions: These cases show that neurophysiology and ultrasound together contribute in diagnosis of peripheral nerve tumors. Ultrasonography is not able to certainly define the type of tumor, but it gives suggestions about discrimination between schwannoma and neurofibroma.
S215
P612 Small and large fibre neuropathy in patients with diabetes type 1 compared with type 2: a follow-up study S. Løseth 1,2 , E. Stålberg 3 , S. Lindal 4 , R. Jorde 5 , S.I. Mellgren 6 University of Tromsø, Tromsø, Norway; 2 University Hospital of North Norway, Department of Clinical Neurophysiology, Tromsø, Norway; 3 Uppsala University Hospital, Department of Clinical Neurophysiology, Uppsala, Sweden; 4 University Hospital of North Norway, Department of Pathology, Tromsø, Norway; 5 University Hospital of North Norway, Department of Internal Medicine, Tromsø, Norway; 6 University Hospital of North Norway, Department of Neurology, Tromsø, Norway 1
Question: Are there differences in the spectrum of large and small fibre involvement in patients with diabetes type 1 versus those with type 2? Methods: Fifty-nine patients (35 type 1 and 24 type 2 diabetes) were included in a follow-up study after 5 years. Nerve conduction studies (NCS), quantitative sensory testing (QST) at the distal calf and skin biopsy for quantification of intraepidermal nerve fibre density (IENFD) in addition to symptom scoring and clinical evaluations were performed. Z-scores were calculated to adjust for the physiologic effects of age, height and gender. Results: Patients with type 1 diabetes were younger with longer disease duration; they had higher HbA1c and lower BMI. Neuropathic symptoms tended to be more frequent in type 2 (54% versus 37%; ns). Comparing data to the baseline study, the overall NCS score was more abnormal after 5 years in both type 1 (p=0.006) and type 2 diabetes (p=0.02). IENFD became significantly lower only in those with type 2 (reduction from 7.9±4.8 to 4.3±2.8 fibres/mm, p=0.006). Cold perception threshold was higher in type 2 at follow-up compared to baseline (p=0.049). Between the two types of diabetes the difference of progression of abnormalities was only significant for the IENFD (more progression in type 2, p=0.048). Conclusions: A 5 year follow-up study in diabetics showed progression of large fibre neuropathy in both type 1 and type 2. Small fibre neuropathy seems to progress more rapidly in those with type 2.
P613 Detection of early neuropathy in type 2 diabetes mellitus R. Remli 1 , S.A. Md Rani 1 , W.N.N. Wan Yahya 1 , R. Sahathevan 1 , Z. Md Zain 2 , N. Mohamed Ibrahim 1 , R. Azman Ali 1 , H.J. Tan 1 1 National University of Malaysia, Medical Department, Kuala Lumpur, Malaysia; 2 National University of Malaysia, Community Health Department, Kuala Lumpur, Malaysia Question: To determine the frequency and predictors of asymptomatic lower limb neuropathy amongst type 2 diabetic patients in University Kebangsaan Malaysia Medical Centre (UKMMC). Methods: This was a cross sectional study which recruited diabetic patients in UKM Medical Centra who did not have any neuropathy symptoms. All patients who obtained a score of “0” in diabetic neuropathy symptoms score (unsteadiness in walking, neuropathic pain, paraesthesia, numbness [1] (Table 1).
Figure 1. The frequency of nerve conduction parameters abnormalities in motor and sensory nerves.
All patients were subjected to a neurological examination to ascertain their and nerve conduction studies. Result: Ninety diabetic patients who were asymptomatic for neuropathy were recruited. Of these, 81 patients (90%) had abnormal NCS and 9 patients (10%) had normal NCS. From 81 asymptomatic neuropathy patients, 14 (15.6%) had pure motor neuropathy, 12 (12.2%) had pure sensory neuropathy and 56 (62%) had mixed sensorimotor neuropathy (Fig. 1). Duration of diabetes, age of diabetic patients and presence of retinopathy were found to be significantly associated with the presence of asymptomatic neuropathy. Using multivariate analysis only the duration of diabetes more than 4 years was found to be an independent risk factor for neuropathy (Table 2). Conclusion: The frequency of asymptomatic neuropathy in type 2 DM in this study was high. This study highlights the importance of the NCS in determining the presence of asymptomatic neuropathy in type 2 diabetes mellitus patients. The early detection of DPN in type 2 DM patients who had diabetes for more than 4 years may reduce the detrimental consequences associated with it. Reference: [1] Meijer JWG, Smit AJ, Sonderent EV et al. Symptoms scoring system to diagnose distal polyneuropathy in diabetes: the Diabetic Neuropathy Symptom Score. Diabetic Medicine. Vol 19; 11: 962-965.
P614 Micromutations in PMP22 gene in patients with severe inherited neuropathies: report of a family M. Alcantara 1 , D. Portugal 2 , L.F. Oliveira 3 , M. Venturini 2 1 Sarah Rehabilitation Hospitals, Neurophysiology, Fortaleza, Brazil; 2 Sarah Rehabilitation Hospitals, Neurology, Fortaleza, Brazil; 3 Sarah Rehabilitation Hospitals, Pediatrics, Fortaleza, Brazil Question: Charcot-Marie-Tooth (CMT) 1A is commonly caused by the duplication of peripheral myelin protein 22 gene (PMP22dupl). Micromutations of PMP22 are rare causes of CMT and may lead to variable clinical phenotypes, ranging from mild disease to severe demyelinating neuropathy. Methods: We report an unusual presentation of CMT disease and its possible association with single nucleotide polymorphisms (SNPs) in coding exons of PMP22. Results: Two siblings, brother and sister, age 4 and 7 years respectively, born of non-consanguineous parents, presented with claw hands, diffuse weakness and atrophy, pes cavus and steppage gait. Their father had mild distal weakness and ulnar and peroneal motor nerve conduction velocities (MNCVs) were unobtainable. Nerve conduction studies in the whole pedigree showed an asymmetrical motor-sensory neuropathy, worse in upper limbs and more severe in the offspring. One striking difference among the siblings was the preservation or median sensory nerves in the sister and the severe compromise of all upper limb nerves in the brother. Possible conduction blocks of motor nerves were present only in siblings. Two SNPs were detected in PMP22 sequencing in siblings (IVS3-17G>A and IVS4+33C>T) and one in the father (IVS3-17G>A). Mutations in EGR2, MPZ and PMPdupl/deletion were absent. Conclusions: Atypical forms of CMT disease might be related to de novo micromutations in PMP22. Particularly severe autosomal dominant demyelinating neuropathies can appear and even bring about an anticipation phenomenum. Further studies are necessary to ascribe the value of SNPs
S216
Abstracts of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
Abstract P614 – Figure 1. Nerve conduction studies recorded from the father.
Abstract P614 – Figure 2. Nerve conduction studies recorded from the siblings.
in this context and sequencing of the gene is necessary when common mutations are absent.
P615 Polyneuropathy in HyperCKemia K. Abeler, S. Løseth, H. Lilleng, S.I. Bekkelund University hospital of North Norway, Clinical neurophysiology, Tromsø, Norway Question: Creatine kinase (CK) is a commonly used biomarker of neuromuscular disease. It is usually considered a marker of myopathy, but hyperCKemia is also described in polyneuropathy especially in amyotrophic lateral sclerosis and postpolio syndrome. We aimed to assess whether the prevalence of polyneuropathy is increased in persons with elevated CK compared to persons with normal CK. Methods: Individuals with persistent hyperCKemia (n=121) and age and gender matched controls (n=129) were identified in a population study (n=12,828). They were examined with neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG). The neurophysiological diagnosis of polyneuropathy was based on NCS-criteria according to Dyck and neuropathic EMG pattern. Results: We identified 63 persons with polyneuropathy according to our neurophysiological definition. Prevalence of polyneuropathy was higher in the hyperCKemia group (n=39, 32.8%) compared to the control group (n=24, 18.6%) (p=0.013). NCS of the tibial nerve showed decreased compound motor action potential (p<0.0001), decreased motor conduction velocity (p=0.002) and increased F-wave latency (p=0.003). EMG showed significantly increased average motor unit potential amplitude in three of four muscles. Conclusion: Polyneuropathy was more common in persons with persistent hyperCKemia in our population sample. This finding indicates that even mild to moderate polyneuropathy may lead to some instability of the muscle cell membrane and leakage of Creatine Kinase.
P616 Neurophysiology and ultrasound in diagnosis of isolated peripheral nerve tumors. Literature revision and personal experience D. Coraci 1 , V. Santilli 1 , C. Erra 2 , P. De Franco 3 , L. Padua 2,3 Sapienza University, Board of Physical Medicine and Rehabilitation, Rome, Italy; 2 Università Cattolica del Sacro Cuore, Institute of Neurology, Rome, Italy; 3 Don Gnocchi ONLUS Foundation, Milan, Italy
1
Question: Primary nerve tumors can affect any peripheral nerve and can be benign, malignant, symptomatic, or asymptomatic. In this pathology, neurophysiologic examination presents an important role to define the possible lack of function of the nerve. However, sometimes, this evaluation cannot give all the information to make diagnosis. On the other hand, ultrasonography allows us to visualize the peripheral nerves and underline the morphologic changes in nerve structure. Our work shows the usefulness of the association of neurophysiology and ultrasound. Methods: We present a literature revision of the use of ultrasound in peripheral nerve tumor study and a collection of 10 cases where the combined use of clinic, neurophysiology and ultrasound guided the diagnostic process of nerve tumors. Results: All the patients presented a clinic pattern of nerve involvement and everyone was evaluated with neurophysiology which confirmed a mononeuropathy, but without the possibility of a sure diagnosis. The following ultrasound evaluation allowed to visualize a focal lesion, compatible with a nerve tumor. Conclusions: These cases show that neurophysiology and ultrasound together contribute in diagnosis of peripheral nerve tumors. Ultrasonography is not able to certainly define the type of tumor, but it gives suggestions about discrimination between schwannoma and neurofibroma.