T. Kyriakides | Democritus University of Thrace (original) (raw)

Papers by T. Kyriakides

Spinocerebellar ataxia type 10 belongs to the group of neurodegenerative diseases known as autoso... more Spinocerebellar ataxia type 10 belongs to the group of neurodegenerative diseases known as autosomal dominant cerebellar ataxias. Genetic studies in patients with SCA so far revealed 12 genes responsible for ADSCA and 12 mapped loci without gene identification. SCA10 is characterized by progressive ataxia and seizures. The underlying mutation is a large expansion of an ATTCT repeat in intron 9 of the SCA10 gene. Our aim is to determine the relative frequency of SCA10 in Cyprus, which constitutes part of our wider effort to identify the genetic defects of the Cypriot SCA sporadic patients and families, which prove to be exceptional in comparison with other populations. We analyzed the ATTCT repeats in 53 SCA patients, previously excluded from other genes (FRDA, SCA1-3, SCA6-8, SCA12, SCA17 and DRPLA). We also determined the size of repeats in 58 normal controls from the Cypriot polulation. The repeat lengths were analyzed by polymerase chain reaction followed by fragment analysis. Southern blot analysis was performed for samples with one allele detected, in order to confirm homozygosity or presence of a SCA10 expansion. Normal control sample repeat lengths ranged from 11 to 20 with 81% heterozygosity and the 14 repeats allele is more frequent (37%) in the Cypriot population. In the patient group, repeats ranged from 11 to19 with 83% heterozygosity. The rest of them (17%) have been confirmed to be homozygous for the normal range allele. Therefore the SCA10 mutation does not exist in the Cypriot SCA population under study. In conclusion, our results agree with other studies demonstrating that SCA10 is rare in populations other than the Mexican.

Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases, 2011

A direct correlation of QEMG with muscle biopsy findings might help delineate the sensitivity of ... more A direct correlation of QEMG with muscle biopsy findings might help delineate the sensitivity of QEMG in identifying muscle pathology as well as provide information on electrophysiological-histological correlations. In a study of 31 patients with a variety of myopathies we found that the sensitivity of QEMG was between 24 to 69% depending of the specific method of signal analysis. The positive predictive value of abnormal QEMG was more than 90% while its negative predictive value was only about 20%. Amplitude outlier analysis was superior especially in minimally weak muscles (MRC > 4) and was particularly sensitive at detecting increased variability in fiber size and more subtle myopathic changes.

Electromyography and clinical neurophysiology, 2005

Symptoms of disequilibrium in multiple sclerosis (MS) are common. Neurogenic vestibular evoked po... more Symptoms of disequilibrium in multiple sclerosis (MS) are common. Neurogenic vestibular evoked potentials (NVsEPs) are saccular responses to tone-pip acoustic stimuli and are recordable from the parietal areas ipsilaterally to the stimulated ear. We wished to determine possible correlations of abnormal findings in NVsEP with clinical neurological findings related to the vestibular system, and demyelination seen on MRI. NVsEPs were performed by delivering a 1 kHz tone-pip stimulus monoaurally with contralateral masking noise via headphones. Brainstem auditory evoked potentials were performed in the standard manner. Thirty-three patients had either been diagnosed with MS or had possible MS. There is statistical evidence that the presence of symptoms is likely to give an abnormal NVsEP, but no correlation exists between the presence or absence of vestibular symptoms and signs and an abnormal BAEP. No correlation was found between the presence of brainstem lesions on MRI and an abnormal...

Electromyography and clinical neurophysiology

To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using h... more To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using high intensity auditory clicks. The same stimulus is used in myogenic vestibular evoked potentials which has been shown to evoke potentials in the vestibular division of the vestibulocochlear nerve. A whole head recording with surface EEG electrodes was performed using high intensity clicks in one normal volunteer to determine the best recording position for vestibular evoked potentials. The results were compared to responses at moderate click intensities used for brainstem auditory evoked potentials (BAEPs). The difference in the location of the two responses on the scalp was assumed to be from the vestibular system. Responses specific to the high intensity clicks were best obtained in the parietal areas, with no reproducible responses obtained in the same area with moderate intensity clicks normally used in BAEPs. Recordings in neurologically normal volunteers showed a consistent respon...

The largest subgroup of integrins is that containing the beta1 subunit. beta1 integrins have been... more The largest subgroup of integrins is that containing the beta1 subunit. beta1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis, and mechanotransduction. Global deletion of beta1 integrin expression results in embryonic death at ca. embryonic day 5 (E5), a developmental time point too early to determine the effects of this integrin on vascular development. To elucidate the specific role of beta1 integrin in the vasculature, we conditionally deleted the beta1 gene in the endothelium. Homozygous deletion of beta1 integrins in the endothelium resulted in failure of normal vascular patterning, severe fetal growth retardation, and embryonic death at E9.5 to 10, although there were no overt effects on vasculogenesis. Heterozygous endothelial beta1 gene deletion did not diminish fetal or postnatal survival, but it reduced beta1 subunit expression in endothelial cells from adult mice by approximately 40%. These mice demonstrated abnormal vascular remodeling in response to experimentally altered in vivo blood flow and diminished vascularization in healing wounds. These data demonstrate that endothelial expression of beta1 integrin is required for developmental vascular patterning and that endothelial beta1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how beta1 integrin expression is modulated may have significant clinical importance.

Production of energy in mitochondria, by the means of oxidative phosphorylation, strictly depends... more Production of energy in mitochondria, by the means of oxidative phosphorylation, strictly depends upon respiratory chain complexes which are encoded by both the mitochondrial DNA (mtDNA) and the nuclear genome (nDNA). Respiratory chain complexes are formed, for the most part by subunits, of nuclear origin, while several indispensable complex-assembling proteins are of nuclear origin. Accurate replication and efficient maintenance of mtDNA are also essential for the respiratory chain to function properly. Mitochondrial disorders caused by nD-NA defects have been the object of increasing attention in the past few years, establishing themselves as an important and relatively prevalent group of pathologies, and challenging the relevance of diseases caused by inherited mutations of mtDNA itself.

Neurology, 2011

Duchenne muscular dystrophy (DMD) is considered a biological phenomenon, possibly due to genetic ... more Duchenne muscular dystrophy (DMD) is considered a biological phenomenon, possibly due to genetic or epigenetic mechanisms. It was exciting to read the article by Pegoraro et al.r describing the discovery of osteopontin as a possible modifier gene.

Journal of the Neurological Sciences, 2009

ABSTRACT Purpose: Habitually when pattern shift visual evoked potentials (PSVEP) are conducted on... more ABSTRACT Purpose: Habitually when pattern shift visual evoked potentials (PSVEP) are conducted on a patient for suspicion of a neurological disorder, the P100 latency is the factor that plays the dominant role in determining whether the test is normal. Traditionally the amplitude of the response is not given much consideration. Patients with normal PSVEPs would be diagnosed as normal if only latencies are considered. We asked the question “Can normal P100 latencies with abnormalities in the interocular amplitudes signify for an abnormality in the brain?” Method: 24/587 PSVEPs of patients were found with P100 latencies that were within normal limits, but the interocular N75-P100 amplitude difference was 50% or more. Brain MRIs concurrent with the time of testing were also looked at for lesions and compared. 5 of the 24 studies were omitted due to the absence of patient history or brain MRI. The age range of the patients was 14 to 68 with a mean average age of 34 years. There were 13 females and 6 males. Monocular PSVEPs were done using 1” checks at a distance of 1 meter and at an average of approximately 100 stimulations. Results: Of the 19 studies 15 had positive brain MRIs for demyelinating lesions, 1 was positive for atrophy, and 3 were negative for lesions. Patient Diagnosis VEP side with reduced amplitude MRI abnormalities AY MS Right Bil WMLs and CC KS MS Right Bil WMLs and CC HM MS Right Bil WMLs and CC LP MS Right Bil WMLs (R>L) MA MS Right Bil WMLs, rt occ. lobe and CS PC MS Right Bil WMLs and rt occ. lobe PC MS Left Left temporal PP MS Right Bil WMLs and CC DA ISP Right Occ. horns, CC and lt frontal lobe IC Unspec.Demyel. Right Brainstem KM Sturge-Weber Right Rt hemisphere PD E Left Rt hippocampal atrophy PN E Left WMLs TA NF-I Right Rt thalamus and frontal TE Diabetes/Vascular Left Lt temporal WMLs TN Lupus Right Prominence of optic nerve sheaths PY Unspec. Demyel. Right Negative PM Unspec. Demyel. Left Negative MK Idiop. Myelitis Right Negative Figure 1: Of the 15 positive MRI cases 4 were concordant with the side of the lower amplitude of the PSVEP. 10 cases had multiple and bilateral lesions. (CC= Corpus Callosum, CS=Centrum Semiovale, E=Epilepsy, ISP=Idiopathic Spastic Paraparesis, MS=Multiple Sclerosis, NF-I=Neurofibromatosis Type I, WML=White Matter Lesion) On average, the interocular N75-P100 amplitude difference was at 61%. Figure 2: Difference in interocular amplitudes with normal latencies Conclusion: Customarily the classical impression of a normal PSVEP would not lead to a definite diagnosis. This study indicates that the difference in PSVEP interocular N75-P100 amplitudes can signify for an abnormality in the brain even if the P100 latencies are within normal limits. Furthermore, brain imaging should be done when a N75-P100 interocular amplitude difference is observed. Due to the small number of patients we could not delineate the lesion involved in the difference in amplitudes and further studies are necessary to evaluate these findings. References: 1. Hood DC et al. An interocular comparison of the multifocal VEP: a possible technique for detecting local damage to the optic nerve. Invest Opthalmol Vis Sci. 2000 May; 41(6):1580-7. 2. Katsumi O et al. Pattern reversal VERas a tool for evaluating unbalanced visual inputs between the two eyes. Jpn J Opthalmol. 1988;32(1):86-97. 3. Shahrokhi F et al. Pattern shift visual evoked responses. Two hundred patients with optic neuritis and/or multiple sclerosis. Arch Neurol. 1978 Feb;35(2):65-71.

Journal of Autoimmunity, 2013

Double-seronegative myasthenia gravis (dSN-MG, without detectable AChR and MuSK antibodies) prese... more Double-seronegative myasthenia gravis (dSN-MG, without detectable AChR and MuSK antibodies) presents a serious gap in MG diagnosis and understanding. Recently, autoantibodies against the low-density lipoprotein receptor-related protein 4 (LRP4) have been identified in several dSN-MG sera, but with dramatic frequency variation (∼2-50%). We have developed a cell based assay (CBA) based on human LRP4 expressing HEK293 cells, for the reliable and efficient detection of LRP4 antibodies. We have screened about 800 MG patient sera from 10 countries for LRP4 antibodies. The overall frequency of LRP4-MG in the dSN-MG group (635 patients) was 18.7% but with variations among different populations (range 7-32.7%). Interestingly, we also identified double positive sera: 8/107 anti-AChR positive and 10/67 anti-MuSK positive sera also had detectable LRP4 antibodies, predominantly originating from only two of the participating groups. No LRP4 antibodies were identified in sera from 56 healthy controls tested, while 4/110 from patients with other neuroimmune diseases were positive. The clinical data, when available, for the LRP4-MG patients were then studied. At disease onset symptoms were mild (81% had MGFA grade I or II), with some identified thymic changes (32% hyperplasia, none with thymoma). On the other hand, double positive patients (AChR/LRP4-MG and MuSK/LRP4-MG) had more severe symptoms at onset compared with any single positive MG subgroup. Contrary to MuSK-MG, 27% of ocular dSN-MG patients were LRP4 antibody positive. Similarly, contrary to MuSK antibodies, which are predominantly of the IgG4 subtype, LRP4 antibodies were predominantly of the IgG1 and IgG2 subtypes. The prevalence was higher in women than in men (female/male ratio 2.5/1), with an average disease onset at ages 33.4 for females and 41.9 for males. Overall, the response of LRP4-MG patients to treatment was similar to published responses of AChR-MG rather than to MuSK-MG patients.

Electromyography and clinical neurophysiology

To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a... more To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP ...

Spinocerebellar ataxia type 10 belongs to the group of neurodegenerative diseases known as autoso... more Spinocerebellar ataxia type 10 belongs to the group of neurodegenerative diseases known as autosomal dominant cerebellar ataxias. Genetic studies in patients with SCA so far revealed 12 genes responsible for ADSCA and 12 mapped loci without gene identification. SCA10 is characterized by progressive ataxia and seizures. The underlying mutation is a large expansion of an ATTCT repeat in intron 9 of the SCA10 gene. Our aim is to determine the relative frequency of SCA10 in Cyprus, which constitutes part of our wider effort to identify the genetic defects of the Cypriot SCA sporadic patients and families, which prove to be exceptional in comparison with other populations. We analyzed the ATTCT repeats in 53 SCA patients, previously excluded from other genes (FRDA, SCA1-3, SCA6-8, SCA12, SCA17 and DRPLA). We also determined the size of repeats in 58 normal controls from the Cypriot polulation. The repeat lengths were analyzed by polymerase chain reaction followed by fragment analysis. Southern blot analysis was performed for samples with one allele detected, in order to confirm homozygosity or presence of a SCA10 expansion. Normal control sample repeat lengths ranged from 11 to 20 with 81% heterozygosity and the 14 repeats allele is more frequent (37%) in the Cypriot population. In the patient group, repeats ranged from 11 to19 with 83% heterozygosity. The rest of them (17%) have been confirmed to be homozygous for the normal range allele. Therefore the SCA10 mutation does not exist in the Cypriot SCA population under study. In conclusion, our results agree with other studies demonstrating that SCA10 is rare in populations other than the Mexican.

Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases, 2011

A direct correlation of QEMG with muscle biopsy findings might help delineate the sensitivity of ... more A direct correlation of QEMG with muscle biopsy findings might help delineate the sensitivity of QEMG in identifying muscle pathology as well as provide information on electrophysiological-histological correlations. In a study of 31 patients with a variety of myopathies we found that the sensitivity of QEMG was between 24 to 69% depending of the specific method of signal analysis. The positive predictive value of abnormal QEMG was more than 90% while its negative predictive value was only about 20%. Amplitude outlier analysis was superior especially in minimally weak muscles (MRC > 4) and was particularly sensitive at detecting increased variability in fiber size and more subtle myopathic changes.

Electromyography and clinical neurophysiology, 2005

Symptoms of disequilibrium in multiple sclerosis (MS) are common. Neurogenic vestibular evoked po... more Symptoms of disequilibrium in multiple sclerosis (MS) are common. Neurogenic vestibular evoked potentials (NVsEPs) are saccular responses to tone-pip acoustic stimuli and are recordable from the parietal areas ipsilaterally to the stimulated ear. We wished to determine possible correlations of abnormal findings in NVsEP with clinical neurological findings related to the vestibular system, and demyelination seen on MRI. NVsEPs were performed by delivering a 1 kHz tone-pip stimulus monoaurally with contralateral masking noise via headphones. Brainstem auditory evoked potentials were performed in the standard manner. Thirty-three patients had either been diagnosed with MS or had possible MS. There is statistical evidence that the presence of symptoms is likely to give an abnormal NVsEP, but no correlation exists between the presence or absence of vestibular symptoms and signs and an abnormal BAEP. No correlation was found between the presence of brainstem lesions on MRI and an abnormal...

Electromyography and clinical neurophysiology

To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using h... more To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using high intensity auditory clicks. The same stimulus is used in myogenic vestibular evoked potentials which has been shown to evoke potentials in the vestibular division of the vestibulocochlear nerve. A whole head recording with surface EEG electrodes was performed using high intensity clicks in one normal volunteer to determine the best recording position for vestibular evoked potentials. The results were compared to responses at moderate click intensities used for brainstem auditory evoked potentials (BAEPs). The difference in the location of the two responses on the scalp was assumed to be from the vestibular system. Responses specific to the high intensity clicks were best obtained in the parietal areas, with no reproducible responses obtained in the same area with moderate intensity clicks normally used in BAEPs. Recordings in neurologically normal volunteers showed a consistent respon...

The largest subgroup of integrins is that containing the beta1 subunit. beta1 integrins have been... more The largest subgroup of integrins is that containing the beta1 subunit. beta1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis, and mechanotransduction. Global deletion of beta1 integrin expression results in embryonic death at ca. embryonic day 5 (E5), a developmental time point too early to determine the effects of this integrin on vascular development. To elucidate the specific role of beta1 integrin in the vasculature, we conditionally deleted the beta1 gene in the endothelium. Homozygous deletion of beta1 integrins in the endothelium resulted in failure of normal vascular patterning, severe fetal growth retardation, and embryonic death at E9.5 to 10, although there were no overt effects on vasculogenesis. Heterozygous endothelial beta1 gene deletion did not diminish fetal or postnatal survival, but it reduced beta1 subunit expression in endothelial cells from adult mice by approximately 40%. These mice demonstrated abnormal vascular remodeling in response to experimentally altered in vivo blood flow and diminished vascularization in healing wounds. These data demonstrate that endothelial expression of beta1 integrin is required for developmental vascular patterning and that endothelial beta1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how beta1 integrin expression is modulated may have significant clinical importance.

Production of energy in mitochondria, by the means of oxidative phosphorylation, strictly depends... more Production of energy in mitochondria, by the means of oxidative phosphorylation, strictly depends upon respiratory chain complexes which are encoded by both the mitochondrial DNA (mtDNA) and the nuclear genome (nDNA). Respiratory chain complexes are formed, for the most part by subunits, of nuclear origin, while several indispensable complex-assembling proteins are of nuclear origin. Accurate replication and efficient maintenance of mtDNA are also essential for the respiratory chain to function properly. Mitochondrial disorders caused by nD-NA defects have been the object of increasing attention in the past few years, establishing themselves as an important and relatively prevalent group of pathologies, and challenging the relevance of diseases caused by inherited mutations of mtDNA itself.

Neurology, 2011

Duchenne muscular dystrophy (DMD) is considered a biological phenomenon, possibly due to genetic ... more Duchenne muscular dystrophy (DMD) is considered a biological phenomenon, possibly due to genetic or epigenetic mechanisms. It was exciting to read the article by Pegoraro et al.r describing the discovery of osteopontin as a possible modifier gene.

Journal of the Neurological Sciences, 2009

ABSTRACT Purpose: Habitually when pattern shift visual evoked potentials (PSVEP) are conducted on... more ABSTRACT Purpose: Habitually when pattern shift visual evoked potentials (PSVEP) are conducted on a patient for suspicion of a neurological disorder, the P100 latency is the factor that plays the dominant role in determining whether the test is normal. Traditionally the amplitude of the response is not given much consideration. Patients with normal PSVEPs would be diagnosed as normal if only latencies are considered. We asked the question “Can normal P100 latencies with abnormalities in the interocular amplitudes signify for an abnormality in the brain?” Method: 24/587 PSVEPs of patients were found with P100 latencies that were within normal limits, but the interocular N75-P100 amplitude difference was 50% or more. Brain MRIs concurrent with the time of testing were also looked at for lesions and compared. 5 of the 24 studies were omitted due to the absence of patient history or brain MRI. The age range of the patients was 14 to 68 with a mean average age of 34 years. There were 13 females and 6 males. Monocular PSVEPs were done using 1” checks at a distance of 1 meter and at an average of approximately 100 stimulations. Results: Of the 19 studies 15 had positive brain MRIs for demyelinating lesions, 1 was positive for atrophy, and 3 were negative for lesions. Patient Diagnosis VEP side with reduced amplitude MRI abnormalities AY MS Right Bil WMLs and CC KS MS Right Bil WMLs and CC HM MS Right Bil WMLs and CC LP MS Right Bil WMLs (R>L) MA MS Right Bil WMLs, rt occ. lobe and CS PC MS Right Bil WMLs and rt occ. lobe PC MS Left Left temporal PP MS Right Bil WMLs and CC DA ISP Right Occ. horns, CC and lt frontal lobe IC Unspec.Demyel. Right Brainstem KM Sturge-Weber Right Rt hemisphere PD E Left Rt hippocampal atrophy PN E Left WMLs TA NF-I Right Rt thalamus and frontal TE Diabetes/Vascular Left Lt temporal WMLs TN Lupus Right Prominence of optic nerve sheaths PY Unspec. Demyel. Right Negative PM Unspec. Demyel. Left Negative MK Idiop. Myelitis Right Negative Figure 1: Of the 15 positive MRI cases 4 were concordant with the side of the lower amplitude of the PSVEP. 10 cases had multiple and bilateral lesions. (CC= Corpus Callosum, CS=Centrum Semiovale, E=Epilepsy, ISP=Idiopathic Spastic Paraparesis, MS=Multiple Sclerosis, NF-I=Neurofibromatosis Type I, WML=White Matter Lesion) On average, the interocular N75-P100 amplitude difference was at 61%. Figure 2: Difference in interocular amplitudes with normal latencies Conclusion: Customarily the classical impression of a normal PSVEP would not lead to a definite diagnosis. This study indicates that the difference in PSVEP interocular N75-P100 amplitudes can signify for an abnormality in the brain even if the P100 latencies are within normal limits. Furthermore, brain imaging should be done when a N75-P100 interocular amplitude difference is observed. Due to the small number of patients we could not delineate the lesion involved in the difference in amplitudes and further studies are necessary to evaluate these findings. References: 1. Hood DC et al. An interocular comparison of the multifocal VEP: a possible technique for detecting local damage to the optic nerve. Invest Opthalmol Vis Sci. 2000 May; 41(6):1580-7. 2. Katsumi O et al. Pattern reversal VERas a tool for evaluating unbalanced visual inputs between the two eyes. Jpn J Opthalmol. 1988;32(1):86-97. 3. Shahrokhi F et al. Pattern shift visual evoked responses. Two hundred patients with optic neuritis and/or multiple sclerosis. Arch Neurol. 1978 Feb;35(2):65-71.

Journal of Autoimmunity, 2013

Double-seronegative myasthenia gravis (dSN-MG, without detectable AChR and MuSK antibodies) prese... more Double-seronegative myasthenia gravis (dSN-MG, without detectable AChR and MuSK antibodies) presents a serious gap in MG diagnosis and understanding. Recently, autoantibodies against the low-density lipoprotein receptor-related protein 4 (LRP4) have been identified in several dSN-MG sera, but with dramatic frequency variation (∼2-50%). We have developed a cell based assay (CBA) based on human LRP4 expressing HEK293 cells, for the reliable and efficient detection of LRP4 antibodies. We have screened about 800 MG patient sera from 10 countries for LRP4 antibodies. The overall frequency of LRP4-MG in the dSN-MG group (635 patients) was 18.7% but with variations among different populations (range 7-32.7%). Interestingly, we also identified double positive sera: 8/107 anti-AChR positive and 10/67 anti-MuSK positive sera also had detectable LRP4 antibodies, predominantly originating from only two of the participating groups. No LRP4 antibodies were identified in sera from 56 healthy controls tested, while 4/110 from patients with other neuroimmune diseases were positive. The clinical data, when available, for the LRP4-MG patients were then studied. At disease onset symptoms were mild (81% had MGFA grade I or II), with some identified thymic changes (32% hyperplasia, none with thymoma). On the other hand, double positive patients (AChR/LRP4-MG and MuSK/LRP4-MG) had more severe symptoms at onset compared with any single positive MG subgroup. Contrary to MuSK-MG, 27% of ocular dSN-MG patients were LRP4 antibody positive. Similarly, contrary to MuSK antibodies, which are predominantly of the IgG4 subtype, LRP4 antibodies were predominantly of the IgG1 and IgG2 subtypes. The prevalence was higher in women than in men (female/male ratio 2.5/1), with an average disease onset at ages 33.4 for females and 41.9 for males. Overall, the response of LRP4-MG patients to treatment was similar to published responses of AChR-MG rather than to MuSK-MG patients.

Electromyography and clinical neurophysiology

To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a... more To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP ...