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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. 30 JUNE 37 41 Cited By :3

Objectives. To define the incidence and prevalence of familial amyloidotic polyneuropathy (FAP) TTRVal30Met on the island of Cyprus. To study the clinical phenotype and genetic features of FAP TTRVal30Met in the Cypriot population. Methods. The clinical and neurogenetic databases were used to identify probands with FAP TTRVal30Met and detailed family trees were constructed. Potential carriers of the mutation were identified from the family trees and assessed clinically and genetically. Transthyretin was completely sequenced in patients and potential carriers. Results. Thirty-six patients carrying the TTRVal30Met mutation (one homozygote) from 22 families were identified. On 1 December 2003 the prevalence of FAP was 3.72/100,000 while the incidence is estimated to be 0.69/100,000 per year. The phenotype observed was characteristic for a length dependent sensorimotor and autonomic neuropathy with neuropathic pain. Mean age of onset was 46 years. Penetrance is estimated to be 28% and positive anticipation in the age of onset is found. Conclusion. FAP is relatively prevalent in Cyprus which may be considered as another endemic focus of the disease in Europe. The mean age of onset and penetrance is different from the Portuguese and Swedish populations. Understanding the biological factors that determine these differences could potentially lead to therapeutic advances. 16 1 32 37 Cited By :12

The molecular mechanisms underlying the selective neurodegeneration of motor neurons in amyotrophic lateral sclerosis (ALS) are inadequately understood. Recent breakthroughs have implicated impaired axonal transport, mediated by molecular motors, as a key element for disease onset and progression. The current work identifies the expression of 15 kinesin-like motors in healthy human motor cortex, including three novel isoforms. Our comprehensive quantitative mRNA analysis in control and sporadic ALS (SALS) motor cortex specimens detects SALS-specific down-regulation of KIF1Bbeta and novel KIF3Abeta, two isoforms we show to be enriched in the brain, and also of SOD1, a key enzyme linked to familial ALS. This is accompanied by a marked reduction of KIF3Abeta protein levels. In the motor cortex KIF3Abeta localizes in cholinergic neurons, including upper motor neurons. No mutations causing splicing defects or altering protein-coding sequences were identified in the genes of the three proteins. The present study implicates two motor proteins as possible candidates in SALS pathology.

Objectives: To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. Methods: 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. Results: 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 response were found. Conclusion: Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required. 44 3 167 173 Cited By :11

Objectives: 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. Methods: 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. Results: 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 response with a negative polarity at around 3ms, which we therefore called N3. Two case studies are presented. The first case is a patient with unilateral sensorineural hearing loss with NVESTEPs present, suggesting that NVESTEPs is not a cochlear response. The second case is a patient with multiple sclerosis with demyelinating lesions in the pons and an unobtainable NVESTEP response. Conclusion: NVESTEPs is a possible new diagnostic technique that may be specific for the vestibular pathway. It has potential use in patients with symptoms of dizziness, subclinical symptoms in multiple sclerosis, and in disorders specific for the vestibular nerve. 43 7 399 408 Cited By :13

In amyotrophic lateral sclerosis (ALS) reactive oxygen species and apoptosis are implicated in disease pathogenesis. Melatonin with its anti-oxidant and anti-apoptotic properties is expected to ameliorate disease phenotype. The aim of this study was to assess possible neuroprotection of melatonin in the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. Four groups of mice, 14 animals each, were injected intraperitoneally with 0 mg/kg, 0.5 mg/kg, 2.5 mg/kg and 50 mg/kg of melatonin from age 40 days. The primary end points were; disease onset, disease duration, survival and rotarod performance. No statistically significant difference in disease onset between the four groups was found. Survival was significantly reduced with the 0.5 mg/kg and 50 mg/kg doses and tended to be reduced with the 2.5 mg/kg dose. Histological analysis of spinal cords revealed increased motoneuron loss in melatonin treated mice. Melatonin treated animals were associated with increased oxidative stress as assessed with 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation. Histochemistry and Western blot data of spinal cord from melatonin treated mice revealed upregulation of human SOD1 compared to untreated mice. In addition, real-time PCR revealed a dose dependent upregulation of human SOD1 in melatonin treated animals. Thus, intraperitoneal melatonin, at the doses used, does not ameliorate and perhaps exacerbates phenotype in the G93ASOD1 mouse ALS model. This is probably due to melatonin's effect on upregulating gene expression of human toxic SOD1. This action presumably overrides any of its direct anti-oxidant and anti-apoptotic properties. Fil: Dardiotis, Efthimios . The Cyprus Institute of Neurology and Genetics; Chipre Fil: Panayiotou, Elena . The Cyprus Institute of Neurology and Genetics; Chipre Fil: Feldman, Mariana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Hadjisavvas, Andreas . The Cyprus Institute of Neurology and Genetics; Chipre Fil: Malas, Stavros . The Cyprus Institute of Neurology and Genetics; Chipre Fil: Vonta, Ilia. National Technical University of Athens; Grecia Fil: Hadjigeorgiou, Georgios . Centre for Research and Technology-Thessaly; Grecia Fil: Kyriakou, Kyriakos . The Cyprus Institute of Neurology and Genetics; Chipre Fil: Kyriakides, Theodoros . The Cyprus Institute of Neurology and Genetics; Chipre

Background: Ocular abnormalities have been known to occur in hereditary amyloidotic polyneuropathy since the 1950s. While vitreous opacities and scalloped pupils were described early it has become evident that every component of the eye from the conjunctiva to the retinal vasculature can be involved. Reports from the major centres in Japan, Portugal and Sweden, which primarily treat patients with ATTRV30M, have indicated that with the increased longevity seen in patients treated with liver transplantation the frequency of the more severe eye findings, notably vitreous opacities and subsequent glaucoma, are being detected more frequently. Methods: In an attempt to confirm that the experience was similar in a broader range of locales we performed a survey of ten treatment centres in eight countries to determine the frequency of severe ocular abnormalities (vitreous opacities and glaucoma) in 804 patients with V30M disease and whether there was any relationship to treatment with liver transplantation or the transthyretin stabilizer tafamidis. Results: The data indicate that the frequency of these abnormalities increases with increasing duration of disease. In patients broadly matched for duration of disease the frequency was higher in subjects who had undergone liver transplantation than in those who were untreated. Conclusions: Retrospective surveys are subject to a number of potential biases. In this case, the major potential confounders were defining the time of disease onset and physician bias in choice of therapy, particularly regarding the choice of patients and the time in their course when they should undergo liver transplantation, and when and whether they should receive tafamidis. Nonetheless it appears that the incidence of severe ocular abnormalities in V30M subjects from centres around the world is similar to those found in centres in the areas endemic for this variant protein. The incidence increased with duration of disease regardless of therapy with the highest frequencies seen in patients more than ten years after diagnosis who had undergone liver transplantation.

BACKGROUND: ATTRV30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by amyloid deposition composed of aggregated misfolded TTR monomers with the V30M mutation. The age of onset in patients with ATTRV30M varies in different foci and the mechanism behind it is still unknown. METHODS: The tertiary neurology center following all ATTRV30M patients in Cyprus was used to collect demographic data to estimate; prevalence, incidence, penetrance, anticipation, time from disease onset to diagnosis and transplantation. Ocular, cardiac and leptomeningeal involvement in transplanted patients was explored. Correlation of C1q tagging SNPs with age of disease onset was carried out. RESULTS: Prevalence and incidence for ATTRV30M neuropathy in Cyprus are 5.4/100,000 and 0.3/100,000 respectively. Mean age of onset is 40.6 years and anticipation is 8.3 years. Penetrance reaches 51% and 75% by the ages of 50 and 80 years respectively. In liver transplanted patients rates of ocular, cardiac and leptomeningeal involvement were estimated to be 60%, 20% and 16%, respectively. C1q polymorphisms correlated with age of disease onset. CONCLUSIONS: ATTRV30M neuropathy has a rising prevalence in Cyprus due to improved survival of patients. Late onset complications are becoming a major problem. Complement C1q appears to be a modifier in this disease.