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The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. CA extern

Myotonic Dystrophies (DM, Dystrophia Myotonia) are autosomal dominant inherited myopathies with a high prevalence across different ethnic regions. Despite some differences, mainly due to the pattern of muscle involvement and the age of onset, both forms, DM1 and DM2, share many clinical and genetic similarities. In this study, we retrospectively analyzed the medical record files of 561 Greek patients, 434 with DM1 and 127 with DM2 diagnosed in two large academic centers between 1994–2020. The mean age at onset of symptoms was 26.2 ± 15.3 years in DM1 versus 44.4 ± 17.0 years in DM2 patients, while the delay of diagnosis was 10 and 7 years for DM1 and DM2 patients, respectively. Muscle weakness was the first symptom in both types, while myotonia was more frequent in DM1 patients. Multisystemic involvement was detected in the great majority of patients, with cataracts being one of the most common extramuscular manifestations, even in the early stages of disease expression. In conclusion, the present work, despite some limitations arising from the retrospective collection of data, is the first record of a large number of Greek patients with myotonic dystrophy and emphasizes the need for specialized neuromuscular centers that can provide genetic counseling and a multidisciplinary approach.

Introduction:COVID-19 pandemic caused a major disruption to healthcare system. A year after COVID-19 outbreak, the question remains to what extent the lockdowns changed the volume of non-infected patients who were admitted to the Neurologic Department (ND). To determine the impact of the pandemic´s first year on a tertiary ND. Methods:non-infected patients admitted to ND between March 2020 and February 2021 were examined. A control group was generated for the same time interval starting from March 2019. Primary outcomes were the number of patients presenting with neurologic complaint who were admitted to the hospital and the diagnosis type. Secondary outcomes were hospitalization length and patients´ outcome. Results:overall, 816 patients (49.4% females) were admitted during the predetermined periods. Median age was 55 years. Median length of hospitalization was six days. We observed a 47.2% reduction in our department´s admissions during pandemic (n=282). None of the examined variables (type of neurologic diagnosis, age, gender, hospitalization length and outcome) changed significantly during pandemic. However, the number of patients admitted during the pandemic with a diagnosis categorized as “other” was statistically significant lower compared to the year before COVID-19 (p=0.007). Hospitalization length was associated only with patients´ age. Conclusion:our study examined for the first-time the consequences of the first year of COVID-19 pandemic on ND admissions. COVID-19 outbreak resulted in decreased admissions. Delays in seeking medical consultation for urgent or undiagnosed neurologic conditions require rigorous long-term monitoring to fully understand the impact of COVID-19 pandemic on patients with neurologic diseases.

Evidence for nusinersen administration in adult 5q spinal muscular atrophy (5q-SMA) patients is scarce and based on real-world observational data. The present systematic review and meta-analysis aimed to explore the efficacy and safety of nusinersen in patients older than 12 years of age with 5q-SMA. We searched MEDLINE, EMBASE, the Cochrane Library, and grey literature through April 2021. Cross-sectional studies, case reports, review articles, and studies with follow-up less than 6 months were excluded. We included 12 records (seven case-series, five cohorts) representing 11 population cohorts and enrolling 428 SMA patients. We observed statistically significant improvements on motor function Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores at the longest follow-up assessments [SMD = 0.17(95% CI 0.01–0.33), SMD = 0.22(95% CI 0.06–0.38), respectively]. HFMSE and RULM significant improvements were also detected at the subgroup analysis during 10 and 14 months. HFMSE and RULM amelioration occurred earlier in patients with SMA type 3 or 4 during short-term analysis (≤ 6 months). 6-min walk tests (6MWT) and pulmonary function tests did not change. Minimal clinically important differences in HFMSE and RULM were observed in 43.3% (95% CI 34.5–52.3) and 38.9% (95% CI 27.7–50.7), respectively. Severe adverse events were reported in 2% (95% CI 0–5.8). Treatment withdrawal rate was 3% (95% CI 0.5–6.6). Despite the low quality of evidence and the unmet need for randomized data to establish the safety and efficacy of nusinersen in adults, our meta-analysis confirms that nusinersen is a valuable treatment option for older patients with longer-disease duration. Trial registration: PROSPERO database CRD42020223109. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01200-3.

Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1–5 (S1PR1–5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymphocytes from secondary lymphoid organs. Since the inflammatory process is a key element of immune-mediated diseases, including multiple sclerosis (MS), S1PR modulators are currently used to ameliorate systemic immune responses. The ubiquitous expression of S1PRs by immune, intestinal and neural cells has significant implications for the regulation of the gut–brain axis. The dysfunction of this bidirectional communication system may be a significant factor contributing to MS pathogenesis, since an impaired intestinal barrier could lead to interaction between immune cells and microbiota with a potential to initiate abnormal local and systemic immune responses towards the central nervous system (CNS). It appears that the secondary mechanisms of S1PR modulators affecting the gut immune system, the intestinal barrier and directly the CNS, are coordinated to promote therapeutic effects. The scope of this review is to focus on S1P−S1PR functions in the cells of the CNS, the gut and the immune system with particular emphasis on the immunologic effects of S1PR modulation and its implication in MS.

A total of 178 consecutive patients with definite sALS without frontotemporal dementia (FTD) were enrolled in this study, after complete clinical evaluation. A Repeat-Primed Polymerase Chain Reacti...

Since the introduction of disease modifying treatments there is an unmet need to identify biomarkers of spinal muscular atrophy (SMA) natural history. We performed a systematic review and meta-analysis to summarize available evidence. We searched MEDLINE, Embase, Cochrane Library and gray literature until February 2021. The primary outcome was biomarkers longitudinal course in adolescents and adults. The secondary outcome was the discrimination of patients from controls. We included 42 records examining 606 patients from 19 population cohorts over a maximum follow-up of 17-years. Lung function and serum biomarkers could not depict disease progression. We identified potential biomarkers of disease activity [SMA functional rating scale, MoviPlate, pinch strength, compound muscle action potential (CMAP), motor unit number estimation (MUNE)] that require further investigation. Data regarding Hammersmith functional motor scale expanded, Revised upper limb module, 6-minute walk test were contradictory impeding any pooled estimate. The pooled analysis regarding our secondary outcome revealed that upper limb CMAP amplitudes and MUNE mean values differed significantly between SMA patients and controls [mean difference -3.63(-6.2, -1.06), -119.74(-153.93, -85.56) respectively]. Given the lack of natural history data on this population, our qualitative synthesis and meta-analysis could provide valuable evidence and identify promising predictive biomarkers requiring further longitudinal examination. PROSPERO Registration: CRD42021235605.

A total of 178 consecutive patients with definite sALS without frontotemporal dementia (FTD) were enrolled in this study, after complete clinical evaluation. A Repeat-Primed Polymerase Chain Reaction (RP-PCR) protocol was applied to detect the G

The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study. We performed nerve conduction studies and electromyography of upper and lower extremities on 36 beta-thalassemia major (β-thal) patients. The electrophysiological findings were correlated with demographic data and laboratory parameters of the disease. Patients with β-thal present polyneuropathy or myopathy at (50%). Polyneuropathy was detected in (38.9%) and myopathy in (27.8%), while polyneuropathy and myopathy were present at (16.7%) with an overlap of the diseases in 1/3 of the patients. There was not a statistically significant correlation of polyneuropathy and myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin, and ferritin. However, there was a statistically significant correlation of polyneuropathy and myopathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver. Our findings suggest that iron overload plays a key role in the pathogenesis of polyneuropathy and myopathy in β-thal patients, and performing heart and liver MRI for the prediction of such lesions in an annual basis is warranted.

Dysphagia is common in Amyotrophic lateral sclerosis (ALS). ALS shows significant phenotypic variability. It is characterized by progressive weakness and/or spasticity of muscles. Dysphagia symptoms vary. Aspiration is often silent and cognitive dysfunction is common. The purpose of the study was to evaluate tongue strength measurements, dysphagia questionnaire, the presence of pharyngeal secretions, and FEES findings in dysphagia management in ALS.Twenty-five patients completed the Eating Assessment Tool-10 (EAT-10), had their Maximum Isometric Tongue Pressure (MITP), and endurance measured and underwent Flexible Endoscopic Evaluation of Swallowing (FEES) providing 31 examinations.Out of 25 patients, 76% were self-reported as dysphagic (EAT-10≥3) with a mean EAT-10 at 14.95 (±7.96). ALS patients had significantly decreased tongue strength (mean MITPanterior: 31.69 ± 17.32kPa). Comparing examinations of dysphagic and non-dysphagic status the mean MITPa of non-dysphagic was significantly greater (52.33 ± 10.97 kPa versus 20.6 ± 12.67 kPa), p0.001. FEES detected aspiration in 10 out of 31 examinations [Penetration Aspiration Scale(PAS) ≥6]. Aspirator status examinations showed statistically significantly worse cough (p = 0.001), tongue strength (p = 0.001) and endurance (p = 0.003), pharyngeal secretions (p0.001), velopharyngeal sufficiency (p = 0.006), pharyngeal squeeze (p = 0.009), vocal cords' movements (p = 0.001), pharyngeal pooling (p0.001), EAT-10 (p = 0.001) and bulbar subscale of ALS Functioning Rating Scale-Revised (b-ALSFRS-R) scores (p = 0.014) compared to non-aspirator status. Correlation analysis indicated that the feeding status had strong statistically significant correlations with the EAT-10 score (rho = -0.816), anterior tongue strength (rho = 0.735), secretions (rho = -0.811), pharyngeal pooling (rho = -0.712) and PAS (rho = -0.676) at FEES, and b-ALSFRS-R score (rho = 0.791), all p0.001. The EAT-10 had strong statistically significant correlations with the MITPa (r = -0.794, p0.001), secretions (rho = 0.668, p0.001), and b-ALSFRS-R score (rho = -0.766, p = 0.001). The FEES findings had strong statistically significant correlations with the anterior tongue strength (pooling: rho = -0.784), and secretions (PAS: rho = 0.723; pooling: rho = 0.671), all p0.001. For the questionnaire, tongue strength and pharyngeal secretions, ROC analysis assessed cut-off points and discriminating ability to predict aspiration status (Area Under the Curve: 0.838; 0.845 and 0.93, respectively). EAT-10 with a cut-off at 8 was able to predict aspirator status with a sensitivity of 100% and a specificity of 42.9% (negative predictive value-NPV = 100%). A cut-off value of 22KPa for the MITPa discriminated aspirator status (sensitivity = 80%, specificity = 89.5%, NPV = 89.5%). The quantity of secretions observed upon endoscopy with a cut-off value at 1 was able to predict aspirator status (sensitivity = 90%, specificity = 80%, NPV = 94.1%).Reduced tongue strength, questionnaire-reported symptoms, pharyngeal secretions, and FESS findings can guide identification of patients with ALS at risk of inefficient and unsafe swallowing.

Objective To investigate whether neurofilament light polypeptide (NfL) level in cerebrospinal fluid (CSF), currently a prognostic biomarker of neurodegeneration in patients with multiple sclerosis (MS), may be a potential biomarker of cognitive dysfunction in MS. Methods This observational case–control study included patients with MS. CSF levels of NfL were determined using enzyme-linked immunosorbent assay. Cognitive function was measured with the Brief International Cognitive Assessment for MS (BICAMS) battery and Paced Auditory Serial Addition Test (PASAT3), standardized to the Greek population. Results Of 39 patients enrolled (aged 42.7 ± 13.6 years), 36% were classified as cognitively impaired according to BICAMS z-scores (–0.34 ± 1.13). Relapsing MS was significantly better than progressive forms regarding BICAMS z-score (mean difference [MD] 1.39; 95% confidence interval [CI] 0.54, 2.24), Symbol Digit Modality Test score (MD 1.73; 95% CI 0.46, 3.0) and Greek Verbal Learning Test (MD 1.77; 95% CI 0.82, 2.72). An inversely proportional association between CSF NfL levels and BICAMS z-scores was found in progressive forms of MS (rp = –0.944). Conclusions This study provides preliminary evidence for an association between CSF NfL levels and cognition in progressive forms of MS, which requires validation in larger samples.

Background: Several European studies examined the role of C9orf72 repeat expansion in patients with Huntington-disease like phenotypes (HD-L). The scope of our study is to investigate the expansion frequency in a Greek HD-L cohort and the meta-analysis of all published cases. This will be of use in genetic counseling of these cases. Methods: A cohort of 74 patients with HD-L and 67 healthy controls were screened for the C9orf72 expansion status. Case-controls comparison was assessed with the Pearson’s chi-square statistic for a 2 × 2 table. A systematic database search was conducted and seven studies, including the current study, were considered eligible for inclusion in a meta-analysis considering a total of 812 patients with HD phenocopies. Pooled mutation frequency was calculated using a Random Effects model or the Mantel-Haezsel fixed effects model, depending on the observed heterogeneity. Results: In our cohort, one patient was found to have a pathologic expansion of C9orf72, and none from the control group (chi-square: 0.91, p-value: 0.34). Pooled mutation frequency was found at 2% (CI: 1–3%) with low heterogeneity (I2:15%). Discussion: Based on this meta-analysis the recommendation for genetic testing for C9orf72 expansions is further solidified.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease that belongs to the group of motor neuron diseases. Motor deficits like reduce in tongue strength, may coexist with cognitive deficits compatible with frontotemporal dementia (FTD), also known as frontotemporal lobar degeneration (FTLD). FTD is a neurodegenerative syndrome with two main clinical variants: behavioral (bvFTD) and language or Primary Progressive Aphasia (PPA). ALS and FTD have significant clinical and neuropathological overlapping so that for some researchers they are "the ends of the same disease spectrum". A key intervention in this patient population is the speech language therapy (SLT), a specific form of cognitive intervention, which evaluates communication skills and designs a personalized intervention plan to improve communication abilities. It has been used in patients with aphasia of different etiologies and has been shown to be effective. There is limited research in SLT interventions in patients in FTD-ALS spectrum, and the initial findings indicate success to some extent. Due to progressive neurodegeneration in FTD-ALS spectrum, the main goal of the intervention is not the complete rehabilitation of linguistic deficits but the reduction and, if possible, the delay of language decline in order to improve patient's communication and the quality of his/her life. In this paper, we critically review the reported approaches of speech language therapy (SLT) for monitoring language impairments and the impact of interventions in patients with FTD-ALS spectrum. Initial findings are supporting more systematic treatment of speech and language impairment in patients in the FTD-ALS spectrum.

The thalassemias are the most common single gene disorder in the world. Over the last years, several reports have demonstrated neurological complications in beta-thalassemia patients. In most cases, these complications remained subclinical and were detected only during neuropsychological, neurophysiological, or neuroimaging evaluation. Cognitive impairment, abnormal findings on evoked potentials, complications due to extramedullary hematopoiesis, cerebrovascular disease, and peripheral neuropathy comprise the broad spectrum of neurological involvement. Chronic hypoxia, iron overload, desferrioxamine neurotoxicity, and bone marrow expansion are implicated, but sufficient explanatory evidence is lacking and development of biomarkers is needed. This review summarizes current knowledge of the neurological complications. As life expectancy for beta-thalassemia patients increases, we support the use of neurophysiological, neuropsychological, or neuroimaging monitoring, enabling the evaluation of neural pathway impairment, to achieve appropriate management and as a result a better quality of life for this patient group.

Background:Alzheimer's Disease (AD) and Vascular Dementia (VaD) are the most common causes of dementia in older people. Both diseases appear to have similar clinical symptoms, such as deficits in attention and executive function, but specific cognitive domains are affected. Current cohort studies have shown a close relationship between αβ deposits and age-related macular degeneration (Johnson et al., 2002; Ratnayaka et al., 2015). Additionally, a close link between the thinning of the retinal nerve fiber (RNFL) and AD patients has been described, while it has been proposed that AD patients suffer from a non-specific type of color blindness (Pache et al., 2003).Methods:Our study included 103 individuals divided into three groups: A healthy control group (n = 35), AD (n = 32) according to DSM-IV-TR, NINCDS-ADRDA criteria, and VaD (n = 36) based on ΝΙΝDS-AIREN, as well as Magnetic Resonance Imaging (MRI) results. The severity of patient's cognitive impairment, was measured with the Mini-Mental State Examination (MMSE) and was classified according to the Reisberg global deterioration scale (GDS). Visual perception was examined using the Ishihara plates: “Ishihara Color Vision Test - 38 Plate.”Results:The three groups were not statistically different for demographic data (age, gender, and education). The Ishihara color blindness test has a sensitivity of 80.6% and a specificity of 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance is used.Conclusions:Ishihara Color Vision Test - 38 Plate is a promising potential method as an easy and not time-consuming screening test for the differential diagnosis of dementia between AD and VaD.

IntroductionCognitive impairment (CI) can present in 40%–70% of MS patients and in the early stages of the disease. The Brief International Cognitive assessment for MS (BICAMS) is a brief, practical and potentially universal battery for cognitive assessment in MS.AimTo correlate cognitive function with clinical parameters as disease type, EDSS, and disease durationMethodsThe cognitive function was measured with the validated to the Greek population BICAMS tool, which consists of the Symbol Digit Modalities Test (SDMT), the Greek Verbal Learning Test (GVLT) and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results36% patients classified as impaired according to the BICAMS battery. Progressive types of disease had worst scores than the relapsing in the SDMT (MD=1.73; 95% CI: 0.46, 3.0; p=0.009), GVLT (MD=1.77; 95% CI: 0.82, 2.72; p=0.001) and BICAMS z-score (MD=1.39; 95% CI: 0.54, 2.24; p=0.002). The two groups were also different in EDSS (pDiscussionEarly management of CI can lead to improvement in the patient’s quality of life. Progressing types of the disease might benefit from early cognitive assessment in the disease course.

Extrapyramidal symptoms are observed in frontotemporal dementia (FTD). 123I-FP-CIT (DaT scan) single photon emission computed tomography (SPECT) can detect loss of presynaptic dopamine transporters in the striatum. We aimed to evaluate the dopaminergic status of the striatum in patients with FTD using DaT scan. Seven patients (age range 65–76 years), who fulfilled the Neary criteria and in whom the diagnosis of FTD was confirmed by hexamethylpropyleneamine oxime SPECT, were included in the study. The severity of the extrapyramidal symptoms was evaluated by the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS). SPECT using 123I-FP-CIT was done. A (region – occipital)/occipital ratio was calculated for the striatum, putamen and caudate nucleus. The results were compared with those of the 7 age-matched normal controls. The uptake of the radiotracer in the right and left striatum was reduced to 62% (p = 0.000) and 68% (p = 0.000), respectively, compared to controls. The motor UPDRS score of the patients with FTD showed a negative correlation to the uptake of the radiotracer. The presynaptic dopamine transporter in FTD is impaired, related to the severity of the extrapyramidal symptoms. Since an effective treatment for FTD is still to be established, there is a need for evaluating the efficacy of dopaminergic drugs.

Background: Increasing evidence suggests that gangliosides act as important mediators in both demyelination and remyelination. Objective: The purpose of the present study was to investigate the presence of IgM antibodies against GM1, GD1b and GQ1b gangliosides in the sera of in patients who suffered from Parkinson’s disease in correlation with the clinical parameters. Method: The present research is based on the investigation of 44 patients (63.7-73.3 years) for anti-ganglioside antibodies and 44 healthy age- matched individuals, as normal controls, using Enzyme-Linked Immuno-Sorbent Assays. Results: The patients revealed increased levels of the tested antibodies, compared to normal controls (p=0.0005). A correlation between IgM anti-GM1 and the level of cognitive impairment (Minimental State Examination, p=0.003; Unified Parkinson’s Disease Rating Scale I, p=0.013) was also noticed. Conclusion: A peripheral neuroimmune response may occur in patients who suffer from Parkinson’s disease especially those with cognitive impairment. Further investigation is needed to establish a direct connection between that immune response and disease pathophysiology.

Objective/ background Muscle Rippling can be described as waves of involuntary muscular contractions, occurring spontaneously or induced after mechanical percussion. We present two cases of rippling muscle disorders associated with: (a) myasthenia gravis and (b) with neurogenic disorders. Case 1 Male patient, age 70 presented 7 years ago with dysphagia and mild dysarthria was diagnosed with (AchR +) myasthenia gravis. Neurophysiology confirmed the diagnosis with repetitive stimulation. He responded to pyridostigmine and after 4 years of treatment he developed muscle rippling (lower > upper limbs). CPK levels were mildly elevated. EMG revealed widespread spontaneous activity in the form of continuous fasciculations while recruitment and MUAP’s were normal. Morvan’s syndrome was excluded after negative anti- VGKC testing. The patient responded well to pyridostigmine’s dose decrease with the aid of immunosuppressive azathioprine, manifesting only limited fasciculations after exercise. Case 2 Male patient, age 55, presented with 5-year history of muscle rippling, a mild increase of CPK. Nerve conduction studies revealed a neuropathy, with decreased or absent sensory action potentials and EMG showed widespread spontaneous activity, in the form of fasciculations, with concomitant chronic denervation (MUAP’s of prolonged duration and increased amplitude with decreased recruitment). Genetic testing excluded Kennedy’s disease and the patient was diagnosed as peripheral polyneuropathy. Discussion Rippling of muscle is usually associated to myopathies and most cases are connected to caveolin mutations. However, muscle rippling should only be considered as a sign of muscular hyperexcitability. Abnormalities in calcium homeostasis in the sarcoplasmic reticulum have been proposed as the most probable causes.

The differential diagnosis between essential tremor (ET) and Parkinson's disease (PD) may be, in some cases, very difficult on clinical grounds alone. In addition, it is accepted that a small percentage of ET patients presenting symptoms and signs of possible PD may progress finally to a typical pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4-iodophenyl) nortropane, also called FP-CIT, labelled with (123)I (commercially known as DaTSCAN) has been proven to be useful in the differential diagnosis between PD and ET and to confirm dopaminergic degeneration in patients with parkinsonism. The aim of this study is to identify dopaminergic degeneration in patients with PD and distinguish them from others with ET using semi-quantitative SPECT (123)I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV), in addition with the respective ones of patients referred as suffering from ET, as well as, of patients with a PD diagnosis at an initial stage with a unilateral presentation of motor signs.Twenty-eight patients suffering from ET (10 males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this study. In addition, 33 patients (11 males and 22 females) with an established diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT images and measure the radiopharmaceutical uptake in the striatum (S), as well as the caudate nucleus (CN) and putamen (P) in all individuals.Qualitative (Visual) interpretation of the SPECT data did not find any difference in the uptake of the radiopharmaceutical at the level of the S, CN and P between NV and ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in the P of all PD patients. Semiquantitative analysis revealed significant differences between NV and ET patients in the striatum, reduced in the latter. There was also a significant reduction in the tracer accumulation in the left putamen of patients with right hemi-parkinsonism compared to ET and NV. Patients with left hemi-parkinsonism, demonstrated reduced radioligand uptake in the right putamen in comparison with ET and NV. Clinical follow-up of 20 patients with ET at (so many months afterwards) revealed no significant change in clinical presentation, particularly no signs of PD. Follow-up DaTSCAN performed in 10 of them (so many months afterwards) was negative in all but one. This one had an equivocal baseline study which deteriorated 12 months later.Our results do not support the hypothesis of a link between essential tremor and Parkinson's disease. However, it appears that ET patients have a small degree of striatal dopaminergic degeneration. If this is due to alterations in the nigrostriatl pathway or of other origin it is not clear. Follow-up studies of essential tremor patients are warranted to assess progression of disease and to understand better the possible cause for striatal dopaminergic degeneration.

Objective To describe the first published case of recurrent facial nerve palsy associated with bilateral sudden sensorineural hearing loss of autoimmune origin. Case report A 33-year-old male presented with acute facial palsy on the left following a vesicular herpetic eruption in the external ear canal on the same side. Serologic measurements demonstrated an elevation of IgM antibodies against herpes simplex virus but not for varicella-zoster virus, confirming a Ramsay Hunt-like syndrome due to herpes simplex virus. The following four months, the patient exhibited other three episodes of facial palsy, well responded to steroid treatment. During the clinical course, a sudden sensorineural hearing loss was also diagnosed, initially on the left side and then on both sides. The autoimmune markers such as the antinuclear antibody and the anti-gangliosides antibodies (anti-GM1, anti-GQ1b) were found positive. Despite steroid treatment, hearing did not show any improvement, remaining moderate on the right and severe on the left. Conclusion Recurrent facial nerve palsy and bilateral sudden sensorineural hearing loss could be the expression of autoimmune disturbances. The initial triggered factor could be the herpes simplex virus infection, such as a Ramsay Hunt-like syndrome.

Purpose of this study was to examine pupil size changes and mobility in normal subjects and in heart failure (HF) patients.Sixteen stable patients with New York Heart Association (NYHA) class II or III heart failure and sixteen control subjects were studied. Pupillary reaction to light was recorded and nine parameters from this data were measured, reported and then compared in both groups of subjects.Patients with HF had abnormal pupillary function compared with normal subjects. Pupillary light reflex variables differed significantly between two groups (p0.05) except baseline radius (R1), minimum radius (R2) and time for maximum constriction (T3). A significant decrease in maximum constriction velocity (VCmax; p0.001) and maximum constriction acceleration (ACmax; p0.001) was observed in HF subjects. Furthermore, significantly higher values in percentage recovery-redilatation (%R; p0.001), percentage R2/R1 (%R2/R1; p0.05), latency (T1; p0.05) and time for maximum velocity (T2; p0.05) were found in the same group.Of the parameters studied, R1 and %R are governed mainly by the action of the sympathetic nervous system, through norepinephrine. The rest are governed mainly by parasympathetic nervous system, through acetylcholine. The results of our study demonstrate generalized adrenergic activation and parasympathetic withdrawal, which are present in HF.

In the present study, we carried out a comparative immunohistochemical analysis of aurora-A and aurora-B expression in 40 patients with primary glioblastomas, and attempted to identify any associations with Ki-67 index and the patients' clinical features. The impact of various treatment modalities and proliferative activity on patient outcome was also assessed. Immunohistochemistry was carried out using formalin-fixed and paraffin-embedded tissue sections. Aurora-A expression was higher in tumors with high Ki-67 expression (p=0.01) and was positively, though marginally, related to aurora-B expression (p=0.085). Aurora-B expression was not linked to Ki-67 expression (p=0.182). Lower aurora-A immunohistochemical expression, chemotherapy administration, and tumor localization in one lobe of the brain implied a greater probability of patient survival in univariate analysis (p=0.044, p=0.008, p=0.041, respectively). Ki-67 and aurora-B immunoreactivities were not associated with patient survival (p=0.918 and p=0.539, respectively). To our knowledge, for the first time, the association between aurora-A and aurora-B expression, the correlation of aurora-A with Ki-67 index, and the prognostic impact of aurora-A expression were assessed in glioblastomas. Although we addressed a prognostic connotation of aurora-A, we presume that aurora-A and aurora-B play a complicated role within glioblastomas. Further examinations of larger series are required, so that definite conclusions can be drawn.

Purpose We present the unusual occurrence of two distinct neoplasms in a 42-year-old woman with an operated pituitary adenoma 18 years ago. Methods Clinical history, magnetic resonance imaging studies and histopathological findings were utilized for our diagnostic considerations. Results Concomitant presence of a cerebellar medulloblastoma secondary disseminated within the spinal canal and a pituitary macroadenoma, was identified. Conclusion To the best of our knowledge, this is the first reported case in which these two neoplasms are simultaneously occurred in the same individual. A short review of the literature is performed.

This study is an attempt to determine, the in vivo action of leptin on this hypophysiotropic hypothalamic area, by evaluating the concentrations of luteinizing hormone (LH) and follicular stimulating hormone (FSH) in the serum.The experiments were done by stereotaxic injection of recombinant rat leptin (rrleptin) into the third cerebral ventricle (V3) of adult female Wistar rats. Subjects were divided into five groups. Group A included normal intact animals. In Group B, the rats were stereotaxically administered with rrleptin in the V3. The rats, in Groups C, D and E, were subjected to electrolytic lesion of the arcuate nucleus (ARC), of the ventromedial nucleus (VMH) and of both of these hypothalamic nuclei, respectively. Immediately after the electric lesion, they were intracranially injected with rrleptin. Blood samplings for serum LH and FSH levels estimation were performed three times: 1) just before any stereotaxic procedure, 2) six hours, and 3) twenty-four hours after leptin administration.The results showed that serum LH levels increased dramatically in group B, six hours after leptin administration. The LH levels in Groups C, D and E presented the same pattern with a lower peak. The FSH levels were doubled six hours after leptin administration in all groups without any exception. Both LH and FSH serum levels reverted to the initial basic levels after 24 hours.The significant conclusion derived from this study is that ARC and VMH, which are responsible for controlling the tonic secretion of gonadotropins, respond in a different way for the FSH and LH secretion. This also suggests that some other mechanism(s) or factor(s) may additionally participate in the control of the tonic component of FSH secretion.

Extrapyramidal symptoms are observed in frontotemporal dementia (FTD). (123)I-FP-CIT (DaT scan) single photon emission computed tomography (SPECT) can detect loss of presynaptic dopamine transporters in the striatum. We aimed to evaluate the dopaminergic status of the striatum in patients with FTD using DaT scan. Seven patients (age range 65-76 years), who fulfilled the Neary criteria and in whom the diagnosis of FTD was confirmed by hexamethylpropyleneamine oxime SPECT, were included in the study. The severity of the extrapyramidal symptoms was evaluated by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). SPECT using (123)I-FP-CIT was done. A (region - occipital)/occipital ratio was calculated for the striatum, putamen and caudate nucleus. The results were compared with those of the 7 age-matched normal controls. The uptake of the radiotracer in the right and left striatum was reduced to 62% (p = 0.000) and 68% (p = 0.000), respectively, compared to controls. The motor UPDRS score of the patients with FTD showed a negative correlation to the uptake of the radiotracer. The presynaptic dopamine transporter in FTD is impaired, related to the severity of the extrapyramidal symptoms. Since an effective treatment for FTD is still to be established, there is a need for evaluating the efficacy of dopaminergic drugs.

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S219 tool in the assessment of traumatic nerve lesions. Sometimes in traumatic nerve lesions multiple site damages can be observed. To identify cases of traumatic double site radial nerve involvement assessed through US. Methods: We retrospectively evaluated 36 patients admitted to our neurophysiology lab from January 2010 to March 2013 for traumatic radial nerve lesions following humeral fractures. All those patients underwent clinical, electrodiagnostic and sonographic evaluation. Results: In 14 patients a double site involvement of radial and posterior interosseous nerve was observed through US. Conclusions: Multiple site nerve lesions following a trauma can be suspected based on clinical evaluation (presence of non homogeneous motor or sensory deficit) but are difficult to demonstrate through electrodiagnostic assessment. US can help to detect unexpected nerve impairment and can help identify multiple site traumatic nerve lesions showing that they are often more frequent than we can diagnose with neurophysiology alone. P625 Multimodal assessment of small fiber neuropathy: laser evoked potentials or skin biopsy? C. Creac’h1,2, J.-P. Camdessanche3, F. Robert3, J.-C. Antoine3, R. Peyron1,2, P. Convers2,3 1CHU Saint-Etienne, Pain Center, Saint-Etienne, France; 2Inserm 1028-Central Integration of Pain Lab, Centre for Neurosciences, Lyon & Saint-Etienne, France; 3CHU Saint-Etienne, Neurology, Saint-Etienne, France Question: Laser Evoked Potentials (LEPs) and Skin Biopsy (SB) are both considered as reliable methods for assessing a diagnosis of Small Fiber Neuropathy (SFN). The issue is whether these two methods are redundant or not. Methods: We selected 67 patients (42F, 25M; 54±14 years) with probable pure painful SFN including the feet. All of them had thermo-algesic hypesthesia (either observed clinically or confirmed by quantitative sensory testing). LEPs was considered as abnormal if N2P2 was abnormal on at least 2 areas out of the 8 explored (third cervical dermatoma, hands, thighs, feet). SB was considered as abnormal if the density of intra-epidermal nerve fibers (IENFD) was abnormal either on proximal (thighs) or distal (leg) areas. We compared the sensitivity of these techniques and explored clinical factors that may predict these results. Results: Only 58% of patients had abnormal IENFD while 79% of patients had abnormal LEPs. The concordancy between SB and LEPs was 55% on proximal areas and 51% on distal areas. There was 2.5 fold more patients with abnormal LEPs and normal SB than patients with normal LEPs and abnormal SB (23 vs 9 patients). These results were not explained by the length-dependent characteristics of SFN nor by the duration of pain evolution. Burning pain was the only clinical factor predicting abnormal SB (OR=4.1; p=0.024). Conclusions: The discrepancies between LEPs and SB may provide in part from differential lesions of A delta and C fibers. In practice we may recommend to record LEPs in a first approach in case of expected painful pure SFN. P627 Is precautionary neurophysiological monitoring useful for beta-thalassemia patients? P. Nemtsas1, V. Perifanis2, E. Koutsouraki1, A. Orologas1, M. Arnaoutoglou1 1University General Hospital of Thessaloniki AHEPA, 1st Department of Neurology, Thessaloniki, Greece; 2University General Hospital of Thessaloniki AHEPA, First Propedeutic Department of Internal Medicine, Thessaloniki, Greece The thalassemias are the most common single gene disorder in the world. Over the last years, a limited number of studies, mainly in children, have demonstrated a mild peripheral neuropathy in b-thalassemia patients. Chronic hypoxia, iron overload, desferrioxamine (DFO) neurotoxicity and bone marrow expansion are implicated, but sufficient explanatory evidence and biomarkers development is envisaged. We perform motor conduction studies of the median, ulnar, peroneal and tibial nerves, as well as sensory conduction studies of the median, ulnar, peroneal and sural nerves in adults. For the first time to our knowledge, we use extended EMG studies (brachioradialis, abductor digiti quinti (hand), extensors carpi radialis, anterior tibialis, quadriceps rectus femoris) to reveal and better analyze peripheral neuropathy in these patients. Our findings are correlated with the history, the laboratory findings and the medication followed. As life expectancy for b-thalassemia patients extends, we support the use of neurophysiologic monitoring in order to achieve the appropriate management and as a result a better life quality for this patient group. P628 Electrophysiological data of DSMA1 patients in the Netherlands X. Stalpers1, A. Verrips1, B.-T. Poll-The2, J.M. Cobben3, I. Snoeck4, I. de Coo5, A. Brooks6, S. Bulk7, R. Gooskens8, A. Fock9, C. Verschuuren-Bemelmans10, R. Sinke10, M. de Visser11, H. Lemmink10 1Canisius Wilhelmina Hospital, Neurology, Nijmegen, Netherlands; 2Emma Children’s Hospital, Academic Medical Center, Pediatric Neurology, Amsterdam, Netherlands; 3Emma Children’s Hospital, Academic Medical Center, Pediatric Genetics, Amsterdam, Netherlands; 4Juliana Children’s Hospital, Pediatrics, The Hague, Netherlands; 5Erasmus Medical Center, Neurology, Rotterdam, Netherlands; 6Erasmus Medical Center, Clinical Genetics, Rotterdam, Netherlands; 7Wilhelmina Children’s Hospital, University Medical Center Utrecht, Medical Genetics, Utrecht, Netherlands; 8Wilhelmina Children’s Hospital, University Medical Center Utrecht, Neurology, Utrecht, Netherlands; 9University Medical Center Groningen, Neurology, Groningen, Netherlands; 10University Medical Center Groningen, Genetics, Groningen, Netherlands; 11Academic Medical Center, Neurology, Amsterdam, Netherlands Question: What are characteristic electrophysiological findings in DSMA1 patients? Background: Distal spinal muscular atrophy type 1 (DSMA1) is a rare disorder with distal muscle weakness, hypotonia and early respiratory difficulties as most striking symptoms. The pathophysiology is unknown. Some think the anterior horn cell is primarily affected, followed by degeneration of axons, others think it is vice versa. The former is supported by spinal cord autopsy data and findings in the animal model, the latter is supported by sural nerve biopsies and the early and severe changes in nerve conduction studies. Methods: We collected electrophysiological data of 10 Dutch DSMA1 patients. Results: Electrophysiological findings showed mostly reduced or absent compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes. Nerve conduction velocities are markedly reduced and could be in the demyelinating range. Distal motor latency (DML) was generally not in the demyelinating range, considering CMAP amplitudes below 1mV being less trustworthy. None of the patients showed evidence for conduction block. Electromyography could be normal or show spontaneous muscle fiber activity and reinnervation. Electrodiagnostic findings best fit an axonal neuropathy (Table 1, see p. S220). Conclusions: In these 10 Dutch DSMA1 patients, electrodiagnostic findings suggest a severe axonal neuropathy. Our findings make the anterior horn cell as the primary site of the disorder less likely. References: Diers A, Kaczinski M, Grohmann K, et al. The ultrastructure of peripheral nerve, motor-end plate and skeletal muscle in patients suffering from spinal muscular atrophy with respiratory distress type 1 (SMARD1). Acta Neuropathol 2005;110;289-97. P629 A neurophysiological study of A-delta fibres in demyelinating and axonal polyneuropathies through cutaneous silent period recordings D. Lopergolo1, B. Isak1,2, M. Gabriele1, E. Onesti1, G. Tartaglia1, A. Biasiotta1, S. La Cesa1, G. Di Stefano1, A. Truini1, M. Inghilleri1 1“Sapienza” University of Rome, Department of Neurology and Psychiatry, Rome, Italy; 2Marmara University, Istanbul, Turkey Introduction: Cutaneous silent period (CSP) is a brief pause in voluntary muscle contraction following noxious cutaneous nerve stimulation which allows to study small myelinated fibres. We investigated CSP in patients with demyelinating or axonal polyneuropathy (PNP) in order to evaluate the involvement of A-delta fibres. Furthermore we estimated the correlation of CSP parameters with presence of neuropathic pain in these group of patients. Materials and methods: Eighty demyelinating PNP patients, 178 axonal PNP patients and 265 healthy controls underwent clinical [neurological examination, Medical Research Council Score, DN4 Questionnaire] and electrophysiological [motor root conduction time (MRCT), compound muscle action potentials (CMAP), sensory nerve action potentials (SNAP) and CSP

HbOThrace is an abnormal hemoglobin which is constructed by defective beta chains (Glu121--Lys121). It mostly characterises the Muslim minority of the Thrace region. During the last 6 years, our department detected HbOThrace in 118 cases. Four groups were formed, the first consisted of cases of HbOThrace trait with normal iron and ferritin levels, the second of cases of HbOThrace hemoglobinopathy, the third of cases of HbOThrace/Hb beta zero hemoglobinopathy and the fourth of cases of HbOThrace trait with low iron and ferritin levels. The second, third and fourth group were compared with the first one. The conclusion is that the presence of HbOThrace leads to a mild hypochromic anemia, with no clinical findings, but the coexistence of beta zero gene or iron deficiency produces more pronounced laboratory findings and even clinically evident anemia.

Background Clear cell renal cell carcinomas (ccRCCs) constitute the most common renal carcinomas, characterized by a relatively aggressive clinical course. Thus, scientific research is targeting towards the identification of immunohistochemical and molecular markers that could be useful regarding diagnosis, appropriate therapy and prediction of prognosis. In the present study we assessed and correlated the expression of caspase-8, phosphorylated p38 mitogen-activated protein kinase (p-p38) and bcl-2 protein with histopathological features and clinical outcome of 27 patients with ccRCCs. Method Immunohistochemistry in formalin-fixed and paraffin-embedded tissue sections was performed. The associations among various features were assessed utilizing statistical analysis. Results We found that increased expression of cytoplasmic caspase-8 and bcl-2 protein was strongly associated with low Fuhrman's grade of carcinomas (p = 0.019 and p = 0.041, respectively). On the other hand, increased p-p38 expression was significantly related to high Fuhrman's grade (p = 0.006). Moreover, high bcl-2 expression was correlated with low pathological stage of ccRCCs (p = 0.026). Increased expression of cytoplasmic caspase-8 as well as low-grade tumors (grade 1 and 2) implied a greater probability of patients' survival, in univariate statistical analysis (p = 0.037 and p = 0.019, respectively). Neither p-p38 nor bcl-2 expression was significantly linked to patients' survival. There were not emerged statistically significant associations among caspase-8, p-p38 kinase and bcl-2 protein. Conclusion For the first time the prognostic impact of caspase-8 and p-p38 was studied in a series of ccRCCs, using immunohistochemistry in formalin-fixed and paraffin-embedded tissue sections. The suggestive relationship of caspase-8 with patients' clinical outcome, as well as the role of p-p38 within different grade categories, mandates further studies in larger cohorts of RCCs.

Recent advances in mobile phone technology have placed an impressive array of sensing and communication equipment at the hands of an ever-growing number of people. One of the areas which can potentially be transformed by the availability of what is essentially a cheap, ubiquitous networked sensor, is that of remote diagnosis of movement disorders, such as Parkinson's disease. This work describes a smartphone-based method for detecting and quantifying the hand tremor associated with movement disorders using signals from the accelerometer and gyroscope embedded in the patient's phone. Our approach is web-based and user-friendly, requiring minimal user interaction. In clinical experiments with twenty subjects, we found that by combining both accelerometer and gyroscope signals, we were able to correctly identify those with hand tremor, using very simple signal metrics.

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