Sakir Delil

Collection and Analysis of a Parkinson Speech Dataset With Multiple Types of Sound Recordings

There has been an increased interest in speech pattern analysis applications of Parkinsonism for building predictive telediagnosis and telemonitoring models. For this purpose, we have collected a wide variety of voice samples, including sustained vowels, words, and sentences compiled from a set of speaking exercises for people with Parkinsons disease. There are two main issues in learning from such a dataset that consists of multiple speech recordings per subject: 1) How predictive these various types, e.g., sustained vowels versus words, of voice samples are in Parkinsons disease (PD) diagnosis? 2) How well the central tendency and dispersion metrics serve as representatives of all sample recordings of a subject? In this paper, investigating our Parkinson dataset using well-known machine learning tools, as reported in the literature, sustained vowels are found to carry more PD-discriminative information. We have also found that rather than using each voice recording of each subject as an independent data sample, representing the samples of a subject with central tendency and dispersion metrics improves generalization of the predictive model.

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1GLU7ALA), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1GLU7ALA, compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1GLU7ALA relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system.

A hospital-based study: risk factors in development of motor complications in 555 Parkinson's patients on levodopa therapy.

OBJECTIVES Although levodopa (LD) is the gold standard therapy for symptomatic treatment of Parkinsons disease (PD), the chronic use of LD leads to the development of motor complications in almost all patients. PATIENTS AND METHODS We assessed the presence and risk factors for motor complications in PD patients on LD therapy. We examined 555 PD patients on LD for the presence or absence of wearing-off (WO+/-) and dyskinesia (DK+/-). RESULTS WO was present in 46.3%, and DK in 30.1% of patients. The mean age at onset of symptoms were earlier in WO(+)/DK(+) groups (p<0.001). The duration of PD was longer in WO(+)/DK(+) groups (p<0.001). The time between the first symptom and the occurrence of WO/DK, or LD initiation were not significantly different. The initial LD dose was significantly higher in WO(+) compared to WO(-) (300.1mg/d versus 232.5mg/d, p<0.001), and DK(+) compared to DK(-) groups (291.4 mg/d versus 251.9 mg/d, p=0.001). The time until dopamine agonist (DA) initiation was longer in WO(+)/DK(+) groups (p<0.001). WO (p<0.001) and DK (p=0.002) were more common in patients with H&Y stages 3+4. UPDRS scores were higher in WO(+) and DK(+) patients (p<0.001 and p=0.027). CONCLUSION Our study showed that the development of motor complications was associated with early onset PD, longer disease duration, advanced disease, higher initial LD dose, longer LD use, and late DA initiation, but not with the timing of LD initiation.

Evaluation of the Tibial Nerve with Shear-Wave Elastography: A Potential Sonographic Method for the Diagnosis of Diabetic Peripheral Neuropathy

Purpose To evaluate the value of shear-wave elastography (SWE) in the detection of diabetic peripheral neuropathy (DPN) of the tibial nerve. Materials and Methods This study was approved by the institutional review board, and written informed consent was obtained from all study participants. The study included 20 diabetic patients with DPN (10 men, 10 women), 20 diabetic patients without DPN (eight men, 12 women), and 20 healthy control subjects (nine men, 11 women). The tibial nerve was examined at 4 cm proximal to the medial malleolus with gray-scale ultrasonography and SWE. The nerve cross-sectional area (in square centimeters) and the mean nerve stiffness (in kilopascals) within the range of the image were recorded. Inter- and intrareader variability, differences among groups, and correlation of clinical and electrophysiologic evaluation were assessed with intraclass correlation coefficients, the Mann Whitney U test, and the Wilcoxon signed rank test. Results Between diabetic patients with and diabetic patients without DPN, mean age (60 years [range, 38-79 years] vs 61 years [range, 46-75 years], respectively), mean duration of diabetes (10 years [range, 1-25 years] vs 10 years [range, 2-26 years]), and mean body mass index (31.4 kg/m2 [range, 24.7-48.1 kg/m2] vs 29.8 kg/m2 [range, 22.9-44.0 kg/m2]) were not significantly different. Diabetic patients without DPN had significantly higher stiffness values on the right side compared with control subjects (P < .001). Patients with DPN had much higher stiffness values on both sides compared with both diabetic patients without DPN (P < .001) and healthy control subjects (P < .001). A cutoff value of 51.0 kPa at 4 cm proximal to the medial malleolus revealed a sensitivity of 90% (95% confidence interval [CI]: 75.4%, 96.7%) and a specificity of 85.0% (95% CI: 74.9%, 91.7%). Conclusion Tibial nerve stiffness measurements appear to be highly specific in the diagnosis of established DPN. The increased stiffness in subjects without DPN might indicate that the nerve is affected by diabetes.

Interobserver variability of seizure semiology between two neurologist and caregivers

PURPOSE We aimed to compare the extent of inter-observer variability in the description of seizure semiology between both neurologists and caregivers. METHOD We prospectively investigated 93 consecutive patients monitored over the past 5 years in our video-EEG unit. The videotaped seizures of the patients were reviewed independently by two neurologists who were blind to the clinical data. The questionnaires were completed by neurologists and caregivers. Interobserver rate of agreement between neurologists and caregivers was analyzed by using the kappa analysis and intraclass correlation coefficients. RESULTS There was excellent agreement for questions regarding whether the patients eyes remained open, laterality of head deviation, arm movements, and ictal period. On the other hand, interobserver rate of agreement was fair to moderate for the laterality of hand automatisms, the presence of nose-wiping, and oral clonic jerks. CONCLUSION Besides variability in interobserver agreement among clinicians, the variability or concordance between physicians and caregivers are also of great importance, especially in case of epilepsy, where the accurate description of the attacks is the major determinant of an accurate diagnosis.

The role of sleep electroencephalography in patients with new onset epilepsy

PURPOSE An increased propensity for seizures is associated with different stages of the sleep-wake cycle. In this study, we prospectively analyzed patients with new-onset epilepsy and investigated the clinical correlates of the yield obtained from sleep electroencephalography (EEG) recordings in patients with a normal wakefulness EEG. METHODS All patients admitted to our epilepsy unit due to unprovoked epileptic seizures and not yet treated with antiepileptic drugs were recruited consecutively for the last three years. All had a routine EEG at wakefulness (WEEG), and those with no epileptiform activity had a video-EEG recording during sleep (SEEG). RESULTS We investigated a total of 241 patients; 129 patients (53.5%) had both wakefulness and sleep EEG recordings. The patients with abnormal WEEG were older than those with normal WEEG (p = 0.005). Abnormal WEEG was detected in only 31.2% of patients with focal seizures, but in 77.3% of patients with generalized seizures (p < 0.001). WEEG was abnormal in 44.0% of patients with diurnal seizures, but in 27.5% of nocturnal seizures (p = 0.007). Abnormal WEEG was present in 75.5% of patients with a presumed genetic origin and in 59.3% of patients with structural etiology (p < 0.001). Sleep EEG detected an abnormality in 41.8% of patients with normal WEEG; of these, 82.8% were focal abnormalities. In contrast, the majority of abnormalities detected in WEEG were generalized (55.8%, p < 0.001). CONCLUSION Our results showed a greater likelihood of abnormal WEEG in older patients and in those with generalized epilepsy, diurnally precipitating seizures, and epilepsy of presumed genetic origin.

Compatibility of MRI and FDG-PET findings with histopathological results in patients with focal cortical dysplasia

PURPOSE The present study aimed to determine if the specific characteristics of fluorodeoxyglucose-positron emission tomography (FDG-PET) analyses of the FCD subgroups were compatible with the magnetic resonance imaging (MRI) and clinical findings of the patients in these subgroups. METHODS This study included 71 patients who had a presurgical evaluation workup performed due to drug-resistant seizures, who underwent epilepsy surgery, and who were histopathologically diagnosed with FCD. Relationships involving MRI and FDG-PET findings and clinical data from pathological subgroups and patients were assessed. RESULTS According to the International League Against Epilepsy (ILAE) classifications of FCD, 28 of the patients were type I and 43 were type II. FCD was visible on the MRI scans of 53 patients, and a majority of this group was classified as type II FCD (n=34). Of these 53 patients, FCD was located in the temporal area of 21 patients, the extratemporal area of 29 patients. Of the patients who exhibited FDG-PET hypometabolism (PET-positive), 23 were classified as temporal, 17 as frontal, 11 showed involvement of the posterior cortex. The age of seizure onset was younger in PET-positive patients (p=0.032), and histopathological analyses revealed that 23 patients had type I FCD and 30 patients had type II FCD. CONCLUSION PET scans reveal a lesion by showing hypometabolism in patients who have refractory epilepsy and an early age of onset with FCD. The lesions of MRI-negative/PET-positive FCD patients tend to be localized in the temporal lobe and that FCD may be localized in the frontal lobe of MRI-negative/PET-negative patients. However, the histopathological examinations of MRI-positive/PET-positive, MRI-negative/PET-positive, and MRI-negative/PET-negative patients did not exhibit a particular histopathological subtype.

Seizure Outcome of Patients with Magnetic Resonance Imaging–Negative Epilepsies: Still An Ongoing Debate

BACKGROUND Surgical results regarding MRI-negative epilepsy were presented and related clinical and histopathological parameters were discussed. METHODS Thirty-six MRI-negative epilepsy patients were retrospectively analyzed. Histopathological specimens were re-reviewed by 2 blind neuropathologists and re-classified based on the current classifications. RESULTS The mean age at surgery and seizure onset was 24.5 years and 9.3 years, respectively. Eight patients were younger than 18 years. Mean duration of seizures was 15.3 years. All but 2 underwent invasive monitorization. Eighteen patients had hypometabolism on FDG-PET with temporal lobe involvement in majority (66.7%). Hypometabolism was found in all patients with hippocampal sclerosis (HS), which was present in 50% and 66.7% of focal cortical dysplasia (FCD) type I and II patients, respectively. The frontal lobe resection was the most frequent type of operation followed by resections in temporal, parietal and occipital lobes. In 7 patients, multilobar resection was performed. Histopathological diagnosis was FCD type I, II, III, HS, and gliosis in 14, 12, 2, 3 and 2 patients, respectively. The mean follow-up was 5.8 years. Seventeen patients were seizure free and favorable outcome (Engels I and II) was found in 69.7%. FCD type I tend to have more favorable seizure outcome. Duration of epilepsy and hypometabolism on FDG-PET was significantly related to outcome, whereas involved lobe was not. CONCLUSIONS Our results suggest it is worth pursuing resective surgery in adults as well as in children with drug-resistant epilepsy with normal MRI.

Misdiagnosis of menstruation-related recurrent hypersomnia as epilepsy in a patient with generalized epileptic discharges

Recurrent hypersomnias are very rare with two subtypes as Kleine-Levin syndrome and menstruation-related hypersomnia, which is very rarely encountered worldwide. Here, we report a young girl with menstruation-related recurrent hypersomnia, who was misdiagnosed as epilepsy due to co-existing generalized epileptic discharges. The importance of this comorbidity in terms of differential diagnosis of the attacks is discussed.

Magnetic resonance imaging findings in probable Creutzfeld-Jacob disease: comparison with electroencephalography and cerebrospinal fluid characteristics

Background Creutzfeld-Jacob disease (CJD) is a rare, progressive disease that has a vast clinical manifestation range. Cranial magnetic resonance imaging (MRI), electroencephalography (EEG), and measurement of 14-3-3 in cerebrospinal fluid (CSF) may offer a pragmatic approach in the diagnosis of CJD as an alternative to histopathological confirmation. Purpose To present the symptoms and signs of the CJD patients in regard to radiological and neurophysiological findings. Material and Methods We collected all cases with the diagnosis of probable CJD admitted to our neurology department between June 2010 and June 2014. The medical records and laboratory data, clinical features, results of MRI (including diffusion weighted images), EEG and CSF evaluations, and other laboratory data to exclude other possible diagnoses were recorded. None of the patients underwent biopsy or autopsy for histological diagnosis. Results Of 20 patients, 11 (55%) were men and nine (45%) were women. The mean age at disease onset was 60.0 ± 9.5 years (age range, 47–80 years). All patients without exception had characteristic abnormalities in DWI and/or FLAIR on admission, about 4 months after the initial symptom. Periodic complexes on EEGs characteristic for CJD were detected only in 10 patients (50%) on admission and in 13 patients (65%) during disease course. Out of 14 patients who underwent CSF examination, 11 (78.5%) were positive for 14-3-3 protein. Conclusion Although the definite diagnosis of CJD is made histopathologically, we aimed to discuss the value of magnetic resonance imaging in the diagnosis of CJD in respect to EEG findings and protein 14-3-3 levels in CSF.