Two cases with mitochondrial membrane protein-associated neurodegeneration: genetic features and long-term clinical follow-up.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological disease with childhood or adult onset. It is a subtype of clinically and genetically heterogeneous group of disorders, collectively known as neurodegeneration with brain iron accumulation . MPAN is generally associated with biallelic pathogenic variants in C19orf12. Herein, we describe genetic and clinical findings of two MPAN cases from Turkey. In the first case, we have identified the relatively common pathogenic variant of C19orf12 in the homozygous state, which causes late-onset MPAN. The second case was homozygous for an essential splice-site variation.

Clinical and genetic features of PKAN patients in a tertiary centre in Turkey.

OBJECTIVE: Pantothenate kinase-associated neurodegeneration (PKAN) is caused by mutations of the pantothenate kinase 2 (PANK2) gene. The major clinical sign of PKAN is dystonia and the eye-of-the-tiger pattern on the MRI has been a clue for the diagnosis. We aim to discuss clinical and genetic findings of 22 PKAN patients from 13 families. METHODS: Twenty-two patients were clinically diagnosed with PKAN and screened for PANK2 mutations. The patients were classified according to their onset age and progression rate. RESULTS: Mutation screening revealed 5 novel and 7 previously reported sequence variants in PANK2. The variants identified were in the form of missense changes, small exonic deletions and intronic mutations with a probable splicing effect. The presenting features were dystonia and gait disturbance in early onset patients, whereas the presenting symptoms were variable for the late onset group. The progression rate of the disease was not uniform. CONCLUSION: The current report is the first patient series of PKAN from Turkey that expands the clinical and genetic spectrum of the disease.

Preventing Sciatic Nerve Injury due to Intramuscular Injection: Ten-Year Single-Center Experience and Literature Review.

AIM: Sciatic nerve injury is the most frequent and serious complication of intramuscular gluteal injection. This study aims to highlight the incidence and causes of this continuing problem and to discuss the relevant literature. < p < MATERIAL and METHODS: A total of 217 subjects who were diagnosed with sciatic nerve injury in our neurophysiology laboratory between 2003 and 2013 were examined. Sensory and motor transmission studies and needle electromyography were performed by conventional methods in the two lower legs and the results were compared between each leg. RESULTS: Of the subjects who experienced a sciatic injury secondary to intramuscular injection, 59 (27.2%) were female and 158 (72.8%) were male. In all subjects, the dorsogluteal site of the buttocks was selected for intramuscular injection. Sciatica occurred on the right side in 91 subjects, on the left side in 125, and bilaterally in one. The peroneal nerve was more affected than the tibial nerve. The most used agents were non-steroidal anti-inflammatory drugs. According to follow-up electromyography findings of 103 subjects, significant sequelae remained in 2/3 of cases. CONCLUSION: The occurrence of sciatic neuropathy after gluteal injection causing permanent sequelae and leading to medicolegal problems is relatively rare. We suggest a double quadrant drawing technique in each gluteal region. We also draw attention to this issue with postgraduate and in-service training programs of medical staff, and providing continuity in education can reduce this serious complication.

Gene expression profiles of autophagy-related genes in multiple sclerosis.

Multiple sclerosis (MS) is an imflammatory disease of central nervous system caused by genetic and environmental factors that remain largely unknown. Autophagy is the process of degradation and recycling of damaged cytoplasmic organelles, macromolecular aggregates, and long-lived proteins. Malfunction of autophagy contributes to the pathogenesis of neurological diseases, and autophagy genes may modulate the T cell survival. We aimed to examine the expression levels of autophagy-related genes. The blood samples of 95 unrelated patients (aged 17-65years, 37 male, 58 female) diagnosed as MS and 95 healthy controls were used to extract the RNA samples. After conversion to single stranded cDNA using polyT priming: the targeted genes were pre-amplified, and 96×78 (samples×primers) qRT-PCR reactions were performed for each primer pair on each sample on a 96.96 array of Fluidigm BioMark™. Compared to age- and sex-matched controls, gene expression levels of ATG16L2, ATG9A, BCL2, FAS, GAA, HGS, PIK3R1, RAB24, RGS19, ULK1, FOXO1, HTT were significantly altered (false discovery rate<0.05). Thus, altered expression levels of several autophagy related genes may affect protein levels, which in turn would influence the activity of autophagy, or most probably, those genes might be acting independent of autophagy and contributing to MS pathogenesis as risk factors. The indeterminate genetic causes leading to alterations in gene expressions require further analysis.

The Effect of Circadian Melatonin Levels on Inflammation and Neurocognitive Functions Following Coronary Bypass Surgery.

PURPOSE: In this study, the relationship between the plasma levels of melatonin and intercellular adhesion molecule-1 (ICAM-1), which plays role in several intercellular interactions including inflammatory and immune responses, and early neurocognitive functions associated with ischaemia-reperfusion injury during open heart surgery is examined. METHODS: Forty patients who were to undergo elective coronary artery bypass grafting (CABG) were divided into two groups, those who underwent their operations at 8 AM (group I; n = 20) and those who underwent their operations at 1 PM (group II; n = 20). Blood samples were collected prior to surgery (S1), when the aortic cross clamp was removed (S2) and 4 (S3) and 24 h after the surgery (S4). Neuropsychiatric assessment was conducted one day before and seven days after surgery. RESULTS: Melatonin levels measured during and after surgery were also significantly higher in Group 1. ICAM-1 levels were significantly lower in Group 1 at S2 and S3. Significant deterioration was observed in postoperative neurocognitive function compared with preoperative functions in Group 2 more than Group 1. CONCLUSION: We hypothesise that the greater preservation of neurocognitive functions in the morning patients is associated with elevated melatonin levels, which reduce the damage from ischaemia-reperfusion injury.

Investigation of the Rho-kinase 2 gene Thr431Asn polymorphism in migraine.

BACKGROUND: Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. AIM: This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. MATERIALS AND METHODS: A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. RESULTS: Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. CONCLUSION: This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population.

Colchicine treatment in children with familial Mediterranean fever: is it a risk factor for neuromyopathy?

BACKGROUND: We cared for a 17-year-old adolescent with familial Mediterranean fever under colchicine treatment. Because of the increased creatinine kinase level (3937 U/L) observed in this individual, we planned to assess all pediatric patients with familial Mediterranean fever under colchicine treatment to detect any resultant neuromyopathy. METHODS: The study included 88 children with familial Mediterranean fever who were receiving colchicine. The patient with myopathy was not included in the study. Serum creatinine kinase levels were measured and nerve conduction studies were carried out in all patients. RESULTS: The study included 88 patients (47 female, 53.4%) with an average age of 10.1 ± 3.35 years. The average period of colchicine use was 28.25 ± 17.66 months. Side effects of colchicine were detected in 10 patients (11%)--as diarrhea in eight patients, leukopenia in one patient, and hair loss in one patient. Nerve conduction studies determined incidental carpal tunnel syndrome in only one patient. CONCLUSIONS: Our study did not suggest an elevated risk of neuromyopathy associated with the use of colchicine for familial Mediterranean fever.

Is increased red cell distribution width (RDW) indicating the inflammation in Alzheimer's disease (AD)?

Increasing evidence indicates that inflammation has a substantial role in the pathogenesis and progression of AD. RDW, a measure of heterogeneity in the size of circulating erythrocytes, is associated with inflammatory markers in many numerous diseases. Present study was undertaken to assess the interrelationships between RDW and AD. A total of 197 patients with AD (male/female: 96/101, mean age 76.2 ± 6.9) and 133 patients as controls with normal cognitive function (male/female: 72/61, mean age 71.68 ± 5.3) were enrolled in this cross-sectional study. RDW values of all participants were measured. Mini-Mental State Examination (MMSE) and clock drawing tests were performed for cognitive assessment. DSM-IV and NINCDS-ADRDA criteria were used for diagnosis of AD. The mean RDW values were significantly higher in AD group (13.93 ± 1.1 vs. 13.24 ± 1.2; p<0.001) and also a negative moderate correlation between RDW and MMSE was identified (r: -0.453; p<0.001). After adjusting for confounders, RDW has the strongest association with AD (odd ratio (OR) 1.51, CI=1.10-2.07). In present study RDW levels were significantly increased in patients with AD. Whereas elevated RDW value is usually considered as a novel biomarker of inflammation, the results of our study may support the role of inflammation in pathophysiology of AD. Furthermore the correlation of RDW with poorer cognition status suggests that it may be used as a marker of AD severity.

Long-term survival in metastatic malignant melanoma: ipilimumab followed by vemurafenib in a patient with brain metastasis.

A 46-year-old man was diagnosed with brain metastasis after a two-year history of melanoma. Paliative radiotherapy was administered followed by dacarbazine, temozolamide, ipilimumab, stereotactic radiosurgery, ipilimumab reinduction and finally vemurafenib, to which the patient showed objective responses. The patient received vemurafenib for four months and died after progresive disease. Long-term follow-ups after surgery have been reported in the literature. However, in patients with unresectable metastases, outcomes are mostly detrimental. The present patient survived for 40 months after brain metastasis. The unusually long survival observed in the present case indicates the sequential effectiveness of radiotherapy, chemotherapy, ipilimumab, stereotactic radiosurgery and vemurafenib.

Computed tomography based measurement of the dimensions of foramen ovale and rotundum in trigeminal neuralgia.

OBJECTIVES: To compare sizes of the foramen ovale and rotundum in trigeminal neuralgia (TN) patients and healthy individuals on CT images. METHODS: Twenty-one TN patients and 24 healthy volunteers were included in this retrospectively designed study, carried out at the Department of Anatomy, Medical School, Gaziantep University, Gaziantep, Turkey, between May 2004 and August 2009. The dimension of the foramen ovale on the cross-sectional images, and the foramen rotundum on coronal sections on CT images were examined. RESULTS: The mean sizes of the foramen rotundum on the right and left sides were 3.04 x 3.2 mm and 2.8 x 2.9 mm in TN patients, and 2.4 x 3.2 mm and 2.5 x 3.1 mm in controls. The mean sizes of the foramen ovale on the right and left sides were 4.8 x 6.04 mm and 4.9 x 5.5 mm in TN patients, and 3.7 x 8.2 mm and 4.1 x 7.6 mm in controls. The dimensions of left and right foramens were not significantly different in both TN patients and controls (p > 0.05). Furthermore, a statistically significant difference was not found between the foraminal dimensions of the TN patients and controls (p > 0.05). CONCLUSION: This study revealed that the sizes of foramen ovale and rotundum are highly symmetrical in both groups, suggesting that sizes of the foramina are not associated with the occurrence of TN.

Electrophysiologic assessment of the subclinical changes in facial functions after parotidectomy.

OBJECTIVE: Our objective was to evaluate whether there was a subclinical change in the functions of the facial nerve after parotidectomy. METHODS: Facial nerve functions of 21 patients who had parotidectomy between January 1999 and December 2003 were assessed using electromyography (EMG) at least 5 years after the surgery. RESULTS: There was no significant difference between both sides of the face in the EMG amplitudes (P > 0.05) except for the amplitudes obtained from the site of nasolabial sulcus (P < 0.05). In the patients who underwent total parotidectomy, the EMG amplitudes were significantly different for both sides of the face (P < 0.05). No significant difference was found in the comparison of other measurements performed by EMG. CONCLUSIONS: Tumor histopathologic type (benign or malignant) and type of parotidectomy (superficial or total) do not cause a subclinical dysfunction of the facial nerve after parotidectomy in the patients who also have clinically normal facial functions. The only exception to this contention is the subclinical dysfunction in nasal branches of the facial nerve in total parotidectomy cases.

Aortic elastic properties of patients with neurocardiogenic syncope.

OBJECTIVE: Neurocardiogenic syncope (NCS) is a common clinical problem; however, hemodynamic mechanism is not clearly understood. Aim of the present study was to investigate aortic elastic parameters of patients with NCS provoked by head-up tilt test. MATERIAL AND METHOD: We conducted a prospective study of 40 cases referred to our institution for head-up tilt testing. Group I constituted as 22 patients who developed mixed response and were enrolled for analysis. Hemodynamic data were compared with subjects of negative head-up tilt test (Group II). Aorta-diastolic and aorta-systolic diameters, aortic strain, aortic distensibility, aortic elastic modulus, and aortic stiffness index were calculated from transthoracic echocardiographically derived diameters of thoracic aorta. RESULTS: Aortic distensibility (mean+/-SD; 2.7+/-1.2 cm2xdyn(-1)x10(-6) vs 4.0+/-1.2 cm2xdyn(-1)x10(-6), P=0.003) and aortic strain index (mean+/-SD; 7.0+/-1.8% vs 8.7+/-2.9%, P=0.042) were lower, and aortic stiffness index (mean+/-SD; 27.6+/-10.9 vs 20.9+/-6.18, P=0.035) and aortic elastic modulus (mean+/-SD; 0.94+/-0.7 cm2xdyn(-1)x10(-6) vs 0.49+/-0.1 cm2xdyn(-1)x10(-6), P=0.009) were higher in patients in Group I compared with those in Group II. There was no difference between two groups for following clinical variables: aorta-diastolic and aorta-systolic diameters, systolic and diastolic blood pressure, pulse pressure, E/A, weight, height, and body mass index. CONCLUSIONS: Findings of this study have shown that elastic properties of aorta are impaired in patients with NCS. The data suggest that increase in aortic stiffness might be one of the determinants responsible for NCS. This proposal of novel link should be confirmed in further studies.

Cryptogenic stroke in two cases with left atrial band: coincidence or cause?

Congenital left atrial band (LAB) has been reported previously. However, clinical significance of the LAB has not been clearly defined. Although LAB is generally known as a benign entity, it has been reported to be associated with Chiari's network, patent foramen ovale, mitral valve prolapse, mitral regurgitation, and supraventricular arrhythmias. In this case report we report LAB in a 34-year-old male and 56-year-old female with cryptogenic stroke. To our knowledge, the association of LAB with cardioembolic events has not been reported previously. Lack of other potential risk factors of cardioembolic stroke and normal laboratory examinations lead us to suggest that LAB might be the cause of cardioembolism in the present two cases. In conclusion, in cases with ischaemic stroke, especially the ones with undetermined aetiology, LAB should be kept in mind as a potential cause of cardioembolism.

R-R interval variation and sympathetic skin response in fibromyalgia.

BACKGROUND: This study proposed to assess the autonomic nervous system (ANS) functions in fibromyalgia (FM) by using two electrophysiological tests, sympathetic skin response (SSR) and the heart rate variability named R-R interval variation (RRIV). METHODS: Sympathetic skin response and RRIV were studied in 29 female patients with FM and 22 healthy age-matched female controls. R-R interval variation at rest (R%), during deep breathing (D%), the difference between D% and R% (D-R) and the ratio of D-R% (D/R) were determined. Pain threshold was measured using a mechanical algometer. RESULTS: R-R interval variation at rest (R%) and D/R did not show significant difference between patients and controls, whereas D% and D-R were significantly lower in patients compared to controls. SSR latencies of patients' hands and feet had no significant difference compared to controls' hand and feet SSR latencies. SSR latencies of patients' hands correlated significantly with control point score, total myalgic score, Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating Scale. Sympathetic skin response latencies of patients' feet correlated only with HARS. CONCLUSIONS: Analysis of heart rate variability may be useful and complementary to clinical examination in patients with symptoms of dysfunction in cardiovascular reflex pathways.

Primary hydatid cyst of the head and neck diagnosed with ultrasound and computed tomography: a report of two cases.

Hydatid cysts of the head and neck are rare, even in countries where echinococcal infestation is endemic. This report presents two patients with hydatid cyst, diagnosed using ultrasonography and computed tomography, in whom the cysts were located between the right cervical paravertebral muscles and below the superficial muscles of the right temporal region.

Using the blink reflex as measured by electromyogram to assess cranial nerve involvement in people affected by leprosy.

Damage to the peripheral nervous system is particularly frequent in leprosy patients. Trigeminal and facial nerves are among the most commonly affected. The aim of our study was to evaluate the efficacy of the blink reflex as a method for diagnosis of cranial nerve involvement in people affected by leprosy. We studied 37 affected people (mean age: 38 yrs, 20 female and 17 male) and 35 age-matched healthy subjects (mean age: 34 yrs, 20 female and 15 male). Blink reflexes were obtained after unilateral electrical stimulation of the supraorbital nerve for quantitative analysis of 3 responses, early ipsilateral phasic component (R1), late ipsilateral tonic component (R2i), and late contralateral tonic component (R2c). Nerve conduction parameters were studied in all subjects. The latencies of both the ipsilateral early phasic component (R1) and bilateral late tonic components (R2i and R2c) in people affected by leprosy were significantly prolonged compared with the controls. Out of 37 people affected by leprosy, 22 (59%) showed abnormalities R1 latency, 28 (75%) R2i latency and 31 (83%) R2c latency. No correlation was observed between prolonged latencies and duration of the disease. We conclude that blink reflex testing, which can be easily and rapidly performed in an EMG laboratory using standard equipment, can provide useful and objective information for the diagnosis of cranial nerve lesions and for the determination of the degree thereof.

Auditory p300 event-related potentials in fibromyalgia patients.

This study assessed the cognitive brain function measured by the cognitive P300 auditory event-related potentials (ERPs) in female fibromyalgia (FM) patients and compared the results with those from healthy age and education-matched controls. The relationship of the P300 potentials to the pain threshold of patients was also investigated. The P300 component of the auditory ERPs were studied in 11 female FM patients and 10 age and education-matched healthy controls. None of the patients were taking antidepressants such as amitriptyline or serotonin-reuptake inhibitors. The P300 latencies of the patients were not significantly different whereas the N2P3 amplitudes were significantly lower than the controls. The P300 latencies in the patients negatively correlated with the total myalgic scores (TMS) (r= -0.73) and the control point scores (CPS) (r=-0.85). On the other hand, the P300 amplitudes showed a significant correlation with the TMS (r=0.61) and the CPS (r=0.60). There was no significant correlation between the anxiety and depression scores with the P300 latency or amplitudes. These results showed cognitive impairment, which was mainly expressed by the lower N2P3 amplitudes in patients with FM, and its clinical relevance requires further research.