Optical coherence tomography angiography (OCTA) in differential diagnosis of aquaporin-4 antibody seronegative NMOSD and multiple sclerosis.

BACKROUND: Optic neuritis(ON) is a common feature of both relapsing-remitting multiple sclerosis(RRMS) and neuromyelitis optica spectrum disorders(NMOSD). It is crucial to early differentiate these two diseases, as they differ in pathophysiology and treatment. OBJECTIVE: To compare NMOSD and RRMS patients using optical coherence tomography(OCT) and OCT angiography(OCTA) to assess retinal microvascular network differences. METHODS: Fourteen RRMS (28 eyes) and 9 NMOSD patients(18 eyes), and 11 controls were enrolled. Seropositivity for aquaporin-4 antibody (anti-AQP4 Abs) was 44.4%. Peripapillary and macular retinal nerve fiber layer(RNFL) thickness, superficial peripapillary and macular vessel density(VD), area, perimeter and circularity of foveal avascular zone(FAZ) were analyzed. RESULTS: OCTA showed reduction in peripapillary and macular VD and FAZ size in NMOSD+ON compared to RRMS+ON and controls (p = 0.001, p<0.001 and p = 0.010, p<0.001 respectively). Peripapillary VD was similar in RRMS +ON and controls. Peripapillary VD in monophasic seronegative NMOSD+ON eyes was significantly lower than monophasic RRMS+ON eyes (p = 0.030), which was no different from controls. FAZ area was smaller in unaffected eyes in NMOSD than RRMS and controls. CONCLUSIONS: Both OCT and OCTA revealed considerable differences between RRMS and NMOSD patients, providing promising results in favor of clinical utility of OCTA in differential diagnosis of ON, particularly in anti-AQP4 antibody negative patients. OCTA might be a useful biomarker in differentiating NMOSD from MS.

Idiopathic Intracranial Hypertension: Etiological factors, Clinical Features, and Prognosis.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) occurs due to increased intracranial pressure (ICP), is most commonly encountered in obese women, and may lead to loss of vision. This study aimed to determine the demographic features, clinical signs and symptoms, and radiological findings of patients with IIH, and to investigate the factors associated with the prognosis. METHODS: Patients with IIH who were examined and followed-up between January 1992-January 2012 in the Neuro-ophthalmology Unit were retrospectively evaluated. Patients were diagnosed based on the modified Dandy criteria. RESULTS: The mean age of 59 patients included in the study (female, 88.1%) was 30.25±13.12 years. Reported complaints were headache (78.0%), transient visual obscuration (45.8%), nausea (32.2%), dizziness (16.9%), and diplopia (13.6%). Of the patients 69.4% had visual field deficits, and 71% had papilledema (66.1% were bilateral). The rate of obesity was 20.3%. The prognosis was good in 64.7% of the patients, and 35.3% of the patients clinically worsened. Recurrence of symptoms was observed in 33% of the patients and 4 patients had severe permanent vision loss. Demographic features, initial complaints, mean ICP, and pathological magnetic resonance imaging findings were not associated with the prognosis. Delay in treatment and generalized constriction in the visual field were associated with the poor prognosis. CONCLUSION: Compared to patients with IIH in the western population, obesity was less frequent in the present study. Initial visual field defects, especially the generalized constriction and delay to treatment were related to poor prognosis. Cessation of medical treatment was a factor for recurrence. Early diagnosis and appropriate treatment may subside the severity of permanent vision loss in fulminant IIH.

Contingent negative variation is associated with cognitive dysfunction and secondary progressive disease course in multiple sclerosis.

BACKGROUND AND PURPOSE: The relationship between contingent negative variation (CNV), which is an event-related potential, and cognition in multiple sclerosis (MS) has not been examined previously. The primary objective of the present study was thus to determine the association between CNV and cognition in a sample of MS patients. METHODS: The subjects of this study comprised 66 MS patients [50 with relapsing-remitting MS (RRMS) and 16 with secondary progressive MS (SPMS)] and 40 matched healthy volunteers. A neuropsychological battery was administered to all of the subjects; CNV recordings were made from the Cz, Fz, and Pz electrodes, and the amplitude and area under the curve (AUC) were measured at each electrode. RESULTS: RRMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls at Pz. SPMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls, and CNVs with a smaller amplitude than the RRMS patients at both Cz and Pz. After correcting for multiple comparisons, a lower CNV amplitude at Pz was significantly associated with worse performance on measures of speed of information processing, verbal fluency, verbal learning, and verbal recall. CONCLUSIONS: CNV may serve as a marker for disease progression and cognitive dysfunction in MS. Further studies with larger samples and wider electrode coverage are required to fully assess the value of CNV in these areas.

The cooling effect on proinflammatory cytokines interferon-gamma, tumor necrosis factor-alpha, and nitric oxide in patients with multiple sclerosis.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS) in young adults. The proinflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and nitric oxide (NO) which are known to be produced by inflammatory cells play a key role in the pathogenesis of MS. Some metabolic changes may have an effect on axonal transmission, and white blood cells NO and other inflammatory mediators such as cytokines may be affected from cooling process. In this study, we evaluated the effects of body cooling procedure on proinflammatory cytokines such as TNF-α, IFN-γ, and NO levels. Twenty patients with MS were evaluated. Thirteen of the patients were women, 7 were men (mean age: 33.6 ± 7.5 yrs.). Body temperature was reduced by an average of 1°C approximately in 1 hour with using the "Medivance Arctic Sun Temperature Management System" device. In our study, the decrease in TNF-α, IFN-γ levels after the cooling procedure has no statistical significance, whereas the decrease in the mean level of NO level after the cooling procedure is 4.63 ± 7.4 µmol/L which has statistical significance (P = 0.002). These results suggested that the decrease in NO level improves conduction block in demyelinated axonal segments after cooling procedure in multiple sclerosis.

Intrathecal sICAM-1 production in multiple sclerosis--correlation with triple dose Gd-DTPA MRI enhancement and IgG index.

In this study the aim was to evaluate the intrathecal sICAM-1 production in multiple sclerosis (MS) patients during relapse and remission. In addition to this, we assessed whether there is a correlation between intrathecal sICAM-1 production and other disease activity markers such as IgG index and gadolinium enhancement in magnetic resonance imaging (MRI). Twenty four relapsing-remitting MS patients were included in the study. Serum and cerebrospinal fluid (CSF) samples were obtained both during relapse and remission. The soluble form of ICAM (sICAM) was measured by the ELISA method in serum and CSF. Cranial MRI with triple dose gadolinium injection was performed for each patient both during relapse and remission. Serum levels of sICAM-1 (245.23 +/- 92.88 ng/ml) were higher during relapse than those in remission (219.90 +/- 110.94 ng/ml), but the difference was not statistically significant. In relapse periods CSF levels of sICAM-1 (1.304 +/- 0.92 ng/ml) were higher than those in remission (1.06 +/- 0.86 ng/ml), but this was not significant. However, during relapse periods patients had significantly higher sICAM-1 index values (1.76 +/- 0.60) than those found during remission periods (1.01 +/- 0.44) (p < 0.05). The IgG index values were higher in relapse periods than in remission (0.88 +/- 0.37 vs. 0.67 +/- 0.28) (p < 0.005). On T1 weighted images following triple dose Gd injection, at least two or more enhancing lesions were present in 22/24 of the patients (91%) in relapse and 4/24 of the patients (19%) in remission. There was strong correlation both between the sICAM-1 index and Gd enhancement (r =0 .72 p < 0.05) and sICAM-1 index and IgG index in relapse (r = 0.69 p < 0.05). In conclusion, there is association between high sICAM-1 and IgG indices, as well as between high sICAM-1 index and Gd enhancing MRI lesions in relapsing MS patients.

Visual evoked potential is superior to triple dose magnetic resonance imaging in the diagnosis of optic nerve involvement.

The aim of this study was to evaluate whether VEP is sensitive to optic neuritis (ON) when compared with triple dose orbital MRI. Twenty-four relapsing-remitting MS (RRMS) patients were included in the study. Group I (n = 10) patients with acute ON, Group II (n = 8): patients presenting with a current relapse who had the history of ON in the previous relapses. Group III (n = 6): patients presenting with a current relapse but with no history of ON. Neuro-ophtalmological evaluation. VEP investigation and orbital MRI with triple dose (0.3 mmol/kg) gadolinium (Gd) were carried out for all. VEP was found to be 70% sensitive and 12.5% specific to the acute ON, whereas orbital MRI with triple dose Gd was 70% sensitive and 100% specific. In chronic ON, the sensitivity of orbital MRI is 0%, whereas the VEP is still 75% sensitive to chronic optic nerve involvement and can distinguish the pathology 100% specifically. In conclusion, orbital MRI with triple dose Gd is not more sensitive than VEP in determining the acute optic nerve pathologies but it is a 100% specific method. The results suggest that VEP is superior to the orbital MRI in determining the chronic optic nerve involvement.

Validity and reliability of the Turkish Migraine Disability Assessment (MIDAS) questionnaire.

OBJECTIVES: The aim of this study is to assess the comprehensibility, internal consistency, patient-physician reliability, test-retest reliability, and validity of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in patients with headache. BACKGROUND: MIDAS questionnaire has been developed by Stewart et al and shown to be reliable and valid to determine the degree of disability caused by migraine. DESIGN AND METHODS: This study was designed as a national multicenter study to demonstrate the reliability and validity of Turkish version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12 (visit 3) visits in terms of disease severity and comprehensibility, internal consistency, test-retest reliability, and validity of MIDAS. Since the severity of the disease has been found to change significantly at visit 2 compared to visit 1, test-retest reliability was assessed using the MIDAS scores of a subgroup of patients whose disease severity remained unchanged (up to +/-3 days difference in the number of days with headache between visits 1 and 2). RESULTS: A total of 306 patients (86.2% female, mean age: 35.0 +/- 9.8 years) were enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that "they had fully understood the MIDAS questionnaire" in visits 1, 2, and 3, respectively. A highly positive correlation was found between physician and patient and the applied total MIDAS scores in all three visits (Spearman correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P <.001). Internal consistency of MIDAS was assessed using Cronbach's alpha and was found at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician applied MIDAS scores, respectively. Total MIDAS score showed good test-retest reliability (R= 0.68). Both the number of days with headache and the total MIDAS scores were positively correlated at all visits with correlation coefficients between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) between the total MIDAS score at week 12 and the number of days with headache at visit 2 + visit 3, which quantify headache-related disability over a 3-month period similar to MIDAS questionnaire. CONCLUSION: These findings demonstrated that the Turkish translation is equivalent to the English version of MIDAS in terms of internal consistency, test-retest reliability, and validity. Physicians can reliably use the Turkish translation of the MIDAS questionnaire in defining the severity of illness and its treatment strategy when applied as a self-administered report by migraine patients themselves.

Headache in sleep apnea syndrome.

OBJECTIVE: To find out whether there is a relationship between the headache characteristics and polysomnographic findings in patients with prediagnosis of the sleep apnea syndrome (SAS) and, if there is, to search for its possible cause. BACKGROUND: Chronic morning headache is considered by many to be an important part of the SAS. Some reports support this relationship, and some do not. METHODS: We questioned 75 patients with SAS about headache. Headaches were classified according to the International Headache Society (IHS-88) system. We evaluated the relationship between headache and polysomnographic findings. RESULTS: There was no statistically significant relationship between headache and apnea hypopnea index (AHI) or minimal oxygen saturation (P >.05). CONCLUSIONS: We could not demonstrate a statistically significant relationship between headache, AHI, and minimal oxygen saturation in our patients with SAS.

Cortical relay time for long latency reflexes in patients with definite multiple sclerosis.

BACKGROUND: Long latency reflexes (LLR) include afferent sensory, efferent motor and central transcortical pathways. It is supposed that the cortical relay time (CRT) reflects the conduction of central transcortical loop of LLR. Recently, evidence related to the cortical involvement in multiple sclerosis (MS) has been reported in some studies. Our aim was to investigate the CRT alterations in patients with MS. METHODS: Upper extremity motor evoked potentials (MEP), somatosensory evoked potentials (SEP) and LLR were tested in 28 patients with MS and control subjects (n=22). The patients with MS were classified according to the clinical form (relapsing-remitting [R-R] and progressive groups). The MS patients with secondary progressive and primary progressive forms were considered as the "progressive" group. CRT for LLR was calculated by subtracting the peak latency of somatosensory evoked potentials (SEP) and that of motor evoked potentials (MEP) by transcranial magnetic stimulation from the onset latency of the second component of LLR (LLR2) (CRT = LLR2 - [MEP latency + N20 latency]) RESULTS: Cortical relay time was calculated as 7.4 +/- 0.9 ms in control subjects. Cortical relay time was prolonged in patients with MS (11.2 +/- 2.9 ms) (p<0.0001). The latencies of LLR, MEP and SEP were also prolonged in patients with MS. Cortical relay time was not correlated with disease severity and clinical form in contrast to other tests. CONCLUSIONS: Our findings suggested that CRT can be a valuable electrophysiological tool in patients with MS. Involvement of extracortical neural circuits between sensory and motor cortices or cortical involvement due to MS may cause these findings.

Cortical silent period and motor evoked potentials in patients with multiple sclerosis.

In order to determine the importance of central motor conduction time (CMCT) and silent period (SP) in patients with multiple sclerosis (MS), we enrolled this clinical and electrophysiological study. Additionally, we planned to compare the correlation between electrophysiological findings and clinical status. We examined 58 patients with definite MS and 31 controls. Patients were classified as relapsing-remitting (N: 37), secondary progressive (N: 21) groups. Eleven out of 58 patients with MS had no neurological findings (subclinical patients). We evaluated CMCT and the duration of SP. Prolonged CMCT latency was shown in 75.2% of patients. We observed SP abnormalities in 69% of patients. In subclinical patients, SP abnormalities (six of 11) were observed more common than CMCT (two of 11). The duration of SP was extremely prolonged in MS patients with cerebellar dysfunction. When the both electrophysiological parameters are taken into account, the abnormality ratio was determined as 89.7%. Our results indicate that CMCT and SP analysis are complementary tests in evaluating motor pathways of patients with MS. We observed a relationship between cerebellar dysfunction and SP prolongation. It is suggested that, SP can be applied in patients with pure cerebellar dysfunction and it can be a valuable test in subclinical cases with MS.

Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study.

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes.

Comparison of preseptal and pretarsal injections of botulinum toxin in the treatment of blepharospasm and hemifacial spasm.

Although the beneficial effect of subcutaneous injections of botulinum toxin type A (BTX-A) is well known in both blepharospasm and hemifacial spasm, the position of the injection sites around the orbicularis oculi may influence the effectiveness and side effects. Here we report results of preseptal and pretarsal BTX-A injections in 53 patients (25 blepharospasm and 28 hemifacial spasm) in whom we used both injection techniques successively. Pretarsal injections were used in 102 out of 186 treatments in blepharospasm group and in 84 out of 202 treatments in hemifacial spasm group. Pretarsal BTX-A treatment produced significantly higher response rate and longer duration of maximum response in both patient groups. This technique was also associated with a lower frequency of major side effects such asptosis. We concluded that injections of BTX-A into the pretarsal, rather than the preseptal portion of the orbicularis oculiis more effective for treatment of involuntary eyelid closure due to contractions of this muscle.