Sleep disturbance and cognitive decline in multiple sclerosis patients with isolated optic neuritis as the first demyelinating event.

PURPOSE: Multiple sclerosis (MS) patients whose first demyelinating event is optic neuritis have been claimed to display a milder disease course and reduced physical disability. Our aim was to investigate the impact of the clinical features of the first clinical episode on cognitive disability and sleep dysfunction in MS. METHODS: A total of 26 (10 with optic neuritis as the first clinical event) MS patients were recruited. A comprehensive sleep study was performed, and a panel of tests were administered to examine cognitive and motor performance. Serum levels of sleep-related mediators orexin-A and melatonin were measured by enzyme-linked immunosorbent assay. Subjective sleep quality was evaluated by Pittsburgh sleep quality test, and daytime excessive sleepiness was tested by Epworth sleepiness scale. RESULTS: MS patients with the first clinical episode of optic neuritis and patients with at least one optic neuritis attack exhibited increased daytime sleepiness, higher sleep efficiency and NREM duration and lower total wake time. Patients with a history of optic neuritis obtained more favorable scores in neuropsychological tests measuring executive functions and complex attention as compared to those who had never experienced optic neuritis. Melatonin and orexin-A levels were lower in patients with optic neuritis onset. The higher no. of optic neuritis attacks was associated with reduced wake time and higher symbol digit modalities test scores. CONCLUSIONS: Having a history of optic neuritis is associated with improved sleep quality and executive functions but increased daytime sleepiness. Reduction of orexin-A and melatonin levels might be one of the underlying mechanisms.

Corneal Biomechanical Properties in Obstructive Sleep Apnea Syndrome.

OBJECTIVES: To investigate the corneal biomechanical properties and anterior segment parameters in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-four eyes of 54 patients with OSAS and 20 eyes of 20 healthy subjects were included. Patients with mild and moderate OSAS (Respiratory Disturbance Index [RDI] <30) enrolled in group 1, those with severe OSAS (RDI≥30) in group 2 and controls in group 3. Corneal biomechanical properties including corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) were measured with ocular response analyzer. Maximum (Kmax), minimum (Kmin), and mean simulated (SimKm) keratometry values, corneal astigmatism (CA), and central corneal thickness (CCT) were evaluated with Pentacam Scheimpflug imaging. RESULTS: The mean CH and CRF were significantly lower in group 2. The mean CH was 10.9±1.4 mm Hg in group 1, 10.1±1.1 mm Hg in group 2, and 12.1±1.2 mm Hg in group 3 (P<0.001). The mean CRF was 11.1±1.8 mm Hg in group 1, 9.9±1.1 mm Hg in group 2, and 12.2±1.2 mm Hg in group 3 (P<0.001). The CH and CRF values were similar between the groups 1 and 3 (P=0.867 and P=0.743). Corneal-compensated intraocular pressure, IOPg, Kmax, Kmin, SimKm, CA, and CCT values were not statistically different among the three groups. CONCLUSIONS: Patients with severe OSAS had lower CH and CRF values. The lower CH and CRF values in the severe group were possibly related to changes of the structural properties in the cornea.

Prevalence of insomnia and its clinical correlates in a general population in Turkey.

AIM: The prevalence of insomnia is influenced by environmental factors. This study aimed to investigate the prevalence of insomnia and its sociodemographic and clinical correlates in a general population-based survey in Turkey. METHODS: This population-based study included 4758 subjects among 5021 who participated in the Turkish Adult Population Epidemiology of Sleep Disorders study. Questionnaire items evaluating insomnia were adapted from the International Classification of Sleep Disorders II and the DSM-IV-TR. Subjects with restless legs syndrome were excluded. RESULTS: Insomnia was found to be associated with older age (18-24 years, 9.8%; 25-44 years, 11.7%; 45-64 years, 13.8%; 65 years or older, 13.9%), lower income level (<500 USD, 16.5%), time spent watching TV (6-8 h or more, 18.4%), tea consumption in the evening (≥6 glasses, 14.5%) and smoking status (current and ex-smoker, both 14.2%) in multiple logistic regression analysis. In respect to other medical disorders, insomnia was significantly associated with the presence of hypertension, diabetes and heart diseases after the adjustment for relevant risk factors for each disease, across all age and sex groups. CONCLUSIONS: Insomnia is a major health problem in our population, affecting subjects in the working age group and those of lower socioeconomic status. It should especially be screened in patients with chronic diseases. A relatively low proportion of insomnia diagnosed as a sleep disorder suggests that this condition and its clinical correlates are possibly under-recognized.

Arterial and venous thrombosis of the cerebral vasculature in GAPO syndrome.

A 37-year-old male, previously diagnosed with GAPO syndrome, was admitted to our hospital complaining of recurrent episodes of transient weakness and numbness in his left arm for 3 months, and severe headache with progressive dysphagia for 15 days. His cranial magnetic resonance (MR) images showed multiple ischemic foci in the bilateral periventricular and supraventricular white matter. Cerebral MR-angiography showed total occlusion of the right internal carotid artery and moderate stenosis in the left internal carotid. We also detected chronic thrombotic changes in the distal left sigmoid sinus, proximal right sigmoid sinus, and bilateral jugular veins on cerebral MR-venography. He was diagnosed with dilated cardiomyopathy at age 31 years, which was reported as a novel association; and later he had a myocardial infarction at age 34 years. To the best of our knowledge, this is the first patient with GAPO syndrome and arterial atherosclerosis in cerebral-as well as coronary-arteries and intracranial venous thrombosis. We report the evolution of the disease in this patient, who died at age 38 years due to respiratory failure secondary to lower respiratory tract infection.

The prevalence of migraine in restless legs syndrome.

OBJECTIVE: While previous studies have investigated the prevalence of restless legs syndrome (RLS) in patients with migraine, we aimed to explore the prevalence and characteristics of migraine in adult patients diagnosed with RLS. BACKGROUNDS: The association of primary headaches, especially of migraine, with RLS has recently attracted much attention. Migraine prevalence was reported to be higher in patients with RLS than in the general population, and the role of dopamine was strengthened. METHODS: We evaluated 265 consecutive adult RLS patients (137 males and 128 females) followed up in a Sleep Disorders Unit and diagnosed according to criteria defined by the International Restless Legs Syndrome Study Group (IRLSSG). RLS characteristics, and the severity, were performed by using the IRLSSG severity scale. The diagnosis of headache subtypes was defined by the International Classification of Headache Disorders. Gender, age, age at RLS onset, duration of RLS, family history of RLS, family history of headache, presence of depression, any treatments given for RLS, and the change in headache following RLS treatment were questioned. RESULTS: The mean age of the study population was 50.4 ± 12.8 years, mean age at RLS onset was 41.6 ± 13.2 years, and mean disease duration was 8.40 ± 8.6 years. Of these, 163 patients had headache; 40 of them were diagnosed to have migraine-type headache (15.1%). The presence of migraine-type headache was 9.4% in males with RLS, and 21.1% in female RLS patients. In RLS patients with migraine, 67.5% were females, while 48.0% of RLS patients with other types of headache were females (P = .032), and only 41.2% of RLS patients without headache were females (P = .005). The severity of RLS was significantly higher in patients with migraine compared with those without headache (P < .001). The presence of depression, the family history of RLS, and headache were also higher in patients with migraine compared with RLS patients with other types of headache or those without headache. Thirty-six patients with headache reported partial or substantial benefit from RLS treatment. CONCLUSIONS: Our results did not suggest higher rates of migraine-type headache in RLS patients when compared with population-based prevalence studies from Turkey. Alternatively, the severity of RLS was significantly higher in patients with migraine. Although the increase in these scores does not constitute a relationship etiopathogenetic, it suggests a correlation between the type cross-model nociceptive systems. Moreover, the family history of RLS was higher in patients with migraine. The prevalence of migraine in patients with RLS, however, waits to be better demonstrated.

Unilateral cerebellar and brain stem hypoplasia in a child with a postnatal diagnosis of dissecting aneurysm in basilar artery.

Cerebellum is highly vulnerable in the prenatal period. Increasing experience with fetal imaging studies has demonstrated that unilateral cerebellar hypoplasia (UCH) is mainly prenatally acquired, representing disruption rather than a true malformation. Here, we report the case of a 17-month-old boy presented with a sudden onset of abnormal eye movements, who was diagnosed during routine fetal screening with UCH and brain stem hypoplasia and suffered from cerebral palsy; however, no posterior arterial system pathology was detected on cranial magnetic resonance images at that time. Following this acute event, diagnostic neuroradiological interventions revealed a dissecting aneurysm with a saccular component in midbasilar arterial segment and hypoplastic left posterior cerebral artery, which may support the ischemic disruptive mechanism in the development of prenatally detected UCH in this child. The pathogenetic mechanisms for cerebellar disruption are certainly multifactorial in origin, although ischemic arterial etiologies were often undervalued.

A polysomnographic and clinical study of sleep disorders in patients with Behçet and neuro-Behçet syndrome.

Brainstem is the most common site of involvement in neuro-Behçet syndrome (NBS). On the other hand, the critical importance of this anatomical region in the regulation of sleep has been disregarded in the literature. We aimed to investigate the microstructure of sleep in patients with Behçet syndrome (BS) and NBS. Patients were allocated to 2 groups: (1) BS without any neurological involvement and (2) NBS with brainstem lesions only. A control group was also enrolled in this study. The comparison of polysomnographic parameters between all patients (BS and NBS) with the control group showed that sleep onset was longer (p = 0.006), the duration of superficial NREM sleep stage (N2) was significantly longer (p = 0.018), and the respiratory disturbance index was significantly higher (p = 0.034) in patients. Sleep apnea and restless legs syndrome are more commonly observed in BS and NBS. Our findings emphasize the importance of questioning the quality of sleep and its disorders in patients with BS in order to better handle the common somatic complaints in these patients, such as fatigue or daytime sleepiness

Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey.

BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

Cyclic alternating pattern analysis in REM sleep behavior disorder.

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a type of REM parasomnia characterized by complex motor activity during REM sleep. In this study, cyclic alternating pattern (CAP) in patients with idiopathic RBD was analyzed to evaluate the expression of arousal instability of NREM sleep. METHODS: A total of 31 idiopathic RBD patients and age- and gender-matched 21 control subjects were consecutively recruited. Conventional sleep polysomnographic recording parameters and CAP parameters were compared between RBD and the control group. RESULTS: The number of CAP cycles (120.13 ± 113.56, p = 0.007), CAP sequences (20.9 ± 18.15, p < 0.001), CAP index (25.14 ± 24.44, p = 0.017), and CAP rate (24.07 ± 13.22, p = 0.016) were all significantly higher in RBD patients compared to the control group. The increase in CAP sequences was observed in phase A2 and A3 subtypes while phase A1 subtype was significantly lower in RBD patients. A significant positive correlation was observed between disease duration with total CAP time (r = 0.289, p = 0.042) and A3 index (r = 0.32, p = 0.024). There was a negative correlation between the age and A1 index (r = -0.4491, p = 0.0001). CONCLUSION: To our knowledge this is the first polysomnographic clinical study which evaluated CAP parameters in RBD. Increased CAP rate found may be considered as a sign showing that NREM sleep may also be affected in RBD patients. Therefore, CAP analysis may be important to enlighten the pathogenesis of parasomnias.

A pilot study of the effects of non-invasive mechanical ventilation on the prognosis of ischemic cerebrovascular events in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for ischemic cerebrovascular diseases, and results in worse prognosis and higher mortality. We aimed to investigate the effects of early treatment of OSAS on the prognosis of ischemic stroke. We prospectively evaluated patients with acute supratentorial ischemic stroke and OSAS on admission (acute stage), at second week (subacute stage) and at second month (chronic stage); 11 (73.3%) out of 15 patients put on the non-invasive mechanical ventilation treatment within 48 h of stroke constituted the treatment group, and 13 patients constituted the control group. Patients with OSAS treatment showed significantly better prognosis and better functioning in activities of daily living in both subacute and chronic stages. The rate of shrinkage of the ischemic lesion was higher in the treatment group, though not significant. The early and effective treatment of OSAS provides a better clinical prognosis in ischemic stroke. The beneficial effects on radiological parameters need to be further studied.

Unilateral cerebellar hypoplasia with different clinical features.

Unilateral cerebellar hypoplasia (UCH) is a rare pathological condition characterized by the loss of volume in cerebellar hemispheres ranging from mild asymptomatic to severe symptomatic cases. As the designation of UCH remains problematic, the underlying etiopathogenesis also lacks explanation. We investigated the patients admitted to Departments of Child Neurology, Neurology, and Genetics between the years 1992 and 2010 and detected 12 patients with unilateral cerebellar volume loss, with the exclusion of all other cerebellar pathologies. The ages of patients ranged between 6 months to 55 years. Five patients had a delay in developmental milestones, and one of these was diagnosed with neurofibromatosis type 1. Two patients had epileptic seizures, one patient had peripheral facial paralysis as a component of Moebius syndrome, and four patients were incidentally diagnosed during etiological work-up for headache. The clinical outcomes of patients varied from healthy subjects to marked developmental impairment. Radiologically, five patients had severe disproportionate UCH, six had moderate disproportionate, and one had mild proportionate UCH. Cerebellar peduncles were affected in all, and vermis was partly hypoplastic in eight patients. Brainstem was involved in four patients, and seven patients showed involvement of white matter and/or corpus callosum. Imaging features supported that patients with severe disproportionate UCH also displayed additional cerebral and commissural changes, which were related to ischemic or vascular injuries, implying a prenatally acquired disruption. In the presence of such a wide spectrum of clinical and radiological features, a prenatally acquired lesion and, thus, a disruption seem to be more explanatory rather than a primary developmental process or malformation in the etiopathogenesis of unilateral cerebellar hypoplasia.

Peripheral blood B cell subset ratios and expression levels of B cell-associated genes are altered in benign multiple sclerosis.

The interplay between the immune system, sleep dysfunction and cognitive impairment participates in the progression of disability in multiple sclerosis (MS). Our aim was to identify molecular pathways and B cell associated with separate components of MS disability. Benign MS, non-benign MS patients and healthy controls were recruited. Patients underwent polysomnography and cognitive studies. Microarray and bioinformatics analysis performed using peripheral blood mononuclear cell samples identified B cell-associated genes with the most significantly altered expression. Expression levels of these genes were validated by real-time PCR and peripheral blood cell subsets were examined by flow cytometry. Putative correlations among clinical and laboratory parameters were investigated by correlation network analysis. Sleep and cognitive functions were equally impaired in BMS and NBMS. BMS patients showed significantly reduced memory B cell and increased regulatory B cell percentages than NBMS patients. Among genes that were selected by bioinformatics, levels of BLK, BLNK, BANK1, FCRL2, TGFB1 and KCNS3 genes were significantly different among study subgroups. Correlation network analysis showed associations among physical-cognitive disability and sleep dysfunction measures of MS versus expression levels of selected genes. BMS and NBMS differ by physical disability but not cognitive and sleep dysfunction. Different components of disability in MS are associated with peripheral blood B cell ratios and B cell related gene expression levels. Thus, it is likely that altered B cell functions participate in the progression of disability in MS.

Quantitative analysis of reduced arm swing frequency in essential tremor.

BACKGROUND: Essential tremor (ET) has recently been accepted as a heterogeneous disorder which may be associated with synuclein pathology or a variety of other genetic disorders. METHODS: We observed decreased arm swing frequency in 18 of 136 definite ET patients, and recorded the associated arm movements in 18 ET patients and 33 sex- and age-matched healthy controls. RESULTS: The mean frequency of the right arm (p = 0.047), left arm (p = 0.025) and leg (p = 0.030), and the mean arm/leg frequency on the right side (p = 0.048) were significantly lower in ET patients. The mean frequencies for both arms and legs were significantly lower for the more affected side of the body (p = 0.034 and p = 0.036, respectively). CONCLUSION: We conclude that ET may be associated with decreased arm and leg swing frequencies, especially on the more affected side of the body.

The role of osteopontin: a shared pathway in the pathogenesis of multiple sclerosis and osteoporosis?

Osteopontin (OPN) was suggested to have a role in the pathophysiology of MS and in bone metabolism. However, we formerly reported increased presence of osteoporosis in MS patients independent of corticosteroid treatment, there is only limited information about the mechanism of bone loss. In this study, we investigated the role of OPN on bone mineral density in MS patients. Thirty-three relapsing-remitting (RR), 12 secondary progressive (SP), and 5 primary progressive (PP) MS patients and 30 healthy controls were prospectively enrolled. Students' t test, chi-square test, and Pearson correlations were used. The mean OPN level was 155.4+/-81.8 ng/ml in controls, and 15.9+/-36.2 ng/ml in MS patients (p<0.001).No statistical difference was observed among RR, SP and PPMS patients (p=0.162). No relationship was found between OPN levels and age at onset of disease (p=0.830), gender (p=0.785), MS subtypes (p=0.330), disease duration (p=0.744), or EDSS scores (p=0.633).About 34% of MS patients versus 10.3% of controls had osteoporosis (p=0.017).Osteopontin levels showed no significant correlation with osteoporosis in controls, but were lower in MS patients with osteoporosis in femur neck (r=0.85, p=0.010).The cumulative dose of corticosteroid treatment did not correlate with OPN levels (p=0.285).In conclusion, our results suggest that OPN may have a role as a shared cytokine in pathogenesis of MS and osteoporosis.

Misdiagnosis due to gastrointestinal symptoms in an adolescent with probable autonomic status epilepticus and Panayiotopoulos syndrome.

Panayiotopoulos syndrome is a common benign epilepsy affecting otherwise healthy children that present with autonomic seizures, in which nausea, retching, and vomiting are particularly common and prominent. Because of the unusual ictal symptoms and lengthy manifestations, misdiagnosis is a common major problem. We describe a young girl with intractable and lengthy vomiting attacks, several admissions to hospitals, and extensive gastroenterological workup for several years from early childhood. On all previous occasions the diagnosis varied from psychosomatic disease, to functional dyspepsia, to cyclic vomiting syndrome. The possibility of autonomic epileptic seizures and Panayiotopoulos syndrome, though likely, was not considered.

Insomnia and Dysautonomia with Contactin-Associated Protein 2 and Leucine-Rich Glioma Inactivated Protein 1 Antibodies: A "Forme Fruste" of Morvan Syndrome?

Morvan syndrome (MoS) is typically characterized by neuromyotonia, sleep dysfunction, dysautonomia, and cognitive dysfunction. However, MoS patients with mild peripheral nerve hyperexcitability (PNH) or encephalopathy features have been described. A 46-year-old woman presented with a 2-month history of constipation, hyperhidrosis, and insomnia. Neurologic examination revealed muscle twitching and needle electromyography showed myokymic discharges in all limbs. No clinical or electrophysiological features of neuromyotonia were present. Although the patient denied any cognitive symptoms, neuropsychological assessment revealed executive dysfunction, while other cognitive domains were preserved. Cranial and spinal MRIs were unrevealing and tumor investigation proved negative. Polysomnography examination revealed total insomnia, which was partially reversed upon immune-modulatory therapy. Investigation of a broad panel of antibodies revealed serum leucine-rich glioma inactivated protein 1 and contactin-associated protein 2 antibodies. The features of this case indicate that the presentation of PNH syndromes may show significant variability and that MoS patients may not necessarily exhibit full-scale PNH and encephalopathy symptoms.