Arda Yilmaz

SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia

Background: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common form of complex hereditary spastic paraplegia. The genetic lesion underlying ARHSP-TCC was localized to chromosome 15q13-q15 and given the designation SPG11. Recently, the gene encoding spatacsin (KIAA1840) has been shown to contain mutations that underlie the majority of ARHSP-TCC cases. Methods: We present a complete analysis of the 40 coding exons of this gene in patients with sporadic (n = 25) or familial (20 probands) complex hereditary spastic paraplegia with and without thinning of the corpus callosum. Results: We identified seven mutations, including deletions, insertions, and nonsense mutations, which were all predicted to lead to premature truncation of the protein. Conclusion: We conclude that mutations on KIAA1840 are frequent in complex autosomal recessive hereditary spastic paraplegia but an infrequent cause of sporadic complex hereditary spastic paraplegia. GLOSSARY: ARHSP = autosomal recessive hereditary spastic paraplegia; HSP = hereditary spastic paraplegia; TCC = thin corpus callosum.

The diagnostic role of serum inflammatory and soluble proteins on dementia subtypes: correlation with cognitive and functional decline.

In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer’s disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1β, IL-2, IL-6, IL-18, TNF-α, β-Amlyloid 1–40 and α1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels of α1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1β and NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI.

Elevated blood lead concentrations in essential tremor : a case-control study in Mersin, Turkey

Background Essential tremor (ET) is one of the most common neurologic disorders. Aside from underlying susceptibility genes, recent studies have also begun to focus on environmental toxic factors. Yet there remains a paucity of information on such factors, making studies of environmental factors important. A recent study in New York City found blood lead concentrations to be elevated in ET cases compared with matched controls. Chronic exposure to lead produces cerebellar damage, and this could predispose individuals to develop ET. Objective The aim of this study was to determine whether the elevation in blood lead concentrations observed in a single study in New York was similarly present in ET cases sampled from a completely different geographic region. Methods Blood lead concentrations were measured in 105 ET cases and 105 controls at Mersin University, Mersin, Turkey. Results The median blood lead concentration was 2.7 μg/dL in ET cases compared with 1.5 μg/dL in controls (p < 0.001). In an unadjusted logistic regression model, blood lead concentration was associated with diagnosis: odds ratio (OR) = 4.01; 95% confidence interval (CI), 2.53–6.37; p < 0.001 (i.e., each 1-μg/dL increase in blood lead concentration was associated with a 4-fold increased odds of ET). This association was more robust when cases were compared with a subsample of controls who did not share the same home environment (OR = 8.13; 95% CI, 3.05–21.65; p < 0.001). In adjusted models, results were similar. Conclusions These data replicate those of a previous study in New York and demonstrate an association between the environmental toxicant lead and a common neurologic disorder.

Abnormal MRI in a patient with ‘headache with neurological deficits and CSF lymphocytosis (HaNDL)’:

A 27-year-old woman was admitted to the Emergency Department with right upper-extremity numbness and mild weakness followed by a bifrontal throbbing headache for 30 min, which was similar to a headache lasting for 12 h that had occurred 3 days ago. Laboratory tests were unremarkable except for cerebrospinal fluid (CSF) lymphocytic pleocytosis. On the following day, a headache episode with left hemiparesis and hemihypoaesthesia, left hemifield visio-spatial inattention, anosagnosia and confusion recurred. The headache was diagnosed as headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome according to the criteria of the second edition of the International Classification of Headache Disorders. Simultaneously performed magnetic resonance imaging (MRI) revealed swelling of the grey matter, CSF enhancement in the sulci of the right temporal and occipital regions and hypoperfusion of the same brain regions. During the following 10 days two more similar episodes recurred and during the ensuing 12 months the patient remained headache free. Neuroimaging findings of the HaNDL syndrome are always thought as virtually normal. MRI abnormalities in our patient have not been reported in HaNDL syndrome previously, although they have been reported in hemiplegic migraine patients before. The findings in our case suggest that hemiplegic migraine and HaNDL syndrome may share a common pathophysiological pathway resulting in similar imaging findings and neurological symptoms.

Holter monitoring for 24 hours in patients with thromboembolic stroke and sinus rhythm diagnosed in the emergency department

It is well known that patients with ischemic stroke show ST-T abnormalities and various rhythm abnormalities on an electrocardiogram (ECG). The most commonly encountered rhythm abnormality is atrial fibrillation. It was recently shown that paroxysmal atrial fibrillation (PAF) is an important causative factor in patients with stroke. Detection of PAF is important in identifying the cause, prognosis, and treatment in patients with thromboembolic stroke. Investigators in the present study followed patients with thromboembolic stroke who had been admitted to the emergency department in sinus rhythm; 24-h Holter monitoring was used, and patients were assessed at referral and every 6 h for 24 h with ECG, which was used to detect rhythm disturbances, especially PAF. In 26 patients with stroke who came to the emergency department, acute thromboembolic stroke was diagnosed on the basis of magnetic resonance imaging; no rhythm abnormalities were noted on Holter monitoring. Eighteen patients were male and 8 were female (mean age: 66±13 y). Arrhythmia was identified on ECG in 3 patients (11%) and on 24-h Holter monitoring in 24 patients (92%). PAF was diagnosed in 3 patients (11%) on ECG and in 11 patients (42%) on Holter monitoring. In 2 patients, nonsustained ventricular tachycardia was detected only on Holter monitoring, which was found to be significantly superior to ECG for the detection of arrhythmias (P < .001). Investigators found no significant relationship between PAF and variables such as hypertension, diabetes, coronary artery disease, history of myocardial infarction, ST-T changes, and elevations in cardiac markers. However, a significant relationship (P < .01) was seen between nonsustained ventricular tachycardia and a history of myocardial infarction. No relationship was discerned between arrhythmia and stroke localization. Study results suggested that (1) PAF is a commonly diagnosed rhythm abnormality, and (2) Holter monitoring is superior to routine ECG for the detection of arrhythmias such as PAF in patients anticipated to have thromboembolic stroke with sinus rhythm.

Multiple Cranial Nerve Involvement Caused by Brucella melitensis

A case of neurobrucellosis complicated by optic, abducens and vestibulocochlear nerve palsies is reported. Brucella melitensis was isolated in the cerebrospinal fluid, and the patient was diagnosed with retrobulbar neuritis. Despite medical treatment, the patient developed optic atrophy. Multiple cranial nerve involvement should be kept in mind in patients presenting with blurred vision and double vision, especially in regions where brucellosis is endemic.

Posterior leukoencephalopathy after combination chemotherapy in a patient with lymphoma

Posterior leukoencephalopathy syndrome is a recently described syndrome involving mainly parieto-occipital gray/white matter of the brain. It occurs secondary to various clinical entities, like hypertension and immunosuppressive therapy. Few cases after combination chemotherapy have been reported. This study describes a 36-year-old woman with primary refractory T-cell lymphoma, who developed central nervous system toxicity due to treatment with intrathecal methotrexate and intravenous ifosfamide, idarubicine and etoposide given as a salvage regimen. Both clinical features as well as magnetic resonance imaging findings were typical for posterior leukoencephalopathy syndrome. The patient died despite anti-hypertensive therapy and haemodialysis. Central nervous system toxicity related to chemotherapeutics and posterior leukoencephalopathy syndrome are discussed briefly.

A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study

BACKGROUND Based on a number of small observational studies, cerebral venous sinus thrombosis has diverse clinical and imaging features, risk factors, and variable outcome. In a large, multicenter cerebral venous thrombosis (VENOST) study, we sought to more precisely characterize the clinical characteristics of Caucasian patients. METHODS All data for the VENOST study were collected between the years 2000 and 2015 from the clinical follow-up files. Clinical and radiological characteristics, risk factors, and outcomes were compared in terms of age and sex distribution. RESULTS Among 1144 patients 68% were women, and in older age group (>50 years) male patients were more prevalent (16.6% versus 27.8%). The most frequent symptoms were headache (89.4%) and visual field defects (28.9%) in men, and headache (86.1%) and epileptic seizures (26.8%) in women. Gynecological factors comprised the largest group in women, in particular puerperium (18.3%). Prothrombotic conditions (26.4%), mainly methylenetetrahydrofolate reductase mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders. 8.1% of patients had infection-associated and 5.2% had malignancy-related etiology that was significantly higher in men and older age group. Parenchymal involvement constitutively hemorrhagic infarcts, malignancy, and older age was associated with higher Rankin score. Epileptic seizures had no effect on prognosis. CONCLUSIONS Clinical and radiological findings were consistent with previous larger studies but predisposing factors were different with a higher incidence of puerperium. Oral contraceptive use was not a prevalent risk factor in our cohort. Malignancy, older age, and hemorrhagic infarcts had worse outcome.

Community-acquired hypernatremia in elderly and very elderly patients admitted to the hospital: Clinical characteristics and outcomes

Summary Background The clinical features, outcome and cost burden of community-acquired hypernatremia (CAH) in elderly and very elderly patients are not well known. Our aim was to investigate the etiologies, reasons for admission, clinical courses, outcomes, complications, and cost assessments of the elderly patients with CAH. Material/Methods We conducted a retrospective study in our tertiary hospital. Elderly and very elderly patients evaluated in the emergency department (ED) from January 1, 2010 to December 31, 2010 (n=4960) were included. Totally, 102 patients older than 65 years and diagnosed with CAH were evaluated. The patients were divided into 2 main groups according to their age: elderly (65–74 years old) (group 1) (n=38), and very elderly (>74 years) (group 2) (n=64). Results Our overall observed prevalence of CAH was 2.0% (n=102, 102/4960). In particular, the prevalences of CAH in group 1 and group 2 were 1.0% (38/3651) and 4.8% (64/1309), respectively (p<0.001). Totally, 62 patients had been treated by renin-angiotensin system (RAS) blockers (ie, ACE-inhibitors). Alzheimer’s disease had been diagnosed in 46.1% of the subjects. The mean Katz scores at the time of admission were 2.4±1.9 and 1.1±1.0 in group 1 and 2, respectively (p<0.001). The mean cost was higher in group 2 than in group 1 (2407.13±734.54 USD, and 2141.12±1387.14 USD, respectively) (p<0.01). The need for intensive care was significantly greater in group 2 as compared to group 1. Conclusions The important determinants of “CAH” in elderly subjects are accompanying Alzheimer’s disease, oral intake impairment, and concomitant treatment with RAS blockers.

Epileptic nystagmus in a patient with nonconvulsive status epilepticus

Epileptic nystagmus (EN) is a rare form of rhythmic eye oscillations occurring during seizure activity. Not only convulsive states, but also nonconvulsive status may represent with EN and this phenomenon may be the only motor manifestation of seizure activity. Epileptic activation of a cortical saccade region may be distinguished from activation of a cortical pursuit region clinically as activation of pursuit regions results in nystagmus slow phases that bring the eyes across the midline. Horizontal EN results most commonly from seizure activity involving the occipital cortex. In this report, horizontal EN in a patient with nonconvulsive status epilepticus (NCSE) is described with clinical, radiological and electrophysiological findings that occur probably due to posterior leukoencephalopathy syndrome.