Burcu Zeydan

Infliximab is a plausible alternative for neurologic complications of Behçet disease

Objective: We evaluated the effectiveness of infliximab in patients with neuro-Behçet syndrome for whom other immunosuppressive medications had failed. Methods: Patients whose common immunosuppressive medications fail in recurrent neuro-Behçet syndrome need an alternative. We report our experience with the tumor necrosis factor α blocker infliximab for long-term treatment of neuro-Behçet syndrome. We recruited patients within a multidisciplinary referral practice of Behçet disease and prospectively followed everyone with a neurologic symptom(s). Patients (n = 16) with ≥2 neurologic bouts (excluding purely progressive disease) while on another immunosuppressive treatment were switched to and successfully sustained on infliximab (5 mg/kg in weeks 0, 2, and 6, then once every 8 weeks; minimum follow-up duration ≥12 months). Infliximab was stopped within 2 months after initiation in one patient because of pulmonary and CNS tuberculosis. Results: Patients had stepwise worsening due to relapses in the Expanded Disability Status Scale modified for neuro-Behçet syndrome before switching to infliximab (median score of 5.0, range 2.0–7.0; median neuro-Behçet syndrome duration 29.1 months, range 5.0–180.7). Median duration of preinfliximab immunosuppressive medication use was 20.0 months (range 3.0–180.7). In all 15 patients, during infliximab treatment (median score 4.0, range 2.0–7.0; median duration 39.0 months, range 16.0–104.9 months), neurologic relapses were completely aborted and there was no further disability accumulation. Conclusion: We observed a significant beneficial effect of infliximab in neuro-Behçet syndrome. Classification of evidence: This study provides Class IV evidence that for patients with neuro-Behçet syndrome whose other immunosuppressive medications failed, infliximab prevents further relapses and stabilizes disability.

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

BACKGROUNDnBased 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.nnnMETHODSnAll 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.nnnRESULTSnAmong 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.nnnCONCLUSIONSnClinical 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.

Identification of 3 Novel Patients with CLCN2 -Related Leukoencephalopathy due to CLCN2 Mutations

Dear Sir, ClC-2 is a chloride channel, which plays an important role in brain ion and water homeostasis both in mice and humans [1]. CLCN2-related leukoencephalopathy (CC2L) is a recently identified rare disorder, caused by autosomal recessive mutations in CLCN2, which results in ClC-2 chloride channel dysfunction and myelin microvacuolization with characteristic brain MRI features of leukoencephalopathy [2]. We report three patients with CC2L, who carry genetically verified CLCN2 mutations and were presented between 1999 and 2014 to our clinic.

Electrophysiological Investigations in Orthostatic Myoclonus: Preliminary Findings

We report the clinical and electrophysiological findings in seven patients with orthostatic myoclonus (OM) associated with gait initiation failure and falls. OM is one of the causes of unsteadiness of stance and gait, and it may develop as a symptom of neurodegenerative disorders. Both positive myoclonic bursts and negative myoclonus may be seen in electrophysiological recordings, and electrophysiological analysis suggests a subcortical origin for OM.

Visually evoked startle response in a patient with epilepsy: a case report and review of the literature.

ABSTRACT Both symptomatic and genetic, cases with hyperekplexia or startle seizures induced by acoustic stimuli, are previously reported. By contrast, startle response induced by visual stimuli is rare. While visual stimuli are more commonly associated with startle seizures, here we present an 11-year-old girl with epilepsy, motor-mental retardation, and spastic tetraparesis, who had repetitive startle responses by photic stimulation during the electroencephalogram recording, without any spike-and-wave discharges associated with the startles. We report this unique case with startle responses induced both by acoustic and photic stimuli and review the literature related to this exceptionally rare combination of symptoms.

Long-term follow-up of two siblings with adult-onset neuronal ceroid lipofuscinosis, Kufs type A

Reports on the clinical presentation of adult-onset neuronal ceroid lipofuscinoses (NCL) are scarce compared to infantile- and childhood-onset forms. Here, we aimed to present detailed temporal evolution of clinical and electrophysiological features of two siblings with adult-onset NCL and homozygous mutation in the CLN6 gene. We retrospectively analysed medical records and electrophysiological data in order to delineate evolution of clinical and electrophysiological findings. Electrophysiological studies included routine EEG and video-EEG, as well as polymyographic analysis of myoclonus and brainstem reflex studies. Both patients had seizures and cerebellar signs. Despite the slow progression of ataxia, they developed no mental deterioration, but had severe obsessive compulsive disorder and depression. EEG revealed frequent generalized spikes, polyspikes, and waves, prominent on awakening and during photic stimulation without significant change throughout the clinical course. Abnormalities concerning the blink reflex, auditory startle response, and startle response to somatosensory inputs manifested within four years. The patients underwent transient and mild improvement with valproate, whereas ataxia and seizures were dramatically ameliorated following high-dose piracetam. Patients with adult-onset NCL may present with slowly progressive ataxia, persistent photosensitivity, and seizures without dementia or extrapyramidal findings. Brainstem abnormalities become more evident with time, in line with ataxia. Piracetam is effective for both seizures and ataxia.

Behçet’s disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study

OBJECTIVEnThis study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçets disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST).nnnMETHODSnVENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis.nnnRESULTSnBD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%).nnnCONCLUSIONSnBD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).

MEDIAL TEMPORAL LOBE NEURODEGENERATION OBSERVED IN WOMEN WHO UNDERWENT BILATERAL OOPHORECTOMY BEFORE THE ONSET OF MENOPAUSE

self-reported, defined as inability or difficulty in recognizing a familiar face at four meters. Through a standardized neuropsychological evaluation, four cognitive domains (global cognition (MMSE and MMSE-blind), verbal fluency (IST), executive function (TMT) and visuospatial abilities (BVRT)) were assessed up to six times over 12 years of follow-up. To analyze the baseline cognitive performance and cognitive decline over time according to visual loss, we used joint models, which accounted for differential attrition in participants with or without visual loss. These models jointly analyze the longitudinal marker (repeated measures of cognitive scores) and the time to dropout. Results:At baseline, 8.4% had mild near VI, 4.1% had moderate to severe near VI and 5.1% had distance VF loss. Participants with near VI and distance VF loss had lower baseline performances in verbal fluency, global cognition, executive function and visuospatial abilities. Regarding changes over time, no significant differences were observed by visual loss status, except for MMSE where participants with mild near VI exhibited a faster cognitive decline (b1⁄4-0.02, p1⁄40.04); nevertheless, this faster cognitive decline was no longer significant with the blind version of the MMSE (without vision-related items) (b1⁄4-0.01, p1⁄40.11). Conclusions: In this large elderly general population-based cohort, we found that participants with visual loss had lower baseline performances in several cognitive tests. However, evidences of faster cognitive decline over time are limited.

PITTSBURGH COMPOUND-B BINDING IN WHITE MATTER HYPERINTENSITIES IS ASSOCIATED WITH LOSS OF WHITE MATTER INTEGRITY ON DTI

Neuroscience and Mental Health, Melbourne, Australia; Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; Austin Health, Heidelberg, Australia; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Commonwealth Scientific and Industrial Research Organisation, Brisbane, Australia; Royal Melbourne Hospital, Melbourne, Australia. Contact e-mail: nawaf.yassi@ unimelb.edu.au

INVESTIGATION OF PITTSBURGH COMPOUND-B BINDING IN WHITE MATTER HYPERINTENSITIES

Sex (F/M) 85/81 64/59 21/21 0.859 47/43 38/37 0.877 77/65 8/15 0.115 APOEe4 (-/+) 133/32 123/42 32/10 0.498 74/16 59/16 0.693 114/28 19/4 1.000 LTPAQ 21-40 106.37(100.69) 114.62 (104.43) 82.22(85.44) 0.072 102.44 (101.54) 11.09 (100.13) 0.584 102.60 (98.75) 129.66(111.43) 0.233 41-60 137.87 (109.58) 142.46 (110.39) 124.40 (107.33) 0.358 148.02 (121.72) 125.68 (92.28) 0.193 137.72 (109.78) 138.77(110.80) 0.966 Total (21-60) 244.24 (178.86) 257.09 (179.36) 206.62 (174.04) 0.115 250.46 (191.07) 236.78 (163.97) 0.626 240.33 (175.82) 268.43(199.07) 0.486