The role of aquaporin-4 antibodies in Chinese patients with neuromyelitis optica

We determined the presence of aquaporin-4 (AQP4) antibodies by indirect immunofluorescence in human AQP4-transfected cells, and evaluated the diagnostic and prognostic relevance of AQP4 antibodies in 210 Chinese patients with neuromyelitis optica (NMO), high-risk NMO (HR-NMO), classic multiple sclerosis (MS), and other neurologic diseases. Patients were enrolled from The General Hospital of the Chinese People’s Liberation Army and followed-up for a median of 2 years. The patients with HR-NMO had optico-spinal MS (OSMS; n = 3), longitudinally extensive transverse myelitis (TM) (n = 35), recurrent optic neuritis (ON) (n = 2), ON with Sjögren’s syndrome (n = 1) and TM positive for Sjögren-A(SSA) antibody (n = 1). The sensitivity and specificity of AQP4 antibodies in NMO were 70.9% and 91%, respectively. The median AQP4 antibody titer was significantly higher in patients with NMO (1:320) than in those with HR-NMO (1:100) and MS (1:50). Relapse of ON or TM was more likely in patients with AQP4 seropositive, than AQP4 seronegative, HR-NMO. Among AQP4 seropositive patients, 66.7% (36/55) had severe ON, 75.9% (41/55) had TM, and 55.6% (30/55) had spinal cord lesions longer than three segments, and there were relapses in eight of 55 patients with ON (14.8%) and 19 of 55 patients with TM (35.2%) during the 2-year follow-up. In conclusion, our study reveals that AQP4 antibody is a sensitive and specific biomarker for discrimination of NMO, classic MS, and other neurological diseases, and is particularly useful for the diagnosis of HR-NMO. AQP4 antibody-positive patients showed higher frequencies of relapse of ON or TM compared with AQP4 antibody-negative patients.     

Serum uric acid levels and their correlation with clinical and cerebrospinal fluid parameters in patients with neuromyelitis optica

Although uric acid (UA) concentration has been considered a surrogate marker for monitoring the progression of multiple sclerosis (MS), less is known about the relationship between UA and the progression of neuromyelitis optica (NMO). We therefore investigated the correlations between serum UA concentrations and the clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors assessed in patients with NMO included gender, disease duration, disease disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24 hour immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean serum UA concentrations were compared in patients with NMO and in a control group of patients with cerebral infarction (CI). We found that mean serum UA concentrations were significantly lower in patients with NMO compared to those with CI (206.81 compared to 274.00 μmol/L, p = 0.00). Serum UA concentration was correlated directly with NMO duration (p = 0.013) and was inversely correlated with the Expanded Disability Status Scale score (p = 0.021). Patients with NMO with lower serum UA concentrations tended to be positive for OB, to have higher CSF protein and MBP concentrations, and to have higher WBC counts and 24 hour IgG index, but no correlation was statistically significant. UA may be a useful surrogate marker for monitoring NMO activity.     

Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI

When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8 year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2 years and all of the patients within the first 5 years, with a 5 year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p = 0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p = 0.004) and incomplete visual acuity recovery (⩽6/12) after 1 year (p = 0.002). Lower conversion rates were found in patients with optic disc edema (p = 0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5 years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate.     

Common CYP7A1 promoter polymorphism associated with risk of neuromyelitis optica

Neuromyelitis optica (NMO) is a severe idiopathic inflammatory disease of the central nervous system primarily affecting the optic nerves and spinal cord. In this study, we generated genome-wide SNP data from NMO patients and normal controls (53 cases and 240 controls), and followed up on the association signals with samples from a larger number of inflammatory demyelinating diseases, including NMO (n = 93), multiple sclerosis (MS, n = 71), idiopathic recurrent transverse myelitis (IRTM, n = 57), and normal controls (n = 240). Statistical analyses revealed that a common promoter SNP in CYP7A1 has a protective/gene dose-dependent effect on the risk of NMO (P = 0.0004). A stronger association between the variables and subsequently, a higher protective effect (lower OR) on the risk of NMO were observed among patients carrying the “G/G” genotype of rs3808607 than those with the “T/G” genotype (OR = 0.38/P = 0.01 vs. OR = 0.12/P = 0.0004, respectively). The associations which were only observed in patients with NMO suggest that there are differences in the genetic etiology of the inflammatory demyelinating diseases (NMO, classical MS, and IRTM).     

The utility of multimodal evoked potentials in multiple sclerosis prognostication

The ability to predict disability development in multiple sclerosis (MS) is limited. While abnormalities of evoked potentials (EP) have been associated with disability, the prognosticating utility of EP in MS remains to be fully elucidated. The present study assessed the utility of multimodal EP as a prognostic biomarker of disability in a cohort of clinically heterogeneous MS patients. Median and tibial nerve somatosensory, visual, and brainstem auditory EP were performed at initial assessment on 63 MS patients (53 relapsing–remitting and 10 secondary progressive) who were followed for an average of 2 years. A combined EP score (CEPS) was calculated consisting of the total number of abnormal EP tests, and was correlated with the Expanded Disability Status Scale (EDSS) at baseline and follow-up. There was a significant correlation between multimodal EP and baseline and follow-up EDSS. Specifically, tibial nerve P37 latencies correlated with EDSS (R_BASELINE = 0.49, p < 0.01; R_FOLLOW-UP = 0.47, p < 0.01), as did the median nerve N13 (R_BASELINE = 0.40, p < 0.01; R_FOLLOW-UP = 0.35, p < 0.05) and N20 latencies (R_BASELINE = 0.43, p < 0.01; R_FOLLOW-UP = 0.47, p < 0.01), and P100 full-field (R_BASELINE = 0.50, p < 0.001; R_FOLLOW-UP = 0.45, p < 0.001) and central field latencies (R_BASELINE = 0.60, p < 0.001; R_FOLLOW-UP = 0.50, p < 0.001). In addition, there was a significant correlation between the CEPS with baseline (R = 0.65, p < 0.001) and follow-up (R = 0.57, p < 0.01) EDSS. In contrast, white matter disease burden, as measured by T2 lesion load, exhibited a weaker correlation with EDSS (R_BASELINE = 0.28, p < 0.05). In conclusion, these findings suggest that abnormalities of EP, as quantified by the novel CEPS, may be a useful biomarker for prognosticating clinical disability in MS, and may aid in the quantification of MS disease severity and in guiding therapeutic decisions.     

Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases

IntroductioStereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases.Patients and methodsWe performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression.ResultsWe identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p < 0.0001), and thus larger V100% (p < 0.0001), V50% (p < 0.0001), V12 Gy (p < 0.0001), and V10 Gy (p = 0.0002), compared to the rest of the cohort. Single-fraction treatment (p = 0.0025) and diabetes (p = 0.019) were also significantly associated with symptomatic RN.ConclusionSRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12 Gy, or V10 Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.     

Evaluation of cerebrovascular reserve using xenon-enhanced CT scanning in patients with symptomatic middle cerebral artery stenosis

Cerebrovascular reserve (CVR) is an important prognostic factor in patients with major cerebral arterial steno-occlusive disease. However, few studies have examined CVR in symptomatic intracranial stenosis without ipsilateral extracranial internal carotid artery stenosis. This study sought to evaluate CVR in patients with symptomatic middle cerebral artery (MCA) stenosis using xenon-enhanced computed tomography (Xe/CT) with acetazolamide (ACZ) challenge. Twelve patients with symptomatic MCA stenosis were recruited. All patients were examined by Xe/CT to quantitatively measure resting cerebral blood flow (CBF) and received ACZ challenge to evaluate CVR. For resting CBF, no significant differences were found between the sides in four regions of interest. After the ACZ challenge test, the CVR was significantly different between hemispheres (ipsilateral versus contralateral CVR: 12.9 ± 24.3% versus 28.0 ± 16.8%, respectively; p = 0.005) and in the MCA territory (ipsilateral versus contralateral CVR: 8.7 ± 24.7% versus 29.3 ± 24%, respectively; p = 0.003). However, no significant differences in CVR were detected between cortical comparisons and white matter comparisons from the two sides. Thus, ACZ-challenge Xe/CT is useful for the measurement of CBF and CVR in these patients. Impaired CVR is an important characteristic of patients with symptomatic MCA stenosis.     

Evaluation of patients with multiple sclerosis using a combination of morphometrical features and clinical scores

Our aim was to measure cerebellum volume (CV), sclerotic plaque numbers (PN), and plaque surface area (SA) in the parietal lobe, and to investigate the relationship between CV and PN or SA in the parietal lobe, and the clinical status of patients with multiple sclerosis (MS). MRIs were performed in 14 patients with relapsing-remitting MS (RRMS), 13 patients with secondary progressive MS (SPMS), and 26 healthy control participants. The Cavalieri method was used to measure CV and SA. The cerebellum volume was significantly reduced in MS patients compared to controls (p < 0.01). In all patients, CV was negatively correlated with the duration of the disease, relapse number, and Expanded Disability Status Scale (EDSS) scores (p < 0.01). CV was related to mean PN in both the right and left parietal lobes (p < 0.01) and mean SA (p < 0.05) in RRMS patients; CV was also correlated with mean PN (p < 0.01) and mean SA (p < 0.05) in SPMS patients. The progression index (Pi) values were 2.03 ± 0.4 in RRMS patients and 0.83 ± 0.2 in SPMS patients (p = 0.023, t = 2.612) (where Pi = EDSS/time from onset in years). We propose that atrophy begins both in the supratentorial and infratentorial areas simultaneously in the RR stage, and that the Cavalieri method can be used to predict SPMS among patients with RRMS.     

Blink reflex in patients with postparalytic facial syndrome and blepharospasm: Trigeminal and auditory stimulation

ObjectiveThe enhancement of blink reflex (BR) excitability was shown in patients with postparalytic facial syndrome (PFS) and essential blepharospasm (EB). We prospectively investigated patients with PFS and EB whether BR alterations demonstrated by trigeminal stimulation will similarly be observed upon auditory stimulation.MethodsFifteen patients with PFS, 15 patients with EB, and 30 healthy volunteers were involved. Electrically stimulated trigeminal BR and auditory BR were studied bilaterally.ResultsThe mean R2 amplitude and duration values were highest in EB patients, being significantly higher than PFS patients (p < 0.05) and control group (p < 0.01). The mean R2 duration in PFS patients were also significantly longer in compared to control group (p = 0.025). EB patients showed a higher mean R (auditory) amplitude and duration than PFS patients (p < 0.05) and controls (p < 0.04). The mean R (auditory) duration was longer on symptomatic side of PFS patients in compared to controls (p = 0.05).ConclusionsWe observed that there is an enhanced excitability of BR circuit in postparalytic facial syndrome and essential blepharospasm, which could be evoked by auditory stimulation in addition to trigeminal stimulation.SignificanceThe enhanced excitability in patients with EB and PFS probably originates from the final common pathway of BR circuit, namely facial motor or premotor neurons.     

Minimally invasive transforaminal lumbar interbody fusion for spondylolisthesis in patients with significant obesity

Comparative studies evaluating efficacy and safety of minimally invasive spinal fusion between patients with significant obesity (body mass index [BMI] ? 35 kg/m²) and those of normal weight are scarce. We examined complication rates and outcomes for minimally invasive transforaminal lumbar interbody fusion (MITLIF) in patients with significant obesity and those of normal weight undergoing treatment for symptomatic spondylolisthesis. Patients with a BMI ? 35 kg/m² or <25 kg/m² undergoing elective MITLIF for symptomatic spondylolisthesis for the period 2006–09 were identified. Of the 16 patients identified, nine patients with a mean BMI of 37.4 kg/m² were included in the obese group, while seven patients with a mean BMI of 23.4 kg/m² comprised the normal weight group. Estimated blood loss (EBL), operative time, complication rate, length of hospital stay, and clinical outcomes were assessed. Outcome measures included patient-reported visual analog scale (VAS) score for pain and the Oswestry Disability Index (ODI) questionnaire completed by the patient. No significant differences were found in blood loss (p = 0.436), hospital stay (p = 0.606), or number of surgical complications (p = 0.920) between the two groups. Mean follow-up intervals were 15.0 months for patients with obesity, and 18.6 months for those of normal weight. Both groups had significant improvements in VAS (obese, p = 0.003; normal, p = 0.016) and ODI (obese, p = 0.020; normal, p = 0.034) scores. There were no statistically significant differences between normal weight and obese groups in postoperative VAS (p = 0.728) and ODI (p = 0.886) scores. Patients with significant obesity experienced clinical improvement similar to that of patients with normal weight, suggesting that obesity does not impact MITLIF outcomes. In addition, both groups experienced similar complication rates, operative times, EBL, and length of hospital stay.     

Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson’s disease

Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson’s disease (PD) patients undergoing DBS procedure between 2008–2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson’s Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00–1.02; p = 0.005), high Joint National Committee (JNC) class (p < 0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2–17; p < 0.0001) and duration of PD >10 years (RR 1.2; 95%CI 1.1–1.3; p = 0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p = 0.1) and levodopa equivalent dose (p = 0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p = 0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications.     

Outcomes and cost-effectiveness of gamma knife radiosurgery and whole brain radiotherapy for multiple metastatic brain tumors

We aimed to analyze the outcomes and cost-effectiveness of gamma knife radiosurgery (GKRS) and whole brain radiotherapy (WBRT) for multiple metastatic brain tumors. Over a period of 5 years, 156 patients with multiple metastatic brain tumors were enrolled and freely assigned by the referring doctors to either gamma knife radiosurgery (GKRS, Group A, n = 56), or to whole brain radiotherapy (WBRT, Group B, n = 100). The follow-up time was set at 1200 days (3.3 years) post-treatment. The number of tumors, patient age, extent of systemic disease and Karnofsky performance scale (KPS) score, were recorded and recursive partitioning analysis used. The outcomes analyzed were: mortality, survival time, neurological complications, post-treatment KPS score, quality-adjusted life years (QALY), and cost-effectiveness. A paired t-test was used for statistical analysis. Mortality rates for patients receiving GKRS and WBRT were 81.1% and 93.0%, respectively (p = 0.05). The mortality rate was lower for GKRS (74.4%) than for WBRT (97.1%) in patients with initial KPS ? 70 (p = 0.02). The mortality rate was also significantly lower for GKRS (78.9%) than WBRT (95.5%) in patients with 2–5 tumors (p < 0.05). Post-treatment KPS score (mean ± standard deviation [s.d.] was higher for patients receiving GKRS (73.8 ± 13.2) than for those receiving WBRT (45.5 ± 26.0), p < 0.01. The median survival time for GKRS and WBRT was 9.5 months and 8.3 months, respectively, p = 0.72. The mean (± s.d.) QALY was 0.76 ± 0.23 for GKRS and 0.59 ± 0.18 for WBRT, respectively (p < 0.05). The cost-effectiveness per unit of QALY was better for the GKRS treatment (US$10,381/QALY) than in the WBRT treatment (US$17,622/QALY), p < 0.05. The cost-effectiveness per KPS score was also higher for the GKRS treatment (US$139/KPS score) than for WBRT (US$229/KPS score), p < 0.01. Thus, the mortality rate for multiple metastatic brain tumors treated by GKRS is significantly better with a good initial KPS score and when the tumor number is 2–5. GKRS results in a better post-treatment KPS score, QALY, and higher cost-effectiveness than WBRT for treating multiple metastatic brain tumors.     

The effect of war stress on multiple sclerosis exacerbations and radiological disease activity

ObjectiveThe relationship between stressful life events and multiple sclerosis (MS) exacerbations or radiological disease activity is at best controversial. The aim of this study is to examine the relationship between exposure to war-related events incurred during the July 2006 Israeli–Lebanese war and clinical relapses and MRI disease activity among Lebanese MS patients.MethodsWe studied a group of 216 patients with clinically definite relapsing remitting MS (RRMS), on whom clinical data was available for the war period and for the preceding and following year(s). The number of relapses was determined during the war period and during similar periods over a 3-year span. All patients with brain MRI during the war period had their scans reviewed for evidence of disease activity as defined by the presence of gadolinium enhancing (Gd+) lesions. A group of patients with brain MRI performed outside the war period was used for comparison.ResultsThe total number of relapses during the war period (n = 23) was significantly higher than during non-war periods (mean = 8.4, SD = 0.86) (p = 0.006). Of the 18 patients with brain MRI during the war, 5/7 with relapses and 1/11 without relapses had Gd+ lesions (p = 0.013). More patients had Gd+ lesions during the war period (33%) compared to controls (13%) (p = 0.075).InterpretationOur study shows that exposure to war-related events is likely to lead to an increase in both clinical relapses and MRI disease activity in patients with MS.     

Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users

We conducted a meta-analysis on the available data from studies investigating SERTs in ecstasy users and polydrug using controls. From 7 studies we compared data from 157 ecstasy users and 148 controls across 14 brain regions. The main effect suggested ecstasy/MDMA related SERT reductions (SMD = 0.52, 95% CIs [0.40, 0.65]; Z = 8.36, p < .01, I² = 89%). A significant effect of subgroups (X² = 37.41, df = 13, p < .01, I² = 65.3%) suggested differential effects across brain ROIs. Ecstasy users showed significant SERT reductions in 11 out of the 14 regions, including every neocortical and limbic region analysed. Greatest effects were observed in the occipital cortex (SMD = 1.09, 95% CIs [0.70, 1.48]). No group effects were observed in subcortical areas of the caudate, putamen and midbrain. Literature on Postsynaptic 5HT_2A receptor imaging was synthesised with these results. We conclude that, in line with preclinical data, serotonin axons with the longest projections from the raphe nuclei appear to be most affected by ecstasy/MDMA use.     

At the boundary of the self: The insular cortex in patients with childhood-onset schizophrenia,their healthy siblings,and normal volunteers

The insular cortex (insula), whose normal function involves delineating the boundary between self and non-self stimuli, has been implicated in the pathophysiology of the positive symptoms of schizophrenia, including hallucinations and delusions. Childhood-onset schizophrenia (COS), that includes the onset of psychosis before age 13, is a severe and continuous form of the illness which shows profound and global progressive cortical brain abnormalities during adolescence which merge in the adult pattern with age. Using prospectively acquired anatomic brain magnetic resonance imaging (MRI) scans, a matched sample of COS patients, their nonpsychotic full siblings and healthy volunteers, we measured insular volume using the FreeSurfer automated software. COS patients (n = 98; 234 scans) had significantly lower right (p = 0.003), left (p < 0.001), and total (p < 0.001) insular volumes than healthy volunteers (n = 100; 248 scans). Right insular volume negatively correlated with positive symptoms as measured by the Scale for the Assessment of Positive Symptoms (SAPS) (p = 0.02), while both left (p = 0.01) and right (p = 0.006) insula volumes were positively correlated with overall functioning, as measured by the Children's Global Assessment Scale (CGAS) scores. COS siblings (n = 71; 153 scans), on the other hand, did not differ significantly from normal volunteers suggesting that the insular deficits are more related to the illness state than a familial endophenotype. These results also highlight the salience of the insula in positive symptoms of schizophrenia perhaps resulting from the inability to discriminate between self from the non-self in COS. Further work to connect insular deficits to other neurocircuitries is warranted.     

Sleep parameters associated with long-term outcome following subthalamic deep brain stimulation in Parkinson's disease

IntroductionWe aimed to investigate the effects of changes in sleep architecture on long-term clinical outcome in patients with Parkinson's disease (PD) who underwent deep brain stimulation of subthalamic nuclei (STN DBS).MethodsWe followed up eight PD patients before and three years after STN DBS surgery. In addition to clinical assessments, polysomnography (PSG) followed by multiple sleep latency tests was performed before and after STN DBS, while stimulator was ON and OFF.ResultsSubjective sleep latency was significantly decreased (P = 0.033) and sleep duration was increased (P = 0.041), as measured by Pittsburgh sleep quality index. Latency to REM sleep stage was shortened after surgery with STN DBS ON (P = 0.002). Index of central type of abnormal respiratory events was significantly increased while stimulator was ON (P = 0.034). Total number of major body movements was found to be increased when stimulator was turned OFF (P = 0.012). Among PSG data obtained during STN DBS ON, it was observed that duration of N3 sleep was negatively correlated with UPDRS scores at 1st (P = 0.038) and 3rd (P = 0.045) post-operative years. Among PSG variables during STN DBS OFF, durations of N3 sleep (P = 0.017) and REM sleep (P = 0.041) were negatively correlated with UPDRS scores at post-operative 1st year.ConclusionDisturbances in sleep architecture are associated with higher UPDRS scores and worse prognosis at 1st and 3rd post-operative years. Similar results obtained while stimulator was OFF at the end of 1st year support the presence of microlesion effect after STN DBS, which is probably not long lasting.     

Outcomes of middle fossa craniotomy for the repair of superior semicircular canal dehiscence

Superior semicircular canal dehiscence (SSCD) is a rare defect of the arcuate eminence that causes an abnormal connection between the superior semicircular canal and middle cranial fossa. Patients often present with a variety of auditory and vestibular symptoms. Trigger avoidance is the initial strategy, but surgery may be necessary in debilitating cases. We retrospectively reviewed SSCD patients undergoing repair via a middle fossa craniotomy between March 2011 and September 2015. Forty-nine patients undergoing 58 surgeries were identified. Autophony was the most common symptom at presentation (n = 44; 90%). Mean follow-up was 10.9 months, with 100% of patients reporting resolution of at least one symptom. Aural fullness was the most commonly resolved symptom following surgical repair (n = 19/22; 86%). Hearing loss (n = 11/25; 44%) and tinnitus (n = 11/38; 29%) were the most common symptoms to persist following surgery. The most common symptom to develop after surgery was disequilibrium (n = 4/18; 22%). Upon comparing the overall pre-operative and post-operative groups, the number of patients with autophony (p < 0.0001), aural fullness (p = 0.0006), hearing loss (p = 0.0119), disequilibrium (p = 0.0002), sound- and pressure-induced vertigo (p < 0.0001), and tinnitus (p < 0.0001) were significantly different. Improved clinical outcomes were demonstrated in patients undergoing SSCD repair through a middle cranial fossa approach. The most common presenting symptom (autophony) was also most likely to resolve after surgery. Hearing loss is less amenable to surgical correction. Disequilibrium developed in a small number of patients after repair.     

Examining perceived stigma of children with newly-diagnosed epilepsy and their caregivers over a two-year period

The purpose of this study was to examine the following: 1) the course of perceived epilepsy-related stigma among children newly diagnosed with epilepsy (n = 39) and their caregivers (n = 97) over a two-year period, 2) the influence of seizure absence/presence on children and caregivers' perception of epilepsy-related stigma, and 3) the congruence of child and caregiver perception of child epilepsy-related stigma. Participants completed a measure of perceived epilepsy-related stigma at three time points, and seizure status was collected at the final time point. Results indicated that both caregivers (t_1,76 = − 2.57, p < .01) and children with epilepsy (t_1,29 = − 3.37, p < .01) reported decreasing epilepsy-related stigma from diagnosis to two years postdiagnosis. No significant differences were found in caregiver and child reports of perceived stigma for children experiencing seizures compared with children who have been seizure-free for the past year. Results revealed poor caregiver–child agreement of perceived epilepsy-related stigma at all three time points. These data suggest that while children with epilepsy initially perceive epilepsy-related stigma at diagnosis, their perception of stigma decreases over time. Having a better understanding of the course of epilepsy-related stigma provides clinicians with information regarding critical times to support families with stigma reduction interventions.     

Corneal nerve microstructure in Parkinson’s disease

Ocular surface changes and blink abnormalities are well-established in Parkinson’s disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinson’s disease. This case-control study examined the ocular surface in patients with moderately severe Parkinson’s disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinson’s disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinson’s disease, ten were male and the mean age was 65.5 ± 8.6 years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinson’s disease (7.56 ± 2.4 mm/mm²) compared with controls (15.91 ± 2.6 mm/mm²) (p < 0.0001). Corneal sensitivity did not differ significantly between the patients with Parkinson’s disease (0.79 ± 1.2 mBAR) and the control group (0.26 ± 0.35 mBAR), p = 0.12. Sub-basal nerve density was not significantly different between the eye ipsilateral to the side of the body with most-severe motor symptoms, and the contralateral eye. There was a significant positive correlation between ACE-R scores and sub-basal corneal nerve density (R² = 0.66, p = 0.02). This is the first study to report a significant reduction in corneal sub-basal nerve density in Parkinson’s disease and demonstrate an association with cognitive dysfunction. These results provide further evidence to support the involvement of the peripheral nervous system in Parkinson’s disease, previously thought to be a central nervous system disorder.